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Sample records for rapidly progressive infection

  1. Acute HIV infection with rapid progression to AIDS

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    Marcio de Oliveira Silva

    Full Text Available Acute HIV infection is rarely recognized as the signs and symptoms are normally unspecific and can persist for days or weeks. The normal HIV course is characterized by a progressive loss of CD4+ cells, which normally leads to severe immunodeficiency after a variable time interval. The mean time from initial infection to development of clinical AIDS is approximately 8-10 years, but it is variable among individuals and depends on a complex interaction between virus and host. Here we describe an extraordinary case of a man who developed Pneumocisits jiroveci pneumonia within one month after sexual exposure to HIV-1, and then presented with 3 consecutive CD4 counts bellow 200 cells/mm³ within 3 months, with no other opportunistic disease. Although antiretroviral therapy (AZT+3TC+ATZ/r was started, with full adherence of the patient, and genotyping indicating no primary antiretroviral resistance mutations, he required more than six months to have a CD4 restoration to levels above 200 cells/mm³ and 10 months to HIV-RNA to become undetectable.

  2. Early depletion of proliferating B cells of germinal center in rapidly progressive simian immunodeficiency virus infection

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    Zhang Zhiqiang; Casimiro, Danilo R.; Schleif, William A.; Chen, Minchun; Citron, Michael; Davies, Mary-Ellen; Burns, Janine; Liang, Xiaoping; Fu, Tong-Ming; Handt, Larry; Emini, Emilio A.; Shiver, John W.

    2007-01-01

    Lack of virus specific antibody response is commonly observed in both HIV-1-infected humans and SIV-infected monkeys with rapid disease progression. However, the mechanisms underlying this important observation still remain unclear. In a titration study of a SIVmac239 viral stock, three out of six animals with viral inoculation rapidly progressed to AIDS within 5 months. Unexpectedly, there was no obvious depletion of CD4 + T cells in both peripheral and lymph node (LN) compartments in these animals. Instead, progressive depletion of proliferating B cells and disruption of the follicular dendritic cell (FDC) network in germinal centers (GC) was evident in the samples collected at as early as 20 days after viral challenge. This coincided with undetectable, or weak and transient, virus-specific antibody responses over the course of infection. In situ hybridization of SIV RNA in the LN samples revealed a high frequency of SIV productively infected cells and large amounts of accumulated viral RNA in the GCs in these animals. Early severe depletion of GC proliferating B cells and disruption of the FDC network may thus result in an inability to mount a virus-specific antibody response in rapid progressors, which has been shown to contribute to accelerated disease progression of SIV infection

  3. Complicated acute appendicitis presenting as a rapidly progressive soft tissue infection of the abdominal wall: a case report.

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    Beerle, Corinne; Gelpke, Hans; Breitenstein, Stefan; Staerkle, Ralph F

    2016-12-01

    We report a case of a rare complication of acute appendicitis with perforation through the abdominal wall. The case points out that an intraabdominal origin should be considered in patients presenting with rapidly spreading soft tissue infections of the trunk. A 58-year-old European woman presented to our hospital with a 1-week history of severe abdominal pain accompanied by rapidly spreading erythema and emphysema of the lower abdomen. On admission, the patient was in septic shock with leukocytosis and elevation of C-reactive protein. Among other diagnoses, necrotizing fasciitis was suspected. Computed tomography showed a large soft tissue infection with air-fluid levels spreading through the lower abdominal wall. During the operation, we found a perforated appendicitis breaking through the fascia and causing a rapidly progressive soft tissue infection of the abdominal wall. Appendicitis was the origin of the soft tissue infection. The abdominal wall was only secondarily involved. Even though perforated appendicitis as an etiology of a rapidly progressive soft tissue infection of the abdominal wall is very rare, it should be considered in the differential diagnosis of abdominal wall cellulitis. The distinction between rapidly spreading subcutaneous infection with abscess formation and early onset of necrotizing fasciitis is often difficult and can be confirmed only by surgical intervention.

  4. Successful recovery of infective endocarditis-induced rapidly progressive glomerulonephritis by steroid therapy combined with antibiotics: a case report

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    Kikkawa Ryuichi

    2004-12-01

    Full Text Available Abstract Background The mortality rate among patients with infective endocarditis, especially associated with the presence of complications or coexisting conditions such as renal failure and the use of combined medical and surgical therapy remains still high. Prolonged parenteral administration of a bactericidal antimicrobial agent or combination of agents is usually recommended, however, the optimal therapy for infective endocarditis associated with renal injury is not adequately defined. Case presentation Patient was a 24-years old man who presented to our hospital with fever, fatigue, and rapidly progressive glomerulonephritis. He had a history of ventricular septum defect (VSD. A renal biopsy specimen revealed crescentic glomerulonephritis and echocardiogram revealed VSD with vegetation on the tricuspid valve. Specimens of blood demonstrated Propionibacterium Acnes. The intensive antibiotic therapy with penicillin G was started without clinical improvement of renal function or resolution of fever over the next 7 days. After the short-term treatment of low dose of corticosteroid combined with continuous antibiotics, high fever and renal insufficiency were dramatically improved. Conclusion Although renal function in our case worsened despite therapy with antibiotics, a short-term and low dose of corticosteroid therapy with antibiotics was able to recover renal function and the patient finally underwent tricuspid valve-plasty and VSD closure. We suggest that the patients with rapidly progressive glomerulonephritis associated with infective endocarditis might be treated with a short-term and low dose of corticosteroid successfully.

  5. Rapid disease progression in human immunodeficiency virus type 1-infected individuals with adverse reactions to trimethoprim-sulfamethoxazole prophylaxis

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    Veenstra, J.; Veugelers, P. J.; Keet, I. P.; van der Ven, A. J. A. M.; Miedema, F.; Lange, J. M.; Coutinho, R. A.

    1997-01-01

    We studied the relation between the occurrence of adverse reactions to trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis and the subsequent course of human immunodeficiency virus (HIV) infection in a cohort of homosexual men. Adverse reactions to TMP-SMZ were associated with a more rapid

  6. Rapidly Progressive Quadriplegia and Encephalopathy.

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    Wynn, DonRaphael; McCorquodale, Donald; Peters, Angela; Juster-Switlyk, Kelsey; Smith, Gordon; Ansari, Safdar

    2016-11-01

    A woman aged 77 years was transferred to our neurocritical care unit for evaluation and treatment of rapidly progressive motor weakness and encephalopathy. Examination revealed an ability to follow simple commands only and abnormal movements, including myoclonus, tongue and orofacial dyskinesias, and opsoclonus. Imaging study findings were initially unremarkable, but when repeated, they demonstrated enhancement of the cauda equina nerve roots, trigeminal nerve, and pachymeninges. Cerebrospinal fluid examination revealed mildly elevated white blood cell count and protein levels. Serial electrodiagnostic testing demonstrated a rapidly progressive diffuse sensory motor axonopathy, and electroencephalogram findings progressed from generalized slowing to bilateral periodic lateralized epileptiform discharges. Critical details of her recent history prompted a diagnostic biopsy. Over time, the patient became completely unresponsive with no further abnormal movements and ultimately died. The differential diagnosis, pathological findings, and diagnosis are discussed with a brief review of a well-known yet rare diagnosis.

  7. Rapidly Progressive Disseminated Sporotrichosis as the First Presentation of HIV Infection in a Patient with a Very Low CD4 Cell Count.

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    de Oliveira-Esteves, Isis Cristine Morávia Ribeiro; Almeida Rosa da Silva, Guilherme; Eyer-Silva, Walter de Araujo; Basílio-de-Oliveira, Rodrigo Panno; de Araujo, Luciana Ferreira; Martins, Carlos José; Neves-Motta, Rogério; Velho Mendes de Azevedo, Marcelo Costa; Signorini, Dario José Hart Pontes; Francisco da Cunha Pinto, Jorge; Moura, Lívia Machado; Laterça, Rafael Jacyntho; Pereira, Diogo Raphael Garcia de Oliveira; do Lago, Isabela Vieira; Raphael de Almeida Ferry, Fernando

    2017-01-01

    Sporotrichosis is a human and animal disease caused by species of the Sporothrix schenckii complex. It is classically acquired through traumatic inoculation of fungal elements. Most frequently, sporotrichosis presents as a fixed cutaneous or as a lymphocutaneous form. A much smaller number of cases occur as cutaneous disseminated and disseminated forms. These cases require immediate diagnosis and management to reduce morbidity and mortality. We present the case of a 34-year-old male patient in whom the first presentation of HIV infection was a rapidly progressive sporotrichosis with multiple cutaneous lesions, a high fungal burden in tissues, and pulmonary involvement. He had an extremely low CD4 cell count (06/mm 3 ). Treatment with amphotericin B deoxycholate led to complete clinical resolution. Sporotrichosis remains a neglected opportunistic infection among HIV-infected patients in Rio de Janeiro state, Brazil, and awareness of this potentially fatal infection is of utmost importance if treatment is not to be delayed and if potentially devastating complications are to be avoided.

  8. Rapidly Progressive Corticobasal Degeneration Syndrome

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    Ana Herrero Valverde

    2011-08-01

    Full Text Available Introduction: Corticobasal syndrome (CBS has a heterogeneous clinical presentation with no specific pathologic substratum. Its accurate diagnosis is a challenge for neurologists; in order to establish CBS definitively, postmortem confirmation is required. Some clinical and radiological features can help to distinguish it from other neurodegenerative conditions, such as Creutzfeldt-Jakob disease (CJD. Clinical Case: A 74-year-old woman presented with language impairment, difficulty in walking and poor attentiveness that had begun 10 days before. Other symptoms, such as asymmetrical extra-pyramidal dysfunction, limb dystonia and ‘alien limb’ phenomena, were established over the next 2 months, with rapid progression. Death occurred 3 months after symptom onset. Laboratory results were normal. Initially, imaging only showed restricted diffusion with bilateral parieto-occipital gyri involvement on DWI-MRI, with unspecific EEG changes. An autopsy was performed. Brain neuropathology confirmed sporadic CJD (sCJD. Conclusions: CBS is a heterogeneous clinical syndrome whose differential diagnosis is extensive. CJD can occasionally present with clinical characteristics resembling CBS. MRI detection of abnormalities in some sequences (FLAIR, DWI, as previously reported, has high diagnostic utility for sCJD diagnosis – especially in early stages – when other tests can still appear normal. Abnormalities on DWI sequencing may not correlate with neuropathological findings, suggesting a functional basis to explain the changes found.

  9. An Unusual Case of Rapidly Progressive Hyperbilirubinemia

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    Kimberly M. Thornton

    2013-01-01

    Full Text Available We present an unusual case of hyperbilirubinemia with rapid early progression leading to bilirubin encephalopathy in a term neonate. Despite early recognition and intervention, the total serum bilirubin reached a maximum level of 39 mg/dL at 32 hours of life. Prior to an emergent exchange transfusion, the patient’s diagnostic evaluation was significant for Coombs-negative microangiopathic hemolytic anemia and thrombocytopenia. Further testing revealed a deficiency of ADAMTS13 protein, or von Willebrand factor-cleaving protease, a finding diagnostic of congenital thrombotic thrombocytopenic purpura, or Upshaw-Schulman syndrome. This rare disease is often misdiagnosed, especially in the newborn period.

  10. Rapidly Progressive Spontaneous Spinal Epidural Abscess

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    Abdurrahman Aycan

    2016-01-01

    Full Text Available Spinal epidural abscess (SEA is a rare disease which is often rapidly progressive. Delayed diagnosis of SEA may lead to serious complications and the clinical findings of SEA are generally nonspecific. Paraspinal abscess should be considered in the presence of local low back tenderness, redness, and pain with fever, particularly in children. In case of delayed diagnosis and treatment, SEA may spread to the epidural space and may cause neurological deficits. Magnetic resonance imaging (MRI remains the method of choice in the diagnosis of SEA. Treatment of SEA often consists of both medical and surgical therapy including drainage with percutaneous entry, corpectomy, and instrumentation.

  11. Syndromes of rapidly progressive cognitive decline-our experience

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    Sadanandavalli Retnaswami Chandra

    2017-01-01

    Full Text Available Background: Dementias are fairly slowly progressive degenerative diseases of brain for which treatment options are very less and carry a lot of burden on family and society. A small percentage of them are rapidly progressive and mostly carry a different course outcome. However, there are no definite criteria other than the time line for these patients. Aims: The aim of this was to identify and categorize the causes and course of rapidly progressive dementias seen in our center. Settings and Design: Patients who presented with rapid deterioration of cognitive functions within weeks to 1 year between 2011 and December 2016 were evaluated. Patients and Methods: All patients underwent all mandatory tests for dementia including brain imaging. Complete vasculitis workup, autoimmune encephalitis profile including Voltage Gated Potassium Channel, N-methyl-D-aspartic acid receptor, glutamic acid-decarboxylase, thyroid-peroxidase antibody, cerebrospinal fluid, and other special tests such as duodenal biopsy and paraneoplastic workup were done based on clinical indications. Results and Conclusions: Out of 144 patients 42 had immune-mediated encephalopathy, 18 had Creutzfeldt-Jakob disease, 3 had Vitamin B12 deficiency, 63 had infection with neurocysticercosis, 7 had tuberculosis, 2 had HIV, 1 had herpes simplex encephalitis, 1 had neurosyphilis, 1 Whipples disease, 1 had Subacute Sclerosing Panencephalitis, 1 had Mass lesion, 3 had Frontotemporal dementia, and 3 had small vessel disease. Good majority of these patients have infective and immune-mediated causes and less number belong to degenerative group. Therefore, caution is needed to look for treatable cause as it carries a different treatment options and outcome.

  12. Serodiagnosis of dengue infection using rapid immunochromatography test in patients with probable dengue infection.

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    Kidwai, Aneela Altaf; Jamal, Qaiser; Saher; Mehrunnisa; Farooqi, Faiz-ur-rehman; Saleem-Ullah

    2010-11-01

    To determine the frequency of seropositive dengue infection using rapid immunochromatographic assay in patients with probable dengue infection as per WHO criteria. A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immunochromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results.

  13. Serodiagnosis of dengue infection using rapid immuno chromatography test in patients with probable dengue infection

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    Kidwai, A.A.; Jamal, Q.; Mehrunnisa, S.; Farooqi, F.R.

    2010-01-01

    Objective: To determine the frequency of seropositive dengue infection using rapid immuno chromatographic assay in patients with probable dengue infection as per WHO criteria. Method: A cross-sectional observational study was conducted at Abbasi Shaheed Hospital, Karachi from July 2008 to January 2009. Patients presenting with acute febrile illness, rashes, bleeding tendencies, leucopenia and or thrombocytopenia were evaluated according to WHO criteria for probable dengue infection. Acute phase sera were collected after 5 days of the onset of fever as per WHO criteria. Serology was performed using rapid immuno chromatographic (ICT) assay with differential detection of IgM and IgG. A primary dengue infection was defined by a positive IgM band and a negative IgG band whereas secondary infection was defined by a positive IgG band with or without positive IgM band. Result: Among 599 patients who met the WHO criteria for dengue infection, 251(41.9%) were found to be ICT reactive among whom 42 (16.73%) had primary infection. Secondary infection was reported in 209 (83.26%). Acute phase sera of 348 (58.09%) were ICT non reactive. Four patients died because of dengue shock syndrome among which three had secondary infection. Conclusion: Early identification of secondary infection in acute phase sera using rapid ICT is valuable in terms of disease progression and mortality. However in highly suspected cases of dengue infection clinical management should not rely on negative serological results. (author)

  14. Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

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    Krabbe, Simon; Engelhart, Merete; Thybo, Sören

    2017-01-01

    This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal......, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma....

  15. Progressive outer retinal necrosis: manifestation of human immunodeficiency virus infection.

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    Lo, Phey Feng; Lim, Rongxuan; Antonakis, Serafeim N; Almeida, Goncalo C

    2015-05-06

    We present the case of a 54-year-old man who developed progressive outer retinal necrosis (PORN) as an initial manifestation of HIV infection without any significant risk factors for infection with HIV. PORN is usually found as a manifestation of known AIDS late in the disease. Our patient presented with transient visual loss followed by decrease in visual acuity and facial rash. Subsequent investigation revealed anterior chamber tap positive for varicella zoster virus (VZV), as well as HIV positivity, with an initial CD4 count of 48 cells/µL. Systemic and intravitreal antivirals against VZV, and highly active antiretroviral therapy against HIV were started, which halted further progression of retinal necrosis. This case highlights the importance of suspecting PORN where there is a rapidly progressive retinitis, and also testing the patient for HIV, so appropriate treatment can be started. 2015 BMJ Publishing Group Ltd.

  16. Rapid diagnosis of sexually transmitted infections.

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    Otero-Guerra, Luis; Fernández-Blázquez, Ana; Vazquez, Fernando

    Sexually transmitted infections (STIs) are responsible for an enormous burden of morbidity and mortality. Worldwide, millions of cases of STIs, such as syphilis, chlamydia, or gonorrhoea occur every year, and there is now an increase in antimicrobial resistance in pathogens, such as gonococcus. Delay in diagnosis is one of the factors that justifies the difficulty in controlling these infections. Rapid diagnostic tests allow the introduction of aetiological treatment at the first visit, and also leads to treating symptomatic and asymptomatic patients more effectively, as well as to interrupt the epidemiological transmission chain without delay. The World Health Organisation includes these tests in its global strategy against STIs. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Frosted branch angiitis associated with rapidly progressive glomerulonephritis.

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    Gupta Amod

    2002-01-01

    Full Text Available Simultaneous occurrence of frosted branch angiitis and immune-mediated rapidly progressive glomerulonephritis is reported. The two diseases possibly share a common immune mechanism. Patients of frosted branch angiitis should undergo complete systemic evaluation including renal function tests even if the patient is systemically asymptomatic.

  18. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

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    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

  19. Alteration of cell cycle progression by Sindbis virus infection

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    Yi, Ruirong; Saito, Kengo [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Isegawa, Naohisa [Laboratory Animal Center, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan); Shirasawa, Hiroshi, E-mail: sirasawa@faculty.chiba-u.jp [Department of Molecular Virology, Graduate School of Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba 260-8670 (Japan)

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  20. Alteration of cell cycle progression by Sindbis virus infection

    International Nuclear Information System (INIS)

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-01-01

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G 1 phase preferred to proliferate during S/G 2 phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G 1 phase than in cells infected during S/G 2 phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases

  1. Rapidly progressive cryptogenic organising pneumonia presenting as a lung mass

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    Akram, Saeed; Irfan, Muhammad; Aftab, Kanwal

    2009-01-01

    A very rare case of a rapidly progressive variant of cryptogenic organising pneumonia (COP) presenting as a focal mass-like lesion with compression of the large airways leading to respiratory failure is described. A 60-year-old lady presented to the Aga Khan University Hospital Emergency Department in hypoxaemic respiratory failure with a 6-day history of dyspnoea, productive cough and fever. Chest x ray showed a right upper lobe mass-like lesion compressing the large airways and right pleural effusion. She deteriorated in the Emergency Department and was intubated due to worsening hypoxaemic respiratory failure. The pleural fluid and bronchoscopic specimens were negative on microbiological and cytological examination. CT-guided right lung biopsy revealed chronic non-specific inflammation without granuloma and malignancy. COP was diagnosed on video-assisted thoracoscopic (VATS) lung biopsy. She was successfully treated with high dose steroids and discharged in a stable condition; her 3-month follow-up chest x rays showed complete resolution of the lung lesion with some residual fibrosis. PMID:21686529

  2. Establishment of human papillomavirus infection requires cell cycle progression.

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    Dohun Pyeon

    2009-02-01

    Full Text Available Human papillomaviruses (HPVs are DNA viruses associated with major human cancers. As such there is a strong interest in developing new means, such as vaccines and microbicides, to prevent HPV infections. Developing the latter requires a better understanding of the infectious life cycle of HPVs. The HPV infectious life cycle is closely linked to the differentiation state of the stratified epithelium it infects, with progeny virus only made in the terminally differentiating suprabasal compartment. It has long been recognized that HPV must first establish its infection within the basal layer of stratified epithelium, but why this is the case has not been understood. In part this restriction might reflect specificity of expression of entry receptors. However, this hypothesis could not fully explain the differentiation restriction of HPV infection, since many cell types can be infected with HPVs in monolayer cell culture. Here, we used chemical biology approaches to reveal that cell cycle progression through mitosis is critical for HPV infection. Using infectious HPV16 particles containing the intact viral genome, G1-synchronized human keratinocytes as hosts, and early viral gene expression as a readout for infection, we learned that the recipient cell must enter M phase (mitosis for HPV infection to take place. Late M phase inhibitors had no effect on infection, whereas G1, S, G2, and early M phase cell cycle inhibitors efficiently prevented infection. We conclude that host cells need to pass through early prophase for successful onset of transcription of the HPV encapsidated genes. These findings provide one reason why HPVs initially establish infections in the basal compartment of stratified epithelia. Only this compartment of the epithelium contains cells progressing through the cell cycle, and therefore it is only in these cells that HPVs can establish their infection. By defining a major condition for cell susceptibility to HPV infection, these

  3. Case of Rapid Progression of Hemiatrophy on the Face: A New Clinical Entity?

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    Hisashi Nomura

    2015-01-01

    Full Text Available A lot of diseases, including lupus profundus, morphea, lipodystrophy, and Parry-Romberg syndrome, may manifest progressive hemifacial atrophy. These diseases usually progress slowly and rapid progression of atrophy is extremely rare. We report a case of elderly-onset rapid progression of hemifacial atrophy only in three weeks. Our case did not meet variable differential diagnoses. We discuss the clinical character of the patient against the past of literature and suppose it may be a new clinical entity.

  4. Defective proviruses rapidly accumulate during acute HIV-1 infection

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    Bruner, Katherine M.; Murray, Alexandra J.; Pollack, Ross A.; Soliman, Mary G.; Laskey, Sarah B.; Capoferri, Adam A.; Lai, Jun; Strain, Matthew C.; Lada, Steven M.; Hoh, Rebecca; Ho, Ya-Chi; Richman, Douglas D.; Deeks, Steven G.; Siliciano, Janet D.; Siliciano, Robert F.

    2016-01-01

    Although antiretroviral therapy (ART) suppresses viral replication to clinically undetectable levels, HIV-1 persists in CD4+ T cells in a latent form not targeted by the immune system or ART1–5. This latent reservoir is a major barrier to cure. Many individuals initiate ART during chronic infection, and in this setting, most proviruses are defective6. However, the dynamics of the accumulation and persistence of defective proviruses during acute HIV-1 infection are largely unknown. Here we show that defective proviruses accumulate rapidly within the first few weeks of infection to make up over 93% of all proviruses, regardless of how early ART is initiated. Using an unbiased method to amplify near full-length proviral genomes from HIV-1 infected adults treated at different stages of infection, we demonstrate that early ART initiation limits the size of the reservoir but does not profoundly impact the proviral landscape. This analysis allows us to revise our understanding of the composition of proviral populations and estimate the true reservoir size in individuals treated early vs. late in infection. Additionally, we demonstrate that common assays for measuring the reservoir do not correlate with reservoir size. These findings reveal hurdles that must be overcome to successfully analyze future HIV-1 cure strategies. PMID:27500724

  5. [Rapidly progressive compromise of cranial pairs as neurosyphilis manifestation].

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    Baccaro, Fernando; Moldes, Sofía; Novelli Poisson, Paola; Arduin, Julieta; Valerga, Mario

    2012-01-01

    Syphilis remains a common disease throughout the world, being neurosyphilis a relatively common manifestation. A case of a 34 years old male with HIV and neurosyphilis is presented, characterized by a clinical course evidenced by progressive palsy of cranial nerves. This case is unusual and a rare presentation of progressive cranial involvement with swallowing deficit, have found no similar data in the literature.

  6. Acute Viral Respiratory Infection Rapidly Induces a CD8+ T Cell Exhaustion-like Phenotype.

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    Erickson, John J; Lu, Pengcheng; Wen, Sherry; Hastings, Andrew K; Gilchuk, Pavlo; Joyce, Sebastian; Shyr, Yu; Williams, John V

    2015-11-01

    Acute viral infections typically generate functional effector CD8(+) T cells (TCD8) that aid in pathogen clearance. However, during acute viral lower respiratory infection, lung TCD8 are functionally impaired and do not optimally control viral replication. T cells also become unresponsive to Ag during chronic infections and cancer via signaling by inhibitory receptors such as programmed cell death-1 (PD-1). PD-1 also contributes to TCD8 impairment during viral lower respiratory infection, but how it regulates TCD8 impairment and the connection between this state and T cell exhaustion during chronic infections are unknown. In this study, we show that PD-1 operates in a cell-intrinsic manner to impair lung TCD8. In light of this, we compared global gene expression profiles of impaired epitope-specific lung TCD8 to functional spleen TCD8 in the same human metapneumovirus-infected mice. These two populations differentially regulate hundreds of genes, including the upregulation of numerous inhibitory receptors by lung TCD8. We then compared the gene expression of TCD8 during human metapneumovirus infection to those in acute or chronic lymphocytic choriomeningitis virus infection. We find that the immunophenotype of lung TCD8 more closely resembles T cell exhaustion late into chronic infection than do functional effector T cells arising early in acute infection. Finally, we demonstrate that trafficking to the infected lung alone is insufficient for TCD8 impairment or inhibitory receptor upregulation, but that viral Ag-induced TCR signaling is also required. Our results indicate that viral Ag in infected lungs rapidly induces an exhaustion-like state in lung TCD8 characterized by progressive functional impairment and upregulation of numerous inhibitory receptors. Copyright © 2015 by The American Association of Immunologists, Inc.

  7. Rapidly progressive periodontal disease associated with human immunodeficiency virus

    International Nuclear Information System (INIS)

    Hezaim, K.A.; Javed, F.; Askar, A.; Rasheed, A.A.

    2012-01-01

    Severe periodontal inflammation with generalized dental plaque accumulation, spontaneous and severe gingival bleeding, fungal infection, and inter dental papillae necrosis are presented in a patient infected with human immunodeficiency virus (HIV). Bite-wing radiographs revealed a generalized horizontal alveolar bone loss of 7-8 millimetres in both arches. Erythematous patches were noted on the gingival mucosa in both jaws. DNA testing was performed to identify the periodontopathogens. The patient had no signs or symptoms of acquired immunodeficiency syndrome. This case-report presents the massive periodontal destruction that occurred in a patient infected with HIV. Therefore, it is highly recommended that patients infected with HIV should be regularly monitored to aid in early detection and to provide proper management of periodontal inflammatory conditions to minimize its destruction. (author)

  8. CRF19_cpx is an Evolutionary fit HIV-1 Variant Strongly Associated With Rapid Progression to AIDS in Cuba.

    Science.gov (United States)

    Kouri, Vivian; Khouri, Ricardo; Alemán, Yoan; Abrahantes, Yeissel; Vercauteren, Jurgen; Pineda-Peña, Andrea-Clemencia; Theys, Kristof; Megens, Sarah; Moutschen, Michel; Pfeifer, Nico; Van Weyenbergh, Johan; Pérez, Ana B; Pérez, Jorge; Pérez, Lissette; Van Laethem, Kristel; Vandamme, Anne-Mieke

    2015-03-01

    Clinicians reported an increasing trend of rapid progression (RP) (AIDS within 3 years of infection) in Cuba. Recently infected patients were prospectively sampled, 52 RP at AIDS diagnosis (AIDS-RP) and 21 without AIDS in the same time frame (non-AIDS). 22 patients were sampled at AIDS diagnosis (chronic-AIDS) retrospectively assessed as > 3 years infected. Clinical, demographic, virological, epidemiological and immunological data were collected. Pol and env sequences were used for subtyping, transmission cluster analysis, and prediction of resistance, co-receptor use and evolutionary fitness. Host, immunological and viral predictors of RP were explored through data mining. Subtyping revealed 26 subtype B strains, 6 C, 6 CRF18_cpx, 9 CRF19_cpx, 29 BG-recombinants and other subtypes/URFs. All patients infected with CRF19 belonged to the AIDS-RP group. Data mining identified CRF19, oral candidiasis and RANTES levels as the strongest predictors of AIDS-RP. CRF19 was more frequently predicted to use the CXCR4 co-receptor, had higher fitness scores in the protease region, and patients had higher viral load at diagnosis. CRF19 is a recombinant of subtype D (C-part of Gag, PR, RT and nef), subtype A (N-part of Gag, Integrase, Env) and subtype G (Vif, Vpr, Vpu and C-part of Env). Since subtypes D and A have been associated with respectively faster and slower disease progression, our findings might indicate a fit PR driving high viral load, which in combination with co-infections may boost RANTES levels and thus CXCR4 use, potentially explaining the fast progression. We propose that CRF19 is evolutionary very fit and causing rapid progression to AIDS in many newly infected patients in Cuba.

  9. Microbiological characteristics of subgingival microbiota in adult periodontitis, localized juvenile periodontitis and rapidly progressive periodontitis subjects.

    Science.gov (United States)

    Nonnenmacher, C; Mutters, R; de Jacoby, L F

    2001-04-01

    To describe the prevalence of the cultivable subgingival microbiota in periodontal diseases and to draw attention to the polymicrobial nature of periodontic infections. The study population consisted of 95 patients, 51 females and 44 males, aged 14-62 years. Twenty-nine patients exhibited adult periodontitis (AP), six localized juvenile periodontitis (LJP), and 60 rapidly progressive periodontitis (RPP). Two to four pooled bacterial samples were obtained from each patient. Samples were collected with sterile paper points from the deepest periodontal pockets. The samples were cultured under anaerobic and microaerophilic conditions using selective and non-selective media. Isolates were characterized to species level by conventional biochemical tests and by a commercial rapid test system. Prevotella intermedia and Capnocytophaga spp. were the most frequently detected microorganisms in all diagnostic groups. Porphyromonas gingivalis and Peptostreptococcus micros were found more frequently in AP and RPP patients, while Actinobacillus actinomycetemcomitans and Eikenella corrodens were associated with AP, LJP and RPP patients. The other bacterial species, including Actinomyces spp., Streptococcus spp. and Eubacterium spp., were detected at different levels in the three disease groups. The data show the complexity of the subgingival microbiota associated with different periodontal disease groups, indicating that the detection frequency and levels of recovery of some periodontal pathogens are different in teeth affected by different forms of periodontal disease.

  10. A rapid method for titration of ascovirus infectivity.

    Science.gov (United States)

    Han, Ningning; Chen, Zishu; Wan, Hu; Huang, Guohua; Li, Jianhong; Jin, Byung Rae

    2018-05-01

    Ascoviruses are a recently described family and the traditional plaque assay and end-point PCR assay have been used for their titration. However, these two methods are time-consuming and inaccurate to titrate ascoviruses. In the present study, a quick method for the determination of the titer of ascovirus stocks was developed based on ascovirus-induced apoptosis in infected insect cells. Briefly, cells infected with serial dilutions of virus (10 -2 -10 -10 ) for 24 h were stained with trypan blue. The stained cells were counted, and the percentage of nonviable cells was calculated. The stained cell rate was compared between virus-infected and control cells. The minimum-dilution group that had a significant difference compared with control and the maximum-dilution group that had no significant difference were selected and then compared each well of the two groups with the average stained cell rate of control. The well was marked as positive well if the stained cell rate was higher than the average stained cell rate of control wells; otherwise, the well was marked as negative wells. The percentage of positive wells were calculated according to the number of positive. Subsequently, the virus titer was calculated through the method of Reed and Muench. This novel method is rapid, simple, reproducible, accurate, and less material-consuming and eliminates the subjectivity of the other procedures for titrating ascoviruses. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. [Real-time PCR in rapid diagnosis of Aeromonas hydrophila necrotizing soft tissue infections].

    Science.gov (United States)

    Kohayagawa, Yoshitaka; Izumi, Yoko; Ushita, Misuzu; Niinou, Norio; Koshizaki, Masayuki; Yamamori, Yuji; Kaneko, Sakae; Fukushima, Hiroshi

    2009-11-01

    We report a case of rapidly progressive necrotizing soft tissue infection and sepsis followed by a patient's death. We suspected Vibrio vulnificus infection because the patient's underlying disease was cirrhosis and the course extremely rapid. No microbe had been detected at death. We extracted DNA from a blood culture bottle. SYBR green I real-time PCR was conducted but could not detect V. vulnificus vvh in the DNA sample. Aeromonas hydrophila was cultured and identified in blood and necrotized tissue samples. Real-time PCR was conducted to detect A. hydrophila ahh1, AHCYTOEN and aerA in the DNA sample extracted from the blood culture bottle and an isolated necrotized tissue strain, but only ahh1 was positive. High-mortality in necrotizing soft tissue infections makes it is crucial to quickly detect V. vulnificus and A. hydrophila. We found real-time PCR for vvh, ahh1, AHCYTOEN, and aerA useful in detecting V. vulnificus and A. hydrophila in necrotizing soft tissue infections.

  12. Progress on high-performance rapid prototype aluminum mirrors

    Science.gov (United States)

    Woodard, Kenneth S.; Myrick, Bruce H.

    2017-05-01

    Near net shape parts can be produced using some very old processes (investment casting) and the relatively new direct metal laser sintering (DMLS) process. These processes have significant advantages for complex blank lightweighting and costs but are not inherently suited for producing high performance mirrors. The DMLS process can provide extremely complex lightweight structures but the high residual stresses left in the material results in unstable mirror figure retention. Although not to the extreme intricacy of DMLS, investment casting can also provide complex lightweight structures at considerably lower costs than DMLS and even conventional wrought mirror blanks but the less than 100% density for casting (and also DMLS) limits finishing quality. This paper will cover the progress that has been made to make both the DMLS and investment casting processes into viable near net shape blank options for high performance aluminum mirrors. Finish and figure results will be presented to show performance commensurate with existing conventional processes.

  13. Predictors of disease progression in HIV infection: a review

    Directory of Open Access Journals (Sweden)

    Ananworanich Jintanat

    2007-05-01

    Full Text Available Abstract During the extended clinically latent period associated with Human Immunodeficiency Virus (HIV infection the virus itself is far from latent. This phase of infection generally comes to an end with the development of symptomatic illness. Understanding the factors affecting disease progression can aid treatment commencement and therapeutic monitoring decisions. An example of this is the clear utility of CD4+ T-cell count and HIV-RNA for disease stage and progression assessment. Elements of the immune response such as the diversity of HIV-specific cytotoxic lymphocyte responses and cell-surface CD38 expression correlate significantly with the control of viral replication. However, the relationship between soluble markers of immune activation and disease progression remains inconclusive. In patients on treatment, sustained virological rebound to >10 000 copies/mL is associated with poor clinical outcome. However, the same is not true of transient elevations of HIV RNA (blips. Another virological factor, drug resistance, is becoming a growing problem around the globe and monitoring must play a part in the surveillance and control of the epidemic worldwide. The links between chemokine receptor tropism and rate of disease progression remain uncertain and the clinical utility of monitoring viral strain is yet to be determined. The large number of confounding factors has made investigation of the roles of race and viral subtype difficult, and further research is needed to elucidate their significance. Host factors such as age, HLA and CYP polymorphisms and psychosocial factors remain important, though often unalterable, predictors of disease progression. Although gender and mode of transmission have a lesser role in disease progression, they may impact other markers such as viral load. Finally, readily measurable markers of disease such as total lymphocyte count, haemoglobin, body mass index and delayed type hypersensitivity may come into favour

  14. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons

    DEFF Research Database (Denmark)

    Kamara, David A; Nielsen, Lene Ryom; Ross, Michael

    2014-01-01

    No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90ml/min/1.73m2 (using Cockcroft Gault) in the Data...

  15. Rapid Molecular Microbiologic Diagnosis of Prosthetic Joint Infection

    Science.gov (United States)

    Cazanave, Charles; Greenwood-Quaintance, Kerryl E.; Hanssen, Arlen D.; Karau, Melissa J.; Schmidt, Suzannah M.; Gomez Urena, Eric O.; Mandrekar, Jayawant N.; Osmon, Douglas R.; Lough, Lindsay E.; Pritt, Bobbi S.; Steckelberg, James M.

    2013-01-01

    We previously showed that culture of samples obtained by prosthesis vortexing and sonication was more sensitive than tissue culture for prosthetic joint infection (PJI) diagnosis. Despite improved sensitivity, culture-negative cases remained; furthermore, culture has a long turnaround time. We designed a genus-/group-specific rapid PCR assay panel targeting PJI bacteria and applied it to samples obtained by vortexing and sonicating explanted hip and knee prostheses, and we compared the results to those with sonicate fluid and periprosthetic tissue culture obtained at revision or resection arthroplasty. We studied 434 subjects with knee (n = 272) or hip (n = 162) prostheses; using a standardized definition, 144 had PJI. Sensitivities of tissue culture, of sonicate fluid culture, and of PCR were 70.1, 72.9, and 77.1%, respectively. Specificities were 97.9, 98.3, and 97.9%, respectively. Sonicate fluid PCR was more sensitive than tissue culture (P = 0.04). PCR of prosthesis sonication samples is more sensitive than tissue culture for the microbiologic diagnosis of prosthetic hip and knee infection and provides same-day PJI diagnosis with definition of microbiology. The high assay specificity suggests that typical PJI bacteria may not cause aseptic implant failure. PMID:23658273

  16. Rapidly-growing mycobacterial infection: a recognized cause of early-onset prosthetic joint infection.

    Science.gov (United States)

    Jitmuang, Anupop; Yuenyongviwat, Varah; Charoencholvanich, Keerati; Chayakulkeeree, Methee

    2017-12-28

    Prosthetic joint infection (PJI) is a major complication of total hip and total knee arthroplasty (THA, TKA). Although mycobacteria are rarely the causative pathogens, it is important to recognize and treat them differently from non-mycobacterial infections. This study aimed to compare the clinical characteristics, associated factors and long-term outcomes of mycobacterial and non-mycobacterial PJI. We conducted a retrospective case-control study of patients aged ≥18 years who were diagnosed with PJI of the hip or knee at Siriraj Hospital from January 2000 to December 2012. Patient characteristics, clinical data, treatments and outcomes were evaluated. A total of 178 patients were included, among whom 162 had non-mycobacterial PJI and 16 had mycobacterial PJI. Rapidly growing mycobacteria (RGM) (11) and M. tuberculosis (MTB) (5) were the causative pathogens of mycobacterial PJI. PJI duration and time until onset were significantly different between mycobacterial and non-mycobacterial PJI. Infection within 90 days of arthroplasty was significantly associated with RGM infection (OR 21.86; 95% CI 4.25-112.30; p infection. RGM were the major pathogens of early onset PJI after THA and TKA. Both a high clinical index of suspicion and mycobacterial cultures are recommended when medically managing PJI with negative cultures or non-response to antibiotics. Removal of infected implants was associated with favorable outcomes.

  17. Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

    Directory of Open Access Journals (Sweden)

    James R Roede

    Full Text Available Progression of Parkinson's disease (PD is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

  18. Serum metabolomics of slow vs. rapid motor progression Parkinson's disease: a pilot study.

    Science.gov (United States)

    Roede, James R; Uppal, Karan; Park, Youngja; Lee, Kichun; Tran, Vilinh; Walker, Douglas; Strobel, Frederick H; Rhodes, Shannon L; Ritz, Beate; Jones, Dean P

    2013-01-01

    Progression of Parkinson's disease (PD) is highly variable, indicating that differences between slow and rapid progression forms could provide valuable information for improved early detection and management. Unfortunately, this represents a complex problem due to the heterogeneous nature of humans in regards to demographic characteristics, genetics, diet, environmental exposures and health behaviors. In this pilot study, we employed high resolution mass spectrometry-based metabolic profiling to investigate the metabolic signatures of slow versus rapidly progressing PD present in human serum. Archival serum samples from PD patients obtained within 3 years of disease onset were analyzed via dual chromatography-high resolution mass spectrometry, with data extraction by xMSanalyzer and used to predict rapid or slow motor progression of these patients during follow-up. Statistical analyses, such as false discovery rate analysis and partial least squares discriminant analysis, yielded a list of statistically significant metabolic features and further investigation revealed potential biomarkers. In particular, N8-acetyl spermidine was found to be significantly elevated in the rapid progressors compared to both control subjects and slow progressors. Our exploratory data indicate that a fast motor progression disease phenotype can be distinguished early in disease using high resolution mass spectrometry-based metabolic profiling and that altered polyamine metabolism may be a predictive marker of rapidly progressing PD.

  19. Progress toward Development of a Vaccine against Congenital Cytomegalovirus Infection

    Science.gov (United States)

    Permar, Sallie R.; Plotkin, Stanley A.

    2017-01-01

    ABSTRACT A vaccine against congenital human cytomegalovirus (CMV) infection is a major public health priority. Congenital CMV causes substantial long-term morbidity, particularly sensorineural hearing loss (SNHL), in newborns, and the public health impact of this infection on maternal and child health is underrecognized. Although progress toward development of a vaccine has been limited by an incomplete understanding of the correlates of protective immunity for the fetus, knowledge about some of the key components of the maternal immune response necessary for preventing transplacental transmission is accumulating. Moreover, although there have been concerns raised about observations indicating that maternal seropositivity does not fully prevent recurrent maternal CMV infections during pregnancy, it is becoming increasing clear that preconception immunity does confer some measure of protection against both CMV transmission and CMV disease (if transmission occurs) in the newborn infant. Although the immunity to CMV conferred by both infection and vaccination is imperfect, there are encouraging data emerging from clinical trials demonstrating the immunogenicity and potential efficacy of candidate CMV vaccines. In the face of the knowledge that between 20,000 and 30,000 infants are born with congenital CMV in the United States every year, there is an urgent and compelling need to accelerate the pace of vaccine trials. In this minireview, we summarize the status of CMV vaccines in clinical trials and provide a perspective on what would be required for a CMV immunization program to become incorporated into clinical practice. PMID:29046308

  20. Estimating progression rates for human papillomavirus infection from epidemiological data.

    Science.gov (United States)

    Jit, Mark; Gay, Nigel; Soldan, Kate; Hong Choi, Yoon; Edmunds, William John

    2010-01-01

    A Markov model was constructed in order to estimate type-specific rates of cervical lesion progression and regression in women with high-risk human papillomavirus (HPV). The model was fitted to age- and type-specific data regarding the HPV DNA and cytological status of women undergoing cervical screening in a recent screening trial, as well as cervical cancer incidence. It incorporates different assumptions about the way lesions regress, the accuracy of cytological screening, the specificity of HPV DNA testing, and the age-specific prevalence of HPV infection. Combinations of assumptions generate 162 scenarios for squamous cell carcinomas and 54 scenarios for adenocarcinomas. Simulating an unscreened cohort of women infected with high-risk HPV indicates that the probability of an infection continuing to persist and to develop into invasive cancer depends on the length of time it has already persisted. The scenarios and parameter sets that produce the best fit to available epidemiological data provide a basis for modeling the natural history of HPV infection and disease.

  1. Rapid progression of gliomatosis cerebri to secondary glioblastoma, factors that affects the progression rate: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hee Kyung; Yu, In Kyu; Kim, Seung Min; Kim, Joo Heon; Lee, Seung Hoon; Lee, Seung Yeon [Eulji University Hospital, Daejeon (Korea, Republic of)

    2017-03-15

    Glioblastomas may develop de novo or through progression from low-grade or anaplastic astrocytomas. The term 'primary glioblastoma' refers to a glioblastoma that lacks a precursor lesion and has a clinical history of less than three months. On the other hand, the term 'secondary glioblastoma' indicates that the glioblastoma has progressed from a low-grade tumor after a long latency period and often manifests in younger patients. These subtypes of glioblastoma develop via different genetic pathways, and they differ in prognosis and response to therapy. Thus, differential diagnosis of these subtypes and prediction of the factors that affect the progression from low-grade diffuse astrocytoma to secondary glioblastoma would be clinically very important. We present a rare case of secondary glioblastoma, which developed only three months after the follow up imaging evaluations, with a history of low grade glioma, and present the factors that cause rapid progression.

  2. Rapidly Progressive Osteoarthritis: a Review of the Clinical and Radiologic Presentation.

    Science.gov (United States)

    Flemming, Donald J; Gustas-French, Cristy N

    2017-07-01

    The purpose of this paper is to review the distinct clinical and radiographic features that may lead to prompt diagnosis of rapidly progressive osteoarthritis (RPOA) and thus obviate unnecessary and costly diagnostic workup. RPOA is uncommon but is more frequently seen in practice because of the aging population. RPOA is a destructive arthropathy that occurs most commonly in elderly women but can also be seen in patients that have sustained trauma. The dramatic radiologic manifestations of RPOA can lead to diagnostic confusion with other arthropathies, infection, and osteonecrosis. RPOA was originally described in the hip but may also involve the shoulder. The etiology of RPOA is not well understood, but subchondral fracture probably plays a role in the development of dramatic destruction of the joint that is seen in affected patients. Early diagnosis may reduce the complexity of surgical management. RPOA is an uncommon condition that occurs most frequently in elderly woman or in patients who have sustained trauma. Prompt recognition of the clinical and radiologic features of this arthropathy can reduce unnecessary diagnostic workup and complexity of surgical intervention.

  3. Temporal progression of 'Candidatus Liberibacter asiaticus' infection in citrus and acquisition efficiency by Diaphorina citri.

    Science.gov (United States)

    Coletta-Filho, Helvecio D; Daugherty, Matthew P; Ferreira, Cléderson; Lopes, João R S

    2014-04-01

    Over the last decade, the plant disease huanglongbing (HLB) has emerged as a primary threat to citrus production worldwide. HLB is associated with infection by phloem-limited bacteria ('Candidatus Liberibacter' spp.) that are transmitted by the Asian citrus psyllid, Diaphorina citri. Transmission efficiency varies with vector-related aspects (e.g., developmental stage and feeding periods) but there is no information on the effects of host-pathogen interactions. Here, acquisition efficiency of 'Candidatus Liberibacter asiaticus' by D. citri was evaluated in relation to temporal progression of infection and pathogen titer in citrus. We graft inoculated sweet orange trees with 'Ca. L. asiaticus'; then, at different times after inoculation, we inspected plants for HLB symptoms, measured bacterial infection levels (i.e., titer or concentration) in plants, and measured acquisition by psyllid adults that were confined on the trees. Plant infection levels increased rapidly over time, saturating at uniformly high levels (≈10(8) copy number of 16S ribosomal DNA/g of plant tissue) near 200 days after inoculation-the same time at which all infected trees first showed disease symptoms. Pathogen acquisition by vectors was positively associated with plant infection level and time since inoculation, with acquisition occurring as early as the first measurement, at 60 days after inoculation. These results suggest that there is ample potential for psyllids to acquire the pathogen from trees during the asymptomatic phase of infection. If so, this could limit the effectiveness of tree rouging as a disease management tool and would likely explain the rapid spread observed for this disease in the field.

  4. Association between Hlaantigens and Progression of HIV Infection in Greek Haemophiliacs

    Directory of Open Access Journals (Sweden)

    Chr. Papasteriades

    1993-01-01

    Full Text Available The frequencies of HLA antigens in 33 HIV seronegative and in 88 HIV seropositive haemophiliacs, who have been followed for at least 6 years since seroconversion or first HIV positive test. were evaluated in relation to disease susceptibility and disease progression. A high frequency of HLA-A2 and -DR2 antigens and a low frequency of HLA-A9 were found to characterize HIV seropositive patients (p<0.05. Progressors to symptomatic CDC stage IV had a higher frequency of HLA-A9 (p<0.01 and DR3. Rapid decline of CD4+ T cells in these patients was associated with HLA-A9, -DR I and DR3. Our data suggest that HLA antigens may contribute to susceptibility to HIV infection and disease progression in Greek haemophiliacs.

  5. Natural Besnoitia besnoiti infections in cattle: chronology of disease progression.

    Science.gov (United States)

    Gollnick, Nicole S; Scharr, Julia C; Schares, Gereon; Langenmayer, Martin C

    2015-02-14

    Bovine besnoitiosis is an emerging protozoan disease in cattle. Neither vaccines nor chemotherapeutic drugs are currently available for prevention and treatment of Besnoitia besnoiti infections. Therefore the implementation of appropriate disease management strategies is of utmost importance. The aim of this longitudinal study was to complement current knowledge on the chronology of disease progression. This was realized by correlating clinical findings in early stages of naturally acquired bovine besnoitiosis with results of real-time PCR of skin biopsies and of two western immunoblots and an immunofluorescent antibody test (IFAT). Animals for this study were obtained by i) closely monitoring a cow-calf operation with a high prevalence of bovine besnoitiosis for cases of acute disease, and by ii) conducting a 12-week cohabitation experiment on pasture with five healthy heifers, a healthy bull and five B. besnoiti infected cows. A control group of six healthy heifers was kept at a minimal distance of 20 m. Further, the spectrum of potential insect vectors was determined. Infected cattle were followed up to a maximum of 221 days after first detection of B. besnoiti antibodies. Two severely affected cows developed visible and palpable alterations of skin, a decrease in body condition despite good feed intake, and chronic bovine besnoitiosis-associated laminitis leading to non-healing sole ulcers. The cows also had high reciprocal IFAT titers and high loads of parasite DNA in skin samples. Two heifers developed a mild clinical course characterized by few parasitic cysts visible in the scleral conjunctivae and vestibula vaginae. Both heifers became infected during the time of high insect activity of the species Musca domestica, Musca autumnalis, Haematobia irritans, and Stomoxys calcitrans. When a third heifer became subclinically infected, low insect activity was recorded. None of the six control heifers contracted a B. besnoiti infection. In chronic besnoitiosis

  6. Host genetic risk factors for West Nile virus infection and disease progression.

    Directory of Open Access Journals (Sweden)

    Abigail W Bigham

    Full Text Available West Nile virus (WNV, a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune function in 753 individuals infected with WNV including: 422 symptomatic WNV cases and 331 cases with asymptomatic infections. After applying a Bonferroni correction for multiple tests and controlling for population stratification, SNPs in IRF3 (OR 0.54, p = 0.035 and MX1, (OR 0.19, p = 0.014 were associated with symptomatic WNV infection and a single SNP in OAS1 (OR 9.79, p = 0.003 was associated with increased risk for West Nile encephalitis and paralysis (WNE/P. Together, these results suggest that genetic variation in the interferon response pathway is associated with both risk for symptomatic WNV infection and WNV disease progression.

  7. Recombinase Polymerase Amplification Assay for Rapid Diagnostics of Dengue Infection.

    Directory of Open Access Journals (Sweden)

    Ahmed Abd El Wahed

    Full Text Available Over 2.5 billion people are exposed to the risk of contracting dengue fever (DF. Early diagnosis of DF helps to diminish its burden on public health. Real-time reverse transcription polymerase amplification assays (RT-PCR are the standard method for molecular detection of the dengue virus (DENV. Real-time RT-PCR analysis is not suitable for on-site screening since mobile devices are large, expensive, and complex. In this study, two RT-recombinase polymerase amplification (RT-RPA assays were developed to detect DENV1-4.Using two quantitative RNA molecular standards, the analytical sensitivity of a RT-RPA targeting the 3´non-translated region of DENV1-4 was found to range from 14 (DENV4 to 241 (DENV1-3 RNA molecules detected. The assay was specific and did not cross detect other Flaviviruses. The RT-RPA assay was tested in a mobile laboratory combining magnetic-bead based total nucleic acid extraction and a portable detection device in Kedougou (Senegal and in Bangkok (Thailand. In Kedougou, the RT-RPA was operated at an ambient temperature of 38 °C with auxiliary electricity tapped from a motor vehicle and yielded a clinical sensitivity and specificity of 98% (n=31 and 100% (n=23, respectively. While in the field trial in Bangkok, the clinical sensitivity and specificity were 72% (n=90 and 100%(n=41, respectively.During the first 5 days of infection, the developed DENV1-4 RT-RPA assays constitute a suitable accurate and rapid assay for DENV diagnosis. Moreover, the use of a portable fluorescence-reading device broadens its application potential to the point-of-care for outbreak investigations.

  8. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Directory of Open Access Journals (Sweden)

    Bruno Scarpellini

    Full Text Available We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR, before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment.Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD] was detected.Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  9. Plasma Metabolomics Biosignature According to HIV Stage of Infection, Pace of Disease Progression, Viremia Level and Immunological Response to Treatment.

    Science.gov (United States)

    Scarpellini, Bruno; Zanoni, Michelle; Sucupira, Maria Cecilia Araripe; Truong, Hong-Ha M; Janini, Luiz Mario Ramos; Segurado, Ismael Dale Cotrin; Diaz, Ricardo Sobhie

    2016-01-01

    We evaluated plasma samples HIV-infected individuals with different phenotypic profile among five HIV-infected elite controllers and five rapid progressors after recent HIV infection and one year later and from 10 individuals subjected to antiretroviral therapy, five of whom were immunological non-responders (INR), before and after one year of antiretroviral treatment compared to 175 samples from HIV-negative patients. A targeted quantitative tandem mass spectrometry metabolomics approach was used in order to determine plasma metabolomics biosignature that may relate to HIV infection, pace of HIV disease progression, and immunological response to treatment. Twenty-five unique metabolites were identified, including five metabolites that could distinguish rapid progressors and INRs at baseline. Severe deregulation in acylcarnitine and sphingomyelin metabolism compatible with mitochondrial deficiencies was observed. β-oxidation and sphingosine-1-phosphate-phosphatase-1 activity were down-regulated, whereas acyl-alkyl-containing phosphatidylcholines and alkylglyceronephosphate synthase levels were elevated in INRs. Evidence that elite controllers harbor an inborn error of metabolism (late-onset multiple acyl-coenzyme A dehydrogenase deficiency [MADD]) was detected. Blood-based markers from metabolomics show a very high accuracy of discriminating HIV infection between varieties of controls and have the ability to predict rapid disease progression or poor antiretroviral immunological response. These metabolites can be used as biomarkers of HIV natural evolution or treatment response and provide insight into the mechanisms of the disease.

  10. [Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review].

    Science.gov (United States)

    Liang, Y; Wei, H; Yu, X; Huang, W; Luo, X P

    2017-02-02

    Objective: To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty. Method: A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" . Result: The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (heightTurner syndrome is reported. Although short stature and ovarian dysgenesis are common in TS, precocious puberty may occur in TS, which is liable to cause delayed diagnosis and misdiagnosis. Careful examination is recommended for patients with unusual growth pattern, even though girls have normal height in accord with standard growth curve or spontaneous puberty. Evaluation for TS and subsequent investigation should be prompted.

  11. Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus

    Science.gov (United States)

    Hughes, Joseph; Biek, Roman; Litster, Annette; Willett, Brian J.; Hosie, Margaret J.

    2015-01-01

    Analysing the evolution of feline immunodeficiency virus (FIV) at the intra-host level is important in order to address whether the diversity and composition of viral quasispecies affect disease progression. We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at a rate of 1.16×10−3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3–V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3–V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation. Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximum evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared with human immunodeficiency virus might explain why many naturally infected cats do not progress rapidly to AIDS. PMID:25535323

  12. Covertly active and progressing neurochemical abnormalities in suppressed HIV infection.

    Science.gov (United States)

    Cysique, Lucette A; Jugé, Lauriane; Gates, Thomas; Tobia, Michael; Moffat, Kirsten; Brew, Bruce J; Rae, Caroline

    2018-01-01

    To assess whether HIV-related brain injury is progressive in persons with suppressed HIV infection. Seventy-three HIV+ virally suppressed men and 35 HIV- men, screened for psychiatric and alcohol/drug use disorders, underwent neuropsychological evaluation and proton magnetic resonance spectroscopy ( 1 H-MRS) at baseline and after and 23 ± 5 months. 1 H-MRS included brain regions known to be vulnerable to HIV and aging: frontal white matter (FWM), posterior cingulate cortex (PCC), and caudate area (CA). Major brain metabolites such as creatine (Cr: marker of cellular energy), N -acetyl aspartate (NAA: marker of neuronal integrity), choline (marker of cellular membrane turnover), glutamate/glutamine (excitatory/inhibitory neurotransmitter), and myo -Inositol (mI: marker of neuroinflammation) were calculated with reference to water signal. Neurocognitive decline was corrected for practice effect and baseline HIV-associated neurocognitive disorder (HAND) status. Across the study period, 44% had intact cognition, 42% stable HAND (including the single case that improved), 10% progressing HAND, and 4% incident HAND. When analyzing the neurochemical data per neurocognitive trajectories, we found decreasing PCC Cr in all subgroups compared with controls ( p < 0.002). In addition, relative to the HIV- group, stable HAND showed decreasing FWM Cr, incident HAND showed steep FWM Cr reduction, whereas progressing HAND had a sharply decreasing PCC NAA and reduced but stable CA NAA. When analyzing the neurochemical data at the group level (HIV+ vs HIV- groups), we found stable abnormal metabolite concentrations over the study period: decreased FWM and PCC Cr (both p < 0.001), decreased PCC NAA and CA NAA (both p < 0.05) and PCC mI increase ( p < 0.05). HIV duration and historical HAND had modest effects on metabolite changes. Our study reveals covertly active or progressing HIV-related brain injury in the majority of this virally suppressed cohort, reflecting ongoing

  13. Lethal Nipah virus infection induces rapid overexpression of CXCL10.

    Directory of Open Access Journals (Sweden)

    Cyrille Mathieu

    Full Text Available Nipah virus (NiV is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10, an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.

  14. Clinicopathological Correlates in a PRNP P102L Mutation Carrier with Rapidly Progressing Parkinsonism-dystonia

    Science.gov (United States)

    Umeh, Chizoba C.; Kalakoti, Piyush; Greenberg, Michael K; Notari, Silvio; Cohen, Yvonne; Gambetti, Pierluigi; Oblak, Adrian L.; Ghetti, Bernardino; Mari, Zoltan

    2015-01-01

    Parkinsonism-dystonia is rare in carriers of PRNP P102L mutation. Severity and distribution of prion protein (PrP) deposition may influence the clinical presentation. We present such clinic-pathological correlation in a 56-year-old male with a PRNP P102L mutation associated with a phenotype characterized by rapidly progressing parkinsonism-dystonia. The patient was studied clinically (videotaped exams, brain MRIs); molecular genetically (gene sequence analysis); and neuropathologically (histology, immunohistochemistry) during his 7-month disease course. The patient had parkinsonism, apraxia, aphasia, and dystonia, which progressed rapidly. Molecular genetic analysis revealed PRNP P102L mutation carrier status. Brain MRIs revealed progressive global volume loss and T2/FLAIR hyperintensity in neocortex and basal ganglia. Postmortem examination showed neuronal loss, gliosis, spongiform changes, and PrP deposition in the striatum. PrP immunohistochemistry revealed widespread severe PrP deposition in the thalamus and cerebellar cortex. Based on the neuropathological and molecular-genetic analysis, the rapidly progressing parkinsonism-dystonia correlated with nigrostriatal, thalamic, and cerebellar pathology. PMID:27617269

  15. Successful autologous hematopoietic stem cell transplantation for a patient with rapidly progressive localized scleroderma.

    Science.gov (United States)

    Nair, Velu; Sharma, Ajay; Sharma, Sanjeevan; Das, Satyaranjan; Bhakuni, Darshan S; Narayanan, Krishnan; Nair, Vivek; Shankar, Subramanian

    2015-03-01

    Autologous hematopoietic stem cell transplant (HSCT) for rapidly progressive disease has not been reported in localized scleroderma. Our patient, a 16-year-old girl had an aggressive variant of localized scleroderma, mixed subtype (linear-generalized) with Parry Romberg syndrome, with no internal organ involvement, that was unresponsive to immunosuppressive therapy and was causing rapid disfigurement. She was administered autologous HSCT in June 2011 and has maintained drug-free remission with excellent functional status at almost 3.5 years of follow-up. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

  16. Unilaterally and rapidly progressing white matter lesion and elevated cytokines in a patient with Tay-Sachs disease.

    Science.gov (United States)

    Hayase, Tomomi; Shimizu, Jun; Goto, Tamako; Nozaki, Yasuyuki; Mori, Masato; Takahashi, Naoto; Namba, Eiji; Yamagata, Takanori; Momoi, Mariko Y

    2010-03-01

    We report the case of a girl with Tay-Sachs disease who had convulsions and deteriorated rapidly after an upper respiratory infection at the age of 11 months. At the age of 16 months, her seizures became intractable and magnetic resonance imaging of the brain showed high signal intensity on T2-weighted images and marked swelling in the white matter and basal nucelei of the right hemisphere. Her seizures and right hemisphere lesion improved with glycerol and dexamethasone treatment. When dexamethasone was discontinued, her symptoms worsened and lesions later appeared in the left hemisphere. Her cerebrospinal fluid showed elevated levels of the cytokines TNF-alpha and IL-5. It is considered that inflammation contributes to disease progression in Tay-Sachs disease.

  17. Rapid and sensitive detection of potyvirus infecting tropical tuber ...

    African Journals Online (AJOL)

    A reverse transcription polymerase chain reaction assay using potyvirus specific primers designed from the core of the coat protein was carried out, and a cDNA fragment of 327 bp was obtained from most of the potyviruses infecting the tropical tuber crops. Reverse transcription polymerase chain reaction (RT-PCR) ...

  18. Chemokines and Chemokine Receptors in Susceptibility to HIV-1 Infection and Progression to AIDS

    Directory of Open Access Journals (Sweden)

    Animesh Chatterjee

    2012-01-01

    Full Text Available A multitude of host genetic factors plays a crucial role in susceptibility to HIV-1 infection and progression to AIDS, which is highly variable among individuals and populations. This review focuses on the chemokine-receptor and chemokine genes, which were extensively studied because of their role as HIV co-receptor or co-receptor competitor and influences the susceptibility to HIV-1 infection and progression to AIDS in HIV-1 infected individuals.

  19. Emerging Zika Virus Infection: A Rapidly Evolving Situation.

    Science.gov (United States)

    Bordi, Licia; Avsic-Zupanc, Tatjana; Lalle, Eleonora; Vairo, Francesco; Capobianchi, Maria Rosaria; da Costa Vasconcelos, Pedro Fernando

    2017-01-01

    Zika virus is a mosquito-borne flavivirus, firstly identified in Uganda and responsible for sporadic human cases in Africa and Asia until recently, when large outbreak occurred in Pacific Ocean and the Americas. Since the main vectors during its spread outside of Africa have been Ae. albopictus and Ae. aegypti mosquitoes, which are widely distributed all over the world, there is urgent need for a coordinated response for prevention and spread of ZIKV epidemics.Despite clinical manifestation of Zika virus infection are usually mild and self limiting, there are reports suggesting, during the recent epidemic, an association of ZIKV infection with severe consequences, including fetal/newborn microcephaly, due to vertical in utero transmission, autoimmune-neurological presentations including cranial nerve dysfunction, and Guillain-Barré Syndrome in adults. The primary mode of transmission of Zika virus between humans is through the bite of an infected female mosquito of the Aedes genus, but also sexual and blood transfusion transmission may occur. Moreover, a case of non-sexual spread from one person to another has been described, indicating that we still have more to learn about Zika transmission.Biological basis for pathogenetic effects are under investigation. Laboratory diagnosis is challenging since, so far, there are no "gold standard" diagnostic tools, and the low and short viremia in the acute phase, and together with the high cross-reactivity among the members of flavivirus genus are the most challenging aspects to be overcome.

  20. Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum).

    Science.gov (United States)

    Kocan, R; Hershberger, P; Sanders, G; Winton, J

    2009-10-01

    Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 degrees C, 15 degrees C and 20 degrees C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean-day-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 degrees C for 16 weeks then subjected to forced swimming at 10 degrees C, 15 degrees C and 20 degrees C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 degrees C (P = 0.02) and highly significant at 20 degrees C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas.

  1. Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum)

    Science.gov (United States)

    Kocan, R.; Hershberger, P.; Sanders, G.; Winton, J.

    2009-01-01

    Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 ??C, 15 ??C and 20 ??C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced mean-day-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 ??C for 16 weeks then subjected to forced swimming at 10 ??C, 15 ??C and 20 ??C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 ??C (P = 0.02) and highly significant at 20 ??C (P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas. ?? 2009 Blackwell Publishing Ltd.

  2. The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections

    DEFF Research Database (Denmark)

    Williams, John E; Cairns, Matthew; Njie, Fanta

    2016-01-01

    BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern.METHODS: Primigravidae and secu......BACKGROUND: Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern.METHODS: Primigravidae...... in 540 women; these were not associated with maternal anemia, placental malaria, or low birth weight. CONCLUSIONS: The sensitivity of an RDT to detect malaria in primigravidae and secundigravidae was high at enrollment in 3 of 4 countries and, in Ghana, at subsequent ANC visits. In Ghana, RDT negative...... malaria infections were not associated with adverse birth outcomes but missed infections were uncommon....

  3. [Autopsy case of Lissauer's general paresis with rapidly progressive left hemiparesis].

    Science.gov (United States)

    Kato, Hiroko; Yoshida, Mari; Ando, Tetsuo; Sugiura, Makoto; Hashizume, Yoshio

    2009-06-01

    A 48-years-old man presented with slowly progressive bradykinesia, personality change and rapidly progressive left hemiparesis. On admission, he presented dementia, poor judgment, left hemiparesis. MRI revealed a widespread high intensity area in right hemisphere and MRA was almost normal. Serological tests of serum and CSF demonstrated high titers of antibodies to Treponema pallidum. He was treated for syphilis with daily penicillin injections without improvement. He died of sepsis eight months after admission. At autopsy, the brain weighed 1,100 g and the right cerebral hemisphere was atrophic, especially in frontal base, temporal, parietal, angular, and posterior regions covered by thickened, fibrotic leptomeninges. Microscopically, chronic meningoencephalitis was observed. Severe neuronal loss with gliosis was seen in the right cerebral cortices. Scattered rod-shaped microglia and inflammatory cell infiltration were visible in the cerebral parenchyma. The dorsal column of the spinal cord was not involved and meningovascular syphilis was unclear. The distribution of the encephalitic lesions was well correlated with the clinical and neuroradiological findings. This was a rare autopsy case presenting Lissauer's general paresis, clinically manifesting as rapidly progressive stroke-like episode.

  4. Research progress on the pathogenesis of rapid eye movement sleep behavior disorder and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Hai-yang JIANG

    2017-10-01

    Full Text Available Rapid eye movement sleep behavior disorder (RBD is a sleep disorder characterized by the disappearance of muscle relaxation and enacting one's dreams during rapid eye movement (REM, with most of the dreams being violent or aggressive. Prevalence of RBD, based on population, is 0.38%-2.01%, but it becomes much higher in patients with neurodegenerative diseases, especially α - synucleinopathies. RBD may herald the emergence of α-synucleinopathies by decades, thus it may be used as an effective early marker of neurodegenerative diseases. In this review, we summarized the progress on the pathogenesis of RBD and its relationship with neurodegenerative diseases. DOI: 10.3969/j.issn.1672-6731.2017.10.003

  5. Plasmablastic myeloma presenting as rapidly progressive renal failure in a young adult

    Directory of Open Access Journals (Sweden)

    M Srija

    2014-01-01

    Full Text Available Multiple myeloma (MM is a condition where there is malignant proliferation of plasma cells. There is a strong correlation with age, peaking at 60-70 years. The clinical course in adolescents and young individuals is generally indolent and the survival is longer. We report a case of a 28-year-old male, who was diagnosed to have plasmablastic myeloma, an atypical variant of MM with a poor prognosis, presenting as rapidly progressive renal failure. He was given induction chemotherapy and then underwent autologous peripheral blood stem cell transplantation.

  6. The Performance of a Rapid Diagnostic Test in Detecting Malaria Infection in Pregnant Women and the Impact of Missed Infections

    NARCIS (Netherlands)

    Williams, John E.; Cairns, Matthew; Njie, Fanta; Laryea Quaye, Stephen; Awine, Timothy; Oduro, Abraham; Tagbor, Harry; Bojang, Kalifa; Magnussen, Pascal; ter Kuile, Feiko O.; Woukeu, Arouna; Milligan, Paul; Chandramohan, Daniel; Greenwood, Brian

    2016-01-01

    Intermittent screening and treatment in pregnancy (ISTp) is a potential strategy for the control of malaria during pregnancy. However, the frequency and consequences of malaria infections missed by a rapid diagnostic test (RDT) for malaria are a concern. Primigravidae and secundigravidae who

  7. [Outcome of rapidly progressive glomerulonephritis post-streptococcal disease in children].

    Science.gov (United States)

    Jellouli, Manel; Maghraoui, Sondos; Abidi, Kamel; Hammi, Yosra; Goucha, Rim; Naija, Ouns; Zarrouk, Chokri; Gargah, Tahar

    2015-11-01

    Rapidly progressive glomerulonephritis is a rare form of postinfectious glomerulonephritis. The aim of this study was to describe the outcome of our patients with severe post-streptococcal glomerulonephritis. This retrospective study was conducted in the department of pediatrics in Charles-Nicolle Hospital during a period of 13 years (1997-2009). Twenty-seven children were identified. The mean age was 8.7 years. All patients presented renal failure at presentation. The mean serum creatinine at presentation was 376.9 μmol/L. Six patients presented nephrotic syndrome. Twenty-six children had renal biopsies. Renal biopsies showed crescents in 24 cases. Eighteen children received pulse dose of corticosteroids (66.6%) and 6 children (22%) received pulse dose of corticosteroids and cyclophosphamide. Eleven patients required dialysis. At last follow-up, 22 patients (81.5%) had normal kidney function, 2 had renal dysfunction and 3 reached end stage renal disease. The only significant determinant for renal survival was the supportive dialysis (P=0.015). Rapidly progressive glomerulonephritis is uncommon. There have been significant advancements in supportive, as well as specific therapy, but the outcome continues to be poor. Copyright © 2015 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  8. Poorly differentiated ductal adenocarcinoma of the pancreas with rapid progression in a young man.

    Science.gov (United States)

    Tezuka, Koji; Ishiyama, Tomoharu; Takeshita, Akiko; Matsumoto, Hidekazu; Jingu, Akira; Kikuchi, Jiro; Yamaya, Hideyuki; Ohe, Rintaro; Ishizawa, Tetsuya

    2018-04-16

    Pancreatic cancer in young adults is very rare. We report a case of young-onset poorly differentiated pancreatic ductal adenocarcinoma with rapid progression and poor prognosis in a 31-year-old Japanese man with no obvious family history of malignancy. Preoperative examinations revealed a mass lesion in the body of the pancreas, accompanied by a slightly dilated main pancreatic duct distal to the mass lesion. Pancreatic cancer with acute pancreatitis was suspected because of an elevation of serum pancreatic enzyme and tumor marker, along with imaging findings. Distal pancreatectomy with resection of the common hepatic artery and splenectomy along with lymph node dissection was performed. Microscopically, the tumor was mainly composed of poorly differentiated ductal adenocarcinoma. The postoperative course was uneventful, but the patient had multiple liver metastases 2 months postoperatively, in spite of adjuvant chemotherapy, and died 8 months postoperatively. This case may represent a rare instance of young-onset poorly differentiated ductal adenocarcinoma with rapid progression and may indicate potential risk factors of pancreatic cancer in young adults.

  9. Comprehensive and Methodical: Diagnostic and Management Approaches to Rapidly Progressive Dementia.

    Science.gov (United States)

    Mahajan, Supriya; Appleby, Brian S

    2017-09-30

    Purpose of review The sudden emergence of a change in cognitive abilities or behavior is an important symptom that warrants medical evaluation and may represent the early stages of a rapidly progressive dementia (RPD). To correctly ascertain the cause of RPD in a given patient, the clinician must be methodical and knowledgeable about the range of potential causes and must move forward with supportive treatment, and in some cases empiric treatment, based on clinical features alone. Recent findings Significant advances in prion disease biomarkers, the molecular features of rapidly progressive Alzheimer's disease, and new detection of autoimmune limbic encephalitis disease entities have caused a shift in the diagnostic and treatment framework of RPD. Additionally, in the past decade, emerging retrospective data have led to suggested treatments in autoimmune encephalitis that, if instituted early, can protect patients against residual deficits and disease relapse. Summary Here, we provide an integrative clinical and diagnostic treatment approach that is applicable to the various forms of RPD. We have highlighted the clinical features of selected types of RPD that have experienced advances in the last 10-15 years.

  10. P53-mediated rapid induction of apoptosis conveys resistance to viral infection in Drosophila melanogaster.

    Directory of Open Access Journals (Sweden)

    Bo Liu

    2013-02-01

    Full Text Available Arthropod-borne pathogens account for millions of deaths each year. Understanding the genetic mechanisms controlling vector susceptibility to pathogens has profound implications for developing novel strategies for controlling insect-transmitted infectious diseases. The fact that many viruses carry genes that have anti-apoptotic activity has long led to the hypothesis that induction of apoptosis could be a fundamental innate immune response. However, the cellular mechanisms mediating the induction of apoptosis following viral infection remained enigmatic, which has prevented experimental verification of the functional significance of apoptosis in limiting viral infection in insects. In addition, studies with cultured insect cells have shown that there is sometimes a lack of apoptosis, or the pro-apoptotic response happens relatively late, thus casting doubt on the functional significance of apoptosis as an innate immunity. Using in vivo mosquito models and the native route of infection, we found that there is a rapid induction of reaper-like pro-apoptotic genes within a few hours following exposure to DNA or RNA viruses. Recapitulating a similar response in Drosophila, we found that this rapid induction of apoptosis requires the function of P53 and is mediated by a stress-responsive regulatory region upstream of reaper. More importantly, we showed that the rapid induction of apoptosis is responsible for preventing the expression of viral genes and blocking the infection. Genetic changes influencing this rapid induction of reaper-like pro-apoptotic genes led to significant differences in susceptibility to viral infection.

  11. Easy and Rapid Detection of Mumps Virus by Live Fluorescent Visualization of Virus-Infected Cells.

    Directory of Open Access Journals (Sweden)

    Tadanobu Takahashi

    Full Text Available Mumps viruses show diverse cytopathic effects (CPEs of infected cells and viral plaque formation (no CPE or no plaque formation in some cases depending on the viral strain, highlighting the difficulty in mumps laboratory studies. In our previous study, a new sialidase substrate, 2-(benzothiazol-2-yl-4-bromophenyl 5-acetamido-3,5-dideoxy-α-D-glycero-D-galacto-2-nonulopyranosidonic acid (BTP3-Neu5Ac, was developed for visualization of sialidase activity. BTP3-Neu5Ac can easily and rapidly perform histochemical fluorescent visualization of influenza viruses and virus-infected cells without an antiviral antibody and cell fixation. In the present study, the potential utility of BTP3-Neu5Ac for rapid detection of mumps virus was demonstrated. BTP3-Neu5Ac could visualize dot-blotted mumps virus, virus-infected cells, and plaques (plaques should be called focuses due to staining of infected cells in this study, even if a CPE was not observed. Furthermore, virus cultivation was possible by direct pick-up from a fluorescent focus. In conventional methods, visible appearance of the CPE and focuses often requires more than 6 days after infection, but the new method with BTP3-Neu5Ac clearly visualized infected cells after 2 days and focuses after 4 days. The BTP3-Neu5Ac assay is a precise, easy, and rapid assay for confirmation and titration of mumps virus.

  12. Research Progress on Systemic Lupus Erythematosus Complicated with Infection

    Directory of Open Access Journals (Sweden)

    Zhang Weisan

    2015-06-01

    Full Text Available In recent years, in treatment standardization of systemic lupus erythematosus (SLE, infections and serious complications became the leading cause of death related to this disease, exceeding those of renal involvement and lupus encephalopathy. SLE coinfection is mainly related to defects in humoral immunity and cellular immunity, SLE disease activity, and doses of hormone and immune inhibitors.

  13. Progression of experimental chronic Aleutian mink disease virus infection

    DEFF Research Database (Denmark)

    Jensen, Trine Hammer; Chriél, Mariann; Hansen, Mette Sif

    2016-01-01

    Aleutian mink disease virus (AMDV) is found world-wide and has a major impact on mink health and welfare by decreasing reproduction and fur quality. In the majority of mink, the infection is subclinical and the diagnosis must be confirmed by serology or polymerase chain reaction (PCR). Increased ...

  14. Lack of HIV infection among truck drivers in Iran using rapid HIV test

    Directory of Open Access Journals (Sweden)

    Hossain Jabbari

    2010-01-01

    Full Text Available Background: The aim of this study was to evaluate the prevalence of HIV infection in Iranian long distance truck drivers using rapid HIV test. Methods: The study included 400 consecutive participants in Bazargan city, north-west of Iran in the late 2008 and the early 2009. Results: No HIV infection was observed among these long distance truck drivers. Conclusions: Although results of this study is plausible compared to other similar studies, repeated surveys are necessary to know the trend of HIV infection in truckers in Iran.

  15. An unusual case of rapidly progressive contractures: Case report and brief review

    Directory of Open Access Journals (Sweden)

    Subasree R

    2008-01-01

    Full Text Available An 8-year-old boy, diagnosed as cervical dystonia, was referred to our tertiary center. After a trivial trauma he had developed painful lumps in the axial region, which was followed by restricted movements of neck, shoulder, and abdominal muscles over 4 months. He had kyphoscoliosis, torticollis, rigid abdomen, and multiple muscle contractures. He also had short great toes. A detailed skeletal survey showed calcification in the soft tissues surrounding the shoulder anterior chest wall, thorax, and paraspinal muscles; there was also beaking of vertebrae, which was confirmed by CT thorax. This report showcases the diagnostic challenge posed by myositis ossificans progressiva, which can rarely cause rapidly progressing muscle contractures. A brief review of literature is also presented.

  16. Research progress of follicular cytotoxic T cells in HIV infection

    Directory of Open Access Journals (Sweden)

    Guo Ming

    2018-04-01

    Full Text Available Recently, a new type of CD8+ T-cell subset, namely, the chemokine (C-X-C motif receptor 5 (CXCR5+ cluster of differentiation (CD8+ T-cell subset (also called the follicular cytotoxic T-cell (TFC subgroup, has been discovered around B-cell follicles. The discovery has aroused widespread interest. However, the processes and mechanisms of TFCs taking part in the immune response of the germinal center and their specific roles must still be clearly identified. This article reviews domestic and foreign studies on factors regulating the phenotype, physiological functions, maturity, and differentiation of TFCs and roles and clinical significance of these cells in HIV infection. This review has shown good application prospects for TFCs. The author believes that further studies on TFCs can provide another tool for cytotherapy to control or cure chronic viral infections or tumors.

  17. Male patients presenting with rapidly progressive puberty associated with malignant tumors

    Directory of Open Access Journals (Sweden)

    Soo Jung Kim

    2016-03-01

    Full Text Available In males, precocious puberty (PP is defined as the development of secondary sexual characteristics before age 9 years. PP is usually idiopathic; though, organic abnormalities including tumors are more frequently found in male patients with PP. However, advanced puberty in male also can be an important clinical manifestation in tumors. We report 2 cases of rapidly progressive puberty in males, each associated with a germ-cell tumor. First, an 11-year-old boy presented with mild fever and weight loss for 1 month. Physical examination revealed a pubertal stage of G3P3 with 10-mL testes. Investigations revealed advanced bone age (16 years with elevated basal luteinizing hormone and testosterone levels. An anterior mediastinal tumor was identified by chest radiography and computed tomography, and elevated α-fetoprotein (AFP and β-human chorionic gonadotropin (β-hCG levels were noted. Histopathologic analysis confirmed a yolk-sac tumor. Second, a 12-year-old boy presented with diplopia, polydipsia, and polyuria for 4 months. Physical examination revealed a pubertal stage of G3P3 with 8-mL testes. Bone age was advanced (16 years and laboratory tests indicated panhypopituitarism with elevated testosterone level. A mixed germ-cell tumor was diagnosed with elevated AFP and β-hCG levels. Of course, these patients also have other symptoms of suspecting tumors, however, rapidly progressive puberty can be the more earlier screening sign of tumors. Therefore, in male patients with accelerated or advanced puberty, malignancy should be considered, with evaluation of tumor markers. In addition, advanced puberty in male should be recognized more widely as a unique sign of neoplasm.

  18. Elevated Basal Pre-infection CXCL10 in Plasma and in the Small Intestine after Infection Are Associated with More Rapid HIV/SIV Disease Onset.

    Directory of Open Access Journals (Sweden)

    Mickaël J Ploquin

    2016-08-01

    Full Text Available Elevated blood CXCL10/IP-10 levels during primary HIV-1 infection (PHI were described as an independent marker of rapid disease onset, more robust than peak viremia or CD4 cell nadir. IP-10 enhances the recruitment of CXCR3+ cells, which include major HIV-target cells, raising the question if it promotes the establishment of viral reservoirs. We analyzed data from four cohorts of HIV+ patients, allowing us to study IP-10 levels before infection (Amsterdam cohort, as well as during controlled and uncontrolled viremia (ANRS cohorts. We also addressed IP-10 expression levels with regards to lymphoid tissues (LT and blood viral reservoirs in patients and non-human primates. Pre-existing elevated IP-10 levels but not sCD63 associated with rapid CD4 T-cell loss upon HIV-1 infection. During PHI, IP-10 levels and to a lesser level IL-18 correlated with cell-associated HIV DNA, while 26 other inflammatory soluble markers did not. IP-10 levels tended to differ between HIV controllers with detectable and undetectable viremia. IP-10 was increased in SIV-exposed aviremic macaques with detectable SIV DNA in tissues. IP-10 mRNA was produced at higher levels in the small intestine than in colon or rectum. Jejunal IP-10+ cells corresponded to numerous small and round CD68neg cells as well as to macrophages. Blood IP-10 response negatively correlated with RORC (Th17 marker gene expression in the small intestine. CXCR3 expression was higher on memory CD4+ T cells than any other immune cells. CD4 T cells from chronically infected animals expressed extremely high levels of intra-cellular CXCR3 suggesting internalization after ligand recognition. Elevated systemic IP-10 levels before infection associated with rapid disease progression. Systemic IP-10 during PHI correlated with HIV DNA. IP-10 production was regionalized in the intestine during early SIV infection and CD68+ and CD68neg haematopoietic cells in the small intestine appeared to be the major source of IP-10.

  19. Peranan Terapi Awal dan Terapi Pemeliharaan pada Rapidly Progressive Periodontitis Type 1

    Directory of Open Access Journals (Sweden)

    Anita H. Joedo

    2015-08-01

    Full Text Available Rapidly Progressive Periodontitis (RPP is a severe form of a periodontal disease which starts since a puberty age. The disease if a generalized periodontal destruction without a specific distribution mode: it develops more progressively but does not in accordance to local factors. The first step to the RPP treatment is initial therapy: i.e. DHE, scaling and root planing, and eliminating predisposing local factors and continued with a maintence therapy which will support the success of a surgery later. A study case: a 21-year old RPP woman showed hyperaemia, an abscess, a 10 mm mesial pocket depth, a 5 mm distal pocker depth, a 5 mm buccal pocket depth, a 2nd degree tooth mobility and a 3 mm buccal recession on 25. In the initial therapy she was given an amoxicillin, a metronidazole for killing a supra and subgingival baterial, vitamins B and C, and also a chlorhexidine 0.2% mouth wash for a week. After a week the abscess and the inflammation decreased, but the mobility was still in the same condition and the DHE was still evaluated because of the patient's social factor, the FO was delayed. The next visit was done every 2 monts for a year for maintenance care. The clinical result showed the gingival inflammation and the tooth mobility disappeared. Radiographically, the alveolar bone showed more radiopaque and the lamina dura was seen. In conclusio, the initial and the maintenance therapy was seen to heal the RPP.

  20. Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia

    International Nuclear Information System (INIS)

    Marienhagen, J.; Eilles, C.; Weingaertner, U.; Blaha, L.; Zerr, I.; Poser, S.

    1999-01-01

    We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [de

  1. Severe hyponatraemia with absence of hyperkalaemia in rapidly progressive Addison's disease.

    Science.gov (United States)

    Thompson, Michael D; Kalmar, Eileen; Bowden, Sasigarn A

    2015-05-28

    We present a case of rapidly progressing Addison's disease in adrenal crisis with severe hyponatraemia and absence of hyperkalaemia in a 10-year-old girl. She presented with 2 weeks of vomiting, fatigue and weight loss. Her serum electrolytes obtained 1 week prior to presentation were normal, except for mild hyponatraemia at 131 mmol/L, which dropped to 112 mmol/L on admission. She had normal serum potassium, low-serum osmolality, with elevated urine sodium and osmolality, indistinguishable from syndrome of inappropriate antidiuretic hormone (SIADH). Subsequently, Addison's disease was diagnosed on the basis of gingival hyperpigmentation and undetectable cortisol on adrenocorticotropic hormone stimulation test. She rapidly responded to stress dose hydrocortisone, followed by hydrocortisone and fludrocortisone replacement therapy. The absence of hyperkalaemia in the presence of severe hyponatraemia cannot rule out Addison's disease in children. The mechanism of hypo-osmolar hyponatraemia in primary adrenal insufficiency and clinical clues to differentiate it from SIADH are discussed. 2015 BMJ Publishing Group Ltd.

  2. Occult hepatitis B virus infection is not associated with disease progression of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cho, Junhyeon; Lee, Sang Soo; Choi, Yun Suk; Jeon, Yejoo; Chung, Jung Wha; Baeg, Joo Yeong; Si, Won Keun; Jang, Eun Sun; Kim, Jin-Wook; Jeong, Sook-Hyang

    2016-11-14

    To clarify the prevalence of occult hepatitis B virus (HBV) infection (OBI) and the association between OBI and liver disease progression, defined as development of liver cirrhosis or hepatocellular carcinoma (HCC), worsening of Child-Pugh class, or mortality in cases of chronic hepatitis C virus (HCV) infection. This prospective cohort study enrolled 174 patients with chronic HCV infection (chronic hepatitis, n = 83; cirrhosis, n = 47; HCC, n = 44), and evaluated disease progression during a mean follow-up of 38.7 mo. OBI was defined as HBV DNA positivity in 2 or more different viral genomic regions by nested polymerase chain reaction using 4 sets of primers in the S, C, P and X open reading frame of the HBV genome. The overall OBI prevalence in chronic HCV patients at enrollment was 18.4%, with 16.9%, 25.5% and 13.6% in the chronic hepatitis C, liver cirrhosis and HCC groups, respectively ( P = 0.845). During follow-up, 52 patients showed disease progression, which was independently associated with aspartate aminotransferase > 40 IU/L, Child-Pugh score and sustained virologic response (SVR), but not with OBI positivity. In 136 patients who were not in the SVR state during the study period, OBI positivity was associated with neither disease progression, nor HCC development. The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans.

  3. Nosocomial rapidly growing mycobacterial infections following laparoscopic surgery: CT imaging findings.

    Science.gov (United States)

    Volpato, Richard; de Castro, Claudio Campi; Hadad, David Jamil; da Silva Souza Ribeiro, Flavya; Filho, Ezequiel Leal; Marcal, Leonardo P

    2015-09-01

    To identify the distribution and frequency of computed tomography (CT) findings in patients with nosocomial rapidly growing mycobacterial (RGM) infection after laparoscopic surgery. A descriptive retrospective study in patients with RGM infection after laparoscopic surgery who underwent CT imaging prior to initiation of therapy. The images were analyzed by two radiologists in consensus, who evaluated the skin/subcutaneous tissues, the abdominal wall, and intraperitoneal region separately. The patterns of involvement were tabulated as: densification, collections, nodules (≥1.0 cm), small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated nodules. Twenty-six patients met the established criteria. The subcutaneous findings were: densification (88.5%), small nodules (61.5%), small pseudocavitated nodules (23.1 %), nodules (38.5%), pseudocavitated nodules (15.4%), and collections (26.9%). The findings in the abdominal wall were: densification (61.5%), pseudocavitated nodules (3.8%), and collections (15.4%). The intraperitoneal findings were: densification (46.1%), small nodules (42.3%), nodules (15.4%), and collections (11.5%). Subcutaneous CT findings in descending order of frequency were: densification, small nodules, nodules, small pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo-fascial plane CT findings were: densification, collections, and pseudocavitated nodules. The intraperitoneal CT findings were: densification, small nodules, nodules, and collections. • Rapidly growing mycobacterial infection may occur following laparoscopy. • Post-laparoscopy mycobacterial infection CT findings are densification, collection, and nodules. • Rapidly growing mycobacterial infection following laparoscopy may involve the peritoneal cavity. • Post-laparoscopy rapidly growing mycobacterial intraperitoneal infection is not associated with ascites or lymphadenopathy.

  4. First reported case of fulminant TB with progression of infection from lungs to the genitourinary region

    Directory of Open Access Journals (Sweden)

    Tatjana Adzic-Vukicevic

    Full Text Available ABSTRACT Although tuberculosis (TB is a curable disease, it continues to be one of the leading infections associated with death in the world. Extra-pulmonary TB (EPTB occurs in approximately 10% of the total cases, presenting with lymph nodes, pleura, bone and genitourinary tract as the most common locations. Genitourinary tuberculosis, the second most common EPTB, is very difficult to diagnose unless there is a high index of suspicion. Isolated TB orchitis or prostatitis without clinical evidence of renal involvement is a rare entity among genitourinary tuberculosis. We presented the first reported case of TB prostatitis and orchitis associated with pulmonary TB and the presence of an acute massive caseous pneumonia in an immunocompetent man. Despite the anti-TB therapy, the patient presented a rapid progression of disease and deterioration of general conditions taking to death, which occurred four days after TB treatment had started. Disseminated TB is a relatively uncommon cause of acute massive caseous pneumonia; however, there should always be suspicion of the disease, since it is a potentially treatable cause. This rare case supports the assertion that TB should be considered as an important differential diagnosis of genitourinary tumors irrespective of evidence of active TB elsewhere in the body.

  5. Clinical management of rapidly growing mycobacterial cutaneous infections in patients after mesotherapy.

    Science.gov (United States)

    Regnier, Stéphanie; Cambau, Emmanuelle; Meningaud, Jean-Paul; Guihot, Amelie; Deforges, Lionel; Carbonne, Anne; Bricaire, François; Caumes, Eric

    2009-11-01

    Increasing numbers of patients are expressing an interest in mesotherapy as a method of reducing body fat. Cutaneous infections due to rapidly growing mycobacteria are a common complication of such procedures. We followed up patients who had developed cutaneous infections after undergoing mesotherapy during the period October 2006-January 2007. Sixteen patients were infected after mesotherapy injections performed by the same physician. All patients presented with painful, erythematous, draining subcutaneous nodules at the injection sites. All patients were treated with surgical drainage. Microbiological examination was performed on specimens that were obtained before and during the surgical procedure. Direct examination of skin smears demonstrated acid-fast bacilli in 25% of the specimens that were obtained before the procedure and 37% of the specimens obtained during the procedure; culture results were positive in 75% of the patients. Mycobacterium chelonae was identified in 11 patients, and Mycobacterium frederiksbergense was identified in 2 patients. Fourteen patients were treated with antibiotics, 6 received triple therapy as first-line treatment (tigecycline, tobramycin, and clarithromycin), and 8 received dual therapy (clarithromycin and ciprofloxacin). The mean duration of treatment was 14 weeks (range, 1-24 weeks). All of the patients except 1 were fully recovered 2 years after the onset of infection, with the mean time to healing estimated at 6.2 months (range, 1-15 months). This series of rapidly growing mycobacterial cutaneous infections highlights the difficulties in treating such infections and suggests that in vitro susceptibility to antibiotics does not accurately predict their clinical efficacy.

  6. A rapid method for infectivity titration of Andes hantavirus using flow cytometry.

    Science.gov (United States)

    Barriga, Gonzalo P; Martínez-Valdebenito, Constanza; Galeno, Héctor; Ferrés, Marcela; Lozach, Pierre-Yves; Tischler, Nicole D

    2013-11-01

    The focus assay is currently the most commonly used technique for hantavirus titer determination. This method requires an incubation time of between 5 and 11 days to allow the appearance of foci after several rounds of viral infection. The following work presents a rapid Andes virus (ANDV) titration assay, based on viral nucleocapsid protein (N) detection in infected cells by flow cytometry. To this end, an anti-N monoclonal antibody was used that was developed and characterized previously. ANDV N could be detected as early as 6 h post-infection, while viral release was not observed until 24-48 h post-infection. Given that ANDV detection was performed during its first round of infection, a time reduction for titer determination was possible and provided results in only two days. The viral titer was calculated from the percentage of N positive cells and agreed with focus assay titers. Furthermore, the assay was applied to quantify the inhibition of ANDV cell entry by patient sera and by preventing endosome acidification. This novel hantavirus titration assay is a highly quantitative and sensitive tool that facilitates infectivity titration of virus stocks, rapid screening for antiviral drugs, and may be further used to detect and quantify infectious virus in human samples. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. A Rapid Blood Test To Determine the Active Status and Duration of Acute Viral Infection.

    Science.gov (United States)

    Zheng, Tianyu; Finn, Caroline; Parrett, Christopher J; Dhume, Kunal; Hwang, Ji Hae; Sidhom, David; Strutt, Tara M; Li Sip, Yuen Yee; McKinstry, Karl K; Huo, Qun

    2017-11-10

    The ability to rapidly detect and diagnose acute viral infections is crucial for infectious disease control and management. Serology testing for the presence of virus-elicited antibodies in blood is one of the methods used commonly for clinical diagnosis of viral infections. However, standard serology-based tests have a significant limitation: they cannot easily distinguish active from past, historical infections. As a result, it is difficult to determine whether a patient is currently infected with a virus or not, and on an optimal course of action, based off of positive serology testing responses. Here, we report a nanoparticle-enabled blood test that can help overcome this major challenge. The new test is based on the analysis of virus-elicited immunoglobulin G (IgG) antibody present in the protein corona of a gold nanoparticle surface upon mixing the gold nanoparticles with blood sera. Studies conducted on mouse models of influenza A virus infection show that the test gives positive responses only in the presence of a recent acute viral infection, approximately between day 14 and day 21 following the infection, and becomes negative thereafter. When used together with the traditional serology testing, the nanoparticle test can determine clearly whether a positive serology response is due to a recent or historical viral infection. This new blood test can provide critical clinical information needed to optimize further treatment and/or to determine if further quarantining should be continued.

  8. Pregnancy and HIV Disease Progression in an Early Infection Cohort from Five African Countries.

    Science.gov (United States)

    Wall, Kristin M; Rida, Wasima; Haddad, Lisa B; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Kilembe, William; Allen, Susan; Inambao, Mubiana; Yang, Annie H; Latka, Mary H; Anzala, Omu; Sanders, Eduard J; Bekker, Linda-Gail; Edward, Vinodh A; Price, Matt A

    2017-03-01

    Understanding associations between pregnancy and HIV disease progression is critical to provide appropriate counseling and care to HIV-positive women. From 2006 to 2011, women less than age 40 with incident HIV infection were enrolled in an early HIV infection cohort in Kenya, Rwanda, South Africa, Uganda, and Zambia. Time-dependent Cox models evaluated associations between pregnancy and HIV disease progression. Clinical progression was defined as a single CD4 measurement pregnancy. Among 222 women, 63 experienced clinical progression during 783.5 person-years at risk (8.0/100). Among 205 women, 87 experienced immunologic progression during 680.1 person-years at risk (12.8/100). The association between pregnancy and clinical progression was adjusted hazard ratio [aHR] = 0.7; 95% confidence interval (CI): 0.2, 1.8. The association between pregnancy and immunologic progression was aHR = 1.7; 95% CI: 0.9, 3.3. Models controlled for age; human leukocyte antigen alleles A*03:01, B*45, B*57; CD4 set point; and HIV-1 subtype. CD4 measurements before versus after pregnancies were not different. In this cohort, pregnancy was not associated with increased clinical or immunologic HIV progression. Similarly, we did not observe meaningful deleterious associations of pregnancy with CD4s. Our findings suggest that HIV-positive women may become pregnant without harmful health effects occurring during the pregnancy. Evaluation of longer-term impact of pregnancy on progression is warranted.

  9. Rapid detection of human infections with fluorine-18 fluorodeoxyglucose and positron emission tomography: preliminary results

    International Nuclear Information System (INIS)

    Sugawara, Yoshifumi; Kison, P.V.; Russo, J.E.; Zasadny, K.R.; Braun, D.K.; Wahl, R.L.

    1998-01-01

    The purpose of this study was to evaluate the feasibility of 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) and positron emission tomography (PET) for rapid detection of human infections. Eleven patients who were known or suspected to be harboring various infections were studied with FDG-PET. Dynamic scans over the putative infection sites were performed immediately after FDG (370 MBq) injection through 60 min, and static images including multiple projection images were then obtained. FDG uptake was assessed visually into four grades (0, normal; 1, probably normal; 2, probably abnormal; 3, definitely abnormal). For the semiquantitative index of FDG uptake in infections, the standardized uptake value of FDG normalized to the predicted lean body mass (SUV-lean, SUL) was determined from the images obtained at 50-60 min after FDG injection. PET results were compared with final clinical diagnoses. Eleven lesions in eight patients, which were interpreted as grade 2 or 3 by FDG-PET, were all concordant with active infectious foci. The SUL values of infections ranged from 0.97 to 6.69. In two patients, FDG-PET correctly showed no active infection. In one patient, it was difficult to detect infectious foci by FDG-PET due to substantial normal background uptake of FDG. In total, FDG-PET correctly diagnosed the presence or absence of active infection in 10 of 11 patients. Fusion images of PET with computed tomography showed the most intense FDG uptake to be within an abscess wall. In conclusion, FDG-PET appears to be a promising modality for rapid imaging of active human infections. More extensive clinical evaluation is warranted to determine the accuracy of this method. (orig.)

  10. Rapidly progressive polyneuropathy due to dry beriberi in a man: a case report

    Directory of Open Access Journals (Sweden)

    Lekwuwa Godwin

    2010-12-01

    Full Text Available Abstract Introduction We describe a case of rapidly progressive and severely debilitating polyneuropathy in a patient with confirmed hypovitaminosis B1, consistent with dry beriberi. Crucially, this is a treatable condition, although sometimes with incomplete recovery, but it is probably under-recognized yet increasingly common given increasing levels of alcohol abuse in the western world. Case presentation A 49-year-old Caucasian British man presented with progressive weakness of both lower limbs of approximately seven months' duration. He noted difficulty climbing stairs. He also complained of lethargy, and loss of muscle bulk, including his thighs. He had a history of type 2 diabetes mellitus and admitted prior alcohol abuse but denied excessive alcohol intake in the five years prior to presentation. Initial clinical and neurophysiological examinations were consistent with a mild peripheral neuropathy and probable proximal myopathy. However, over the subsequent four months he evolved a marked tetraparesis, with profound sensory disturbance of all limbs. Repeat neurophysiology revealed a widespread polyneuropathy with extensive acute and sub-acute denervation changes in all four limbs, and reduced or absent sensory nerve action potentials. Hypovitaminosis B1 was confirmed (45 nmol/L, reference range 66-200 nmol/L. His rapid clinical deterioration was in keeping with dry beriberi. He was treated with thiamine. Subsequent follow-up revealed slow but significant improvement, such that by 15-16 months from the initial onset of symptoms, and approximately six months after the onset of his marked tetraparesis, he was able to stand independently and was gradually gaining confidence in walking pending a period of in-patient neurorehabilitation. Conclusion A potentially wide differential diagnosis exists for this type of presentation. Confirming hypovitaminosis B1 by requesting the assay prior to vitamin replacement ensures accurate diagnosis and

  11. Research Progress on Diagnosis Methods for Fungal Infection

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    Feng Hua

    2015-12-01

    Full Text Available In recent years, owing to abuse of antibiotics, extensive use of antitumor drugs and immunosuppressive agents and other reasons, an increasing number of people suffered from fungal infection. In this situation, researchers proposed new diagnosis methods, such as G test, galactomannan (GM test, and polymerase chain reaction (PCR. G test is simple, quick, and highly sensitive and can detect multiple fungi; however, it cannot distinguish fungal types and may result in false positive and false negative results. GM test is less time consuming and feature highly positive detection rates but can simply be used in inspection of invasive aspergillosis. However, optimal positive critical values of GM test remain controversial. PCR is currently one of the fastest methods but is not formally used in clinical practice because of its lack of standardized operation and evaluation criteria. This study reviews the above three methods with the aim of discovering and summarizing their advantages and disadvantages to facilitate research and development of new diagnosis methods.

  12. Acute respiratory infections in Pakistan: Have we made any progress?

    International Nuclear Information System (INIS)

    Khan, T.A.; Madni, S.A.; Zaidi, A.K.M.

    2004-01-01

    Acute respiratory infections (ARI) are the leading cause of death in young children in Pakistan, responsible for 20-30% of child deaths under age 5 years. This paper summarizes the research and technical development efforts over the last 15 years which have contributed to improving the effectiveness of the case management strategy to reduce mortality from 5' pneumonia in children in Pakistan. Community intervention is viable, effective and practical. Rising antimicrobial resistance among commonly used and A low-cost oral agent is of significant concern. Appropriate monitoring and evaluation of the impact of the ARI control programme is lacking. Lack of funding for programmatic activities, lack of coordination with other child survival programs, inadequate training for community health workers and general practitioners in the private sector, lack of public awareness about seeking timely and appropriate care and insufficient planning and support for ARI in the programmatic activities at provincial and district levels are major hindrances in decreasing the burden of ARI in the country. The recent introduction of the community-based Lady Health Worker (LHW) Programme and WHO and UNICEF-sponsored integrated management of childhood illness initiative present ideal opportunities for re-emphasizing early case detection and appropriate case management of ARI. Ultimately, focusing on preventive strategies such as improving nutrition, reducing indoor pollution, improving mass vaccination, as well as introduction of new vaccines effective against important respiratory pathogens will likely have the most impact on reducing severe ARI and deaths from severe disease. (author)

  13. Detection of gonococcal infection : pros and cons of a rapid test.

    Science.gov (United States)

    Vickerman, Peter; Peeling, Rosanna W; Watts, Charlotte; Mabey, David

    2005-01-01

    WHO estimates that 62 million cases of gonorrhea occur annually worldwide. Untreated infection can cause serious long-term complications, especially in women. In addition, Neisseria gonorrheae infection can facilitate HIV transmission, and babies born to infected mothers are at risk of ocular infection, which can lead to blindness. Where diagnostic facilities are lacking, gonorrhea can be treated syndromically. However, this inevitably leads to over-treatment, especially in women in whom the syndrome of vaginal discharge may be due not to N. gonorrheae infection but to several other more prevalent conditions. Over-treatment is a major concern because of widespread N. gonorrheae antibiotic resistance. Moreover, a high proportion of gonorrhea cases are asymptomatic and so do not present for syndromic management. Such cases will only be detected by screening tests. The gold standard test for the detection of N. gonorrheae is culture, which has high sensitivity and specificity. However, it requires well trained staff and its performance is affected by specimen transport conditions. Other options include microscopy and tests that detect gonococcal antigen or nucleic acid. Nucleic acid amplification tests (NAATs) have higher sensitivity and can be used on non-invasive samples (urine). However, they can cross-react with other Neisseria species and are expensive, requiring highly trained staff and sophisticated equipment. In settings where patients are asked to return for laboratory results, some infected patients never receive treatment as they fail to return for their test results. This reduction in treatment, and the possible onward transmission of N. gonorrheae during any delay in treatment, means that a rapid test of lower sensitivity may be more effective if it results in patients being treated at the initial visit. Indeed, even with the low sensitivity of currently available rapid tests (50-70%), modeling shows that they can outperform gold standard tests in

  14. Usefulness of clinical data and rapid diagnostic tests to identify bacterial etiology in adult respiratory infections

    Directory of Open Access Journals (Sweden)

    Pilar Toledano-Sierra

    2015-01-01

    Full Text Available Respiratory tract infections are a common complaint and most of them, such as common cold and laryngitis, are viral in origin, so antibiotic use should be exceptional. However, there are other respiratory tract infections (sinusitis, pharyngitis, lower respiratory tract infections, and exacerbations of chronic obstructive pulmonary disease where a bacterial etiology is responsible for a non-negligible percentage, and antibiotics are often empirically indicated. The aim of the study is to identify the strength of the data obtained from the symptoms, physical examination and rapid diagnostic methods in respiratory infections in which antibiotic use is frequently proposed in order to improve diagnosis and influence the decision to prescribe these drugs. The review concludes that history, physical examination and rapid tests are useful to guide the need for antibiotic treatment in diseases such as acute sinusitis, acute pharyngitis, exacerbation of lower respiratory tract infection and chronic obstructive pulmonary disease. However, no isolated data is accurate enough by itself to confirm or rule out the need for antibiotics. Therefore, clinical prediction rules bring together history and physical examination, thereby improving the accuracy of the decision to indicate or not antibiotics.

  15. Detection and monitoring of human bocavirus 1 infection by a new rapid antigen test

    Directory of Open Access Journals (Sweden)

    A.H.L. Bruning

    2016-05-01

    Full Text Available Clinically relevant diagnosis of human bocavirus 1 (HBoV1 is challenging, as the virus is frequently detected in asymptomatic patients, and cofindings with other respiratory viruses are common. The clinical value of current diagnostic methods, such as PCR, is therefore low, and alternative diagnostic strategies are needed. We describe for the first time the use of an antigen detection assay for the rapid identification of HBoV1 in a paediatric patient with respiratory tract infection symptoms. We estimate the duration of active HBoV1 infection to be 6 days.

  16. The effectiveness of electromagnetic terahertz radiation use in the treatment of patients with rapidly progressive periodontitis

    Directory of Open Access Journals (Sweden)

    Zelenova A.V.

    2015-12-01

    Full Text Available The aim: to increase the efficiency of treatment of patients with rapidly progressive periodontitis (RPP using electromagnetic radiation at terahertz frequencies of molecular spectrum of radiation and absorption of nitric oxide 150,176-150,664 GHz. Material and methods. The study involved 50 patients with RPP, which according to the method of therapy were divided into 2 groups: group 1 included patients receiving conventional therapy, group 2 consisted of patients who, along with traditional therapy received EHF-therapy device "Orbit" YAKUL.941526.001. The control group consisted of 20 healthy subjects with intact periodontium. For the non-invasive study of tissue blood flow in the periodontal tissue Doppler ultrasound was used MiniMax-Doppler-Phono. The study of the microvasculature of periodontitis has been conducted. To determine the reactivity of microvascular periodontal tissue reflex functional tests on the indirect effect of the cold were performed. Results. Reductions achieved values of periodontal indices, especially important index PMA, a significant increase in the linear blood flow indices, decreased pulse pressure gradient and the index followed appropriate reduction to their cold test. Conclusion. The proposed complex therapy can accelerate the relief of inflammation in the periodontal tissues of the complex, to improve the elastic properties of blood vessels, reduce their tone and restore microcirculation in periodontal tissues.

  17. HPLC method for rapidly following biodiesel fuel transesterification reaction progress using a core-shell column.

    Science.gov (United States)

    Allen, Samuel J; Ott, Lisa S

    2012-07-01

    There are a wide and growing variety of feedstocks for biodiesel fuel. Most commonly, these feedstocks contain triglycerides which are transesterified into the fatty acid alkyl esters (FAAEs) which comprise biodiesel fuel. While the tranesterification reaction itself is simple, monitoring the reaction progress and reaction products is not. Gas chromatography-mass spectrometry is useful for assessing the FAAE products, but does not directly address either the tri-, di-, or monoglycerides present from incomplete transesterification or the free fatty acids which may also be present. Analysis of the biodiesel reaction mixture is complicated by the solubility and physical property differences among the components of the tranesterification reaction mixture. In this contribution, we present a simple, rapid HPLC method which allows for monitoring all of the main components in a biodiesel fuel transesterification reaction, with specific emphasis on the ability to monitor the reaction as a function of time. The utilization of a relatively new, core-shell stationary phase for the HPLC column allows for efficient separation of peaks with short elution times, saving both time and solvent.

  18. Structured approach to design of diagnostic test evaluation studies for chronic progressive infections in animals

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew

    2011-01-01

    Diagnostic test evaluations (DTEs) for chronic infections are challenging because a protracted incubation period has to be considered in the design of the DTE, and the adverse effects of infection may be widespread and progressive over an animal's entire life. Frequently, the specific purpose......) than originally intended. The objective of this paper is to outline a structured approach to the design and conduct of a DTE for diagnostic tests used for chronic infections in animals, and intended for different purposes. We describe the process from reflections about test purpose and the underlying...... of the test is not formally considered when a test is evaluated. Therefore, the result is often a DTE where test sensitivity and specificity estimates are biased, either because of problems with establishing the true infection status or because the test detects another aspect of the infection (and analyte...

  19. Rapidly growing non-tuberculous mycobacteria infection of prosthetic knee joints: A report of two cases.

    Science.gov (United States)

    Kim, Manyoung; Ha, Chul-Won; Jang, Jae Won; Park, Yong-Beom

    2017-08-01

    Non-tuberculous mycobacteria (NTM) cause prosthetic knee joint infections in rare cases. Infections with rapidly growing non-tuberculous mycobacteria (RGNTM) are difficult to treat due to their aggressive clinical behavior and resistance to antibiotics. Infections of a prosthetic knee joint by RGNTM have rarely been reported. A standard of treatment has not yet been established because of the rarity of the condition. In previous reports, diagnoses of RGNTM infections in prosthetic knee joints took a long time to reach because the condition was not suspected, due to its rarity. In addition, it is difficult to identify RGNTM in the lab because special identification tests are needed. In previous reports, after treatment for RGNTM prosthetic infections, knee prostheses could not be re-implanted in all cases but one, resulting in arthrodesis or resection arthroplasty; this was most likely due to the aggressiveness of these organisms. In the present report, two cases of prosthetic knee joint infection caused by RGNTM (Mycobacterium abscessus) are described that were successfully treated, and in which prosthetic joints were finally reimplanted in two-stage revision surgery. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Rapid lung MRI in children with pulmonary infections: Time to change our diagnostic algorithms.

    Science.gov (United States)

    Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Singh, Meenu; Agarwal, Ritesh; Bhatia, Anmol; Lee, Edward Y

    2016-05-01

    To determine the diagnostic utility of a new rapid MRI protocol, as compared with computed tomography (CT) for the detection of various pulmonary and mediastinal abnormalities in children with suspected pulmonary infections. Seventy-five children (age range of 5 to 15 years) with clinically suspected pulmonary infections were enrolled in this prospective study, which was approved by the institutional ethics committee. All patients underwent thoracic MRI (1.5T) and CT (64 detector) scan within 48 h of each other. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MRI were evaluated with CT as a standard of reference. Inter-observer agreement was measured with the kappa coefficient. MRI with a new rapid MRI protocol demonstrated sensitivity, specificity, PPV, and NPV of 100% for detecting pulmonary consolidation, nodules (>3 mm), cyst/cavity, hyperinflation, pleural effusion, and lymph nodes. The kappa-test showed almost perfect agreement between MRI and multidetector CT (MDCT) in detecting thoracic abnormalities (k = 0.9). No statistically significant difference was observed between MRI and MDCT for detecting thoracic abnormalities by the McNemar test (P = 0.125). Rapid lung MRI was found to be comparable to MDCT for detecting thoracic abnormalities in pediatric patients with clinically suspected pulmonary infections. It has a great potential as the first line cross-sectional imaging modality of choice in this patient population. However, further studies will be helpful for confirmation of our findings. © 2015 Wiley Periodicals, Inc.

  1. Vitamin D and clinical disease progression in HIV infection: results from the EuroSIDA study

    DEFF Research Database (Denmark)

    Viard, Jean-Paul; Souberbielle, Jean-Claude; Kirk, Ole

    2011-01-01

    BACKGROUND:: We examined the association between vitamin D [25(OH)D] level and disease progression in HIV infection. METHODS:: Within the EuroSIDA study, 2000 persons were randomly selected for 25(OH)D measurement in stored plasma samples closest to study entry. 25(OH)D results were stratified...

  2. Development and clinical evaluation of a rapid diagnostic kit for feline leukemia virus infection.

    Science.gov (United States)

    Kim, Won-Shik; Chong, Chom-Kyu; Kim, Hak-Yong; Lee, Gyu-Cheol; Jeong, Wooseog; An, Dong-Jun; Jeoung, Hye-Young; Lee, Jae-In; Lee, Young-Ki

    2014-01-01

    Feline leukemia virus (FeLV) causes a range of neoplastic and degenerative diseases in cats. To obtain a more sensitive and convenient diagnosis of the disease, we prepared monoclonal antibodies specific for the FeLV p27 to develop a rapid diagnostic test with enhanced sensitivity and specificity. Among these antibodies, we identified two clones (hybridomas 8F8B5 and 8G7D1) that specifically bound to FeLV and were very suitable for a diagnostic kit. The affinity constants for 8F8B5 and 8G7D1 were 0.35 × 10⁸ and 0.86 × 10⁸, respectively. To investigate the diagnostic abilities of the rapid kit using these antibodies, we performed several clinical studies. Assessment of analytical sensitivity revealed that the detection threshold of the rapid diagnostic test was 2 ng/mL for recombinant p27 and 12.5 × 10⁴ IU/mL for FeLV. When evaluating 252 cat sera samples, the kit was found to have a kappa value of 0.88 compared to polymerase chain reaction (PCR), indicating a significant correlation between data from the rapid diagnostic test and PCR. Sensitivity and specificity of the kit were 95.2% (20/21) and 98.5% (257/261), respectively. Our results demonstrated that the rapid diagnostic test would be a suitable diagnostic tool for the rapid detection of FeLV infection in cats.

  3. Rapidly progressive glomerulonephritis in adolescents – aetiology and treatment based on case reports

    Directory of Open Access Journals (Sweden)

    Beata Banaszak

    2017-06-01

    Full Text Available Rapidly progressive glomerulonephritis is a disease characterised by an abrupt drop in glomerular filtration rate in a short period of time, which is caused by crescent formation seen in at least 50% of glomeruli. Two cases presented below illustrate rapid progressive glomerulonephritis in adolescents as a disease of heterogeneous aetiology that can develop both in the course of primary glomerulopathies and glomerulopathies secondary to systemic vasculitis. In the first case of an 11-year-old girl, nephritic syndrome with renal failure was accompanied by the presence of anti-myeloperoxidase antibodies in the serum, which in combination with the histopathological picture of the kidneys indicating pauci-immune rapidly progressive glomerulonephritis was the basis for the diagnosis of renal limited vasculitis. In the second case of a 16-year-old boy, an adverse course of acute post-streptococcal glomerulonephritis with features of severe and persistent glomerular filtration impairment was an indication for the verification of the diagnosis and identification of rapidly progressive glomerulonephritis based on a biopsy examination. Prompt diagnosis and inclusion of combined immunosuppressive therapy provided the chance to preserve renal function.

  4. Decrease in PSCA expression caused by Helicobacter pylori infection may promote progression to severe gastritis

    Science.gov (United States)

    Toyoshima, Osamu; Tanikawa, Chizu; Yamamoto, Ryuta; Watanabe, Hidenobu; Yamashita, Hiroharu; Sakitani, Kosuke; Yoshida, Shuntaro; Kubo, Michiaki; Matsuo, Keitaro; Ito, Hidemi; Koike, Kazuhiko; Seto, Yasuyuki; Matsuda, Koichi

    2018-01-01

    SNP rs2294008 in Prostate Stem Cell Antigen (PSCA) and decreased PSCA expression are associated with gastric cancer. The objective of this study is to investigate the role of rs2294008 and PSCA expression in the gastritis-gastric cancer carcinogenic pathway. We conducted a case-control association study of H. pylori-infected gastritis and gastric cancer. rs2294008 was associated with the progression to chronic active gastritis (P = 9.4 × 10–5; odds ratio = 3.88, TT + TC vs CC genotype), but not with H. pylori infection per se nor with the progression from active gastritis to gastric cancer. We also assessed the association of rs2294008 with PSCA mRNA expression in the gastric mucosa at various disease stages and found that rs2294008 was associated with PSCA expression (P = 1.3 × 10–12). H. pylori infection (P = 5.1 × 10–8) and eradication therapy (P gastritis compared with mild gastritis only among T allele carriers. Our findings revealed the regulation of PSCA expression by host genetic variation and bacterial infection might contribute to gastritis progression after H. pylori infection. PMID:29423095

  5. Field evaluation of a dual rapid diagnostic test for HIV infection and syphilis in Lima, Peru.

    Science.gov (United States)

    Bristow, Claire C; Leon, Segundo R; Huang, Emily; Brown, Brandon J; Ramos, Lourdes B; Vargas, Silver K; Flores, Juan A; Caceres, Carlos F; Klausner, Jeffrey D

    2016-05-01

    Screening for HIV and syphilis in key populations is recommended by the WHO to reduce the morbidity, mortality and transmission associated with undiagnosed and untreated infections. Rapid point-of-care tests that can detect multiple infections with a single fingerprick whole blood specimen using a single device are gaining popularity. We evaluated the field performance of a rapid dual HIV and syphilis test in people at high risk of HIV and syphilis infections. Participants included men who have sex with men and transgender women recruited in Lima, Peru. Reference standard testing for detection of HIV and syphilis infections, conducted using blood samples from venipuncture, included Treponema pallidum particle agglutination and fourth-generation HIV enzyme immunoassay for which positive results had a confirmation HIV Western blot test. For the evaluation test, SD BIOLINE HIV/Syphilis Duo test (Standard Diagnostics, Korea), a fingerprick blood specimen was used. Sensitivity and specificity were calculated and the exact binomial method was used to determine 95% CIs. A total of 415 participants were recruited for the study. The dual test sensitivity for detection of T. pallidum infection was 89.2% (95% CI 83.5% to 93.5%) and specificity 98.8% (95% CI 96.5% to 99.8%). For detection of HIV infection, the sensitivity of the dual test was 99.1% (95% CI 94.8% to 100%) and specificity 99.4% (95% CI 97.7% to 99.9%). This high performing dual test should be considered for the use in clinical settings to increase uptake of simultaneous testing of HIV and syphilis and accelerate time to treatment for those who need it. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  6. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Science.gov (United States)

    Ma, Frank Y; Han, Yingjie; Nikolic-Paterson, David J; Kolkhof, Peter; Tesch, Greg H

    2015-01-01

    Steroidal mineralocorticoid receptor antagonists (MRAs) are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis. Accelerated anti-glomerular basement membrane (GBM) glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid) from day 0 until being killed on day 15 of disease. Mice were examined for renal injury. Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ) and profibrotic molecules (collagen I, fibronectin). In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction). The non-steroidal MRA (BR-4628) provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  7. Suppression of Rapidly Progressive Mouse Glomerulonephritis with the Non-Steroidal Mineralocorticoid Receptor Antagonist BR-4628.

    Directory of Open Access Journals (Sweden)

    Frank Y Ma

    Full Text Available Steroidal mineralocorticoid receptor antagonists (MRAs are effective in the treatment of kidney disease; however, the side effect of hyperkalaemia, particularly in the context of renal impairment, is a major limitation to their clinical use. Recently developed non-steroidal MRAs have distinct characteristics suggesting that they may be superior to steroidal MRAs. Therefore, we explored the benefits of a non-steroidal MRA in a model of rapidly progressive glomerulonephritis.Accelerated anti-glomerular basement membrane (GBM glomerulonephritis was induced in groups of C57BL/6J mice which received no treatment, vehicle or a non-steroidal MRA (BR-4628, 5mg/kg/bid from day 0 until being killed on day 15 of disease. Mice were examined for renal injury.Mice with anti-GBM glomerulonephritis which received no treatment or vehicle developed similar disease with severe albuminuria, impaired renal function, glomerular tuft damage and crescents in 40% of glomeruli. In comparison, mice which received BR-4628 displayed similar albuminuria, but had improved renal function, reduced severity of glomerular tuft lesions and a 50% reduction in crescents. The protection seen in BR-4628 treated mice was associated with a marked reduction in glomerular macrophages and T-cells and reduced kidney gene expression of proinflammatory (CCL2, TNF-α, IFN-γ and profibrotic molecules (collagen I, fibronectin. In addition, treatment with BR-4626 did not cause hyperkalaemia or increase urine Na+/K+ excretion (a marker of tubular dysfunction.The non-steroidal MRA (BR-4628 provided substantial suppression of mouse crescentic glomerulonephritis without causing tubular dysfunction. This finding warrants further investigation of non-steroidal MRAs as a therapy for inflammatory kidney diseases.

  8. Rapid Progression of Metastatic Pulmonary Calcification and Alveolar Hemorrhage in a Patient with Chronic Renal Failure and Primary Hyperparathyroidism

    International Nuclear Information System (INIS)

    Yoon, Eun Joo; Kim, Dong Hun; Yoon, Seong Ho; Suk, Eun Ha

    2013-01-01

    Metastatic pulmonary calcification (MPC) is common in patients with chronic renal failure. The authors experienced a patient with chronic renal failure and primary hyperparathyroidism by parathyroid adenoma accompanied with rapid progressions of MPC and alveolar hemorrhage. Recent chest radiographs, compared with previous chest radiographs, showed rapid accumulation of calcification in both upper lungs. Following up on the high-resolution CT scan after five years demonstrates more increased nodules in size and ground glass opacity. The patient was diagnosed with MPC and alveolar hemorrhage by transbronchial lung biopsy. We assumed rapid progression of MPC and alveolar hemorrhage in underlying chronic renal failures could be a primary hyperparathyroidism which may be caused by parathyroid adenoma detected incidentally. Therefore parathyroid adenoma was treated with ethanol injections. Herein, we have reported on CT findings of MPC with alveolar hemorrhage and reviewed our case along with other articles.

  9. Rapid detection of Ganoderma-infected oil palms by microwave ergosterol extraction with HPLC and TLC.

    Science.gov (United States)

    Muniroh, M S; Sariah, M; Zainal Abidin, M A; Lima, N; Paterson, R R M

    2014-05-01

    Detection of basal stem rot (BSR) by Ganoderma of oil palms was based on foliar symptoms and production of basidiomata. Enzyme-Linked Immunosorbent Assays-Polyclonal Antibody (ELISA-PAB) and PCR have been proposed as early detection methods for the disease. These techniques are complex, time consuming and have accuracy limitations. An ergosterol method was developed which correlated well with the degree of infection in oil palms, including samples growing in plantations. However, the method was capable of being optimised. This current study was designed to develop a simpler, more rapid and efficient ergosterol method with utility in the field that involved the use of microwave extraction. The optimised procedure involved extracting a small amount of Ganoderma, or Ganoderma-infected oil palm suspended in low volumes of solvent followed by irradiation in a conventional microwave oven at 70°C and medium high power for 30s, resulting in simultaneous extraction and saponification. Ergosterol was detected by thin layer chromatography (TLC) and quantified using high performance liquid chromatography with diode array detection. The TLC method was novel and provided a simple, inexpensive method with utility in the field. The new method was particularly effective at extracting high yields of ergosterol from infected oil palm and enables rapid analysis of field samples on site, allowing infected oil palms to be treated or culled very rapidly. Some limitations of the method are discussed herein. The procedures lend themselves to controlling the disease more effectively and allowing more effective use of land currently employed to grow oil palms, thereby reducing pressure to develop new plantations. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Genital Human Papillomavirus Infection Progression to External Genital Lesions: The HIM Study.

    Science.gov (United States)

    Sudenga, Staci L; Ingles, Donna J; Pierce Campbell, Christine M; Lin, Hui-Yi; Fulp, William J; Messina, Jane L; Stoler, Mark H; Abrahamsen, Martha; Villa, Luisa L; Lazcano-Ponce, Eduardo; Giuliano, Anna R

    2016-01-01

    Human papillomavirus (HPV) causes two types of external genital lesions (EGLs) in men: genital warts (condyloma) and penile intraepithelial neoplasia (PeIN). The purpose of this study was to describe genital HPV progression to a histopathologically confirmed HPV-related EGL. A prospective analysis nested within the HPV Infection in Men (HIM) study was conducted among 3033 men. At each visit, visually distinct EGLs were biopsied; the biopsy specimens were subjected to pathologic evaluation and categorized by pathologic diagnoses. Genital swabs and biopsies were used to identify HPV types using the Linear Array genotyping method for swabs and INNO-LiPA for biopsy specimens. EGL incidence was determined among 1788 HPV-positive men, and cumulative incidence rates at 6, 12, and 24 mo were estimated. The proportion of HPV infections that progressed to EGL was also calculated, along with median time to EGL development. Among 1788 HPV-positive men, 92 developed an incident EGL during follow-up (9 PeIN and 86 condyloma). During the first 12 mo of follow-up, 16% of men with a genital HPV 6 infection developed an HPV 6-positive condyloma, and 22% of genital HPV 11 infections progressed to an HPV 11-positive condyloma. During the first 12 mo of follow-up, 0.5% of men with a genital HPV 16 infection developed an HPV 16-positive PeIN. Although we expected PeIN to be a rare event, the sample size for PeIN (n=10) limited the types of analyses that could be performed. Most EGLs develop following infection with HPV 6, 11, or 16, all of which could be prevented with the 4-valent HPV vaccine. In this study, we looked at genital human papillomavirus (HPV) infections that can cause lesions in men. The HPV that we detected within the lesions could be prevented by a vaccine. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  11. Hypercytotoxicity and rapid loss of NKp44+ innate lymphoid cells during acute SIV infection.

    Directory of Open Access Journals (Sweden)

    Haiying Li

    2014-12-01

    Full Text Available HIV/SIV infections break down the integrity of the gastrointestinal mucosa and lead to chronic immune activation and associated disease progression. Innate lymphoid cells (ILCs, distinguishable by high expression of NKp44 and RORγt, play key roles in mucosal defense and homeostasis, but are depleted from gastrointestinal (GI tract large bowel during chronic SIV infection. However, less is known about the kinetics of ILC loss, or if it occurs systemically. In acute SIV infection, we found a massive, up to 8-fold, loss of NKp44+ILCs in all mucosae as early as day 6 post-infection, which was sustained through chronic disease. Interestingly, no loss of ILCs was observed in mucosa-draining lymph nodes. In contrast, classical NK cells were not depleted either from gut or draining lymph nodes. Both ILCs and NK cells exhibited significantly increased levels of apoptosis as measured by increased Annexin-V expression, but while classical NK cells also showed increased proliferation, ILCs did not. Interestingly, ILCs, which are normally noncytolytic, dramatically upregulated cytotoxic functions in acute and chronic infection and acquired a polyfunctional phenotype secreting IFN-γ, MIP1-β, and TNF-α, but decreased production of the prototypical cytokine, IL-17. Classical NK cells had less dramatic functional change, but upregulated perforin expression and increased cytotoxic potential. Finally, we show that numerical and functional loss of ILCs was due to increased apoptosis and ROR γt suppression induced by inflammatory cytokines in the gut milieu. Herein we demonstrate the first evidence for acute, systemic, and permanent loss of mucosal ILCs during SIV infection associated with reduction of IL-17. The massive reduction of ILCs involves apoptosis without compensatory de novo development/proliferation, but the full mechanism of depletion and the impact of functional change so early in infection remain unclear.

  12. Vertically acquired hepatitis C virus infection: Correlates of transmission and disease progression.

    Science.gov (United States)

    Tovo, Pier-Angelo; Calitri, Carmelina; Scolfaro, Carlo; Gabiano, Clara; Garazzino, Silvia

    2016-01-28

    The worldwide prevalence of hepatitis C virus (HCV) infection in children is 0.05%-0.4% in developed countries and 2%-5% in resource-limited settings, where inadequately tested blood products or un-sterile medical injections still remain important routes of infection. After the screening of blood donors, mother-to-child transmission (MTCT) of HCV has become the leading cause of pediatric infection, at a rate of 5%. Maternal HIV co-infection is a significant risk factor for MTCT and anti-HIV therapy during pregnancy seemingly can reduce the transmission rate of both viruses. Conversely, a high maternal viral load is an important, but not preventable risk factor, because at present no anti-HCV treatment can be administered to pregnant women to block viral replication. Caution is needed in adopting obstetric procedures, such as amniocentesis or internal fetal monitoring, that can favor fetal exposure to HCV contaminated maternal blood, though evidence is lacking on the real risk of single obstetric practices. Mode of delivery and type of feeding do not represent significant risk factors for MTCT. Therefore, there is no reason to offer elective caesarean section or discourage breast-feeding to HCV infected parturients. Information on the natural history of vertical HCV infection is limited. The primary infection is asymptomatic in infants. At least one quarter of infected children shows a spontaneous viral clearance (SVC) that usually occurs within 6 years of life. IL-28B polymorphims and genotype 3 infection have been associated with greater chances of SVC. In general, HCV progression is mild or moderate in children with chronic infection who grow regularly, though cases with marked liver fibrosis or hepatic failure have been described. Non-organ specific autoantibodies and cryoglobulins are frequently found in children with chronic infection, but autoimmune diseases or HCV associated extrahepatic manifestations are rare.

  13. Influence of model assumptions about HIV disease progression after initiating or stopping treatment on estimates of infections and deaths averted by scaling up antiretroviral therapy

    Science.gov (United States)

    Sucharitakul, Kanes; Boily, Marie-Claude; Dimitrov, Dobromir

    2018-01-01

    Background Many mathematical models have investigated the population-level impact of expanding antiretroviral therapy (ART), using different assumptions about HIV disease progression on ART and among ART dropouts. We evaluated the influence of these assumptions on model projections of the number of infections and deaths prevented by expanded ART. Methods A new dynamic model of HIV transmission among men who have sex with men (MSM) was developed, which incorporated each of four alternative assumptions about disease progression used in previous models: (A) ART slows disease progression; (B) ART halts disease progression; (C) ART reverses disease progression by increasing CD4 count; (D) ART reverses disease progression, but disease progresses rapidly once treatment is stopped. The model was independently calibrated to HIV prevalence and ART coverage data from the United States under each progression assumption in turn. New HIV infections and HIV-related deaths averted over 10 years were compared for fixed ART coverage increases. Results Little absolute difference (ART coverage (varied between 33% and 90%) if ART dropouts reinitiated ART at the same rate as ART-naïve MSM. Larger differences in the predicted fraction of HIV-related deaths averted were observed (up to 15pp). However, if ART dropouts could only reinitiate ART at CD4ART interruption did not affect the fraction of HIV infections averted with expanded ART, unless ART dropouts only re-initiated ART at low CD4 counts. Different disease progression assumptions had a larger influence on the fraction of HIV-related deaths averted with expanded ART. PMID:29554136

  14. Surgical site infections due to rapidly growing mycobacteria in puducherry, India.

    Science.gov (United States)

    Kannaiyan, Kavitha; Ragunathan, Latha; Sakthivel, Sulochana; Sasidar, A R; Muralidaran; Venkatachalam, G K

    2015-03-01

    Rapidly growing Mycobacteria are increasingly recognized, nowadays as an important pathogen that can cause wide range of clinical syndromes in humans. We herein describe unrelated cases of surgical site infection caused by Rapidly growing Mycobacteria (RGM), seen during a period of 12 months. Nineteen patients underwent operations by different surgical teams located in diverse sections of Tamil Nadu, Pondicherry, Karnataka, India. All patients presented with painful, draining subcutaneous nodules at the infection sites. Purulent material specimens were sent to the microbiology laboratory. Gram stain and Ziehl-Neelsen staining methods were used for direct examination. Culture media included blood agar, chocolate agar, MacConkey agar, Sabourauds agar and Lowenstein-Jensen medium for Mycobacteria. Isolated microorganisms were identified and further tested for antimicrobial susceptibility by standard microbiologic procedures. Mycobacterium fortuitum and M.chelonae were isolated from the purulent drainage obtained from wounds by routine microbiological techniques from all the specimens. All isolates analyzed for antimicrobial susceptibility pattern were sensitive to clarithromycin, linezolid and amikacin but were variable to ciprofloxacin, rifampicin and tobramycin. Our case series highlights that a high level of clinical suspicion should be maintained for patients presenting with protracted soft tissue lesions with a history of trauma or surgery as these infections not only cause physical but also emotional distress that affects both the patients and the surgeon.

  15. Comparison of rapid diagnostic tests to detect Mycobacterium avium subsp. paratuberculosis disseminated infection in bovine liver.

    Science.gov (United States)

    Zarei, Mehdi; Ghorbanpour, Masoud; Tajbakhsh, Samaneh; Mosavari, Nader

    2017-08-01

    Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne's disease, a chronic enteritis in cattle and other domestic and wild ruminants. The presence of MAP in tissues other than intestines and associated lymph nodes, such as meat and liver, is a potential public health concern. In the present study, the relationship between the results of rapid diagnostic tests of the Johne's disease, such as serum ELISA, rectal scraping PCR, and acid-fast staining, and the presence of MAP in liver was evaluated. Blood, liver, and rectal scraping samples were collected from 200 slaughtered cattle with unknown Johne's disease status. ELISA was performed to determine the MAP antibody activity in the serum. Acid-fast staining was performed on rectal scraping samples, and PCR was performed on rectal scraping and liver samples. PCR-positive liver samples were used for mycobacterial culture. Overall, the results of this study demonstrated that MAP can be detected and cultured from liver of slaughtered cattle and rapid diagnostic tests of Johne's disease have limited value in detecting cattle with MAP infection in liver. These findings show that the presence of MAP in liver tissue may occur in cows with negative results for rapid diagnostic tests and vice versa. Hence, liver might represent another possible risk of human exposure to MAP. Given concerns about a potential zoonotic role for MAP, these results show the necessity to find new methods for detecting cattle with MAP disseminated infection.

  16. Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.

    Directory of Open Access Journals (Sweden)

    Bulbulgul Aumakhan

    Full Text Available BACKGROUND: The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear. METHODS: Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit. RESULTS: A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004, an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001 and 51 to 101 reduced CD4+ T cells/mm(3 over time compared to asymptomatic HSV-2 infection (trend p<0.001. CONCLUSIONS: HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.

  17. Connexin 43 astrocytopathy linked to rapidly progressive multiple sclerosis and neuromyelitis optica.

    Directory of Open Access Journals (Sweden)

    Katsuhisa Masaki

    Full Text Available BACKGROUND: Multiple sclerosis (MS and neuromyelitis optica (NMO occasionally have an extremely aggressive and debilitating disease course; however, its molecular basis is unknown. This study aimed to determine a relationship between connexin (Cx pathology and disease aggressiveness in Asian patients with MS and NMO. METHODS/PRINCIPAL FINDINGS: Samples included 11 autopsied cases with NMO and NMO spectrum disorder (NMOSD, six with MS, and 20 with other neurological diseases (OND. Methods of analysis included immunohistochemical expression of astrocytic Cx43/Cx30, oligodendrocytic Cx47/Cx32 relative to AQP4 and other astrocytic and oligodendrocytic proteins, extent of demyelination, the vasculocentric deposition of complement and immunoglobulin, and lesion staging by CD68 staining for macrophages. Lesions were classified as actively demyelinating (n=59, chronic active (n=58 and chronic inactive (n=23. Sera from 120 subjects including 30 MS, 30 NMO, 40 OND and 20 healthy controls were examined for anti-Cx43 antibody by cell-based assay. Six NMO/NMOSD and three MS cases showed preferential loss of astrocytic Cx43 beyond the demyelinated areas in actively demyelinating and chronic active lesions, where heterotypic Cx43/Cx47 astrocyte oligodendrocyte gap junctions were extensively lost. Cx43 loss was significantly associated with a rapidly progressive disease course as six of nine cases with Cx43 loss, but none of eight cases without Cx43 loss regardless of disease phenotype, died within two years after disease onset (66.7% vs. 0%, P=0.0090. Overall, five of nine cases with Cx43 loss and none of eight cases without Cx43 loss had distal oligodendrogliopathy characterized by selective myelin associated glycoprotein loss (55.6% vs. 0.0%, P=0.0296. Loss of oligodendrocytic Cx32 and Cx47 expression was observed in most active and chronic lesions from all MS and NMO/NMOSD cases. Cx43-specific antibodies were absent in NMO/NMOSD and MS patients. CONCLUSIONS

  18. The sensitivity and the specifity of rapid antigen test in streptococcal upper respiratory tract infections.

    Science.gov (United States)

    Gurol, Yesim; Akan, Hulya; Izbirak, Guldal; Tekkanat, Zuhal Tazegun; Gunduz, Tehlile Silem; Hayran, Osman; Yilmaz, Gulden

    2010-06-01

    It is aimed to detect the sensitivity and specificity of rapid antigen detection of group A beta hemolytic streptococci from throat specimen compared with throat culture. The other goal of the study is to help in giving clinical decisions in upper respiratory tract infections according to the age group, by detection of sensitivity and positive predictive values of the rapid tests and throat cultures. Rapid antigen detection and throat culture results for group A beta hemolytic streptococci from outpatients attending to our university hospital between the first of November 2005 and 31st of December 2008 were evaluated retrospectively. Throat samples were obtained by swabs from the throat and transported in the Stuart medium and Quickvue Strep A [Quidel, San Diego, USA] cassette test was applied and for culture, specimen was inoculated on 5% blood sheep agar and identified according to bacitracin and trimethoprim-sulphametaxazole susceptibility from beta hemolytic colonies. During the dates between the first of November 2005 and 31st of December 2008, from 453 patients both rapid antigen detection and throat culture were evaluated. Rapid antigen detection sensitivity and specificity were found to be 64.6% and 96.79%, respectively. The positive predictive value was 80.95% whereas negative predictive value was 92.82%. Kappa index was 0.91. When the results were evaluated according to the age groups, the sensitivity and the positive predictive value of rapid antigen detection in children were 70%, 90.3% and in adults 59.4%, 70.4%. When bacterial infection is concerned to prevent unnecessary antibiotic use, rapid streptococcal antigen test (RSAT) is a reliable method to begin immediate treatment. To get the maximum sensitivity of RSAT, the specimen collection technique used and education of the health care workers is important. While giving clinical decision, it must be taken into consideration that the sensitivity and the positive predictive value of the RSAT is quite

  19. Polymerase chain reaction (PCR) for rapid diagnosis and differentiation of parapoxvirus and orthopoxvirus infections in camels

    International Nuclear Information System (INIS)

    Khalafalla, A.I.; Buettner, M.; Rziha, H.-J.

    2005-01-01

    Rapid identification and differentiation of camel pox (CMP) and camel contagious ecthyma (CCE) were achieved by polymerase chain reaction (PCR) with primers that distinguish Orthopoxvirus (OPV) and Parapovirus (PPV). Forty scab specimens collected from sick camels and sheep were treated by 3 different DNA extraction procedures and examined by PCR. The sensitivity of the PCR was compared with that of electron microscopy and virus isolation in cell culture. Procedure 1, in which viral DNA was extracted directly from scab specimens followed by PCR, proved to be superior and more sensitive. Procedure 2 enables a fast specific diagnosis of PPV and OPV infections directly from scab materials without the need for DNA extraction. These assays provide a rapid and feasible alternative to electron microscopy and virus isolation. (author)

  20. Case report of a 28-year-old male with the rapid progression of steroid-resistant central nervous system vasculitis diagnosed by a brain biopsy.

    Science.gov (United States)

    Takahashi, Keigo; Sato, Hideki; Hattori, Hidenori; Takao, Masaki; Takahashi, Shinichi; Suzuki, Norihiro

    2017-09-30

    A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

  1. Murine Neonates Infected with Yersinia enterocolitica Develop Rapid and Robust Proinflammatory Responses in Intestinal Lymphoid Tissues

    Science.gov (United States)

    Siefker, David T.; Echeverry, Andrea; Brambilla, Roberta; Fukata, Masayuki; Schesser, Kurt

    2014-01-01

    Neonatal animals are generally very susceptible to infection with bacterial pathogens. However, we recently reported that neonatal mice are highly resistant to orogastric infection with Yersinia enterocolitica. Here, we show that proinflammatory responses greatly exceeding those in adults arise very rapidly in the mesenteric lymph nodes (MLN) of neonates. High-level induction of proinflammatory gene expression occurred in the neonatal MLN as early as 18 h postinfection. Marked innate phagocyte recruitment was subsequently detected at 24 h postinfection. Enzyme-linked immunosorbent spot assay (ELISPOT) analyses indicated that enhanced inflammation in neonatal MLN is contributed to, in part, by an increased frequency of proinflammatory cytokine-secreting cells. Moreover, both CD11b+ and CD11b− cell populations appeared to play a role in proinflammatory gene expression. The level of inflammation in neonatal MLN was also dependent on key bacterial components. Y. enterocolitica lacking the virulence plasmid failed to induce innate phagocyte recruitment. In contrast, tumor necrosis factor alpha (TNF-α) protein expression and neutrophil recruitment were strikingly higher in neonatal MLN after infection with a yopP-deficient strain than with wild-type Y. enterocolitica, whereas only modest increases occurred in adults. This hyperinflammatory response was associated with greater colonization of the spleen and higher mortality in neonates, while there was no difference in mortality among adults. This model highlights the dynamic levels of inflammation in the intestinal lymphoid tissues and reveals the protective (wild-type strain) versus harmful (yopP-deficient strain) consequences of inflammation in neonates. Moreover, these results reveal that the neonatal intestinal lymphoid tissues have great potential to rapidly mobilize innate components in response to infection with bacterial enteropathogens. PMID:24478090

  2. Progress in research, control and elimination of helminth infections in Asia.

    Science.gov (United States)

    Utzinger, Jürg; Brattig, Norbert W; Leonardo, Lydia; Zhou, Xiao-Nong; Bergquist, Robert

    2015-01-01

    Global health has substantially improved over the past 20 years. In low- and middle-income countries, in particular, great strives have been made in the control of communicable diseases, including helminth infections. Nevertheless, the most marginalised communities still suffer from infectious diseases that are intimately connected with poverty and lack of access to essential commodities and services, such as clean water, improved sanitation and sufficient food. A two-pronged approach is thus necessary: (i) intensifying control in remaining high-endemicity areas and pockets of high transmission; and (ii) moving from morbidity control to interruption of disease transmission in low-endemicity areas with the goal of local elimination. The latter will require new tools and strategies, going hand-in-hand with strong partnerships and new strategic alliances. In this special issue of Acta Tropica, 35 articles are featured that, together, provide an up-to-date overview of the latest progress made in research, control and elimination of helminth infections in East and Southeast Asia. The first 12 articles expound tools and approaches for improved detection, surveillance and monitoring of helminth infections. Control and elimination approaches for the most important helminth infections are revisited in the next 20 articles. The three remaining articles are cross-cutting pieces examining the interface of agriculture, environment and helminth infections and providing a rationale for integrated, multi-sectorial control approaches that are necessary for sustaining helminthiasis control and progressively moving towards elimination. An interesting aspect revealed through an in-depth analysis of the provenance of the 35 contributions is that the People's Republic of China emerges as a key player in global health, which is documented through its prominent role in research and control of helminth infection and networking throughout Asia. Policy implications are discussed and will

  3. Time of Progression to Osteopenia/Osteoporosis in Chronically HIV-Infected Patients: Screening DXA Scan

    Science.gov (United States)

    Negredo, Eugenia; Bonjoch, Anna; Gómez-Mateu, Moisés; Estany, Carla; Puig, Jordi; Perez-Alvarez, Nuria; Rosales, Joaquin; di Gregorio, Silvana; del Rio, Luis; Gómez, Guadalupe; Clotet, Bonaventura

    2012-01-01

    Background Algorithms for bone mineral density (BMD) management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA) scan should be performed by assessing time of progression to osteopenia/osteoporosis. Methods All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis) was assessed using the Kaplan–Meier method. Strata (tertiles) were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. Results Of 391 patients (1,639 DXAs), 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6%) with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: “low-risk" (baseline minimum T score >−0.2 SD), “middle-risk" (between −0.2 and −0.6 SD), and “high-risk" (from −0.6 to −1 SD); median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (ppatients with osteopenia, 23.7% progressed to osteoporosis; median progression time was >8.5 years. Progression time was >8.2 years in “low-risk" tertile (T score between −1.1 and −1.6 SD), >8.5 years in “middle-risk" (between −1.6 and −2), and 3.2 years in “high-risk" (from −2 to −2.4) (ppatients with bone demineralization could reduce fracture–related morbidity/mortality. PMID:23056229

  4. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease.

    Science.gov (United States)

    Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E

    2017-11-01

    Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.

  5. ANCA-GBM dot-blot : Evaluation of an assay in the differential diagnosis of patients presenting with rapidly progressive glomerulonephritis

    NARCIS (Netherlands)

    Rutgers, Abraham; Damoiseaux, Jan; Roozendaal, Caroline; Limburg, Pieter C; Stegeman, Coen A; Tervaert, Jan Willem Cohen

    Rapidly progressive glomerulonephritis (RPGN) is characterized by rapid and progressive loss of renal function and the presence of crescentic glomerulonephritis (CGN). Early diagnosis and appropriate treatment is mandatory to prevent death and/or renal failure. We have evaluated an ANCA-GBM dot-blot

  6. Genome-Wide Search for Host Association Factors during Ovine Progressive Pneumonia Virus Infection.

    Directory of Open Access Journals (Sweden)

    Jesse Thompson

    Full Text Available Ovine progressive pneumonia virus (OPPV is an important virus that causes serious diseases in sheep and goats with a prevalence of 36% in the USA. Although OPPV was discovered more than half of a century ago, little is known about the infection and pathogenesis of this virus. In this report, we used RNA-seq technology to conduct a genome-wide probe for cellular factors that are associated with OPPV infection. A total of approximately 22,000 goat host genes were detected of which 657 were found to have been significantly up-regulated and 889 down-regulated at 12 hours post-infection. In addition to previously known restriction factors from other viral infections, a number of factors which may be specific for OPPV infection were uncovered. The data from this RNA-seq study will be helpful in our understanding of OPPV infection, and also for further study in the prevention and intervention of this viral disease.

  7. Rapid instrumental and separation methods for monitoring radionuclides in food and environmental samples. Progress report

    International Nuclear Information System (INIS)

    Bhat, I.S.; Shukla, V.K.; Singh, A.N.; Nair, C.K.G.; Hingorani, S.B.; Dey, N.N.; Jha, S.K.; Rao, D.D.

    1995-01-01

    surface barrier detector, in close agreement. Presently the liquid scintillation counter is used with discriminator settling adjusted to count Pu alpha pulses and also the output from the liquid scintillator is connected to a 2K MCA to see the alpha spectrum. The unit at present does not have the Pulse Shape Analyser (PSA) unit which is being planned to be incorporated in the system to improve the resolution. The work is in progress for direct extraction to a liquid scintillation cocktail containing extracting reagents like high mol. amine (TIOA) and Di2 ethyl hexyl phosphoric acid and then count by liquid scintillation counting. Solvent extraction using specific reagent and then direct liquid scintillation counting is being investigated as a general rapid method for beta and alpha emitters in environmental samples

  8. Rapid host immune response and viral dynamics in herpes simplex virus-2 infection

    Science.gov (United States)

    Schiffer, Joshua T; Corey, Lawrence

    2014-01-01

    Herpes Simplex Virus-2 (HSV-2) is episodically shed throughout the human genital tract. While high viral load correlates with development of genital ulcers, shedding also commonly occurs even when ulcers are not present, allowing for silent transmission during coitus and contributing to high seroprevalence of HSV-2 worldwide. Frequent viral reactivation occurs despite diverse and complementary host and viral mechanisms within ganglionic tissue that predispose towards latency, suggesting that viral replication may be constantly occurring in a small minority of neurons within the ganglia. Within genital mucosa, the in vivo expansion and clearance rates of HSV-2 are extremely rapid. Resident dendritic cells and memory HSV-specific T cells persist at prior sites of genital tract reactivation, and in conjunction with prompt innate recognition of infected cells, lead to rapid containment of infected cells. Shedding episodes vary greatly in duration and severity within a single person over time: this heterogeneity appears best explained by variation in the densities of host immunity across the genital tract. The fact that immune responses usually control viral replication in genital skin prior to development of lesions provides optimism that enhancing such responses could lead to effective vaccines and immunotherapies. PMID:23467247

  9. Estimating past hepatitis C infection risk from reported risk factor histories: implications for imputing age of infection and modeling fibrosis progression

    Directory of Open Access Journals (Sweden)

    Busch Michael P

    2007-12-01

    Full Text Available Abstract Background Chronic hepatitis C virus infection is prevalent and often causes hepatic fibrosis, which can progress to cirrhosis and cause liver cancer or liver failure. Study of fibrosis progression often relies on imputing the time of infection, often as the reported age of first injection drug use. We sought to examine the accuracy of such imputation and implications for modeling factors that influence progression rates. Methods We analyzed cross-sectional data on hepatitis C antibody status and reported risk factor histories from two large studies, the Women's Interagency HIV Study and the Urban Health Study, using modern survival analysis methods for current status data to model past infection risk year by year. We compared fitted distributions of past infection risk to reported age of first injection drug use. Results Although injection drug use appeared to be a very strong risk factor, models for both studies showed that many subjects had considerable probability of having been infected substantially before or after their reported age of first injection drug use. Persons reporting younger age of first injection drug use were more likely to have been infected after, and persons reporting older age of first injection drug use were more likely to have been infected before. Conclusion In cross-sectional studies of fibrosis progression where date of HCV infection is estimated from risk factor histories, modern methods such as multiple imputation should be used to account for the substantial uncertainty about when infection occurred. The models presented here can provide the inputs needed by such methods. Using reported age of first injection drug use as the time of infection in studies of fibrosis progression is likely to produce a spuriously strong association of younger age of infection with slower rate of progression.

  10. Temporal Progression of Lesions in Guinea Pigs Infected With Lassa Virus.

    Science.gov (United States)

    Bell, T M; Shaia, C I; Bearss, J J; Mattix, M E; Koistinen, K A; Honnold, S P; Zeng, X; Blancett, C D; Donnelly, G C; Shamblin, J D; Wilkinson, E R; Cashman, K A

    2017-05-01

    Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes. Guinea pigs developed viremia on day 5 to 6 postexposure (PE), with clinical signs appearing by day 7 to 8 PE. Complete blood counts revealed lymphopenia and thrombocytopenia. Gross pathologic findings included skin lesions and congested lungs. Histologic lesions consisted of cortical lymphoid depletion by day 6 to 7 PE with lymphohistiocytic interstitial pneumonia at 7 to 8 days PE. Scattered hepatocellular degeneration and cell death were also noted in the liver and, to a lesser extent, in other tissues including the haired skin, lung, heart, adrenal gland, lymph nodes, thymus, and spleen. The first cell types to demonstrate staining for viral antigen were fibroblastic reticular cells and macrophages/dendritic cells in the lymph nodes on day 5 to 6 PE. This study demonstrates similarities between Lassa viral disease in human infections and experimental guinea pig infection. These shared pathologic characteristics support the utility of guinea pigs as an additional animal model for vaccine and therapeutic development under the Food and Drug Administration's Animal Rule.

  11. Progression of chronic pulmonary tuberculosis in mice intravenously infected with ethambutol resistant Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Srivastava S

    2008-01-01

    Full Text Available Purpose: Ethambutol (EMB is an important first line drug, however little information on its molecular mechanism of resistance and pathogenicity of resistant isolates is available. Present work was designed to study virulence of the EMB resistant M. tuberculosis strains and the host responses in-vivo on infection of EMB resistant M. tuberculosis using Balb/c mouse model of infection. Methods: Three groups of Balb/c mice (female, age 4-6 wk; 21 mice in each group were infected intravenously with 106 CFU of M. tuberculosis H37Rv and two EMB resistant clinical isolates. Age and sex matched control animals were mock inoculated with Middlebrook 7H9 broth alone. At 10, 20, 30, 40, 50, 60, and 70 days post-infection three animals from each group were sacrificed by cervical dislocation and lung tissue was collected for further analysis. Results: Infection with EMB resistant M. tuberculosis led to progressive and chronic disease with significantly high bacillary load (p=0.02. Massive infiltration and exacerbated lung pathology with increased expression of IFN-γ and TNF-α was observed in lungs of mice infected with EMB resistant strains. The present study suggests that infection with EMB resistant M. tuberculosis leads to chronic infection with subsequent loss of lung function, bacterial persistence with elevated expression of TNF-α resulting in increased lung pathology. Conclusion: These findings highlight that EMB resistant M. tuberculosis regulates host immune response differentially and its pathogenicity is different from drug sensitive strains of M. tuberculosis.

  12. Emphysema Distribution and Diffusion Capacity Predict Emphysema Progression in Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Leung, Janice M; Malagoli, Andrea; Santoro, Antonella; Besutti, Giulia; Ligabue, Guido; Scaglioni, Riccardo; Dai, Darlene; Hague, Cameron; Leipsic, Jonathon; Sin, Don D.; Man, SF Paul; Guaraldi, Giovanni

    2016-01-01

    Background Chronic obstructive pulmonary disease (COPD) and emphysema are common amongst patients with human immunodeficiency virus (HIV). We sought to determine the clinical factors that are associated with emphysema progression in HIV. Methods 345 HIV-infected patients enrolled in an outpatient HIV metabolic clinic with ≥2 chest computed tomography scans made up the study cohort. Images were qualitatively scored for emphysema based on percentage involvement of the lung. Emphysema progression was defined as any increase in emphysema score over the study period. Univariate analyses of clinical, respiratory, and laboratory data, as well as multivariable logistic regression models, were performed to determine clinical features significantly associated with emphysema progression. Results 17.4% of the cohort were emphysema progressors. Emphysema progression was most strongly associated with having a low baseline diffusion capacity of carbon monoxide (DLCO) and having combination centrilobular and paraseptal emphysema distribution. In adjusted models, the odds ratio (OR) for emphysema progression for every 10% increase in DLCO percent predicted was 0.58 (95% confidence interval [CI] 0.41–0.81). The equivalent OR (95% CI) for centrilobular and paraseptal emphysema distribution was 10.60 (2.93–48.98). Together, these variables had an area under the curve (AUC) statistic of 0.85 for predicting emphysema progression. This was an improvement over the performance of spirometry (forced expiratory volume in 1 second to forced vital capacity ratio), which predicted emphysema progression with an AUC of only 0.65. Conclusion Combined paraseptal and centrilobular emphysema distribution and low DLCO could identify HIV patients who may experience emphysema progression. PMID:27902753

  13. Rapid Disease Progression With Delay in Treatment of Non-Small-Cell Lung Cancer

    International Nuclear Information System (INIS)

    Mohammed, Nasiruddin; Kestin, Larry Llyn; Grills, Inga Siiner; Battu, Madhu; Fitch, Dwight Lamar; Wong, Ching-yee Oliver; Margolis, Jeffrey Harold; Chmielewski, Gary William; Welsh, Robert James

    2011-01-01

    Purpose: To assess rate of disease progression from diagnosis to initiation of treatment for Stage I-IIIB non-small-cell lung cancer (NSCLC). Methods and Materials: Forty patients with NSCLC underwent at least two sets of computed tomography (CT) and 18-fluorodeoxyglucose positron emission tomography (PET) scans at various time intervals before treatment. Progression was defined as development of any new lymph node involvement, site of disease, or stage change. Results: Median time interval between first and second CT scans was 13.4 weeks, and between first and second PET scans was 9.0 weeks. Median initial primary maximum tumor dimension (MTD) was 3.5 cm (0.6-8.5 cm) with a median standardized uptake value (SUV) of 13.0 (1.7-38.5). The median MTD increased by a median of 1.0 cm (mean, 1.6 cm) between scans for a median relative MTD increase of 35% (mean, 59%). Nineteen patients (48%) progressed between scans. Rate of any progression was 13%, 31%, and 46% at 4, 8, and 16 weeks, respectively. Upstaging occurred in 3%, 13%, and 21% at these intervals. Distant metastasis became evident in 3%, 13%, and 13% after 4, 8, and 16 weeks, respectively. T and N stage were associated with progression, whereas histology, grade, sex, age, and maximum SUV were not. At 3 years, overall survival for Stage III patients with vs. without progression was 18% vs. 67%, p = 0.05. Conclusions: With NSCLC, treatment delay can lead to disease progression. Diagnosis, staging, and treatment initiation should be expedited. After 4-8 weeks of delay, complete restaging should be strongly considered.

  14. Rapid Growth of Uropathogenic Escherichia coli during Human Urinary Tract Infection

    Directory of Open Access Journals (Sweden)

    Valerie S. Forsyth

    2018-03-01

    Full Text Available Uropathogenic Escherichia coli (UPEC strains cause most uncomplicated urinary tract infections (UTIs. These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical sites. Here, we hypothesize that UPEC isolates adapt to and grow more rapidly within the urinary tract than other E. coli isolates and survive in that niche. To date, there has not been a reliable method available to measure their growth rate in vivo. Here we used two methods: segregation of nonreplicating plasmid pGTR902, and peak-to-trough ratio (PTR, a sequencing-based method that enumerates bacterial chromosomal replication forks present during cell division. In the murine model of UTI, UPEC strain growth was robust in vivo, matching or exceeding in vitro growth rates and only slowing after reaching high CFU counts at 24 and 30 h postinoculation (hpi. In contrast, asymptomatic bacteriuria (ABU strains tended to maintain high growth rates in vivo at 6, 24, and 30 hpi, and population densities did not increase, suggesting that host responses or elimination limited population growth. Fecal strains displayed moderate growth rates at 6 hpi but did not survive to later times. By PTR, E. coli in urine of human patients with UTIs displayed extraordinarily rapid growth during active infection, with a mean doubling time of 22.4 min. Thus, in addition to traditional virulence determinants, including adhesins, toxins, iron acquisition, and motility, very high growth rates in vivo and resistance to the innate immune response appear to be critical phenotypes of UPEC strains.

  15. A Rapid Method for Quantifying Viable Mycobacterium avium subsp. paratuberculosis in Cellular Infection Assays

    Science.gov (United States)

    Pooley, Hannah B.; de Silva, Kumudika; Purdie, Auriol C.; Begg, Douglas J.; Whittington, Richard J.

    2016-01-01

    ABSTRACT Determining the viability of bacteria is a key outcome of in vitro cellular infection assays. Currently, this is done by culture, which is problematic for fastidious slow-growing bacteria such as Mycobacterium avium subsp. paratuberculosis, where it can take up to 4 months to confirm growth. This study aimed to identify an assay that can rapidly quantify the number of viable M. avium subsp. paratuberculosis cells in a cellular sample. Three commercially available bacterial viability assays along with a modified liquid culture method coupled with high-throughput quantitative PCR growth detection were assessed. Criteria for assessment included the ability of each assay to differentiate live and dead M. avium subsp. paratuberculosis organisms and their accuracy at low bacterial concentrations. Using the culture-based method, M. avium subsp. paratuberculosis growth was reliably detected and quantified within 2 weeks. There was a strong linear association between the 2-week growth rate and the initial inoculum concentration. The number of viable M. avium subsp. paratuberculosis cells in an unknown sample was quantified based on the growth rate, by using growth standards. In contrast, none of the commercially available viability assays were suitable for use with samples from in vitro cellular infection assays. IMPORTANCE Rapid quantification of the viability of Mycobacterium avium subsp. paratuberculosis in samples from in vitro cellular infection assays is important, as it allows these assays to be carried out on a large scale. In vitro cellular infection assays can function as a preliminary screening tool, for vaccine development or antimicrobial screening, and also to extend findings derived from experimental animal trials. Currently, by using culture, it takes up to 4 months to obtain quantifiable results regarding M. avium subsp. paratuberculosis viability after an in vitro infection assay; however, with the quantitative PCR and liquid culture method

  16. Ultra-violet resonance Raman spectroscopy for the rapid discrimination of urinary tract infection bacteria.

    Science.gov (United States)

    Jarvis, Roger M; Goodacre, Royston

    2004-03-19

    The ability to identify pathogenic organisms rapidly provides significant benefits to clinicians; in particular, with respect to best prescription practices and tracking of recurrent infections. Conventional bioassays require 3-5 days before identification of an organism can be made, thus compromising the effectiveness with which patients can be treated for bacterial infections. We analysed 20 clinical isolates of urinary tract infections (UTI) by ultra-violet resonance Raman (UVRR) spectroscopy, utilising 244 nm excitation delivering approximately 0.1 mW laser power at the sample, with typical spectral collection times of 120 s. UVRR results in resonance-enhanced Raman signals for certain chromophoric segments of macromolecules, intensifying those selected bands above what would otherwise be observed for a normal Raman experiment. Utilising the whole-organism 'fingerprints' obtained by UVRR we were able to discriminate successfully between UTI pathogens using chemometric cluster analyses. This work demonstrates significant improvements in the speed with which spectra can be obtained by Raman spectroscopic techniques for the discrimination of clinical bacterial samples.

  17. A rapid and quantitative assay for measuring antibody-mediated neutralization of West Nile virus infection

    International Nuclear Information System (INIS)

    Pierson, Theodore C.; Sanchez, Melissa D.; Puffer, Bridget A.; Ahmed, Asim A.; Geiss, Brian J.; Valentine, Laura E.; Altamura, Louis A.; Diamond, Michael S.; Doms, Robert W.

    2006-01-01

    West Nile virus (WNV) is a neurotropic flavivirus within the Japanese encephalitis antigenic complex that is responsible for causing West Nile encephalitis in humans. The surface of WNV virions is covered by a highly ordered icosahedral array of envelope proteins that is responsible for mediating attachment and fusion with target cells. These envelope proteins are also primary targets for the generation of neutralizing antibodies in vivo. In this study, we describe a novel approach for measuring antibody-mediated neutralization of WNV infection using virus-like particles that measure infection as a function of reporter gene expression. These reporter virus particles (RVPs) are produced by complementation of a sub-genomic replicon with WNV structural proteins provided in trans using conventional DNA expression vectors. The precision and accuracy of this approach stem from an ability to measure the outcome of the interaction between antibody and viral antigens under conditions that satisfy the assumptions of the law of mass action as applied to virus neutralization. In addition to its quantitative strengths, this approach allows the production of WNV RVPs bearing the prM-E proteins of different WNV strains and mutants, offering considerable flexibility for the study of the humoral immune response to WNV in vitro. WNV RVPs are capable of only a single round of infection, can be used under BSL-2 conditions, and offer a rapid and quantitative approach for detecting virus entry and its inhibition by neutralizing antibody

  18. Hyperspectral image analysis for rapid and accurate discrimination of bacterial infections: A benchmark study.

    Science.gov (United States)

    Arrigoni, Simone; Turra, Giovanni; Signoroni, Alberto

    2017-09-01

    With the rapid diffusion of Full Laboratory Automation systems, Clinical Microbiology is currently experiencing a new digital revolution. The ability to capture and process large amounts of visual data from microbiological specimen processing enables the definition of completely new objectives. These include the direct identification of pathogens growing on culturing plates, with expected improvements in rapid definition of the right treatment for patients affected by bacterial infections. In this framework, the synergies between light spectroscopy and image analysis, offered by hyperspectral imaging, are of prominent interest. This leads us to assess the feasibility of a reliable and rapid discrimination of pathogens through the classification of their spectral signatures extracted from hyperspectral image acquisitions of bacteria colonies growing on blood agar plates. We designed and implemented the whole data acquisition and processing pipeline and performed a comprehensive comparison among 40 combinations of different data preprocessing and classification techniques. High discrimination performance has been achieved also thanks to improved colony segmentation and spectral signature extraction. Experimental results reveal the high accuracy and suitability of the proposed approach, driving the selection of most suitable and scalable classification pipelines and stimulating clinical validations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Using MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis: a case report of a patient with mitral valve infective endocarditis caused by Abiotrophia defectiva

    DEFF Research Database (Denmark)

    Holler, Jon Gitz; Pedersen, Line; Calum, Henrik

    2011-01-01

    A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed.......A case of infective endocarditis caused by Abiotrophia defectiva is presented. The use of MALDI-TOF mass spectrometry as a rapid and accurate diagnostic tool in infective endocarditis is discussed....

  20. Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients.

    Science.gov (United States)

    Hønge, Bl; Jespersen, S; Medina, C; Té, Ds; da Silva, Zj; Ostergaard, L; Laursen, Al; Wejse, C; Krarup, H; Erikstrup, C

    2014-10-01

    In the case of coinfection with HIV and hepatitis B virus (HBV) and/or hepatitis C virus (HCV), hepatic disease progression is often accelerated, with higher rates of liver cirrhosis and liver-related mortality. We aimed to evaluate the performance of the rapid tests used routinely to detect HBV surface antigen (HBsAg) and anti-HCV among HIV-infected patients in Guinea-Bissau. Blood samples from HIV-infected patients in Guinea-Bissau were stored after testing for HBsAg and anti-HCV with rapid tests. Samples were subsequently re-tested for HBsAg and anti-HCV in Denmark. Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended on the antigen and antibody concentrations, respectively. Sex, age, CD4 cell count and antiretroviral therapy status did not differ between false negative and true positive samples in either of the tests. The study is limited by a low number of anti-HCV positive samples. New diagnostic rapid tests should always be evaluated in the setting in which they will be used before implementation. © 2014 British HIV Association.

  1. Successful Surgical Management of Retinopathy of Prematurity Showing Rapid Progression despite Extensive Retinal Photocoagulation.

    Science.gov (United States)

    Gadkari, Salil S; Kulkarni, Sucheta R; Kamdar, Rushita R; Deshpande, Madan

    2015-01-01

    The management of retinopathy of prematurity (ROP) can be challenging in preterm babies with a gestational age premature infant presented with "hybrid" zone 1 disease in the right eye and aggressive posterior ROP in the left eye. Both eyes were adequately treated with laser photocoagulation; however, the eyes deteriorated and progressed to stage 4 ROP. Both eyes eventually underwent intravitreal bevacizumab followed by lens sparing vitrectomy with good anatomical and visual outcome. Anticipation of progression despite laser photocoagulation in certain clinical scenarios, frequent follow-up and timely surgical intervention is paramount.

  2. Rapid-Growing Mycobacteria Infections in Medical Tourists: Our Experience and Literature Review.

    Science.gov (United States)

    Singh, Mansher; Dugdale, Caitlin M; Solomon, Isaac H; Huang, Anne; Montgomery, Mary W; Pomahac, Bohdan; Yawetz, Sigal; Maguire, James H; Talbot, Simon G

    2016-09-01

    "Medical tourism" has gained popularity over the past few decades. This is particularly common with patients seeking elective cosmetic surgery in the developing world. However, the risk of severe and unusual infectious complications appears to be higher than for patients undergoing similar procedures in the United States. The authors describe their experience with atypical mycobacterial infections in cosmetic surgical patients returning to the United States postoperatively. A review of patient medical records presenting with infectious complications after cosmetic surgery between January 2010 and July 2015 was performed. Patients presenting with mycobacterial infections following cosmetic surgery were reviewed in detail. An extensive literature review was performed for rapid-growing mycobacteria (RGM) related to cosmetic procedures. Between January 2010 and July 2015, three patients presented to our institution with culture-proven Mycobacterium abscessus at the sites of recent cosmetic surgery. All had surgery performed in the developing world. The mean age of these patients was 36 years (range, 29-44 years). There was a delay of up to 16 weeks between the initial presentation and correct diagnosis. All patients were treated with surgical drainage and combination antibiotics with complete resolution. We present series of patients with mycobacterial infections after cosmetic surgery in the developing world. This may be related to the endemic nature of these bacteria and/or inadequate sterilization or sterile technique. Due to low domestic incidence of these infections, diagnosis may be difficult and/or delayed. Consulting physicians should have a low threshold to consider atypical etiologies in such scenarios. 5 Therapeutic. © 2016 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.

  3. Colpocytological abnormalities in HIV infected and uninfected pregnant women: prevalence, persistence and progression.

    Science.gov (United States)

    Carriero, Carmine; Fascilla, Fabiana Divina; Cramarossa, Paola; Lepera, Achiropita; Bettocchi, Stefano; Vimercati, Antonella

    2018-02-01

    In this retrospective case-control study, we analyse data of 48 HIV-positive pregnant patients, versus a control group of 99 HIV-negative pregnant women, followed as outpatients by our department from 2009 to 2014. The aims of the study were to investigate the prevalence, persistence and progression of cervical squamous intraepithelial lesions (SIL) in each group and to correlate colpo-cytological lesions to the socio-demographic and clinical-laboratory findings in the HIV + pregnant women. In our study we observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions. Pap smear and colposcopy should be part of routine care for HIV-infected pregnant women because these lesions behave aggressively in these patients. Success of prevention depends on massive access of patients to screening. HAART reduces viral load and maintains CD4 count and can affect progression of SIL. Multidisciplinary services on the same site appear to be one promising strategy to improve compliance in patients. Impact Statement What is already known on this subject: Our study provided novel information on a highly vulnerable population of young HIV + pregnant women. What the results of this study add: We observed that immunosuppression, HPV infection and vaginal coinfections were predictive of cervical lesions remarkable with colposcopy. We could consider these important risk factors to evaluate to establish an appropriate strategy of management for these patients. What the implications are of these findings for clinical practice and/or further research: Association of the risk between SIL presence and HIV and HPV infection also deserves additional investigation. We believe that Pap smears and colposcopies should be part of the routine care for HIV-infected women because these lesions behave particularly aggressively in these patients.

  4. Time of progression to osteopenia/osteoporosis in chronically HIV-infected patients: screening DXA scan.

    Directory of Open Access Journals (Sweden)

    Eugenia Negredo

    Full Text Available BACKGROUND: Algorithms for bone mineral density (BMD management in HIV-infected patients are lacking. Our objective was to assess how often a dual-energy x-ray absorptiometry (DXA scan should be performed by assessing time of progression to osteopenia/osteoporosis. METHODS: All DXA scans performed between 2000 and 2009 from HIV-infected patients with at least two DXA were included. Time to an event (osteopenia and osteoporosis was assessed using the Kaplan-Meier method. Strata (tertiles were defined using baseline minimum T scores. Differences between strata in time to an event were compared with the log-rank test. RESULTS: Of 391 patients (1,639 DXAs, 49.6% had osteopenia and 21.7% osteoporosis at their first DXA scan. Of the 112 (28.6% with normal BMD, 35.7% progressed to osteopenia; median progression time was 6.7 years. These patients were stratified: "low-risk" (baseline minimum T score >-0.2 SD, "middle-risk" (between -0.2 and -0.6 SD, and "high-risk" (from -0.6 to -1 SD; median progression time to osteopenia was 8.7, >7.2, and 1.7 years, respectively (p8.5 years. Progression time was >8.2 years in "low-risk" tertile (T score between -1.1 and -1.6 SD, >8.5 years in "middle-risk" (between -1.6 and -2, and 3.2 years in "high-risk" (from -2 to -2.4 (p<0.0001. CONCLUSIONS: Our results may help to define the BMD testing interval. The lowest T score tertiles would suggest recommending a subsequent DXA in 1-2 years; in the highest tertiles, ≥6 years. Early intervention in patients with bone demineralization could reduce fracture-related morbidity/mortality.

  5. A rapidly progressing, deadly disease ofActias selene(Indian moon ...

    Indian Academy of Sciences (India)

    2015-07-08

    Jul 8, 2015 ... moon moth) larvae associated with a mixed bacterial and baculoviral infection. J. Biosci. ... assisted laser desorption/ionization time-of-flight mass spec- ... The two smallest larvae are first instar, the middle-sized larva is the.

  6. Increased common carotid artery wall thickness is associated with rapid progression of asymptomatic carotid stenosis.

    Science.gov (United States)

    Diomedi, Marina; Scacciatelli, Daria; Misaggi, Giulia; Balestrini, Simona; Balucani, Clotilde; Sallustio, Fabrizio; Di Legge, Silvia; Stanzione, Paolo; Silvestrini, Mauro

    2014-01-01

    This study aimed to identify clinical and ultrasound imaging predictors of progression of carotid luminal narrowing in subjects with asymptomatic moderate internal carotid artery (ICA) stenosis. A total of 571 subjects with asymptomatic moderate (50-69%) ICA stenoses were enrolled. They underwent ultrasound examination at baseline and after 12 months. Demographics, vascular risk factors, medications, plaque characteristics (surface and echogenicity) and common carotid intima-media thickness (IMT) were collected. At the follow-up examination, any change of ICA stenosis was graded in three categories (i) ≥70% to near occlusion, (ii) near occlusion, and (iii) occlusion. Progression of stenosis was defined as an increase in the stenosis degree by at least one category from baseline to follow-up. At 12 months, progression occurred in 142 subjects (prevalence rate 25%). At the multivariable logistic model, pathological IMT values (considered as binary variable: normal: ≤1 mm vs. pathologic: >1 mm) significantly predicted the risk for plaque progression after adjusting the model for possible confounders (OR 2.28, 95% CI 1.18-4.43, P = .014, multivariable logistic model). Our results confirm the role of carotid wall thickening as a marker of atherosclerosis. Carotid IMT measurement should be considered to implement risk stratification in patients with asymptomatic carotid disease.

  7. Psycho-immunology and HIV infection : biopsychosocial determinants of distress, immunological parameters, and disease progression in homosexual men infected with human immunodeficiency virus-1

    NARCIS (Netherlands)

    C.L. Mulder (Niels)

    1994-01-01

    textabstractSubjects who have tested positive for the presence of antibodies against Human Immunodeficiency Virus Type I (further abbreviated as HIV), have to live with a lifethreatening infection. At present, no definite medical cure is available that prevents progression of HIV infection.

  8. Pulmonary infection by Yersinia pestis rapidly establishes a permissive environment for microbial proliferation.

    Science.gov (United States)

    Price, Paul A; Jin, Jianping; Goldman, William E

    2012-02-21

    Disease progression of primary pneumonic plague is biphasic, consisting of a preinflammatory and a proinflammatory phase. During the long preinflammatory phase, bacteria replicate to high levels, seemingly uninhibited by normal pulmonary defenses. In a coinfection model of pneumonic plague, it appears that Yersinia pestis quickly creates a localized, dominant anti-inflammatory state that allows for the survival and rapid growth of both itself and normally avirulent organisms. Yersinia pseudotuberculosis, the relatively recent progenitor of Y. pestis, shows no similar trans-complementation effect, which is unprecedented among other respiratory pathogens. We demonstrate that the effectors secreted by the Ysc type III secretion system are necessary but not sufficient to mediate this apparent immunosuppression. Even an unbiased negative selection screen using a vast pool of Y. pestis mutants revealed no selection against any known virulence genes, demonstrating the transformation of the lung from a highly restrictive to a generally permissive environment during the preinflammatory phase of pneumonic plague.

  9. Constriction of juxta-ductal aorta and rapid progression of obstruction in a newborn

    Directory of Open Access Journals (Sweden)

    Awasthy Neeraj

    2010-01-01

    Full Text Available A 13-day-old baby girl presenting with features of congestive cardiac failure was found to have coarctation of the aorta (CoA and patent ductus arteriosus (PDA by echocardiography. Doppler spectral display revealed moderate CoA. Echocardiogram, 12 hours later, showed severe juxtaductal aortic coarctation with spontaneous closure of PDA. This case emphasises the need to keep a close watch on the progress of CoA in the neonatal period, even if the duct has narrowed to a small size thus demonstrating the role of constriction of juxtaductal aorta in pathogenesis of coaractation. Closure of even asmall PDA can cause acute progression CoA in the presence of posterior shelf.

  10. Constriction of juxta-ductal aorta and rapid progression of obstruction in a newborn

    International Nuclear Information System (INIS)

    Awasthy, Neeraj; Tomar, Munesh; Radhakrishnan, Sitaraman; Iyer, Krishna Subramoney

    2010-01-01

    A 13-day-old baby girl presenting with features of congestive cardiac failure was found to have coarctation of the aorta (CoA) and patent ductus arteriosus (PDA) by echocardiography. Doppler spectral display revealed moderate CoA. Echocardiogram, 12 hours later, showed severe juxtaductal aortic coarctation with spontaneous closure of PDA. This case emphasises the need to keep a close watch on the progress of CoA in the neonatal period, even if the duct has narrowed to a small size thus demonstrating the role of constriction of juxtaductal aorta in pathogenesis of coaractation. Closure of even asmall PDA can cause acute progression CoA in the presence of posterior shelf

  11. Rapidly progressive effusive constrictive pericarditis caused by methicillin sensitive Staphylococcus aureus (MSSA). samraakhtar@hotmail.com.

    Science.gov (United States)

    Akhtar, Naveed; Khalid, Ayesha; Ahmed, Waqas; Rasheed, Khalid

    2010-04-01

    Effusive-constrictive pericarditis is a clinical syndrome characterized by concurrent pericardial effusion and pericardial constriction, where constrictive hemodynamics are persistent after effusion is drained. It may present at any point along the clinical course, from the occurrence of an effusion to the development of chronic pericardial constriction. We refer an unusual case of effusive constrictive pericarditis developing rapidly within days, following purulent pericarditis secondary to chest trauma.

  12. Mixing and matching Bevalac programs: Rapid-switching of ions and other operations highlights: Progress report

    International Nuclear Information System (INIS)

    Lothrop, F.; Alonso, J.; Krebs, G.; Miller, R.; Stevenson, R.

    1987-03-01

    Rapid switching of ion, energy, and beam line has been accomplished on a routine basis; typical transfer time is 1 to 2 minutes in worst case situations. Operational efficiency has been improved by substantial reduction of inter-experiment tune time and improved optics in the external beam area installed in 1985. A comparison of current research efficiency and previous year efficiency is given. It is shown that compatibility and productivity for two simultaneous, independent research programs are not mutually exclusive

  13. New strategy for rapid diagnosis and characterization of fungal infections: the example of corneal scrapings.

    Directory of Open Access Journals (Sweden)

    Pablo Goldschmidt

    Full Text Available PURPOSE: The prognosis of people infected with Fungi especially immunocompromised depends on rapid and accurate diagnosis to capitalize on time administration of specific treatments. However, cultures produce false negative results and nucleic-acid amplification techniques require complex post-amplification procedures to differentiate relevant fungal types. The objective of this work was to develop a new diagnostic strategy based on real-time polymerase-chain reaction high-resolution melting analysis (PCR-HRM that a detects yeasts and filamentous Fungi, b differentiates yeasts from filamentous Fungi, and c discriminates among relevant species of yeasts. METHODS: PCR-HRM detection limits and specificity were assessed with a isolated strains; b human blood samples experimentally infected with Fungi; c blood experimentally infected with other infectious agents; d corneal scrapings from patients with suspected fungal keratitis (culture positive and negative and e scrapings from patients with suspected bacterial, viral or Acanthamoeba infections. The DNAs were extracted and mixed with primers diluted in the MeltDoctor® HRM Master Mix in 2 tubes, the first for yeasts, containing the forward primer CandUn (5'CATGCCTGTTTGAGCGTC and the reverse primer FungUn (5'TCCTCCGCTT ATTGATATGCT and the second for filamentous Fungi, containing the forward primer FilamUn (5'TGCCTGTCCGAGCGTCAT and FungUn. Molecular probes were not necessary. The yields of DNA extraction and the PCR inhibitors were systematically monitored. RESULTS: PCR-HRM detected 0.1 Colony Forming Units (CFU/µl of yeasts and filamentous Fungi, differentiated filamentous Fungi from yeasts and discriminated among relevant species of yeasts. PCR-HRM performances were higher than haemoculture and sensitivity and specificity was 100% for culture positive samples, detecting and characterizing Fungi in 7 out 10 culture negative suspected fungal keratitis. CONCLUSIONS: PCR-HRM appears as a new, sensitive

  14. Progressive Hypertrophic Genital Herpes in an HIV-Infected Woman despite Immune Recovery on Antiretroviral Therapy

    Directory of Open Access Journals (Sweden)

    Mark H. Yudin

    2008-01-01

    Full Text Available Most HIV-infected individuals are coinfected by Herpes simplex virus type 2 (HSV-2. HSV-2 reactivates more frequently in HIV-coinfected individuals with advanced immunosuppression, and may have very unusual clinical presentations, including hypertrophic genital lesions. We report the case of a progressive, hypertrophic HSV-2 lesion in an HIV-coinfected woman, despite near-complete immune restoration on antiretroviral therapy for up to three years. In this case, there was prompt response to topical imiquimod. The immunopathogenesis and clinical presentation of HSV-2 disease in HIV-coinfected individuals are reviewed, with a focus on potential mechanisms for persistent disease despite apparent immune reconstitution. HIV-infected individuals and their care providers should be aware that HSV-2 may cause atypical disease even in the context of near-comlpete immune reconstitution on HAART.

  15. Gut Microbiota in HIV Infection: Implication for Disease Progression and Management

    Directory of Open Access Journals (Sweden)

    Felix Chinweije Nwosu

    2014-01-01

    Full Text Available Survival rates among HIV patients have significantly improved since the introduction of antiretroviral therapy (ART in HIV management. However, persistent disease progression and clinical complications in virally suppressed individuals point to additional contributing factors other than HIV replication; microbial translocation is one such factor. The role of underlying commensal microbes and microbial products that traverse the intestinal lumen into systemic circulation in the absence of overt bacteraemia is under current investigation. This review focuses on current knowledge of the complex microbial communities and microbial markers involved in the disruption of mucosal immune T-cells in the promotion of inflammatory processes in HIV infections. Unanswered questions and aims for future studies are addressed. We provide perspective for discussing potential future therapeutic strategies focused on modulating the gut microbiota to abate HIV disease progression.

  16. Rapid Quantitative Serological Test for Detection of Infection with Mycobacterium leprae, the Causative Agent of Leprosy

    Science.gov (United States)

    Balagon, Marivic F.; Maghanoy, Armi; Orcullo, Florenda M.; Cang, Marjorie; Dias, Ronaldo Ferreira; Collovati, Marco; Reed, Steven G.

    2014-01-01

    Leprosy remains an important health problem in a number of regions. Early detection of infection, followed by effective treatment, is critical to reduce disease progression. New sensitive and specific tools for early detection of infection will be a critical component of an effective leprosy elimination campaign. Diagnosis is made by recognizing clinical signs and symptoms, but few clinicians are able to confidently identify these. Simple tests to facilitate referral to leprosy experts are not widely available, and the correct diagnosis of leprosy is often delayed. In this report, we evaluate the performance of a new leprosy serological test (NDO-LID). As expected, the test readily detected clinically confirmed samples from patients with multibacillary (MB) leprosy, and the rate of positive results declined with bacterial burden. NDO-LID detected larger proportions of MB and paucibacillary (PB) leprosy than the alternative, the Standard Diagnostics leprosy test (87.0% versus 81.7% and 32.3% versus 6.5%, respectively), while also demonstrating improved specificity (97.4% versus 90.4%). Coupled with a new cell phone-based test reader platform (Smart Reader), the NDO-LID test provided consistent, objective test interpretation that could facilitate wider use in nonspecialized settings. In addition, results obtained from sera at the time of diagnosis, versus at the end of treatment, indicated that the quantifiable nature of this system can also be used to monitor treatment efficacy. Taken together, these data indicate that the NDO-LID/Smart Reader system can assist in the diagnosis and monitoring of MB leprosy and can detect a significant number of earlier-stage infections. PMID:24478496

  17. Nosocomial rapidly growing mycobacterial infections following laparoscopic surgery: CT imaging findings

    International Nuclear Information System (INIS)

    Volpato, Richard; Campi de Castro, Claudio; Hadad, David Jamil; Silva Souza Ribeiro, Flavya da; Filho, Ezequiel Leal; Marcal, Leonardo P.

    2015-01-01

    To identify the distribution and frequency of computed tomography (CT) findings in patients with nosocomial rapidly growing mycobacterial (RGM) infection after laparoscopic surgery. A descriptive retrospective study in patients with RGM infection after laparoscopic surgery who underwent CT imaging prior to initiation of therapy. The images were analyzed by two radiologists in consensus, who evaluated the skin/subcutaneous tissues, the abdominal wall, and intraperitoneal region separately. The patterns of involvement were tabulated as: densification, collections, nodules (≥1.0 cm), small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated nodules. Twenty-six patients met the established criteria. The subcutaneous findings were: densification (88.5 %), small nodules (61.5 %), small pseudocavitated nodules (23.1 %), nodules (38.5 %), pseudocavitated nodules (15.4 %), and collections (26.9 %). The findings in the abdominal wall were: densification (61.5 %), pseudocavitated nodules (3.8 %), and collections (15.4 %). The intraperitoneal findings were: densification (46.1 %), small nodules (42.3 %), nodules (15.4 %), and collections (11.5 %). Subcutaneous CT findings in descending order of frequency were: densification, small nodules, nodules, small pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo-fascial plane CT findings were: densification, collections, and pseudocavitated nodules. The intraperitoneal CT findings were: densification, small nodules, nodules, and collections. (orig.)

  18. Nosocomial rapidly growing mycobacterial infections following laparoscopic surgery: CT imaging findings

    Energy Technology Data Exchange (ETDEWEB)

    Volpato, Richard [Cassiano Antonio de Moraes University Hospital, Department of Diagnostic Radiology, Vitoria, ES (Brazil); Campi de Castro, Claudio [University of Sao Paulo Medical School, Department of Radiology, Cerqueira Cesar, Sao Paulo (Brazil); Hadad, David Jamil [Cassiano Antonio de Moraes University Hospital, Nucleo de Doencas Infecciosas, Department of Internal Medicine, Vitoria, ES (Brazil); Silva Souza Ribeiro, Flavya da [Laboratorio de Patologia PAT, Department of Diagnostic Radiology, Unit 1473, Vitoria, ES (Brazil); Filho, Ezequiel Leal [UNIMED Diagnostico, Department of Diagnostic Radiology, Unit 1473, Vitoria, ES (Brazil); Marcal, Leonardo P. [The University of Texas M D Anderson Cancer Center, Department of Diagnostic Radiology, Unit 1473, Houston, TX (United States)

    2015-09-15

    To identify the distribution and frequency of computed tomography (CT) findings in patients with nosocomial rapidly growing mycobacterial (RGM) infection after laparoscopic surgery. A descriptive retrospective study in patients with RGM infection after laparoscopic surgery who underwent CT imaging prior to initiation of therapy. The images were analyzed by two radiologists in consensus, who evaluated the skin/subcutaneous tissues, the abdominal wall, and intraperitoneal region separately. The patterns of involvement were tabulated as: densification, collections, nodules (≥1.0 cm), small nodules (<1.0 cm), pseudocavitated nodules, and small pseudocavitated nodules. Twenty-six patients met the established criteria. The subcutaneous findings were: densification (88.5 %), small nodules (61.5 %), small pseudocavitated nodules (23.1 %), nodules (38.5 %), pseudocavitated nodules (15.4 %), and collections (26.9 %). The findings in the abdominal wall were: densification (61.5 %), pseudocavitated nodules (3.8 %), and collections (15.4 %). The intraperitoneal findings were: densification (46.1 %), small nodules (42.3 %), nodules (15.4 %), and collections (11.5 %). Subcutaneous CT findings in descending order of frequency were: densification, small nodules, nodules, small pseudocavitated nodules, pseudocavitated nodules, and collections. The musculo-fascial plane CT findings were: densification, collections, and pseudocavitated nodules. The intraperitoneal CT findings were: densification, small nodules, nodules, and collections. (orig.)

  19. Rapid progression of mediastinal tumor within a few days: A case report of T cell lymphoblastic lymphoma

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Tae Ran; Lee, Young Kyung; Jun, Hyun Jung; Jung, Eun Ah; Son, Jin Sung [Seoul Medical Center, Seoul (Korea, Republic of)

    2016-05-15

    T-cell lymphoblastic lymphoma is a highly aggressive tumor derived from lymphocyte of the thymus, which accounts for 2% of non-Hodgkin's lymphoma. The disease occurs most commonly in adolescent and young adult males. It often results in respiratory emergency because of high proliferation rate. In this case, we confirmed the rapid progression of T-cell lymphoblastic lymphoma through the chest CT scan with one week interval. Three days of empirical chemotherapy resulted in substantial reduction of mediastinal mass, pleural thickening and pleural effusion.

  20. A Simple Diet- and Chemical-Induced Murine NASH Model with Rapid Progression of Steatohepatitis, Fibrosis and Liver Cancer.

    Science.gov (United States)

    Tsuchida, Takuma; Lee, Youngmin A; Fujiwara, Naoto; Ybanez, Maria; Allen, Brittany; Martins, Sebastiao; Fiel, M Isabel; Goossens, Nicolas; Chou, Hsin-I; Hoshida, Yujin; Friedman, Scott L

    2018-03-20

    Although the majority of patients with nonalcoholic fatty liver disease (NAFLD) have only steatosis without progression, a sizable fraction develop non-alcoholic steatohepatitis (NASH), which can lead to cirrhosis and hepatocellular carcinoma (HCC). Many established diet-induced mouse models for NASH require 24-52 weeks, which makes testing for drug response costly and time consuming. We have sought to establish a murine NASH model with rapid progression of extensive fibrosis and HCC by using a western diet (WD), which is high-fat, high-fructose and high-cholesterol, combined with low dose weekly intraperitoneal carbon tetrachloride (CCl 4 ), which served as an accelerator. C57BL/6J mice were fed a normal chow diet (ND) ± CCl 4 or WD ± CCl 4 for 12 and 24 weeks. Addition of CCl 4 exacerbated histological features of NASH, fibrosis, and tumor development induced by WD, which resulted in stage 3 fibrosis at 12 weeks and HCC development at 24 weeks. Furthermore, whole liver transcriptomic analysis indicated that dysregulated molecular pathways in WD/CCl 4 mice and immunologic features were closely similar to those of human NASH. Our mouse NASH model exhibits rapid progression of advanced fibrosis and HCC, and mimics histological, immunological and transcriptomic features of human NASH, suggesting that it will be a useful experimental tool for preclinical drug testing. A carefully characterized model has been developed in mice that recapitulates the progressive stages of human fatty liver disease, from simple steatosis, to inflammation, fibrosis and cancer. The functional pathways of gene expression and immune abnormalities in this model closely resemble human disease. The ease and reproducibility of this model makes it ideal to study disease pathogenesis and test new treatments. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  1. Rapid Detection and Identification of Human Hookworm Infections through High Resolution Melting (HRM) Analysis

    Science.gov (United States)

    Ngui, Romano; Lim, Yvonne A. L.; Chua, Kek Heng

    2012-01-01

    Background Hookworm infections are still endemic in low and middle income tropical countries with greater impact on the socioeconomic and public health of the bottom billion of the world's poorest people. In this study, a real-time polymerase chain reaction (PCR) coupled with high resolution melting-curve (HRM) analysis was evaluated for an accurate, rapid and sensitive tool for species identification focusing on the five human hookworm species. Methods Real-time PCR coupled with HRM analysis targeting the second internal transcribed spacer (ITS-2) of nuclear ribosomal DNA as the genetic marker was used to identify and distinguish hookworm species in human samples. Unique and distinct characteristics of HRM patterns were produced for each of the five hookworm species. The melting curves were characterized by peaks of 79.24±0.05°C and 83.00±0.04°C for Necator americanus, 79.12±0.10°C for Ancylostoma duodenale, 79.40±0.10°C for Ancylostoma ceylanicum, 79.63±0.05°C for Ancylostoma caninum and 79.70±0.14°C for Ancylostoma braziliense. An evaluation of the method's sensitivity and specificity revealed that this assay was able to detect as low as 0.01 ng/µl hookworm DNA and amplification was only recorded for hookworm positive samples. Conclusion The HRM assay developed in this study is a rapid and straightforward method for the diagnosis, identification and discrimination of five human hookworms. This assay is simple compared to other probe-based genotyping methods as it does not require multiplexing, DNA sequencing or post-PCR processing. Therefore, this method offers a new alternative for rapid detection of human hookworm species. PMID:22844538

  2. Rapid detection and identification of human hookworm infections through high resolution melting (HRM analysis.

    Directory of Open Access Journals (Sweden)

    Romano Ngui

    Full Text Available BACKGROUND: Hookworm infections are still endemic in low and middle income tropical countries with greater impact on the socioeconomic and public health of the bottom billion of the world's poorest people. In this study, a real-time polymerase chain reaction (PCR coupled with high resolution melting-curve (HRM analysis was evaluated for an accurate, rapid and sensitive tool for species identification focusing on the five human hookworm species. METHODS: Real-time PCR coupled with HRM analysis targeting the second internal transcribed spacer (ITS-2 of nuclear ribosomal DNA as the genetic marker was used to identify and distinguish hookworm species in human samples. Unique and distinct characteristics of HRM patterns were produced for each of the five hookworm species. The melting curves were characterized by peaks of 79.24±0.05°C and 83.00±0.04°C for Necator americanus, 79.12±0.10°C for Ancylostoma duodenale, 79.40±0.10°C for Ancylostoma ceylanicum, 79.63±0.05°C for Ancylostoma caninum and 79.70±0.14°C for Ancylostoma braziliense. An evaluation of the method's sensitivity and specificity revealed that this assay was able to detect as low as 0.01 ng/µl hookworm DNA and amplification was only recorded for hookworm positive samples. CONCLUSION: The HRM assay developed in this study is a rapid and straightforward method for the diagnosis, identification and discrimination of five human hookworms. This assay is simple compared to other probe-based genotyping methods as it does not require multiplexing, DNA sequencing or post-PCR processing. Therefore, this method offers a new alternative for rapid detection of human hookworm species.

  3. Transmission and selection of macrolide resistant Mycoplasma genitalium infections detected by rapid high resolution melt analysis.

    Directory of Open Access Journals (Sweden)

    Jimmy Twin

    Full Text Available BACKGROUND: Mycoplasma genitalium (MG causes urethritis, cervicitis and pelvic inflammatory disease. The MG treatment failure rate using 1 g azithromycin at an Australian Sexual Health clinic in 2007-9 was 31% (95%CI 23-40%. We developed a rapid high resolution melt analysis (HRMA assay targeting resistance mutations in the MG 23S rRNA gene, and validated it against DNA sequencing by examining pre- and post-treatment archived samples from MG-infected patients. METHODOLOGY/PRINCIPAL FINDINGS: Available MG-positive pre-treatment (n = 82 and post-treatment samples from individuals with clinical treatment failure (n = 20 were screened for 23S rRNA gene mutations. Sixteen (20% pre-treatment samples possessed resistance mutations (A2058G, A2059G, A2059C, which were significantly more common in patients with symptomatic azithromycin-treatment failure (12/26; 44% than in those clinically cured (4/56; 7%, p<0.001. All 20 patients experiencing azithromycin-failure had detectable mutations in their post-treatment samples. In 9 of these cases, the same mutational types were present in both pre- and post-treatment samples indicating transmitted resistance, whilst in 11 of these cases (55%, mutations were absent in pre-treatment samples indicating likely selection of resistant isolates have occurred. HRMA was able to detect all mutational changes determined in this study by DNA sequencing. An additional HRMA assay incorporating an unlabelled probe was also developed to detect type 4 single-nucleotide polymorphisms found in other populations, with a slightly lower sensitivity of 90%. CONCLUSIONS/SIGNIFICANCE: Treatment failure is associated with the detection of macrolide resistance mutations, which appear to be almost equally due to selection of resistant isolates following exposure to 1 g azithromycin and pre-existing transmitted resistance. The application of a rapid molecular assay to detect resistance at the time of initial detection of infection allows

  4. Advanced and rapidly progressing head and neck cancer: good palliation following intralesional bleomycin.

    LENUS (Irish Health Repository)

    Quintyne, Keith Ian

    2011-09-01

    The authors herein report the case of a 61-year-old man undergoing adjuvant therapy for locally advanced laryngeal cancer, who developed parastomal recurrence in his radiation field around his tracheotomy site, while he was undergoing radiation therapy, and compromised the secure placement of his tracheotomy tube and maintenance of his upper airway. MRI restaging and biopsy confirmed recurrence and progressive disease in his mediastinum. He underwent local therapy with intralesional bleomycin with good palliation, and ability to maintain the patency of his upper airway.

  5. Progress in Rapidly-Tunable External Cavity Quantum Cascade Lasers with a Frequency-Shifted Feedback

    Directory of Open Access Journals (Sweden)

    Arkadiy Lyakh

    2016-04-01

    Full Text Available The recent demonstration of external cavity quantum cascade lasers with optical feedback, controlled by an acousto-optic modulator, paves the way to ruggedized infrared laser systems with the capability of tuning the emission wavelength on a microsecond scale. Such systems are of great importance for various critical applications requiring ultra-rapid wavelength tuning, including combustion and explosion diagnostics and standoff detection. In this paper, recent research results on these devices are summarized and the advantages of the new configuration are analyzed in the context of practical applications.

  6. Rapid in situ gamma spectrometric determination of fallout radioactivity in the environment. Progress report

    International Nuclear Information System (INIS)

    Zombori, Peter

    1995-01-01

    The main aim of the present CRP is to identify the existing analytical methods and develop new ones, if possible, which provide rapid, reliable, and detailed information on the radioactive contamination of the environment after a major nuclear accident. Gamma spectrometry has long been regarded as one of the most applicable radioanalytical techniques but its use for environmental studies requires some further considerations. There are two possible approaches to measure environmental radioactivity: (a) taking samples of the different environmental media and measuring them in a laboratory or (b) taking the spectrometer to the place of interest and making in situ measurements. In the former case sampling is a crucial factor hindering the rapid analysis while the latter case is not always reliable due to the problems and uncertainties of the measurement interpretation. The application of in situ gamma spectrometry for the determination of environmental radioactivity has become increasingly attractive since the advent of the high resolution semiconductor gamma detectors, especially, more recently, portable high purity Ge diodes (HpGe). The applicability of this technique was very well proved after the Chernobyl reactor accident when in situ spectrometry played an important role in the rapid evaluation of the fall-out situation. Our measurements provided information on the amount and composition of the radioactive contamination of the ground surface already in the first hours. These measurements enabled us to predict the time variation of the environmental radioactivity after the stabilization of the situation. The portability of the system was an important factor in performing a rapid and efficient survey in different parts of the country. A serious disadvantage of this method is, however, that it requires some knowledge about the radionuclide distribution in the soil, which is normally determined by tedious and time consuming sample analysis of the different soil

  7. The diagnostic accuracy of the rapid dipstick test to predict asymptomatic urinary tract infection of pregnancy.

    Science.gov (United States)

    Eigbefoh, J O; Isabu, P; Okpere, E; Abebe, J

    2008-07-01

    Untreated urinary tract infection can have devastating maternal and neonatal effects. Thus, routine screening for bacteriuria is advocated. This study was designed to evaluate the diagnostic accuracy of the rapid dipstick test to predict urinary tract infection in pregnancy with the gold standard of urine microscopy, culture and sensitivity acting as the control. The urine dipstick test uses the leucocyte esterase, nitrite and test for protein singly and in combination. The result of the dipstick was compared with the gold standard, urine microscopy, culture and sensitivity using confidence interval for proportions. The reliability and validity of the urine dipstick was also evaluated. Overall, the urine dipstick test has a poor correlation with urine culture (p = 0.125, CI 95%). The same holds true for individual components of the dipstick test. The overall sensitivity of the urine dipstick test was poor at 2.3%. Individual sensitivity of the various components varied between 9.1% for leucocyte esterase and the nitrite test to 56.8% for leucocyte esterase alone. The other components of the dipstick test, the test of nitrite, test for protein and combination of the test (leucocyte esterase, nitrite and proteinuria) appear to decrease the sensitivity of the leucocyte esterase test alone. The ability of the urine dipstick test to correctly rule out urinary tract infection (specificity) was high. The positive predictive value for the dipstick test was high, with the leucocyte esterase test having the highest positive predictive value compared with the other components of the dipstick test. The negative predictive value (NPV) was expectedly highest for the leucocyte esterase test alone with values higher than the other components of the urine dipstick test singly and in various combinations. Compared with the other parameters of the urine dipstick test, singly and in combination, leucocyte esterase appears to be the most accurate (90.25%). The dipstick test has a

  8. Evaluation of rapid diagnostic test kits for feline leukemia virus infection using samples from naturally infected cats

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    Jiayou Liu

    2016-09-01

    Full Text Available Objectives Feline leukemia virus (FeLV is a potentially life-threatening oncogenic retrovirus. The p27 viral core protein is produced by the virus in infected feline cells, is found in the cytoplasm in several blood cells and can be free in the serum and plasma. ELISA or particle-based immunoassay are commonly used to detect the presence of the p27 core protein in samples obtained from blood. The objective of this study was to compare the performance of several in-clinic tests: the SNAP Feline Triple Test (IDEXX Laboratories, the WITNESS FeLV-FIV Test (Zoetis and the VetScan Feline FeLV/FIV Rapid Test (Abaxis. Methods The sample population (100 positive, 105 negative samples consisted of serum and plasma samples submitted to IDEXX’s worldwide reference laboratory for feline retrovirus testing. Virus isolation and reverse transcriptase PCR results were not available and so samples were judged to be positive or negative based on the results of the ViraCHEK FeLV (Zoetis microtiter plate assay. Results The percentage of samples positive and negative for FeLV p27 antigen using the three in-clinic tests compared with the ViraCHEK method were as follows: IDEXX Feline Triple (positive 98.0%, negative 100%; Zoetis WITNESS (positive 79.0%, negative 97.1%; Abaxis VetScan (positive 73.0%, negative 97.1%. Conclusions and relevance The SNAP Feline Triple Test demonstrated a high level of agreement for FeLV-positive and FeLV-negative samples when assessed in this model. Results of FeLV assays can vary among tests.

  9. Evaluation of rapid diagnostic test kits for feline leukemia virus infection using samples from naturally infected cats.

    Science.gov (United States)

    Liu, Jiayou; O'Connor, Thomas; Beall, Melissa; Chandrashekar, Ramaswamy; Lappin, Michael

    2016-01-01

    Feline leukemia virus (FeLV) is a potentially life-threatening oncogenic retrovirus. The p27 viral core protein is produced by the virus in infected feline cells, is found in the cytoplasm in several blood cells and can be free in the serum and plasma. ELISA or particle-based immunoassay are commonly used to detect the presence of the p27 core protein in samples obtained from blood. The objective of this study was to compare the performance of several in-clinic tests: the SNAP Feline Triple Test (IDEXX Laboratories), the WITNESS FeLV-FIV Test (Zoetis) and the VetScan Feline FeLV/FIV Rapid Test (Abaxis). The sample population (100 positive, 105 negative samples) consisted of serum and plasma samples submitted to IDEXX's worldwide reference laboratory for feline retrovirus testing. Virus isolation and reverse transcriptase PCR results were not available and so samples were judged to be positive or negative based on the results of the ViraCHEK FeLV (Zoetis) microtiter plate assay. The percentage of samples positive and negative for FeLV p27 antigen using the three in-clinic tests compared with the ViraCHEK method were as follows: IDEXX Feline Triple (positive 98.0%, negative 100%); Zoetis WITNESS (positive 79.0%, negative 97.1%); Abaxis VetScan (positive 73.0%, negative 97.1%). The SNAP Feline Triple Test demonstrated a high level of agreement for FeLV-positive and FeLV-negative samples when assessed in this model. Results of FeLV assays can vary among tests.

  10. MM1+2C sporadic Creutzfeldt-Jakob disease presenting as rapidly progressive nonfluent aphasia.

    Science.gov (United States)

    Allegri, Ricardo F; Bartoloni, Leonardo; Iturry, Mónica; Romero, Carlos; Begué, Christián; Sevlever, Gustavo; Taratuto, Ana Lía

    2014-01-01

    We report a 77-year-old man, presenting with progressive aphasia as an initial symptom, who developed severe dementia over the course of 20 months. Frontal cortex PrPSc western blot was type 2 and codon 129 was MM; brain neuropathology showed cortical vacuoles with perivacuolar PrP immunostaining characteristic of MM2C. Cerebellum showed focal coarse, patchy staining in different sections of the molecular layer, diffuse fine punctuate and coarse PrP immunopositive deposits in the granule cell layer, and focal synaptic immunostaining in the molecular layer, suggestive of MM1+2C by histotyping. This clinical presentation has not yet been described in an MM1+2C subtype by histotyping.

  11. Cobalamin C Deficiency Shows a Rapidly Progressing Maculopathy With Severe Photoreceptor and Ganglion Cell Loss

    Science.gov (United States)

    Bonafede, Lucas; Ficicioglu, Can H.; Serrano, Leona; Han, Grace; Morgan, Jessica I. W.; Mills, Monte D.; Forbes, Brian J.; Davidson, Stefanie L.; Binenbaum, Gil; Kaplan, Paige B.; Nichols, Charles W.; Verloo, Patrick; Leroy, Bart P.; Maguire, Albert M.; Aleman, Tomas S.

    2015-01-01

    Purpose To describe in detail the retinal structure and function of a group of patients with cobalamin C (cblC) disease. Methods Patients (n = 11, age 4 months to 15 years) with cblC disease (9/11, early onset) diagnosed by newborn screening underwent complete ophthalmic examinations, fundus photography, near-infrared reflectance imaging, and spectral-domain optical coherence tomography (SD-OCT). Electroretinograms (ERGs) were performed in a subset of patients. Results Patients carried homozygous or compound heterozygote mutations in the methylmalonic aciduria and homocystinuria type C (MMACHC) gene. Late-onset patients had a normal exam. All early-onset patients showed a maculopathy; older subjects had a retina-wide degeneration (n = 4; >7 years of age). In general, retinal changes were first observed before 1 year of age and progressed within months to a well-established maculopathy. Pseudocolobomas were documented in three patients. Measurable visual acuities ranged from 20/200 to 20/540. Nystagmus was present in 8/11 patients; 5/6 patients had normal ERGs; 1/6 had reduced rod-mediated responses. Spectral-domain OCT showed macular thinning, with severe ganglion cell layer (GCL) and outer nuclear layer (ONL) loss. Inner retinal thickening was observed in areas of total GCL/ONL loss. A normal lamination pattern in the peripapillary nasal retina was often seen despite severe central and/or retina-wide disease. Conclusions Patients with early-onset cblC and MMACHC mutations showed an early-onset, unusually fast-progressing maculopathy with severe central ONL and GCL loss. An abnormally thickened inner retina supports a remodeling response to both photoreceptor and ganglion cell degeneration and/or an interference with normal development in early-onset cblC. PMID:26658511

  12. Importance of a Rapid and Accurate Diagnosis in Strongyloides Stercoralis and Human T-Lymphotropic Virus 1 Co-infection: A Case Report and Review of the Literature.

    Science.gov (United States)

    Quintero, Olga; Berini, Carolina A; Waldbaum, Carlos; Avagnina, Alejandra; Juarez, María; Repetto, Silvia; Sorda, Juan; Biglione, Mirna

    2017-01-01

    Strongyloides (S.) stercoralis and Human T-Lymphotropic Virus 1 (HTLV-1) share some endemic regions such as Japan, Jamaica, and South America and are mostly diagnosed elsewhere in immigrants from endemic areas. This co-infection has not been documented in Argentina although both pathogens are endemic in the Northwest. We present a case of S. stercoralis and HTLV-1 co-infection with an initial presentation due to gastrointestinal symptoms which presented neither eosinophilia nor the presence of larvae in stool samples in a non-endemic area for these infections. A young Peruvian woman living in Buenos Aires attended several emergency rooms and finally ended up admitted in a gastroenterology ward due to incoercible vomiting, diarrhea, abdominal pain, fever, and weight loss. Gastrointestinal symptoms started 3 months before she returned to Argentina from a trip to Peru. She presented malnutrition and abdominal distension parameters. HIV-1 and other immunodeficiencies were discarded. The serial coproparasitological test was negative. Computed tomography showed diffuse thickening of duodenal and jejunal walls. At the beginning, vasculitis was suspected and corticosteroid therapy was initiated. The patient worsened rapidly. Skin, new enteral biopsies, and a new set of coproparasitological samples revealed S. stercoralis . Then, HTLV-1 was suspected and infection was confirmed. Ivermectin and albendazole were administrated, until the stool sample remained negative for 2 weeks. Larvae were not observed in fresh stool, Ritchie method, and agar culture 1 week post-treatment. Although she required initial support with parenteral nutrition due to oral intolerance she slowly progressed favorably. It has been highly recommended to include a rapid and sensitive PCR strategy in the algorithm to confirm Strongyloides infection, which has demonstrated to improve early diagnosis in patients at-risk of disseminated strongyloidiasis.

  13. Importance of a Rapid and Accurate Diagnosis in Strongyloides Stercoralis and Human T-Lymphotropic Virus 1 Co-infection: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Olga Quintero

    2017-12-01

    Full Text Available Strongyloides (S. stercoralis and Human T-Lymphotropic Virus 1 (HTLV-1 share some endemic regions such as Japan, Jamaica, and South America and are mostly diagnosed elsewhere in immigrants from endemic areas. This co-infection has not been documented in Argentina although both pathogens are endemic in the Northwest. We present a case of S. stercoralis and HTLV-1 co-infection with an initial presentation due to gastrointestinal symptoms which presented neither eosinophilia nor the presence of larvae in stool samples in a non-endemic area for these infections. A young Peruvian woman living in Buenos Aires attended several emergency rooms and finally ended up admitted in a gastroenterology ward due to incoercible vomiting, diarrhea, abdominal pain, fever, and weight loss. Gastrointestinal symptoms started 3 months before she returned to Argentina from a trip to Peru. She presented malnutrition and abdominal distension parameters. HIV-1 and other immunodeficiencies were discarded. The serial coproparasitological test was negative. Computed tomography showed diffuse thickening of duodenal and jejunal walls. At the beginning, vasculitis was suspected and corticosteroid therapy was initiated. The patient worsened rapidly. Skin, new enteral biopsies, and a new set of coproparasitological samples revealed S. stercoralis. Then, HTLV-1 was suspected and infection was confirmed. Ivermectin and albendazole were administrated, until the stool sample remained negative for 2 weeks. Larvae were not observed in fresh stool, Ritchie method, and agar culture 1 week post-treatment. Although she required initial support with parenteral nutrition due to oral intolerance she slowly progressed favorably. It has been highly recommended to include a rapid and sensitive PCR strategy in the algorithm to confirm Strongyloides infection, which has demonstrated to improve early diagnosis in patients at-risk of disseminated strongyloidiasis.

  14. Imbalance of tumor necrosis factor receptors during progression in bovine leukemia virus infection

    International Nuclear Information System (INIS)

    Konnai, Satoru; Usui, Tatsufumi; Ikeda, Manabu; Kohara, Junko; Hirata, Toh-ichi; Okada, Kosuke; Ohashi, Kazuhiko; Onuma, Misao

    2005-01-01

    Previously, we found an up-regulation of tumor necrosis factor alpha (TNF)-α and an imbalance of TNF receptors in sheep experimentally infected with bovine leukemia virus (BLV). In order to investigate the different TNF-α-induced responses, in this study we examined the TNF-α-induced proliferative response and the expression levels of two distinct TNF receptors on peripheral blood mononuclear cells (PBMC) derived from BLV-uninfected cattle and BLV-infected cattle that were aleukemic (AL) or had persistent lymphocytosis (PL). The proliferative response of PBMC isolated from those cattle with PL in the presence of recombinant bovine TNF-α (rTNF-α) was significantly higher than those from AL cattle and uninfected cattle and the cells from PL cattle expressed significantly higher mRNA levels of TNF receptor type II (TNF-RII) than those from AL and BLV-uninfected cattle. No difference was found in TNF-RI mRNA levels. Most cells expressing TNF-RII in PL cattle were CD5 + or sIgM + cells and these cells showed resistance to TNF-α-induced apoptosis. Additionally, there were significant positive correlations between the changes in provirus load and TNF-RII mRNA levels, and TNF-α-induced proliferation and TNF-RII mRNA levels. These data suggest that imbalance in the expression of TNF receptors could at least in part contribute to the progression of lymphocytosis in BLV infection

  15. Genetic factors associated with slow progression of HIV among perinatally-infected Indian children.

    Science.gov (United States)

    Chaudhuri, Riya Pal; Neogi, Ujjwal; Rao, Shwetha D; Shet, Anita

    2014-10-01

    To study the association between common AIDS restriction genes and slow disease progression among perinatally-infected children in India. ART-naïve children were identified and selected host factors including CCR5-∆32, SDF1-3'A, CCR5-59029G, HLA-B*27, B*57 were studied using allele-specific PCR-RFLP and SSPGo HLA typing kits. Among 165 children, 10 (6%) long-term non-progressors and 8 (5%) slow progressors were identified. For comparison, 12 children with normal progression of HIV were included. The frequencies of CCR5-∆32 deletion, SDF1-3'A and CCR5-59029G did not differ significantly. HLA-B*27 and B*57 were observed only in long-term non-progressors or slow progressors, who also harbored either SDF1-3'A and/or CCR5-59029G. There is an association between host genetic factors and slow disease progression in this population.

  16. Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

    Science.gov (United States)

    Pembroke, Thomas; Deschenes, Marc; Lebouché, Bertrand; Benmassaoud, Amine; Sewitch, Maida; Ghali, Peter; Wong, Philip; Halme, Alex; Vuille-Lessard, Elise; Pexos, Costa; Klein, Marina B; Sebastiani, Giada

    2017-10-01

    Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to

  17. Rapid, serial, non-invasive assessment of drug efficacy in mice with autoluminescent Mycobacterium ulcerans infection.

    Directory of Open Access Journals (Sweden)

    Tianyu Zhang

    Full Text Available Buruli ulcer (BU caused by Mycobacterium ulcerans is the world's third most common mycobacterial infection. There is no vaccine against BU and surgery is needed for patients with large ulcers. Although recent experience indicates combination chemotherapy with streptomycin and rifampin improves cure rates, the utility of this regimen is limited by the 2-month duration of therapy, potential toxicity and required parenteral administration of streptomycin, and drug-drug interactions caused by rifampin. Discovery and development of drugs for BU is greatly hampered by the slow growth rate of M. ulcerans, requiring up to 3 months of incubation on solid media to produce colonies. Surrogate markers for evaluating antimicrobial activity in real-time which can be measured serially and non-invasively in infected footpads of live mice would accelerate pre-clinical evaluation of new drugs to treat BU. Previously, we developed bioluminescent M. ulcerans strains, demonstrating proof of concept for measuring luminescence as a surrogate marker for viable M. ulcerans in vitro and in vivo. However, the requirement of exogenous substrate limited the utility of such strains, especially for in vivo experiments.For this study, we engineered M. ulcerans strains that express the entire luxCDABE operon and therefore are autoluminescent due to endogenous substrate production. The selected reporter strain displayed a growth rate and virulence similar to the wild-type parent strain and enabled rapid, real-time monitoring of in vitro and in vivo drug activity, including serial, non-invasive assessments in live mice, producing results which correlated closely with colony-forming unit (CFU counts for a panel of drugs with various mechanisms of action.Our results indicate that autoluminescent reporter strains of M. ulcerans are exceptional tools for pre-clinical evaluation of new drugs to treat BU due to their potential to drastically reduce the time, effort, animals, compound

  18. Acute gouty arthritis and rapidly progressive renal failure as manifestation of multiple myeloma: clinical case description

    Directory of Open Access Journals (Sweden)

    O.V. Gudym

    2017-08-01

    Full Text Available The article describes a clinical case of multiple myeloma in 78-year-old man, its clinical onset was as an acute attack of gout. The patient was admitted to hospital due to the development of the first acute attack of gout. The attack was characterized by polyarthricular joint lesion of the upper and lower extremities, pronounced inflammatory reaction, insufficient response to the use of non-steroidal anti-inflammatory drugs, and a high level of hyperuricemia. The serum uric acid concentration ranged from 636 to 712 μmol/l. The study of the synovial fluid of the inflamed knee joint made it possible to reveal uric acid crystals and to confirm the diagnosis of acute gouty arthritis. Simultaneously, the patient had significant renal impairment: creatinine was 574 μmol/l, urea — 39.9 mmol/l, glomerular filtration rate according to CKD-EPI — 8 ml/min. The daily proteinuria was 1.8 g. A retrospective assessment of laboratory parameters allowed to reveal completely normal indicators of renal function 6 months ago. Considering the development of acute gouty arthritis, its polyarticular nature, persistent course, rapid involvement of new joints, high uric acid levels during an acute attack exceeding 600 μmol/l (10 mg/dL, rapid development of renal failure within 6 months until the terminal stage, it was suggested the secondary nature of gout on the background of kidney damage by another pathological process. Further clinical, laboratory and instrumental studies allowed verifying multiple myeloma with renal damage. Bence Jones protein in the urine was not detected, there was also no evidence of hyperproteinemia. However, pain in the spine, ribs and chest was the basis for carrying out an X-ray study of the bones of the skeleton. Changes in the skeleton typical for multiple myeloma have been identified. Myelogram showed a high content of plasma cells (21.1 %, electrophoresis of blood proteins showed a high M-gradient (30.42 %, and a cytochemical

  19. Rapid Diagnosis of IHN Virus Infection in Salmon and Steelhead Trout, Final Report.

    Energy Technology Data Exchange (ETDEWEB)

    Leong, JoAnn Ching

    1984-12-01

    The main objective for this study was the development of a rapid diagnostic method for IHN virus in fish tissue samples. The rationale for developing new techniques for diagnosing IHNV infection was that present methods were time consuming and dependent on virus neutralization by specific antisera, a reagent that was not readily available or reliable. Fish pathologists required a rapid detection method which was sensitive enough to detect virus strain differences so that they could provide data for effective management decisions in controlling the spread of IHNV. Bonneville Power Administration's (BPA) role in efforts in fish diseases and more generically the protection, mitigation, and enhancement of Columbia River salmon and steelhead populations, is mandated by Congress through the Pacific Northwest Electric Power Planning and Conservation Act (Regional Act), Pub. L. 96-501. Section 4 (h) of the Regional Act directs the Northwest Power Planning Council to develop a Fish and Wildlife Program. BPA's Administrator is authorized in Section 4 (h) (10) (A) to ''use funds and the authorities available to the extent affected by the development and operation of any hydroelectric project of the Columbia River and its tributaries''. The fund is to be used to implement measures that are consistent with the Council's Fish and Wildlife Program. The research detailed in this final report is consistent with these objectives. This final report has been prepared as part of BPA's policy to encourage the preservation and dissemination of research results by publication in scientific journals.

  20. Large cross-sectional study of presbycusis reveals rapid progressive decline in auditory temporal acuity.

    Science.gov (United States)

    Ozmeral, Erol J; Eddins, Ann C; Frisina, D Robert; Eddins, David A

    2016-07-01

    The auditory system relies on extraordinarily precise timing cues for the accurate perception of speech, music, and object identification. Epidemiological research has documented the age-related progressive decline in hearing sensitivity that is known to be a major health concern for the elderly. Although smaller investigations indicate that auditory temporal processing also declines with age, such measures have not been included in larger studies. Temporal gap detection thresholds (TGDTs; an index of auditory temporal resolution) measured in 1071 listeners (aged 18-98 years) were shown to decline at a minimum rate of 1.05 ms (15%) per decade. Age was a significant predictor of TGDT when controlling for audibility (partial correlation) and when restricting analyses to persons with normal-hearing sensitivity (n = 434). The TGDTs were significantly better for males (3.5 ms; 51%) than females when averaged across the life span. These results highlight the need for indices of temporal processing in diagnostics, as treatment targets, and as factors in models of aging. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Primary pleural leiomyosarcoma with rapid progression and fatal outcome: a case report

    Directory of Open Access Journals (Sweden)

    Rais Ghizlane

    2012-04-01

    Full Text Available Abstract Introduction Leiomyosarcomas are neoplasms of smooth muscles that most commonly arise from the uterus, gastrointestinal tract, or soft tissue. Primary pleural leiomyosarcoma is extremely rare. To the best of our knowledge, only nine cases have been published to date. Because of the rarity of pleural leiomyosarcoma and its similarity (clinical and histological to other pleural neoplasms, particularly sarcomatous mesothelioma, diagnosis is often difficult. Case presentation A 58-year-old North African man was admitted with complaints of dyspnea and chest pain to our hospital. Chest computed tomography revealed right pleural effusion and pleural thickening. A transthoracic needle biopsy yielded a diagnosis of leiomyosarcoma, and tumor cells were strongly and uniformly positive for vimentin, a smooth muscle actin at immunohistochemical analysis. A general examination did not show any metastatic lesions in other areas. One month after diagnosis, the tumor grew rapidly, with pulmonary invasion, and therefore he was treated only by palliative care. He died from respiratory failure one month later. Because no organ of origin of the leiomyosarcoma, other than the pleura, was detected, this case was diagnosed as a primary pleural leiomyosarcoma. Conclusions Although leiomyosarcoma originating from the pleura is rare, this entity is increasingly described. The purpose of presenting this case report is to raise awareness among clinicians to consider this clinical entity as a differential diagnosis when a pleural mass is identified.

  2. Final Progress Report: Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes Feasibility Study

    International Nuclear Information System (INIS)

    Rawool-Sullivan, Mohini; Bounds, John Alan; Brumby, Steven P.; Prasad, Lakshman; Sullivan, John P.

    2012-01-01

    This is the final report of the project titled, 'Isotope Identification Algorithm for Rapid and Accurate Determination of Radioisotopes,' PMIS project number LA10-HUMANID-PD03. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). It summarizes work performed over the FY10 time period. The goal of the work was to demonstrate principles of emulating a human analysis approach towards the data collected using radiation isotope identification devices (RIIDs). Human analysts begin analyzing a spectrum based on features in the spectrum - lines and shapes that are present in a given spectrum. The proposed work was to carry out a feasibility study that will pick out all gamma ray peaks and other features such as Compton edges, bremsstrahlung, presence/absence of shielding and presence of neutrons and escape peaks. Ultimately success of this feasibility study will allow us to collectively explain identified features and form a realistic scenario that produced a given spectrum in the future. We wanted to develop and demonstrate machine learning algorithms that will qualitatively enhance the automated identification capabilities of portable radiological sensors that are currently being used in the field.

  3. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons : the D:A:D study

    NARCIS (Netherlands)

    Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J; Schölvinck, Elisabeth H.

    2014-01-01

    BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

  4. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    NARCIS (Netherlands)

    Kamara, David A.; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A.; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D.; Smith, Colette J.; Powderly, B.; Shortman, N.; Moecklinghoff, C.; Reilly, G.; Franquet, X.; Ryom, L.; Sabin, C. A.; Kamara, D.; Smith, C.; Phillips, A.; Mocroft, A.; Tverland, J.; Mansfeld, M.; Nielsen, J.; Raben, D.; Lundgren, J. D.; Brandt, R. Salbøl; Rickenbach, M.; Fanti, I.; Krum, E.; Hillebregt, M.; Geffard, S.; Sundström, A.; Prins, J. M.; Kuijpers, T. W.; Scherpbier, H. J.; van der Meer, J. T. M.; Wit, F. W. M. N.; Godfried, M. H.; Nellen, F. J. B.; Lange, J. M. A.; Geerlings, S. E.; van Vugt, M.; Pajkrt, D.; Grijsen, M. L.; Wiersinga, W. J.; Goorhuis, A.; Hovius, J. W. R.

    2014-01-01

    No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data

  5. Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

    NARCIS (Netherlands)

    Kamara, D.A.; Ryom, L.; Ross, M.; Kirk, O.; Reiss, P.; Morlat, P.; Moranne, O.; Fux, C.A.; Mocroft, A.; Sabin, C.; Lundgren, J.D.; Smith, C.J.; Koopmans †, P.P.; Keuter, M.; Ven, A.J.A.M. van der; Hofstede, H.J.M. ter; Dofferhoff, A.S.M.; Warris, A.; Crevel, R. van; et al.,

    2014-01-01

    BACKGROUND: No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the

  6. Rapid progression of massive hepatic calcification visible by CT: The case of a dialysed patient

    International Nuclear Information System (INIS)

    Gorycki, T.; Szarmach, A.; Szymanska-Dubowik, A.

    2008-01-01

    There have been single reported cases of patients with diffuse hepatic calcifications revealed 4-36 months after the first examination in the course of hemodialysis-treated renal failure, severe heart failure, shock liver, primary amyloidosis, or corticosteroid administration. In the presented case, many different factors for liver calcification and dynamic tomographic manifestation are seen. A 23-year-old man who was on hemodialysis because of acute renal failure after a motor vehicle accident (multiorgan trauma) with occurrence of hypovolemic shock was admitted to the hospital's intensive care unit presenting with clostridial infection of the lower extremities. During his stay at a prior hospital, ultrasonography did not reveal hepatic lesions. He underwent 22 sessions of treatment with hyperbaric oxygen as well as several necrectomies and amputation of both lower limbs. Abdominal CT performed three weeks after the accident demonstrated diffuse hepatic calcification which was later confirmed during autopsy. Liver parenchymal calcifications may be related to elevated calcium-phosphorus products in the uremic state and after multiple bone fractures and possible ischemic liver injury. Although a definitive explanation for the unusually short time of the appearance of liver calcification was not obtained, it may be related to many factors acting synergistically. Hyperbaric oxygen treatment is of unknown significance in this process. CT plays a basic role in detecting and assessing liver calcifications forming both diffuse lesions and those with well-defined borders. Diffuse calcifications revealed by CT must be analyzed together with the patient's history, especially considering renal and heart failure, bone fractures, states of shock, and treatment. Diffuse liver calcifications in these patients after respiratory therapy and transfusions when no subcapsular hematoma is found should be considered of metabolic origin. (author)

  7. Effect of intensive plasma exchange (PE) in rapidly progressive crescentic glomerulonephritis (RPCGN).

    Science.gov (United States)

    D'Amico, G; Sinico, R; Fornasieri, A; Ferrario, F; Colasanti, G; Porri, M T; Paracchini, M L; Gibelli, A

    1983-07-01

    Ten adult patients with RPCGN (crescents in greater than 70% of glomeruli), primary in 6 and associated with systemic diseases in 4, were treated with PE, associated with oral steroids (P) and cyclophosphamide (C) in all cases and with intravenous methylprednisolone pulses (MP) in 7 cases. Four out of ten patients were anuric and needed dialysis treatment at the start of treatment. Therapeutic benefit, i.e. reversal of the trend to further deterioration and substantial improvement of GFR, was achieved in 8 out of 10 patients (80%), including 2 of 4 anuric patients, and in 7 of those (8) who had still active cellular crescents (87.5%). Similar therapeutic benefit had been achieved only in 10% of a comparable population of 10 patients with RPCGN treated before 1980 with P and C, without PE or MP pulses. It is difficult to establish whether the better therapeutic results in the more recently treated group were due to PE or to MP pulses of to both the new approaches, even though the clinical improvement obtained in all the 3 patients treated with PE without concomitant MP suggest a specific beneficial role for PE. RPCGN is a catastrophic illness characterized by progressive deterioration of kidney function, resulting in oliguria and uremia, usually within weeks or months. The most consistent histopathologic finding is the presence of extensive glomerular crescents resulting from proliferation of the extracapillary epithelial cell lining of Bowman's capsule. It is apparent that RPCGN is not a homogeneous entity, clinically, histologically or immunohistologically, but rather a clinicopathologic syndrome, the features of which may be seen in a variety of systemic disorders, including SLE, polyarteritis nodosa, Wegener's granulomatosis, Henoch-Schönlein purpura, cryoglobulinemia, and subacute bacterial endocarditis.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Cutting edge: Rapid recovery of NKT cells upon institution of highly active antiretroviral therapy for HIV-1 infection

    NARCIS (Netherlands)

    van der Vliet, Hans J. J.; van Vonderen, Marit G. A.; Molling, Johan W.; Bontkes, Hetty J.; Reijm, Martine; Reiss, Peter; van Agtmael, Michiel A.; Danner, Sven A.; van den Eertwegh, Alfons J. M.; von Blomberg, B. Mary E.; Scheper, Rik J.

    2006-01-01

    CD1d-restricted NKT cells play important regulatory roles in various immune responses and are rapidly and selectively depleted upon infection with HIV-1. The cause of this selective depletion is incompletely understood, although it is in part due to the high susceptibility of CD4+ NKT cells to

  9. Evaluation of a rapid diagnostic test for yaws infection in a community surveillance setting.

    Directory of Open Access Journals (Sweden)

    Michael Marks

    2014-09-01

    Full Text Available Yaws is a non-venereal treponemal infection caused by Treponema pallidum ssp. pertenue. The WHO has launched a worldwide control programme, which aims to eradicate yaws by 2020. The development of a rapid diagnostic test (RDT for serological diagnosis in the isolated communities affected by yaws is a key requirement for the successful implementation of the WHO strategy. We conducted a study to evaluate the utility of the DPP test in screening for yaws, utilizing samples collected as part of a community prevalence survey conducted in the Solomon Islands. 415 serum samples were tested using both traditional syphilis serology (TPPA and quantitative RPR and the Chembio DPP Syphilis Screen and Confirm RDT. We calculated the sensitivity and specificity of the RDT as compared to gold standard serology. The sensitivity of the RDT against TPPA was 58.5% and the specificity was 97.6%. The sensitivity of the RDT against RPR was 41.7% and the specificity was 95.2%. The sensitivity of the DPP was strongly related to the RPR titre with a sensitivity of 92.0% for an RPR titre of >1/16. Wider access to DPP testing would improve our understanding of worldwide yaws case reporting and the test may play a key role in assessing patients presenting with yaws like lesions in a post-mass drug administration (MDA setting.

  10. Direct typing of Canine parvovirus (CPV) from infected dog faeces by rapid mini sequencing technique.

    Science.gov (United States)

    V, Pavana Jyothi; S, Akila; Selvan, Malini K; Naidu, Hariprasad; Raghunathan, Shwethaa; Kota, Sathish; Sundaram, R C Raja; Rana, Samir Kumar; Raj, G Dhinakar; Srinivasan, V A; Mohana Subramanian, B

    2016-12-01

    Canine parvovirus (CPV) is a non-enveloped single stranded DNA virus with an icosahedral capsid. Mini-sequencing based CPV typing was developed earlier to detect and differentiate all the CPV types and FPV in a single reaction. This technique was further evaluated in the present study by performing the mini-sequencing directly from fecal samples which avoided tedious virus isolation steps by cell culture system. Fecal swab samples were collected from 84 dogs with enteritis symptoms, suggestive of parvoviral infection from different locations across India. Seventy six of these samples were positive by PCR; the subsequent mini-sequencing reaction typed 74 of them as type 2a virus, and 2 samples as type 2b. Additionally, 25 of the positive samples were typed by cycle sequencing of PCR products. Direct CPV typing from fecal samples using mini-sequencing showed 100% correlation with CPV typing by cycle sequencing. Moreover, CPV typing was achieved by mini-sequencing even with faintly positive PCR amplicons which was not possible by cycle sequencing. Therefore, the mini-sequencing technique is recommended for regular epidemiological follow up of CPV types, since the technique is rapid, highly sensitive and high capacity method for CPV typing. Copyright © 2016. Published by Elsevier B.V.

  11. Rapid implementation of evidence-based guidelines for imaging after first urinary tract infection.

    Science.gov (United States)

    Jerardi, Karen E; Elkeeb, Dena; Weiser, Jason; Brinkman, William B

    2013-09-01

    The American Academy of Pediatrics published a new guideline for management of first urinary tract infection (UTI) in children aged 2 to 24 months in September 2011. The imaging evaluation changed from the previous guideline to recommend voiding cystourethrogram (VCUG) only for patients with an abnormal renal and bladder ultrasound (RBUS). The objective was to decrease the proportion of guideline-eligible children with a normal RBUS who underwent VCUG from median of 92% for patients treated as inpatients and 100% for patients treated in the emergency department to 5% in both settings. This was a quality improvement implementation study in a large academic medical center. Key drivers included: appropriate guideline knowledge, timely identification of guideline eligible patients, and effective communication with the community-based primary care provider. A multidisciplinary team developed and tested interventions. Impact was assessed with annotated run charts. Statistical comparisons were made with χ(2) analysis and Fisher's exact test. The proportion of children with first UTI and normal RBUS who underwent VCUG decreased from a median of 92% to 0% within 1 month of initiating the project among those hospitalized and from 100% to 40% within 4 months among those diagnosed in the emergency department. Rates have been sustained for 12 months and 8 months, respectively. Interventions using the electronic medical record and ordering system were most impactful. Rapid adoption of evidence-based UTI care across multiple settings is achievable. Practice change occurred faster and to a greater magnitude in the inpatient setting compared with the outpatient setting.

  12. A multiplex RT-PCR assay for the rapid and differential diagnosis of classical swine fever and other pestivirus infections.

    Science.gov (United States)

    Díaz de Arce, Heidy; Pérez, Lester J; Frías, Maria T; Rosell, Rosa; Tarradas, Joan; Núñez, José I; Ganges, Llilianne

    2009-11-18

    Classical swine fever is a highly contagious viral disease causing severe economic losses in pig production almost worldwide. All pestivirus species can infect pigs, therefore accurate and rapid pestivirus detection and differentiation is of great importance to assure control measures in swine farming. Here we describe the development and evaluation of a novel multiplex, highly sensitive and specific RT-PCR for the simultaneous detection and rapid differentiation between CSFV and other pestivirus infections in swine. The universal and differential detection was based on primers designed to amplify a fragment of the 5' non-coding genome region for the detection of pestiviruses and a fragment of the NS5B gene for the detection of classical swine fever virus. The assay proved to be specific when different pestivirus strains from swine and ruminants were evaluated. The analytical sensitivity was estimated to be as little as 0.89TCID(50). The assay analysis of 30 tissue homogenate samples from naturally infected and non-CSF infected animals and 40 standard serum samples evaluated as part of two European Inter-laboratory Comparison Tests conducted by the European Community Reference Laboratory, Hanover, Germany proved that the multiplex RT-PCR method provides a rapid, highly sensitive, and cost-effective laboratory diagnosis for classical swine fever and other pestivirus infections in swine.

  13. Reversal of the Progression of Fatal Coronavirus Infection in Cats by a Broad-Spectrum Coronavirus Protease Inhibitor.

    Directory of Open Access Journals (Sweden)

    Yunjeong Kim

    2016-03-01

    Full Text Available Coronaviruses infect animals and humans causing a wide range of diseases. The diversity of coronaviruses in many mammalian species is contributed by relatively high mutation and recombination rates during replication. This dynamic nature of coronaviruses may facilitate cross-species transmission and shifts in tissue or cell tropism in a host, resulting in substantial change in virulence. Feline enteric coronavirus (FECV causes inapparent or mild enteritis in cats, but a highly fatal disease, called feline infectious peritonitis (FIP, can arise through mutation of FECV to FIP virus (FIPV. The pathogenesis of FIP is intimately associated with immune responses and involves depletion of T cells, features shared by some other coronaviruses like Severe Acute Respiratory Syndrome Coronavirus. The increasing risks of highly virulent coronavirus infections in humans or animals call for effective antiviral drugs, but no such measures are yet available. Previously, we have reported the inhibitors that target 3C-like protease (3CLpro with broad-spectrum activity against important human and animal coronaviruses. Here, we evaluated the therapeutic efficacy of our 3CLpro inhibitor in laboratory cats with FIP. Experimental FIP is 100% fatal once certain clinical and laboratory signs become apparent. We found that antiviral treatment led to full recovery of cats when treatment was started at a stage of disease that would be otherwise fatal if left untreated. Antiviral treatment was associated with a rapid improvement in fever, ascites, lymphopenia and gross signs of illness and cats returned to normal health within 20 days or less of treatment. Significant reduction in viral titers was also observed in cats. These results indicate that continuous virus replication is required for progression of immune-mediated inflammatory disease of FIP. These findings may provide important insights into devising therapeutic strategies and selection of antiviral compounds for

  14. Transmitted/Founder Viruses Rapidly Escape from CD8+ T Cell Responses in Acute Hepatitis C Virus Infection.

    Science.gov (United States)

    Bull, Rowena A; Leung, Preston; Gaudieri, Silvana; Deshpande, Pooja; Cameron, Barbara; Walker, Melanie; Chopra, Abha; Lloyd, Andrew R; Luciani, Fabio

    2015-05-01

    The interaction between hepatitis C virus (HCV) and cellular immune responses during very early infection is critical for disease outcome. To date, the impact of antigen-specific cellular immune responses on the evolution of the viral population establishing infection and on potential escape has not been studied. Understanding these early host-virus dynamics is important for the development of a preventative vaccine. Three subjects who were followed longitudinally from the detection of viremia preseroconversion until disease outcome were analyzed. The evolution of transmitted/founder (T/F) viruses was undertaken using deep sequencing. CD8(+) T cell responses were measured via enzyme-linked immunosorbent spot (ELISpot) assay using HLA class I-restricted T/F epitopes. T/F viruses were rapidly extinguished in all subjects associated with either viral clearance (n = 1) or replacement with viral variants leading to establishment of chronic infection (n = 2). CD8(+) T cell responses against 11 T/F epitopes were detectable by 33 to 44 days postinfection, and 5 of these epitopes had not previously been reported. These responses declined rapidly in those who became chronically infected and were maintained in the subject who cleared infection. Higher-magnitude CD8(+) T cell responses were associated with rapid development of immune escape variants at a rate of up to 0.1 per day. Rapid escape from CD8(+) T cell responses has been quantified for the first time in the early phase of primary HCV infection. These rapid escape dynamics were associated with higher-magnitude CD8(+) T cell responses. These findings raise questions regarding optimal selection of immunogens for HCV vaccine development and suggest that detailed analysis of individual epitopes may be required. A major limitation in our detailed understanding of the role of immune response in HCV clearance has been the lack of data on very early primary infection when the transmitted viral variants successfully establish

  15. Delayed Disease Progression in Cynomolgus Macaques Infected with Ebola Virus Makona Strain.

    Science.gov (United States)

    Marzi, Andrea; Feldmann, Friederike; Hanley, Patrick W; Scott, Dana P; Günther, Stephan; Feldmann, Heinz

    2015-10-01

    In late 2013, the largest documented outbreak of Ebola hemorrhagic fever started in Guinea and has since spread to neighboring countries, resulting in almost 27,000 cases and >11,000 deaths in humans. In March 2014, Ebola virus (EBOV) was identified as the causative agent. This study compares the pathogenesis of a new EBOV strain, Makona, which was isolated in Guinea in 2014 with the prototype strain from the 1976 EBOV outbreak in the former Zaire. Both strains cause lethal disease in cynomolgus macaques with similar pathologic changes and hallmark features of Ebola hemorrhagic fever. However, disease progression was delayed in EBOV-Makona-infected animals, suggesting decreased rather than increased virulence of this most recent EBOV strain.

  16. Candidiasis: a fungal infection--current challenges and progress in prevention and treatment.

    Science.gov (United States)

    Hani, Umme; Shivakumar, Hosakote G; Vaghela, Rudra; Osmani, Riyaz Ali M; Shrivastava, Atul

    2015-01-01

    Despite therapeutic advances candidiasis remains a common fungal infection most frequently caused by C. albicans and may occur as vulvovaginal candidiasis or thrush, a mucocutaneous candidiasis. Candidiasis frequently occurs in newborns, in immune-deficient people like AIDS patients, and in people being treated with broad spectrum antibiotics. It is mainly due to C. albicans while other species such as C. tropicalis, C. glabrata, C. parapsilosis and C. krusei are increasingly isolated. OTC antifungal dosage forms such as creams and gels can be used for effective treatment of local candidiasis. Whereas, for preventing spread of the disease to deeper vital organs, candidiasis antifungal chemotherapy is preferred. Use of probiotics and development of novel vaccines is an advanced approach for the prevention of candidiasis. Present review summarizes the diagnosis, current status and challenges in the treatment and prevention of candidiasis with prime focus on host defense against candidiasis, advancements in diagnosis, probiotics role and recent progress in the development of vaccines against candidiasis.

  17. Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease.

    Science.gov (United States)

    Hill, Rebecca M; Kuijper, Sanne; Lindsey, Janet C; Petrie, Kevin; Schwalbe, Ed C; Barker, Karen; Boult, Jessica K R; Williamson, Daniel; Ahmad, Zai; Hallsworth, Albert; Ryan, Sarra L; Poon, Evon; Robinson, Simon P; Ruddle, Ruth; Raynaud, Florence I; Howell, Louise; Kwok, Colin; Joshi, Abhijit; Nicholson, Sarah Leigh; Crosier, Stephen; Ellison, David W; Wharton, Stephen B; Robson, Keith; Michalski, Antony; Hargrave, Darren; Jacques, Thomas S; Pizer, Barry; Bailey, Simon; Swartling, Fredrik J; Weiss, William A; Chesler, Louis; Clifford, Steven C

    2015-01-12

    We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, and all patients in this group died of rapidly progressive disease postrelapse. To study this interaction, we investigated a transgenic model of MYCN-driven medulloblastoma and found spontaneous development of Trp53 inactivating mutations. Abrogation of p53 function in this model produced aggressive tumors that mimicked characteristics of relapsed human tumors with combined P53-MYC dysfunction. Restoration of p53 activity and genetic and therapeutic suppression of MYCN all reduced tumor growth and prolonged survival. Our findings identify P53-MYC interactions at medulloblastoma relapse as biomarkers of clinically aggressive disease that may be targeted therapeutically. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Pregnancy and HIV infection

    OpenAIRE

    Mete Sucu; Cihan Cetin; Mehmet Ozsurmeli; Ghanim Khatib; Ceren Cetin; Cuneyt Evruke

    2016-01-01

    The management of Human Immunodeficiency Virus (HIV) infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinician...

  19. Progressive increase in central nervous system immune activation in untreated primary HIV-1 infection.

    Science.gov (United States)

    Suh, Joome; Sinclair, Elizabeth; Peterson, Julia; Lee, Evelyn; Kyriakides, Tassos C; Li, Fang-Yong; Hagberg, Lars; Fuchs, Dietmar; Price, Richard W; Gisslen, Magnus; Spudich, Serena

    2014-12-03

    Central nervous system (CNS) inflammation is a mediator of brain injury in HIV infection. To study the natural course of CNS inflammation in the early phase of infection, we analyzed longitudinal levels of soluble and cellular markers of inflammation in cerebrospinal fluid (CSF) and blood, beginning with primary HIV-1 infection (PHI). Antiretroviral-naïve subjects identified as having PHI (less than one year since HIV transmission) participated in phlebotomy and lumbar puncture at baseline and at variable intervals thereafter. Mixed-effects models were used to analyze longitudinal levels of CSF neopterin and percentages of activated cluster of differentiation (CD)4+ and CD8+ T-cells (co-expressing CD38 and human leukocyte antigen-D-related (HLA-DR)) in blood and CSF. A total of 81 subjects were enrolled at an average of 100 days after HIV transmission and had an average follow-up period of 321 days, with the number of visits ranging from one to 13. At baseline, the majority of subjects had CSF neopterin concentrations above the upper limit of normal. The baseline concentration was associated with the longitudinal trajectory of CSF neopterin. In subjects with baseline levels of less than 21 nmol/L, a cutoff value obtained from a mixed-effects model, CSF neopterin increased by 2.9% per 10 weeks (n = 33; P <0.001), whereas it decreased by 6.7% in subjects with baseline levels of more than 21 nmol/L (n = 11; P = 0.001). In a subset with available flow cytometry data (n = 42), the percentages of activated CD4+ and CD8+ T-cells in CSF increased by 0.8 (P <0.001) and 0.73 (P = 0.02) per 10 weeks, respectively. Neopterin levels and the percentages of activated CD4+ and CD8+ T-cells in CSF progressively increase in most subjects without treatment during early HIV-1 infection, suggesting an accrual of intrathecal inflammation, a major contributor to neuropathology in HIV infection.

  20. High-sensitive and rapid detection of Mycobacterium tuberculosis infection by IFN-γ release assay among HIV-infected individuals in BCG-vaccinated area

    Directory of Open Access Journals (Sweden)

    Jiang Weimin

    2009-05-01

    Full Text Available Abstract Background An accurate test for Mycobacterium tuberculosis infection is urgently needed in immunosuppressed populations. The aim of this study was to investigate the diagnostic power of enzyme-linked immunospot (ELISPOT-based IFN-γ release assay in detecting active and latent tuberculosis in HIV-infected population in bacillus Calmette-Guerin (BCG-vaccinated area. A total of 100 HIV-infected individuals including 32 active tuberculosis patients were recruited. An ELISPOT-based IFN-γ release assay, T-SPOT.TB, was used to evaluate the M. tuberculosis ESAT-6 and CFP-10 specific IFN-γ response. Tuberculin skin test (TST was performed for all recruited subjects. Results The subjects were divided into group HIV+ATB (HIV-infected individuals with active tuberculosis, n = 32, group HIV+LTB (HIV-infected individuals with positive results of T-SPOT.TB assay, n = 46 and group HIV only (HIV-infected individuals with negative results of T-SPOT.TB assay and without evidence of tuberculosis infection, n = 22. In group HIV+ATB and HIV+LTB, T-SPOT.TB positive rate in subjects with TST P 85% in patients with TB treatment for less than 1 month and CD4+ T cells ≥200/μl, while for patients treated for more than 3 months and CD4+ T cells Conclusion ELISPOT-based IFN-γ release assay is more sensitive and rapid for the diagnosis of TB infection in Chinese HIV-infected individuals with history of BCG vaccination, and could be an effective tool for guiding preventive treatment with isoniazid in latently infected people and for TB control in China.

  1. Immunological Basis for Rapid Progression of Diabetes in Older NOD Mouse Recipients Post BM-HSC Transplantation.

    Directory of Open Access Journals (Sweden)

    Nan Wang

    Full Text Available Type I diabetes (T1D, mediated by autoreactive T cell destruction of insulin-producing islet beta cells, has been treated with bone marrow-derived hematopoietic stem cell (BM-HSC transplantation. Older non-obese diabetic (NOD mice recipients (3m, at disease-onset stage receiving syngeneic BM-HSC progressed more rapidly to end-stage diabetes post-transplantation than younger recipients (4-6w, at disease-initiation stage. FACS analyses showed a higher percentage and absolute number of regulatory T cells (Treg and lower proportion of proliferating T conventional cells (Tcon in pancreatic lymph nodes from the resistant mice among the younger recipients compared to the rapid progressors among the older recipients. Treg distribution in spleen, mesenteric lymph nodes (MLN, blood and thymus between the two groups was similar. However, the percentage of thymic Tcon and the proliferation of Tcon in MLN and blood were lower in the young resistants. These results suggest recipient age and associated disease stage as a variable to consider in BM-HSC transplantation for treating T1D.

  2. Discordant Impact of HLA on Viral Replicative Capacity and Disease Progression in Pediatric and Adult HIV Infection.

    Directory of Open Access Journals (Sweden)

    Emily Adland

    2015-06-01

    Full Text Available HLA class I polymorphism has a major influence on adult HIV disease progression. An important mechanism mediating this effect is the impact on viral replicative capacity (VRC of the escape mutations selected in response to HLA-restricted CD8+ T-cell responses. Factors that contribute to slow progression in pediatric HIV infection are less well understood. We here investigate the relationship between VRC and disease progression in pediatric infection, and the effect of HLA on VRC and on disease outcome in adult and pediatric infection. Studying a South African cohort of >350 ART-naïve, HIV-infected children and their mothers, we first observed that pediatric disease progression is significantly correlated with VRC. As expected, VRCs in mother-child pairs were strongly correlated (p = 0.004. The impact of the protective HLA alleles, HLA-B*57, HLA-B*58:01 and HLA-B*81:01, resulted in significantly lower VRCs in adults (p<0.0001, but not in children. Similarly, in adults, but not in children, VRCs were significantly higher in subjects expressing the disease-susceptible alleles HLA-B*18:01/45:01/58:02 (p = 0.007. Irrespective of the subject, VRCs were strongly correlated with the number of Gag CD8+ T-cell escape mutants driven by HLA-B*57/58:01/81:01 present in each virus (p = 0.0002. In contrast to the impact of VRC common to progression in adults and children, the HLA effects on disease outcome, that are substantial in adults, are small and statistically insignificant in infected children. These data further highlight the important role that VRC plays both in adult and pediatric progression, and demonstrate that HLA-independent factors, yet to be fully defined, are predominantly responsible for pediatric non-progression.

  3. Influence of Vehicles Used for Oral Dosing of Test Molecules on the Progression of Mycobacterium tuberculosis Infection in Mice

    OpenAIRE

    Singh, Shubhra; Dwivedi, Richa; Chaturvedi, Vinita

    2014-01-01

    Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate-80 on the progression of Mycobacterium tuberculosis infection in mice. Infection was monitored by physical (survival time and body weight) and bacteriological (viable counts in lungs) parameters. Compared with water, corn oil significantly improved both ...

  4. A rapid non-destructive method for quantification of fungal infection on barley and malt

    DEFF Research Database (Denmark)

    Bodevin, Sabrina; Larsen, Tone Glarborg; Lok, Finn

    indicate that the videometerlab® equipment can accurately evaluate the percentage of global fungal infection in kernels. Discussion: We believe that this system will be able to discriminate between kernels infected from non-infected ones in mixed samples. This system will allow to quantify the level...

  5. Label-free bimodal waveguide immunosensor for rapid diagnosis of bacterial infections in cirrhotic patients.

    Science.gov (United States)

    Maldonado, Jesús; González-Guerrero, Ana Belén; Domínguez, Carlos; Lechuga, Laura M

    2016-11-15

    Spontaneous bacterial peritonitis is an acute bacterial infection of ascitic fluid; it has a high incidence in cirrhotic patients and it is associated with high mortality. In such a situation, early diagnosis and treatment is crucial for the survival of the patient. However, bacterial analysis in ascitic fluid is currently based on culture methods, which are time-consuming and laborious. We report here the application of a photonic interferometer biosensor based on a bimodal waveguide (BiMW) for the rapid and label-free detection of bacteria directly in ascitic fluid. The device consists of a straight waveguide in which two modes of the same polarization interfere while interacting with the external medium through their evanescent fields. A bimolecular event occurring on the sensor area of the device (e.g. capturing bacteria) will differently affect each light mode, inducing a variation in the phase of the light exiting at the output of the waveguide. In this work, we demonstrate the quantitative detection of Bacillus cereus in buffer medium and Escherichia coli in undiluted ascitic fluid from cirrhotic patients. In the case of Bacillus cereus detection, the device was able to specifically detect bacteria at relevant concentrations in 12.5min and in the case of Escherichia coli detection, the analysis time was 25min. Extrapolation of the data demonstrated that the detection limits of the biosensor could reach few bacteria per milliliter. Based on the results obtained, we consider that the BiMW biosensor is positioned as a promising new clinical tool for user-friendly, cost-effective and real-time microbiological analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Visual loop-mediated isothermal amplification (LAMP) for the rapid diagnosis of Enterocytozoon hepatopenaei (EHP) infection.

    Science.gov (United States)

    T, Sathish Kumar; A, Navaneeth Krishnan; J, Joseph Sahaya Rajan; M, Makesh; K P, Jithendran; S V, Alavandi; K K, Vijayan

    2018-05-01

    The emerging microsporidian parasite Enterocytozoon hepatopenaei (EHP), the causative agent of hepatopancreatic microsporidiosis, has been widely reported in shrimp-farming countries. EHP infection can be detected by light microscopy observation of spores (1.7 × 1 μm) in stained hepatopancreas (HP) tissue smears, HP tissue sections, and fecal samples. EHP can also be detected by polymerase chain reaction (PCR) targeting the small subunit (SSU) ribosomal RNA (rRNA) gene or the spore wall protein gene (SWP). In this study, a rapid, sensitive, specific, and closed tube visual loop-mediated isothermal amplification (LAMP) protocol combined with FTA cards was developed for the diagnosis of EHP. LAMP primers were designed based on the SSU rRNA gene of EHP. The target sequence of EHP was amplified at constant temperature of 65 °C for 45 min and amplified LAMP products were visually detected in a closed tube system by using SYBR™ green I dye. Detection limit of this LAMP protocol was ten copies. Field and clinical applicability of this assay was evaluated using 162 field samples including 106 HP tissue samples and 56 fecal samples collected from shrimp farms. Out of 162 samples, EHP could be detected in 62 samples (47 HP samples and 15 fecal samples). When compared with SWP-PCR as the gold standard, this EHP LAMP assay had 95.31% sensitivity, 98.98% specificity, and a kappa value of 0.948. This simple, closed tube, clinically evaluated visual LAMP assay has great potential for diagnosing EHP at the farm level, particularly under low-resource circumstances.

  7. Zika virus infection, transmission, associated neurological disorders and birth abnormalities: A review of progress in research, priorities and knowledge gaps

    Directory of Open Access Journals (Sweden)

    Yitades Gebre

    2016-10-01

    Full Text Available On February 1, 2016, the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern. Furthermore, few studies demonstrated that there was an increased evidence of causal relationship of Zika virus (ZIKAV infection and microcephaly, birth abnormalities and neurological disorders such as Guillain–Barré syndrome. ZIKAV transmission occurs mainly by the bite of infected mosquitos (Aedes species, but there are also reports that infections could occur via the placenta, breast milk, saliva, blood transfusion and sex. This article reviews the global efforts, progress in scientific research to understand the pathogenesis of ZIKAV infection & disease, clinical presentations, congenital transmission and autoimmune neurological disorders. The paper further explores the knowledge gaps, future priority research agenda for strategic response including vector control and prevention. We conducted a systematic literature review to synthesise available evidence on ZIKAV infection and its vector and host interaction from electronic databases.

  8. Zika virus infection, transmission, associated neurological disorders and birth abnormalities: A review of progress in research, priorities and knowledge gaps

    Institute of Scientific and Technical Information of China (English)

    Yitades Gebre; Nikkiah Forbes; Teshome Gebre

    2016-01-01

    On February 1, 2016, the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern. Furthermore, few studies demonstrated that there was an increased evidence of causal relationship of Zika virus(ZIKAV) infection and microcephaly, birth abnormalities and neurological disorders such as Guillain–Barre′ syndrome.ZIKAV transmission occurs mainly by the bite of infected mosquitos(Aedes species), but there are also reports that infections could occur via the placenta, breast milk, saliva,blood transfusion and sex. This article reviews the global efforts, progress in scientific research to understand the pathogenesis of ZIKAV infection & disease, clinical presentations, congenital transmission and autoimmune neurological disorders. The paper further explores the knowledge gaps, future priority research agenda for strategic response including vector control and prevention. We conducted a systematic literature review to synthesise available evidence on ZIKAV infection and its vector and host interaction from electronic databases.

  9. PRO-QUEST: a rapid assessment method based on progressive saturation for quantifying exchange rates using saturation times in CEST.

    Science.gov (United States)

    Demetriou, Eleni; Tachrount, Mohamed; Zaiss, Moritz; Shmueli, Karin; Golay, Xavier

    2018-03-05

    To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T 1 of water and B 1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer-weighted imaging. Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo. © 2018 International Society for Magnetic Resonance in Medicine.

  10. Progression of biopsy-measured liver fibrosis in untreated patients with hepatitis C infection: non-Markov multistate model analysis.

    Directory of Open Access Journals (Sweden)

    Peter Bacchetti

    Full Text Available BACKGROUND: Fibrosis stages from liver biopsies reflect liver damage from hepatitis C infection, but analysis is challenging due to their ordered but non-numeric nature, infrequent measurement, misclassification, and unknown infection times. METHODS: We used a non-Markov multistate model, accounting for misclassification, with multiple imputation of unknown infection times, applied to 1062 participants of whom 159 had multiple biopsies. Odds ratios (OR quantified the estimated effects of covariates on progression risk at any given time. RESULTS: Models estimated that progression risk decreased the more time participants had already spent in the current stage, African American race was protective (OR 0.75, 95% confidence interval 0.60 to 0.95, p = 0.018, and older current age increased risk (OR 1.33 per decade, 95% confidence interval 1.15 to 1.54, p = 0.0002. When controlled for current age, older age at infection did not appear to increase risk (OR 0.92 per decade, 95% confidence interval 0.47 to 1.79, p = 0.80. There was a suggestion that co-infection with human immunodeficiency virus increased risk of progression in the era of highly active antiretroviral treatment beginning in 1996 (OR 2.1, 95% confidence interval 0.97 to 4.4, p = 0.059. Other examined risk factors may influence progression risk, but evidence for or against this was weak due to wide confidence intervals. The main results were essentially unchanged using different assumed misclassification rates or imputation of age of infection. DISCUSSION: The analysis avoided problems inherent in simpler methods, supported the previously suspected protective effect of African American race, and suggested that current age rather than age of infection increases risk. Decreasing risk of progression with longer time already spent in a stage was also previously found for post-transplant progression. This could reflect varying disease activity, with recent progression indicating

  11. Therapeutic PD-L1 and LAG-3 blockade rapidly clears established blood-stage Plasmodium infection

    Science.gov (United States)

    Butler, Noah S.; Moebius, Jacqueline; Pewe, Lecia L.; Traore, Boubacar; Doumbo, Ogobara K.; Tygrett, Lorraine T.; Waldschmidt, Thomas J.; Crompton, Peter D.; Harty, John T.

    2011-01-01

    Plasmodium infection of erythrocytes induces clinical malaria. Parasite-specific CD4+ T cells correlate with reduced parasite burdens and severity of human malaria, and are required to control blood-stage infection in mice. However, the characteristics of CD4+ T cells that determine protection or parasite persistence remain unknown. Here we show that P. falciparum infection of humans increased expression of an inhibitory receptor (PD-1) associated with T cell dysfunction. In vivo blockade of PD-L1 and LAG-3 restored CD4+ T cell function, amplified T follicular helper cell and germinal center B cell and plasmablast numbers, enhanced protective antibodies and rapidly cleared blood-stage malaria in mice. Thus, chronic malaria drives specific T cell dysfunction, which can be rescued to enhance parasite control using inhibitory therapies. PMID:22157630

  12. Rapid selection of escape mutants by the first CD8 T cell responses in acute HIV-1 infection

    Energy Technology Data Exchange (ETDEWEB)

    Korber, Bette Tina Marie [Los Alamos National Laboratory

    2008-01-01

    The recent failure of a vaccine that primes T cell responses to control primary HIV-1 infection has raised doubts about the role of CD8+ T cells in early HIV-1 infection. We studied four patients who were identified shortly after HIV-1 infection and before seroconversion. In each patient there was very rapid selection of multiple HIV-1 escape mutants in the transmitted virus by CD8 T cells, including examples of complete fixation of non-synonymous substitutions within 2 weeks. Sequencing by single genome amplification suggested that the high rate of virus replication in acute infection gave a selective advantage to virus molecules that contained simultaneous and gained sequential T cell escape mutations. These observations show that whilst early HIV-1 specific CD8 T cells can act against virus, rapid escape means that these T cell responses are unlikely to benefit the patient and may in part explain why current HIV-1 T cell vaccines may not be protective.

  13. Self Test Kit: Rapid Diagnosis of Urogenital Infections in Military Women

    Science.gov (United States)

    2000-09-01

    Page 22 R eferences ............................................................................ P age 23 A ppendices ...external dysuria which is more associated with vulvar or vaginal infection). Acute urethritis is most often due to Chlamydia trachomatis or Neisseria...gonorrhoeae. The vast majority of lower urinary tract infections in women are cystitis rather than urethritis. Acute , uncomplicated cystitis in young

  14. An atypical cause of rapidly progressing breast lump with abscess formation: Pure squamous cell carcinoma of the breast.

    Science.gov (United States)

    Cilekar, Murat; Erkasap, Serdar; Oner, Ulku; Akici, Murat; Ciftci, Evrim; Dizen, Hayrettin; Turel, Serkan; Kavak, Ozgu I; Yilmaz, Sezgin

    2015-01-01

    Squamous cell carcinoma (SCC) is a rare type of breast malignancy and little is known about long-term outcome. In the present report, the clinical features, histopathologic findings and postoperative course of a patient with squamous cell carcinoma are described. We have treated a 47-years-old woman who admitted for right breast mass without any discharge, bleeding and pain. The tumor was, 3 × 2 × 1.5 cm in size with central abscess formation. The result of surgical biopsy revealed large cell keratinizing type of SCC. The metastatic work-up studies ruled out any other probable sources of primary tumor. The patient was performed modified radical mastectomy and axillary dissection and received two cycles of chemotherapy. Squamous cell carcinoma of the breast (SCCB) is a rare entity and should be considered in patients with rapidly progressing breast mass. It should also be considered in breast lesions with abscess formation. The initial therapeutic approach should be surgical excision after histopathological diagnosis.

  15. EU-approved rapid tests might underestimate bovine spongiform encephalopathy infection in goats

    NARCIS (Netherlands)

    Meloni, Daniela; Bozzetta, Elena; Langeveld, Jan P.M.; Groschup, Martin H.; Goldmann, Wilfred; Andrèoletti, Olivier; Lantier, Isabelle; Keulen, Van Lucien; Bossers, Alex; Pitardi, Danilo; Nonno, Romolo; Sklaviadis, Theodoros; Ingravalle, Francesco; Peletto, Simone; Colussi, Silvia; Acutis, Pier Luigi

    2017-01-01

    We report the diagnostic sensitivity of 3 EU-approved rapid tests (ELISAs; 1 from IDEXX and 2 from Bio-Rad) for the detection of transmissible spongiform encephalopathy diseases in goats. Ninety-eight goat brainstem samples were tested. All the rapid tests had 100% specificity and ≥80% sensitivity,

  16. Research progress on influencing factors of hospital infection and prevention and control measures

    Directory of Open Access Journals (Sweden)

    He Wenlong

    2015-03-01

    Full Text Available Hospital infections are associated with the emergence of hospitals. As the understanding of hospital infections deepen and prevention and control measures improve, hospital infections have become manageable. In recent years, affected by the increase in invasive treatment technology, antimicrobial abuse, and other factors, the control of hospital infection has encountered new problems. This paper reviews the influencing factors of hospital infections and their prevention and control measures.

  17. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, P. Ø.; Rasmussen, Thomas Bovbjerg

    2005-01-01

    The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis patients. P. aeruginosa colonizes the lungs by forming biofilm microcolonies throughout the lung. Quorum sensing (QS) renders the biofilm bacteria highly tolerant......-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology...... and phagocytosis by PMNs, as well as leading to an improved outcome of pulmonary infections....

  18. Rapid improvement of Henoch-Schonlein purpura associated with the treatment of Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Turgay Ulas

    2012-01-01

    Full Text Available Helicobacter pylori (H. pylori are one of the most common bacterial infections, seen in humans, worldwide and their possible relationships to different diseases are a focus of attention nowadays. H. pylori may cause some extra intestinal manifestations some of which are dermatological conditions, including Henoch-Schönlein purpura (HSP, chronic urticaria and atopic dermatitis. We describe a 49-year-old man who presented with HSP triggered by gastric H. pylori infection. Treatment of H. Pylori infection was accompanied by prompt resolution of the gastrointestinal manifestations and purpuric rashes. These findings suggest a causative role for H. pylori in the occurrence of HSP.

  19. Rapid and widely disseminated acute phase protein response after experimental bacterial infection of pigs

    DEFF Research Database (Denmark)

    Skovgaard, Kerstin; Mortensen, Shila; Boye, Mette

    2009-01-01

    The acute phase protein response is a well-described generalized early host response to tissue injury, inflammation and infection, observed as pronounced changes in the concentrations of a number of circulating serum proteins. The biological function of this response and its interplay with other...... parts of innate host defence reactions remain somewhat elusive. In order to gain new insight into this early host defence response in the context of bacterial infection we studied gene expression changes in peripheral lymphoid tissues as compared to hepatic expression changes, 14-18 h after lung...... with measurements of interleukin-6 and selected acute phase proteins in serum. C-reactive protein and serum amyloid A were clearly induced 14-18 h after infection. Extrahepatic expression of acute phase proteins was found to be dramatically altered as a result of the lung infection with an extrahepatic acute phase...

  20. Sequential Dysfunction and Progressive Depletion of Candida albicans-Specific CD4 T Cell Response in HIV-1 Infection

    Science.gov (United States)

    Liu, Fengliang; Fan, Xiuzhen; Auclair, Sarah; Ferguson, Monique; Sun, Jiaren; Soong, Lynn; Hou, Wei; Redfield, Robert R.; Birx, Deborah L.; Ratto-Kim, Silvia; Robb, Merlin L.; Kim, Jerome H.; Michael, Nelson L.; Hu, Haitao

    2016-01-01

    Loss of immune control over opportunistic infections can occur at different stages of HIV-1 (HIV) disease, among which mucosal candidiasis caused by the fungal pathogen Candida albicans (C. albicans) is one of the early and common manifestations in HIV-infected human subjects. The underlying immunological basis is not well defined. We have previously shown that compared to cytomegalovirus (CMV)-specific CD4 cells, C. albicans-specific CD4 T cells are highly permissive to HIV in vitro. Here, based on an antiretroviral treatment (ART) naïve HIV infection cohort (RV21), we investigated longitudinally the impact of HIV on C. albicans- and CMV-specific CD4 T-cell immunity in vivo. We found a sequential dysfunction and preferential depletion for C. albicans-specific CD4 T cell response during progressive HIV infection. Compared to Th1 (IFN-γ, MIP-1β) functional subsets, the Th17 functional subsets (IL-17, IL-22) of C. albicans-specific CD4 T cells were more permissive to HIV in vitro and impaired earlier in HIV-infected subjects. Infection history analysis showed that C. albicans-specific CD4 T cells were more susceptible to HIV in vivo, harboring modestly but significantly higher levels of HIV DNA, than CMV-specific CD4 T cells. Longitudinal analysis of HIV-infected individuals with ongoing CD4 depletion demonstrated that C. albicans-specific CD4 T-cell response was preferentially and progressively depleted. Taken together, these data suggest a potential mechanism for earlier loss of immune control over mucosal candidiasis in HIV-infected patients and provide new insights into pathogen-specific immune failure in AIDS pathogenesis. PMID:27280548

  1. Acute lyme infection presenting with amyopathic dermatomyositis and rapidly fatal interstitial pulmonary fibrosis: a case report

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    Nguyen Hanh

    2010-06-01

    Full Text Available Abstract Introduction Dermatomyositis has been described in the setting of lyme infection in only nine previous case reports. Although lyme disease is known to induce typical clinical findings that are observed in various collagen vascular diseases, to our knowledge, we believe that our case is the first presentation of acute lyme disease associated with amyopathic dermatomyositis, which was then followed by severe and fatal interstitial pulmonary fibrosis only two months later. Case presentation We present a case of a 64-year-old African-American man with multiple medical problems who was diagnosed with acute lyme infection after presenting with the pathognomonic rash and confirmatory serology. In spite of appropriate antimicrobial therapy for lyme infection, he developed unexpected amyopathic dermatomyositis and then interstitial lung disease. Conclusions This case illustrates a potential for lyme disease to produce clinical syndromes that may be indistinguishable from primary connective tissue diseases. An atypical and sequential presentation (dermatomyositis and interstitial lung disease of a common disease (lyme infection is discussed. This case illustrates that in patients who are diagnosed with lyme infection who subsequently develop atypical muscular, respiratory or other systemic complaints, the possibility of severe rheumatological and pulmonary complications should be considered.

  2. Viral infection causes rapid sensitization to lipopolysaccharide: central role of IFN-alpha beta

    DEFF Research Database (Denmark)

    Nansen, A; Randrup Thomsen, A

    2001-01-01

    LPS is the major active agent in the pathogenesis of Gram-negative septic shock. In this report we have studied the influence of concurrent viral infection on the outcome of LPS-induced shock. We find that infection with vesicular stomatitis virus sensitizes mice to LPS at an early time point...... following infection. Treatment of mice with the chemical IFN inducer, polyinosinic:polycytidylic acid, has a similar effect. This hypersensitivity to LPS correlated with hyperproduction of TNF-alpha in vivo. The cellular and molecular mechanisms underlying this phenomenon were investigated using Ab......-depleted and gene-targeted mice. Our results revealed that while NK cell depletion and elimination of IFN-gamma partially protected against the sensitizing effects of vesicular stomatitis virus and polyinosinic:polycytidylic acid, the most striking effect was observed in IFN-alphabetaR-deficient mice. Thus...

  3. Progress and Problems in Understanding and Managing Primary Epstein-Barr Virus Infections

    Science.gov (United States)

    Odumade, Oludare A.; Hogquist, Kristin A.; Balfour, Henry H.

    2011-01-01

    Summary: Epstein-Barr virus (EBV) is a gammaherpesvirus that infects a large fraction of the human population. Primary infection is often asymptomatic but results in lifelong infection, which is kept in check by the host immune system. In some cases, primary infection can result in infectious mononucleosis. Furthermore, when host-virus balance is not achieved, the virus can drive potentially lethal lymphoproliferation and lymphomagenesis. In this review, we describe the biology of EBV and the host immune response. We review the diagnosis of EBV infection and discuss the characteristics and pathogenesis of infectious mononucleosis. These topics are approached in the context of developing therapeutic and preventative strategies. PMID:21233512

  4. Polymer based biosensor for rapid electrochemical detection of virus infection of human cells

    DEFF Research Database (Denmark)

    Kiilerich-Pedersen, Katrine; Poulsen, Claus R.; Jain, Titoo

    2011-01-01

    The demand in the field of medical diagnostics for simple, cost efficient and disposable devices is growing. Here, we present a label free, all-polymer electrochemical biosensor for detection of acute viral disease. The dynamics of a viral infection in human cell culture was investigated in a mic...

  5. Rapid appraisal of human intestinal helminth infections among schoolchildren in Osh oblast, Kyrgyzstan.

    Science.gov (United States)

    Steinmann, Peter; Usubalieva, Jumagul; Imanalieva, Cholpon; Minbaeva, Gulnara; Stefiuk, Kayte; Jeandron, Aurelie; Utzinger, Jürg

    2010-12-01

    A population-representative lot quality assurance sampling (LQAS) survey was conducted in 2009 to determine the prevalence of intestinal helminth infections among schoolchildren across Osh oblast, Kyrgyzstan. The diagnostic approach consisted of duplicate Kato-Katz thick smears from a single stool sample and an adhesive tape test. A questionnaire was administered to identify risk factors for infections. A total of 1262 schoolchildren aged 6-15 years were recruited; 41% of them harboured at least one of the eight identified helminth species. The two most prevalent helminths were Ascaris lumbricoides (23.1%) and Enterobius vermicularis (19.3%). Lower prevalences were found for Hymenolepis nana (4.4%), Fasciola hepatica (1.9%) and Dicrocoelium dendriticum (1.8%). Washing raw vegetables was a protective factor with regard to A. lumbricoides infection (odds ratio (OR)=0.69, p=0.022); tap water was borderline protective (OR=0.56, p=0.057). Children of the richest families were at a lower risk of E. vermicularis infection than the poorest ones (OR=0.41, p=0.011). Sharing the bed with more than one person was a risk factor for E. vermicularis infection (OR=2.0, p=0.002). The results call for targeted interventions against intestinal helminths in Osh oblast. In a first stage, annual deworming of schoolchildren and other high-risk groups with albendazole or mebendazole should be implemented, and reliable diagnosis and additional anthelminthic drugs should be made available. Subsequently, transmission control including locally-adapted health education, improved water supply and adequate sanitation should become the central features. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Science.gov (United States)

    Morrison, Susan; John-Stewart, Grace; Egessa, John J; Mubezi, Sezi; Kusemererwa, Sylvia; Bii, Dennis K; Bulya, Nulu; Mugume, Francis; Campbell, James D; Wangisi, Jonathan; Bukusi, Elizabeth A; Celum, Connie; Baeten, Jared M

    2015-01-01

    During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  7. Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding.

    Directory of Open Access Journals (Sweden)

    Susan Morrison

    Full Text Available During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART, despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.

  8. Progression from productive infection to integration and oncogenic transformation in human papillomavirus type 59-immortalized foreskin keratinocytes.

    Science.gov (United States)

    Spartz, Helena; Lehr, Elizabeth; Zhang, Benyue; Roman, Ann; Brown, Darron R

    2005-05-25

    Studies of changes in the virus and host cell upon progression from human papillomavirus (HPV) episomal infection to integration are critical to understanding HPV-related malignant transformation. However, there exist only a few in vitro models of both productive HPV infection and neoplastic progression on the same host background. We recently described a unique foreskin keratinocyte cell line (ERIN 59) that contains HPV 59 (a close relative of HPV 18). Early passages of ERIN 59 cells (passages 9-13) contained approximately 50 copies of episomes/cell, were feeder cell-dependent, and could be induced to differentiate and produce infectious virus in a simple culture system. We now report that late passage cells (passages greater than 50) were morphologically different from early passage cells, were feeder cell independent, and did not differentiate or produce virus. These late passage cells contained HPV in an integrated form. An integration-derived oncogene transcript was expressed in late passage cells. The E2 open reading frame was interrupted in this transcript at nucleotide 3351. Despite a lower viral genome copy number in late passage ERIN 59 cells, expression of E6/E7 oncogene transcripts was similar to early passage cells. We conclude that ERIN 59 cells are a valuable cell line representing a model of progression from HPV 59 episomal infection and virus production to HPV 59 integration and associated oncogenic transformation on the same host background.

  9. Transcriptional Profiling of Immune-Related Genes in Leishmania infantum-Infected Mice: Identification of Potential Biomarkers of Infection and Progression of Disease

    Directory of Open Access Journals (Sweden)

    Eduardo Ontoria

    2018-06-01

    Full Text Available Leishmania spp. is a protozoan parasite that affects millions of people around the world. At present, there is no effective vaccine to prevent leishmaniases in humans. A major limitation in vaccine development is the lack of precise understanding of the particular immunological mechanisms that allow parasite survival in the host. The parasite-host cell interaction induces dramatic changes in transcriptome patterns in both organisms, therefore, a detailed analysis of gene expression in infected tissues will contribute to the evaluation of drug and vaccine candidates, the identification of potential biomarkers, and the understanding of the immunological pathways that lead to protection or progression of disease. In this large-scale analysis, differential expression of 112 immune-related genes has been analyzed using high-throughput qPCR in spleens of infected and naïve Balb/c mice at four different time points. This analysis revealed that early response against Leishmania infection is characterized by the upregulation of Th1 markers and M1-macrophage activation molecules such as Ifng, Stat1, Cxcl9, Cxcl10, Ccr5, Cxcr3, Xcl1, and Ccl3. This activation doesn't protect spleen from infection, since parasitic burden rises along time. This marked difference in gene expression between infected and control mice disappears during intermediate stages of infection, probably related to the strong anti-inflammatory and immunosuppresory signals that are activated early upon infection (Ctla4 or remain activated throughout the experiment (Il18bp. The overexpression of these Th1/M1 markers is restored later in the chronic phase (8 wpi, suggesting the generation of a classical “protective response” against leishmaniasis. Nonetheless, the parasitic burden rockets at this timepoint. This apparent contradiction can be explained by the generation of a regulatory immune response characterized by overexpression of Ifng, Tnfa, Il10, and downregulation Il4 that

  10. Parasite load induces progressive spleen architecture breakage and impairs cytokine mRNA expression in Leishmania infantum-naturally infected dogs.

    Science.gov (United States)

    Cavalcanti, Amanda S; Ribeiro-Alves, Marcelo; Pereira, Luiza de O R; Mestre, Gustavo Leandro; Ferreira, Anna Beatriz Robottom; Morgado, Fernanda N; Boité, Mariana C; Cupolillo, Elisa; Moraes, Milton O; Porrozzi, Renato

    2015-01-01

    Canine Visceral Leishmaniasis (CVL) shares many aspects with the human disease and dogs are considered the main urban reservoir of L. infantum in zoonotic VL. Infected dogs develop progressive disease with a large clinical spectrum. A complex balance between the parasite and the genetic/immunological background of the host are decisive for infection evolution and clinical outcome. This study comprised 92 Leishmania infected mongrel dogs of various ages from Mato Grosso, Brazil. Spleen samples were collected for determining parasite load, humoral response, cytokine mRNA expression and histopathology alterations. By real-time PCR for the ssrRNA Leishmania gene, two groups were defined; a low (lowP, n = 46) and a high parasite load groups (highP, n = 42). When comparing these groups, results show variable individual humoral immune response with higher specific IgG production in infected animals but with a notable difference in CVL rapid test optical densities (DPP) between highP and lowP groups. Splenic architecture disruption was characterized by disorganization of white pulp, more evident in animals with high parasitism. All cytokine transcripts in spleen were less expressed in highP than lowP groups with a large heterogeneous variation in response. Individual correlation analysis between cytokine expression and parasite load revealed a negative correlation for both pro-inflammatory cytokines: IFNγ, IL-12, IL-6; and anti-inflammatory cytokines: IL-10 and TGFβ. TNF showed the best negative correlation (r2 = 0.231; pdogs with high parasite load associated with a structural modification in the splenic lymphoid micro-architecture. We also discuss the possible mechanism responsible for the uncontrolled parasite growth and clinical outcome.

  11. CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

    Directory of Open Access Journals (Sweden)

    Johanna Maria Eberhard

    Full Text Available Mucosal-associated invariant T (MAIT cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+ MAIT and CD161-TCRVα7.2(+ T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161(+ MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161(+ MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161-TCRVα7.2(+T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161(+ MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.

  12. Targeted Treatment for Bacterial Infections: Prospects for Pathogen-Specific Antibiotics Coupled with Rapid Diagnostics

    OpenAIRE

    Maxson, Tucker; Mitchell, Douglas A.

    2015-01-01

    Antibiotics are a cornerstone of modern medicine and have significantly reduced the burden of infectious diseases. However, commonly used broad-spectrum antibiotics can cause major collateral damage to the human microbiome, causing complications ranging from antibiotic-associated colitis to the rapid spread of resistance. Employing narrower spectrum antibiotics targeting specific pathogens may alleviate this predicament as well as provide additional tools to expand an antibiotic repertoire th...

  13. Diagnostic accuracy of the rapid urine lipoarabinomannan test for pulmonary tuberculosis among HIV-infected adults in Ghana-findings from the DETECT HIV-TB study

    DEFF Research Database (Denmark)

    Bjerrum, Stephanie; Kenu, Ernest; Lartey, Margaret

    2015-01-01

    BACKGROUND: Rapid diagnostic tests are urgently needed to mitigate HIV-associated tuberculosis (TB) mortality. We evaluated diagnostic accuracy of the rapid urine lipoarabinomannan (LAM) test for pulmonary TB and assessed the effect of a two-sample strategy. METHODS: HIV-infected adults eligible...

  14. Rapid outer-surface protein C DNA tattoo vaccination protects against Borrelia afzelii infection.

    Science.gov (United States)

    Wagemakers, A; Mason, L M K; Oei, A; de Wever, B; van der Poll, T; Bins, A D; Hovius, J W R

    2014-12-01

    Borrelia afzelii is the predominant Borrelia species causing Lyme borreliosis in Europe. Currently there is no human vaccine against Lyme borreliosis, and most research focuses on recombinant protein vaccines against Borrelia burgdorferi sensu stricto. DNA tattooing is a novel vaccination method that can be applied in a rapid vaccination schedule. We vaccinated C3H/HeN mice with B. afzelii strain PKo OspC (outer-surface protein C) using a codon-optimized DNA vaccine tattoo and compared this with recombinant protein vaccination in a 0-2-4 week vaccination schedule. We also assessed protection by DNA tattoo in a 0-3-6 day schedule. DNA tattoo and recombinant OspC vaccination induced comparable total IgG responses, with a lower IgG1/IgG2a ratio after DNA tattoo. Two weeks after syringe-challenge with 5 × 10(5) B. afzelii spirochetes most vaccinated mice had negative B. afzelii tissue DNA loads and all were culture negative. Furthermore, DNA tattoo vaccination in a 0-3-6 day regimen also resulted in negative Borrelia loads and cultures after challenge. To conclude, DNA vaccination by tattoo was fully protective against B. afzelii challenge in mice in a rapid vaccination protocol, and induces a favorable humoral immunity compared to recombinant protein vaccination. Rapid DNA tattoo is a promising vaccination strategy against spirochetes.

  15. A recombinase polymerase amplification assay for rapid detection of Crimean-Congo Haemorrhagic fever Virus infection.

    Directory of Open Access Journals (Sweden)

    Laura C Bonney

    2017-10-01

    Full Text Available Crimean-Congo Haemorrhagic fever Virus (CCHFV is a rapidly emerging vector-borne pathogen and the cause of a virulent haemorrhagic fever affecting large parts of Europe, Africa, the Middle East and Asia.An isothermal recombinase polymerase amplification (RPA assay was successfully developed for molecular detection of CCHFV. The assay showed rapid (under 10 minutes detection of viral extracts/synthetic virus RNA of all 7 S-segment clades of CCHFV, with high target specificity. The assay was shown to tolerate the presence of inhibitors in crude preparations of mock field samples, indicating that this assay may be suitable for use in the field with minimal sample preparation. The CCHFV RPA was successfully used to screen and detect CCHFV positives from a panel of clinical samples from Tajikistan.The assay is a rapid, isothermal, simple-to-perform molecular diagnostic, which can be performed on a light, portable real-time detection device. It is ideally placed therefore for use as a field-diagnostic or in-low resource laboratories, for monitoring of CCHF outbreaks at the point-of-need, such as in remote rural regions in affected countries.

  16. Viral hepatitis and rapid diagnostic test based screening for HBsAg in HIV-infected patients in rural Tanzania.

    Directory of Open Access Journals (Sweden)

    Fabian C Franzeck

    Full Text Available BACKGROUND: Co-infection with hepatitis B virus (HBV is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg before initiation of combination antiretroviral therapy (cART is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. METHODS: Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. RESULTS: Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47, 169/272 (63% subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439. HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0% subjects. Of these, 7/25 (28% were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6% and specificity at 100% (95% CI, 98.9-100%. Antibodies to HCV (anti-HCV were found in 10/272 (3.7%, 95% CI 2.0-6.4% of patients. CONCLUSION: This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa.

  17. Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression using experimental data

    Science.gov (United States)

    Available diagnostic assays for Mycobacterium avium subsp paratuberculosis (MAP) have poor sensitivities and cannot detect early stages of the infection, therefore, there is need to find new diagnostic markers for early infection detection and disease stages. We analyzed longitudinal IFN- gamma, ELI...

  18. Interaction between PNPLA3 I148M variant and age at infection in determining fibrosis progression in chronic hepatitis C.

    Directory of Open Access Journals (Sweden)

    Stella De Nicola

    Full Text Available BACKGROUND AND AIMS: The PNPLA3 I148M sequence variant favors hepatic lipid accumulation and confers susceptibility to hepatic fibrosis and hepatocellular carcinoma. The aim of this study was to estimate the effect size of homozygosity for the PNPLA3 I148M variant (148M/M on the fibrosis progression rate (FPR and the interaction with age at infection in chronic hepatitis C (CHC. METHODS: FPR was estimated in a prospective cohort of 247 CHC patients without alcohol intake and diabetes, with careful estimation of age at infection and determination of fibrosis stage by Ishak score. RESULTS: Older age at infection was the strongest determinant of FPR (p<0.0001. PNPLA3 148M/M was associated with faster FPR in individuals infected at older age (above the median, 21 years; -0.64±0.2, n = 8 vs. -0.95±0.3, n = 166 log10 FPR respectively; p = 0.001; confirmed for lower age thresholds, p<0.05, but not in those infected at younger age (p = ns. The negative impact of PNPLA3 148M/M on fibrosis progression was more marked in subjects at risk of altered hepatic lipid metabolism (those with grade 2-3 steatosis, genotype 3, and overweight; p<0.05. At multivariate analysis, PNPLA3 148M/M was associated with FPR (incremental effect 0.08±0.03 log10 fibrosis unit per year; p = 0.022, independently of several confounders, and there was a significant interaction between 148M/M and older age at infection (p = 0.025. The association between 148M/M and FPR remained significant even after adjustment for steatosis severity (p = 0.032. CONCLUSIONS: We observed an interaction between homozygosity for the PNPLA3 I148M variant and age at infection in determining fibrosis progression in CHC patients.

  19. Emergence of CD134 cysteine-rich domain 2 (CRD2)-independent strains of feline immunodeficiency virus (FIV) is associated with disease progression in naturally infected cats.

    Science.gov (United States)

    Bęczkowski, Paweł M; Techakriengkrai, Navapon; Logan, Nicola; McMonagle, Elizabeth; Litster, Annette; Willett, Brian J; Hosie, Margaret J

    2014-11-28

    Feline immunodeficiency virus (FIV) infection is mediated by sequential interactions with CD134 and CXCR4. Field strains of virus vary in their dependence on cysteine-rich domain 2 (CRD2) of CD134 for infection. Here, we analyse the receptor usage of viral variants in the blood of 39 naturally infected cats, revealing that CRD2-dependent viral variants dominate in early infection, evolving towards CRD2-independence with disease progression. These findings are consistent with a shift in CRD2 of CD134 usage with disease progression.

  20. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    Energy Technology Data Exchange (ETDEWEB)

    Vani, R; Sridevi, T S; Kalkura, S Narayana [Crystal Growth Centre, Anna University, Chennai 600 025 (India); Raja, Subramaniya Bharathi; Savithri, K; Devaraj, S Niranjali [Department of Biochemistry, University of Madras, Chennai 600 025 (India); Girija, E K [Department of Physics, Periyar University, Salem 636 011 (India); Thamizhavel, A, E-mail: kalkurasn@annauniv.edu, E-mail: kalkura@yahoo.com [Tata Institute of Fundamental Research, Mumbai 400005 (India)

    2011-07-15

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m{sup 2} g{sup -1} and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  1. Periodontal disease and Helicobacter pylori infection: a community-based study using serology and rapid urease test.

    Science.gov (United States)

    Nisha, Krishnavilasom J; Nandakumar, Krishnankutty; Shenoy, Kottacherry T; Janam, Presanthila

    2016-02-01

    The aims of the present study were to assess the prevalence of periodontal disease and Helicobacter pylori (H. pylori) infection and their associations within a predefined Indian population. A community-based cross-sectional study of 500 selected individuals using a questionnaire, oral examination, rapid urease testing of dental plaque, and serological examination for immunoglobulin G antibody to H. pylori was carried out. Periodontal disease and H. pylori infection were prevalent in more than 50% of the population. Age, smoking, and diabetic status of the individuals were risk factors for periodontal disease after multivariate analysis, and a lack of proper sewage and waste disposal facilities were found to increase the risk of H. pylori infection. Although there was no association between periodontal disease and H. pylori seropositivity in the community, a highly-significant association was found between periodontal disease and colonization of H. pylori in dental plaque. Because periodontal disease is associated with the increased colonization of H. pylori, new treatment modalities, such as plaque control measures, should be employed for the complete management of H. pylori-associated gastric disease. © 2014 Wiley Publishing Asia Pty Ltd.

  2. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    International Nuclear Information System (INIS)

    Vani, R; Sridevi, T S; Kalkura, S Narayana; Raja, Subramaniya Bharathi; Savithri, K; Devaraj, S Niranjali; Girija, E K; Thamizhavel, A

    2011-01-01

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m 2 g -1 and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  3. Surfactant free rapid synthesis of hydroxyapatite nanorods by a microwave irradiation method for the treatment of bone infection

    Science.gov (United States)

    Vani, R.; Bharathi Raja, Subramaniya; Sridevi, T. S.; Savithri, K.; Niranjali Devaraj, S.; Girija, E. K.; Thamizhavel, A.; Narayana Kalkura, S.

    2011-07-01

    Mesoporous nanocrystalline hydroxyapatite (nHAp) rods of size 40-75 nm long and 25 nm wide (resembling bone mineral) were synthesized under microwave irradiation without using any surfactants or modifiers. The surface area and average pore size of the nHAp were found to be 32 m2 g - 1 and 4 nm, respectively. Rifampicin (RIF) and ciprofloxacin (CPF) loaded nHAp displayed an initial burst followed by controlled release (zero order kinetics). Combination of CPF and RIF loaded nHAp showed enhanced bacterial growth inhibition against Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis) and Escherichia coli (E coli) compared to individual agent loaded nHAp and pure nHAp. In addition, decreased bacterial adhesion (90%) was observed on the surface of CPF plus RIF loaded nHAp. The biocompatibility test toward MG63 cells infected with micro-organisms showed better cell viability and alkaline phosphatase activity (ALP) for the combination of CPF and RIF loaded nHAp. The influence on cell viability of infected MG63 cells was attributed to the simultaneous and controlled release of CPF and RIF from nHAp, which prevented the emergence of subpopulations that were resistant to each other. Hence, apart from the issue of the rapid synthesis of nHAp without surfactants or modifiers, the simultaneous and controlled release of dual drugs from nHAp would be a simple, non-toxic and cost-effective method to treat bone infections.

  4. Impaired Subset Progression and Polyfunctionality of T Cells in Mice Exposed to Methamphetamine during Chronic LCMV Infection.

    Science.gov (United States)

    Sriram, Uma; Hill, Beth L; Cenna, Jonathan M; Gofman, Larisa; Fernandes, Nicole C; Haldar, Bijayesh; Potula, Raghava

    2016-01-01

    Methamphetamine (METH) is a widely used psychostimulant that severely impacts the host's innate and adaptive immune systems and has profound immunological implications. T cells play a critical role in orchestrating immune responses. We have shown recently how chronic exposure to METH affects T cell activation using a murine model of lymphocytic choriomeningitis virus (LCMV) infection. Using the TriCOM (trinary state combinations) feature of GemStone™ to study the polyfunctionality of T cells, we have analyzed how METH affected the cytokine production pattern over the course of chronic LCMV infection. Furthermore, we have studied in detail the effects of METH on splenic T cell functions, such as cytokine production and degranulation, and how they regulate each other. We used the Probability State Modeling (PSM) program to visualize the differentiation of effector/memory T cell subsets during LCMV infection and analyze the effects of METH on T cell subset progression. We recently demonstrated that METH increased PD-1 expression on T cells during viral infection. In this study, we further analyzed the impact of PD-1 expression on T cell functional markers as well as its expression in the effector/memory subsets. Overall, our study indicates that analyzing polyfunctionality of T cells can provide additional insight into T cell effector functions. Analysis of T cell heterogeneity is important to highlight changes in the evolution of memory/effector functions during chronic viral infections. Our study also highlights the impact of METH on PD-1 expression and its consequences on T cell responses.

  5. Loop-mediated isothermal amplification: rapid detection of Angiostrongylus cantonensis infection in Pomacea canaliculata

    Directory of Open Access Journals (Sweden)

    Zhuo MingMing

    2011-10-01

    Full Text Available Abstract Background Angiostrongylus cantonensis is a zoonotic parasite that causes eosinophilic meningitis in humans. The most common source of infection with A. cantonensis is the consumption of raw or undercooked mollusks (e.g., snails and slugs harbouring infectious third-stage larvae (L3. However, the parasite is difficult to identify in snails. The purpose of this study was to develop a quick, simple molecular method to survey for A. cantonensis in intermediate host snails. Findings We used a loop-mediated isothermal amplification (LAMP assay, which was performed using Bst DNA polymerase. Reactions amplified the A. cantonensis 18S rRNA gene and demonstrated high sensitivity; as little as 1 fg of DNA was detected in the samples. Furthermore, no cross-reactivity was found with other parasites such as Toxoplasma gondii, Plasmodium falciparum, Schistosoma japonicum, Clonorchis sinensis, Paragonimus westermani and Anisakis. Pomacea canaliculata snails were exposed to A. cantonensis first-stage larvae (L1 in the laboratory, and L3 were observed in the snails thirty-five days after infection. All nine samples were positive as determined by the LAMP assay for A. cantonensis, which was identified as positive by using PCR and microscopy, this demonstrates that LAMP is sensitive and effective for diagnosis. Conclusions LAMP is an appropriate diagnostic method for the routine identification of A. cantonensis within its intermediate host snail P. canaliculata because of its simplicity, sensitivity, and specificity. It holds great promise as a useful monitoring tool for A. cantonensis in endemic regions.

  6. Cryotherapy Reduces Progression of Cervical Intraepithelial Neoplasia Grade 1 in South African HIV-Infected Women: A Randomized, Controlled Trial.

    Science.gov (United States)

    Firnhaber, Cynthia; Swarts, Avril; Goeieman, Bridgette; Rakhombe, Ntombi; Mulongo, Masangu; Williamson, Anna-Lise; Michelow, Pam; Ramotshela, Sibongile; Faesen, Mark; Levin, Simon; Wilkin, Timothy

    2017-12-15

    HIV-infected women are at an increased risk of cervical cancer, especially in resource-limited countries. Cervical cancer prevention strategies focus treating cervical high-grade squamous intraepithelial lesions (HSIL). The management of low-grade squamous intraepithelial lesions (LSIL) in HIV-infected women is unknown. HIV treatment clinic in Johannesburg, South Africa. We randomized HIV-infected women with histologic cervical LSIL to cervical cryotherapy vs. no treatment (standard of care). Cervical high-risk human papillomavirus testing (hrHPV) was performed at baseline. All women underwent cervical cytology and colposcopic biopsies 12 months after enrollment. The primary end point was HSIL on histology at month 12. Chi-square was used to compare arms. Overall, 220 HIV-infected women were randomized to cryotherapy (n = 112) or no treatment (n = 108). Median age was 38 years, 94% were receiving antiretroviral therapy; median CD4 was 499 cells per cubic millimeter, and 59% were hrHPV positive. Cryotherapy reduced progression to HSIL: 2/99 (2%) in the cryotherapy arm and 15/103 (15%) in the no treatment arm developed HSIL, 86% reduction (95% confidence interval: 41% to 97%; P = 0.002). Among 17 HSIL end points, 16 were hrHPV+ at baseline. When restricting the analysis to hrHPV+ women, HSIL occurred in 2/61 (3%) in the cryotherapy arm vs. 14/54 (26%) in the no treatment arm, 87% reduction (95% confidence interval: 47% to 97%; P = 0.0004). Participants in the cryotherapy arm experienced greater regression to normal histology and improved cytologic outcomes. Treatment of cervical LSIL with cryotherapy decreased progression to HSIL among HIV-infected women especially if hrHPV positive. These results support treatment of LSIL in human papillomavirus test-and-treat approaches for cervical cancer prevention in resource-constrained settings.

  7. Toll like receptor7 polymorphisms in relation to disease susceptibility and progression in Chinese patients with chronic HBV infection.

    Science.gov (United States)

    Zhu, Junping; Zhang, Tong; Cao, Lina; Li, Aixin; Zheng, Kai; Zhang, Nan; Su, Bin; Chen, Zhiyun; Chen, Ning; Wu, Hao; He, Qiushui

    2017-09-29

    Toll-like receptors (TLRs) play a key role in innate and adaptive immunity, protecting the host from viral pathogens. We studied the effect of TLR7 polymorphisms on disease susceptibility and progression of chronic hepatitis B (CHB) infection in Chinese adults. Blood samples were taken from 612 patients with confirmed CHB, hepatitis B virus (HBV)-related liver cirrhosis (LC) or hepatocellular carcinoma (HCC) and 293 controls. TLR7 polymorphisms (rs179010-C > T, rs2074109-T > C, and rs179009-A > G) were analyzed by PCR-based sequencing. A significantly higher frequency of TLR7 rs179010 C allele was found in male CHB patients than in controls (74.8% vs 59.5%, P = 0.002). The frequency of rs179009 G allele was markedly increased with disease progression when male patients with CHB, LC and HCC were compared (P = 0.012). The haplotype CTA was significantly associated with an increased susceptibility to CHB among male patients (P = 0.000). Frequency of the haplotype CTG was higher in male patients with HCC than CHB (P = 0.005). No such differences in these allele frequencies were found between female patients and controls. Our results indicated that TLR7 polymorphisms play an important role in disease susceptibility and the progression of CHB infections in Chinese adults, and may partly explain the high incidence of HBV related diseases in Chinese men.

  8. An unusual renal manifestation of chronic HBV infection.

    Science.gov (United States)

    Aravindan, Ananthakrishnapuram; Yong, Jim; Killingsworth, Murray; Strasser, Simone; Suranyi, Michael

    2010-08-01

    Hepatitis B viral infection is usually a self-limiting disease in immunocompetent individuals. Chronic infection can be seen in up to 5% of infected patients. Renal manifestations of chronic HBV infection are usually glomerular. We describe here an uncommon presentation of a patient with chronic HBV infection with very high viral load and rapidly progressive renal failure. Renal biopsy showed features of tubulointerstitial nephritis and tubular epithelial inclusion bodies suggestive of HBV infection. Entecavir treatment slowed down the progression of his renal disease. Tubulointerstitial nephritis should be considered as a part of the differential diagnosis in patients with HBV infection. Early antiviral treatment may halt the progression of renal disease.

  9. Garlic blocks quorum sensing and promotes rapid clearing of pulmonary Pseudomonas aeruginosa infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Rasmussen, Thomas B

    2005-01-01

    to otherwise lethal doses of antibiotics, and protects against the bactericidal activity of polymorphonuclear leukocytes (PMNs). It has been previously demonstrated that QS is inhibited by garlic extract. In this study, the synergistic effects of garlic and tobramycin, and PMNs activities have been evaluated....... P. aeruginosa was grown in vitro in continuous-culture once-through flow chambers with and without garlic extract. The garlic-treated biofilms were susceptible to both tobramycin and PMN grazing. Furthermore, the PMNs showed an increase in respiratory burst activation, when incubated with the garlic......-treated biofilm. Garlic extract was administered as treatment for a mouse pulmonary infection model. Mice were treated with garlic extract or placebo for 7 days, with the initial 2 days being prophylactic before P. aeruginosa was instilled in the left lung of the mice. Bacteriology, mortality, histopathology...

  10. Deep postoperative spine infection treated by negative pressure therapy in patients with progressive spinal deformities.

    Science.gov (United States)

    Canavese, Federico; Marengo, Lorenza; Corradin, Marco; Mansour, Mounira; Samba, Antoine; Andreacchio, Antonio; Rousset, Marie; Dimeglio, Alain

    2018-04-01

    The aim of the study is to review the outcome of using the VAC system in children and adolescents who have developed postoperative spinal infection after posterior instrumented spinal fusion, and to evaluate whether this technique is also feasible in patients treated with posterior instrumented fusion with polyester sublaminar bands. A total of 11 out of 118 consecutive children and adolescents (5 males) with deep postoperative spinal infection were identified; infections were categorised as early (acute), delayed (subacute) or late (chronic) according to time of onset. Irrespective of the etiology and the onset, all the deep infections were managed with the reported technique. All the patients had regular clinical and radiological follow-up. Eight out of 11 patients developed an early (72.7%), 2 a delayed (18.2%) and 1 a late deep postoperative infection (9.1%); 7 out of 11 (63.6%) showed severe mental compromise. No statistically significant differences were observed for mean number of VAC dressing changes (p = 0.81) and mean length of hospitalisation comparing patients with early infection versus patients with delayed or late infections (p = 0.32). Mean number of VAC dressing changes (p = 0.02) and mean number of hospitalisation days (p = 0.05) were higher in patients with underlying neurological disorders than in those without, while mean length of hospitalisation was longer in neuromuscular patients. The application of the VAC system, as an adjunct to surgical debridement and adequate antibiotic therapy, is a reliable method for the treatment of postoperative infection in children and adolescents undergoing spinal instrumentation and fusion. It can reduce the need for further complex soft-tissue procedure, removal of hardware with consequent loss of correction, and pseudoarthrosis. Finally, the use of VAC therapy is not contraindicated in patients treated with hybrid constructs with sublaminar bands. III.

  11. Rapid qualitative urinary tract infection pathogen identification by SeptiFast real-time PCR.

    Directory of Open Access Journals (Sweden)

    Lutz E Lehmann

    2011-02-01

    Full Text Available Urinary tract infections (UTI are frequent in outpatients. Fast pathogen identification is mandatory for shortening the time of discomfort and preventing serious complications. Urine culture needs up to 48 hours until pathogen identification. Consequently, the initial antibiotic regimen is empirical.To evaluate the feasibility of qualitative urine pathogen identification by a commercially available real-time PCR blood pathogen test (SeptiFast® and to compare the results with dipslide and microbiological culture.Pilot study with prospectively collected urine samples.University hospital.82 prospectively collected urine samples from 81 patients with suspected UTI were included. Dipslide urine culture was followed by microbiological pathogen identification in dipslide positive samples. In parallel, qualitative DNA based pathogen identification (SeptiFast® was performed in all samples.61 samples were SeptiFast® positive, whereas 67 samples were dipslide culture positive. The inter-methodological concordance of positive and negative findings in the gram+, gram- and fungi sector was 371/410 (90%, 477/492 (97% and 238/246 (97%, respectively. Sensitivity and specificity of the SeptiFast® test for the detection of an infection was 0.82 and 0.60, respectively. SeptiFast® pathogen identifications were available at least 43 hours prior to culture results.The SeptiFast® platform identified bacterial DNA in urine specimens considerably faster compared to conventional culture. For UTI diagnosis sensitivity and specificity is limited by its present qualitative setup which does not allow pathogen quantification. Future quantitative assays may hold promise for PCR based UTI pathogen identification as a supplementation of conventional culture methods.

  12. Rapid diagnostic test for G6PD deficiency in Plasmodium vivax-infected men: a budget impact analysis based in Brazilian Amazon.

    Science.gov (United States)

    Peixoto, Henry Maia; Brito, Marcelo Augusto Mota; Romero, Gustavo Adolfo Sierra; Monteiro, Wuelton Marcelo; de Lacerda, Marcus Vinícius Guimarães; de Oliveira, Maria Regina Fernandes

    2017-01-01

    The aim of this study was to estimate the incremental budget impact (IBI) of a rapid diagnostic test to detect G6PDd in male patients infected with Plasmodium vivax in the Brazilian Amazon, as compared with the routine protocol recommended in Brazil which does not include G6PDd testing. The budget impact analysis was performed from the perspective of the Brazilian health system, in the Brazilian Amazon for the years 2013, 2014 and 2015. The analysis used a decision model to compare two scenarios: the first consisting of the routine recommended in Brazil which does not include prior diagnosis of dG6PD, and the second based on the use of RDT CareStart™ G6PD (CS-G6PD) in all male subjects diagnosed with vivax malaria. The expected implementation of the diagnostic test was 30% in the first year, 70% the second year and 100% in the third year. The analysis identified negative IBIs which were progressively smaller in the 3 years evaluated. The sensitivity analysis showed that the uncertainties associated with the analytical model did not significantly affect the results. A strategy based on the use of CS-G6PD would result in better use of public resources in the Brazilian Amazon. © 2016 John Wiley & Sons Ltd.

  13. Mouse papillomavirus infections spread to cutaneous sites with progression to malignancy.

    Science.gov (United States)

    Cladel, Nancy M; Budgeon, Lynn R; Cooper, Timothy K; Balogh, Karla K; Christensen, Neil D; Myers, Roland; Majerciak, Vladimir; Gotte, Deanna; Zheng, Zhi-Ming; Hu, Jiafen

    2017-09-25

    We report secondary cutaneous infections in the mouse papillomavirus (MmuPV1)/mouse model. Our previous study demonstrated that cutaneous MmuPV1 infection could spread to mucosal sites. Recently, we observed that mucosal infections could also spread to various cutaneous sites including the back, tail, muzzle and mammary tissues. The secondary site lesions were positive for viral DNA, viral capsid protein and viral particles as determined by in situ hybridization, immunohistochemistry and transmission electron microscopy analyses, respectively. We also demonstrated differential viral production and tumour growth at different secondarily infected skin sites. For example, fewer viral particles were detected in the least susceptible back tissues when compared with those in the infected muzzle and tail, although similar amounts of viral DNA were detected. Follow-up studies demonstrated that significantly lower amounts of viral DNA were packaged in the back lesions. Lavages harvested from the oral cavity and lower genital tracts were equally infectious at both cutaneous and mucosal sites, supporting the broad tissue tropism of this papillomavirus. Importantly, two secondary skin lesions on the forearms of two mice displayed a malignant phenotype at about 9.5 months post-primary infection. Therefore, MmuPV1 induces not only dysplasia at mucosal sites such as the vagina, anus and oral cavity but also skin carcinoma at cutaneous sites. These findings demonstrate that MmuPV1 mucosal infection can be spread to cutaneous sites and suggest that the model could serve a useful role in the study of the viral life cycle and pathogenesis of papillomavirus.

  14. Control and non-progression of HIV-1 infection in sub-Saharan Africa: A case and review

    Directory of Open Access Journals (Sweden)

    P Patel

    2012-08-01

    Full Text Available Elite and viraemic controllers represent unique subsets of HIV-infected patients who may also be long-term non-progressors (LTNPs. LNTPs constitute an estimated 1 - 15% of the total HIV-positive population in the USA and Europe, but less is known about their epidemiology in sub-Saharan Africa. Though the exact mechanisms for long-term non-progression appear to be numerous and are still under investigation, research on elite controllers may hold the key to new therapeutics and vaccine development. The clinical management of such patients can be challenging, as there are no standard guidelines for treatment, particularly in resource-limited settings. We describe the case of an HIV-infected Botswanan man who is likely an elite or viraemic controller.

  15. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults

    DEFF Research Database (Denmark)

    Mocroft, Amanda; Neuhaus, Jacqueline; Peters, Lars

    2012-01-01

    B (HBV) co-infection and progressive CKD among 3,441 antiretroviral-treated clinical trial participants. Progressive CKD was defined as the composite of end-stage renal disease, renal death, or significant glomerular filtration rate (eGFR) decline (25% decline to eGFR 800,000 IU/ml had increased...

  16. Rapid and reliable MALDI-TOF mass spectrometry identification of Candida non-albicans isolates from bloodstream infections.

    Science.gov (United States)

    Pulcrano, Giovanna; Iula, Dora Vita; Vollaro, Antonio; Tucci, Alessandra; Cerullo, Monica; Esposito, Matilde; Rossano, Fabio; Catania, Maria Rosaria

    2013-09-01

    Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) fingerprinting has recently become an effective instrument for rapid microbiological diagnostics and in particular for identification of micro-organisms directly in a positive blood culture. The aim of the study was to evaluate a collection of 82 stored yeast isolates from bloodstream infection, by MALDI-TOF MS; 21 isolates were identified also directly from positive blood cultures and in the presence of other co-infecting micro-organisms. Of the 82 isolates grown on plates, 64 (76%) were correctly identified by the Vitek II system and 82 (100%) by MALDI-TOF MS; when the two methods gave different results, the isolate was identified by PCR. MALDI-TOF MS was unreliable in identifying two isolates (Candida glabrata and Candida parapsilosis) directly from blood culture; however, direct analysis from positive blood culture samples was fast and effective for the identification of yeast, which is of great importance for early and adequate treatment. © 2013. Published by Elsevier B.V. All rights reserved.

  17. Rapid CRISPR/Cas9-Mediated Cloning of Full-Length Epstein-Barr Virus Genomes from Latently Infected Cells

    Directory of Open Access Journals (Sweden)

    Misako Yajima

    2018-04-01

    Full Text Available Herpesviruses have relatively large DNA genomes of more than 150 kb that are difficult to clone and sequence. Bacterial artificial chromosome (BAC cloning of herpesvirus genomes is a powerful technique that greatly facilitates whole viral genome sequencing as well as functional characterization of reconstituted viruses. We describe recently invented technologies for rapid BAC cloning of herpesvirus genomes using CRISPR/Cas9-mediated homology-directed repair. We focus on recent BAC cloning techniques of Epstein-Barr virus (EBV genomes and discuss the possible advantages of a CRISPR/Cas9-mediated strategy comparatively with precedent EBV-BAC cloning strategies. We also describe the design decisions of this technology as well as possible pitfalls and points to be improved in the future. The obtained EBV-BAC clones are subjected to long-read sequencing analysis to determine complete EBV genome sequence including repetitive regions. Rapid cloning and sequence determination of various EBV strains will greatly contribute to the understanding of their global geographical distribution. This technology can also be used to clone disease-associated EBV strains and test the hypothesis that they have special features that distinguish them from strains that infect asymptomatically.

  18. Utility of a rapid immunochromatographic strip test in detecting canine parvovirus infection compared with polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Sundaran S. Tinky

    2015-04-01

    Full Text Available Aim: The present study was undertaken to detect the presence of canine parvovirus (CPV in fecal samples of diarrheic dogs by conventional polymerase chain reaction (PCR and immunochromatographic (IC strip test and to compare the diagnostic potential of these tests. Materials and Methods: A total of 50 fecal samples collected from diarrheic dogs suspected for CPV infection were subjected to PCR using CPV-555 primer amplifying the gene coding for the VP1 protein. These samples were also tested by IC strip test using a commercial rapid Ag test kit. The results were statistically analyzed using McNemar test. Results: A total of 22 samples (44% were detected as positive by PCR, which yielded a specific amplicon of 583 bp. In IC strip test, 18 (36% samples were found to be positive. The sensitivity of the test as compared to PCR was found to be 72.22% and specificity was 92.86%. Positive predictive value and negative predictive value of IC strip test was found to be 88.89% and 81.25%, respectively. Statistical analysis of the results of PCR and IC assay using McNemar test revealed no significant difference (p>0.05. Conclusion: The IC strip test could be employed as a rapid field level diagnostic tool for the diagnosis of canine parvoviral diarrhea.

  19. Rapid CRISPR/Cas9-Mediated Cloning of Full-Length Epstein-Barr Virus Genomes from Latently Infected Cells.

    Science.gov (United States)

    Yajima, Misako; Ikuta, Kazufumi; Kanda, Teru

    2018-04-03

    Herpesviruses have relatively large DNA genomes of more than 150 kb that are difficult to clone and sequence. Bacterial artificial chromosome (BAC) cloning of herpesvirus genomes is a powerful technique that greatly facilitates whole viral genome sequencing as well as functional characterization of reconstituted viruses. We describe recently invented technologies for rapid BAC cloning of herpesvirus genomes using CRISPR/Cas9-mediated homology-directed repair. We focus on recent BAC cloning techniques of Epstein-Barr virus (EBV) genomes and discuss the possible advantages of a CRISPR/Cas9-mediated strategy comparatively with precedent EBV-BAC cloning strategies. We also describe the design decisions of this technology as well as possible pitfalls and points to be improved in the future. The obtained EBV-BAC clones are subjected to long-read sequencing analysis to determine complete EBV genome sequence including repetitive regions. Rapid cloning and sequence determination of various EBV strains will greatly contribute to the understanding of their global geographical distribution. This technology can also be used to clone disease-associated EBV strains and test the hypothesis that they have special features that distinguish them from strains that infect asymptomatically.

  20. Involvement of Hookworm Co-Infection in the Pathogenesis and Progression of Podoconiosis: Possible Immunological Mechanism

    Directory of Open Access Journals (Sweden)

    Damilare O. Famakinde

    2018-03-01

    Full Text Available Podoconiosis is an endemic, non-infectious, geochemical and non-filarial inflammatory cause of tropical elephantiasis. The immunology of podoconiosis is not yet expressly understood. In spite of this, co-infection and co-morbidity with the infectious, soil-transmitted hookworm disease that causes iron deficiency anemia has been found to be predominant among affected individuals living in co-endemic settings, thus creating a more complex immunological interplay that still has not been investigated. Although deworming and iron-rich nutrient supplementation have been suggested in podoconiosis patients living under resource-poor conditions, and it is thought that hookworm infection may help to suppress inflammatory responses, the undisputed link that exists between a non-infectious and an infectious disease may create a scenario whereby during a co-infection, treatment of one exacerbates the other disease condition or is dampened by the debilitation caused by the other. In this paper, we elaborate on the immunopathogenesis of podoconiosis and examine the possible immunological dynamics of hookworm co-infection in the immunopathology of podoconiosis, with a view toward improved management of the disease that will facilitate its feasible elimination.

  1. Progress in the Discovery of Treatments for C. difficile Infection: A Clinical and Medicinal Chemistry Review

    Science.gov (United States)

    Tsutsumi, Lissa S.; Owusu, Yaw B.; Hurdle, Julian G.; Sun, Dianqing

    2014-01-01

    Clostridium difficile is an anaerobic, Gram-positive pathogen that causes C. difficile infection, which results in significant morbidity and mortality. The incidence of C. difficile infection in developed countries has become increasingly high due to the emergence of newer epidemic strains, a growing elderly population, extensive use of broad spectrum antibiotics, and limited therapies for this diarrheal disease. Because treatment options currently available for C. difficile infection have some drawbacks, including cost, promotion of resistance, and selectivity problems, new agents are urgently needed to address these challenges. This review article focuses on two parts: the first part summarizes current clinical treatment strategies and agents under clinical development for C. difficile infection; the second part reviews newly reported anti-difficile agents that have been evaluated or reevaluated in the last five years and are in the early stages of drug discovery and development. Antibiotics are divided into natural product inspired and synthetic small molecule compounds that may have the potential to be more efficacious than currently approved treatments. This includes potency, selectivity, reduced cytotoxicity, and novel modes of action to prevent resistance. PMID:24236721

  2. No predictive value of GC phenotypes for HIV infection and progression to AIDS

    NARCIS (Netherlands)

    Pronk, J. C.; Frants, R. R.; Crusius, B.; Eriksson, A. W.; de Wolf, F.; Boucher, C. A.; Bakker, M.; Goudsmit, J.

    1988-01-01

    The genetic polymorphism of group-specific component (GC) was investigated with isoelectric focusing in 351 homosexual men at risk for HIV infection, 96 male patients with AIDS, and 86 heterosexual controls. No significant differences in GC phenotype distribution were seen between controls and any

  3. The progression of heartworm associated respiratory disease (HARD) in SPF cats 18 months after Dirofilaria immitis infection.

    Science.gov (United States)

    Dillon, A Ray; Blagburn, Bryon L; Tillson, Michael; Brawner, William; Welles, Betsy; Johnson, Calvin; Cattley, Russell; Rynders, Pat; Barney, Sharron

    2017-11-09

    Heartworm-associated respiratory disease (HARD) in cats is induced by the arrival and death of immature adult Dirofilaria immitis in the pulmonary system and is indistinguishable from mature adult heartworm infection. A controlled, blind research study investigated the long-term (18 months post infection, PI) consequences of the inflammatory response associated with the death of immature adult heartworms in cats. Three groups of cats, 10 per group, were infected with 100 third-stage (L3) larvae by subcutaneous injection. Group A cats were treated with selamectin (Revolution®; Zoetis) per label directions at 28 days PI and once monthly for 17 months. Group B cats were treated orally with ivermectin (Ivomec®; Merial) at 150 μg/kg) at 70 days PI, then every 2 weeks for 15 months. Group C cats were untreated PI. At baseline (Day 0) and on Days 70, 110, 168, 240, 309, 380, and 505 PI, peripheral blood, serum, bronchial lavage, and thoracic radiographic images were collected. The selamectin-treated cats (Group A) and ivermectin-treated cats (Group B) were free of heartworms or heartworm fragments at necropsy. All cats became heartworm antibody positive at some time point in the study except for one cat in Group A. Only cats in Group C (all with adult heartworms) were heartworm antigen positive. The heartworm antibody titer for Group B was highest on Days 110 to 168 and then decreased over time and 50% were serologically antibody negative on Day 240. Eosinophilic bronchoalveolar lavage (BAL) cytology and peripheral eosinophilia were most pronounced on Day 110 in all cats. Randomly distributed myofibrocytes in the lungs of some Group A cats suggest that precardiac larval stages were affecting the lungs. Radiographs in Group B cats demonstrated partial resolution of the initial HARD reaction but chronic myofibrocyte proliferation was histologically evident 18 months after infection. HARD was induced by immature adult worm infection with progressive improvement

  4. Herpes zoster, immunological deterioration and disease progression in HIV-1 infection

    NARCIS (Netherlands)

    Veenstra, J.; Krol, A.; van Praag, R. M.; Frissen, P. H.; Schellekens, P. T.; Lange, J. M.; Coutinho, R. A.; van der Meer, J. T.

    1995-01-01

    OBJECTIVE: To study the incidence of herpes zoster, the relationship between herpes zoster and immunological markers, and the prognostic value of herpes zoster for progression of HIV disease. DESIGN AND METHODS: A total of 966 homosexual participants in The Amsterdam Cohort Study were studied.

  5. Insights into the Impact of CD8+ Immune Modulation on Human Immunodeficiency Virus Evolutionary Dynamics in Distinct Anatomical Compartments by Using Simian Immunodeficiency Virus-Infected Macaque Models of AIDS Progression.

    Science.gov (United States)

    Rife Magalis, Brittany; Nolan, David J; Autissier, Patrick; Burdo, Tricia H; Williams, Kenneth C; Salemi, Marco

    2017-12-01

    A thorough understanding of the role of human immunodeficiency virus (HIV) intrahost evolution in AIDS pathogenesis has been limited by the need for longitudinally sampled viral sequences from the vast target space within the host, which are often difficult to obtain from human subjects. CD8 + lymphocyte-depleted macaques infected with simian immunodeficiency virus (SIV) provide an increasingly utilized model of pathogenesis due to clinical manifestations similar to those for HIV-1 infection and AIDS progression, as well as a characteristic rapid disease onset. Comparison of this model with SIV-infected non-CD8 + lymphocyte-depleted macaques also provides a unique opportunity to investigate the role of CD8 + cells in viral evolution and population dynamics throughout the duration of infection. Using several different phylogenetic methods, we analyzed viral gp120 sequences obtained from extensive longitudinal sampling of multiple tissues and enriched leukocyte populations from SIVmac251-infected macaques with or without CD8 + lymphocyte depletion. SIV evolutionary and selection patterns in non-CD8 + lymphocyte-depleted animals were characterized by sequential population turnover and continual viral adaptation, a scenario readily comparable to intrahost evolutionary patterns during human HIV infection in the absence of antiretroviral therapy. Alternatively, animals that were depleted of CD8 + lymphocytes exhibited greater variation in population dynamics among tissues and cell populations over the course of infection. Our findings highlight the major role for CD8 + lymphocytes in prolonging disease progression through continual control of SIV subpopulations from various anatomical compartments and the potential for greater independent viral evolutionary behavior among these compartments in response to immune modulation. IMPORTANCE Although developments in combined antiretroviral therapy (cART) strategies have successfully prolonged the time to AIDS onset in HIV-1

  6. IL-35, a hallmark of immune-regulation in cancer progression, chronic infections and inflammatory diseases.

    Science.gov (United States)

    Teymouri, Manouchehr; Pirro, Matteo; Fallarino, Francesca; Gargaro, Marco; Sahebkar, Amirhosein

    2018-03-25

    Cytokine members of the IL-12 family have attracted enormous attention in the last few years, with IL-35 being the one of the most attractive-suppressive cytokine. IL-35 is an important mediator of regulatory T cell function. Regulatory T cells play key roles in restoring immune homeostasis after facing challenges such as infection by specific pathogens. Moreover, a crucial role for regulatory T cell populations has been demonstrated in several physiological processes, including establishment of fetal-maternal tolerance, maintenance of self-tolerance and prevention of autoimmune diseases. However, a deleterious involvement of immune regulatory T cells has been documented in specific inhibition of immune responses against tumor cells, promotion of chronic infections and establishment of chronic inflammatory disorders. In this review, we attempt to shed light on the concept of immune-homoeostasis on the aforementioned issues, taking IL-35 as the hallmark of regulatory responses. The dilemma between immune-mediated cancer treatment and inflammation is discussed. Histopathological indications of chronic vs. acute infections are elaborated. Moreover, the evidence that IL-35 requires additional immune-regulatory cytokines, such as IL-10 and TGF-β, to induce effective and maximal anti-inflammatory effects suggest that immune-regulation requires multi-factorial analysis of many immune playmakers rather than a specific immune target. © 2018 UICC.

  7. Incidence, clearance, and disease progression of genital human papillomavirus infection in heterosexual men.

    Science.gov (United States)

    Moreira, Edson Duarte; Giuliano, Anna R; Palefsky, Joel; Flores, Carlos Aranda; Goldstone, Stephen; Ferris, Daron; Hillman, Richard J; Moi, Harald; Stoler, Mark H; Marshall, Brooke; Vuocolo, Scott; Guris, Dalya; Haupt, Richard M

    2014-07-15

    In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  8. Development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of Leishmania infection.

    Science.gov (United States)

    Verma, Sandeep; Singh, Ruchi; Sharma, Vanila; Bumb, Ram Avtar; Negi, Narendra Singh; Ramesh, V; Salotra, Poonam

    2017-03-23

    Leishmaniasis is a spectrum of diseases with great relevance to public health. Conventional diagnostic methods are time consuming, needing trained personnel. A robust, rapid and cost effective diagnostic test is warranted for on-time diagnosis and field application. We have developed a loop mediated isothermal amplification (LAMP) assay with primers (n = 6) based on Leishmania donovani kDNA for detection of Leishmania infection, using a closed tube to prevent cross-contamination. The assay was used to detect Leishmania infection in biological samples obtained from patients of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL). The assay was positive for L. donovani, L. tropica and L. major parasites, with the highest sensitivity towards L. donovani (1 fg DNA). The high sensitivity of the assay for detection of L. donovani was reflected in its ability to detect parasite DNA within 30 min of amplification time with a threshold detection limit of ≥25 copies per reaction. The assay detected parasite in 64 of 66 VL blood samples (sensitivity, 96.9%; 95% CI: 89.6-99.2%), 15 of 15 VL bone marrow aspirate samples (sensitivity, 100%; 95% CI:79.6-100%), 65 of 67 PKDL tissue biopsy samples (sensitivity, 97%; 95% CI:89.7-99.2%). The assay was evaluated in a few cases of CL wherein it was found positive in 8 of 10 tissue biopsies (sensitivity, 80%; 95% CI: 49-94.3%). The assay was negative in all control blood (n = 76) and tissue biopsy (n = 24) samples (specificity, 100%; 95% CI: 96.3-100%). Further, the assay was evaluated for its utility in assessment of cure in treated VL and PKDL patients. The assay detected parasite DNA in 2 of 20VL blood samples and 2 of 21 PKDL tissue samples. Out of 4 cases that were positive for parasite DNA at post treatment stage, 2 patients (1VL and 1 PKDL) returned with relapse. The study demonstrated a Leishmania genus specific closed tube LAMP assay for reliable and rapid

  9. Grapevine rootstock effects on scion sap phenolic levels, resistance to Xylella fastidiosa infection, and progression of Pierce’s disease

    Directory of Open Access Journals (Sweden)

    Christopher Michael Wallis

    2013-12-01

    Full Text Available The xylem-limited bacterium Xylella fastidiosa (Xf causes Pierce’s disease (PD, an important disease of grapevine, Vitis vinifera L.. Grapevine rootstocks were developed to provide increased resistance to root disease, but rootstock effects on cane and vine diseases remain unclear. Grapevines that consisted of Cabernet Sauvignon or Chardonnay grafted to 13 different rootstocks were inoculated with Xf and evaluated for PD severity and Xf titer after six months. A subset of six rootstock/scion combinations had xylem sap phenolic levels assessed in non-infected and Xf-infected grapevines. Vigor also was analyzed by measuring root lengths and masses. Cabernet Sauvignon grafted to 101-14MG, 1103P, 420A, or Schwarzmann had reduced PD severity compared to Cabernet Sauvignon grafted to 110R, 5BB, or SO4. Chardonnay grafted to Salt Creek or Freedom had reduced PD severity compared to Chardonnay grafted to RS3 or Schwarzmann. Chardonnay grafted to RS3 had greater Xf titer than Chardonnay grafted to 101-14MG, Freedom, or Salt Creek. No other differences in Xf titer among rootstocks were observed. Of the six scion/rootstock combinations which had xylem sap phenolics analyzed, Chardonnay/ RS3 had the highest levels of most phenolics whereas Cabernet Sauvignon/101-14MG had the lowest phenolic levels. However, Chardonnay/101-14MG, which had mild PD symptoms, had greater sap levels of caftaric acid than other scion/rootstock combinations. Sap levels of caftaric acid, methyl salicylate, a procyanidin trimer, and quinic acid were greater in Xf-infected versus non-infected grapevines. Chardonnay on 101-14MG or Salt Creek had greater root mass than Chardonnay on RS3. Cabernet Sauvignon on 101-14MG had greater root mass than Cabernet Sauvignon on 110R. These results identified rootstocks with the capacity for reducing PD symptom progression. Rootstocks also were shown to affect Xf titer, xylem sap phenolic levels, and plant vigor.

  10. Treatment and disease progression in a birth cohort of vertically HIV-1 infected children in Ukraine

    Directory of Open Access Journals (Sweden)

    Pilipenko Tatyana

    2010-11-01

    Full Text Available Abstract Background Ukraine has the highest HIV prevalence (1.6% and is facing the fastest growing epidemic in Europe. Our objective was to describe the clinical, immunological and virological characteristics, treatment and response in vertically HIV-infected children living in Ukraine and followed from birth. Methods The European Collaborative Study (ECS is an ongoing cohort study, in which HIV-1 infected pregnant women are enrolled and followed in pregnancy, and their children prospectively followed from birth. ECS enrolment in Ukraine started in 2000 initially with three sites, increasing to seven sites by 2009. Results A total of 245 infected children were included in the cohort by April 2009, with a median age of 23 months at most recent follow-up; 33% (n = 77 had injecting drug using mothers and 85% (n = 209 were infected despite some use of antiretroviral prophylaxis for prevention of mother-to-child transmission. Fifty-five (22% children had developed AIDS, at a median age of 10 months (IQR = 6-19. The most prevalent AIDS indicator disease was Pneumocystis jiroveci pneumonia (PCP. Twenty-seven (11% children had died (median age, 6.2 months. Overall, 108 (44% children had started highly active antiretroviral treatment (HAART, at a median 18 months of age; median HAART duration was 6.6 months to date. No child discontinued HAART and 92% (100/108 remained on their first-line HAART regimen to date. Among children with moderate/severe immunosuppression, 36% had not yet started HAART. Among children on HAART, 71% (69/97 had no evidence of immunosuppression at their most recent visit; the median reduction in HIV RNA was 4.69 log10 copies/mL over a median of 10 months treatment. From survival analysis, an estimated 94%, 84% and 81% of children will be alive and AIDS-free at 6, 12 and 18 months of age, respectively. However, survival increased significantly over time: estimated survival rates to 12 months of age were 87% for children born in 2000

  11. The endothelin system has a significant role in the pathogenesis and progression of Mycobacterium tuberculosis infection.

    Science.gov (United States)

    Correa, Andre F; Bailão, Alexandre M; Bastos, Izabela M D; Orme, Ian M; Soares, Célia M A; Kipnis, Andre; Santana, Jaime M; Junqueira-Kipnis, Ana Paula

    2014-12-01

    Tuberculosis (TB) remains a major global health problem, and although multiple studies have addressed the relationship between Mycobacterium tuberculosis and the host on an immunological level, few studies have addressed the impact of host physiological responses. Proteases produced by bacteria have been associated with important alterations in the host tissues, and a limited number of these enzymes have been characterized in mycobacterial species. M. tuberculosis produces a protease called Zmp1, which appears to be associated with virulence and has a putative action as an endothelin-converting enzyme. Endothelins are a family of vasoactive peptides, of which 3 distinct isoforms exist, and endothelin 1 (ET-1) is the most abundant and the best-characterized isoform. The aim of this work was to characterize the Zmp1 protease and evaluate its role in pathogenicity. Here, we have shown that M. tuberculosis produces and secretes an enzyme with ET-1 cleavage activity. These data demonstrate a possible role of Zmp1 for mycobacterium-host interactions and highlights its potential as a drug target. Moreover, the results suggest that endothelin pathways have a role in the pathogenesis of M. tuberculosis infections, and ETA or ETB receptor signaling can modulate the host response to the infection. We hypothesize that a balance between Zmp1 control of ET-1 levels and ETA/ETB signaling can allow M. tuberculosis adaptation and survival in the lung tissues. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  12. The Irish paradigm on the natural progression of hepatitis C virus infection: an investigation in a homogeneous patient population infected with HCV 1b (review).

    LENUS (Irish Health Repository)

    Fanning, Liam J

    2012-02-03

    The aetiological agent of chronic hepatitis C is the hepatitis C virus. The hepatitis C virus is spread by parenteral transmission of body fluids, primarily blood or blood products. In 1989, after more than a decade of research, HCV was isolated and characterised. The hepatitis C viral genome is a positive-sense, single-stranded RNA molecule approximately 9.4 kb in length, which encodes a polyprotein of about 3100 amino acids. There are 6 main genotypes of HCV, each further stratified by subtype. In 1994, a cohort of women was identified in Ireland as having been iatrogenically exposed to the hepatitis C virus. The women were all young and exposed as a consequence of the receipt of HCV 1b contaminated anti-D immunoglobulin. The source of the infection was identified as an acutely infected female. As part of a voluntary serological screening programme involving 62,667 people, 704 individuals were identified as seropositive for exposure to the hepatitis C virus; 55.4% were found to be positive for the viral genome 17 years after exposure. Of these women 98% had evidence of inflammation, but surprisingly, a remarkable 49% showed no evidence of fibrosis. Clinicopathology and virological analysis has identified associations between viral load and the histological activity index for inflammation, and, between inflammation and levels of the liver enzyme alanine aminotransferase. Infection at a younger age appears to protect individuals from progression to advanced liver disease. Molecular analyses of host immunogenetic elements shows that particular class II human leukocyte associated antigen alleles are associated with clearance of the hepatitis C virus. Additional class II alleles have been identified that are associated with stable viraemia over an extended period of patient follow-up. Although, investigation of large untreated homogeneous cohorts is likely to become more difficult, as the efficacy of anti-viral therapy improves, further investigation of host and viral

  13. A rapid crosstalk of human gammadelta T cells and monocytes drives the acute inflammation in bacterial infections.

    Directory of Open Access Journals (Sweden)

    Matthias Eberl

    2009-02-01

    Full Text Available Vgamma9/Vdelta2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. We previously demonstrated that the primary target for Vgamma9/Vdelta2 T cells is (E-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP, an essential metabolite produced by a large range of pathogens. Here we wished to study the consequence of this unique responsiveness in microbial infection. The majority of peripheral Vgamma9/Vdelta2 T cells shares migration properties with circulating monocytes, which explains the presence of these two distinct blood cell types in the inflammatory infiltrate at sites of infection and suggests that they synergize in anti-microbial immune responses. Our present findings demonstrate a rapid and HMB-PP-dependent crosstalk between Vgamma9/Vdelta2 T cells and autologous monocytes that results in the immediate production of inflammatory mediators including the cytokines interleukin (IL-6, interferon (IFN-gamma, tumor necrosis factor (TNF-alpha, and oncostatin M (OSM; the chemokines CCL2, CXCL8, and CXCL10; and TNF-related apoptosis-inducing ligand (TRAIL. Moreover, under these co-culture conditions monocytes differentiate within 18 hours into inflammatory dendritic cells (DCs with antigen-presenting functions. Addition of further microbial stimuli (lipopolysaccharide, peptidoglycan induces CCR7 and enables these inflammatory DCs to trigger the generation of CD4(+ effector alphabeta T cells expressing IFN-gamma and/or IL-17. Importantly, our in vitro model replicates the responsiveness to microbes of effluent cells from peritoneal dialysis (PD patients and translates directly to episodes of acute PD-associated bacterial peritonitis, where Vgamma9/Vdelta2 T cell numbers and soluble inflammatory mediators are elevated in patients infected with HMB-PP-producing pathogens. Collectively, these findings suggest a direct link between invading pathogens, microbe

  14. Risk of iatrogenic human immunodeficiency virus infection through transfusion of blood tested by inappropriately stored or expired rapid antibody assays in a Zambian hospital

    NARCIS (Netherlands)

    Consten, E. C.; van der Meer, J. T.; de Wolf, F.; Heij, H. A.; Henny, P. C.; van Lanschot, J. J.

    1997-01-01

    BACKGROUND: The purpose of this study was to estimate the risk of human immunodeficiency virus (HIV) infection via the transfusion of blood tested by inappropriately stored or expired rapid antibody assays in Zambia. STUDY DESIGN AND METHODS: Surgical patients (n = 370) were tested with antibody

  15. Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

    International Nuclear Information System (INIS)

    Oka, Takashi; Sato, Hiaki; Ouchida, Mamoru; Utsunomiya, Atae; Yoshino, Tadashi

    2011-01-01

    Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed

  16. Cumulative Epigenetic Abnormalities in Host Genes with Viral and Microbial Infection during Initiation and Progression of Malignant Lymphoma/Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Oka, Takashi, E-mail: oka@md.okayama-u.ac.jp [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Sato, Hiaki [Department of Medical Technology, Graduate School of Health Science, Okayama University Medical School, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Ouchida, Mamoru [Department of Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan); Utsunomiya, Atae [Department of Hematology, Imamura Bun-in Hospital, 11-23 Kamoike Shinnmachi, Kagoshima, 890-0064 (Japan); Yoshino, Tadashi [Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558 (Japan)

    2011-02-04

    Although cancers have been thought to be predominantly driven by acquired genetic changes, it is becoming clear that microenvironment-mediated epigenetic alterations play important roles. Aberrant promoter hypermethylation is a prevalent phenomenon in human cancers as well as malignant lymphoma/leukemia. Tumor suppressor genes become frequent targets of aberrant hypermethylation in the course of gene-silencing due to the increased and deregulated DNA methyltransferases (DNMTs). The purpose of this article is to review the current status of knowledge about the contribution of cumulative epigenetic abnormalities of the host genes after microbial and virus infection to the crisis and progression of malignant lymphoma/leukemia. In addition, the relevance of this knowledge to malignant lymphoma/leukemia assessment, prevention and early detection will be discussed.

  17. Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

    Directory of Open Access Journals (Sweden)

    Gabriela Turk

    2018-01-01

    Full Text Available Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC and viral load (VL levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA and C-C chemokine receptor type 5 (CCR5 genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL-10, interferon gamma-induced protein (IP-10, soluble IL-2 receptor alpha (sIL-2Rα and tumor necrosis factor alpha (TNF-α levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF-2 and macrophage inflammatory protein (MIP-1β correlated directly with CD4+ T-cell activation (p < 0.05. However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85. Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

  18. Peripheral ovine progressive pneumonia provirus levels correlate with and predict histological tissue lesion severity in naturally infected sheep.

    Science.gov (United States)

    Herrmann-Hoesing, Lynn M; Noh, Susan M; White, Stephen N; Snekvik, Kevin R; Truscott, Thomas; Knowles, Donald P

    2009-04-01

    Studies were undertaken to determine whether anti-ovine progressive pneumonia virus (OPPV) antibody responses in serum or OPP provirus levels in peripheral blood associate with the degree of histologically measured tissue lesions in naturally OPPV-infected sheep. Sections of formalin-fixed, paraffin-embedded, and hematoxylin- and eosin-stained lung, mammary gland, carpal synovial membrane, and brain tissues from 11 OPPV-infected ewes (mean age of 8.6 years) and 5 OPPV-uninfected ewes (mean age of 6 years) were evaluated for lesion severity. Ovine progressive pneumonia (OPP) provirus levels and anti-OPPV antibody titers in peripheral blood and serum samples, respectively, were measured upon euthanasia and 3 years prior to euthanasia. Both mean peripheral OPP provirus levels and mean serum anti-surface envelope glycoprotein (anti-SU) antibody titers at the time of euthanasia were significantly higher in ewes with moderate to severe histological lesions than in ewes with no to mild histological lesions. However, although mean peripheral blood OPP provirus levels at euthanasia and 3 years prior to euthanasia significantly correlated with the highest histological lesion score for any affected tissue (two-tailed P values, 0.03 and 0.02), mean serum anti-SU antibody titers, anti-capsid antibody titers, and anti-transmembrane 90 antibody titers at euthanasia did not show a significant correlation with the highest histological lesion score for any tissue (two-tailed P values, 0.32, 0.97, and 0.18, respectively). These data are the first to show that OPP provirus levels predict and correlate with the extent of OPPV-related histological lesions in various OPPV-affected tissues. These findings suggest that peripheral OPP provirus levels quantitatively contribute more to the development of histological lesions than the systemic anti-SU antibody host immune response.

  19. Atypical rapid progression of osteoarticular amyloidosis involving the hip in a patient on hemodialysis using polyacrylonitrile membranes

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kenneth S. [University of Wisconsin School of Medicine and Public Health, Department of Radiology, University of Wisconsin Hospital and Clinics, Madison, WI (United States); Holsbeeck, Marnix T. van [Wayne State School of Medicine, Department of Radiology, Henry Ford Hospital, Detroit, MI (United States); Abbud, Alexander [Wayne State School of Medicine, Department of Pathology, Henry Ford Hospital, Detroit, MI (United States)

    2010-01-15

    Amyloidosis related to dialysis is a well-known complication affecting many organ systems, in particular the musculoskeletal system. In 1985 Shirahama et al. (Biochem Biophys Res Commun 53:705-709, 1985) identified beta-2 microglobulin (MG) as the offending constituent by using protein purification techniques. Amyloidosis has been increasing in prevalence because of longer life spans and increased chronic medical conditions such as end-stage renal disease. When dialysis-related amyloidosis involves the musculoskeletal system, it affects the shoulder girdle, the so called shoulder pad sign, the wrist, hip, knee, and spine (Resnick, Diagnosis of bone and joint disorders, 4th edn., pp. 2054-2058 and 2176-2183, 2002). Other osteoarticular manifestations of amyloidosis include osteoporosis, lytic lesions, and pathologic fractures. It has been well documented that the prevalence of amyloid is dependent on duration of dialysis - over 90% in patients on dialysis for over 7 years (Jadoul, Nephrol Dial Transplant 13:61-64, 1998). However, a recent changeover to high-flux membranes used in hemofiltration has been reported to delay its onset (Campistol et al., Contrib Nephrol 125:76-85, 1999). We report on the radiographic, nuclear medicine, and computed tomography (CT) findings of osteoarticular amyloidosis involving the hip, and sequence its atypical rapid onset. The imaging, histopathological findings, and differential diagnosis are discussed. (orig.)

  20. Progression of pathogenic events in cynomolgus macaques infected with variola virus.

    Directory of Open Access Journals (Sweden)

    Victoria Wahl-Jensen

    Full Text Available Smallpox, caused by variola virus (VARV, is a devastating human disease that affected millions worldwide until the virus was eradicated in the 1970 s. Subsequent cessation of vaccination has resulted in an immunologically naive human population that would be at risk should VARV be used as an agent of bioterrorism. The development of antivirals and improved vaccines to counter this threat would be facilitated by the development of animal models using authentic VARV. Towards this end, cynomolgus macaques were identified as adequate hosts for VARV, developing ordinary or hemorrhagic smallpox in a dose-dependent fashion. To further refine this model, we performed a serial sampling study on macaques exposed to doses of VARV strain Harper calibrated to induce ordinary or hemorrhagic disease. Several key differences were noted between these models. In the ordinary smallpox model, lymphoid and myeloid hyperplasias were consistently found whereas lymphocytolysis and hematopoietic necrosis developed in hemorrhagic smallpox. Viral antigen accumulation, as assessed immunohistochemically, was mild and transient in the ordinary smallpox model. In contrast, in the hemorrhagic model antigen distribution was widespread and included tissues and cells not involved in the ordinary model. Hemorrhagic smallpox developed only in the presence of secondary bacterial infections - an observation also commonly noted in historical reports of human smallpox. Together, our results support the macaque model as an excellent surrogate for human smallpox in terms of disease onset, acute disease course, and gross and histopathological lesions.

  1. Year in review 2010: Critical Care - infection

    DEFF Research Database (Denmark)

    Pagani, Leonardo; Afshari, Arash; Harbarth, Stephan

    2011-01-01

    established approaches to the optimal management of infections in the intensive care unit. Rapid infection diagnosis, antibiotic dosing and optimization through pharmacologic indices, progress in the implementation of effective antimicrobial stewardship and infection control programs, and management of fungal...... infections are some of the most relevant issues in this special patient population. During the last 18 months, Critical Care and other journals have provided a wide array of descriptive and interventional clinical studies and scientific reports helping clinical investigators and critical care physicians...

  2. Female human pluripotent stem cells rapidly lose X chromosome inactivation marks and progress to a skewed methylation pattern during culture.

    Science.gov (United States)

    Geens, M; Seriola, A; Barbé, L; Santalo, J; Veiga, A; Dée, K; Van Haute, L; Sermon, K; Spits, C

    2016-04-01

    Does a preferential X chromosome inactivation (XCI) pattern exist in female human pluripotent stem cells (hPSCs) and does the pattern change during long-term culture or upon differentiation? We identified two independent phenomena that lead to aberrant XCI patterns in female hPSC: a rapid loss of histone H3 lysine 27 trimethylation (H3K27me3) and long non-coding X-inactive specific transcript (XIST) expression during culture, often accompanied by erosion of XCI-specific methylation, and a frequent loss of random XCI in the cultures. Variable XCI patterns have been reported in female hPSC, not only between different hPSC lines, but also between sub-passages of the same cell line, however the reasons for this variability remain unknown. Moreover, while non-random XCI-linked DNA methylation patterns have been previously reported, their origin and extent have not been investigated. We investigated the XCI patterns in 23 human pluripotent stem cell (hPSC) lines, during long-term culture and after differentiation, by gene expression analysis, histone modification assessment and study of DNA methylation. The presence and location of H3K27me3 was studied by immunofluorescence, XIST expression by real-time PCR, and mono- or bi-allelic expression of X-linked genes was studied by sequencing of cDNA. XCI-specific DNA methylation was analysed using methylation-sensitive restriction and PCR, and more in depth by massive parallel bisulphite sequencing. All hPSC lines showed XCI, but we found a rapid loss of XCI marks during the early stages of in vitro culture. While this loss of XCI marks was accompanied in several cases by an extensive erosion of XCI-specific methylation, it did not result in X chromosome reactivation. Moreover, lines without strong erosion of methylation frequently displayed non-random DNA methylation, which occurred independently from the loss of XCI marks. This bias in X chromosome DNA methylation did not appear as a passenger event driven by clonal culture

  3. HAART slows progression to anal cancer in HIV-infected MSM.

    Science.gov (United States)

    Duncan, Katrina C; Chan, Keith J; Chiu, Connie G; Montaner, Julio S G; Coldman, Andy J; Cescon, Angela; Au-Yeung, Christopher G; Wiseman, Sam M; Hogg, Robert S; Press, Natasha M

    2015-01-28

    Antiretrovirals do not prevent anal intraepithelial neoplasia. However, the influence of antiretrovirals in the natural history of invasive anal cancer is less clear. The objective is to investigate the impact of antiretrovirals in the time to the development of anal cancer in HIV-positive MSM. A retrospective analysis of cases of anal cancer in a cohort of HIV-positive MSM receiving antiretrovirals between 1988 and 2008. Time from first CD4 cell count or HIV RNA viral load test to anal cancer diagnosis was analysed using Cox regression and Kaplan-Meier curves. Anal cancer cases treated in the era prior to HAART (cancer cases (n = 37) were compared with a cohort of 1654 HIV-positive MSM on antiretrovirals. Antiretrovirals were started in the pre-HAART era by 70% of cancer cases, and median CD4 cell count nadir was 70 cells/μl (10-130). Time to development of anal cancer was shorter for cases treated during the pre-HAART era [adjusted hazard ratio (AHR) 3.04, 95% confidence interval (95% CI) 1.48-6.24, P = 0.002], with a CD4 cell count nadir less than 100 cells/μl (AHR 2.21, 95% CI 1.06-4.62, P = 0.035) and longer duration of CD4 cell count less than 100 cells/μl (AHR 1.33, 95% CI 1.11-1.58, P = 0.002). Results show that severe immunosuppression and starting therapy pre-HAART are associated with an increased risk of anal cancer. HIV-positive MSM initiating antiretrovirals during the HAART era (1996-2008) had a longer time to the development of anal cancer than those treated pre-HAART. Our results suggest that early use of HAART may delay progression to anal cancer.

  4. PCR-based verification of positive rapid diagnostic tests for intestinal protozoa infections with variable test band intensity.

    Science.gov (United States)

    Becker, Sören L; Müller, Ivan; Mertens, Pascal; Herrmann, Mathias; Zondie, Leyli; Beyleveld, Lindsey; Gerber, Markus; du Randt, Rosa; Pühse, Uwe; Walter, Cheryl; Utzinger, Jürg

    2017-10-01

    Stool-based rapid diagnostic tests (RDTs) for pathogenic intestinal protozoa (e.g. Cryptosporidium spp. and Giardia intestinalis) allow for prompt diagnosis and treatment in resource-constrained settings. Such RDTs can improve individual patient management and facilitate population-based screening programmes in areas without microbiological laboratories for confirmatory testing. However, RDTs are difficult to interpret in case of 'trace' results with faint test band intensities and little is known about whether such ambiguous results might indicate 'true' infections. In a longitudinal study conducted in poor neighbourhoods of Port Elizabeth, South Africa, a total of 1428 stool samples from two cohorts of schoolchildren were examined on the spot for Cryptosporidium spp. and G. intestinalis using an RDT (Crypto/Giardia DuoStrip; Coris BioConcept). Overall, 121 samples were positive for G. intestinalis and the RDT suggested presence of cryptosporidiosis in 22 samples. After a storage period of 9-10 months in cohort 1 and 2-3 months in cohort 2, samples were subjected to multiplex PCR (BD Max™ Enteric Parasite Panel, Becton Dickinson). Ninety-three percent (112/121) of RDT-positive samples for G. intestinalis were confirmed by PCR, with a correlation between RDT test band intensity and quantitative pathogen load present in the sample. For Cryptosporidium spp., all positive RDTs had faintly visible lines and these were negative on PCR. The performance of the BD Max™ PCR was nearly identical in both cohorts, despite the prolonged storage at disrupted cold chain conditions in cohort 1. The Crypto/Giardia DuoStrip warrants further validation in communities with a high incidence of diarrhoea. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Gnotobiotic IL-10; NF-kappaB mice develop rapid and severe colitis following Campylobacter jejuni infection.

    Directory of Open Access Journals (Sweden)

    Elisabeth Lippert

    2009-10-01

    Full Text Available Limited information is available on the molecular mechanisms associated with Campylobacter jejuni (C. jejuni induced food-borne diarrheal illnesses. In this study, we investigated the function of TLR/NF-kappaB signaling in C. jejuni induced pathogenesis using gnotobiotic IL-10(-/-; NF-kappaB(EGFP mice. In vitro analysis showed that C. jejuni induced IkappaB phosphorylation, followed by enhanced NF-kappaB transcriptional activity and increased IL-6, MIP-2alpha and NOD2 mRNA accumulation in infected-mouse colonic epithelial cells CMT93. Importantly, these events were blocked by molecular delivery of an IkappaB inhibitor (Ad5IkappaBAA. NF-kappaB signalling was also important for C.jejuni-induced cytokine gene expression in bone marrow-derived dendritic cells. Importantly, C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice developed mild (day 5 and severe (day 14 ulcerating colonic inflammation and bloody diarrhea as assessed by colonoscopy and histological analysis. Macroscopic analysis showed elevated EGFP expression indicating NF-kappaB activation throughout the colon of C. jejuni associated IL-10(-/-; NF-kappaB(EGFP mice, while fluorescence microscopy revealed EGFP positive cells to be exclusively located in lamina propria mononuclear cells. Pharmacological NF-kappaB inhibition using Bay 11-7085 did not ameliorate C. jejuni induced colonic inflammation. Our findings indicate that C. jejuni induces rapid and severe intestinal inflammation in a susceptible host that correlates with enhanced NF-kappaB activity from lamina propria immune cells.

  6. Chronic Subdural Hematoma development in Accelerated phase of Chronic Myeloid Leukaemia presenting with seizure and rapid progression course with fatal outcome

    Directory of Open Access Journals (Sweden)

    Raheja Amol

    2015-06-01

    Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy

  7. Biofilm in group A streptococcal necrotizing soft tissue infections

    DEFF Research Database (Denmark)

    Siemens, Nikolai; Chakrakodi, Bhavya; Shambat, Srikanth Mairpady

    2016-01-01

    Necrotizing fasciitis caused by group A streptococcus (GAS) is a life-threatening, rapidly progressing infection. At present, biofilm is not recognized as a potential problem in GAS necrotizing soft tissue infections (NSTI), as it is typically linked to chronic infections or associated with forei...

  8. Zika virus infection, transmission, associated neurological disorders and birth abnormalities:A review of progress in research, priorities and knowledge gaps

    Institute of Scientific and Technical Information of China (English)

    Yitades Gebre; Nikkiah Forbes; Teshome Gebre

    2016-01-01

    On February 1, 2016, the World Health Organization declared that the cluster of microcephaly cases and other neurological disorders constitute public health emergency of international concern. Furthermore, few studies demonstrated that there was an increased evidence of causal relationship of Zika virus (ZIKAV) infection and micro-cephaly, birth abnormalities and neurological disorders such as Guillain–Barr ´e syndrome. ZIKAV transmission occurs mainly by the bite of infected mosquitos (Aedes species), but there are also reports that infections could occur via the placenta, breast milk, saliva, blood transfusion and sex. This article reviews the global efforts, progress in scientific research to understand the pathogenesis of ZIKAV infection & disease, clinical pre-sentations, congenital transmission and autoimmune neurological disorders. The paper further explores the knowledge gaps, future priority research agenda for strategic response including vector control and prevention. We conducted a systematic literature review to synthesise available evidence on ZIKAV infection and its vector and host interaction from electronic databases.

  9. Value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection

    Directory of Open Access Journals (Sweden)

    BAO Teng

    2017-08-01

    Full Text Available ObjectiveTo investigate the clinical value of HBsAg level in dynamic monitoring of disease progression in patients with chronic HBV infection. MethodsA retrospective analysis was performed for the clinical data of 1107 patients with different clinical stages of chronic HBV infection who had not received antiviral therapy at the time of hospitalization in The Second Affiliated Hospital of Anhui Medical University from May 2011 to December 2015, and according to the disease status, they were divided into HBeAg-positive chronic hepatitis B (CHB group, HBeAg-negative CHB group, compensated liver cirrhosis group (LC-C group, decompensated liver cirrhosis group (LC-D group, and primary liver cancer (PLC group. These groups were compared in terms of HBsAg expression and the association between HBsAg and clinical features. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between any two groups; the t-test was used for comparison of continuous data between two groups. The chi-square test was used for comparison of categorical data between these groups. Pearson correlation analysis was also performed. ResultsThere was a significant difference in serum HBsAg level between the HBeAg-positive CHB group, HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=100.45, P<0.001. The HBeAg-positive CHB group had significantly higher levels of HBsAg and HBV DNA than the HBeAg-negative CHB group (t= 16.67 an 16.22, both P<0.001. There were significant differences in HBsAg and HBV DNA levels between the HBeAg-positive CHB group, LC-C group, LC-D group, and PLC group (F= 42.92 and 27.38, both P<0.001, as well as between the HBeAg-negative CHB group, LC-C group, LC-D group, and PLC group (F=6.04 and 4.10, both P<0.05. HBV DNA level was significantly different across patients with different HBsAg levels (<1000 IU/ml, 1000-20 000 IU

  10. Impact of viral hepatitis co-infection on response to antiretroviral therapy and HIV disease progression in the HIV-NAT cohort

    NARCIS (Netherlands)

    Law, W. Phillip; Duncombe, Chris J.; Mahanontharit, Apicha; Boyd, Mark A.; Ruxrungtham, Kiat; Lange, Joep M. A.; Phanuphak, Praphan; Cooper, David A.; Dore, Gregory J.

    2004-01-01

    OBJECTIVE: To examine the impact of viral hepatitis co-infection on HIV disease outcomes following commencement of combination antiretroviral therapy in a developing country setting. METHODS: HIV RNA suppression, CD4 cell count recovery, and HIV disease progression were examined within a cohort of

  11. Current hemoglobin levels are more predictive of disease progression than hemoglobin measured at baseline in patients receiving antiretroviral treatment for HIV type 1 infection

    DEFF Research Database (Denmark)

    Kowalska, Justyna D; Mocroft, Amanda; Blaxhult, Anders

    2007-01-01

    The role of hemoglobin levels as an independent prognostic marker of progression to AIDS and/or death in HIV-infected patients starting combination antiretroviral therapy (cART) was investigated. A total of 2,579 patients from the EuroSIDA cohort with hemoglobin, CD4 cell count, and HIV RNA viral...

  12. Hepatitis C virus infection in HIV-infected patients.

    Science.gov (United States)

    Sulkowski, Mark S

    2007-10-01

    The hepatitis C virus (HCV) is a spherical enveloped RNA virus of the Flaviviridae family, classified within the Hepacivirus genus. Since its discovery in 1989, HCV has been recognized as a major cause of chronic hepatitis and hepatic fibrosis that progresses in some patients to cirrhosis and hepatocellular carcinoma. In the United States, approximately 4 million people have been infected with HCV, and 10,000 HCVrelated deaths occur each year. Due to shared routes of transmission, HCV and HIV co-infection are common, affecting approximately one third of all HIV-infected persons in the United States. In addition, HIV co-infection is associated with higher HCV RNA viral load and a more rapid progression of HCV-related liver disease, leading to an increased risk of cirrhosis. HCV infection may also impact the course and management of HIV disease, particularly by increasing the risk of antiretroviral drug-induced hepatotoxicity. Thus, chronic HCV infection acts as an opportunistic disease in HIV-infected persons because the incidence of infection is increased and the natural history of HCV infection is accelerated in co-infected persons. Strategies to prevent primary HCV infection and to modify the progression of HCV-related liver disease are urgently needed among HIV/HCV co-infected individuals.

  13. Alcohol Types and HIV Disease Progression Among HIV-Infected Drinkers Not Yet on Antiretroviral Therapy in Russia and Uganda.

    Science.gov (United States)

    Asiimwe, Stephen B; Fatch, Robin; Patts, Gregory; Winter, Michael; Lloyd-Travaglini, Christine; Emenyonu, Nneka; Muyindike, Winnie; Kekibiina, Allen; Blokhina, Elena; Gnatienko, Natalia; Kruptisky, Evgeny; Cheng, Debbie M; Samet, Jeffrey H; Hahn, Judith A

    2017-11-01

    In HIV-infected drinkers, alcohol types more likely to cause inflammation could plausibly increase the risk of HIV disease progression. We therefore assessed the association between alcohol type and plasma HIV RNA level (HIV viral load) among HIV-infected drinkers not on antiretroviral therapy (ART) in Russia and Uganda. We analyzed the data of participants from cohorts in Russia and Uganda and assessed their HIV viral load at enrollment by the alcohol type predominantly consumed. We defined predominant alcohol type as the alcohol type contributing >50% of total alcohol consumption in the 1 month (Russia) or 3 months (Uganda) prior to enrollment. Using multiple linear regression, we compared log 10 HIV viral load by predominant alcohol type, controlling for age, gender, socioeconomic status, total number of standard drinks, frequency of drinking ≥6 drinks/occasion, and in Russia, history of injection drug use. Most participants (99.2% of 261 in Russia and 98.9% of 352 in Uganda) predominantly drank one alcohol type. In Russia, we did not find evidence for differences in viral load levels between drinkers of fortified wine (n = 5) or hard liquor (n = 49), compared to drinkers of beer/low-ethanol-content cocktails (n = 163); however, wine/high-ethanol-content cocktail drinkers (n = 42) had higher mean log 10 viral load than beer/low-ethanol-content cocktail drinkers (β = 0.38, 95% CI 0.07-0.69; p = 0.02). In Uganda, we did not find evidence for differences in viral load levels between drinkers of locally-brewed beer (n = 41), commercially-distilled spirits (n = 38), or locally-distilled spirits (n = 43), compared to drinkers of commercially-made beer (n = 218); however, wine drinkers (n = 8) had lower mean log 10 HIV viral load (β = -0.65, 95% CI -1.36 to 0.07, p = 0.08), although this did not reach statistical significance. Among HIV-infected drinkers not yet on ART in Russia and Uganda, we observed an association between the

  14. Variations in the Biological Functions of HIV-1 Clade C Envelope in a SHIV-Infected Rhesus Macaque during Disease Progression.

    Directory of Open Access Journals (Sweden)

    For Yue Tso

    Full Text Available A better understanding of how the biological functions of the HIV-1 envelope (Env changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection of macaque with SHIV, expressing HIV-1 clade C Env V1-V5 region. By using this model, we examined the changes in biological functions of Env in the infected animal over the entire disease course. Our data showed an increase in the neutralization resistance phenotype over time and coincided with the decrease in the net charges of the V1-V5 region. Infection of PBMC with provirus expressing various Env clones, isolated from the infected animal over time, showed a surprisingly better replicative fitness for viruses expressing the Env from early time point. Biotinylation and ELISA data also indicated a decrease of cell-surface-associated Env and virion-associated gp120 content with disease progression. This decrease did not affect the CD4-binding capability of Env, but were positively correlated with the decrease of Env fusion ability. Interestingly, some of these changes in biological functions reverted to the pre-AIDS level during advance AIDS. These data suggested a dynamic relationship between the Env V1-V5 region with the host immune pressure. The observed changes of biological functions in this setting might reflect and predict those occurring during natural disease progression in human.

  15. Rapid Re-Infection with Soil-Transmitted Helminths after Triple-Dose Albendazole Treatment of School-Aged Children in Yunnan, People's Republic of China

    Science.gov (United States)

    Yap, Peiling; Du, Zun-Wei; Wu, Fang-Wei; Jiang, Jin-Yong; Chen, Ran; Zhou, Xiao-Nong; Hattendorf, Jan; Utzinger, Jürg; Steinmann, Peter

    2013-01-01

    Post-treatment soil-transmitted helminth re-infection patterns were studied as part of a randomized controlled trial among school-aged children from an ethnic minority group in Yunnan province, People's Republic of China. Children with a soil-transmitted helminth infection (N = 194) were randomly assigned to triple-dose albendazole or placebo and their infection status monitored over a 6-month period using the Kato-Katz and Baermann techniques. Baseline prevalence of Trichuris trichiura, Ascaris lumbricoides, hookworm, and Strongyloides stercoralis were 94.5%, 93.3%, 61.3%, and 3.1%, respectively, with more than half of the participants harboring triple-species infections. For the intervention group (N = 99), the 1-month post-treatment cure rates were 96.7%, 91.5%, and 19.6% for hookworm, A. lumbricoides, and T. trichiura, respectively. Egg reduction rates were above 88% for all three species. Rapid re-infection with A. lumbricoides was observed: the prevalence 4 and 6 months post-treatment was 75.8% and 83.8%, respectively. Re-infection with hookworm and T. trichiura was considerably slower. PMID:23690551

  16. Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

    Science.gov (United States)

    Chittiprol, Seetharamaiah; Kumar, Adarsh M; Satishchandra, P; Taranath Shetty, K; Bhimasena Rao, R S; Subbakrishna, D K; Philip, Mariyamma; Satish, K S; Ravi Kumar, H; Kumar, Mahendra

    2008-01-01

    Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls

  17. New LightCycler PCR for Rapid and Sensitive Quantification of Parvovirus B19 DNA Guides Therapeutic Decision-Making in Relapsing Infections

    Science.gov (United States)

    Harder, Timm C.; Hufnagel, Markus; Zahn, Katrin; Beutel, Karin; Schmitt, Heinz-Josef; Ullmann, Uwe; Rautenberg, Peter

    2001-01-01

    Detection of parvovirus B19 DNA offers diagnostic advantages over serology, particularly in persistent infections of immunocompromised patients. A rapid, novel method of B19 DNA detection and quantification is introduced. This method, a quantitative PCR assay, is based on real-time glass capillary thermocycling (LightCycler [LC]) and fluorescence resonance energy transfer (FRET). The PCR assay allowed quantification over a dynamic range of over 7 logs and could quantify as little as 250 B19 genome equivalents (geq) per ml as calculated for plasmid DNA (i.e., theoretically ≥5 geq per assay). Interrater agreement analysis demonstrated equivalence of LC-FRET PCR and conventional nested PCR in the diagnosis of an active B19 infection (kappa coefficient = 0.83). The benefit of the new method was demonstrated in an immunocompromised child with a relapsing infection, who required an attenuation of the immunosuppressive therapy in addition to repeated doses of immunoglobulin to eliminate the virus. PMID:11724854

  18. Tc-99m-bicisate (ECD)-brain-SPECT in rapidly progressive dementia; Hirn-SPECT mit Tc-99m-Bicisat (ECD) bei rasch progredientem dementiellen Syndrom

    Energy Technology Data Exchange (ETDEWEB)

    Marienhagen, J.; Eilles, C. [Regensburg Univ. (Germany). Abt. fuer Nuklearmedizin; Weingaertner, U.; Blaha, L. [Bezirkskrankenhaus Mainkofen (Germany). Psychiatrische Klinik; Zerr, I.; Poser, S. [Goettingen Univ. (Germany). Klinik und Poliklinik fuer Neurologie

    1999-07-01

    We present a 61-year-old male patient with progressive dementia. A brain SPECT with Tc-99m-bicisate was performed for confirmation of clinically suspected Alzheimer-dementia. At the time of the SPECT-investigation marked apraxia and aphasia besides severe dementia were present. Electrophysiological as well as anatomical neuroimaging findings showed non-diagnostic alterations. SPECT revealed distinct perfusion defects, which made Alzheimer Dementia unlikely. The further course of the patient was determined by rapidly progressive deterioration with development of akinetic mutism. Thereafter, increased levels of neuron-specific enolase as well as 14-3-3 proteins were found in the cerebro-spinal fluid (CSF). The patient finally died with signs of cerebral decortication. Due to the clinical course and the CSF-findings the patient's final diagnosis was Creutzfeld-Jakob-disease, nevertheless no autopsy was performed. The presented case report underscores the clinical utility of perfusion brain SPECT in the differential diagnosis of dementias. (orig.) [German] Wir berichten ueber einen 61jaehrigen Patienten mit progredientem dementiellen Syndrom, der unter der Verdachtsdiagnose einer Demenz vom Alzheimer-Typ (DAT) zur Hirn-SPECT-Untersuchung mit TC-99m-Bicisat (ECD) vorgestellt wurde. Zum Untersuchungszeitpunkt bestanden neben dem Vollbild einer Demenz eine ausgepraegte Apraxie und Aphasie bei unspezifischen Veraenderungen im EEG sowie der neuroradiologischen Bildgebung. In der Hirn-SPECT-Untersuchung fanden sich fuer eine DAT untypische ausgedehnte, vorwiegend rechtshemisphaerische Perfusionsstoerungen. Im weiteren Verlauf rasche Progredienz des Krankheitsbildes mit Entwicklung eines akinetischen Mutismus sowie Nachweis erhoehter Werte der neuronspezifischen Enolase und des 14-3-3-Proteins im Liquor. Der Patient verstarb schliesslich unter dem Bild einer Decortication. Aufgrund des klinischen Verlaufs sowie der Liquorbefunde wurde, da eine autoptische Befundsicherung

  19. Association of gene polymorphism of SDF1(CXCR12 with susceptibility to HIV-1 infection and AIDS disease progression: A meta-analysis.

    Directory of Open Access Journals (Sweden)

    Jiwei Ding

    Full Text Available Genetic polymorphism of viral receptors is relevant to risks of HIV-1 infection, while it is still under debated whether the polymorphism of SDF1, a unique ligand for HIV-1 coreceptor CXCR4, is associated with HIV susceptibility and AIDS disease progression. Therefore, we provided an updated quantitative assessment by meta-analysis from 16 case-control and 7 cohort studies.Articles reporting the relationship between SDF1 polymorphism and HIV susceptibility or AIDS progression were retrieved from PubMed, Embase and Ovid electronic databases up to Apr 2017. Data were pooled by odds ratios (ORs for HIV-1 infection with 95% confidence intervals (CIs and summary relative hazards (RHs for AIDS progression with 95% CIs using 1987 Center for Disease Control (CDC case definition of AIDS (CDC87 and 1993 Center for Disease Control (CDC case definition of AIDS (CDC93 and death as endpoints.As a result, 16 studies regarding susceptibility to HIV-1 infection with 2803 HIV-infected patients and 3697 healthy individuals and 7 studies regarding disease progression with 4239 subjects were included in the meta-analysis. For risks of infection, no evidences indicated SDF1 polymorphism was associated with the risk of HIV-1 infection in all genetic models (recessive model: OR = 0.94, 95% Cl: 0.75-1.17; homozygous model: OR = 0.89, 95% Cl: 0.70-1.15; heterozygous model: OR = 1.06, 95% Cl: 0.83-1.35; allele model: OR = 0.95, 95% Cl: 0.79-1.13, Furthermore, we failed to find an delayed AIDS progression except in some specific cohorts including MACS cohorts (RH = 0.38, 95% Cl: 0.17-0.59 for time to AIDS; RH = 0.27, 95% Cl: 0.07-0.46 for time to death at the study entry.Overall, no significant association was found between SDF1 polymorphism and HIV susceptibility. A protective effect of SDF1 on AIDS progression and death was seen especially in two studies based on the same cohorts. In conclusion, SDF1 polymorphism exerts a moderate protective effect against AIDS disease

  20. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study.

    Directory of Open Access Journals (Sweden)

    Unnop Jaisamrarn

    Full Text Available The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681 was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN or clearance of infection, and associated determinants.Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+ associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs. Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65, 9.65 (5.97-15.60, 5.68 (3.50-9.21, 5.38 (2.87-10.06 and 3.87 (2.38-6.30 for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear.Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

  1. Natural history of progression of HPV infection to cervical lesion or clearance: analysis of the control arm of the large, randomised PATRICIA study.

    Science.gov (United States)

    Jaisamrarn, Unnop; Castellsagué, Xavier; Garland, Suzanne M; Naud, Paulo; Palmroth, Johanna; Del Rosario-Raymundo, Maria Rowena; Wheeler, Cosette M; Salmerón, Jorge; Chow, Song-Nan; Apter, Dan; Teixeira, Julio C; Skinner, S Rachel; Hedrick, James; Szarewski, Anne; Romanowski, Barbara; Aoki, Fred Y; Schwarz, Tino F; Poppe, Willy A J; Bosch, F Xavier; de Carvalho, Newton S; Germar, Maria Julieta; Peters, Klaus; Paavonen, Jorma; Bozonnat, Marie-Cecile; Descamps, Dominique; Struyf, Frank; Dubin, Gary O; Rosillon, Dominique; Baril, Laurence

    2013-01-01

    The control arm of PATRICIA (PApilloma TRIal against Cancer In young Adults, NCT00122681) was used to investigate the risk of progression from cervical HPV infection to cervical intraepithelial neoplasia (CIN) or clearance of infection, and associated determinants. Women aged 15-25 years were enrolled. A 6-month persistent HPV infection (6MPI) was defined as detection of the same HPV type at two consecutive evaluations over 6 months and clearance as ≥2 type-specific HPV negative samples taken at two consecutive intervals of approximately 6 months following a positive sample. The primary endpoint was CIN grade 2 or greater (CIN2+) associated with the same HPV type as a 6MPI. Secondary endpoints were CIN1+/CIN3+ associated with the same HPV type as a 6MPI; CIN1+/CIN2+/CIN3+ associated with an infection of any duration; and clearance of infection. The analyses included 4825 women with 16,785 infections (3363 women with 6902 6MPIs). Risk of developing a CIN1+/CIN2+/CIN3+ associated with same HPV type as a 6MPI varied with HPV type and was significantly higher for oncogenic versus non-oncogenic types. Hazard ratios for development of CIN2+ were 10.44 (95% CI: 6.96-15.65), 9.65 (5.97-15.60), 5.68 (3.50-9.21), 5.38 (2.87-10.06) and 3.87 (2.38-6.30) for HPV-16, HPV-33, HPV-31, HPV-45 and HPV-18, respectively. HPV-16 or HPV-33 6MPIs had ~25-fold higher risk for progression to CIN3+. Previous or concomitant HPV infection or CIN1+ associated with a different HPV type increased risk. Of the different oncogenic HPV types, HPV-16 and HPV-31 infections were least likely to clear. Cervical infections with oncogenic HPV types increased the risk of CIN2+ and CIN3+. Previous or concomitant infection or CIN1+ also increased the risk. HPV-16 and HPV-33 have by far the highest risk of progression to CIN3+, and HPV-16 and HPV-31 have the lowest chance of clearance.

  2. The monomeric GTPase RabA2 is required for progression and maintenance of membrane integrity of infection threads during root nodule symbiosis.

    Science.gov (United States)

    Dalla Via, Virginia; Traubenik, Soledad; Rivero, Claudio; Aguilar, O Mario; Zanetti, María Eugenia; Blanco, Flavio Antonio

    2017-04-01

    Progression of the infection canal that conducts rhizobia to the nodule primordium requires a functional Rab GTPase located in Golgi/trans-Golgi that also participate in root hair polar growth. Common bean (Phaseolus vulgaris) symbiotically associates with its partner Rhizobium etli, resulting in the formation of root nitrogen-fixing nodules. Compatible bacteria can reach cortical cells in a tightly regulated infection process, in which the specific recognition of signal molecules is a key step to select the symbiotic partner. In this work, we show that RabA2, a monomeric GTPase from common bean, is required for the progression of the infection canal, referred to as the infection thread (IT), toward the cortical cells. Expression of miss-regulated mutant variants of RabA2 resulted in an increased number of abortive infection events, including bursting of ITs and a reduction in the number of nodules. Nodules formed in these plants were small and contained infected cells with disrupted symbiosome membranes, indicating either early senescence of these cells or defects in the formation of the symbiosome membrane during bacterial release. RabA2 localized to mobile vesicles around the IT, but mutations that affect GTP hydrolysis or GTP/GDP exchange modified this localization. Colocalization of RabA2 with ArfA1 and a Golgi marker indicates that RabA2 localizes in Golgi stacks and the trans-Golgi network. Our results suggest that RabA2 is part of the vesicle transport events required to maintain the integrity of the membrane during IT progression.

  3. Progression of HPV infection to detectable cervical lesions or clearance in adult women: Analysis of the control arm of the VIVIANE study.

    Science.gov (United States)

    Skinner, S Rachel; Wheeler, Cosette M; Romanowski, Barbara; Castellsagué, Xavier; Lazcano-Ponce, Eduardo; Del Rosario-Raymundo, M Rowena; Vallejos, Carlos; Minkina, Galina; Pereira Da Silva, Daniel; McNeil, Shelly; Prilepskaya, Vera; Gogotadze, Irina; Money, Deborah; Garland, Suzanne M; Romanenko, Viktor; Harper, Diane M; Levin, Myron J; Chatterjee, Archana; Geeraerts, Brecht; Struyf, Frank; Dubin, Gary; Bozonnat, Marie-Cécile; Rosillon, Dominique; Baril, Laurence

    2016-05-15

    The control arm of the phase III VIVIANE (Human PapillomaVIrus: Vaccine Immunogenicity ANd Efficacy; NCT00294047) study in women >25 years was studied to assess risk of progression from cervical HPV infection to detectable cervical intraepithelial neoplasia (CIN). The risk of detecting CIN associated with the same HPV type as the reference infection was analysed using Kaplan-Meier and multivariable Cox models. Infections were categorised depending upon persistence as 6-month persistent infection (6MPI) or infection of any duration. The 4-year interim analysis included 2,838 women, of whom 1,073 (37.8%) experienced 2,615 infections of any duration and 708 (24.9%) experienced 1,130 6MPIs. Infection with oncogenic HPV types significantly increased the risk of detecting CIN grade 2 or greater (CIN2+) versus non-oncogenic types. For 6MPI, the highest risk was associated with HPV-33 (hazard ratio [HR]: 31.9 [8.3-122.2, p 25 years in this study was similar to that in women 15-25 years in PATRICIA. © 2015 The Authors and GlaxoSmithKline. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

  4. Identification of gene products suppressed by human immunodeficiency virus type 1 infection or gp120 exposure of primary human astrocytes by rapid subtraction hybridization.

    Science.gov (United States)

    Su, Zao-Zhong; Kang, Dong-Chul; Chen, Yinming; Pekarskaya, Olga; Chao, Wei; Volsky, David J; Fisher, Paul B

    2003-06-01

    Neurodegeneration and human immunodeficiency virus type 1 (HIV-1)-associated dementia (HAD) are the major disease manifestations of HIV-1 colonization of the central nervous system (CNS). In the brain, HIV-1 replicates in microglial cells and infiltrating macrophages and it persists in a low-productive, noncytolytic state in astrocytes. Astrocytes play critical roles in the maintenance of the brain microenvironment, responses to injury, and in neuronal signal transmission, and disruption of these functions by HIV-1 could contribute to HAD. To better understand the potential effects of HIV-1 on astrocyte biology, the authors investigated changes in gene expression using an efficient and sensitive rapid subtraction hybridization approach, RaSH. Primary human astrocytes were isolated from abortus brain tissue, low-passage cells were infected with HIV-1 or mock infected, and total cellular RNAs were isolated at multiple time points over a period of 1 week. This approach is designed to identify gene products modulated early and late after HIV-1 infection and limits the cloning of genes displaying normal cell-cycle fluctuations in astrocytes. By subtracting temporal cDNAs derived from HIV-1-infected astrocytes from temporal cDNAs made from uninfected cells, 10 genes displaying reduced expression in infected cells, termed astrocyte suppressed genes (ASGs), were identified and their suppression was confirmed by Northern blot hybridization. Both known and novel ASGs, not reported in current DNA databases, that are down-regulated by HIV-1 infection are described. Northern blotting confirms suppression of the same panel of ASGs by treatment of astrocytes with recombinant HIV-1 envelope glycoprotein, gp120. These results extend our previous analysis of astrocyte genes induced or enhanced by HIV-1 infection and together they suggest that HIV-1 and viral proteins have profound effects on astrocyte physiology, which may influence their function in the CNS.

  5. Dam's infection progress and within-herd prevalence as predictors of Mycobacterium avium subsp. paratuberculosis ELISA response in Danish Holstein cattle

    DEFF Research Database (Denmark)

    Nielsen, Søren Saxmose; Hansen, Kira Frello; Kvist, Louise

    2016-01-01

    potentially important for MAP transmission control. The objective of this study was therefore to assess the dam's infection progress and the within-herd test-prevalence as predictors of MAP infection in Danish dairy cattle. MAP specific antibody ELISA records from 95,025 dam-offspring pairs were combined...... with test-prevalence estimates from 939 Danish Holstein herds. The odds of testing ELISA-positive given the within-herd test-prevalence and the time-period a dam had had MAP specific antibodies were estimated for the offspring. Both dams and offspring were tested as adults, and parity-group was used...

  6. Near-Infrared Spectroscopy, a Rapid Method for Predicting the Age of Male and Female Wild-Type and Wolbachia Infected Aedes aegypti.

    Directory of Open Access Journals (Sweden)

    Maggy T Sikulu-Lord

    2016-10-01

    Full Text Available Estimating the age distribution of mosquito populations is crucial for assessing their capacity to transmit disease and for evaluating the efficacy of available vector control programs. This study reports on the capacity of the near-infrared spectroscopy (NIRS technique to rapidly predict the ages of the principal dengue and Zika vector, Aedes aegypti. The age of wild-type males and females, and males and females infected with wMel and wMelPop strains of Wolbachia pipientis were characterized using this method. Calibrations were developed using spectra collected from their heads and thoraces using partial least squares (PLS regression. A highly significant correlation was found between the true and predicted ages of mosquitoes. The coefficients of determination for wild-type females and males across all age groups were R2 = 0.84 and 0.78, respectively. The coefficients of determination for the age of wMel and wMelPop infected females were 0.71 and 0.80, respectively (P< 0.001 in both instances. The age of wild-type female Ae. aegypti could be identified as < or ≥ 8 days old with an accuracy of 91% (N = 501, whereas female Ae. aegypti infected with wMel and wMelPop were differentiated into the two age groups with an accuracy of 83% (N = 284 and 78% (N = 229, respectively. Our results also indicate NIRS can distinguish between young and old male wild-type, wMel and wMelPop infected Ae. aegypti with accuracies of 87% (N = 253, 83% (N = 277 and 78% (N = 234, respectively. We have demonstrated the potential of NIRS as a predictor of the age of female and male wild-type and Wolbachia infected Ae. aegypti mosquitoes under laboratory conditions. After field validation, the tool has the potential to offer a cheap and rapid alternative for surveillance of dengue and Zika vector control programs.

  7. Rapid promotion and progression of fibrovascular polyps by inflammation and/or hyperplasia in hamster check pouch: implications for carcinogenesis assay.

    Science.gov (United States)

    McGaughey, C; Jensen, J L

    1983-03-01

    Tumor initiation by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in dimethyl sulfoxide (DMSO) followed by topical application of retinyl acetate (RA), ethylphenylpropiolate, or acetic acid in DMSO at inflammatory and hyperplasiogenic dose regimens caused the rapid promotion of fibrovascular polyps with dysplastic epithelium in hamster cheek pouch. Such lesions did not occur in control animals initiated with DMBA followed by application of DMSO only, where inflammation was also minimal. At the dose regimen employed, RA caused obvious cytotoxicity and tissue destruction. With EPP and AA, there was no histological evidence of tissue destruction. At dose regimens resulting in minimal inflammation and no apparent cytotoxicity, RA promoted almost no polyps, but a higher yield of other tumor types. Thus, inflammation and/or hyperplasia apparently exerted a strong polyp-promoting and progressive influence. This and other differences between the tumorigenic responses of hamster-pouch mucosa and mouse skin suggest that the former supplement the latter in carcinogenic risk assessment.

  8. Rapidly progressive renal disease as part of Wolfram syndrome in a large inbred Turkish family due to a novel WFS1 mutation (p.Leu511Pro).

    Science.gov (United States)

    Yuca, Sevil Ari; Rendtorff, Nanna Dahl; Boulahbel, Houda; Lodahl, Marianne; Tranebjærg, Lisbeth; Cesur, Yasar; Dogan, Murat; Yilmaz, Cahide; Akgun, Cihangir; Acikgoz, Mehmet

    2012-01-01

    Wolfram syndrome, also named "DIDMOAD" (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is an inherited association of juvenile-onset diabetes mellitus and optic atrophy as key diagnostic criteria. Renal tract abnormalities and neurodegenerative disorder may occur in the third and fourth decade. The wolframin gene, WFS1, associated with this syndrome, is located on chromosome 4p16.1. Many mutations have been described since the identification of WFS1 as the cause of Wolfram syndrome. We identified a new homozygous WFS1 mutation (c.1532T>C; p.Leu511Pro) causing Wolfram syndrome in a large inbred Turkish family. The patients showed early onset of IDDM, diabetes insipidus, optic atrophy, sensorineural hearing impairment and very rapid progression to renal failure before age 12 in three females. Ectopic expression of the wolframin mutant in HEK cells results in greatly reduced levels of protein expression compared to wild-type wolframin, strongly supporting that this mutation is disease-causing. The mutation showed perfect segregation with disease in the family, characterized by early and severe clinical manifestations. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

  9. Francisella tularensis type A Strains Cause the Rapid Encystment of Acanthamoeba castellanii and Survive in Amoebal Cysts for Three Weeks post Infection

    Energy Technology Data Exchange (ETDEWEB)

    El-Etr, S H; Margolis, J; Monack, D; Robison, R; Cohen, M; Moore, E; Rasley, A

    2009-07-28

    Francisella tularensis, the causative agent of the zoonotic disease tularemia, has recently gained increased attention due to the emergence of tularemia in geographical areas where the disease has been previously unknown, and the organism's potential as a bioterrorism agent. Although F. tularensis has an extremely broad host range, the bacterial reservoir in nature has not been conclusively identified. In this study, the ability of virulent F. tularensis strains to survive and replicate in the amoeba Acanthamoeba castellanii was explored. We observe that A. castellanii trophozoites rapidly encyst in response to F. tularensis infection and that this rapid encystment phenotype (REP) is caused by factor(s) secreted by amoebae and/or F. tularensis into the co-culture media. Further, our results indicate that in contrast to LVS, virulent strains of F. tularensis can survive in A. castellanii cysts for at least 3 weeks post infection and that induction of rapid amoeba encystment is essential for survival. In addition, our data indicate that pathogenic F. tularensis strains block lysosomal fusion in A. castellanii. Taken together, these data suggest that the interactions between F. tularensis strains and amoeba may play a role in the environmental persistence of F. tularensis.

  10. Performance of rapid diagnostic test, blood-film microscopy and PCR for the diagnosis of malaria infection among febrile children from Korogwe District, Tanzania

    DEFF Research Database (Denmark)

    Mahende, Coline; Ngasala, Billy; Lusingu, John

    2016-01-01

    with fever and/or history of fever in the previous 48 h attending outpatient clinics. Blood samples were collected for identification of Plasmodium falciparum infection using histidine-rich-protein-2 (HRP-2)-based malaria RDT, light microscopy and conventional PCR. Results: A total of 867 febrile patients......Background: Rapid diagnostic tests (RDT) and light microscopy are still recommended for diagnosis to guide the clinical management of malaria despite difficult challenges in rural settings. The performance of these tests may be affected by several factors, including malaria prevalence and intensity...... of transmission. The study evaluated the diagnostic performance of malaria RDT, light microscopy and polymerase chain reaction (PCR) in detecting malaria infections among febrile children at outpatient clinic in Korogwe District, northeastern Tanzania. Methods: The study enrolled children aged 2-59 months...

  11. Quasispecies evolution of the prototypical genotype 1 porcine reproductive and respiratory syndrome virus early during in vivo infection is rapid and tissue specific.

    Science.gov (United States)

    Lu, Zen H; Wang, Xinglong; Wilson, Alison D; Dorey-Robinson, Daniel L W; Archibald, Alan L; Ait-Ali, Tahar; Frossard, Jean-Pierre

    2017-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major infectious threat to the pig industry worldwide. Increasing evidence suggests that microevolution within a quasispecies population can give rise to high sequence heterogeneity in PRRSV; potentially impacting the pathogenicity of the virus. Here, we report on micro-evolutionary events taking place within the viral quasispecies population in lung and lymph node 3 days post infection (dpi) following experimental in vivo infection with the prototypical Lelystad PRRSV (LV). Sequence analysis revealed 16 high frequency single nucleotide variants (SNV) or differences from the reference LV genome which are assumed to be representative of the consensus inoculum genome. Additionally, 49 other low frequency SNVs were also found in the inoculum population. At 3 dpi, a total of 9 and 10 SNVs of varying frequencies could already be detected in the LV population infecting the lung and lymph nodes, respectively. Interestingly, of these, three and four novel SNVs emerged independently in the two respective tissues when compared to the inoculum. The remaining variants, though already present at lower frequencies in the inoculum, were positively selected and their frequency increased within the quasispecies population. Hence, we were able to determine directly from tissues infected with PRRSV the repertoire of genetic variants within the viral quasispecies population. Our data also suggest that microevolution of these variants is rapid and some may be tissue-specific.

  12. Comparative Infection Progress Analysis of Lettuce big-vein virus and Mirafiori lettuce virus in Lettuce Crops by Developed Molecular Diagnosis Techniques.

    Science.gov (United States)

    Navarro, Jose A; Botella, Francisco; Maruhenda, Antonio; Sastre, Pedro; Sánchez-Pina, M Amelia; Pallas, Vicente

    2004-05-01

    ABSTRACT Nonisotopic molecular dot blot hybridization technique and multiplex reverse transcription-polymerase chain reaction assay for the specific detection of Lettuce big-vein virus (LBVV) and Mirafiori lettuce virus (MiLV) in lettuce tissue were developed. Both procedures were suitable for the specific detection of both viruses in a range of naturally infected lettuce plants from various Spanish production areas and seven different cultivars. The study of the distribution of both viruses in the plant revealed that the highest concentration of LBVV and MiLV occurred in roots and old leaves, respectively. LBVV infection progress in a lettuce production area was faster than that observed for MiLV. In spite of different rates of virus infection progress, most lettuce plants became infected with both viruses about 100 days posttransplant. The appearance of both viruses in lettuce crops was preceded by a peak in the concentration of resting spores and zoosporangia of the fungus vector Olpidium brassicae in lettuce roots.

  13. Infection,

    Science.gov (United States)

    1980-10-16

    characteristic in severe gram-negative sepsis. Hypertriglyceridemia results from an increase in hepatic synthesis in combination with diminished activity of...induced stress, and tissue repair (1). The magnitude and type of nutritional losses caused by an infection reflect both the severity and duration of an... several functional forms of nutrient loss must be anticipated. Functional losses are defined as the within-body losses of nutrients due to infection

  14. MALDI-TOF MS performance compared to direct examination, culture, and 16S rDNA PCR for the rapid diagnosis of bone and joint infections.

    Science.gov (United States)

    Lallemand, E; Coiffier, G; Arvieux, C; Brillet, E; Guggenbuhl, P; Jolivet-Gougeon, A

    2016-05-01

    The rapid identification of bacterial species involved in bone and joint infections (BJI) is an important element to optimize the diagnosis and care of patients. The aim of this study was to evaluate the usefulness of matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) for the rapid diagnosis of bone infections, directly on synovial fluid (SF) or on crushed osteoarticular samples (CS). From January to October 2013, we prospectively analyzed 111 osteoarticular samples (bone and joint samples, BJS) from 78 patients in care at the University Hospital of Rennes, France. The diagnosis procedure leading to the sample collection was linked to a suspicion of infection, inflammatory disease, arthritis, or for any bone or joint abnormalities. Standard bacteriological diagnosis and molecular biology analysis [16S rRNA polymerase chain reaction (PCR) and sequencing] were conducted. In addition, analysis by MALDI-TOF MS was performed directly on the osteoarticular samples, as soon as the amount allowed. Culture, which remains the gold standard for the diagnosis of BJI, has the highest sensitivity (85.9 %) and remains necessary to test antimicrobial susceptibility. The 16S rDNA PCR results were positive in the group with positive BJI (28.6 %) and negative in the group without infection. Direct examination remains insensitive (31.7 %) but more effective than MALDI-TOF MS directly on the sample (6.3 %). The specificity was 100 % in all cases, except for culture (74.5 %). Bacterial culture remains the gold standard, especially enrichment in blood bottles. Direct analysis of bone samples with MALDI-TOF MS is not useful, possibly due to the low inoculum of BJS.

  15. H5N1-SeroDetect EIA and rapid test: a novel differential diagnostic assay for serodiagnosis of H5N1 infections and surveillance.

    Science.gov (United States)

    Khurana, Surender; Sasono, Pretty; Fox, Annette; Nguyen, Van Kinh; Le, Quynh Mai; Pham, Quang Thai; Nguyen, Tran Hien; Nguyen, Thanh Liem; Horby, Peter; Golding, Hana

    2011-12-01

    Continuing evolution of highly pathogenic (HP) H5N1 influenza viruses in wild birds with transmission to domestic poultry and humans poses a pandemic threat. There is an urgent need for a simple and rapid serological diagnostic assay which can differentiate between antibodies to seasonal and H5N1 strains and that could provide surveillance tools not dependent on virus isolation and nucleic acid technologies. Here we describe the establishment of H5N1 SeroDetect enzyme-linked immunosorbent assay (ELISA) and rapid test assays based on three peptides in HA2 (488-516), PB1-F2 (2-75), and M2e (2-24) that are highly conserved within H5N1 strains. These peptides were identified by antibody repertoire analyses of H5N1 influenza survivors in Vietnam using whole-genome-fragment phage display libraries (GFPDLs). To date, both platforms have demonstrated high levels of sensitivity and specificity in detecting H5N1 infections (clade 1 and clade 2.3.4) in Vietnamese patients as early as 7 days and up to several years postinfection. H5N1 virus-uninfected individuals in Vietnam and the United States, including subjects vaccinated with seasonal influenza vaccines or with confirmed seasonal virus infections, did not react in the H5N1-SeroDetect assays. Moreover, sera from individuals vaccinated with H5N1 subunit vaccine with moderate anti-H5N1 neutralizing antibody titers did not react positively in the H5N1-SeroDetect ELISA or rapid test assays. The simple H5N1-SeroDetect ELISA and rapid tests could provide an important tool for large-scale surveillance for potential exposure to HP H5N1 strains in both humans and birds.

  16. Non-reactive HIV-1 Rapid Tests after Sustained Viral Suppression Following Antiretroviral Therapy Initiation During Primary Infection.

    Science.gov (United States)

    Stefic, Karl; Novelli, Sophie; Mahjoub, Nadia; Seng, Remonie; Molina, Jean-Michel; Cheneau, Christine; Barin, Francis; Chaix, Marie-Laure; Meyer, Laurence; Delaugerre, Constance

    2018-03-02

    We assessed the impact of early antiretroviral treatment (ART) on HIV antibody detection by rapid tests in 44 individuals after several years of successful ART. HIV self-tests and point-of-care tests were negative in respectively 30% and 7-9% of cases. These data reinforce the message that patients should never be retested after entering HIV care.

  17. Vorinostat positively regulates synaptic plasticity genes expression and spine density in HIV infected neurons: role of nicotine in progression of HIV-associated neurocognitive disorder

    Science.gov (United States)

    2014-01-01

    Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers. PMID:24886748

  18. Incidence of infection in 39-month-old ewes with TMEM154 diplotypes "1 1," "1 3," and "3 3" after natural exposure to ovine progressive pneumonia virus.

    Science.gov (United States)

    Leymaster, K A; Chitko-McKown, C G; Heaton, M P

    2015-01-01

    Production and well-being of sheep and goats in many countries are harmfully impacted by small ruminant lentiviruses (SRLV) that cause incurable, progressive diseases. Susceptibility to ovine progressive pneumonia virus (OPPV), the North American form of SRLV, is influenced by variants of the ovine transmembrane protein 154 gene (TMEM154). The experimental objective was to estimate additive and dominance effects of TMEM154 haplotypes 1 and 3 on susceptibility of breeding ewes to infection after natural exposure to OPPV from birth to 39 mo of age. Sires and dams were heterozygous for TMEM154 haplotypes 1 and 3, producing ewe lambs with diplotypes "1 1," "1 3," and "3 3." These lambs were raised by mature, infected dams to ensure natural, maternal exposure to OPPV. Ewe lambs (n = 108) were kept for breeding and joined an infected flock of ewes to guarantee natural, nonmaternal exposure to OPPV. Ewes were bred to lamb at 1, 2, and 3 yr of age. Serum samples were collected at breeding, 1 mo before lambing and shortly after weaning each year to monitor infection status to 39 mo of age. During the experiment, 9 of the 108 ewes died while uninfected and data collected on these ewes were not analyzed. Infection status of the remaining 99 ewes at 39 mo of age was analyzed using logistic regression procedures. Effects of ewe type of birth, ewe type of rearing, and breed type of dam were not detected (P > 0.10), and the estimated sire variance component was nil. Ewe diplotype affected infection status (P ewes with diplotypes "1 1," "1 3," and "3 3" were 0.10, 0.88, and 0.89, respectively, and confidence intervals for diplotypes "1 3" and "3 3" were distinct from "1 1." Haplotype 3 was completely dominant to haplotype 1 at 39 mo of age. The probability of infection for ewes with either diplotype "1 3" or "3 3" averaged 8.5 times that of ewes with diplotype "1 1." Diplotype "1 3" and "3 3" ewes were highly susceptible to nonmaternal transmission of OPPV, in contrast to

  19. No influence of GB virus C on disease progression in a Danish cohort of HIV-infected men

    DEFF Research Database (Denmark)

    Ryt-Hansen, Rosa; Katzenstein, Terese L; Gerstoft, Jan

    2006-01-01

    Presumed apathogenic viruses have been suggested to play a role in HIV infection. In some cohorts of HIVpositive patients, GB virus C (GBVC) has been associated with prolonged survival and time to AIDS. We set out to address whether GBVC infection had any influence on survival in a cohort of 112...

  20. Carbapenem-resistant Klebsiella pneumoniae colonization in pediatric and neonatal intensive care units: risk factors for progression to infection.

    Science.gov (United States)

    Akturk, Hacer; Sutcu, Murat; Somer, Ayper; Aydın, Derya; Cihan, Rukiye; Ozdemir, Aslı; Coban, Asuman; Ince, Zeynep; Citak, Agop; Salman, Nuran

    2016-01-01

    Little is known about factors associated with carbapenem-resistant Klebsiella pneumoniae infections in pediatric patients, who are initally colonized with carbapenem-resistant Klebsiella pneumoniae. A retrospective case-control study was conducted involving pediatric and neonatal intensive care units throughout a five-year period (January 2010-December 2014). Clinical and microbiological data were extracted from Hospital Infection Control Committee reports and patients' medical records. Risk factors were assessed in carbapenem-resistant Klebsiella pneumoniae colonized patients who developed subsequent systemic infection (cases) and compared to carbapenem-resistant Klebsiella pneumoniae colonized patients who did not develop infection (controls). Throughout the study period, 2.6% of patients admitted to neonatal intensive care units and 3.6% of patients admitted to pediatric intensive care units had become colonized with carbapenem-resistant Klebsiella pneumoniae. After a mean of 10.6±1.9 days (median: 7 days, range: 2-38 days) following detection of colonization, 39.0% of the carbapenem-resistant Klebsiella pneumoniae colonized patients in pediatric intensive care units and 18.1% of carbapenem-resistant Klebsiella pneumoniae colonized patients in neonatal intensive care units developed systemic carbapenem-resistant Klebsiella pneumoniae infection. Types of systemic carbapenem-resistant Klebsiella pneumoniae infections included bacteremia (n=15, 62.5%), ventilator-associated pneumonia (n=4, 16.6%), ventriculitis (n=2, 8.3%), intraabdominal infections (n=2, 8.3%), and urinary tract infection (n=1, 4.1%). A logistic regression model including parameters found significant in univariate analysis of carbapenem resistant Klebsiella pneumoniae colonization and carbapenem resistant Klebsiella pneumoniae infection groups revealed underlying metabolic disease (OR: 10.1; 95% CI: 2.7-37.2), previous carbapenem use (OR: 10.1; 95% CI: 2.2-40.1), neutropenia (OR: 13.8; 95% CI: 3

  1. Effects of CCR5-delta32 and CCR2-64I alleles on disease progression of perinatally HIV-1-infected children: an international meta-analysis.

    Science.gov (United States)

    Ioannidis, John P A; Contopoulos-Ioannidis, Despina G; Rosenberg, Philip S; Goedert, James J; De Rossi, Anita; Espanol, Teresa; Frenkel, Lisa; Mayaux, Marie-Jeanne; Newell, Marie-Louise; Pahwa, Savita G; Rousseau, Christine; Scarlatti, Gabriella; Sei, Shizuko; Sen, Luisa; O'Brien, Thomas R

    2003-07-25

    Among perinatally infected children, the effects of certain alleles of the CCR5 and CCR2 genes on the rate of disease progression remain unclear. We addressed the effects of CCR5-delta32 and CCR2-64I in an international meta-analysis. Genotype data were contributed from 10 studies with 1317 HIV-1-infected children (7263 person-years of follow-up). Time-to-event analyses were performed stratified by study and racial group. Endpoints included progression to clinical AIDS, death, and death after the diagnosis of clinical AIDS. The time-dependence of the genetic effects was specifically investigated. There was large heterogeneity in the observed rates of disease progression between different cohorts. For progression to clinical AIDS, both CCR5-delta32 and CCR2-64I showed overall non-significant trends for protection [hazard ratios 0.84, 95% confidence interval (CI) 0.58-1.23; and 0.87, 95% CI 0.67-1.14, respectively]. However, analyses of survival showed statistically significant time-dependence. No deaths occurred among CCR5-delta32 carriers in the first 3 years of life, whereas there was no protective effect (hazard ratio 0.95; 95% CI 0.43-2.10) in later years (P=0.01 for the time-dependent model). For CCR2-64I, the hazard ratio for death was 0.69 (95% CI 0.39-1.21) in the first 6 years of life and 2.56 (95% CI 1.26-5.20) in subsequent years (P<0.01 for the time-dependent model). CCR5-delta32 and CCR2-64I offered no clear protection after clinical AIDS had developed. The CCR5-delta32 and CCR2-64I alleles are associated with a decreased risk of death among perinatally infected children, but only for the first years of life.

  2. First report of two rapid-onset fatal infections caused by a newly emerging hypervirulent K. Pneumonia ST86 strain of serotype K2 in China.

    Science.gov (United States)

    Zhang, Yibo; Sun, Jingyong; Mi, Chenrong; Li, Wenhui; Zhao, Shengyuan; Wang, Qun; Shi, Dake; Liu, Luo; Ding, Bingyu; Chang, Yung-Fu; Guo, Hongxiong; Guo, XiaoKui; Li, Qingtian; Zhu, Yongzhang

    2015-01-01

    Here, we present the first report of one suspected dead case and two confirmed rapid-onset fatal infections caused by a newly emerging hypervirulent Klebsiella pneumoniae ST86 strain of serotype K2. The three cases occurred in a surgery ward during 2013 in Shanghai, China. A combination of multilocus sequence typing, pulsed-field gel electrophoresis, phenotypic and PCR tests for detecting virulence factors (VFs) was used to identify the isolates as K2 ST86 strains with common VFs, including Aerobactin and rmpA. Furthermore, the two K2 ST86 strains additionally harbored a distinct VF kfu (responsible for iron uptake system), which commonly existed in invasive K1 strains only. Thus, the unusual presence of both K1 and K2 VFs in the lethal ST86 strain might further enhance its hypervirulence and cause rapid onset of a life-threatening infection. Nevertheless, despite the administration of a combined antibiotic treatment, these three patients all died within 24 h of acute onset, thereby highlighting that the importance of early diagnosis to determine whether the ST86 strains harbor key K2 VF and unusual K1 kfu and whether patients should receive a timely and targeted antibiotic therapy to prevent ST86 induced fatal pneumonia. Finally, even though these patients are clinically improved, keeping on with oral antibiotic treatment for additional 2-3 weeks will be also vital for successfully preventing hvKP reinfection or relapse.

  3. Probing genetic control of swine responses to PRRSV infection: current progress of the PRRS host genetics consortium

    Directory of Open Access Journals (Sweden)

    Lunney Joan K

    2011-06-01

    Full Text Available Abstract Background Understanding the role of host genetics in resistance to porcine reproductive and respiratory syndrome virus (PRRSV infection, and the effects of PRRS on pig health and related growth, are goals of the PRRS Host Genetics Consortium (PHGC. Methods The project uses a nursery pig model to assess pig resistance/susceptibility to primary PRRSV infection. To date, 6 groups of 200 crossbred pigs from high health farms were donated by commercial sources. After acclimation, the pigs were infected with PRRSV in a biosecure facility and followed for 42 days post infection (dpi. Blood samples were collected at 0, 4, 7, 10, 14, 21, 28, 35 and 42 dpi for serum and whole blood RNA gene expression analyses; weekly weights were recorded for growth traits. All data have been entered into the PHGC relational database. Genomic DNAs from all PHGC1-6 pigs were prepared and genotyped with the Porcine SNP60 SNPchip. Results Results have affirmed that all challenged pigs become PRRSV infected with peak viremia being observed between 4-21 dpi. Multivariate statistical analyses of viral load and weight data have identified PHGC pigs in different virus/weight categories. Sera are now being compared for factors involved in recovery from infection, including speed of response and levels of immune cytokines. Genome-wide association studies (GWAS are underway to identify genes and chromosomal locations that identify PRRS resistant/susceptible pigs and pigs able to maintain growth while infected with PRRSV. Conclusions Overall, the PHGC project will enable researchers to discover and verify important genotypes and phenotypes that predict resistance/susceptibility to PRRSV infection. The availability of PHGC samples provides a unique opportunity to continue to develop deeper phenotypes on every PRRSV infected pig.

  4. Toxoplasma gondii infection shifts dendritic cells into an amoeboid rapid migration mode encompassing podosome dissolution, secretion of TIMP-1, and reduced proteolysis of extracellular matrix.

    Science.gov (United States)

    Ólafsson, Einar B; Varas-Godoy, Manuel; Barragan, Antonio

    2018-03-01

    Dendritic cells (DCs) infected by Toxoplasma gondii rapidly acquire a hypermigratory phenotype that promotes systemic parasite dissemination by a "Trojan horse" mechanism in mice. Recent paradigms of leukocyte migration have identified the amoeboid migration mode of DCs as particularly suited for rapid locomotion in extracellular matrix and tissues. Here, we have developed a microscopy-based high-throughput approach to assess motility and matrix degradation by Toxoplasma-challenged murine and human DCs. DCs challenged with T. gondii exhibited dependency on metalloproteinase activity for hypermotility and transmigration but, strikingly, also dramatically reduced pericellular proteolysis. Toxoplasma-challenged DCs up-regulated expression and secretion of tissue inhibitor of metalloproteinases-1 (TIMP-1) and their supernatants impaired matrix degradation by naïve DCs and by-stander DCs dose dependently. Gene silencing of TIMP-1 by short hairpin RNA restored matrix degradation activity in Toxoplasma-infected DCs. Additionally, dissolution of podosome structures in parasitised DCs coincided with abrogated matrix degradation. Toxoplasma lysates inhibited pericellular proteolysis in a MyD88-dependent fashion whereas abrogated proteolysis persevered in Toxoplasma-infected MyD88-deficient DCs. This indicated that both TLR/MyD88-dependent and TLR/MyD88-independent signalling pathways mediated podosome dissolution and the abrogated matrix degradation. We report that increased TIMP-1 secretion and cytoskeletal rearrangements encompassing podosome dissolution are features of Toxoplasma-induced hypermigration of DCs with an impact on matrix degradation. Jointly, the data highlight how an obligate intracellular parasite orchestrates key regulatory cellular processes consistent with non-proteolytic amoeboid migration of the vehicle cells that facilitate its dissemination. © 2017 John Wiley & Sons Ltd.

  5. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Directory of Open Access Journals (Sweden)

    Genevieve E Martin

    Full Text Available Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women.This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+ T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays.HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001, soluble CD163 (sCD163, p = 0.001, sCD14 (p = 0.022, neopterin (p = 0.029 and an increased proportion of CD16(+ monocytes (p = 0.009 compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+ monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002 suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+ T lymphocytes.Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  6. Age-associated changes in monocyte and innate immune activation markers occur more rapidly in HIV infected women.

    Science.gov (United States)

    Martin, Genevieve E; Gouillou, Maelenn; Hearps, Anna C; Angelovich, Thomas A; Cheng, Allen C; Lynch, Fiona; Cheng, Wan-Jung; Paukovics, Geza; Palmer, Clovis S; Novak, Richard M; Jaworowski, Anthony; Landay, Alan L; Crowe, Suzanne M

    2013-01-01

    Aging is associated with immune dysfunction and the related development of conditions with an inflammatory pathogenesis. Some of these immune changes are also observed in HIV infection, but the interaction between immune changes with aging and HIV infection are unknown. Whilst sex differences in innate immunity are recognized, little research into innate immune aging has been performed on women. This cross-sectional study of HIV positive and negative women used whole blood flow cytometric analysis to characterize monocyte and CD8(+) T cell subsets. Plasma markers of innate immune activation were measured using standard ELISA-based assays. HIV positive women exhibited elevated plasma levels of the innate immune activation markers CXCL10 (p<0.001), soluble CD163 (sCD163, p = 0.001), sCD14 (p = 0.022), neopterin (p = 0.029) and an increased proportion of CD16(+) monocytes (p = 0.009) compared to uninfected controls. Levels of the innate immune aging biomarkers sCD163 and the proportion of CD16(+) monocytes were equivalent to those observed in HIV negative women aged 14.5 and 10.6 years older, respectively. CXCL10 increased with age at an accelerated rate in HIV positive women (p = 0.002) suggesting a synergistic effect between HIV and aging on innate immune activation. Multivariable modeling indicated that age-related increases in innate immune biomarkers CXCL10 and sCD163 are independent of senescent changes in CD8(+) T lymphocytes. Quantifying the impact of HIV on immune aging reveals that HIV infection in women confers the equivalent of a 10-14 year increase in the levels of innate immune aging markers. These changes may contribute to the increased risk of inflammatory age-related diseases in HIV positive women.

  7. Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN.

    Science.gov (United States)

    Montoya, Maria; Edwards, Matthew J; Reid, Delyth M; Borrow, Persephone

    2005-02-15

    In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8+ T cells ex vivo. Conventional (CD11chigh CD8+ and CD4+) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping approximately 2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11clowB220+) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type 1 IFN-independent pathways for the functional maturation of DCs during LCMV infection.

  8. Pregnancy and HIV infection

    Directory of Open Access Journals (Sweden)

    Mete Sucu

    2016-12-01

    Full Text Available The management of Human Immunodeficiency Virus (HIV infection is progressing rapidly. In developed countries, the perinatal transmission rates have decreased from 20-30% to 1-2% with the use of antiretroviral therapy and cesarean section. Interventions for the prevention of prenatal transmission has made the prenatal care of pregnant patients with HIV infection more complex. Rapid development of standard care and continuing increase in the distribution of HIV infection has required clinicians taking care of pregnants to have current information. Therefore, in our review we aimed to summarize the prenatal course, treatment and preventive methods for perinatal transmission of HIV. [Archives Medical Review Journal 2016; 25(4.000: 522-535

  9. Therapy-refractory Panton Valentine Leukocidin-positive community-acquired methicillin-sensitive Staphylococcus aureus sepsis with progressive metastatic soft tissue infection: a case report

    Directory of Open Access Journals (Sweden)

    Schefold Joerg C

    2007-12-01

    Full Text Available Abstract We report a case of fulminant multiple organ failure including the Acute Respiratory Distress Syndrome (ARDS, haemodynamic, and renal failure due to community-acquired methicillin-sensitive Panton Valentine Leukocidin (PVL positive spa-type 284 (ST121 Staphylococcus aureus septic shock. The patient's first clinical symptom was necrotizing pneumonia. Despite organism-sensitive triple antibiotic therapy with linezolid, imipenem and clindamycin from the first day of treatment, progressive abscess formation in multiple skeletal muscles was observed. As a result, repeated surgical interventions became necessary. Due to progressive soft tissue infection, the anti-microbial therapy was changed to a combination of clindamycin and daptomycin. Continued surgical and antimicrobial therapy finally led to a stabilisation of the patients' condition. The clinical course of our patient underlines the existence of a "PVL-syndrome" which is independent of in vitro Staphylococcus aureus susceptibility. The PVL-syndrome should not only be considered in patients with soft tissue or bone infection, but also in patients with pneumonia. Such a condition, which may easily be mistaken for uncomplicated pneumonia, should be treated early, aggressively and over a long period of time in order to avoid relapsing infection.

  10. Single tube multiplex real-time PCR for the rapid detection of herpesvirus infections of the central nervous system.

    Science.gov (United States)

    Sankuntaw, Nipaporn; Sukprasert, Saovaluk; Engchanil, Chulapan; Kaewkes, Wanlop; Chantratita, Wasun; Pairoj, Vantanit; Lulitanond, Viraphong

    2011-01-01

    Human herpesvirus infection of immunocompromised hosts may lead to central nervous system (CNS) infection and diseases. In this study, a single tube multiplex real-time PCR was developed for the detection of five herpesviruses (HSV-1, HSV-2, VZV, EBV and CMV) in clinical cerebrospinal fluid (CSF) specimens. Two primer pairs specific for the herpesvirus polymerase gene and five hybridization probe pairs for the specific identification of the herpesvirus types were used in a LightCycler multiplex real-time PCR. A singleplex real-time PCR was first optimized and then applied to the multiplex real-time PCR. The singleplex and multiplex real-time PCRs showed no cross-reactivity. The sensitivity of the singleplex real-time PCR was 1 copy per reaction for each herpesvirus, while that of the multiplex real-time PCR was 1 copy per reaction for HSV-1 and VZV and 10 copies per reaction for HSV-2, EBV and CMV. Intra and inter-assay variations of the single tube multiplex assay were in the range of 0.02%-3.67% and 0.79%-4.35%, respectively. The assay was evaluated by testing 62 clinical CSF samples and was found to have equivalent sensitivity, specificity and agreement as the routine real-time PCR, but reducing time, cost and amount of used sample. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Development of a loop-mediated isothermal amplification method for rapid mass-screening of sand flies for Leishmania infection.

    Science.gov (United States)

    Nzelu, Chukwunonso O; Gomez, Eduardo A; Cáceres, Abraham G; Sakurai, Tatsuya; Martini-Robles, Luiggi; Uezato, Hiroshi; Mimori, Tatsuyuki; Katakura, Ken; Hashiguchi, Yoshihisa; Kato, Hirotomo

    2014-04-01

    Entomological monitoring of Leishmania infection in leishmaniasis endemic areas offers epidemiologic advantages for predicting the risk and expansion of the disease, as well as evaluation of the effectiveness of control programs. In this study, we developed a highly sensitive loop-mediated isothermal amplification (LAMP) method for the mass screening of sand flies for Leishmania infection based on the 18S rRNA gene. The LAMP technique could detect 0.01 parasites, which was more sensitive than classical PCR. The method was robust and could amplify the target DNA within 1h from a crude sand fly template without DNA purification. Amplicon detection could be accomplished by the newly developed colorimetric malachite green (MG)--mediated naked eye visualization. Pre-addition of MG to the LAMP reaction solution did not inhibit amplification efficiency. The field applicability of the colorimetric MG-based LAMP assay was demonstrated with 397 field-caught samples from the endemic areas of Ecuador and eight positive sand flies were detected. The robustness, superior sensitivity, and ability to produce better visual discriminatory reaction products than existing LAMP fluorescence and turbidity assays indicated the field potential usefulness of this new method for surveillance and epidemiological studies of leishmaniasis in developing countries. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

    Directory of Open Access Journals (Sweden)

    Cristian Koepfli

    Full Text Available When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((molFOB, i.e. the number of genetically distinct blood-stage infections over time, and compared it to previously reported values for P. falciparum.P. vivax (molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years.On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR = 1.99, 95% confidence interval (CI95 [1.80, 2.19], (molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001 compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02.P. vivax (molFOB is considerably higher than P. falciparum (molFOB (5.5 clones/child/year-at-risk. The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

  13. Progressive Multifocal Leukoencephalopathy

    Science.gov (United States)

    ... SEARCH Definition Treatment Prognosis Clinical Trials Organizations Publications Definition Progressive multifocal leukoencephalopathy (PML) is a disease of the white matter of the brain, caused by a virus infection ...

  14. Using automated medical records for rapid identification of illness syndromes (syndromic surveillance: the example of lower respiratory infection

    Directory of Open Access Journals (Sweden)

    Dashevsky Inna

    2001-10-01

    Full Text Available Abstract Background Gaps in disease surveillance capacity, particularly for emerging infections and bioterrorist attack, highlight a need for efficient, real time identification of diseases. Methods We studied automated records from 1996 through 1999 of approximately 250,000 health plan members in greater Boston. Results We identified 152,435 lower respiratory infection illness visits, comprising 106,670 episodes during 1,143,208 person-years. Three diagnoses, cough (ICD9CM 786.2, pneumonia not otherwise specified (ICD9CM 486 and acute bronchitis (ICD9CM 466.0 accounted for 91% of these visits, with expected age and sex distributions. Variation of weekly occurrences corresponded closely to national pneumonia and influenza mortality data. There was substantial variation in geographic location of the cases. Conclusion This information complements existing surveillance programs by assessing the large majority of episodes of illness for which no etiologic agents are identified. Additional advantages include: a sensitivity, uniformity and efficiency, since detection of events does not depend on clinicians' to actively report diagnoses, b timeliness, the data are available within a day of the clinical event; and c ease of integration into automated surveillance systems. These features facilitate early detection of conditions of public health importance, including regularly occurring events like seasonal respiratory illness, as well as unusual occurrences, such as a bioterrorist attack that first manifests as respiratory symptoms. These methods should also be applicable to other infectious and non-infectious conditions. Knowledge of disease patterns in real time may also help clinicians to manage patients, and assist health plan administrators in allocating resources efficiently.

  15. Evaluation of the effect of short-term treatment with the integrase inhibitor raltegravir (Isentress) on the course of progressive feline leukemia virus infection.

    Science.gov (United States)

    Boesch, Andrea; Cattori, Valentino; Riond, Barbara; Willi, Barbara; Meli, Marina L; Rentsch, Katharina M; Hosie, Margaret J; Hofmann-Lehmann, Regina; Lutz, Hans

    2015-02-25

    Cats persistently infected with the gammaretrovirus feline leukemia virus (FeLV) are at risk to die within months to years from FeLV-associated disease, such as immunosuppression, anemia or lymphoma/leukemia. The integrase inhibitor raltegravir has been demonstrated to reduce FeLV replication in vitro. The aim of the present study was to investigate raltegravir in vivo for its safety and efficacy to suppress FeLV replication. The safety was tested in three naïve specified pathogen-free (SPF) cats during a 15 weeks treatment period (initially 20mg then 40mg orally b.i.d.). No adverse effects were noted. The efficacy was tested in seven persistently FeLV-infected SPF cats attained from 18 cats experimentally exposed to FeLV-A/Glasgow-1. The seven cats were treated during nine weeks (40mg then 80mg b.i.d.). Raltegravir was well tolerated even at the higher dose. A significant decrease in plasma viral RNA loads (∼5×) was found; however, after treatment termination a rebound effect was observed. Only one cat developed anti-FeLV antibodies and viral RNA loads remained decreased after treatment termination. Of note, one of the untreated FeLV-A infected cats developed fatal FeLV-C associated anemia within 5 weeks of FeLV-A infection. Moreover, progressive FeLV infection was associated with significantly lower enFeLV loads prior to infection supporting that FeLV susceptibility may be related to the genetic background of the cat. Overall, our data demonstrate the ability of raltegravir to reduce viral replication also in vivo. However, no complete control of viremia was achieved. Further investigations are needed to find an optimized treatment against FeLV. (250 words). Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Progression of hepatitis C in the haemophiliac population in Ireland, after 30 years of infection in the pre-DAA treatment era.

    Science.gov (United States)

    Murphy, N; O'Mahony, B; Flanagan, P; Noone, D; White, B; Bergin, C; Norris, S; Thornton, L

    2017-09-01

    Prior to the introduction of viral inactivation of factor concentrates and screening of blood, 225 people with haemophilia became infected with hepatitis C (HCV) in Ireland. Our aim was to assess liver disease progression and mortality in this population after 30 years of infection. Demographic and clinical data were collected from medical records in five hepatology units and one infectious disease unit retrospectively in 2005, and on four subsequent occasions. The participation rate was 73% (165/225). Eighty three percent of patients, who had been tested for RNA (n = 106/128), developed chronic HCV infection. Thirty four percent were co-infected with HIV. All-cause mortality, after approximately 30 years of infection with chronic HCV, was 44% in HIV positive patients and 29% in HIV negative patients. Liver-related mortality was 12.5% and did not vary significantly by HIV status. Thirty seven percent of patients had developed advanced liver disease, including 20% with cirrhosis and 9% with hepatocellular carcinoma. In the pre-interferon-free direct acting antivirals era, 57% (n = 60/106) of patients were treated for HCV, 65% of whom achieved a sustained virological response. Successfully treated patients had few adverse liver outcomes. After 30 years of infection, 40% of the patients who had evidence of chronic HCV had developed advanced liver disease, such as cirrhosis and HCC, or had died from liver-related causes. This proportion is high relative to similar international cohorts despite good anti-HCV treatment uptake and responses. © 2017 John Wiley & Sons Ltd.

  17. Incidence, clinical presentation, and outcome of progressive multifocal leukoencephalopathy in HIV-infected patients during the highly active antiretroviral therapy era: a nationwide cohort study

    DEFF Research Database (Denmark)

    Engsig, Frederik Neess; Hansen, Ann-Brit Eg; Omland, Lars Haukali

    2009-01-01

    BACKGROUND: Human immunodeficiency virus (HIV) infection predisposes to progressive multifocal leukoencephalopathy (PML). Here, we describe the incidence, presentation, and prognosis of PML in HIV-1-infected patients during the period before highly active antiretroviral therapy (HAART) (1995...... at presentation and follow-up. RESULTS: Among 4,649 patients, we identified 47 patients with PML. The incidence rates were 3.3, 1.8, and 1.3 cases per 1000 person-years at risk in 1995-1996, 1997-1999, and 2000-2006, respectively. The risk of PML was significantly associated with low CD4(+) cell count, and 47......% of cases were diagnosed by means of brain biopsy or polymerase chain reaction analysis for JC virus. The predominant neurological symptoms at presentation were coordination disturbance, cognitive defects, and limb paresis. Thirty-five patients died; the median survival time was 0.4 years (95% confidence...

  18. Screening for transfusion transmissible infections using rapid diagnostic tests in Africa: a potential hazard to blood safety?

    Science.gov (United States)

    Prugger, C.; Laperche, S.; Murphy, E. L.; Bloch, E. M.; Kaidarova, Z.; Tafflet, M.; Lefrère, J.-J.; Jouven, X.

    2016-01-01

    Rapid diagnostic tests (RDTs) are routinely used in African blood centres. We analysed data from two cross-sectional studies representing 95 blood centres in 29 African countries. Standardized panels of sera containing varying concentrations of anti-human immunodeficiency virus (HIV) antibodies (Ab), hepatitis B virus antigen (HBsAg) and antihepatitis C virus (HCV) Ab were screened using routine operational testing procedures at the centres. Sensitivity of detection using RDTs was high for HIV Ab-positive samples, but low for intermediately HBsAg (51·5%) and HCV Ab (40·6%)-positive samples. These findings suggest that current RDT use in Africa could pose a hazard to blood safety. PMID:26646317

  19. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Directory of Open Access Journals (Sweden)

    Swee Lin G Chen Yi Mei

    Full Text Available Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR in people with chronic hepatitis C (CHC infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart.CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM using transient elastography [FibroScan] were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa or advanced (METAVIR F3-4/ LSM >9.5 kPa. The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2 to advanced fibrosis at follow-up liver fibrosis assessment.131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62 years with median estimated duration of infection 33-years (IQR 29-38. At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17. 109 (83% participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002. The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343. However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F

  20. Sustained virological response halts fibrosis progression: A long-term follow-up study of people with chronic hepatitis C infection.

    Science.gov (United States)

    Chen Yi Mei, Swee Lin G; Thompson, Alexander J; Christensen, Britt; Cunningham, Georgina; McDonald, Lucy; Bell, Sally; Iser, David; Nguyen, Tin; Desmond, Paul V

    2017-01-01

    Long-term follow-up studies validating the clinical benefit of sustained virological response (SVR) in people with chronic hepatitis C (CHC) infection are lacking. Our aim was to identify rates and predictors of liver fibrosis progression in a large, well characterized cohort of CHC patients in whom paired liver fibrosis assessments were performed more than 10 years apart. CHC patients who had undergone a baseline liver biopsy pre-2004 and a follow up liver fibrosis assessment more than 10 years later (biopsy or liver stiffness measurement (LSM) using transient elastography [FibroScan]) were identified. Subjects who had undergone a baseline liver biopsy but had no follow up fibrosis assessment were recalled for LSM. Fibrosis was categorised as mild-moderate (METAVIR F0-2 / LSM result of ≤ 9.5 kPa) or advanced (METAVIR F3-4/ LSM >9.5 kPa). The primary objective was to assess the association between SVR and the rate of liver fibrosis progression over at least 10 years, defined as an increase from mild-moderate fibrosis at baseline liver biopsy (METAVIR F0-2) to advanced fibrosis at follow-up liver fibrosis assessment. 131 subjects were included in this analysis: 69% male, 82% Caucasian, 60% G1 HCV, 25% G3 HCV. The median age at F/U fibrosis staging was 57 (IQR 54-62) years with median estimated duration of infection 33-years (IQR 29-38). At F/U, liver fibrosis assessment was performed by LSM in 86% and liver biopsy in 14%. The median period between fibrosis assessments was 14-years (IQR 12-17). 109 (83%) participants had received interferon-based antiviral therapy. 40% attained SVR. At F/U, there was a significant increase in the proportion of subjects with advanced liver fibrosis: 27% at baseline vs. 46% at F/U (p = 0.002). The prevalence of advanced fibrosis did not change among subjects who attained SVR, 30% at B/L vs 25% at F/U (p = 0.343). However, advanced fibrosis became more common at F/U among subjects with persistent viremia: 10% at B/L vs 31% at F/U (p

  1. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    Science.gov (United States)

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (Paged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; Page and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  2. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease

    Energy Technology Data Exchange (ETDEWEB)

    Kamdar, Karishma; Khakpour, Samira; Chen, Jingyu; Leone, Vanessa; Brulc, Jennifer; Mangatu, Thomas; Antonopoulos, Dionysios A.; Chang, Eugene B; Kahn, Stacy A.; Kirschner, Barbara S; Young, Glenn; DePaolo, R. William

    2016-01-13

    Chronic inflammatory disorders are thought to arise due to an interplay between predisposing host genetics and environmental factors. For example, the onset of inflammatory bowel disease is associated with enteric proteobacterial infection, yet the mechanistic basis for this association is unclear. We have shown previously that genetic defiency in TLR1 promotes acute enteric infection by the proteobacteria Yersinia enterocolitica. Examining that model further, we uncovered an altered cellular immune response that promotes the recruitment of neutrophils which in turn increases metabolism of the respiratory electron acceptor tetrathionate by Yersinia. These events drive permanent alterations in anti-commensal immunity, microbiota composition, and chronic inflammation, which persist long after Yersinia clearence. Deletion of the bacterial genes involved in tetrathionate respiration or treatment using targeted probiotics could prevent microbiota alterations and inflammation. Thus, acute infection can drive long term immune and microbiota alterations leading to chronic inflammatory disease in genetically predisposed individuals.

  3. Merkel cell polyomavirus IgG antibody levels are associated with progression to AIDS among HIV-infected individuals.

    Science.gov (United States)

    Vahabpour, Rouhollah; Nasimi, Maryam; Naderi, Niloofar; Salehi-Vaziri, Mostafa; Mohajel, Nasir; Sadeghi, Farzin; Keyvani, Hossein; Monavari, Seyed Hamidreza

    2017-04-01

    The association of Merkel cell polyomavirus (MCP y V) with Merkel cell carcinoma (MCC) in immunocompromised individuals has been revealed in a number of surveys. The study of MCP y V specific antibody titers and viral loads in such patients has a great attraction for research groups interested in viral reactivation. In this cross-sectional study to evaluate MCP y V antibody titer, DNA prevalence and viral load in peripheral blood mononuclear cells (PBMCs), we examined 205 HIV-1 infected patients and 100 un-infected controls. The HIV-1 infected patients divided into two groups (HIV/AIDS and non-AIDS) according to their CD4 status. Total IgG antibody titer against MCP y V was analyzed by virus like particle (VLP)-based enzyme linked immunosorbent assay (ELISA). Presence of MCP y V-DNA in subject's PBMCs was examined by quantitative real-time PCR assay. Levels of anti-MCP y V IgG in HIV/AIDS patients were significantly higher than those in non-AIDS HIV-infected and control subjects (p value = <0.001). The prevalence rate of MCP y V-DNA in PBMCs of HIV/AIDS, non-AIDS HIV-infected and un-infected controls were 17%, 16%, and 14% respectively. The MCP y V viral load among the groups ranged between 0.15 to 2.9 copies/10 3 cells (median, 1.9 copies/10 3 cells), with no significant difference between the studied populations (p value = 0.3).

  4. Mycobacterium oryzae sp. nov., a scotochromogenic, rapidly growing species is able to infect human macrophage cell line.

    Science.gov (United States)

    Ramaprasad, E V V; Rizvi, A; Banerjee, S; Sasikala, Ch; Ramana, Ch V

    2016-11-01

    Gram-stain-positive, acid-fast-positive, rapidly growing, rod-shaped bacteria (designated as strains JC290T, JC430 and JC431) were isolated from paddy cultivated soils on the Western Ghats of India. Phylogenetic analysis placed the three strains among the rapidly growing mycobacteria, being most closely related to Mycobacterium tokaiense 47503T (98.8 % 16S rRNA gene sequence similarity), Mycobacterium murale MA112/96T (98.8 %) and a few other Mycobacterium species. The level of DNA-DNA reassociation of the three strains with M. tokaiense DSM 44635T was 23.4±4 % (26.1±3 %, reciprocal analysis) and 21.4±2 % (22.1±4 %, reciprocal analysis). The three novel strains shared >99.9 % 16S rRNA gene sequence similarity and DNA-DNA reassociation values >85 %. Furthermore, phylogenetic analysis based on concatenated sequences (3071 bp) of four housekeeping genes (16S rRNA, hsp65, rpoB and sodA) revealed that strain JC290T is clearly distinct from all other Mycobacteriumspecies. The three strains had diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositolmannosides, unidentified phospholipids, unidentified glycolipids and an unidentified lipid as polar lipids. The predominant isoprenoid quinone for all three strains was MK-9(H2). Fatty acids were C17 : 1ω7c, C16 : 0, C18 : 1ω9c, C16 : 1ω7c/C16 : 1ω6c and C19 : 1ω7c/C19 : 1ω6c for all the three strains. On the basis of phenotypic, chemotaxonomic and phylogenetic data, it was concluded that strains JC290T, JC430 and JC431 are members of a novel species within the genus Mycobacterium and for which the name Mycobacterium oryzae sp. nov. is proposed. The type strain is JC290T (=KCTC 39560T=LMG 28809T).

  5. Rapid tests and urine sampling techniques for the diagnosis of urinary tract infection (UTI) in children under five years: a systematic review.

    Science.gov (United States)

    Whiting, Penny; Westwood, Marie; Watt, Ian; Cooper, Julie; Kleijnen, Jos

    2005-04-05

    Urinary tract infection (UTI) is one of the most common sources of infection in children under five. Prompt diagnosis and treatment is important to reduce the risk of renal scarring. Rapid, cost-effective, methods of UTI diagnosis are required as an alternative to culture. We conducted a systematic review to determine the diagnostic accuracy of rapid tests for detecting UTI in children under five years of age. The evidence supports the use of dipstick positive for both leukocyte esterase and nitrite (pooled LR+ = 28.2, 95% CI: 17.3, 46.0) or microscopy positive for both pyuria and bacteriuria (pooled LR+ = 37.0, 95% CI: 11.0, 125.9) to rule in UTI. Similarly dipstick negative for both LE and nitrite (Pooled LR- = 0.20, 95% CI: 0.16, 0.26) or microscopy negative for both pyuria and bacteriuria (Pooled LR- = 0.11, 95% CI: 0.05, 0.23) can be used to rule out UTI. A test for glucose showed promise in potty-trained children. However, all studies were over 30 years old. Further evaluation of this test may be useful. Dipstick negative for both LE and nitrite or microscopic analysis negative for both pyuria and bacteriuria of a clean voided urine, bag, or nappy/pad specimen may reasonably be used to rule out UTI. These patients can then reasonably be excluded from further investigation, without the need for confirmatory culture. Similarly, combinations of positive tests could be used to rule in UTI, and trigger further investigation.

  6. A novel pre-clinical murine model to study the life cycle and progression of cervical and anal papillomavirus infections.

    Directory of Open Access Journals (Sweden)

    Nancy M Cladel

    Full Text Available Papillomavirus disease and associated cancers remain a significant health burden in much of the world. The current protective vaccines, Gardasil and Cervarix, are expensive and not readily available to the underprivileged. In addition, the vaccines have not gained wide acceptance in the United States nor do they provide therapeutic value. Papillomaviruses are strictly species specific and thus human viruses cannot be studied in an animal host. An appropriate model for mucosal disease has long been sought. We chose to investigate whether the newly discovered mouse papillomavirus, MmuPV1, could infect mucosal tissues in Foxn1nu/Foxn1nu mice.The vaginal and anal canals of Foxn1nu/Foxn1nu mice were gently abraded using Nonoxynol-9 and "Doctor's BrushPicks" and MmuPV1 was delivered into the vaginal tract or the anal canal.Productive vaginal, cervical and anal infections developed in all mice. Vaginal/cervical infections could be monitored by vaginal lavage. Dysplasias were evident in all animals.Anogenital tissues of a common laboratory mouse can be infected with a papillomavirus unique to that animal. This observation will pave the way for fundamental virological and immunological studies that have been challenging to carry out heretofore due to lack of a suitable model system.

  7. A protein microarray for the rapid screening of patients suspected of infection with various food-borne helminthiases.

    Directory of Open Access Journals (Sweden)

    Jia-Xu Chen

    Full Text Available BACKGROUND: Food-borne helminthiases (FBHs have become increasingly important due to frequent occurrence and worldwide distribution. There is increasing demand for developing more sensitive, high-throughput techniques for the simultaneous detection of multiple parasitic diseases due to limitations in differential clinical diagnosis of FBHs with similar symptoms. These infections are difficult to diagnose correctly by conventional diagnostic approaches including serological approaches. METHODOLOGY/PRINCIPAL FINDINGS: In this study, antigens obtained from 5 parasite species, namely Cysticercus cellulosae, Angiostrongylus cantonensis, Paragonimus westermani, Trichinella spiralis and Spirometra sp., were semi-purified after immunoblotting. Sera from 365 human cases of helminthiasis and 80 healthy individuals were assayed with semi-purified antigens by both a protein microarray and the enzyme-linked immunosorbent assay (ELISA. The sensitivity, specificity and simplicity of each test for the end-user were evaluated. The specificity of the tests ranged from 97.0% (95% confidence interval (CI: 95.3-98.7% to 100.0% (95% CI: 100.0% in the protein microarray and from 97.7% (95% CI: 96.2-99.2% to 100.0% (95% CI: 100.0% in ELISA. The sensitivity varied from 85.7% (95% CI: 75.1-96.3% to 92.1% (95% CI: 83.5-100.0% in the protein microarray, while the corresponding values for ELISA were 82.0% (95% CI: 71.4-92.6% to 92.1% (95% CI: 83.5-100.0%. Furthermore, the Youden index spanned from 0.83 to 0.92 in the protein microarray and from 0.80 to 0.92 in ELISA. For each parasite, the Youden index from the protein microarray was often slightly higher than the one from ELISA even though the same antigen was used. CONCLUSIONS/SIGNIFICANCE: The protein microarray platform is a convenient, versatile, high-throughput method that can easily be adapted to massive FBH screening.

  8. Rapid Active Sampling Surveys as a Tool to Evaluate Factors Associated with Acute Gastroenteritis and Norovirus Infection among Children in Rural Guatemala.

    Science.gov (United States)

    Olson, Daniel; Lamb, Molly M; Lopez, Maria R; Paniagua-Avila, Maria A; Zacarias, Alma; Samayoa-Reyes, Gabriela; Cordon-Rosales, Celia; Asturias, Edwin J

    2017-09-01

    We examined burden and factors associated with norovirus (NoV) acute gastroenteritis (AGE) among children in rural Guatemala. Children age 6 weeks to 17 years were enrolled into three AGE surveillance groups, using two-stage cluster sampling: a prospective participatory syndromic surveillance (PSS) cohort and two cross-sectional rapid active sampling (RAS) surveys, conducted from April 2015 to February 2016. Epidemiologic and NoV testing data were used to identify factors associated with NoV infection, AGE, and NoV+ AGE. The three cross-sectional surveys (PSS enrollment visit, RAS Survey 1, and RAS Survey 2) enrolled 1,239 children, who reported 134 (11%) AGE cases, with 20% of AGE and 11% of non-AGE samples positive for NoV. Adjusted analyses identified several modifiable factors associated with AGE and NoV infection. The cross-sectional RAS surveys were practical and cost-effective in identifying population-level risk factors for AGE and NoV, supporting their use as a tool to direct limited public health resources toward high-risk populations.

  9. Diagnostic accuracy of rapid urine dipstick test to predict urinary tract infection among pregnant women in Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia.

    Science.gov (United States)

    Demilie, Tazebew; Beyene, Getenet; Melaku, Selabat; Tsegaye, Wondewosen

    2014-07-29

    Untreated bacteriuria during pregnancy has been shown to be associated with low birth-weight and premature delivery. Therefore, routine screening for bacteriuria is advocated. The decision about how to screen pregnant women for bacteriuria has always been a balance between the cost of screening versus the sensitivity and specificity. This study was designed to evaluate the diagnostic accuracy of the rapid dipstick test to predict urinary tract infection in pregnancy against the gold standard urine culture. A total of 367 mid stream urine samples were collected, inoculated on MacConkey, Manitol salt agar (MSA) and blood agar and incubated aerobically at 37°C for overnight. Specimens were classified as "positive" for urinary tract infection (UTI) if the growth of the pathogen(s) was at a count ≥ 10(5) colony-forming units per milliliter (cfu/mL) of urine and classified as "negative" with growth of UTI(ABU) and 71.4% and 86.7% for symptomatic UTI respectively and for nitrite 35.7% and 98.0% for ABU and 57.1% and 96.7% symptomatic UTI. This study revealed that the use of dipstick leukocyte esterase and nitrite for screening UTI particularly asymptomatic bacteriuria was associated with many false positive and negative results when it was compared against the gold standard culture method. The low sensitivity and positive predictive value of urine dipstick test proved that culture should be used for the diagnosis of UTI.

  10. Interagency partnering for weed prevention--progress on development of a National Early Detection and Rapid Response System for Invasive Plants in the United States

    Science.gov (United States)

    Westbrooks, R.; Westbrooks, R.

    2011-01-01

    Over the past 50 years, experience has shown that interagency groups provide an effective forum for addressing various invasive species issues and challenges on multiple land units. However, more importantly, they can also provide a coordinated framework for early detection, reporting, identification and vouchering, rapid assessment, and rapid response to new and emerging invasive plants in the United States. Interagency collaboration maximizes the use of available expertise, resources, and authority for promoting early detection and rapid response (EDRR) as the preferred management option for addressing new and emerging invasive plants. Currently, an interagency effort is underway to develop a National EDRR System for Invasive Plants in the United States. The proposed system will include structural and informational elements. Structural elements of the system include a network of interagency partner groups to facilitate early detection and rapid response to new invasive plants, including the Federal Interagency Committee for the Management of Noxious and Exotic Weeds (FICMNEW), State Invasive Species Councils, State Early Detection and Rapid Response Coordinating Committees, State Volunteer Detection and Reporting Networks, Invasive Plant Task Forces, and Cooperative Weed Management Areas. Informational elements and products being developed include Regional Invasive Plant Atlases, and EDRR Guidelines for EDRR Volunteer Network Training, Rapid Assessment and Rapid Response, and Criteria for Selection of EDRR Species. System science and technical support elements which are provided by cooperating state and federal scientists, include EDRR guidelines, training curriculum for EDRR volunteers and agency field personnel, plant identification and vouchering, rapid assessments, as well as predictive modeling and ecological range studies for invasive plant species.

  11. Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection

    Science.gov (United States)

    Cross, Robert W.; Boisen, Matthew L.; Millett, Molly M.; Nelson, Diana S.; Oottamasathien, Darin; Hartnett, Jessica N.; Jones, Abigal B.; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A.; Fusco, Marnie L.; Abelson, Dafna M.; Oda, Shunichiro; Brown, Bethany L.; Pham, Ha; Rowland, Megan M.; Agans, Krystle N.; Geisbert, Joan B.; Heinrich, Megan L.; Kulakosky, Peter C.; Shaffer, Jeffrey G.; Schieffelin, John S.; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M.; Wilson, Russell B.; Saphire, Erica Ollmann; Pitts, Kelly R.; Khan, Sheik Humarr; Grant, Donald S.; Geisbert, Thomas W.; Branco, Luis M.; Garry, Robert F.

    2016-01-01

    Background. Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013–2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases. Methods. Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance. Results. The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription–polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 105–9.0 × 108 genomes/mL. Conclusions. The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. PMID:27587634

  12. Analytical Validation of the ReEBOV Antigen Rapid Test for Point-of-Care Diagnosis of Ebola Virus Infection.

    Science.gov (United States)

    Cross, Robert W; Boisen, Matthew L; Millett, Molly M; Nelson, Diana S; Oottamasathien, Darin; Hartnett, Jessica N; Jones, Abigal B; Goba, Augustine; Momoh, Mambu; Fullah, Mohamed; Bornholdt, Zachary A; Fusco, Marnie L; Abelson, Dafna M; Oda, Shunichiro; Brown, Bethany L; Pham, Ha; Rowland, Megan M; Agans, Krystle N; Geisbert, Joan B; Heinrich, Megan L; Kulakosky, Peter C; Shaffer, Jeffrey G; Schieffelin, John S; Kargbo, Brima; Gbetuwa, Momoh; Gevao, Sahr M; Wilson, Russell B; Saphire, Erica Ollmann; Pitts, Kelly R; Khan, Sheik Humarr; Grant, Donald S; Geisbert, Thomas W; Branco, Luis M; Garry, Robert F

    2016-10-15

     Ebola virus disease (EVD) is a severe viral illness caused by Ebola virus (EBOV). The 2013-2016 EVD outbreak in West Africa is the largest recorded, with >11 000 deaths. Development of the ReEBOV Antigen Rapid Test (ReEBOV RDT) was expedited to provide a point-of-care test for suspected EVD cases.  Recombinant EBOV viral protein 40 antigen was used to derive polyclonal antibodies for RDT and enzyme-linked immunosorbent assay development. ReEBOV RDT limits of detection (LOD), specificity, and interference were analytically validated on the basis of Food and Drug Administration (FDA) guidance.  The ReEBOV RDT specificity estimate was 95% for donor serum panels and 97% for donor whole-blood specimens. The RDT demonstrated sensitivity to 3 species of Ebolavirus (Zaire ebolavirus, Sudan ebolavirus, and Bundibugyo ebolavirus) associated with human disease, with no cross-reactivity by pathogens associated with non-EBOV febrile illness, including malaria parasites. Interference testing exhibited no reactivity by medications in common use. The LOD for antigen was 4.7 ng/test in serum and 9.4 ng/test in whole blood. Quantitative reverse transcription-polymerase chain reaction testing of nonhuman primate samples determined the range to be equivalent to 3.0 × 10 5 -9.0 × 10 8 genomes/mL.  The analytical validation presented here contributed to the ReEBOV RDT being the first antigen-based assay to receive FDA and World Health Organization emergency use authorization for this EVD outbreak, in February 2015. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  13. Establishment of reverse transcription loop-mediated isothermal amplification for rapid detection and differentiation of canine distemper virus infected and vaccinated animals.

    Science.gov (United States)

    Liu, Da-Fei; Liu, Chun-Guo; Tian, Jin; Jiang, Yi-Tong; Zhang, Xiao-Zhan; Chai, Hong-Liang; Yang, Tian-Kuo; Yin, Xiu-Chen; Zhang, Hong-Ying; Liu, Ming; Hua, Yu-Ping; Qu, Lian-Dong

    2015-06-01

    Although widespread vaccination against canine distemper virus (CDV) has been conducted for many decades, several canine distemper outbreaks in vaccinated animals have been reported frequently. In order to detect and differentiate the wild-type and vaccine strains of the CDV from the vaccinated animals, a novel reverse transcription loop-mediated isothermal amplification (RT-LAMP) method was developed. A set of four primers-two internal and two external-were designed to target the H gene for the specific detection of wild-type CDV variants. The CDV-H RT-LAMP assay rapidly amplified the target gene, within 60 min, using a water bath held at a constant temperature of 65°C. The assay was 100-fold more sensitive than conventional RT-PCR, with a detection limit of 10(-1)TCID50ml(-1). The system showed a preference for wild-type CDV, and exhibited less sensitivity to canine parvovirus, canine adenovirus type 1 and type 2, canine coronavirus, and canine parainfluenza virus. The assay was validated using 102 clinical samples obtained from vaccinated dog farms, and the results were comparable to a multiplex nested RT-PCR assay. The specific CDV-H RT-LAMP assay provides a simple, rapid, and sensitive tool for the detection of canines infected with wild-type CDV from canines vaccinated with attenuated vaccine. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Rapid and quantitative detection of zoonotic influenza A virus infection utilizing coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT).

    Science.gov (United States)

    Yeo, Seon-Ju; Huong, Dinh Thi; Hong, Nguyen Ngoc; Li, Chun-Ying; Choi, Kyunghan; Yu, Kyoungsik; Choi, Du-Young; Chong, Chom-Kyu; Choi, Hak Soo; Mallik, Shyam Kumar; Kim, Hak Sung; Sung, Haan Woo; Park, Hyun

    2014-01-01

    Great efforts have been made to develop robust signal-generating fluorescence materials which will help in improving the rapid diagnostic test (RDT) in terms of sensitivity and quantification. In this study, we developed coumarin-derived dendrimer-based fluorescent immunochromatographic strip test (FICT) assay with enhanced sensitivity as a quantitative diagnostic tool in typical RDT environments. The accuracy of the proposed FICT was compared with that of dot blot immunoassay techniques and conventional RDTs. Through conjugation of coumarin-derived dendrimers with latex beads, fluorescent emission covering broad output spectral ranges was obtained which provided a distinct advantage of easy discrimination of the fluorescent emission of the latex beads with a simple insertion of a long-pass optical filter away from the excitation wavelength. The newly developed FICT assay was able to detect 100 ng/10 μL of influenza A nucleoprotein (NP) antigen within 5 minutes, which corresponded to 2.5-fold higher sensitivity than that of the dot blot immunoassay or conventional RDTs. Moreover, the FICT assay was confirmed to detect at least four avian influenza A subtypes (H5N3, H7N1, H7N7, and H9N2). On applying the FICT to the clinical swab samples infected with respiratory viruses, our FICT assay was confirmed to differentiate influenza H1N1 infection from other respiratory viral diseases. These data demonstrate that the proposed FICT assay is able to detect zoonotic influenza A viruses with a high sensitivity, and it enables the quantitation of the infection intensity by providing the numerical diagnostic values; thus demonstrating enhanced detectability of influenza A viruses.

  15. Characterization of tuberculous granulomas in different stages of progression and associated tertiary lymphoid tissue in goats experimentally infected with Mycobacterium avium subsp. hominissuis.

    Science.gov (United States)

    Schinköthe, Jan; Köhler, Heike; Liebler-Tenorio, Elisabeth M

    2016-08-01

    Oral infection of goats with Mycobacterium avium subsp. hominissuis (MAH) resulted in a large variety of granulomas in organized gut-associated lymphatic tissues and intestinal lymph nodes. To characterize the cellular composition of granulomas, CD4(+), CD8(+), γδ, B lymphocytes and plasma, CD25(+), CD68(+), MHC-II(+), Ki67(+) and endothelial cells were labeled in consecutive frozen sections by immunohistochemistry and acid fast bacilli (AFB) by Kinyoun stain. Granulomas with extensive necrosis, little mineralization and variable numbers of AFB surrounded by many CD4(+) T cells, but only few epitheloid macrophages were observed in severely sick goats at 2-3mpi. They were interpreted as exuberant immune reaction. Organized granulomas with very few AFB were seen in clinically healthy goats at 13mpi. The necrotic cores were surrounded by a zone of granulomatous infiltrate with many epitheloid macrophages and few lymphocytes. This zone was initially wide and highly vascularized and became progressively smaller. It was enclosed by an increasing layer of connective tissue. All organized granulomas were surrounded by compartimentalized tertiary lymphoid tissue. The granulomas in experimental infection of goats with MAH reflect the heterogeneity of lesions seen in mycobacterial infections of humans and ruminants and are therefore valuable for comparative research. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster.

    Directory of Open Access Journals (Sweden)

    Luigi Marangi

    Full Text Available We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3-5 yrs and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation.

  17. [Urinary tract infections in adults].

    Science.gov (United States)

    Michno, Mikolaj; Sydor, Antoni

    Review of urinary tract infections in adults including etiology, pathogenesis, classification and the most important therapeutic recommendations. Urinary tract infections are still a common clinical problem occurring more often in sexually active women, pregnancy, elderly , after catherization of a urinary bladder and urological surgery as well as in the co-existence of diabetes or nephrolithiasis. Due to the anatomical differences, women suffer more often than men. The main etiological factor is Escherichia coli, even though it plays a lesser role in the complicated infections, than in non-complicated ones. Apart from that, the infections may also be caused by atypical microbes, viruses and fungi. Relapses as well as reinfections are typical features of urinary tract infections and in some cases prolonged infections can spread from lower to upper urinary tract contributing to pyelonephritis, urosepsis or even death. These long-term infections can progress in a hidden, insidious, oligosymptomatic or asymptomatic manner leading to irreversible, progressive deterioration of renal function. They can also mask other diseases such as tuberculosis or neoplasms of the urinary tract, which leads to the delayed diagnosis and treatment. Diagnosis and treatment of urinary tract infections is a complex problem, often requiring specialized procedures as well as hospitalization. The choice of a therapy is determined by the type of infection, general condition, age and coexisting diseases. Rapid diagnosis and implementation of proper pharmacotherapy may shorten the time of treatment and hospitalization, preventing serious complications and reinfections.

  18. Impaired left ventricular systolic function and increased brachial-ankle pulse-wave velocity are independently associated with rapid renal function progression.

    Science.gov (United States)

    Chen, Szu-Chia; Lin, Tsung-Hsien; Hsu, Po-Chao; Chang, Jer-Ming; Lee, Chee-Siong; Tsai, Wei-Chung; Su, Ho-Ming; Voon, Wen-Chol; Chen, Hung-Chun

    2011-09-01

    Heart failure and increased arterial stiffness are associated with declining renal function. Few studies have evaluated the association between left ventricular ejection fraction (LVEF) and brachial-ankle pulse-wave velocity (baPWV) and renal function progression. The aim of this study was to assess whether LVEFfunction was estimated by eGFR slope. The renal end point was defined as ≥25% decline in eGFR. Clinical and echocardiographic parameters were compared and analyzed. After a multivariate analysis, serum hematocrit was positively associated with eGFR slope, and diabetes mellitus, baPWV (P=0.031) and LVEFfunction decline and progression to the renal end point.

  19. Research progress on characteristics of Zika virus and its infection in human%寨卡病毒及其在人类感染中的研究近况

    Institute of Scientific and Technical Information of China (English)

    马亦林

    2016-01-01

    Zika virus was named after the Ugandan forest where it was first isolated in a rhesus monkey in 1947, and the first confirmed human case was reported in 1954 in Nigeria.The incidence of Zika virus disease is very low.In the year 2014, Zika virus infection appeared in the Western hemisphere, and then the virus rapidly spread to Americas, Caribbean and Pacific island countries.Currently more than 30 countries have reported Zika virus infection, and officials estimate there will be 4 million Zika infections. Zika virus disease is a self-limited disease with mild symptoms, however, Zika virus is neuroinvasive.It can be transmitted to infants from mothers who infected in the early months of pregnancy, and may cause microcephaly, retinae macula and optic nerve abnormalities.Guillain-Barré syndrome is also found as a complication of Zika virus infection in some cases.Zika virus is mainly transmitted by aedes mosquito, and no vaccine is available at present, so the prevention of its infection is difficult.This paper reviews the research progress of Zika virus infection, including virus characteristics, epidemiology and clinical feature of Zika infection in human.%寨卡病毒于1947年首次在乌干达森林中一只罗猴体内分离出而命名。1954年尼日利亚首先证实了人类感染寨卡病毒,但发病率很低。自2014年在西半球发现寨卡病毒感染病例后,2015年4月以来该病毒迅速扩散至美洲、加勒比地区及太平洋岛国共30多个国家,将近400万病例,引起全世界的不安。虽然寨卡病毒病的临床表现较轻,绝大多数为自限性,但是该病毒对宿主具有较强的嗜神经性。早期妊娠妇女感染后,病毒会通过胎盘传染给胎儿,造成胎儿大脑发育障碍,出现小头畸形症及眼底黄斑区视神经异常。少数感染者可能出现吉兰-巴雷综合征。寨卡病毒主要通过伊蚊叮咬传播,目前尚无该病毒疫苗,预防工作存在一定难度

  20. Incidence and progression of Parvovirus B19 infection and molecular changes in circulating B19V strains in children with haematological malignancy: A follow up study.

    Science.gov (United States)

    Jain, Amita; Jain, Parul; Kumar, Archana; Prakash, Shantanu; Khan, Danish Nasar; Kant, Ravi

    2018-01-01

    The present study was planned to estimate the incidence of human Parvovirus B19 infection and understand its progression in children suffering with hematological malignancy. The circulating B19V genotypes and viral mutations occurring in strains of B19V over one-year period were also studied. Children with malignancies were enrolled consecutively and were followed up for one-year period. Serum sample was collected at the time of enrolment and each follow up visit and was tested for anti B19V IgG and IgM as well as for B19V DNA. At least one B19V DNA positive sample from each patient was processed for sequencing. For patients positive for B19V DNA >1 time and at least 6 months apart, last positive sample from the same patient was also sequenced to study the nucleotide change over time. We have found very high incidence of B19V infection (100%) in the study population. All the patients tested positive for at least one B19V infection parameter (either antibodies or DNA) at least once, over one year of follow up. Cumulative percent positivity of anti B19V IgG, anti B19V IgM and B19V DNA was 85.3%, 45.2% and 72.1% respectively. Genotype 3b was reported, with occasional nucleotide change over one year period. DNA clearance was delayed in spite of appearance of IgG antibodies. Appearance of IgM class of antibodies was either delayed or absent. To conclude, children with haematological malignancies have high incidence of B19V infection with late and short lived serological response and persistence of DNA for long duration. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. Performance of a High-Sensitivity Rapid Diagnostic Test for Plasmodium falciparum Malaria in Asymptomatic Individuals from Uganda and Myanmar and Naive Human Challenge Infections.

    Science.gov (United States)

    Das, Smita; Jang, Ihn Kyung; Barney, Becky; Peck, Roger; Rek, John C; Arinaitwe, Emmanuel; Adrama, Harriet; Murphy, Maxwell; Imwong, Mallika; Ling, Clare L; Proux, Stephane; Haohankhunnatham, Warat; Rist, Melissa; Seilie, Annette M; Hanron, Amelia; Daza, Glenda; Chang, Ming; Nakamura, Tomoka; Kalnoky, Michael; Labarre, Paul; Murphy, Sean C; McCarthy, James S; Nosten, Francois; Greenhouse, Bryan; Allauzen, Sophie; Domingo, Gonzalo J

    2017-11-01

    Sensitive field-deployable diagnostic tests can assist malaria programs in achieving elimination. The performance of a new Alere™ Malaria Ag P.f Ultra Sensitive rapid diagnostic test (uRDT) was compared with the currently available SD Bioline Malaria Ag P.f RDT in blood specimens from asymptomatic individuals in Nagongera, Uganda, and in a Karen Village, Myanmar, representative of high- and low-transmission areas, respectively, as well as in pretreatment specimens from study participants from four Plasmodium falciparum -induced blood-stage malaria (IBSM) studies. A quantitative reverse transcription PCR (qRT-PCR) and a highly sensitive enzyme-linked immunosorbent assay (ELISA) test for histidine-rich protein II (HRP2) were used as reference assays. The uRDT showed a greater than 10-fold lower limit of detection for HRP2 compared with the RDT. The sensitivity of the uRDT was 84% and 44% against qRT-PCR in Uganda and Myanmar, respectively, and that of the RDT was 62% and 0% for the same two sites. The specificities of the uRDT were 92% and 99.8% against qRT-PCR for Uganda and Myanmar, respectively, and 99% and 99.8% against the HRP2 reference ELISA. The RDT had specificities of 95% and 100% against qRT-PCR for Uganda and Myanmar, respectively, and 96% and 100% against the HRP2 reference ELISA. The uRDT detected new infections in IBSM study participants 1.5 days sooner than the RDT. The uRDT has the same workflow as currently available RDTs, but improved performance characteristics to identify asymptomatic malaria infections. The uRDT may be a useful tool for malaria elimination strategies.

  2. Contribution of Beta-HPV Infection and UV-Damage to Rapid-onset Cutaneous Squamous Cell Carcinoma during BRAF-inhibition Therapy

    Science.gov (United States)

    Cohen, Daniel N.; Lawson, Steven K.; Shaver, Aaron C.; Du, Liping; Nguyen, Harrison P.; He, Qin; Johnson, Douglas B.; Lumbang, Wilfred A.; Moody, Brent R.; Prescott, James L.; Chandra, Pranil K.; Boyd, Alan S.; Zwerner, Jeffrey P.; Robbins, Jason B.; Tyring, Stephen K.; Rady, Peter L.; Chappell, James D.; Shyr, Yu; Infante, Jeffrey R.; Sosman, Jeffrey A.

    2015-01-01

    Purpose BRAF-inhibition (BRAFi) therapy for advanced melanoma carries a high rate of secondary cutaneous squamous cell carcinoma (cSCC) and risk of other cancers. Ultraviolet (UV) radiation and α-genus human papillomavirus (HPV) are highly associated with SCC, but a novel role for β-genus HPV is suspected in BRAFi-cSCC. Cutaneous β-HPV may act in concert with host and environmental factors in BRAFi-cSCC. Experimental Design Primary BRAFi-cSCC tissue DNA isolated from patients receiving vemurafenib (Vem) or dabrafenib from two cancer centers was analyzed for the presence of cutaneous oncogenic viruses and host genetic mutations. Diagnostic specimens underwent consensus dermatopathology review. Clinical parameters for UV exposure and disease course were statistically analyzed in conjunction with histopathology. Results Twenty-nine patients contributed 69 BRAFi-cSCC lesions. BRAFi-cSCC had wart-like features (BRAFi-cSCC-WF) in 22% of specimens. During Vem therapy, BRAFi-cSCC-WF arose 11.6 weeks more rapidly than conventional-cSCC when controlled for gender and UV-exposure (p-value=0.03). Among all BRAFi-cSCC, β-genus HPV-17, HPV-38, HPV-111 were most frequently isolated and novel β-HPV genotypes were discovered (CTR, CRT-11, CRT-22). Sequencing revealed 63% of evaluated BRAFi-cSCCs harbored RAS mutations with PIK3CA, CKIT, ALK and EGFR mutations also detected. Conclusions We examined clinical, histopathologic, viral and genetic parameters in BRAFi-cSCC demonstrating rapid onset; wart-like histomorphology; β-HPV-17, HPV-38, and HPV-111 infection; UV damage; and novel ALK and CKIT mutations. Discovered β-HPV genotypes expand the spectrum of tumor-associated viruses. These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general. PMID:25724524

  3. Disturbance of the gut-associated lymphoid tissue is associated with disease progression in chronic HIV infection.

    Science.gov (United States)

    Hofer, Ursula; Speck, Roberto F

    2009-07-01

    Why and how HIV makes people sick is highly debated. Recent evidence implicates heightened immune activation due to breakdown of the gastrointestinal barrier as a determining factor of lentiviral pathogenesis. HIV-mediated loss of Th17 cells from the gut-associated lymphoid tissue (GALT) impairs mucosal integrity and innate defense mechanisms against gut microbes. Translocation of microbial products from the gut, in turn, correlates with increased immune activation in chronic HIV infection and may further damage the immune system by increasing viral and activation-induced T cell death, by reducing T cell reconstitution due to tissue scarring, and by impairing the function of other cell types, such as gammadelta T cells and epithelial cells. Maintaining a healthy GALT may be the key to reducing the pathogenic potential of HIV.

  4. Implementation of pre-exposure prophylaxis for human immunodeficiency virus infection: progress and emerging issues in research and policy.

    Science.gov (United States)

    Cáceres, Carlos F; Borquez, Annick; Klausner, Jeffrey D; Baggaley, Rachel; Beyrer, Chris

    2016-01-01

    In this article, we present recent evidence from studies focused on the implementation, effectiveness and cost-effectiveness of pre-exposure prophylaxis (PrEP) for HIV infection; discuss PrEP scale-up to date, including the observed levels of access and policy development; and elaborate on key emerging policy and research issues to consider for further scale-up, with a special focus on lower-middle income countries. The 2015 WHO Early Release Guidelines for HIV Treatment and Prevention reflect both scientific evidence and new policy perspectives. Those guidelines present a timely challenge to health systems for the scaling up of not only treatment for every person living with HIV infection but also the offer of PrEP to those at substantial risk. Delivery and uptake of both universal antiretroviral therapy (ART) and PrEP will require nation-wide commitment and could reinvigorate health systems to develop more comprehensive "combination prevention" programmes and support wider testing linked to both treatments and other prevention options for populations at highest risk who are currently not accessing services. Various gaps in current health systems will need to be addressed to achieve strategic scale-up of PrEP, including developing prioritization strategies, strengthening drug regulations, determining cost and funding sources, training health providers, supporting user adherence and creating demand. The initial steps in the scale-up of PrEP globally suggest feasibility, acceptability and likely impact. However, to prevent setbacks in less well-resourced settings, countries will need to anticipate and address challenges such as operational and health systems barriers, drug cost and regulatory policies, health providers' openness to prescribing PrEP to populations at substantial risk, demand and legal and human rights issues. Emerging problems will require creative solutions and will continue to illustrate the complexity of PrEP implementation.

  5. Apigenin has anti-atrophic gastritis and anti-gastric cancer progression effects in Helicobacter pylori-infected Mongolian gerbils.

    Science.gov (United States)

    Kuo, Chao-Hung; Weng, Bi-Chuang; Wu, Chun-Chieh; Yang, Sheau-Fang; Wu, Deng-Chang; Wang, Yuan-Chuen

    2014-02-12

    Apigenin, one of the most common flavonoids, is abundant in celery, parsley, chamomile, passionflower, and other vegetables and fruits. Celery is recognized as a medicinal vegetable in Oriental countries to traditionally treat inflammation, swelling, blood pressure, serum lipid, and toothache. In this study, we investigated apigenin treatment effects on Helicobacter pylori-induced atrophic gastritis and gastric cancer progression in Mongolian gerbils. Five to eight-week-old Mongolian gerbils were inoculated with Helicobacter pylori for four weeks without (atrophic gastritis group) or with N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (gastric cancer group) in drinking water, and were then rested for two weeks. During the 7th-32th (atrophic gastritis group) or the 7th-52th (gastric cancer group) weeks, they were given various doses (0-60 mg/kgbw/day) of apigenin. At the end of the 32th (atrophic gastritis group) or the 52th (atrophic gastritis group) week, all Mongolian gerbils were sacrificed using the CO2 asphyxia method. The histological changes of Helicobacter pylori colonization, neutrophil and monocyte infiltrations, and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils were examined using immunohistochemistry stain and Sydney System scoring. Apigenin treatments (30-60 mg/kgbw/day) effectively decreased atrophic gastritis (atrophic gastritis group) and dysplasia/gastric cancer (gastric cancer group) rates in Mongolian gerbils. Apigenin treatment (60 mg/kgbw/day) significantly decreased Helicobacter pylori colonization and Helicobacter pylori-induced histological changes of neutrophil and monocyte infiltrations and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils. Apigenin has the remarkable ability to inhibit Helicobacter pylori-induced atrophic gastritis and gastric cancer progression as well as possessing potent anti-gastric cancer activity. Copyright © 2013 Elsevier Ireland Ltd. All rights

  6. Dual rapid lateral flow immunoassay fingerstick wholeblood testing for syphilis and HIV infections is acceptable and accurate, Port-au-Prince, Haiti.

    Science.gov (United States)

    Bristow, Claire C; Severe, Linda; Pape, Jean William; Javanbakht, Marjan; Lee, Sung-Jae; Comulada, Warren Scott; Klausner, Jeffrey D

    2016-06-18

    Dual rapid tests for HIV and syphilis infections allow for detection of HIV infection and syphilis at the point-of-care. Those tests have been evaluated in laboratory settings and show excellent performance but have not been evaluated in the field. We evaluated the field performance of the SD BIOLINE HIV/Syphilis Duo test in Port-au-Prince, Haiti using whole blood fingerprick specimens. GHESKIO (Haitian Study Group for Kaposi's Sarcoma and Opportunistic Infections) clinic attendees 18 years of age or older were invited to participate. Venipuncture blood specimens were used for reference testing with standard commercially available tests for HIV and syphilis in Haiti. The sensitivity and specificity of the Duo test compared to the reference standard were calculated. The exact binomial method was used to determine 95 % confidence intervals (CI). Of 298 study participants, 237 (79.5 %) were female, of which 49 (20.7 %) were pregnant. For the HIV test component, the sensitivity and specificity were 99.2 % (95 % CI: 95.8 %, 100 %) and 97.0 % (95 % CI: 93.2 %, 99.0 %), respectively; and for the syphilis component were 96.5 % (95 % CI: 91.2 %, 99.0 %) and 90.8 % (95 % CI: 85.7 %, 94.6 %), respectively. In pregnant women, the sensitivity and specificity of the HIV test component were 93.3 % (95 % CI: 68.0 %, 99.8 %) and 94.1 % (95 % CI: 80.3 %, 99.3 %), respectively; and for the syphilis component were 100 % (95 % CI:81.5 %, 100 %) and 96.8 % (95 % CI:83.3 %, 99.9 %), respectively. The Standard Diagnostics BIOLINE HIV/Syphilis Duo dual test performed well in a field setting in Haiti and should be considered for wider use.

  7. A simple and rapid Hepatitis A Virus (HAV titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations

    Directory of Open Access Journals (Sweden)

    Kaplan Gerardo G

    2008-12-01

    Full Text Available Abstract Background Hepatitis A virus (HAV, the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results We developed an antibiotic resistance titration assay (ARTA based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 μg/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the

  8. Rapid, simple and direct detection of Meloidogyne hapla from infected root galls using loop-mediated isothermal amplification combined with FTA technology.

    Science.gov (United States)

    Peng, Huan; Long, Haibo; Huang, Wenkun; Liu, Jing; Cui, Jiangkuan; Kong, Lingan; Hu, Xianqi; Gu, Jianfeng; Peng, Deliang

    2017-04-03

    The northern root-knot nematode (Meloidogyne hapla) is a damaging nematode that has caused serious economic losses worldwide. In the present study, a sensitive, simple and rapid method was developed for detection of M. hapla in infested plant roots by combining a Flinders Technology Associates (FTA) card with loop-mediated isothermal amplification (LAMP). The specific primers of LAMP were designed based on the distinction of internal transcribed spacer (ITS) sequences between M. hapla and other Meloidogyne spp. The LAMP assay can detect nematode genomic DNA at concentrations low to 1/200 000, which is 100 times more sensitive than conventional PCR. The LAMP was able to highly specifically distinguish M. hapla from other closely related nematode species. Furthermore, the advantages of the FTA-LAMP assay to detect M. hapla were demonstrated by assaying infected root galls that were artificially inoculated. In addition, M. hapla was successfully detected from six of forty-two field samples using FTA-LAMP technology. This study was the first to provide a simple diagnostic assay for M. hapla using the LAMP assay combined with FTA technology. In conclusion, the new FTA-LAMP assay has the potential for diagnosing infestation in the field and managing the pathogen M. hapla.

  9. Changes in Clinical and Microbiological Periodontal Profiles Relate to Progression of Carotid Intima‐Media Thickness: The Oral Infections and Vascular Disease Epidemiology Study

    Science.gov (United States)

    Desvarieux, Moïse; Demmer, Ryan T.; Jacobs, David R.; Papapanou, Panos N.; Sacco, Ralph L.; Rundek, Tatjana

    2013-01-01

    Background No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis. Methods and Results The Oral Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trendperiodontal microbial status (Δetiologic dominance). Conclusion Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average

  10. Horse species symposium: a novel approach to monitoring pathogen progression during uterine and placental infection in the mare using bioluminescence imaging technology and lux-modified bacteria.

    Science.gov (United States)

    Ryan, P L; Christiansen, D L; Hopper, R M; Walters, F K; Moulton, K; Curbelo, J; Greene, J M; Willard, S T

    2011-05-01

    Uterine and placental infections are the leading cause of abortion, stillbirth, and preterm delivery in the mare. Whereas uterine and placental infections in women have been studied extensively, a comprehensive examination of the pathogenic processes leading to this unsatisfactory pregnancy outcome in the mare has yet to be completed. Most information in the literature relating to late-term pregnancy loss in mares is based on retrospective studies of clinical cases submitted for necropsy. Here we report the development and application of a novel approach, whereby transgenically modified bacteria transformed with lux genes of Xenorhabdus luminescens or Photorhabdus luminescens origin and biophotonic imaging are utilized to better understand pathogen-induced preterm birth in late-term pregnant mares. This technology uses highly sensitive bioluminescence imaging camera systems to localize and monitor pathogen progression during tissue invasion by measuring the bioluminescent signatures emitted by the lux-modified pathogens. This method has an important advantage in that it allows for the potential tracking of pathogens in vivo in real time and over time, which was hitherto impossible. Although the application of this technology in domestic animals is in its infancy, investigators were successful in identifying the fetal lungs, sinuses, nares, urinary, and gastrointestinal systems as primary tissues for pathogen invasion after experimental infection of pregnant mares with lux-modified Escherichia coli. It is important that pathogens were not detected in other vital organs, such as the liver, brain, and cardiac system. Such precision in localizing sites of pathogen invasion provides potential application for this novel approach in the development of more targeted therapeutic interventions for pathogen-related diseases in the equine and other domestic species.

  11. Pediatric spinal infections

    Directory of Open Access Journals (Sweden)

    Raj Kumar

    2014-01-01

    Full Text Available The infections of the spinal axis in children are rare when compared with adults. They encompass a large spectrum of diseases ranging from relatively benign diskitis to spinal osteomyleitis and to the rapidly progressive, rare, and potentially devastating spinal epidural, subdural, and intramedullary spinal cord infections. We present a comprehensive review of the literature pertaining to these uncommon entities, in light of our experience from northern India. The most prevalent pediatric spinal infection in Indian scenario is tuberculosis, where an extradural involvement is more common than intradural. The craniovertebral junction is not an uncommon site of involvement in children of our milieu. The majority of pyogenic infections of pediatric spine are associated with congenital neuro-ectodermal defects such as congenital dermal sinus. The clinico-radiological findings of various spinal infections commonly overlap. Hence the endemicity of certain pathogens should be given due consideration, while considering the differential diagnosis. However, early suspicion, rapid diagnosis, and prompt treatment are the key factors in avoiding neurological morbidity and deformity in a growing child.

  12. Progressing features of atypical mycobacterial infection in the lung on conventional and high resolution CT (HRCT) images

    International Nuclear Information System (INIS)

    Tanaka, Daizo; Niwatsukino, Hiroshi; Nakajo, Masayuki; Oyama, Takao

    2001-01-01

    The aim of this study was to clarify the localization of abnormalities within secondary pulmonary lobules and the changes in follow-up studies of pulmonary atypical mycobacterial infection (AMI) by conventional and high-resolution computed tomography (HRCT). Forty-six patients (16 men and 30 women; 43-84 years) with pulmonary AMI (M. intracellulare 36; M. avium 10) in the lung were examined by conventional and HRCT. In peripheral zones, all patients had the nodule located in the terminal or lobular bronchiole, and most of the patients also had nodules accompanied with a wedge-shaped or linear shadow connected with the pleura. In the follow-up scans, new centrilobular nodules appeared in other segments, and consolidation or ground-glass pattern appeared newly and was preceded by nodules. Bronchiectasis became more severe in five of 38 follow-up patients. The common HRCT findings of AMI were centrilobular, peribronchovascular nodules, bronchiectasis, consolidation, and pleural thickening/adhesion. The nodules frequently connected with the pleura. The initial and follow-up studies suggest that the disease may begin in the terminal bronchiole or as preexisting bronchiectasis and spread transbronchially along the draining bronchus or towards the pleura to produce lesions such as new nodules, cavities, consolidation, pleuritis, and bronchiectasis, or more severe bronchiectasis. (author)

  13. Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review.

    Science.gov (United States)

    Warhurst, Geoffrey; Dunn, Graham; Chadwick, Paul; Blackwood, Bronagh; McAuley, Daniel; Perkins, Gavin D; McMullan, Ronan; Gates, Simon; Bentley, Andrew; Young, Duncan; Carlson, Gordon L; Dark, Paul

    2015-05-01

    antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy. SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is

  14. Complete suppression of viral gene expression is associated with the onset and progression of lymphoid malignancy: observations in Bovine Leukemia Virus-infected sheep

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    Burny Arsène

    2007-07-01

    Full Text Available Abstract Background During malignant progression, tumor cells need to acquire novel characteristics that lead to uncontrolled growth and reduced immunogenicity. In the Bovine Leukemia Virus-induced ovine leukemia model, silencing of viral gene expression has been proposed as a mechanism leading to immune evasion. However, whether proviral expression in tumors is completely suppressed in vivo was not conclusively demonstrated. Therefore, we studied viral expression in two selected experimentally-infected sheep, the virus or the disease of which had features that made it possible to distinguish tumor cells from their nontransformed counterparts. Results In the first animal, we observed the emergence of a genetically modified provirus simultaneously with leukemia onset. We found a Tax-mutated (TaxK303 replication-deficient provirus in the malignant B-cell clone while functional provirus (TaxE303 had been consistently monitored over the 17-month aleukemic period. In the second case, both non-transformed and transformed BLV-infected cells were present at the same time, but at distinct sites. While there was potentially-active provirus in the non-leukemic blood B-cell population, as demonstrated by ex-vivo culture and injection into naïve sheep, virus expression was completely suppressed in the malignant B-cells isolated from the lymphoid tumors despite the absence of genetic alterations in the proviral genome. These observations suggest that silencing of viral genes, including the oncoprotein Tax, is associated with tumor onset. Conclusion Our findings suggest that silencing is critical for tumor progression and identify two distinct mechanisms-genetic and epigenetic-involved in the complete suppression of virus and Tax expression. We demonstrate that, in contrast to systems that require sustained oncogene expression, the major viral transforming protein Tax can be turned-off without reversing the transformed phenotype. We propose that suppression

  15. Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

    Directory of Open Access Journals (Sweden)

    Patrick Schmid

    Full Text Available To evaluate the diagnostic performance of seven non-invasive tests (NITs of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients.Transient elastography (TE and six blood tests were compared to histopathological fibrosis stage (METAVIR. Participants were followed over three years with NITs at yearly intervals.Area under the receiver operating characteristic curve (AUROC for significant fibrosis (> = F2 in 105 participants was highest for TE (0.85, followed by FIB-4 (0.77, ELF-Test (0.77, APRI (0.76, Fibrotest (0.75, hyaluronic acid (0.70, and Hepascore (0.68. AUROC for cirrhosis (F4 was 0.97 for TE followed by FIB-4 (0.91, APRI (0.89, Fibrotest (0.84, Hepascore (0.82, ELF-Test (0.82, and hyaluronic acid (0.79. A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response. TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07. 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1. Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years.TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

  16. Progression of Liver Fibrosis in HIV/HCV Co-Infection: A Comparison between Non-Invasive Assessment Methods and Liver Biopsy.

    Science.gov (United States)

    Schmid, Patrick; Bregenzer, Andrea; Huber, Milo; Rauch, Andri; Jochum, Wolfram; Müllhaupt, Beat; Vernazza, Pietro; Opravil, Milos; Weber, Rainer

    2015-01-01

    To evaluate the diagnostic performance of seven non-invasive tests (NITs) of liver fibrosis and to assess fibrosis progression over time in HIV/HCV co-infected patients. Transient elastography (TE) and six blood tests were compared to histopathological fibrosis stage (METAVIR). Participants were followed over three years with NITs at yearly intervals. Area under the receiver operating characteristic curve (AUROC) for significant fibrosis (> = F2) in 105 participants was highest for TE (0.85), followed by FIB-4 (0.77), ELF-Test (0.77), APRI (0.76), Fibrotest (0.75), hyaluronic acid (0.70), and Hepascore (0.68). AUROC for cirrhosis (F4) was 0.97 for TE followed by FIB-4 (0.91), APRI (0.89), Fibrotest (0.84), Hepascore (0.82), ELF-Test (0.82), and hyaluronic acid (0.79). A three year follow-up was completed by 87 participants, all on antiretroviral therapy and in 20 patients who completed HCV treatment (9 with sustained virologic response). TE, APRI and Fibrotest did not significantly change during follow-up. There was weak evidence for an increase of FIB-4 (mean increase: 0.22, p = 0.07). 42 participants had a second liver biopsy: Among 38 participants with F0-F3 at baseline, 10 were progessors (1-stage increase in fibrosis, 8 participants; 2-stage, 1; 3-stage, 1). Among progressors, mean increase in TE was 3.35 kPa, in APRI 0.36, and in FIB-4 0.75. Fibrotest results did not change over 3 years. TE was the best NIT for liver fibrosis staging in HIV/HCV co-infected patients. APRI-Score, FIB-4 Index, Fibrotest, and ELF-Test were less reliable. Routinely available APRI and FIB-4 performed as good as more expensive tests. NITs did not change significantly during a follow-up of three years, suggesting slow liver disease progression in a majority of HIV/HCV co-infected persons on antiretroviral therapy.

  17. Modulation of basal cell fate during productive and transforming HPV-16 infection is mediated by progressive E6-driven depletion of Notch.

    Science.gov (United States)

    Kranjec, Christian; Holleywood, Christina; Libert, Diane; Griffin, Heather; Mahmood, Radma; Isaacson, Erin; Doorbar, John

    2017-08-01

    In stratified epithelia such as the epidermis, homeostasis is maintained by the proliferation of cells in the lower epithelial layers and the concomitant loss of differentiated cells from the epithelial surface. These differentiating keratinocytes progressively stratify and form a self-regenerating multi-layered barrier that protects the underlying dermis. In such tissue, the continual loss and replacement of differentiated cells also limits the accumulation of oncogenic mutations within the tissue. Inactivating mutations in key driver genes, such as TP53 and NOTCH1, reduce the proportion of differentiating cells allowing for the long-term persistence of expanding mutant clones in the tissue. Here we show that through the expression of E6, HPV-16 prevents the early fate commitment of human keratinocytes towards differentiation and confers a strong growth advantage to human keratinocytes. When E6 is expressed either alone or with E7, it promotes keratinocyte proliferation at high cell densities, through the combined inactivation of p53 and Notch1. In organotypic raft culture, the activity of E6 is restricted to the basal layer of the epithelium and is enhanced during the progression from productive to abortive or transforming HPV-16 infection. Consistent with this, the expression of p53 and cleaved Notch1 becomes progressively more disrupted, and is associated with increased basal cell density and reduced commitment to differentiation. The expression of cleaved Notch1 is similarly disrupted also in HPV-16-positive cervical lesions, depending on neoplastic grade. When taken together, these data depict an important role of high-risk E6 in promoting the persistence of infected keratinocytes in the basal and parabasal layers through the inactivation of gene products that are commonly mutated in non-HPV-associated neoplastic squamous epithelia. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great

  18. Background and perspective on rapid progress and deepening of international development of nuclear industry-composition of international nuclear energy business 'cooperation and competition'

    International Nuclear Information System (INIS)

    Kano, Tokio; Kanda, Keji; Ishizuka, Nobuo

    2005-01-01

    Based on the recognition that international development of nuclear industry was important by a viewpoint of international cooperation to neighboring Asian area and also it was the trump that defeated a feeling of domestic confinement, the Japan Atomic Industrial Forum (JAIF) founded Nuclear energy international development gathering' in November 2004. On that occasion our magazine (March, 2005 issue) featured 'prospects and problem of the international development of nuclear energy use'. Slightly for half a year afterwards this nuclear energy international development has been rapidly deepened and become a close-up as a policy of an important strategy of the field of nuclear energy that the government and the private sector were united to make. Therefore the nuclear energy international development was secondly featured from multidirectional points of view such as a background of nuclear energy international development, composition of international nuclear energy business, a main strategy of three makers, approach of finance / a business firm. (T. Tanaka)

  19. Malaria rapid diagnostic tests: Plasmodium falciparum infections with high parasite densities may generate false positive Plasmodium vivax pLDH lines

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    van Esbroeck Marjan

    2010-07-01

    Full Text Available Abstract Background Most malaria rapid diagnostic tests (RDTs detect Plasmodium falciparum and an antigen common to the four species. Plasmodium vivax-specific RDTs target P. vivax-specific parasite lactate dehydrogenase (Pv-pLDH. Previous observations of false positive Pv-pLDH test lines in P. falciparum samples incited to the present study, which assessed P. vivax-specific RDTs for the occurrence of false positive Pv-pLDH lines in P. falciparum samples. Methods Nine P. vivax-specific RDTs were tested with 85 P. falciparum samples of high (≥2% parasite density. Mixed P. falciparum/P. vivax infections were ruled out by real-time PCR. The RDTs included two-band (detecting Pv-pLDH, three-band (detecting P. falciparum-antigen and Pv-pLDH and four-band RDTs (detecting P. falciparum, Pv-pLDH and pan-pLDH. Results False positive Pv-pLDH lines were observed in 6/9 RDTs (including two- three- and four-band RDTs. They occurred in the individual RDT brands at frequencies ranging from 8.2% to 29.1%. For 19/85 samples, at least two RDT brands generated a false positive Pv-pLDH line. Sixteen of 85 (18.8% false positive lines were of medium or strong line intensity. There was no significant relation between false positive results and parasite density or geographic origin of the samples. Conclusion False positive Pv-pLDH lines in P. falciparum samples with high parasite density occurred in 6/9 P. vivax-specific RDTs. This is of concern as P. falciparum and P. vivax are co-circulating in many regions. The diagnosis of life-threatening P. falciparum malaria may be missed (two-band Pv-pLDH RDT, or the patient may be treated incorrectly with primaquine (three- or four-band RDTs.

  20. Rapid Disease Progression of Liver Metastases following Resection in a Liver-Transplanted Patient with Probable Lynch Syndrome – A Case Report and Review of the Literature

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    Noelle Suemi Wassano

    2017-03-01

    Full Text Available Solid organ transplantation provides life-saving therapy for patients with end-stage organ disease, and its outcomes have been improving dramatically over the past few decades. However, substantial morbidity results from chronic immunosuppressive therapy administered to prevent graft rejection. It predisposes patients to several life-threatening complications, such as opportunistic microbial infections and the development of different types of cancers. Here, we presented the case of a young man with probable Lynch syndrome, who developed an aggressive colon carcinoma after long-term immunosuppressive therapy due to a prior liver transplantation. Based on this case report, we attempt to find an answer to the question about the risk of cancer development or recurrence in patients with familial syndromes receiving long-term immunosuppressive therapy and to find out how it can be minimized. Answering these questions is particularly important, given the facts that disease course is substantially more aggressive among transplanted patients and that prognosis is poor due to lack of immunocompetence, especially in the setting of Lynch syndrome.

  1. Permissive cytomegalovirus infection of primary villous term and first trimester trophoblasts.

    Science.gov (United States)

    Hemmings, D G; Kilani, R; Nykiforuk, C; Preiksaitis, J; Guilbert, L J

    1998-06-01

    Forty percent of women with primary cytomegalovirus (CMV) infections during pregnancy infect their fetuses with complications for the baby varying from mild to severe. How CMV crosses the syncytiotrophoblast, the barrier between maternal blood and fetal tissue in the villous placenta, is unknown. Virus may cross by infection of maternal cells that pass through physical breaches in the syncytiotrophoblast or by direct infection of the syncytiotrophoblast, with subsequent transmission to underlying fetal placental cells. In this study, we show that pure (>99.99%), long-term and healthy (>3 weeks) cultures of syncytiotrophoblasts are permissively infected with CMV. Greater than 99% of infectious progeny virus remained cell associated throughout culture periods up to 3 weeks. Infection of term trophoblasts required a higher virus inoculum, was less efficient, and progressed more slowly than parallel infections of placental and human embryonic lung fibroblasts. Three laboratory strains (AD169, Towne, and Davis) and a clinical isolate from a congenitally infected infant all permissively infected trophoblasts, although infection efficiencies varied. The infection of first trimester syncytiotrophoblasts with strain AD169 occurred at higher frequency and progressed more rapidly than infection of term cells but less efficiently and rapidly than infection of fibroblasts. These results show that villous syncytiotrophoblasts can be permissively infected by CMV but that the infection requires high virus titers and proceeds slowly and that progeny virus remains predominantly cell associated.

  2. [Socio-demographic factors associated with the progression of HIV infection and the impact of HAART in a seroconverter cohort in Madrid (1986-2009)].

    Science.gov (United States)

    Monge, Susana; Del Romero, Jorge; Rodríguez, Carmen; de Mendoza, Carmen; de Górgolas, Miguel; Cosín, Jaime; Dronda, Fernando; Pérez-Cecilia, Elisa; Peña, José María; Santos, Ignacio; Rubio, Rafael; Del Amo, Julia

    2012-03-01

    The objective of this work is to study the impact of HAART at a population level and to identify socio-demographic factors that may affect it, which is essential for deciding interventions. An open, prospective cohort of HIV seroconverters recruited in the Centro Sanitario Sandoval (1986-2009), and followed up in collaboration with referral hospitals in the Comunidad Autónoma de Madrid. Cumulative incidence of AIDS and death was calculated by the multiple decrements method, and predictive Fine & Gray models were developed to identify associated factors. A calendar period (<1997; ≥ 1997) was introduced as a proxy of HAART availability. A total of 479 HIV seroconverters were identified. Hazard Ratio (HR) for progression to AIDS was 0.215 (95% CI: 0.11-0.519; P<.01) for the period ≥ 1997. Risk increased with age at the time of seroconversion (for each year older HR=1.071; 95% CI: 1.038-1.105; P<.01), but only prior to 1997. In the following period, only a high educational level showed to be a protective factor (HR=0.982; 95% CI: 0.936-1.031; P=.06). HR for progression to death was 0.134 (95% CI: 0.052-0.346; P<.01) for the period after 1997, 0.383 (95% CI: 0.168-0.875; P=.02) in people with high educational level and 1.048 (95% CI: 1.014-1.084; P<.01) for each year increase in age at seroconversion, both latter effects being homogeneous throughout the two periods. HAART has had a great impact on the risk of progression to AIDS and death, but this benefit appears to be influenced by age at HIV infection and educational level of the patient, which highlights the importance of a global approach to case management and of the implementation of policies that address social inequities in health. Copyright © 2011 Elsevier España, S.L. All rights reserved.

  3. Gram-stain plus MALDI-TOF MS (Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for a rapid diagnosis of urinary tract infection.

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    Almudena Burillo

    Full Text Available Microbiological confirmation of a urinary tract infection (UTI takes 24-48 h. In the meantime, patients are usually given empirical antibiotics, sometimes inappropriately. We assessed the feasibility of sequentially performing a Gram stain and MALDI-TOF MS mass spectrometry (MS on urine samples to anticipate clinically useful information. In May-June 2012, we randomly selected 1000 urine samples from patients with suspected UTI. All were Gram stained and those yielding bacteria of a single morphotype were processed for MALDI-TOF MS. Our sequential algorithm was correlated with the standard semiquantitative urine culture result as follows: Match, the information provided was anticipative of culture result; Minor error, the information provided was partially anticipative of culture result; Major error, the information provided was incorrect, potentially leading to inappropriate changes in antimicrobial therapy. A positive culture was obtained in 242/1000 samples. The Gram stain revealed a single morphotype in 207 samples, which were subjected to MALDI-TOF MS. The diagnostic performance of the Gram stain was: sensitivity (Se 81.3%, specificity (Sp 93.2%, positive predictive value (PPV 81.3%, negative predictive value (NPV 93.2%, positive likelihood ratio (+LR 11.91, negative likelihood ratio (-LR 0.20 and accuracy 90.0% while that of MALDI-TOF MS was: Se 79.2%, Sp 73.5, +LR 2.99, -LR 0.28 and accuracy 78.3%. The use of both techniques provided information anticipative of the culture result in 82.7% of cases, information with minor errors in 13.4% and information with major errors in 3.9%. Results were available within 1 h. Our serial algorithm provided information that was consistent or showed minor errors for 96.1% of urine samples from patients with suspected UTI. The clinical impacts of this rapid UTI diagnosis strategy need to be assessed through indicators of adequacy of treatment such as a reduced time to appropriate empirical treatment or

  4. Additional gonorrhea and Chlamydia infections found with rapid follow-up screening in men who have sex with men with an indication for HIV postexposure prophylaxis

    NARCIS (Netherlands)

    de Vrieze, Nynke H. N.; van Rooijen, Martijn S.; van de Loeff, Maarten Schim; de Vries, Henry J. C.

    2014-01-01

    Sexually transmitted infection was found in 16.5% of the men who have sex with men with a postexposure prophylaxis indication. Chlamydia and gonorrhea screening was repeated after 14 days. Among those who were initially sexually transmitted infection negative, 4.1% had chlamydia or gonorrhea. In

  5. Necrotizing Fasciitis In A Preterm, HIV Infected Baby | Olutekunbi ...

    African Journals Online (AJOL)

    Necrotizing fasciitis (NF) is a rapidly progressive life threatening bacterial infection of the soft tissues. It is commoner in the adult population where it is associated with systemic and local disease conditions such as diabetes mellitus, intravenous drug abuse, dental lesions, trauma and immunosuppression. It is rare in ...

  6. Hypoxia determines survival outcomes of bacterial infection through HIF-1α-dependent reprogramming of leukocyte metabolism

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J.P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Coelho, P.D.S.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N.M.

    2017-01-01

    Hypoxia and bacterial infection frequently coexist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both Staphylococcus aureus and Streptococcus pneumoniae infections rapidly induced progressive neutrophil-mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning ...

  7. Can rapid integrated polymerase chain reaction-based diagnostics for gastrointestinal pathogens improve routine hospital infection control practice? A diagnostic study.

    Science.gov (United States)

    Pankhurst, Louise; Macfarlane-Smith, Louissa; Buchanan, James; Anson, Luke; Davies, Kerrie; O'Connor, Lily; Ashwin, Helen; Pike, Graham; Dingle, Kate E; Peto, Timothy Ea; Wordsworth, Sarah; Walker, A Sarah; Wilcox, Mark H; Crook, Derrick W

    2014-08-01

    Every year approximately 5000-9000 patients are admitted to a hospital with diarrhoea, which in up to 90% of cases has a non-infectious cause. As a result, single rooms are 'blocked' by patients with non-infectious diarrhoea, while patients with infectious diarrhoea are still in open bays because of a lack of free side rooms. A rapid test for differentiating infectious from non-infectious diarrhoea could be very beneficial for patients. To evaluate MassCode multiplex polymerase chain reaction (PCR) for the simultaneous diagnosis of multiple enteropathogens directly from stool, in terms of sensitivity/specificity to detect four common important enteropathogens: Clostridium difficile, Campylobacter spp., Salmonella spp. and norovirus. A retrospective study of fixed numbers of samples positive for C. difficile (n = 200), Campylobacter spp. (n = 200), Salmonella spp. (n = 100) and norovirus (n = 200) plus samples negative for all these pathogens (n = 300). Samples were sourced from NHS microbiology laboratories in Oxford and Leeds where initial diagnostic testing was performed according to Public Health England methodology. Researchers carrying out MassCode assays were blind to this information. A questionnaire survey, examining current practice for infection control teams and microbiology laboratories managing infectious diarrhoea, was also carried out. MassCode assays were carried out at Oxford University Hospitals NHS Trust. Further multiplex assays, carried out using Luminex, were run on the same set of samples at Leeds Teaching Hospitals NHS Trust. The questionnaire was completed by various NHS trusts. Sensitivity and specificity to detect C. difficile, Campylobacter spp., Salmonella spp., and norovirus. Nucleic acids were extracted from 948 clinical samples using an optimised protocol (200 Campylobacter spp., 199 C. difficile, 60 S. enterica, 199 norovirus and 295 negative samples; some samples contained more than one pathogen). Using the Mass

  8. Effects of Hydroxychloroquine on Immune Activation and Disease Progression Among HIV-Infected Patients Not Receiving Antiretroviral Therapy A Randomized Controlled Trial

    Science.gov (United States)

    Paton, Nicholas I.; Goodall, Ruth L.; Dunn, David T.; Franzen, Samuel; Collaco-Moraes, Yolanda; Gazzard, Brian G.; Williams, Ian G.; Fisher, Martin J.; Winston, Alan; Fox, Julie; Orkin, Chloe; Herieka, Elbushra A.; Ainsworth, Jonathan G.; Post, Frank A.; Wansbrough-Jones, Mark; Kelleher, Peter

    2013-01-01

    Context Therapies to decrease immune activation might be of benefit in slowing HIV disease progression. Objective To determine whether hydroxychloroquine decreases immune activation and slows CD4 cell decline. Design, Setting, and Patients Randomized, double-blind, placebo-controlled trial performed at 10 HIV outpatient clinics in the United Kingdom between June 2008 and February 2011. The 83 patients enrolled had asymptomatic HIV infection, were not taking antiretroviral therapy, and had CD4 cell counts greater than 400 cells/μL. Intervention Hydroxychloroquine, 400 mg, or matching placebo once daily for 48 weeks. Main Outcome Measures The primary outcome measure was change in the proportion of activated CD8 cells (measured by the expression of CD38 and HLA-DR surface markers), with CD4 cell count and HIV viral load as secondary outcomes. Analysis was by intention to treat using mixed linear models. Results There was no significant difference in CD8 cell activation between the 2 groups (−4.8% and −4.2% in the hydroxychloroquine and placebo groups, respectively, at week 48; difference, −0.6%; 95% CI, −4.8% to 3.6%; P=.80). Decline in CD4 cell count was greater in the hydroxychloroquine than placebo group (−85 cells/μL vs −23 cells/μL at week 48; difference, −62 cells/μL; 95% CI, −115 to −8; P=.03). Viral load increased in the hydroxychloroquine group compared with placebo (0.61 log10 copies/mL vs 0.23 log10 copies/mL at week 48; difference, 0.38 log10 copies/mL; 95% CI, 0.13 to 0.63; P=.003). Antiretroviral therapy was started in 9 patients in the hydroxychloroquine group and 1 in the placebo group. Trial medication was well tolerated, but more patients reported influenza-like illness in the hydroxychloroquine group compared with the placebo group (29% vs 10%; P=.03). Conclusion Among HIV-infected patients not taking antiretroviral therapy, the use of hydroxychloroquine compared with placebo did not reduce CD8 cell activation but did result in

  9. HPV Infections in Adolescents

    Directory of Open Access Journals (Sweden)

    Anna-Barbara Moscicki

    2007-01-01

    Full Text Available Adolescents who are sexually active have the highest rates of prevalent and incident HPV infection rates with over 50–80% having infections within 2–3 years of initiating intercourse. These high rates reflect sexual behavior and biologic vulnerability. Most infections are transient in nature and cause no cytologic abnormality. However, a small number of adolescents will not clear the infection. Persistence of HPV is strongly linked to the development of high-grade squamous intra-epithelial lesions (HSIL and invasive cancer. The HSIL detected, however, does not appear to progress rapidly to invasive cancer. Understanding the natural history of HPV in adolescents has shed light into optional treatment strategies which include watchful observation of atypical squamous cells of undetermined significance (ASCUS and low grade (LSIL. The association between age of first intercourse and invasive cancer cannot be ignored. Consequently, initiating screening at appropriate times in this vulnerable group is essential. In addition, with the advent of the HPV vaccine, vaccination prior to the onset of sexual activity is critical since most infections occur within a short time frame post initiation.

  10. Human Immunodeficiency Virus (HIV types Western blot (WB band profiles as potential surrogate markers of HIV disease progression and predictors of vertical transmission in a cohort of infected but antiretroviral therapy naïve pregnant women in Harare, Zimbabwe

    Directory of Open Access Journals (Sweden)

    Chirenje Mike Z

    2011-01-01

    Full Text Available Abstract Background Expensive CD4 count and viral load tests have failed the intended objective of enabling access to HIV therapy in poor resource settings. It is imperative to develop simple, affordable and non-subjective disease monitoring tools to complement clinical staging efforts of inexperienced health personnel currently manning most healthcare centres because of brain drain. Besides accurately predicting HIV infection, sequential appearance of specific bands of WB test offers a window of opportunity to develop a less subjective tool for monitoring disease progression. Methods HIV type characterization was done in a cohort of infected pregnant women at 36 gestational weeks using WB test. Student-t test was used to determine maternal differences in mean full blood counts and viral load of mothers with and those without HIV gag antigen bands. Pearson Chi-square test was used to assess differences in lack of bands appearance with vertical transmission and lymphadenopathy. Results Among the 64 HIV infected pregnant women, 98.4% had pure HIV-1 infection and one woman (1.7% had dual HIV-1/HIV-2 infections. Absence of HIV pol antigen bands was associated with acute infection, p = 0.002. All women with chronic HIV-1 infection had antibody reactivity to both the HIV-1 envelope and polymerase antigens. However, antibody reactivity to gag antigens varied among the women, being 100%, 90%, 70% and 63% for p24, p17, p39 and p55, respectively. Lack of antibody reactivity to gag p39 antigen was associated with disease progression as confirmed by the presence of lymphadenopathy, anemia, higher viral load, p = 0.010, 0.025 and 0.016, respectively. Although not statistically significant, women with p39 band missing were 1.4 times more likely to transmit HIV-1 to their infants. Conclusion Absence of antibody reactivity to pol and gag p39 antigens was associated with acute infection and disease progression, respectively. Apart from its use in HIV disease

  11. Necrotising soft tissue infection following mastectomy

    Directory of Open Access Journals (Sweden)

    Jackson P

    2010-03-01

    Full Text Available Necrotising fasciitis is a rare but rapidly progressive soft tissue disease which can lead to extensive necrosis, systemic sepsis and death. Including this case, only 7 other cases have been reported in the world literature with only 2 others affecting the patient post mastectomy.This 59 year old Caucasian lady presented with severe soft tissue infection soon after mastectomy, which was successfully treated with a combination of debridement, triangulation, VAC© dressing and skin grafting.Necrotising soft tissue infections following mastectomy are rapidly progressive and potentially extremely serious. It is essential that a high index of clinical suspicion is maintained together with prompt aggressive treatment in a multidisciplinary environment to prevent worsening physical and psychological sequelae.

  12. Asymptomatic Plasmodium falciparum infection is associated with anaemia in pregnancy and can be more cost-effectively detected by rapid diagnostic test than by microscopy in Kinshasa, Democratic Republic of the Congo.

    Science.gov (United States)

    Matangila, Junior R; Lufuluabo, Jean; Ibalanky, Axel L; Inocêncio da Luz, Raquel A; Lutumba, Pascal; Van Geertruyden, Jean-Pierre

    2014-04-02

    In areas of high malaria transmission, Plasmodium falciparum infection during pregnancy is characterized by malaria-related anaemia, placental malaria and does not always result in clinical symptoms. This situation is associated with poor pregnancy outcomes. The aim of this study was to determine the extent of asymptomatic P. falciparum infection, its relation with anaemia as well as the most cost-effective technique for its diagnosis in healthy pregnant women living in Kinshasa, Democratic Republic of the Congo. In a cross-sectional study design, information on socio-demographic characteristics and cost data were collected in healthy pregnant women attending antenatal care consultations. Plasmodium falciparum infection was diagnosed using rapid diagnostic test (RDT), microscopy and polymerase chain reaction (PCR). Haemoglobin concentration was also determined. In total, 332 pregnant women were enrolled. RDT and microscopy data were available for all the blood samples and 166 samples were analysed by PCR. The prevalence of asymptomatic P. falciparum infection using microscopy, RDTs and PCR, were respectively 21.6%, 27.4% and 29.5%. Taking PCR as a reference, RDTs had a sensitivity of 81.6% and a specificity of 94.9% to diagnose asymptomatic P. falciparum infection. The corresponding values for microscopy were 67.3% and 97.4%. The prevalence of anaemia was 61.1% and asymptomatic malaria increased five times the odds (p anaemia. RDTs were more cost-effective compared to microscopy. Incremental cost-effectiveness ratio was US$ 63.47 per microscopy adequately diagnosed case. These alarming results emphasize the need to actively diagnose and treat asymptomatic malaria infection during all antenatal care visits. Moreover, in DRC, malaria and anaemia control efforts should be strengthened by promoting the use of insecticide-treated nets, intermittent preventive treatment with sulphadoxine-pyrimethamine and iron and folic acid supplements.

  13. Rapid differentiation of rocky mountain spotted fever from chickenpox, measles, and enterovirus infections and bacterial meningitis by frequency-pulsed electron capture gas-liquid chromatographic analysis of sera.

    Science.gov (United States)

    Brooks, J B; McDade, J E; Alley, C C

    1981-01-01

    Normal sera and sera from patients with Rocky Mountain spotted fever, chickenpox, enterovirus infections, measles, and Neisseria meningitidis infections were extracted with organic solvents under acidic and basic conditions and then derivatized with trichloroethanol or heptafluorobutyric anhydride-ethanol to form electron-capturing derivatives of organic acids, alcohols, and amines. The derivatives were analyzed by frequency-pulsed electron capture gas-liquid chromatography (FPEC-GLC). There were unique differences in the FPEC-GLC profiles of sera obtained from patients with these respective diseases. With Rocky Mountain spotted fever patients, typical profiles were detected as early as 1 day after onset of disease and before antibody could be detected in the serum. Rapid diagnosis of Rocky Mountain spotted fever by FPEC-GLC could permit early and effective therapy, thus preventing many deaths from this disease. PMID:7276147

  14. Increased cell division but not thymic dysfunction rapidly affects the T-cell receptor excision circle content of the naive T cell population in HIV-1 infection

    NARCIS (Netherlands)

    Hazenberg, Mette D.; Borleffs, J.C.C.; Otto, S.A.; Cohen Stuart, J.W.T. (James Willem Theodoor); Verschuren, M.C.M. (Martie); Boucher, C.A.B.; Coutinho, R.A.; Lange, Joep M.A.; Rinke de Wit, T.F. (Tobias); Tsegaye, A. (Aster); Dongen, J.J.M. (Jaques) van; Hamann, D. (Dörte); Boer, R.J. de; Miedema, F.

    2000-01-01

    Recent thymic emigrants can be identified by T cell receptor excision circles (TRECs) formed during T-cell receptor rearrangement. Decreasing numbers of TRECs have been observed with aging and in human immunodeficiency virus (HIV)-1 infected individuals, suggesting for thymic impairment. Here,

  15. Free treatment, rapid malaria diagnostic tests and malaria village workers can hasten progress toward achieving the malaria related millennium development goals: the Médecins Sans Frontières experience from Chad, Sierra-Leone and Mali

    Directory of Open Access Journals (Sweden)

    Katie Tayler-Smith

    2011-02-01

    Full Text Available Halving the burden of malaria by 2015 and ensuring that 80% of people with malaria receive treatment is among the health related targets of the Millennium Development Goals (MDGs. Despite political momentum toward achieving this target, progress is slow and many with malaria (particularly in poor and rural communities in Africa are still without access to effective treatment. Finding ways to improve access to anti-malarial treatment in Africa is essential to achieve the malaria related and other MDG targets. During its work in Chad, Sierra Leone and Mali in the period 2004 to 2008, Médecins Sans Frontières showed that it was possible to significantly improve access to effective malaria treatment through: i the removal of health centre level user fees for essential healthcare for vulnerable population groups, ii the introduction of free community based treatment for children using malaria village workers to diagnose and treat simple malaria in communities where geographical and financial barriers limited access to effective malaria care, iii the improved diagnosis and treatment of malaria using rapid diagnosis tests and artemisinin based combination therapy, at both health facilities and in the community. This paper describes and discusses these strategies and their related impact.

  16. Experimental chronic hepatitis B infection of neonatal tree shrews (Tupaia belangeri chinensis: A model to study molecular causes for susceptibility and disease progression to chronic hepatitis in humans

    Directory of Open Access Journals (Sweden)

    Wang Qi

    2012-08-01

    Full Text Available Abstract Background Hepatitis B virus (HBV infection continues to be an escalating global health problem. Feasible and effective animal models for HBV infection are the prerequisite for developing novel therapies for this disease. The tree shrew (Tupaia is a small animal species evolutionary closely related to humans, and thus is permissive to certain human viral pathogens. Whether tree shrews could be chronically infected with HBV in vivo has been controversial for decades. Most published research has been reported on adult tree shrews, and only small numbers of HBV infected newborn tree shrews had been observed over short time periods. We investigated susceptibility of newborn tree shrews to experimental HBV infection as well as viral clearance over a protracted time period. Results Forty-six newborn tree shrews were inoculated with the sera from HBV-infected patients or tree shrews. Serum and liver samples of the inoculated animals were periodically collected and analyzed using fluorescence quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, Southern blot, and immunohistochemistry. Six tree shrews were confirmed and four were suspected as chronically HBV-infected for more than 48 (up to 228 weeks after inoculation, including three that had been inoculated with serum from a confirmed HBV-infected tree shrew. Conclusions Outbred neonatal tree shrews can be long-term chronically infected with HBV at a frequency comparable to humans. The model resembles human disease where also a smaller proportion of infected individuals develop chronic HBV related disease. This model might enable genetic and immunologic investigations which would allow determination of underlying molecular causes favoring susceptibility for chronic HBV infection and disease establishment vs. viral clearance.

  17. Rapid detection of serum antibody by dual-path platform VetTB assay in white-tailed deer infected with Mycobacterium bovis.

    Science.gov (United States)

    Lyashchenko, Konstantin P; Greenwald, Rena; Esfandiari, Javan; O'Brien, Daniel J; Schmitt, Stephen M; Palmer, Mitchell V; Waters, W Ray

    2013-06-01

    Bovine tuberculosis (TB) in cervids remains a significant problem affecting farmed herds and wild populations. Traditional skin testing has serious limitations in certain species, whereas emerging serological assays showed promising diagnostic performance. The recently developed immunochromatographic dual-path platform (DPP) VetTB assay has two antigen bands, T1 (MPB83 protein) and T2 (CFP10/ESAT-6 fusion protein), for antibody detection. We evaluated the diagnostic accuracy of this test by using serum samples collected from groups of white-tailed deer experimentally inoculated with Mycobacterium bovis, M. avium subsp. paratuberculosis, or M. bovis BCG Pasteur. In addition, we used serum samples from farmed white-tailed deer in herds with no history of TB, as well as from free-ranging white-tailed deer culled during field surveillance studies performed in Michigan known to have bovine TB in the wild deer population. The DPP VetTB assay detected antibody responses in 58.1% of experimentally infected animals within 8 to 16 weeks postinoculation and in 71.9% of naturally infected deer, resulting in an estimated test sensitivity of 65.1% and a specificity of 97.8%. The higher seroreactivity found in deer with naturally acquired M. bovis infection was associated with an increased frequency of antibody responses to the ESAT-6 and CFP10 proteins, resulting in a greater contribution of these antigens, in addition to MPB83, to the detection of seropositive animals, compared with experimental M. bovis infection. Deer experimentally inoculated with either M. avium subsp. paratuberculosis or M. bovis BCG Pasteur did not produce cross-reactive antibodies that could be detected by the DPP VetTB assay. The present findings demonstrate the relatively high diagnostic accuracy of the DPP VetTB test for white-tailed deer, especially in the detection of naturally infected animals.

  18. Diagnostic performances of two rapid tests for detection of feline leukemia virus antigen in sera of experimentally feline leukemia virus-infected cats

    Directory of Open Access Journals (Sweden)

    Matthew R Krecic

    2017-12-01

    Full Text Available Objectives The objective of this study was to compare the diagnostic sensitivities and specificities of WITNESS FeLV-FIV (Zoetis and SNAP FIV/FeLV Combo Test (IDEXX for the detection of FeLV p27 antigen in the sera of experimentally feline leukemia virus (FeLV-infected cats. Methods Diagnostic sensitivities of WITNESS and SNAP were determined through testing of 47 serum samples collected from cats day 56 post-experimental infection with a virulent FeLV Rickard strain. Successful experimental infection was confirmed based on observation of FeLV antigen and proviral DNA in anti-coagulated (EDTA whole-blood samples by immunofluorescent antibody (IFA test and PCR, respectively. Diagnostic specificities of both tests were determined through testing of sera of 92 laboratory-housed, non-FeLV-exposed specific pathogen-free (SPF cats. Results Forty-one of 47 blood samples were IFA positive, whereas all 47 samples were PCR positive. All 92 non-FeLV-infected SPF cats were IFA and PCR negative. In comparison to IFA as the reference method, both WITNESS and SNAP tests yielded equivalent sensitivities and specificities of 100% and 97.8%, respectively. In comparison to PCR as the reference method, both WITNESS and SNAP tests likewise performed equivalently, with sensitivities and specificities of 91.5% and 100%, respectively. Conclusions and relevance Sensitivity and specificity of WITNESS FeLV-FIV for identifying FeLV p27 antigen in the sera of these experimentally FeLV-infected and non-FeLV-exposed SPF cats equaled those of the SNAP FIV/FeLV Combo Test. However, all positive results, regardless of the point-of-care test used, should be confirmed before making clinical decisions such as segregation from other cats or euthanasia.

  19. Hepatitis B virus surface antigen and anti-hepatitis C virus rapid tests underestimate hepatitis prevalence among HIV-infected patients

    DEFF Research Database (Denmark)

    Hønge, Bo Langhoff; Jespersen, S; Medina, C

    2014-01-01

    . RESULTS: Two rapid tests were used in Guinea-Bissau: HBsAg Strip Ref 2034 (VEDA.LAB, Alençon, France; sensitivity 62.3%; specificity 99.2%) and HEPA-SCAN (Bhat Bio-Tech, Bangalore, India; sensitivity 57.1%; specificity 99.7%). In the two tests the ability to obtain the correct outcome depended...

  20. Incidence of infection in 39-month-old ewes with TMEM154 diplotypes "1 1," "1 3," and "3 3" after natural exposure to ovine progressive pneumonia virus

    Science.gov (United States)

    Production and well-being of sheep and goats in many countries are harmfully impacted by small ruminant lentiviruses (SRLV) that cause incurable, progressive diseases. Susceptibility to ovine progressive pneumonia virus (OPPV), the North American form of SRLV, is influenced by variants of the ovine...

  1. Kinetics of IFN-gamma and TNF-alpha gene expression and their relationship with disease progression after infection with Mycobacterium tuberculosis in guinea pigs.

    Science.gov (United States)

    Roh, In Soon; Cho, Sungae; Eum, Seok-Yong; Cho, Sang-Nae

    2013-05-01

    Guinea pig is one of the most suitable animal models for Mycobacterium tuberculosis (M. tb) infection since it shows similarities to pulmonary infection in humans. Although guinea pig shows hematogenous spread of M. tb infection into the whole body, immunological studies have mainly focused on granulomatous tissues in lungs and spleens. In order to investigate the time-course of disease pathogenesis and immunological profiles in each infected organ, we performed the following approaches with guinea pigs experimentally infected with M. tb over a 22-week post-infection period. We examined body weight changes, M. tb growth curve, cytokine gene expression (IFN-γ and TNF-α), and histopathology in liver, spleen, lungs and lymph nodes of infected guinea pigs. The body weights of infected guinea pigs did not increase as much as uninfected ones and the number of M. tb bacilli in their organs increased except bronchotracheal lymph node during the experimental period. The gene expression of IFN-γ and TNF-α was induced between 3 and 6 weeks of infection; however, kinetic profiles of cytokine gene expression showed heterogeneity among organs over the study period. Histophathologically granulomatous lesions were developed in all four organs of infected guinea pigs. Although IFN-γ and TNF-α gene expression profiles showed heterogeneity, the granuloma formation was clearly observed in every organ regardless of whether the number of bacilli increased or decreased. However, this protective immunity was accompanied with severe tissue damage in all four organs, which may lead to the death of guinea pigs.

  2. Necrotizing Soft Tissue Infection

    Directory of Open Access Journals (Sweden)

    Sahil Aggarwal, BS

    2018-04-01

    Full Text Available History of present illness: A 71-year-old woman with a history of metastatic ovarian cancer presented with sudden onset, rapidly progressing painful rash in the genital region and lower abdominal wall. She was febrile to 103°F, heart rate was 114 beats per minute, and respiratory rate was 24 per minute. Her exam was notable for a toxic-appearing female with extensive areas of erythema, tenderness, and induration to her lower abdomen, intertriginous areas, and perineum with intermittent segments of crepitus without hemorrhagic bullae or skin breakdown. Significant findings: Computed tomography (CT of the abdominal and pelvis with intravenous (IV contrast revealed inflammatory changes, including gas and fluid collections within the ventral abdominal wall extending to the vulva, consistent with a necrotizing soft tissue infection. Discussion: Necrotizing fasciitis is a serious infection of the skin and soft tissues that requires an early diagnosis to reduce morbidity and mortality. Classified into several subtypes based on the type of microbial infection, necrotizing fasciitis can rapidly progress to septic shock or death if left untreated.1 Diagnosing necrotizing fasciitis requires a high index of suspicion based on patient risk factors, presentation, and exam findings. Definitive treatment involves prompt surgical exploration and debridement coupled with IV antibiotics.2,3 Clinical characteristics such as swelling, disproportionate pain, erythema, crepitus, and necrotic tissue should be a guide to further diagnostic tests.4 Unfortunately, lab values such as white blood cell count and lactate imaging studies have high sensitivity but low specificity, making the diagnosis of necrotizing fasciitis still largely a clinical one.4,5 CT is a reliable method to exclude the diagnosis of necrotizing soft tissue infections (sensitivity of 100%, but is only moderately reliable in correctly identifying such infections (specificity of 81%.5 Given the emergent

  3. Development of a One-Step Probe Based Molecular Assay for Rapid Immunodiagnosis of Infection with M. tuberculosis Using Dried Blood Spots

    DEFF Research Database (Denmark)

    Blauenfeldt, Thomas; Heyckendorf, Jan; Graff Jensen, Sidse

    2014-01-01

    BACKGROUND: Antigen specific release of IP-10 is the most promising alternative marker to IFN-γ for infection with M. tuberculosis. Compared to Interferon-γ release assays (IGRA), IP-10 is released in high levels enabling novel approaches such as field friendly dried blood spots (DBS) and molecular...... was validated and applied for the diagnosis of M. tuberculosis infection in DBS samples from 43 patients with confirmed TB, 13 patients with latent TB and 96 presumed uninfected controls. In parallel, IP-10 and INF-γ levels were measured in Quantiferon (QFT-TB) plasma supernatants. RESULTS: IP-10 m......RNA upregulation was detectable at 4 hours after stimulation (6 fold upregulation) peaking at 8 hours (108 fold upregulation). IFN-γ expression occurred in concert but levels were lower (peak 6.7 fold upregulation). IP-10 gene expression level was significantly higher in patients with tuberculosis (median 31...

  4. Rapid, simple and direct detection of Meloidogyne hapla from infected root galls using loop-mediated isothermal amplification combined with FTA technology

    OpenAIRE

    Peng, Huan; Long, Haibo; Huang, Wenkun; Liu, Jing; Cui, Jiangkuan; Kong, Lingan; Hu, Xianqi; Gu, Jianfeng; Peng, Deliang

    2017-01-01

    The northern root-knot nematode (Meloidogyne hapla) is a damaging nematode that has caused serious economic losses worldwide. In the present study, a sensitive, simple and rapid method was developed for detection of M. hapla in infested plant roots by combining a Flinders Technology Associates (FTA) card with loop-mediated isothermal amplification (LAMP). The specific primers of LAMP were designed based on the distinction of internal transcribed spacer (ITS) sequences between M. hapla and oth...

  5. Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

    CERN Multimedia

    1969-01-01

    Around the laboratories: Dubna: Physics results and progress on bubble chamber techniques; Stanford (SLAC): Operation of a very rapid cycling bubble chamber; Daresbury: Photographs of visitors to the Laboratory; Argonne: Charge exchange injection tests into the ZGS in preparation for a proposed Booster

  6. Human T cell leukemia/lymphoma virus type I infection of a CD4+ proliferative/cytotoxic T cell clone progresses in at least two distinct phases based on changes in function and phenotype of the infected cells

    NARCIS (Netherlands)

    Yssel, H.; de Waal Malefyt, R.; Duc Dodon, M. D.; Blanchard, D.; Gazzolo, L.; de Vries, J. E.; Spits, H.

    1989-01-01

    The effect of human T cell leukemia/lymphoma virus type I (HTLV-I) infection on the function and the phenotype of a human proliferating/cytotoxic T cell clone, specific for tetanus toxin, was investigated. During the period after infection, two distinct phases were observed, based on growth

  7. Evaluation of a rapid immunochromatographic dipstick test for detection of antibodies to Trypanosoma cruzi in dogs experimentally infected with isolates obtained from opossums (Didelphis virginiana), armadillos (Dasypus novemcinctus), and dogs (Canis familiaris) from the United States.

    Science.gov (United States)

    Rosypal, Alexa C; Hill, Roderick; Lewis, Samantha; Barr, Stephen C; Valadas, Samantha; Gennari, Solange Maria; Lindsay, David S

    2011-02-01

    Dogs are reservoir hosts for Trypanosoma cruzi , the causative agent of American trypanosomiasis. A rapid immunochromatographic dipstick test (ICT) is available commercially for canine serological testing. The ICT was developed with the use of sera from South American dogs, but it is not routinely used in the United States. We evaluated the utility of the ICT in detecting anti-T. cruzi antibodies in dogs from the United States. Dogs (N  =  64) were experimentally infected with United States' isolates of T. cruzi from an opossum (Didelphis virginiana), an armadillo (Dasypus novemcinctus), and a domestic dog (Canis familiaris), and were tested after experimental infection. Sera from uninfected United States dogs (n  =  79; hemaculture negative) were used as negative controls. In a blind study, sera were tested by the ICT and compared to the indirect immunofluorescent antibody test with the use of Brazil-strain epimastigotes as antigen. The sensitivity of the ICT was 91% and the specificity was 98% in dogs experimentally infected with United States isolates. Our study indicates that the ICT could be a useful screening tool for serological surveillance of canine T. cruzi exposure in the United States.

  8. Rapid microbiology - raising awareness.

    Science.gov (United States)

    Bailie, Jonathan

    2016-01-01

    A 'high-level overview' of some of the emerging rapid microbiology technologies designed to help healthcare engineering and infection control teams working in hospitals and other healthcare facilities more rapidly identify potentially hazardous levels of waterborne microorganisms in their water systems, enabling them to take prompt remedial action, and a look at the some of the 'pros and cons' of such testing techniques, was given by Nalco technical director, Howard Barnes, the vice-chair of the Legionella Control Association (LCA), at a recent LCA open day. HEJ editor, Jonathan Bailie, reports.

  9. Direct maldi-tof mass spectrometry assay of blood culture broths for rapid identification of Candida species causing bloodstream infections: an observational study in two large microbiology laboratories.

    Science.gov (United States)

    Spanu, Teresa; Posteraro, Brunella; Fiori, Barbara; D'Inzeo, Tiziana; Campoli, Serena; Ruggeri, Alberto; Tumbarello, Mario; Canu, Giulia; Trecarichi, Enrico Maria; Parisi, Gabriella; Tronci, Mirella; Sanguinetti, Maurizio; Fadda, Giovanni

    2012-01-01

    We evaluated the reliability of the Bruker Daltonik's MALDI Biotyper system in species-level identification of yeasts directly from blood culture bottles. Identification results were concordant with those of the conventional culture-based method for 95.9% of Candida albicans (187/195) and 86.5% of non-albicans Candida species (128/148). Results were available in 30 min (median), suggesting that this approach is a reliable, time-saving tool for routine identification of Candida species causing bloodstream infection.

  10. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    OpenAIRE

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-01-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tes...

  11. Rapid detection of Piper yellow mottle virus and Cucumber mosaic virus infecting black pepper (Piper nigrum) by loop-mediated isothermal amplification (LAMP).

    Science.gov (United States)

    Bhat, A I; Siljo, A; Deeshma, K P

    2013-10-01

    The loop-mediated isothermal amplification (LAMP) assay for Piper yellow mottle virus and the reverse transcription (RT) LAMP assay for Cucumber mosaic virus each consisted of a set of five primers designed against the conserved sequences in the viral genome. Both RNA and DNA isolated from black pepper were used as a template for the assay. The results were assessed visually by checking turbidity, green fluorescence and pellet formation in the reaction tube and also by gel electrophoresis. The assay successfully detected both viruses in infected plants whereas no cross-reactions were recorded with healthy plants. Optimum conditions for successful amplification were determined in terms of the concentrations of magnesium sulphate and betaine, temperature, and duration. The detection limit for both LAMP and RT-LAMP was up to 100 times that for conventional PCR and up to one-hundredth of that for real-time PCR. The optimal conditions arrived at were validated by testing field samples of infected vines of three species from different regions. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. A rapid genotyping method for an obligate fungal pathogen, Puccinia striiformis f.sp. tritici, based on DNA extraction from infected leaf and Multiplex PCR genotyping

    Directory of Open Access Journals (Sweden)

    Enjalbert Jérôme

    2011-07-01

    Full Text Available Abstract Background Puccinia striiformis f.sp. tritici (PST, an obligate fungal pathogen causing wheat yellow/stripe rust, a serious disease, has been used to understand the evolution of crop pathogen using molecular markers. However, numerous questions regarding its evolutionary history and recent migration routes still remains to be addressed, which need the genotyping of a large number of isolates, a process that is limited by both DNA extraction and genotyping methods. To address the two issues, we developed here a method for direct DNA extraction from infected leaves combined with optimized SSR multiplexing. Findings We report here an efficient protocol for direct fungal DNA extraction from infected leaves, avoiding the costly and time consuming step of spore multiplication. The genotyping strategy we propose, amplified a total of 20 SSRs in three Multiplex PCR reactions, which were highly polymorphic and were able to differentiate different PST populations with high efficiency and accuracy. Conclusion These two developments enabled a genotyping strategy that could contribute to the development of molecular epidemiology of yellow rust disease, both at a regional or worldwide scale.

  13. Will gay and bisexually active men at high risk of infection use over-the-counter rapid HIV tests to screen sexual partners?

    Science.gov (United States)

    Carballo-Diéguez, Alex; Frasca, Timothy; Dolezal, Curtis; Balan, Ivan

    2012-01-01

    The Food and Drug Administration may license OraQuick™, a rapid HIV test, for over-the-counter (OTC) sale. This study investigated whether HIV-uninfected, non-monogamous, gay and bisexual men who never or rarely use condoms would use the test with partners as a harm-reduction approach. Sixty participants responded to two computer-assisted self-interviews, underwent an in-depth interview, and chose whether to test themselves with OraQuick. Over 80% of the men said they would use the kit to test sexual partners or themselves if it became available OTC. Most participants understood that antibody tests have a window period in which the virus is undetectable, yet saw advantages to using the test to screen partners; 74% tested themselves in our offices. Participants offered several possible strategies to introduce the home-test idea to partners, frequently endorsed mutual testing, and highlighted that home testing could stimulate greater honesty in serostatus disclosure. Participants drew distinctions between testing regular versus occasional partners. Non-monogamous men who have sex with men, who never or rarely use condoms, may nevertheless seek to avoid HIV. Technologies that do not interfere with sexual pleasure are likely to be used when available. Studies are needed to evaluate the advantages and disadvantages of using OTC rapid HIV tests as one additional harm-reduction tool.

  14. Development of a rapid agglutination latex test for diagnosis of enteropathogenic and enterohemorrhagic Escherichia coli infection in developing world: defining the biomarker, antibody and method.

    Directory of Open Access Journals (Sweden)

    Letícia B Rocha

    2014-09-01

    Full Text Available Enteropathogenic and enterohemorrhagic Escherichia coli (EPEC/EHEC are human intestinal pathogens responsible for diarrhea in both developing and industrialized countries. In research laboratories, EPEC and EHEC are defined on the basis of their pathogenic features; nevertheless, their identification in routine laboratories is expensive and laborious. Therefore, the aim of the present work was to develop a rapid and simple assay for EPEC/EHEC detection. Accordingly, the EPEC/EHEC-secreted proteins EspA and EspB were chosen as target antigens.First, we investigated the ideal conditions for EspA/EspB production/secretion by ELISA in a collection of EPEC/EHEC strains after cultivating bacterial isolates in Dulbecco's modified Eagle's medium (DMEM or DMEM containing 1% tryptone or HEp-2 cells-preconditioned DMEM, employing either anti-EspA/anti-EspB polyclonal or monoclonal antibodies developed and characterized herein. Subsequently, a rapid agglutination latex test (RALT was developed and tested with the same collection of bacterial isolates.EspB was defined as a biomarker and its corresponding monoclonal antibody as the tool for EPEC/EHEC diagnosis; the production of EspB was better in DMEM medium. RALT assay has the sensitivity and specificity required for high-impact diagnosis of neglected diseases in the developing world.RALT assay described herein can be considered an alternative assay for diarrhea diagnosis in low-income countries since it achieved 97% sensitivity, 98% specificity and 97% efficiency.

  15. Donor Vδ1+ γδ T cells expand after allogeneic hematopoietic stem cell transplantation and show reactivity against CMV-infected cells but not against progressing B-CLL.

    Science.gov (United States)

    Prinz, Immo; Thamm, Kristina; Port, Matthias; Weissinger, Eva M; Stadler, Michael; Gabaev, Ildar; Jacobs, Roland; Ganser, Arnold; Koenecke, Christian

    2013-05-11

    γδ T lymphocytes play an important role in immune reactions towards infections and malignancies. In particular, Vγ9-Vδ1+ T lymphocytes are thought to play protective antiviral roles in human CMV infection. Recently, Vδ1+ T lymphocytes were proposed to also have anti- B-CLL reactivity. Here we report a case of 48-year-old man who received allogeneic stem cell transplantation for progressive B-CLL. Within one year after transplantation, lymphoma relapsed despite a dramatic increase of Vδ1+ T cells in the patient's blood. In vitro killing assays revealed activity of patient's γδ cells against CMV target cells, but not against the relapsing lymphoma-cells. This argues for a contribution of Vδ1+ cells in the immune reaction against CMV reactivation, but does not support a strong correlation of expanded Vδ1+ T cells and favorable disease outcome in B-CLL patients.

  16. Impact of an HPV6/11/16/18 L1 virus-like particle vaccine on progression to cervical intraepithelial neoplasia in seropositive women with HPV16/18 infection

    DEFF Research Database (Denmark)

    Haupt, Richard M; Wheeler, Cosette M; Brown, Darron R

    2011-01-01

    The impact of a human papillomavirus (HPV) vaccine on development of cervical intraepithelial neoplasia grade 2-3 or adenocarcinoma in situ (CIN2-3/AIS) in women with ongoing HPV16 or 18 infections prevaccination is reported. Seventeen thousand six-hundred and twenty-two women aged 16-26 were.......9). These data suggest HPV vaccination neither reduces nor enhances progression to HPV16/18-related high grade cervical lesions, and cervical cytology screening and corresponding management should continue as per local recommendations. Ultimately, population-based surveillance of vaccinated individuals beyond...

  17. Changes in soluble factor-mediated CD8+ cell-derived antiviral activity in cynomolgus macaques infected with simian immunodeficiency virus SIVmac251: relationship to biological markers of progression.

    Science.gov (United States)

    Dioszeghy, Vincent; Benlhassan-Chahour, Kadija; Delache, Benoit; Dereuddre-Bosquet, Nathalie; Aubenque, Celine; Gras, Gabriel; Le Grand, Roger; Vaslin, Bruno

    2006-01-01

    Cross-sectional studies have shown that the capacity of CD8+ cells from human immunodeficiency virus (HIV)-infected patients and simian immunodeficiency virus (SIV) SIVmac-infected macaques to suppress the replication of human and simian immunodeficiency viruses in vitro depends on the clinical stage of disease, but little is known about changes in this antiviral activity over time in individual HIV-infected patients or SIV-infected macaques. We assessed changes in the soluble factor-mediated noncytolytic antiviral activity of CD8+ cells over time in eight cynomolgus macaques infected with SIVmac251 to determine the pathophysiological role of this activity. CD8+ cell-associated antiviral activity increased rapidly in the first week after viral inoculation and remained detectable during the early phase of infection. The net increase in antiviral activity of CD8+ cells was correlated with plasma viral load throughout the 15 months of follow-up. CD8+ cells gradually lost their antiviral activity over time and acquired virus replication-enhancing capacity. Levels of antiviral activity correlated with CD4+ T-cell counts after viral set point. Concentrations of beta-chemokines and interleukin-16 in CD8+ cell supernatants were not correlated with this antiviral activity, and alpha-defensins were not detected. The soluble factor-mediated antiviral activity of CD8+ cells was neither cytolytic nor restricted to major histocompatibility complex. This longitudinal study strongly suggests that the increase in noncytolytic antiviral activity from baseline and the maintenance of this increase over time in cynomolgus macaques depend on both viral replication and CD4+ T cells.

  18. Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (G4) infection: a cohort study of 71 806 patients.

    Science.gov (United States)

    Saad, Yasmin; Awad, Abobakr; Alakel, Wafaa; Doss, Wahid; Awad, Tahany; Mabrouk, Mahasen

    2018-02-01

    Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110-126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and α-fetoprotein (AFP), and low platelets and serum albumin (P≤0.001). Advanced liver fibrosis (F3-F4) was significantly correlated with DM (P≤0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.

  19. Progressive outer retinal necrosis presenting as cherry red spot.

    Science.gov (United States)

    Yiu, Glenn; Young, Lucy H

    2012-10-01

    To report a case of progressive outer retinal necrosis (PORN) presenting as a cherry red spot. Case report. A 53-year-old woman with recently diagnosed HIV and varicella-zoster virus (VZV) aseptic meningitis developed rapid sequential vision loss in both eyes over 2 months. Her exam showed a "cherry red spot" in both maculae with peripheral atrophy and pigmentary changes, consistent with PORN. Due to her late presentation and the rapid progression of her condition, she quickly developed end-stage vision loss in both eyes. PORN should be considered within the differential diagnosis of a "cherry red spot." Immune-deficient patients with a history of herpetic infection who present with visual loss warrant prompt ophthalmological evaluation.

  20. R5 strains of human immunodeficiency virus type 1 from rapid progressors lacking X4 strains do not possess X4-type pathogenicity in human thymus

    NARCIS (Netherlands)

    Berkowitz, R. D.; van't Wout, A. B.; Kootstra, N. A.; Moreno, M. E.; Linquist-Stepps, V. D.; Bare, C.; Stoddart, C. A.; Schuitemaker, H.; McCune, J. M.

    1999-01-01

    Some individuals infected with only R5 strains of human immunodeficiency virus type 1 progress to AIDS as quickly as individuals harboring X4 strains. We determined that three R5 viruses were much less pathogenic than an X4 virus in SCID-hu Thy/Liv mice, suggesting that R5 virus-mediated rapid

  1. Rapid deterioration of Mooren?s ulcers after conjunctival flap: a review of 2 cases

    OpenAIRE

    Li, Saiqun; Deng, Yuqing; Du, Caiyuan; Huang, Haixiang; Zhong, Jing; Chen, Ling; Wang, Bowen; Yuan, Jin

    2017-01-01

    Background Conjunctival flaps are a widely used treatment for numerous corneal ulcers that are caused by microorganismal infections. However, whether it can be performed on immune-mediated corneal ulcers is controversial. Case presentation We present two cases of Mooren?s ulcer that were treated using conjunctival flap in an attempt to prevent further corneal perforation at their local hospital. A rapid acceleration in ulcer progression was observed after a conjunctival flap was applied. Ulti...

  2. Risk Factor or Social Vaccine? The Historical Progression of the Role of Education in HIV and AIDS Infection in Sub-Saharan Africa

    Science.gov (United States)

    Baker, David P.; Collins, John M.; Leon, Juan

    2008-01-01

    Numerous epidemiological studies from the early years of the tragic HIV and AIDS pandemic in sub-Saharan Africa identified formal education as a risk factor increasing the chance of infection. Instead of playing its usual role as a preventative factor, as has been noted in many other public health cases, until the mid-1990s educated African men…

  3. Effect of deworming on disease progression markers in HIV-1-infected pregnant women on antiretroviral therapy: a longitudinal observational study from Rwanda.

    Science.gov (United States)

    Ivan, Emil; Crowther, Nigel J; Mutimura, Eugene; Rucogoza, Aniceth; Janssen, Saskia; Njunwa, Kato K; Grobusch, Martin P

    2015-01-01

    Deworming human immunodeficiency virus (HIV)-infected individuals on antiretroviral therapy (ART) may be beneficial, particularly during pregnancy. We determined the efficacy of targeted and nontargeted antihelminth therapy and its effects on Plasmodium falciparum infection status, hemoglobin levels, CD4 counts, and viral load in pregnant, HIV-positive women receiving ART. Nine hundred eighty HIV-infected pregnant women receiving ART were examined at 2 visits during pregnancy and 2 postpartum visits within 12 weeks. Women were given antimalarials when malaria-positive whereas albendazole was given in a targeted (n = 467; treatment when helminth stool screening was positive) or nontargeted (n = 513; treatment at all time points, with stool screening) fashion. No significant differences were noted between targeted and nontargeted albendazole treatments for the variables measured at each study visit except for CD4 counts, which were lower (P pregnant HIV-infected women with helminth coinfections receiving ART. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Teste rápido para detecção da infecção pelo HIV-1 em gestantes Rapid test to detect HIV-1 infection among pregnant women

    Directory of Open Access Journals (Sweden)

    Geraldo Duarte

    2001-03-01

    Full Text Available Objetivos: avaliar os resultados do teste de diagnóstico rápido da infecção pelo HIV-1 disponibilizado pelo Ministério da Saúde, para identificação de gestantes contaminadas por este vírus. Métodos: avaliação prospectiva de 443 gestantes sem teste sorológico para HIV no pré-natal, atendidas no Departamento de Ginecologia e Obstetrícia da Faculdade de Medicina de Ribeirão Preto-Universidade de São Paulo (HCFMRP-USP, entre fevereiro e junho de 2000. As amostras destas pacientes foram submetidas ao teste rápido imunocromatográfico, sendo comparadas com ELISA e confirmadas pela aglutinação. Resultados: dentre as 443 gestantes submetidas ao teste rápido (20,1% dos partos no período, 16 apresentaram resultados positivos (3,6%. Nenhuma amostra negativa pelo teste rápido foi positiva pelo ELISA. Entretanto, das 16 amostras positivas pelo teste rápido, duas foram negativas pelos testes confirmatórios. Logo, a sensibilidade do teste rápido foi de 100,0%, especificidade 99,5%, valor preditivo positivo 87,5% e valor preditivo negativo 100,0%. Conclusões: os resultados obtidos na avaliação do teste para o diagnóstico rápido da infecção pelo HIV-1 em gestantes revelaram sensibilidade, especificidade e valores preditivos que o credenciam como recurso extremamente importante na indicação de medidas que reduzem a transmissão perinatal desse vírus.Purpose: to evaluate the results of a rapid diagnostic test for HIV-1 infection made available by the Health Ministry for the identification of pregnant women contaminated by this virus. Methods: we evaluated prospectively 443 pregnant women with no prenatal serologic anti-HIV test seen at the Department of Gynecology and Obstetrics of the Faculty of Medicine of Ribeirão Preto, University of São Paulo, from February to June, 2000. Samples from these patients were submitted to the rapid immunochromatographic test, which was compared with ELISA and submitted to a confirmatory

  5. Tissue printing technique in nitrocelullose membranes: a rapid detection technique for estimating incidence of PVX, PVY, PVS and PLRV viruses infecting potato (Solanum spp.

    Directory of Open Access Journals (Sweden)

    Mónica Guzmán

    2002-07-01

    Full Text Available The ELISA serological technique has been used since the 1970s as a quantative technique for the detection of many groups of virus which infect plants. The immune-impression (IMI in nitrocelullose membrane qualitative technique has been implemented more recently for the detection of different viral groups. In this work, the IMI technique has been adapted for the detection of PVX, PVY PVS and PLRV viruses which attack different species and varieties of potato crop (Solanum spp., such as Egg yolk, Capiro, Morita, Pastusa, Monserrate, Tuquerreña, ICA Puracé and ICA Nariño, all from the Nariño department. The four viruses mentioned above can cause 30% and 60% losses in production, be they acting alone or synergistically. This means that they can easily reduce the economic benefits of a country like Colombia, characterised as being a great potato producer (i.e. more than 2.8 million tons per year. The IMI technique was compared with the ELISA technique (Enzymne Linked Immunosorbent Assay using the same samples, leading to confirmation of the test's sensitivity for detecting the virus. From a total of 800 samples analyzed by IMI from different areas in the Nariño department, 72% incidence for PVY, 38.7% for PVX, 85.6% for PVS and 91.1% for PLRV was found; these estimates were similar or greater than those obtained using ELISA. These results are new for Colombia in terms of imple-menting the easy and sensitive IMI technique for detecting these four viral groups infecting the potato as well as estimating their incidence in Nariño, one of Colombia's most important potato-producing departments. The opportune and flexible detection of virus leads to an effective response to eradicating contaminated material, both material in the field as well as that from in vitro culture. Results lead to it being suggested that implementing IMI could bringing wide benefits for potato seed certification programmes, as they maintain sensitivity and specificity, they

  6. Sensitivity and Specificity of a Prototype Rapid Diagnostic Test for the Detection of Trypanosoma brucei gambiense Infection: A Multi-centric Prospective Study.

    Science.gov (United States)

    Bisser, Sylvie; Lumbala, Crispin; Nguertoum, Etienne; Kande, Victor; Flevaud, Laurence; Vatunga, Gedeao; Boelaert, Marleen; Büscher, Philippe; Josenando, Theophile; Bessell, Paul R; Biéler, Sylvain; Ndung'u, Joseph M

    2016-04-01

    A major challenge in the control of human African trypanosomiasis (HAT) is lack of reliable diagnostic tests that are rapid and easy to use in remote areas where the disease occurs. In Trypanosoma brucei gambiense HAT, the Card Agglutination Test for Trypanosomiasis (CATT) has been the reference screening test since 1978, usually on whole blood, but also in a 1/8 dilution (CATT 1/8) to enhance specificity. However, the CATT is not available in a single format, requires a cold chain for storage, and uses equipment that requires electricity. A solution to these challenges has been provided by rapid diagnostic tests (RDT), which have recently become available. A prototype immunochromatographic test, the SD BIOLINE HAT, based on two native trypanosomal antigens (VSG LiTat 1.3 and VSG LiTat 1.5) has been developed. We carried out a non-inferiority study comparing this prototype to the CATT 1/8 in field settings. The prototype SD BIOLINE HAT, the CATT Whole Blood and CATT 1/8 were systematically applied on fresh blood samples obtained from 14,818 subjects, who were prospectively enrolled through active and passive screening in clinical studies in three endemic countries of central Africa: Angola, the Democratic Republic of the Congo and the Central African Republic. One hundred and forty nine HAT cases were confirmed by parasitology. The sensitivity and specificity of the prototype SD BIOLINE HAT was 89.26% (95% confidence interval (CI) = 83.27-93.28) and 94.58% (95% CI = 94.20-94.94) respectively. The sensitivity and specificity of the CATT on whole blood were 93.96% (95% CI = 88.92-96.79) and 95.91% (95% CI = 95.58-96.22), and of the CATT 1/8 were 89.26% (95% CI = 83.27-93.28) and 98.88% (95% CI = 98.70-99.04) respectively. After further optimization, the prototype SD BIOLINE HAT could become an alternative to current screening methods in primary healthcare settings in remote, resource-limited regions where HAT typically occurs.

  7. Comparasion of polyacrylamide gel electrophoresis (PAGE, immuno-electron microscopy (IEM and enzyme immunoassay (EIA for the rapid diagnosis of rotavirus infection in children

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    H. G. Pereira

    1983-12-01

    Full Text Available Detection of rotavirus RNA by polyacrylamide gel electrophoresis (PAGE proved to be a highly sensitive and rapid diagnostic test. A comparison of this assay with immuno-electron microscopy (IEM and enzyme immunoassay (EIA in 245 faeces from children with gastroenteritis revealed complete agreement between the three assays in 238 (97.14% samples. Among 75 samples positive in at least one of the three assays, negative results were observed in 5 (6.48% by PAGE, in 6 (6.76% by EIA and in none by IEM. Silver staining greatly increased the sensitivity of the PAGE assay. We conclude that although IEM remains the most sensitive and rapid rotavirus diagnostic assay, the PAGE technique has many advantages in its favour, including the non-requirement of expensive equipment, the use of only chemically defined reagents and the capacity to distinguish virus subgroup and variants and to detect non-crossreactive rotaviruses which are missed in serological assays.A evidenciação da presença de ácido ribonucleico (ARN viral por eletroforese em gel de policrilamida (EGPA foi comprovada como um método altamente sensível e rápido para o diagnóstico de infecções por rotavirus. Uma comparação desta prova com a imunomicroscopia eletrônica (IEM e com o ensaio imunoenzimático (EIE no exame de 245 fezes de crianças com gastroenterite revelou completa concordancia entre os três ensaios em 238 (97.14% amostras. Entre 75 amostras positivas pelo menos em um dos três ensaios, resultados negativos foram observados em 5 (6.48% por EGPA, em 6 (6.76% por EIE e em nenhum por IEM. Coloração pela prata aumentou consideravelmente a sensibilidade do ensaio por EGPA. Concluímos que embora a IEM ainda seja a prova mais sensível e rápida para o diagnóstico de infecções por rotavirus, o ensaio por EGPA tem muitas vantagens em seu favor, sendo as principais as de não necessitar equipamentos caros, de empregar exclusivamente reagentes quimicamente definidos, de

  8. Field Evaluation of Capillary Blood Samples as a Collection Specimen for the Rapid Diagnosis of Ebola Virus Infection During an Outbreak Emergency.

    Science.gov (United States)

    Strecker, Thomas; Palyi, Bernadett; Ellerbrok, Heinz; Jonckheere, Sylvie; de Clerck, Hilde; Bore, Joseph Akoi; Gabriel, Martin; Stoecker, Kilian; Eickmann, Markus; van Herp, Michel; Formenty, Pierre; Di Caro, Antonino; Becker, Stephan

    2015-09-01

    Reliable reverse transcription polymerase chain reaction (RT-PCR)-based diagnosis of Ebola virus infection currently requires a blood sample obtained by intravenous puncture. During the current Ebola outbreak in Guinea, we evaluated the usability of capillary blood samples collected from fingersticks of patients suspected of having Ebola virus disease (EVD) for field diagnostics during an outbreak emergency. A total of 120 venous and capillary blood samples were collected from 53 patients admitted to the Ebola Treatment Centre in Guéckédou, Guinea, between July and August 2014. All sample specimens were analyzed by RT-PCR using the RealStar Filovirus Screen RT-PCR Kit 1.0 from altona Diagnostics (Germany). We compared samples obtained by venipuncture and those obtained by capillary blood sampling absorbed onto swab devices. The resulting sensitivity and specificity of tests performed with capillary blood samples were 86.8% (95% confidence interval [CI], 71.9%-95.6%; 33/38 patients) and 100% (95% CI, 84.6%-100%; 22/22 patients), respectively. Our data suggest that capillary blood samples could serve as an alternative to venous blood samples for the diagnosis of EVD in resource-limited settings during a crisis. This can be of particular advantage in cases when venipuncture is difficult to perform-for example, with newborns and infants or when adult patients reject venipuncture for cultural or religious reasons. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

  9. Performance of “VIKIA Malaria Ag Pf/Pan” (IMACCESS®, a new malaria rapid diagnostic test for detection of symptomatic malaria infections

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    Chou Monidarin

    2012-08-01

    Full Text Available Abstract Background Recently, IMACCESS® developed a new malaria test (VIKIA Malaria Ag Pf/Pan™, based on the detection of falciparum malaria (HRP-2 and non-falciparum malaria (aldolase. Methods The performance of this new malaria rapid diagnostic test (RDT was assessed using 1,000 febrile patients seeking malaria treatment in four health centres in Cambodia from August to December 2011. The results of the VIKIA Malaria Ag Pf/Pan were compared with those obtained by microscopy, the CareStart Malaria™ RDT (AccessBio® which is currently used in Cambodia, and real-time PCR (as “gold standard”. Results The best performances of the VIKIA Malaria Ag Pf/Pan™ test for detection of both Plasmodium falciparum and non-P. falciparum were with 20–30 min reading times (sensitivity of 93.4% for P. falciparum and 82.8% for non-P. falciparum and specificity of 98.6% for P. falciparum and 98.9% for non-P. falciparum and were similar to those for the CareStart Malaria™ test. Conclusions This new RDT performs similarly well as other commercially available tests (especially the CareStart Malaria™ test, used as comparator, and conforms to the World Health Organization’s recommendations for RDT performance. It is a good alternative tool for the diagnosis of malaria in endemic areas.

  10. Rapid diagnosis of virulent Pasteurella multocida isolated from farm animals with clinical manifestation of pneumonia respiratory infection using 16S rDNA and KMT1 gene

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    Gamal Mohamedin Hassan

    2016-01-01

    Full Text Available Objective: To characterize intra-isolates variation between clinical isolates of Pasteurella multocida (P. multocida isolated from sheep, cattle and buffalo at molecular level to check the distribution of pneumonia and hemorrhagic septicemia in some regions of Fayoum, Egypt. Methods: These isolates were obtained from various locations in the Fayoum Governorate, Egypt and they were identified by amplifying 16S rDNA and KMT1 genes using their DNA as a template in PCR reaction. Results: The results demonstrated that the five selective isolates of P. multocida had similar size of PCR products that generated one band of 16S rDNA having 1 471 bp and KMT1 gene having 460 bp. The phylogenetic tree and similarity of the five selective isolates of P. multocida which were collected from GenBank database were calculated and analyzed for the nucleotide sequence of 16S rDNA and KMT1 genes. The sequencing result of 16S rRNA gene product (1 471 bp for the five selective isolates of P. multocida showed that the isolates of sheep (FUP2 shared 94.08%, 88.10% homology with the buffalo isolate (FUP8 and cattle isolate (FUP9 respectively, whereas, the buffalo isolate (FUP5 shared 98.18% and 94.40% homology with the cattle isolates (FUP12 and FUP9. Conclusions: The results indicated the relationships of P. multocida isolated from buffalo and cattle rather than the close relationships between P. multocida isolated from cattle and sheep. Diagnosis of P. multocida by 16S rDNA and KMT1 gene sequences was important to determine the antigen that is responsible for protective cover within the same group of animals and to help for the production of new vaccines for the control of microbial infection for domestic animals.

  11. Tennessee's In-state Vulnerability Assessment for a "Rapid Dissemination of Human Immunodeficiency Virus or Hepatitis C Virus Infection" Event Utilizing Data About the Opioid Epidemic.

    Science.gov (United States)

    Rickles, Michael; Rebeiro, Peter F; Sizemore, Lindsey; Juarez, Paul; Mutter, Mitchell; Wester, Carolyn; McPheeters, Melissa

    2018-05-17

    Knowing which factors contribute to county-level vulnerability to a human immunodeficiency virus (HIV)/hepatitis C virus (HCV) outbreak, and which counties are most vulnerable, guides public health and clinical interventions. We therefore examined the impact of locally available indicators related to the opioid epidemic on prior national models of HIV/HCV outbreak vulnerability. Tennessee's 95 counties were the study sample. Predictors from 2012 and 2013 were used, mirroring prior methodology from the US Centers for Disease Control and Prevention (CDC). Acute HCV incidence was the proxy measure of county-level vulnerability. Seventy-eight predictors were identified as potentially predictive for HIV/HCV vulnerability. We used multiple dimension reduction techniques to determine predictors for inclusion and Poisson regression to generate a composite index score ranking county-level vulnerability for HIV/HCV. There was overlap of high-risk counties with the national analysis (25 of 41 counties). The distribution of vulnerability reinforces earlier research indicating that eastern Tennessee is at particularly high risk but also demonstrates that the entire state has high vulnerability. Prior research placed Tennessee among the top states for opioid prescribing, acute HCV infection, and greatest risk for an HIV/HCV outbreak. Given this confluence of risk, the Tennessee Department of Health expanded upon prior work to include more granular, local data, including on opioid prescribing. We also explored nonfatal and fatal overdoses. The more complete statewide view of risk generated, not only in eastern counties but also in the western corridor, will enable local officials to monitor vulnerability and better target resources.

  12. Validation of a commercial insulated isothermal PCR-based POCKIT test for rapid and easy detection of white spot syndrome virus infection in Litopenaeus vannamei.

    Directory of Open Access Journals (Sweden)

    Yun-Long Tsai

    Full Text Available Timely pond-side detection of white spot syndrome virus (WSSV plays a critical role in the implementation of bio-security measures to help minimize economic losses caused by white spot syndrome disease, an important threat to shrimp aquaculture industry worldwide. A portable device, namely POCKIT™, became available recently to complete fluorescent probe-based insulated isothermal PCR (iiPCR, and automatic data detection and interpretation within one hour. Taking advantage of this platform, the IQ Plus™ WSSV Kit with POCKIT system was established to allow simple and easy WSSV detection for on-site users. The assay was first evaluated for its analytical sensitivity and specificity performance. The 95% limit of detection (LOD of the assay was 17 copies of WSSV genomic DNA per reaction (95% confidence interval [CI], 13 to 24 copies per reaction. The established assay has detection sensitivity similar to that of OIE-registered IQ2000™ WSSV Detection and Protection System with serial dilutions of WSSV-positive Litopenaeus vannamei DNA. No cross-reaction signals were generated from infectious hypodermal and haematopoietic necrosis virus (IHHNV, monodon baculovirus (MBV, and hepatopancreatic parvovirus (HPV positive samples. Accuracy analysis using 700 L. vannamei of known WSSV infection status shows that the established assayhassensitivity93.5% (95% CI: 90.61-95.56% and specificity 97% (95% CI: 94.31-98.50%. Furthermore, no discrepancy was found between the two assays when 100 random L. vannamei samples were tested in parallel. Finally, excellent correlation was observed among test results of three batches of reagents with 64 samples analyzed in three different laboratories. Working in a portable device, IQ Plus™ WSSV Kit with POCKIT system allows reliable, sensitive and specific on-site detection of WSSV in L. vannamei.

  13. Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

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    Yu Cong

    2017-04-01

    Full Text Available Nipah virus (NiV is a paramyxovirus (genus Henipavirus that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM model following intratracheal (IT and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT and magnetic resonance imaging (MRI to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human

  14. Loss in lung volume and changes in the immune response demonstrate disease progression in African green monkeys infected by small-particle aerosol and intratracheal exposure to Nipah virus.

    Science.gov (United States)

    Cong, Yu; Lentz, Margaret R; Lara, Abigail; Alexander, Isis; Bartos, Christopher; Bohannon, J Kyle; Hammoud, Dima; Huzella, Louis; Jahrling, Peter B; Janosko, Krisztina; Jett, Catherine; Kollins, Erin; Lackemeyer, Matthew; Mollura, Daniel; Ragland, Dan; Rojas, Oscar; Solomon, Jeffrey; Xu, Ziyue; Munster, Vincent; Holbrook, Michael R

    2017-04-01

    Nipah virus (NiV) is a paramyxovirus (genus Henipavirus) that emerged in the late 1990s in Malaysia and has since been identified as the cause of sporadic outbreaks of severe febrile disease in Bangladesh and India. NiV infection is frequently associated with severe respiratory or neurological disease in infected humans with transmission to humans through inhalation, contact or consumption of NiV contaminated foods. In the work presented here, the development of disease was investigated in the African Green Monkey (AGM) model following intratracheal (IT) and, for the first time, small-particle aerosol administration of NiV. This study utilized computed tomography (CT) and magnetic resonance imaging (MRI) to temporally assess disease progression. The host immune response and changes in immune cell populations over the course of disease were also evaluated. This study found that IT and small-particle administration of NiV caused similar disease progression, but that IT inoculation induced significant congestion in the lungs while disease following small-particle aerosol inoculation was largely confined to the lower respiratory tract. Quantitative assessment of changes in lung volume found up to a 45% loss in IT inoculated animals. None of the subjects in this study developed overt neurological disease, a finding that was supported by MRI analysis. The development of neutralizing antibodies was not apparent over the 8-10 day course of disease, but changes in cytokine response in all animals and activated CD8+ T cell numbers suggest the onset of cell-mediated immunity. These studies demonstrate that IT and small-particle aerosol infection with NiV in the AGM model leads to a severe respiratory disease devoid of neurological indications. This work also suggests that extending the disease course or minimizing the impact of the respiratory component is critical to developing a model that has a neurological component and more accurately reflects the human condition.

  15. Association of antibody to E2 protein of human papillomavirus and p16INK4A with progression of HPV-infected cervical lesions.

    Science.gov (United States)

    Chuerduangphui, Jureeporn; Pientong, Chamsai; Swangphon, Piyawut; Luanratanakorn, Sanguanchoke; Sangkomkamhang, Ussanee; Tungsiriwattana, Thumwadee; Kleebkaow, Pilaiwan; Burassakarn, Ati; Ekalaksananan, Tipaya

    2018-05-09

    Human papillomavirus (HPV) E2 and L1 proteins are expressed in cervical cells during the lytic stage of infection. Overexpression of p16 INK4A is a biomarker of HPV-associated cervical neoplasia. This study investigated antibodies to HPV16 E2, HPV16 L1, and p16 INK4A in sera from women with no squamous intraepithelial lesion (No-SIL) of the cervix, low-grade SIL, high-grade SIL, and cervical squamous cell carcinoma (SCC). HPV DNA was detected by polymerase chain reaction. Anti-E2, -L1, and -p16 INK4A antibodies in sera were determined by western blot. Among 116 samples, 69 (60%) were HPV DNA-positive. Percentages seropositive for anti-E2, -L1, and -p16 INK4A antibodies were 39.6, 22.4, and 23.3%, respectively. Anti-E2 antibody was significantly correlated with HPV DNA-positive cases. Eighty-seven women (75%) were regarded as infected with HPV, having at least one positive result from HPV DNA, L1, or E2 antibody. Antibody to p16 INK4A was associated with HPV infection (odds = 5.444, 95% CI 1.203-24.629, P = 0.028) and precancerous cervical lesions (odds = 5.132, 95% CI 1.604-16.415, P = 0.006). Interestingly, the concurrent detection of anti-E2 and -p16 INK4A antibodies was significantly associated with HPV infection (odds = 1.382, 95% CI 1.228-1.555, P = 0.044). These antibodies might be good candidate biomarkers for monitoring HPV-associated cervical lesion development to cancer.

  16. Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection

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    Alvarez Nadine

    2013-02-01

    Full Text Available Abstract Background Immunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections. Materials and methods Human secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated. Results The passive administration of hsIgA reduces the pneumonic area before challenge with M. tuberculosis. The intratracheal administration of M. tuberculosis preincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury. Conclusions HsIgA purified from colostrum protects against M. tuberculosis infection in an experimental mouse model.

  17. Evaluation of four rapid tests for diagnosis and differentiation of HIV-1 and HIV-2 infections in Guinea-Conakry, West Africa.

    Science.gov (United States)

    Chaillet, Pascale; Tayler-Smith, Katie; Zachariah, Rony; Duclos, Nanfack; Moctar, Diallo; Beelaert, Greet; Fransen, Katrien

    2010-09-01

    With both HIV-1 and HV-2 prevalent in Guinea-Conakry, accurate diagnosis and differentiation is crucial for treatment purposes. Thus, four rapid HIV tests were evaluated for their HIV-1 and HIV-2 diagnostic and discriminative capacity for use in Guinea-Conakry. These included SD Bioline HIV 1/2 3.0 (Standard Diagnostics Inc.), Genie II HIV1/HIV2 (Bio-Rad), First Response HIV Card Test 1-2.0 (PMC Medical) and Immunoflow HIV1-HIV2 (Core Diagnostics). Results were compared with gold standard tests (INNO-LIA HIV-I/II Score) and NEW LAV BLOT II (Bio-Rad). Four hundred and forty three sequential stored HIV-positive serum samples, of known HIV-type, were evaluated. Genie II HIV1/HIV2, Immunoflow HIV1-HIV2 and SD Bioline HIV 1/2 3.0 had 100% sensitivity (95% CI, 98.9-100%) while for First Response HIV Card Test 1-2.0 this was 99.5% (95% CI, 98.2%-99.9%). In terms of discriminatory capacity, Genie II HIV1/HIV2 identified 382/ 384(99.5%) HIV-1 samples, 49/ 52(95%) HIV-2 and 7/7(100%) HIV-positive untypable samples. Immunoflow HIV1-HIV2 identified 99% HIV-1, 67% HIV-2 and all HIV-positive untypable samples. First Response HIV Card Test 1-2.0 identified 94% HIV-1, 64% HIV-2 and 57% HIV-positive untypable samples. SD-Bioline HIV 1/2 3.0 was the worst overall performer identifying 65% HIV-1, 69% HIV-2 and all HIV-positive untypable samples. The use of SD Bioline HIV 1/2 3.0 (the current standard in Guinea-Conakry) as a discriminatory HIV test is poor and may be best replaced by Immunoflow HIV1-HIV2. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  18. Necrotizing soft-tissue infection: Laboratory risk indicator for necrotizing soft tissue infections score

    Directory of Open Access Journals (Sweden)

    Madhuri Kulkarni

    2014-01-01

    Full Text Available Necrotizing soft tissue infections (NSTI can be rapidly progressive and polymicrobial in etiology. Establishing the element of necrotizing infection poses a clinical challenge. A 64-year-old diabetic patient presented to our hospital with a gangrenous patch on anterior abdominal wall, which progressed to an extensive necrotizing lesion within 1 week. Successive laboratory risk indicator for necrotizing softtissue infections (LRINEC scores confirmed the necrotizing element. Cultures yielded Enterococci, Acinetobacter species and Apophysomyces elegans and the latter being considered as an emerging agent of Zygomycosis in immunocompromised hosts. Patient was managed with antibiotics, antifungal treatment and surgical debridement despite which he succumbed to the infection. NSTI′s require an early and aggressive management and LRINEC score can be applied to establish the element of necrotizing pathology. Isolation of multiple organisms becomes confusing to establish the etiological role. Apophysomyces elegans, which was isolated in our patient is being increasingly reported in cases of necrotizing infections and may be responsible for high morbidity and mortality. This scoring has been proposed as an adjunct tool to Microbiological diagnosis when NSTI′s need to be diagnosed early and managed promptly to decrease mortality and morbidity, which however may not come in handy in an immunocompromised host with polymicrobial aggressive infection.

  19. Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Costa Luciano Bello

    2002-01-01

    Full Text Available There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV. We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use, and who gave information about alcohol consumption.Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis was determined based on the relationship between disease stage and duration of infection (years. Logistic regression analysis revealed that age at the time of infection (P or = 40 years (median = 0.47. The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

  20. Emmonsia helica Infection in HIV-Infected Man, California, USA.

    Science.gov (United States)

    Rofael, Martin; Schwartz, Ilan S; Sigler, Lynne; Kong, Li K; Nelson, Nicholas

    2018-01-01

    Emmonsia-like fungi have rarely been reported from North America. We report a fatal case of E. helica infection in a man with advanced HIV infection from California, USA, who had progressive respiratory failure and a brain abscess.

  1. A fatal case of middle east respiratory syndrome corona virus infection in South Korea: Cheat radiography and CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung Eun; Kim, Hyo Lim; Choi, Su Mi [Dept. of Internal Medicine, Yeouido St. Mary' s Hospital, The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2016-06-15

    The outbreak of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infection in South Korea originated from Saudi Arabia. This virus shows high infectivity, and causes outbreaks of severe febrile respiratory infections in health care-associated settings. Herein, we reported a fatal case of MERS-CoV infection with a focus on the pulmonary radiologic findings. The initial chest computed tomography and radiographs of our patient showed ground-glass opacity in patchy distribution, followed by rapid progression of consolidation and pleural effusion in serial studies.

  2. A fatal case of middle east respiratory syndrome corona virus infection in South Korea: Cheat radiography and CT findings

    International Nuclear Information System (INIS)

    Lee, Seung Eun; Kim, Hyo Lim; Choi, Su Mi

    2016-01-01

    The outbreak of Middle East Respiratory Syndrome Corona Virus (MERS-CoV) infection in South Korea originated from Saudi Arabia. This virus shows high infectivity, and causes outbreaks of severe febrile respiratory infections in health care-associated settings. Herein, we reported a fatal case of MERS-CoV infection with a focus on the pulmonary radiologic findings. The initial chest computed tomography and radiographs of our patient showed ground-glass opacity in patchy distribution, followed by rapid progression of consolidation and pleural effusion in serial studies

  3. Prospective evaluation of commercial antibody-based rapid tests in combination with a loop-mediated isothermal amplification PCR assay for detection of Orientia tsutsugamushi during the acute phase of scrub typhus infection.

    Science.gov (United States)

    Blacksell, Stuart D; Paris, Daniel H; Chierakul, Wirongrong; Wuthiekanun, Vanaporn; Teeratakul, Achara; Kantipong, Pacharee; Day, Nicholas P J

    2012-03-01

    Samples from 160 prospectively recruited febrile patients with typhus-like illness in an area of Thailand (Chiang Rai, northern Thailand) where scrub typhus is endemic were used to evaluate the diagnostic capabilities of four rapid immunochromatographic tests (ICTs) for the detection of Orientia tsutsugamushi IgM and total antibodies during acute scrub typhus infection. Of the 160 cases, 54 (34%) had been confirmed to have scrub typhus using the reference scrub typhus infection criteria (STIC), i.e., positive cell culture isolation, an admission IgM antibody titer of ≥1:12,800, a 4-fold rising IgM antibody titer, and/or positivity for ≥2 out of 3 PCR gene targets). The ICTs gave the following sensitivities and specificities: the Panbio IgM ICT, 46% (95% confidence interval [CI], 33 to 60) and 95% (95% CI, 89 to 98), respectively; the Standard Diagnostics IgM ICT, 68% (95% CI, 60 to 75) and 73% (95% CI, 68 to 78), respectively; the AccessBio IgM ICT, 56% (95% CI, 48 to 63) and 90% (95% CI, 87 to 94), respectively; and the AccessBio total antibody ABt ICT, 61% (95% CI, 53 to 68) and 68% (95% CI, 63 to 73), respectively. An isothermal loop amplification (LAMP) PCR assay for scrub typhus demonstrated a sensitivity of 52% (95% CI, 38 to 66) and a specificity of 94% (95% CI, 88 to 98). This study has revealed the diagnostic limitations of antibody-based assays in an acute care setting. However, the combination of ICTs with LAMP usually increased sensitivity with a minimal reduction in specificity. The best combination, the Panbio IgM ICT and LAMP, resulted in a sensitivity of 67% (95% CI, 53 to 79) and a specificity of 91% (95% CI, 83 to 95). The combination of antibody-based assays with DNA- or antigen-based tests shows promise for improved diagnostic sensitivity.

  4. Antiviral therapy during primary simian immunodeficiency virus infection fails to prevent acute loss of CD4+ T cells in gut mucosa but enhances their rapid restoration through central memory T cells.

    Science.gov (United States)

    Verhoeven, David; Sankaran, Sumathi; Silvey, Melanie; Dandekar, Satya

    2008-04-01

    Gut-associated lymphoid tissue (GALT) is an early target of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and a site for severe CD4+ T-cell depletion. Although antiretroviral therapy (ART) is effective in suppressing HIV replication and restoring CD4+ T cells in peripheral blood, restoration in GALT is delayed. The role of restored CD4+ T-cell help in GALT during ART and its impact on antiviral CD8+ T-cell responses have not been investigated. Using the SIV model, we investigated gut CD4+ T-cell restoration in infected macaques, initiating ART during either the primary stage (1 week postinfection), prior to acute CD4+ cell loss (PSI), or during the chronic stage at 10 weeks postinfection (CSI). ART led to viral suppression in GALT and peripheral blood mononuclear cells of PSI and CSI animals at comparable levels. CSI animals had incomplete CD4+ T-cell restoration in GALT. In PSI animals, ART did not prevent acute CD4+ T-cell loss by 2 weeks postinfection in GALT but supported rapid and complete CD4+ T-cell restoration thereafter. This correlated with an accumulation of central memory CD4+ T cells and better suppression of inflammation. Restoration of CD4+ T cells in GALT correlated with qualitative changes in SIV gag-specific CD8+ T-cell responses, with a dominance of interleukin-2-producing responses in PSI animals, while both CSI macaques and untreated SIV-infected controls were dominated by gamma interferon responses. Thus, central memory CD4+ T-cell levels and qualitative antiviral CD8+ T-cell responses, independent of viral suppression, were the immune correlates of gut mucosal immune restoration during ART.

  5. Hypoxia determines survival outcomes of bacterial infection through HIF-1alpha dependent re-programming of leukocyte metabolism *

    OpenAIRE

    Thompson, A.A.R.; Dickinson, R.S.; Murphy, F.; Thomson, J. P.; Marriott, H.M.; Tavares, A.; Willson, J.; Williams, L.; Lewis, A.; Mirchandani, A.; Dos Santos Coelho, P.; Doherty, C.; Ryan, E.; Watts, E.; Morton, N. M.

    2017-01-01

    Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer...

  6. Progress Report

    DEFF Research Database (Denmark)

    Duer, Karsten

    1999-01-01

    Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999.......Progress report describing the work carried out by the Danish participant in the ALTSET project in the period January 1999 to July 1999....

  7. Progress Report

    Science.gov (United States)

    2018-05-16

    This report summarizes the annual progress of EPA’s Clean Air Markets Programs such as the Acid Rain Program (ARP) and the Cross-State Air Pollution Rule (CSAPR). EPA systematically collects data on emissions, compliance, and environmental effects, these data are highlighted in our Progress Reports.

  8. HTLV-1 tax specific CD8+ T cells express low levels of Tim-3 in HTLV-1 infection: implications for progression to neurological complications.

    Directory of Open Access Journals (Sweden)

    Lishomwa C Ndhlovu

    2011-04-01

    Full Text Available The T cell immunoglobulin mucin 3 (Tim-3 receptor is highly expressed on HIV-1-specific T cells, rendering them partially "exhausted" and unable to contribute to the effective immune mediated control of viral replication. To elucidate novel mechanisms contributing to the HTLV-1 neurological complex and its classic neurological presentation called HAM/TSP (HTLV-1 associated myelopathy/tropical spastic paraparesis, we investigated the expression of the Tim-3 receptor on CD8(+ T cells from a cohort of HTLV-1 seropositive asymptomatic and symptomatic patients. Patients diagnosed with HAM/TSP down-regulated Tim-3 expression on both CD8(+ and CD4(+ T cells compared to asymptomatic patients and HTLV-1 seronegative controls. HTLV-1 Tax-specific, HLA-A*02 restricted CD8(+ T cells among HAM/TSP individuals expressed markedly lower levels of Tim-3. We observed Tax expressing cells in both Tim-3(+ and Tim-3(- fractions. Taken together, these data indicate that there is a systematic downregulation of Tim-3 levels on T cells in HTLV-1 infection, sustaining a profoundly highly active population of potentially pathogenic T cells that may allow for the development of HTLV-1 complications.

  9. Single HIV-1 Imaging Reveals Progression of Infection through CA-Dependent Steps of Docking at the Nuclear Pore, Uncoating, and Nuclear Transport.

    Science.gov (United States)

    Francis, Ashwanth C; Melikyan, Gregory B

    2018-04-11

    The HIV-1 core consists of capsid proteins (CA) surrounding viral genomic RNA. After virus-cell fusion, the core enters the cytoplasm and the capsid shell is lost through uncoating. CA loss precedes nuclear import and HIV integration into the host genome, but the timing and location of uncoating remain unclear. By visualizing single HIV-1 infection, we find that CA is required for core docking at the nuclear envelope (NE), whereas early uncoating in the cytoplasm promotes proteasomal degradation of viral complexes. Only docked cores exhibiting accelerated loss of CA at the NE enter the nucleus. Interestingly, a CA mutation (N74D) altering virus engagement of host factors involved in nuclear transport does not alter the uncoating site at the NE but reduces the nuclear penetration depth. Thus, CA protects HIV-1 complexes from degradation, mediates docking at the nuclear pore before uncoating, and determines the depth of nuclear penetration en route to integration. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. The case for early use of rapid whole genome sequencing in management of critically ill infants: Late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease and recurrent infections.

    Science.gov (United States)

    Sweeney, Nathaly M; Nahas, Shareef A; Chowdhury, Shimul; Del Campo, Miguel; Jones, Marilyn C; Dimmock, David P; Kingsmore, Stephen F; Investigators, Rcigm

    2018-03-16

    Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal copy number variants, and single gene mutations. CDH is the most expensive non-cardiac congenital defect: Management frequently requires implementation of Extracorporeal Membrane Oxygenation (ECMO), which increases management expenditures 2.4 - 3.5-fold. The cost of management of CDH has been estimated to exceed $250 million per year. Despite in hospital survival of 80-90%, current management is imperfect, as a great proportion of surviving children have long-term functional deficits. We report the case of a premature infant prenatally diagnosed with CDH and congenital heart disease, who had a protracted and complicated course in the intensive care unit with multiple surgical interventions, including post-cardiac surgery ECMO, gastrostomy tube placement with Nissen fundoplication, tracheostomy for respiratory failure, recurrent infections and developmental delay. Rapid whole genome sequencing (rWGS) identified a de novo, likely pathogenic, c.3096_3100delCAAAG (p.Lys1033Argfs*32) variant in ARID1B, providing a diagnosis of Coffin-Siris syndrome. Her parents elected palliative care and she died later that day. Had rWGS been performed as a neonate, eight months of suffering and futile healthcare utilization may have been avoided. Cold Spring Harbor Laboratory Press.

  11. 5′ Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice

    Directory of Open Access Journals (Sweden)

    Eric Waltari

    2018-03-01

    Full Text Available Using 5′ rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM, and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

  12. 5' Rapid Amplification of cDNA Ends and Illumina MiSeq Reveals B Cell Receptor Features in Healthy Adults, Adults With Chronic HIV-1 Infection, Cord Blood, and Humanized Mice.

    Science.gov (United States)

    Waltari, Eric; Jia, Manxue; Jiang, Caroline S; Lu, Hong; Huang, Jing; Fernandez, Cristina; Finzi, Andrés; Kaufmann, Daniel E; Markowitz, Martin; Tsuji, Moriya; Wu, Xueling

    2018-01-01

    Using 5' rapid amplification of cDNA ends, Illumina MiSeq, and basic flow cytometry, we systematically analyzed the expressed B cell receptor (BCR) repertoire in 14 healthy adult PBMCs, 5 HIV-1+ adult PBMCs, 5 cord blood samples, and 3 HIS-CD4/B mice, examining the full-length variable region of μ, γ, α, κ, and λ chains for V-gene usage, somatic hypermutation (SHM), and CDR3 length. Adding to the known repertoire of healthy adults, Illumina MiSeq consistently detected small fractions of reads with high mutation frequencies including hypermutated μ reads, and reads with long CDR3s. Additionally, the less studied IgA repertoire displayed similar characteristics to that of IgG. Compared to healthy adults, the five HIV-1 chronically infected adults displayed elevated mutation frequencies for all μ, γ, α, κ, and λ chains examined and slightly longer CDR3 lengths for γ, α, and λ. To evaluate the reconstituted human BCR sequences in a humanized mouse model, we analyzed cord blood and HIS-CD4/B mice, which all lacked the typical SHM seen in the adult reference. Furthermore, MiSeq revealed identical unmutated IgM sequences derived from separate cell aliquots, thus for the first time demonstrating rare clonal members of unmutated IgM B cells by sequencing.

  13. Rapid thermal processing of semiconductors

    CERN Document Server

    Borisenko, Victor E

    1997-01-01

    Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

  14. Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium

    International Nuclear Information System (INIS)

    Aribandi, M.; Bazan, C.; Rinaldi, M.G.

    2005-01-01

    This report describes MRI findings of a rare case of biopsy-proven fatal cerebral infection with Chaetomium strumarium in a 28-year-old man with a history of i.v. drug abuse. Magnetic resonance imaging revealed rapidly progressing lesions with irregular peripheral enhancement, possible central haemorrhage and significant mass effect. Only six cases of cerebral infection with Chaetomium have been reported in the English literature. This is the first report in the radiology literature describing the imaging findings. The previously reported cases of cerebral infection by the Chaetomium species are also reviewed Copyright (2005) Blackwell Publishing Asia Pty Ltd

  15. Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium.

    Science.gov (United States)

    Aribandi, M; Bazan Iii, C; Rinaldi, M G

    2005-04-01

    This report describes MRI findings of a rare case of biopsy-proven fatal cerebral infection with Chaetomium strumarium in a 28-year-old man with a history of i.v. drug abuse. Magnetic resonance imaging revealed rapidly progressing lesions with irregular peripheral enhancement, possible central haemorrhage and significant mass effect. Only six cases of cerebral infection with Chaetomium have been reported in the English literature. This is the first report in the radiology literature describing the imaging findings. The previously reported cases of cerebral infection by the Chaetomium species are also reviewed.

  16. Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium

    Energy Technolo