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Sample records for chronic infection predominance

  1. Predominant pathogen competition and core microbiota divergence in chronic airway infection.

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    Rogers, Geraint B; van der Gast, Christopher J; Serisier, David J

    2015-01-01

    Chronic bacterial lung infections associated with non-cystic fibrosis bronchiectasis represent a substantial and growing health-care burden. Where Pseudomonas aeruginosa is the numerically dominant species within these infections, prognosis is significantly worse. However, in many individuals, Haemophilus influenzae predominates, a scenario associated with less severe disease. The mechanisms that determine which pathogen is most abundant are not known. We hypothesised that the distribution of H. influenzae and P. aeruginosa would be consistent with strong interspecific competition effects. Further, we hypothesised that where P. aeruginosa is predominant, it is associated with a distinct 'accessory microbiota' that reflects a significant interaction between this pathogen and the wider bacterial community. To test these hypotheses, we analysed 16S rRNA gene pyrosequencing data generated previously from 60 adult bronchiectasis patients, whose airway microbiota was dominated by either P. aeruginosa or H. influenzae. The relative abundances of the two dominant species in their respective groups were not significantly different, and when present in the opposite pathogen group the two species were found to be in very low abundance, if at all. These findings are consistent with strong competition effects, moving towards competitive exclusion. Ordination analysis indicated that the distribution of the core microbiota associated with each pathogen, readjusted after removal of the dominant species, was significantly divergent (analysis of similarity (ANOSIM), R=0.07, P=0.019). Taken together, these findings suggest that both interspecific competition and also direct and/or indirect interactions between the predominant species and the wider bacterial community may contribute to the predominance of P. aeruginosa in a subset of bronchiectasis lung infections.

  2. Porphyromonas gingivalis: predominant pathogen in chronic periodontitis

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    Ramos Perfecto, Donald; Dpto. de CC. Básicas. Laboratorio de Microbiología Facultad de Odontología Universidad Nacional Mayor de San Marcos.; Moromi Nakata, Hilda; Dpto. de CC. Básicas. Laboratorio de Microbiología Facultad de Odontología Universidad Nacional Mayor de San Marcos.; Martínez Cadillo, Elba; Dpto. de CC. Básicas. Laboratorio de Microbiología Facultad de Odontología Universidad Nacional Mayor de San Marcos.

    2014-01-01

    Porphyromonas gingivalis is a gram negative bacillus predominant in chronic periodontitis, multiple virulence factors make it extremely aggressive. In the gingival sulcus find the conditions for growth,interacting with the host produces a slow but steady destruction of periodontal tissue. Its dominance has been considered a risk factor for systemic inflammatory diseases such as myocardial infarction. Although its susceptibility to a variety of drugs makes possible its handling with antimicrob...

  3. Ear infection - chronic

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    Middle ear infection - chronic; Otitis media - chronic; Chronic otitis media; Chronic ear infection ... up. When this happens, infection can occur. A chronic ear infection develops when fluid or an infection ...

  4. EBV CHRONIC INFECTIONS

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    Eligio Pizzigallo

    2010-08-01

    Full Text Available The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”. Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis. The etiopathogenetic role of EBV is demonstrated only in a well-examined subgroup of patients, while in most of the remaining cases this role should be played by other infectious agents - able to remain in a latent or persistent way in the host – or even by not infectious agents (toxic, neuroendocrine, methabolic, etc.. However, the pathogenetic substrate of the different etiologic forms seems to be the same, much probably represented by the oxidative damage due to the release of pro-inflammatory cytokines as a response to the triggering event (infectious or not infectious. Anyway, recently the scientists turned their’s attention to the genetic predisposition of the subjects affected by the syndrome, so that in the last years the genetic studies, together with those of molecular biology, received a great impulse

  5. EBV CHRONIC INFECTIONS

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    Delia Racciatti

    2010-02-01

    Full Text Available

    The infection from Epstein-Barr virus (EBV or virus of infectious mononucleosis, together with other herpesviruses’ infections, represents a prototype of persistent viral infections characterized by the property of the latency. Although the reactivations of the latent infection are associated with the resumption of the viral replication and eventually with the “shedding”, it is still not clear if this virus can determine chronic infectious diseases, more or less evolutive. These diseases could include some pathological conditions actually defined as “idiopathic”and characterized by the “viral persistence” as the more credible pathogenetic factor. Among the so-called idiopathic syndromes, the “chronic fatigue syndrome” (CFS aroused a great interest around the eighties of the last century when, just for its relationship with EBV, it was called “chronic mononucleosis” or “chronic EBV infection”.

    Today CFS, as defined in 1994 by the CDC of Atlanta (USA, really represents a multifactorial syndrome characterized by a chronic course, where reactivation and remission phases alternate, and by a good prognosis

  6. Are lipid disorders involved in the predominance of human T-lymphotropic virus-1 infections in women?

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    Luciana Debortoli de Carvalho

    2015-12-01

    Full Text Available Abstract INTRODUCTION : The human T-lymphotropic virus-1 (HTLV-1 is associated with chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP, a chronic inflammatory disease. Disturbances in lipid metabolism are involved in inflammatory and demyelinating diseases. METHODS : Plasma levels of triglycerides, total cholesterol, and fractions of HTLV-1-infected individuals of both sexes with different clinical progressions were determined. RESULTS : Elevated levels of triglyceride and very low-density lipoproteins (VLDL were exclusively detected in HTLV-1-infected women from asymptomatic and HAM/TSP groups compared with uninfected individuals (p = 0.02. CONCLUSIONS : Elevated triglyceride and VLDL levels in HTLV-1-infected women may be related to the predominance of HAM/TSP in women.

  7. Reduced sense of agency in chronic schizophrenia with predominant negative symptoms.

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    Maeda, Takaki; Takahata, Keisuke; Muramatsu, Taro; Okimura, Tsukasa; Koreki, Akihiro; Iwashita, Satoru; Mimura, Masaru; Kato, Motoichiro

    2013-10-30

    Self-disturbances in schizophrenia have been regarded as a fundamental vulnerability marker for this disease, and have begun to be studied from the standpoint of an abnormal "sense of agency (SoA)" in cognitive neuroscience. To clarify the nature of aberrant SoA in schizophrenia, it needs to be investigated in various clinical subtypes and stages. The residual type of chronic schizophrenia with predominant negative symptoms (NS) has never been investigated for SoA. Accordingly, we investigated SoA by an original agency attribution task in NS-predominant schizophrenia, and evaluated the dynamic interplay between the predictive and postdictive components of SoA in the optimal cue integration framework. We studied 20 patients with NS-predominant schizophrenia, and compared with 30 patients with paranoid-type schizophrenia and 35 normal volunteers. NS-predominant schizophrenia showed markedly diminished SoA compared to normal controls and paranoid-type schizophrenia, indicating a completely opposite direction in agency attribution compared with excessive SoA demonstrated in paranoid-type schizophrenia. Reduced SoA was detected in experimental studies of schizophrenia for the first time. According to the optimal cue integration framework, these results indicate that there was no increase in compensatory contributions of the postdictive processes despite the existence of inadequate predictions, contrary to the exaggerated postdictive component in paranoid-type schizophrenia.

  8. Prevalence of comorbidities according to predominant phenotype and severity of chronic obstructive pulmonary disease

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    Camiciottoli G

    2016-09-01

    Full Text Available Gianna Camiciottoli,1,2 Francesca Bigazzi,1 Chiara Magni,1 Viola Bonti,1 Stefano Diciotti,3 Maurizio Bartolucci,4 Mario Mascalchi,5 Massimo Pistolesi1 1Section of Respiratory Medicine, Department of Clinical and Experimental Medicine, 2Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, 3Department of Electrical, Electronic, and Information Engineering “Guglielmo Marconi,” University of Bologna, Cesena, 4Department of Diagnostic Imaging, Careggi University Hospital, 5Radiodiagnostic Section, Department of Clinical and Experimental Biomedical Sciences, University of Florence, Florence, Italy Background: In addition to lung involvement, several other diseases and syndromes coexist in patients with chronic obstructive pulmonary disease (COPD. Our purpose was to investigate the prevalence of idiopathic arterial hypertension (IAH, ischemic heart disease, heart failure, peripheral vascular disease (PVD, diabetes, osteoporosis, and anxious depressive syndrome in a clinical setting of COPD outpatients whose phenotypes (predominant airway disease and predominant emphysema and severity (mild and severe diseases were determined by clinical and functional parameters. Methods: A total of 412 outpatients with COPD were assigned either a predominant airway disease or a predominant emphysema phenotype of mild or severe degree according to predictive models based on pulmonary functions (forced expiratory volume in 1 second/vital capacity; total lung capacity %; functional residual capacity %; and diffusing capacity of lung for carbon monoxide % and sputum characteristics. Comorbidities were assessed by objective medical records. Results: Eighty-four percent of patients suffered from at least one comorbidity and 75% from at least one cardiovascular comorbidity, with IAH and PVD being the most prevalent ones (62% and 28%, respectively. IAH prevailed significantly in predominant airway disease, osteoporosis prevailed

  9. Chronic Gastritis and its Association with H. Pylori Infection.

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    Fatema, J; Khan, A H; Uddin, M J; Rahman, M H; Saha, M; Safwath, S A; Alam, M J; Mamun, M A

    2015-10-01

    This cross sectional study was designed to see association of chronic gastritis including its type with H. pylori infection. Consecutive patients undergoing endoscopic examination having histopathological evidence of chronic gastritis were enrolled in the study and was done in Sylhet MAG Osmani Medical College from July 2011 to June 2012. Biopsies were taken from antrum, body and fundus in all patients. Histopathological examinations were done using H-E stain and for detection of H. pylori, rapid urease test, anti-H.pylori antibody test and histopathological test with modified Giemsa stain were done. Patients having results positive in at least two methods were considered infected by H. pylori. Total 80 dyspeptic patients having chronic gastritis were evaluated. Out of them 67(83.8%) had H. pylori infection and 13(16.2%) were H. pylori negative. Among all patients 57(71.2%) had pangastritis and 23(28.8%) had antral gastritis with female and male predominance respectively. H. pylori infection was present in 49(86.0%) cases of pangastritis and 18(78.3%) cases of antral gastritis. H. pylori infection was a little higher among males (34, 50.7%) females (33, 49.3%). H. pylori infection is the predominant cause of chronic gastritis and pangastritis is the major type.

  10. Multiploid CD61+ cells are the pre-dominant cell lineage infected during acute dengue virus infection in bone marrow.

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    Kristina B Clark

    Full Text Available Depression of the peripheral blood platelet count during acute infection is a hallmark of dengue. This thrombocytopenia has been attributed, in part, to an insufficient level of platelet production by megakaryocytes that reside in the bone marrow (BM. Interestingly, it was observed that dengue patients experience BM suppression at the onset of fever. However, few studies focus on the interaction between dengue virus (DENV and megakaryocytes and how this interaction can lead to a reduction in platelets. In the studies reported herein, BM cells from normal healthy rhesus monkeys (RM and humans were utilized to identify the cell lineage(s that were capable of supporting virus infection and replication. A number of techniques were employed in efforts to address this issue. These included the use of viral RNA quantification, nonstructural protein and infectivity assays, phenotypic studies utilizing immunohistochemical staining, anti-differentiation DEAB treatment, and electron microscopy. Cumulative results from these studies revealed that cells in the BM were indeed highly permissive for DENV infection, with human BM having higher levels of viral production compared to RM. DENV-like particles were predominantly observed in multi-nucleated cells that expressed CD61+. These data suggest that megakaryocytes are likely the predominant cell type infected by DENV in BM, which provides one explanation for the thrombocytopenia and the dysfunctional platelets characteristic of dengue virus infection.

  11. Multiple human papilloma virus infections predominant in squamous cell cervical carcinoma in Bandung

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    Edhyana Sahiratmadja

    2015-12-01

    Full Text Available BACKGROUND Persistent infection of high risk genotypes of human papilloma virus (hrHPV has been established as the etiological cause for cervical cancer, and the most prevalent genotypes that infect the cervical tissue are HPV-16 and HPV-18. However, HPV genotype profile has been shown to differ according to geographical distribution across the globe. The present study aimed to determine the HPV genotype distribution in cervical cancer patients from Bandung, Indonesia. METHODS During the period of July – November 2010 viral DNA was extracted from randomly chosen cervical cancer biopsies and subjected to genotype determination using the diagnostic linear array genotyping test (Roche. The distribution of HPV genotypes was explored and the prevalence of HPV genotypes was mapped. RESULTS Of 96 cervical cancer tissue samples, 76 (79.2% were histopathologically classified as squamous cell cervical carcinoma. Due to the high cost of HPV genotyping tests, only twenty-five samples were randomly genotyped. Almost 90% of the cervical cancer patients were multiply infected with HPV-16 in combination with HPV-18, HPV-45, or HPV-52. The HPV-16 genotype had the highest prevalence, all samples being infected with HPV-16. CONCLUSION The cervical cancer cases were predominantly infected by multiple hrHPVs with HPV-16 as the major genotype among other hrHPVs, supporting the carcinogenic role of this hrHPV. Therefore, screening for hrHPVs in the general population is urgently needed as a means of early detection of cervical cancer.

  12. 581 Chronic Urticaria and Infections

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    Aguilar, Nadia; Lugo-Reyes, Saul; Segura Mendez, Nora Hilda; Mendieta, Elizabeth

    2012-01-01

    Background Chronic Urticaria (CU) is a group of diseases that share a distinct skin reaction pattern. Triggering of urticaria by infections has been discussed for many years but the exact role and pathogenesis of mast cell activation by infectious processes is unclear. The remission of annoying spontaneous chronic urticaria has been reported after successful treatment of persistent infections. Objective To describe the infections found in chronic urticaria patients in our service, by performing a complete medical history, physical examination, laboratory studies and cultures. Methods Universe: Consecutive patients with chronic urticaria, with a detailed history, physical examination, laboratory studies underwent clinical viral panel, cultures, biopsy for detection of H. Pylori. Results A total of 50 patients, mostly women 82% and 18% men, mean age 41 years. 42% of the total population had salmonella, proteus infection in 20% and 8% brucellosis. Crossed with urinary tract infection 6% of the population. Five patients had positive stool in 3 patients Endolimax nana was isolated and 2 patients reported Giardia lamblia, 5 patients (10%) women had undergone cervicovaginitis 2 of them infected with S. haemolyticus, the rest was cultivated E. faecalis, and T. Gardenella vaginalis, respectively. Was isolated in 2 patients and one patient H.pilory HCV infection. Conclusions Infections may play a causal role of UC in some cases. Were identified in 42% of cases and gastrointestinal infections by most common cause Salmonellosis. As for genitourinary tract infections, intestinal parasites, Helicobacter pylori, were treated appropriately with antibiotic therapy, found a successful resolution of urticaria mainly in patients infected with Helicobacter pylori. There is growing evidence that persistent infections in chronic urticaria are important triggers, particularly in the case of infection by Helicobacter pylori, so If an infection is identified, it should be appropriately

  13. Chronic helminth infection does not exacerbate Mycobacterium tuberculosis infection.

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    Marc P Hübner

    Full Text Available BACKGROUND: Chronic helminth infections induce a Th2 immune shift and establish an immunoregulatory milieu. As both of these responses can suppress Th1 immunity, which is necessary for control of Mycobacterium tuberculosis (MTB infection, we hypothesized that chronic helminth infections may exacerbate the course of MTB. METHODOLOGY/PRINCIPAL FINDINGS: Co-infection studies were conducted in cotton rats as they are the natural host for the filarial nematode Litomosoides sigmodontis and are an excellent model for human MTB. Immunogical responses, histological studies, and quantitative mycobacterial cultures were assessed two months after MTB challenge in cotton rats with and without chronic L. sigmodontis infection. Spleen cell proliferation and interferon gamma production in response to purified protein derivative were similar between co-infected and MTB-only infected animals. In contrast to our hypothesis, MTB loads and occurrence and size of lung granulomas were not increased in co-infected animals. CONCLUSIONS/SIGNIFICANCE: These findings suggest that chronic filaria infections do not exacerbate MTB infection in the cotton rat model. While these results suggest that filaria eradication programs may not facilitate MTB control, they indicate that it may be possible to develop worm-derived therapies for autoimmune diseases that do not substantially increase the risk for infections.

  14. Helicobacter Infection and Chronic Liver Diseases

    Institute of Scientific and Technical Information of China (English)

    2014-01-01

    This paper reviews the recentHelicobacter infection associated with chronic liver disease. The bacteriology, prevalence, pathogenesis and diagnosis were reviewed. Future work should be conducted on the pathogenesis and treatment of this disease.

  15. [Urinary tract infections and chronic renal failure].

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    Sobotová, D

    2011-01-01

    The paper briefly summarizes issues related to urinary tract infections in adults: predispositions and risk factors, classification, assessment of pathogenicity of bacterial agents, the role of bacteriuria and leucocyturia, interpretation of findings, treatment principles and an association with chronic renal failure. Urinary tract infections are the second most frequent infectious disease in the population. They most often affect women of childbearing potential and then seniors of both sexes who have multiple risk factors. Escherichia coli and Staphylococcus saprophyticus are the most pathogenic towards urinary tract; they are responsible for 85% and 10-15% of cases of acute uncomplicated urinary infections, respectively. Chronic pyelonephritis, a chronic interstitial nephritis, is the fourth most frequent cause of chronic renal failure. Chronic renal failure is a risk factor for the development of urinary infections due to metabolic disorders resulting in secondary immunodeficiencywith a disorder of all components of immunity. In patients with chronic renal failure, urinary tract infections occur most frequently after kidney transplantation when graft pyelonephritis is a life-threatening complication. Therefore, urinary tract infection prevention with co-trimoxazole once daily over at least 6 months is recommended in renal allograft recipients.

  16. Chronic Infection and Venous Thromboembolic Disease.

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    Epaulard, Olivier; Foote, Alison; Bosson, Jean-Luc

    2015-09-01

    Venous thromboembolic disease often arises as a complication of another pathological condition and/or triggering event. Infectious diseases result from both the direct action of the pathogens themselves and their effect on the immune system. The resulting inflammatory process and the coagulation and fibrinolysis processes share common pathways, explaining why infection is associated with thrombosis. In this brief overview, besides certain chronic infectious diseases, we also consider some acute infections, as the mechanisms are likely to be similar, particularly in the initial infective stage or the more acute episodes of a chronic infection. The infectious agent can be viral, bacterial, fungal, or parasitic. However, the literature on the link between infections and venous thromboembolism (VTE) is uneven, favoring infections that are found in more developed countries where physicians have access to VTE diagnostic tools. Thus, large epidemiological studies in this field are restricted to a limited number of the common chronic infectious diseases such as tuberculosis, while for other infections, particularly parasitic and fungal infections, the link with VTE is only evoked in a few scattered case reports.

  17. Bacterial colonization or infection in chronic sinusitis.

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    Pandak, Nenad; Pajić-Penavić, Ivana; Sekelj, Alen; Tomić-Paradžik, Maja; Cabraja, Ivica; Miklaušić, Božana

    2011-12-01

    The aim of this study was the determination of bacteria present in maxillary and ethmoid cavities in patients with chronic sinusitis and to correlate these findings with bacteria simultaneously present in their nasopharynx. The purpose of this correlation was to establish the role of bacteria found in chronically inflamed sinuses and to evaluate if the bacteria present colonized or infected sinus mucosa. Nasopharyngeal and sinus swabs of 65 patients that underwent functional endoscopic sinus surgery were cultivated and at the same time the presence of leukocytes were determined in each swab. The most frequently found bacteria in nasopharynx were Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus spp., Streptococcus viridans and Streptococcus pneumoniae. Maxillary or ethmoidal sinus swabs yielded bacterial growth in 47 (72.31%) patients. The most frequently found bacteria in sinuses were Staphylococcus epidermidis, Staphylococcus aureus, Klebsiella spp. and Streptococci (pneumoniae, viridans and spp.). The insignificant number of leukocytes was present in each sinus and nasopharyngeal swab. Every published microbiology study of chronic sinusitis proved that sinus mucosa were colonized with bacteria and not infected, yet antibiotic therapy was discussed making no difference between infection and colonization. Chronic sinusitis should be considered a chronic inflammatory condition rather than bacterial infection, so routine antibiotic therapy should be avoided. Empiric antibiotic therapy should be prescribed only in cases when the acute exacerbation of chronic sinusitis occurs and the antibiotics prescribed should aim the usual bacteria causing acute sinusitis. In case of therapy failure, antibiotics should be changed having in mind that under certain circumstances any bacteria colonizing sinus mucosa can cause acute exacerbation of chronic sinusitis.

  18. Rhinovirus Infection Induces Degradation of Antimicrobial Peptides and Secondary Bacterial Infection in Chronic Obstructive Pulmonary Disease

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    Patrick Mallia; Joseph Footitt; Rosa Sotero; Annette Jepson; Marco Contoli; Maria-Belen Trujillo-Torralbo; Tatiana Kebadze; Julia Aniscenko; Gregory Oleszkiewicz; Katrina Gray; Message, Simon D.; Kazuhiro Ito; Peter J Barnes; Ian M Adcock; Alberto Papi

    2012-01-01

    Rationale: Chronic obstructive pulmonary disease (COPD) exacerbations are associated with virus (mostly rhinovirus) and bacterial infections, but it is not known whether rhinovirus infections precipitate secondary bacterial infections.

  19. Management of chronic Giardia infection.

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    Escobedo, Angel A; Hanevik, Kurt; Almirall, Pedro; Cimerman, Sérgio; Alfonso, Maydel

    2014-09-01

    Advances in our understanding of chronic giardiasis (CG) may improve our care of patients in this stage of the disease. This review proposes a new concept of CG and highlights the recent advances in our understanding and management of this condition. According to this review, management requires, initially, an accurate diagnosis, which may exclude several conditions that can mimic CG. Optimal treatment requires a tailored approach which includes the recognition of the known modifiable causes of this health condition, assessment of symptoms and potential complications, their treatment utilizing, if necessary, a multidisciplinary team, and an ongoing monitoring for the effect of therapy - weighing the efficacy of individual drugs - all of these together may lead to a successful treatment of CG.

  20. Middle Ear Infection (Chronic Otitis Media) and Hearing Loss

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    ... You Middle Ear Infection (Chronic Otitis Media) and Hearing Loss Middle Ear Infection (Chronic Otitis Media) and Hearing ... learning important speech and language skills. Types of hearing loss Conductive hearing loss is a form of hearing ...

  1. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

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    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  2. [Chronic hepatitis and occult HCV infection].

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    Kowala-Piaskowska, Arleta; Mozer-Lisewska, Iwona; Pham, Tram N Q; Michalak, Tomasz I

    2010-01-01

    Hepatitis C virus (HCV) was discovered in 1989. HCV is a positive single-strand RNA. We all have thought, that HCV can replicate only in liver tissue, but now we know, that HCV can replicate in extrahepatic tissue as well. In about 48-86% of HCV infected patients, chronic hepatitis C (CHC) has been noticed and eventually, after tens of years, liver insufficiency, cirrhosis or hepatocellular carcinoma. The current recommended treatment for CHC is a combination of pegylated-interferon alpha and Ribavirin. Presently it is known, that HCV infection can persist as an occult infection. RNA HCV can be detected in patients after successful treatment for CHC or spontaneous elimination. Persistent HCV replication in hepatocytes or lymphoid cells would likely lead to continuous antigenic stimulation of the immune system. This prolonged replication may contribute to the immune tolerance of HCV, impairment of immune response and even further virus persistence. This occult infection grows more important in transplantation.

  3. Predomination of IL-17-producing tryptase-positive/chymase-positive mast cells in azoospermic chronic testicular inflammation.

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    Chen, S-J; Duan, Y-G; Haidl, G; Allam, J-P

    2016-08-01

    Chronic testicular inflammation and infection have been regarded as important factors in the pathogenesis of azoospermia. As key effector cells in innate and adaptive immune system, mast cells (MCs) were observed in inflammation and autoimmune disease. Furthermore, increased expression of tryptase-positive MCs has been reported in testicular disorders associated with male infertility/subfertility. However, little is known about the potential relationship between MCs and chronic testicular inflammation in azoospermic patients. Moreover, the preferential expression of MCs' subtypes in testis of these patients is still far from being understood. Thus, this study aimed to investigate characteristics of testicular MCs as well as their subtypes in azoospermic men with chronic testicular inflammation (AZI, n = 5) by immunohistochemical techniques. Our results showed significant increase of MCs in AZI, and more importantly, considerable numbers of tryptase-positive/chymase-positive MCs could also be demonstrated in AZI, when compared to control groups representing azoospermia without chronic testicular inflammation (AZW, n = 5) and normal spermatogenesis (NT, n = 5) respectively. Most interestingly, immunofluorescence staining revealed autoimmune-associated interleukin (IL)-17-producing MCs in AZI, whereas co-expression of MC markers with tumour necrosis factor (TNF)-α, IL-10 and IL-1β could not be detected. In conclusion, AZI is associated with significant increase of tryptase-positive/chymase-positive MCs expressing IL-17, and these MCs might contribute to the pathogenesis of AZI.

  4. Pediatric Infective Endocarditis: Has Staphylococcus aureus Overtaken Viridans Group Streptococci as the Predominant Etiological Agent?

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    Aisha Alshammary

    2008-01-01

    Full Text Available BACKGROUND: Viridans group streptococci (VGS have traditionally been the most common etiological agents of infective endocarditis (IE. Advances in cardiovascular surgery and the increasing use of long-term central venous catheters may have altered the epidemiology of pediatric IE.

  5. Altered T cell costimulation during chronic hepatitis B infection.

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    Barboza, Luisa; Salmen, Siham; Peterson, Darrell L; Montes, Henry; Colmenares, Melisa; Hernández, Manuel; Berrueta-Carrillo, Leidith E; Berrueta, Lisbeth

    2009-01-01

    T-cell response to hepatitis B virus (HBV) is vigorous, polyclonal and multi-specific in patients with acute hepatitis who ultimately clear the virus, whereas it is narrow and inefficient in patients with chronic disease, where inappropriate early activation events could account for viral persistence. We investigated the induction of activation receptors and cytokine production in response to HBcAg and crosslinking of CD28 molecules, in CD4+ cells from a group of chronically infected patients (CIP) and naturally immune subjects (NIS). We demonstrated that CD4+ cells from CIP did not increase levels of CD40L and CD69 following stimulation with HBcAg alone or associated to CD28 crosslinking, in contrast to subjects that resolved the infection (p<0.01). Furthermore, CD4+ cells from CIP produced elevated levels of IL-10 in response to HBcAg. These results suggest that a predominant inhibitory environment may be responsible for altered T cell costimulation, representing a pathogenic mechanism for viral persistence.

  6. Baseline Predictors of Mortality among Predominantly Rural-Dwelling End-Stage Renal Disease Patients on Chronic Dialysis Therapies in Limpopo, South Africa.

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    Ramon A Tamayo Isla

    Full Text Available Dialysis therapy for end-stage renal disease (ESRD continues to be the readily available renal replacement option in developing countries. While the impact of rural/remote dwelling on mortality among dialysis patients in developed countries is known, it remains to be defined in sub-Saharan Africa.A single-center database of end-stage renal disease patients on chronic dialysis therapies treated between 2007 and 2014 at the Polokwane Kidney and Dialysis Centre (PKDC of the Pietersburg Provincial Hospital, Limpopo South Africa, was retrospectively reviewed. All-cause, cardiovascular, and infection-related mortalities were assessed and associated baseline predictors determined.Of the 340 patients reviewed, 52.1% were male, 92.9% were black Africans, 1.8% were positive for the human immunodeficiency virus (HIV, and 87.5% were rural dwellers. The average distance travelled to the dialysis centre was 112.3 ± 73.4 Km while 67.6% of patients lived in formal housing. Estimated glomerular filtration rate (eGFR at dialysis initiation was 7.1 ± 3.7 mls/min while hemodialysis (HD was the predominant modality offered (57.1%. Ninety-two (92 deaths were recorded over the duration of follow-up with the majority (34.8% of deaths arising from infection-related causes. Continuous ambulatory peritoneal dialysis (CAPD was a significant predictor of all-cause mortality (HR: 1.62, CI: 1.07-2.46 and infection-related mortality (HR: 2.27, CI: 1.13-4.60. On multivariable cox regression, CAPD remained a significant predictor of all-cause mortality (HR: 2.00, CI: 1.29-3.10 while the risk of death among CAPD patients was also significantly modified by diabetes mellitus (DM status (HR: 4.99, CI: 2.13-11.71.CAPD among predominantly rural dwelling patients in the Limpopo province of South Africa is associated with an increased risk of death from all-causes and infection-related causes.

  7. Methylotroph Infections and Chronic Granulomatous Disease.

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    Falcone, E Liana; Petts, Jennifer R; Fasano, Mary Beth; Ford, Bradley; Nauseef, William M; Neves, João Farela; Simões, Maria João; Tierce, Millard L; de la Morena, M Teresa; Greenberg, David E; Zerbe, Christa S; Zelazny, Adrian M; Holland, Steven M

    2016-03-01

    Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in production of phagocyte-derived reactive oxygen species, which leads to recurrent infections with a characteristic group of pathogens not previously known to include methylotrophs. Methylotrophs are versatile environmental bacteria that can use single-carbon organic compounds as their sole source of energy; they rarely cause disease in immunocompetent persons. We have identified 12 infections with methylotrophs (5 reported here, 7 previously reported) in patients with CGD. Methylotrophs identified were Granulibacter bethesdensis (9 cases), Acidomonas methanolica (2 cases), and Methylobacterium lusitanum (1 case). Two patients in Europe died; the other 10, from North and Central America, recovered after prolonged courses of antimicrobial drug therapy and, for some, surgery. Methylotrophs are emerging as disease-causing organisms in patients with CGD. For all patients, sequencing of the 16S rRNA gene was required for correct diagnosis. Geographic origin of the methylotroph strain may affect clinical management and prognosis.

  8. Predominant involvement of the cerebellum in guinea pigs infected with bovine spongiform encephalopathy (BSE).

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    Furuoka, H; Horiuchi, M; Yamakawa, Y; Sata, T

    2011-05-01

    This study reports the experimental transmission of bovine spongiform encephalopathy (BSE) to guinea pigs and describes the cerebellar lesions in these animals. Guinea pigs were inoculated intracerebrally with 10% brain homogenates from BSE-affected cattle. These animals were designated as the first passage. Second and third passages were subsequently performed. All guinea pigs developed infection at each passage. The mean incubation period of the first passage was 370 days post-infection (dpi) and this decreased to 307 dpi and 309 dpi for the second and third passages, respectively. Mild to severe spongiform degeneration and gliosis were observed in the cerebral cortex, thalamus and brainstem. In addition, the affected animals had marked pathological changes in the cerebellum characterized by severe cortical atrophy associated with Bergmann radial gliosis of the molecular layer and reduction in the width of the granular cell layer. Immunohistochemically, intense PrP(Sc) deposition and scattered plaque-like deposits were observed in the molecular and granular cell layers. Cerebellar lesions associated with severe atrophy of the cortex have not been reported in animal prion diseases, including in the experimental transmission of PrP(Sc) to small rodents. These lesions were similar to the lesions of human kuru or the VV2 variant of sporadic Creutzfeldt-Jakob disease, although typical kuru plaques or florid plaques were not observed in the affected animals.

  9. Chlamydia pneumoniae infection in mice induces chronic lung inflammation, iBALT formation, and fibrosis.

    Directory of Open Access Journals (Sweden)

    Madhulika Jupelli

    Full Text Available Chlamydia pneumoniae (CP lung infection can induce chronic lung inflammation and is associated with not only acute asthma but also COPD exacerbations. However, in mouse models of CP infection, most studies have investigated specifically the acute phase of the infection and not the longer-term chronic changes in the lungs. We infected C57BL/6 mice with 5 × 10(5 CP intratracheally and monitored inflammation, cellular infiltrates and cytokine levels over time to investigate the chronic inflammatory lung changes. While bacteria numbers declined by day 28, macrophage numbers remained high through day 35. Immune cell clusters were detected as early as day 14 and persisted through day 35, and stained positive for B, T, and follicular dendritic cells, indicating these clusters were inducible bronchus associated lymphoid tissues (iBALTs. Classically activated inflammatory M1 macrophages were the predominant subtype early on while alternatively activated M2 macrophages increased later during infection. Adoptive transfer of M1 but not M2 macrophages intratracheally 1 week after infection resulted in greater lung inflammation, severe fibrosis, and increased numbers of iBALTS 35 days after infection. In summary, we show that CP lung infection in mice induces chronic inflammatory changes including iBALT formations as well as fibrosis. These observations suggest that the M1 macrophages, which are part of the normal response to clear acute C. pneumoniae lung infection, result in an enhanced acute response when present in excess numbers, with greater inflammation, tissue injury, and severe fibrosis.

  10. Neurocognitive impairment associated with predominantly early stage HIV infection in Abuja, Nigeria.

    Science.gov (United States)

    Akolo, Christopher; Royal, Walter; Cherner, Mariana; Okwuasaba, Kanayo; Eyzaguirre, Lindsay; Adebiyi, Ruxton; Umlauf, Anya; Hendrix, Terence; Johnson, Joyce; Abimiku, Alashl'e; Blattner, William A

    2014-08-01

    Detailed neuropsychological testing was performed on 133 human immunodeficiency virus (HIV) seropositive (SP) and 77 HIV seronegative (SN) individuals, 86 % with early stage HIV infection in Nigeria, to determine the frequency of HIV-related neurocognitive impairment among the HIV-infected group. The tests were administered to assess the following seven ability domains: speed of information processing, attention/working memory, executive functioning, learning, memory, verbal fluency, and motor function motor. Demographically corrected individual test scores and scores for each domain or reflecting a global deficit (a global deficit score, or GDS) were compared for the SP and SN groups. SP participants were older, had fewer years of education, were more likely to be married, differed in ethnicity, and had higher depression scores than SN individuals. Within the seven ability domains, SP performed worse than SN with respect to speed of information processing, executive function, learning, memory, and verbal fluency and also on the global measure. SP were also more frequently impaired on tests of SIP, and there was a borderline increase in the frequency of global impairment. On the individual tests, SP performed worse than SN on four tests that assessed learning, verbal fluency, memory, and motor function (the Timed Gait). SP subjects, however, performed better than SN on the Finger-tapping test, also a motor task. Performance by SP subjects was not associated on the timed gait which showed a borderline statistically significant correlation with CD4 counts. However, there were significant correlations between viral load measurements and individual tests of speed of information processing, executive function, learning, and verbal fluency and with overall executive function and a borderline correlation with the GDS. Depression scores for SP were associated with impairment on only a single test of executive function. These results demonstrate the ability of these

  11. Predominant role of interferon-γ in the host protective effect of CD8(+) T cells against Neospora caninum infection.

    Science.gov (United States)

    Correia, Alexandra; Ferreirinha, Pedro; Botelho, Sofia; Belinha, Ana; Leitão, Catarina; Caramalho, Íris; Teixeira, Luzia; González-Fernandéz, África; Appelberg, Rui; Vilanova, Manuel

    2015-10-09

    It is well established that CD8(+) T cells play an important role in protective immunity against protozoan infections. However, their role in the course of Neospora caninum infection has not been fully elucidated. Here we report that CD8-deficient mice infected with N. caninum presented higher parasitic loads in the brain and lungs and lower spleen and brain immunity-related GTPases than their wild-type counterparts. Moreover, adoptive transfer of splenic CD8(+) T cells sorted from N. caninum-primed immunosufficient C57BL/10 ScSn mice prolonged the survival of infected IL-12-unresponsive C57BL/10 ScCr recipients. In both C57BL/6 and C57BL/10 ScSn mice CD8(+) T cells are activated and produce interferon-γ (IFN-γ) upon challenged with N. caninum. The host protective role of IFN-γ produced by CD8(+) T cells was confirmed in N. caninum-infected RAG2-deficient mice reconstituted with CD8(+) T cells obtained from either IFN-γ-deficient or wild-type donors. Mice receiving IFN-γ-expressing CD8(+) T cells presented lower parasitic burdens than counterparts having IFN-γ-deficient CD8(+) T cells. Moreover, we observed that N. caninum-infected perforin-deficient mice presented parasitic burdens similar to those of infected wild-type controls. Altogether these results demonstrate that production of IFN-γ is a predominant protective mechanism conferred by CD8(+) T cells in the course of neosporosis.

  12. Role of IL-28B polymorphisms in virologic response to combined pegylated interferon and ribavirin therapy in genotype 4 chronic HCV infected patients with and without cirrhosis

    Directory of Open Access Journals (Sweden)

    Amira Youssef Shaala

    2015-09-01

    Conclusion: In Egypt, where chronic HCV genotype 4 and schistosoma coinfection predominate, both schistosoma infection and cirrhosis are more potent than IL28B polymorphisms as strong baseline negative predictors of hepatitis C treatment response.

  13. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

    Science.gov (United States)

    Ren, Lili; Yang, Donghong; Ren, Xianwen; Li, Mingkun; Mu, Xinlin; Wang, Qi; Cao, Jie; Hu, Ke; Yan, Chunliang; Fan, Hongwei; Li, Xiangxin; Chen, Yusheng; Wang, Ruiqin; An, Fucheng; An, Shuchang; Luo, Ming; Wang, Ying; Xiao, Yan; Xiang, Zichun; Xiao, Yan; Li, Li; Huang, Fang; Jin, Qi; Gao, Zhancheng; Wang, Jianwei

    2017-01-01

    Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs. PMID:28128353

  14. Hepatitis C Virus Infection and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Ayten Kadanali

    2009-02-01

    Full Text Available Background and Aims: A growing pile of evidence supports the notion that pulmonary involvement is one of the extrahepatic manifestations of chronic hepatitis C virus (HCV infection. The objective of this study was to determine the prevalence of HCV infection in patients with chronic obstructive pulmonary disease (COPD, and vice versa.Methods: Two cross-sectional studies were performed: 1. A prevalence study of HCV infection among patients with COPD; 2. A prevalence study of COPD among patients with chronic HCV infection. COPD was diagnosed according to ATS/ERS guidelines. The prevalence of HCV infection in COPD group was compared with the result of a previous study which determined the prevalence of HCV infection in general population. Prevalence of COPD in patients with chronic HCV infection was also compared to those with chronic hepatitis B virus (HBV infection.Results: The study included 108 patients with COPD, 68 patients with chronic HCV infection, and 60 patients with chronic HBV infection. HCV infection was observed in 8.3% of patients with COPD, and 1.2% of the control subjects (P= 0.000. The prevalence of COPD among patients with chronic HCV and HBV infection was 17.6%, and 5%, respectively (P=0.03. Comparing COPD-positive and -negative chronic HCV patients for risk factors for COPD revealed that only the mean age was higher in COPD-positive patients (60.8±9.1 years vs. 46.5±11.5 years, P=0.000. In multivariate analysis, age was found to be the only independent predictor of COPD in HCV group.Conclusions: Patients with COPD have increased prevalence of HCV infection, and patients with HCV infection, have increased prevalence of COPD. COPD may be an extrahepatic disease associated with HCV infection.

  15. Wound Chronicity, Inpatient Care, and Chronic Kidney Disease Predispose to MRSA Infection in Diabetic Foot Ulcers

    Science.gov (United States)

    Yates, Christopher; May, Kerry; Hale, Thomas; Allard, Bernard; Rowlings, Naomi; Freeman, Amy; Harrison, Jessica; McCann, Jane; Wraight, Paul

    2009-01-01

    OBJECTIVE To determine the microbiological profile of diabetes-related foot infections (DRFIs) and the impact of wound duration, inpatient treatment, and chronic kidney disease (CKD). RESEARCH DESIGN AND METHODS Postdebridement microbiological samples were collected from individuals presenting with DRFIs from 1 January 2005 to 31 December 2007. RESULTS A total of 653 specimens were collected from 379 individuals with 36% identifying only one isolate. Of the total isolates, 77% were gram-positive bacteria (staphylococci 43%, streptococci 13%). Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from 23%; risk factors for MRSA included prolonged wound duration (odds ratio 2.31), inpatient management (2.19), and CKD (OR 1.49). Gram-negative infections were more prevalent with inpatient management (P = 0.002) and prolonged wound duration (P < 0.001). Pseudomonal isolates were more common in chronic wounds (P < 0.001). CONCLUSIONS DRFIs are predominantly due to gram-positive aerobes but are usually polymicrobial and increase in complexity with inpatient care and ulcer duration. In the presence of prolonged duration, inpatient management, or CKD, empiric MRSA antibiotic cover should be considered. PMID:19587371

  16. Challenges with current inhaled treatments for chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.

    LENUS (Irish Health Repository)

    Greally, Peter

    2012-06-01

    Pseudomonas aeruginosa (Pa) is the predominant pathogen infecting the airways of patients with cystic fibrosis (CF). Initial colonization is usually transient and associated with non-mucoid strains, which can be eradicated if identified early. This strategy can prevent, or at least delay, chronic Pa infection, which eventually develops in the majority of patients by their late teens or early adulthood. This article discusses the management and latest treatment developments of Pa lung infection in patients with CF, with a focus on nebulized antibiotic therapy.

  17. Phyllanthus species for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping

    2011-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists.......Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists....

  18. RANTES gene single nucleotide polymorphisms and expression in patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    DUAN Zhong-ping; ZHAO Xiu-ying; HUANG De-zhuang; HE Li-xiang; CHEN Yu; ZHAO Chun-hui; ZHENG Bo-jian

    2005-01-01

    Background Regulated on activation, normal T-cell expressed and secreted (RANTES) plays a critical role in T-lymphocyte activation and proliferation. The process is involved in both acute and chronic phases of inflammation. The present study was to ascertain the possible correlations between chronic hepatitis B virus (HBV) infection and the RANTES gene polymorphisms and their expression. Methods The study included 130 HBV negative healthy donors and 152 patients with chronic hepatitis B (CHB) virus infection. The polymerase chain reaction (PCR) and restriction fragment length polymorphisms (RFLPs) were used to detect RANTES gene single nucleotide polymorphisms (SNPs). RANTES levels in the platelet depleted plasma were detected by enzyme linked immunosorbent assay (ELISA). Results RANTES alleles -403G, -28C and In1.1T were the predominant alleles in the subjects studied. No significant correlation was found between CHB infection and the RANTES alleles, while a significant correlation was found between CHB infection and increased RANTES expression in platelet depleted plasma (P<0.05). Conclusions SNPs in RANTES gene do not affect chronic HBV infection or the outcome of interferon-α treatment in patients positive for HBV "e" antigen (HBeAg+). However, patients with CHB infection express the higher levels of plasma RANTES, which is thus associated with CHB infection.

  19. The predominance of alternatively activated macrophages following challenge with cell wall peptide-polysaccharide after prior infection with Sporothrix schenckii.

    Science.gov (United States)

    Alegranci, Pamela; de Abreu Ribeiro, Livia Carolina; Ferreira, Lucas Souza; Negrini, Thais de Cássia; Maia, Danielle Cardoso Geraldo; Tansini, Aline; Gonçalves, Amanda Costa; Placeres, Marisa Campos Polesi; Carlos, Iracilda Zeppone

    2013-08-01

    Sporotrichosis is a subcutaneous mycosis that is caused by the dimorphic fungus Sporothrix schenckii. This disease generally occurs within the skin and subcutaneous tissues, causing lesions that can spread through adjacent lymphatic vessels and sometimes leading to systemic diseases in immunocompromised patients. Macrophages are crucial for proper immune responses against a variety of pathogens. Furthermore, macrophages can play different roles in response to different microorganisms and forms of activation, and they can be divided into "classic" or "alternatively" activated populations, as also known as M1 and M2 macrophages. M1 cells can lead to tissue injury and contribute to pathogenesis, whereas M2 cells promote angiogenesis, tissue remodeling, and repair. The aim of this study was to investigate the roles of M1 and M2 macrophages in a sporotrichosis model. Toward this end, we performed phenotyping of peritoneal exudate cells and evaluated the concomitant production of several immunomediators, including IL-12, IL-10, TGF-β, nitric oxide, and arginase-I activity, which were stimulated ex vivo with cell wall peptide-polysaccharide. Our results showed the predominance of the M2 macrophage population, indicated by peaks of arginase-I activity as well as IL-10 and TGF-β production during the 6th and 8th weeks after infection. These results were consistent with cellular phenotyping that revealed increases in CD206-positive cells over this period. This is the first report of the participation of M2 macrophages in sporotrichosis infections.

  20. Molecular characteristics and stages of chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Ying-Hui Shi; Chang-He Shi

    2009-01-01

    Hepatitis B virus (HBV) is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our understanding of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma (HCC). Those with chronic HBV infection may present in one of the four phases of infection: immune tolerance, immune clearance [hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB)], inactive carrier state, and reactivation (HBeAg-negative CHB). Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.

  1. Polyphasic innate immune responses to acute and chronic LCMV infection: Innate immunity to acute & chronic viral infection

    OpenAIRE

    Norris, Brian A; Uebelhoer, Luke S.; Nakaya, Helder I.; Price, Aryn A; Grakoui, Arash; Pulendran, Bali

    2013-01-01

    Resolution of acute and chronic viral infections requires activation of innate cells to initiate and maintain adaptive immune responses. Here we report that infection with acute Armstrong (ARM) or chronic Clone 13 (C13) strains of lymphocytic choriomeningitis virus (LCMV) led to two distinct phases of innate immune response. During the first 72hr of infection, dendritic cells upregulated activation markers, and stimulated anti-viral CD8+ T cells, independent of viral strain. Seven days after ...

  2. The role of bacterial biofilms in chronic infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas

    2013-01-01

    treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance...... to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my...... previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial aggregation is the default mode, and that subsequent biofilm development progresses by adaptation to nutritional and environmental...

  3. Chronic hepatitis B infection in pregnancy

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    There are no standard guidelines to follow when apatient with chronic hepatitis B infection becomespregnant or desires pregnancy. Topics to considerinclude which patients to treat, when to start treatment,what treatment to use and when to stop treatment.Without any prophylaxis or antiviral therapy, a hepatitisB surface antigen and E antigen positive mother has upto a 90% likelihood of vertical transmission of hepatitisB virus (HBV) to child. Standard of care in the UnitedStates to prevent perinatal transmission consists ofadministration of hepatitis B immune globulin andHBV vaccination to the infant. The two strongest riskfactors of mother to child transmission (MTCT) of HBVinfection despite immunoprophylaxis are high maternalHBV viral load and high activity of viral replication.The goal is to prevent transmission of HBV at birthby decreasing viral load and/or decreasing activity ofthe virus. Although it is still somewhat controversial,most evidence shows that starting antivirals in thethird trimester is effective in decreasing MTCT withoutaffecting fetal development. There is a growing body ofliterature supporting the safety and efficacy of antiviraltherapies to reduce MTCT of hepatitis B. There areno formal recommendations regarding which agent tochoose. Tenofovir, lamivudine and telbivudine have allbeen proven efficacious in decreasing viral load at birthwithout known birth defects, but final decision of whichantiviral medication to use will have to be determinedby physician and patient. The antivirals may bediscontinued immediately if patient is breastfeeding, orwithin first four weeks if infant is being formula fed.

  4. High prevalence of occult hepatitis C virus infection in patients with chronic hepatitis B virus infection.

    Science.gov (United States)

    Castillo, Inmaculada; Bartolomé, Javier; Quiroga, Juan Antonio; Carreño, Vicente

    2013-08-01

    Hepatitis C virus (HCV) infection in the absence of detectable antibodies against HCV and of viral RNA in serum is called occult HCV infection. Its prevalence and clinical significance in chronic hepatitis B virus (HBV) infection is unknown. HCV RNA was tested for in the liver samples of 52 patients with chronic HBV infection and 21 (40 %) of them were positive for viral RNA (occult HCV infection). Liver fibrosis was found more frequently and the fibrosis score was significantly higher in patients with occult HCV than in negative ones, suggesting that occult HCV infection may have an impact on the clinical course of HBV infection.

  5. [Occult hepatitis B virus infection in chronic hepatitis C].

    Science.gov (United States)

    Jang, Jae Young; Park, Eui Ju

    2013-09-01

    Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.

  6. Genus Phyllanthus for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Liu, J; Lin, Haili; McIntosh, H

    2001-01-01

    To evaluate the efficacy and safety of genus Phyllanthus for chronic hepatitis B virus (HBV) infection we performed a systematic review of randomized clinical trials. Randomized trials comparing genus Phyllanthus vs. placebo, no intervention, general nonspecific treatment, other herbal medicine...

  7. Immune regulation in chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Hartling, Hans Jakob; Ballegaard, Vibe Cecilie; Nielsen, Nick Schou;

    2016-01-01

    The immunological result of infection with Hepatitis C virus (HCV) depends on the delicate balance between a vigorous immune response that may clear the infection, but with a risk of unspecific inflammation and, or a less inflammatory response that leads to chronic infection. In general, exhaustion...... and impairment of cytotoxic function of HCV-specific T cells and NK cells are found in patients with chronic HCV infection. In contrast, an increase in immune regulatory functions is found primarily in form of increased IL-10 production possibly due to increased level and function of anti-inflammatory Tregs....... Thus, the major immune players during chronic HCV infection are characterized by a decrease of cytotoxic function and increase of inhibitory functions. This may be an approach to diminish intrahepatic and systemic inflammation. Finally, there has been increasing awareness of regulatory functions...

  8. Ribavirin monotherapy for chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2006-01-01

    Adding ribavirin to interferon improves treatment response for patients with chronic hepatitis C, but the effects of ribavirin monotherapy are unclear. We conducted a systematic review to assess the benefits and harms of ribavirin monotherapy for patients with chronic hepatitis C....

  9. Chronic Pseudomonas aeruginosa lung infection in normal and athymic rats

    DEFF Research Database (Denmark)

    Johansen, H K; Espersen, F; Pedersen, S S

    1993-01-01

    We have compared a chronic lung infection with Pseudomonas aeruginosa embedded in alginate beads in normal and athymic rats with an acute infection with free live P. aeruginosa bacteria. The following parameters were observed and described: mortality, macroscopic and microscopic pathologic change...

  10. Chronic rhinovirus infection in an adult with cystic fibrosis.

    Science.gov (United States)

    Flight, William G; Bright-Thomas, Rowland J; Tilston, Peter; Mutton, Kenneth J; Guiver, Malcolm; Webb, A Kevin; Jones, Andrew M

    2013-11-01

    Rhinovirus is a common cause of exacerbations of cystic fibrosis (CF) and is usually considered a self-limiting infection. We report a case of chronic infection with rhinovirus A type 33 in a 43-year-old male with CF which has persisted for over 2 years.

  11. Chronic hepatitis E virus infection in liver transplant recipients

    NARCIS (Netherlands)

    Haagsma, Elizabeth B.; van den Berg, Arie P.; Porte, Robert J.; Benne, Cornelis A.; Vennema, Harry; Reimerink, Johan H. J.; Koopmans, Marion P. G.

    2008-01-01

    Hepatitis E virus (HEV) infection is known to run a self-limiting course. Sporadic cases of acute hepatitis due to infection with HEV genotype 3, present in pig populations, are increasingly recognized. Zoonotic transmission seems infrequent. The entity of unexplained chronic hepatitis after liver t

  12. Invasive fungal infections in patients with chronic granulomatous disease

    NARCIS (Netherlands)

    Henriet, S.S.V.; Verweij, P.E.; Holland, S.M.; Warris, A.

    2013-01-01

    Invasive fungal infections are a major threat for chronic granulomatous disease (CGD) patients. The present study provides a comprehensive overview of published invasive fungal infections in the CGD host through an extensive review of epidemiological, clinical, diagnostic and therapeutic data. In ad

  13. Chronic hepatitis E infection in lung transplant recipients

    NARCIS (Netherlands)

    Riezebos-Brilman, Annelies; Puchhammer-Stockl, Elisabeth; van der Weide, Hinke Y.; Haagsma, Elizabeth B.; Jaksch, Peter; Bejvl, Isabella; Niesters, Hubert G.; Verschuuren, Erik A. M.

    2013-01-01

    BACKGROUND: Hepatitis E virus (HEV) genotype 3 has been identified in patients with autochthonous HEV infections in developed countries and is currently being recognized as an emerging zoonotic pathogen. HEV infection may lead to a chronic hepatitis in immune-compromised patients. METHODS: We studie

  14. Association of Chronic HBV Infection with Chronic Lymphoproliferative Disorders: A Review and Case Report

    Directory of Open Access Journals (Sweden)

    Inna M. Mulina

    2016-06-01

    Full Text Available This article presents a clinical report on the associated course of chronic hepatitis B virus (HBV infection with Castleman's disease (CD. We noticed the reactivation of previously latent chronic hepatitis B (CHB with high replicative activity of HBV DNA during the treatment of lymphoproliferative disease. This clinical case dictates the need for pre-emptive therapy of HBV infection with nucleoside analogues in patients who are receiving chemotherapy.

  15. Chronic obstructive pulmonary disease and risk of infection

    DEFF Research Database (Denmark)

    Lange, Peter

    2009-01-01

    of bacteria causing acute exacerbations. Also lung infections like pneumonia, lung abscess and empyema are more often seen in patients with COPD than in healthy subjects. With regard to extrapulmonary infections, it seems that COPD patients are not at higher risk of infection compared with subjects without......This review article focuses on the risk of infections in patients with chronic obstructive pulmonary disease (COPD). Throughout the years there have been a number of studies describing the risk of pulmonary infections in patients with COPD, whereas only few studies have focused on the risk...... of infection outside the lungs. With increasing severity of COPD the risk of respiratory tract infection also increases. The impairment of the innate immune system is most likely responsible for both the colonization of respiratory tract with bacteria and for an increased risk of infection with new strains...

  16. The Expression of CD2 in Chronic HBV Infection

    Institute of Scientific and Technical Information of China (English)

    Jie Li; Baotai Qi; Ping Chen; Linjing He; Ping Wang; Yuqiang Ji; Ming Xie

    2008-01-01

    It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells. and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of CD2 expressed on the surface of PBMC, the expression Ievel of CD2 mRNA in PBMC and the percentage of CD2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of CD2 significantly increased with the severity of chronic HBV infection, which suggested that CD2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular & Molecular Immunology.2008; 5(1):69-73.

  17. Chronic hepatitis caused by persistent parvovirus B19 infection

    Directory of Open Access Journals (Sweden)

    Mogensen Trine H

    2010-08-01

    Full Text Available Abstract Background Human infection with parvovirus B19 may lead to a diverse spectrum of clinical manifestations, including benign erythema infectiosum in children, transient aplastic crisis in patients with haemolytic anaemia, and congenital hydrops foetalis. These different diseases represent direct consequences of the ability of parvovirus B19 to target the erythroid cell lineage. However, accumulating evidence suggests that this virus can also infect other cell types resulting in diverse clinical manifestations, of which the pathogenesis remains to be fully elucidated. This has prompted important questions regarding the tropism of the virus and its possible involvement in a broad range of infectious and autoimmune medical conditions. Case Presentation Here, we present an unusual case of persistent parvovirus B19 infection as a cause of chronic hepatitis. This patient had persistent parvovirus B19 viraemia over a period of more than four years and displayed signs of chronic hepatitis evidenced by fluctuating elevated levels of ALAT and a liver biopsy demonstrating chronic hepatitis. Other known causes of hepatitis and liver damage were excluded. In addition, the patient was evaluated for immunodeficiency, since she had lymphopenia both prior to and following clearance of parvovirus B19 infection. Conclusions In this case report, we describe the current knowledge on the natural history and pathogenesis of parvovirus B19 infection, and discuss the existing evidence of parvovirus B19 as a cause of acute and chronic hepatitis. We suggest that parvovirus B19 was the direct cause of this patient's chronic hepatitis, and that she had an idiopathic lymphopenia, which may have predisposed her to persistent infection, rather than bone marrow depression secondary to infection. In addition, we propose that her liver involvement may have represented a viral reservoir. Finally, we suggest that clinicians should be aware of parvovirus B19 as an unusual

  18. Review of Helicobacter pylori infection and chronic renal failure.

    Science.gov (United States)

    Sugimoto, Mitsushige; Yamaoka, Yoshio

    2011-02-01

    Chronic renal failure patients receiving hemodialysis and continuous ambulatory peritoneal dialysis often encounter gastrointestinal troubles over their long treatment period. Helicobacter pylori infection has close association with development of peptic ulcer, gastric cancer and gastric lymphoma, and is thought to be one of the major risk factors for gastrointestinal troubles in dialysis patients. However, it is unclear whether H. pylori infection is directly associated with progression of renal dysfunction and prognosis of chronic renal failure patients. Recent consensus shows that the prevalence of H. pylori infection in chronic renal failure patients is significantly lower than in subjects with normal renal function. In the natural history of H. pylori infection in hemodialysis patients, the prevalence of infection decreases as dialysis periods progressed, in particular within the first four years after the start of treatment. However, the chance of natural eradication becomes rare for patients receiving dialysis treatment for a long time. Moreover, chronic renal failure patients with H. pylori infection have a higher incidence of gastroduodenal diseases, and therefore, are recommended to receive eradication therapies, especially for those receiving treatment for a long time and with higher risks of complication. Intensive endoscopic check-ups for the prevention of gastrointestinal events and the discovery of peptic ulcer and neoplastic diseases at an early phase may be required.

  19. The role of bacterial biofilms in chronic infections.

    Science.gov (United States)

    Bjarnsholt, Thomas

    2013-05-01

    Acute infections caused by pathogenic bacteria have been studied extensively for well over 100 years. These infections killed millions of people in previous centuries, but they have been combated effectively by the development of modern vaccines, antibiotics and infection control measures. Most research into bacterial pathogenesis has focused on acute infections, but these diseases have now been supplemented by a new category of chronic infections caused by bacteria growing in slime-enclosed aggregates known as biofilms. Biofilm infections, such as pneumonia in cystic fibrosis patients, chronic wounds, chronic otitis media and implant- and catheter-associated infections, affect millions of people in the developed world each year and many deaths occur as a consequence. In general, bacteria have two life forms during growth and proliferation. In one form, the bacteria exist as single, independent cells (planktonic) whereas in the other form, bacteria are organized into sessile aggregates. The latter form is commonly referred to as the biofilm growth phenotype. Acute infections are assumed to involve planktonic bacteria, which are generally treatable with antibiotics, although successful treatment depends on accurate and fast diagnosis. However, in cases where the bacteria succeed in forming a biofilm within the human host, the infection often turns out to be untreatable and will develop into a chronic state. The important hallmarks of chronic biofilm-based infections are extreme resistance to antibiotics and many other conventional antimicrobial agents, and an extreme capacity for evading the host defences. In this thesis, I will assemble the current knowledge on biofilms with an emphasis on chronic infections, guidelines for diagnosis and treatment of these infections, before relating this to my previous research into the area of biofilms. I will present evidence to support a view that the biofilm lifestyle dominates chronic bacterial infections, where bacterial

  20. Pronounced phenotype in activated regulatory T cells during a chronic helminth infection.

    Science.gov (United States)

    Layland, Laura E; Mages, Jörg; Loddenkemper, Christoph; Hoerauf, Achim; Wagner, Hermann; Lang, Roland; da Costa, Clarissa U Prazeres

    2010-01-15

    Although several markers have been associated with the characterization of regulatory T cells (Tregs) and their function, no studies have investigated the dynamics of their phenotype during infection. Since the necessity of Tregs to control immunopathology has been demonstrated, we used the chronic helminth infection model Schistosoma mansoni to address the impact on the Treg gene repertoire. Before gene expression profiling, we first studied the localization and Ag-specific suppressive nature of classically defined Tregs during infection. The presence of Foxp3+ cells was predominantly found in the periphery of granulomas and isolated CD4+CD25(hi)Foxp3+ Tregs from infected mice and blocked IFN-gamma and IL-10 cytokine secretion from infected CD4+CD25- effector T cells. Furthermore, the gene expression patterns of Tregs and effector T cells showed that 474 genes were significantly regulated during schistosomiasis. After k-means clustering, we identified genes exclusively regulated in all four populations, including Foxp3, CD103, GITR, OX40, and CTLA-4--classic Treg markers. During infection, however, several nonclassical genes were upregulated solely within the Treg population, such as Slpi, Gzmb, Mt1, Fabp5, Nfil3, Socs2, Gpr177, and Klrg1. Using RT-PCR, we confirmed aspects of the microarray data and also showed that the expression profile of Tregs from S. mansoni-infected mice is simultaneously unique and comparable with Tregs derived from other infections.

  1. Chronic Pseudomonas aeruginosa infection definition: EuroCareCF Working Group report

    DEFF Research Database (Denmark)

    Pressler, T; Bohmova, C; Conway, S;

    2011-01-01

    Chronic pulmonary infection with P. aeruginosa develops in most patients with cystic fibrosis (CF); by adulthood 80% of patients are infected and chronic P. aeruginosa infection is the primary cause of increased morbidity and mortality in CF. Chronic infection is preceded by an intermittent stage...

  2. Extrahepatic manifestations of chronic hepatitis C virus infection

    OpenAIRE

    Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne claire; Saadoun, David

    2016-01-01

    International audience; During hepatitis C virus (HCV) chronic infection, extrahepatic manifestations are frequent and polymorphous. This article reports on a large cohort of patients with HCV-related autoimmune or lymphoproliferative disorders, from mixed cryoglobulinemia vasculitis to frank lymphomas. The relationship between HCV infection and such immune-related diseases has been formally demonstrated by epidemiological, clinical, immunological and pathological data, and results of therape...

  3. Chronic infection with Achromobacter xylosoxidans in cystic fibrosis patients; a retrospective case control study

    DEFF Research Database (Denmark)

    Rønne Hansen, Christine; Pressler, Tacjana; Høiby, Niels

    2006-01-01

    patients (6 males) with chronic A. xylosoxidans infection were matched by age, FEV(1) and body mass index z-score to 15 controls (7 males) at the time of establishment of chronic infection. Clinical parameters of the groups were compared from the time of establishment of chronic infection until spring 2006...... to a decline in lung function in a subgroup of chronically infected CF patients characterised by a rapid increase in specific precipitating antibodies. Cross-infection may possibly occur....

  4. H pylori infection causes chronic pancreatitis in Mongolian gerbils

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system.METHODS: Mongolian gerbils were infected with wild type (WT) H pyloritype Ⅰ strain B128 or its isogenic mutant B128 Acag Y (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and H pylori DNA was analyzed by seminested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry.Cytokine mRNA, gastric pH, plasma gastrin, amylase,lipase, and glucose levels were determined.RESULTS: The H pylori infection rate was 95%.Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immunohistochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals and those developing transmural inflammation and pancreatitis were significantly increased.Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas.CONCLUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.

  5. A case of chronic appendicopathy caused by parasitic infection

    NARCIS (Netherlands)

    A.S. Ramsaransing; R.R. Postema (Roelf); J.L. Simons

    2010-01-01

    textabstractParasitic infection of the appendix is rarely seen, but should be considered in patients with symptoms of chronic appendicitis. It is rarely associated with histological inflammation of the appendix, therefore radiographic imaging, performed during initial workup, remains unremarkable mo

  6. Therapeutic vaccination against chronic hepatitis C virus infection

    NARCIS (Netherlands)

    Ip, Peng Peng; Nijman, Hans W.; Wilschut, Jan; Daemen, Toos

    2012-01-01

    Approximately 170 million people worldwide are chronic carriers of Hepatitis C virus (HCV). To date, there is no prophylactic vaccine available against HCV. The standard-of-care therapy for HCV infection involves a combination of pegylated interferon-α and ribavirin. This therapy, which is commonly

  7. Regulatory T Cells in Chronic Hepatitis B Virus Infection

    NARCIS (Netherlands)

    J.N. Stoop (Jeroen Nicolaas)

    2007-01-01

    textabstractWorldwide 400 million people suffer from chronic hepatitis B virus (HBV) infection and approximately 1 million people die annually from HBV-related disease. To clear HBV, an effective immune response, in which several cell types and cytokines play a role, is important. It is known that p

  8. Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection.

    Science.gov (United States)

    Peel, Trisha N; Bhatti, Deepak; De Boer, Jim C; Stratov, Ivan; Spelman, Denis W

    2010-03-15

    Haemophilus ducreyi is a well recognised causative agent of genital ulcers and chancroid. We report two unusual cases of non-sexually transmitted H. ducreyi infection leading to chronic lower limb ulcers. Both patients were Australian expatriates visiting Australia from the Pacific Islands--one from Papua New Guinea and the other from Vanuatu.

  9. Antiviral Therapy for Chronic HCV Infection - Tolerability and Outcome

    NARCIS (Netherlands)

    R. Maan (Raoel)

    2016-01-01

    textabstractThis thesis describes the safety and outcome of antiviral therapy for chronic HCV infection. In the first chapters, the authors investigated (hematological) adverse events during interferon-based therapy among patients with compensated cirrhosis. By using a patient-tailored approach, int

  10. Phenotypic complementation of genetic immunodeficiency by chronic herpesvirus infection

    Science.gov (United States)

    MacDuff, Donna A; Reese, Tiffany A; Kimmey, Jacqueline M; Weiss, Leslie A; Song, Christina; Zhang, Xin; Kambal, Amal; Duan, Erning; Carrero, Javier A; Boisson, Bertrand; Laplantine, Emmanuel; Israel, Alain; Picard, Capucine; Colonna, Marco; Edelson, Brian T; Sibley, L David; Stallings, Christina L; Casanova, Jean-Laurent; Iwai, Kazuhiro; Virgin, Herbert W

    2015-01-01

    Variation in the presentation of hereditary immunodeficiencies may be explained by genetic or environmental factors. Patients with mutations in HOIL1 (RBCK1) present with amylopectinosis-associated myopathy with or without hyper-inflammation and immunodeficiency. We report that barrier-raised HOIL-1-deficient mice exhibit amylopectin-like deposits in the myocardium but show minimal signs of hyper-inflammation. However, they show immunodeficiency upon acute infection with Listeria monocytogenes, Toxoplasma gondii or Citrobacter rodentium. Increased susceptibility to Listeria was due to HOIL-1 function in hematopoietic cells and macrophages in production of protective cytokines. In contrast, HOIL-1-deficient mice showed enhanced control of chronic Mycobacterium tuberculosis or murine γ-herpesvirus 68 (MHV68), and these infections conferred a hyper-inflammatory phenotype. Surprisingly, chronic infection with MHV68 complemented the immunodeficiency of HOIL-1, IL-6, Caspase-1 and Caspase-1;Caspase-11-deficient mice following Listeria infection. Thus chronic herpesvirus infection generates signs of auto-inflammation and complements genetic immunodeficiency in mutant mice, highlighting the importance of accounting for the virome in genotype-phenotype studies. DOI: http://dx.doi.org/10.7554/eLife.04494.001 PMID:25599590

  11. Chronic Lyme Disease and Co-infections: Differential Diagnosis.

    Science.gov (United States)

    Berghoff, Walter

    2012-01-01

    In Lyme disease concurrent infections frequently occur. The clinical and pathological impact of co-infections was first recognized in the 1990th, i.e. approximately ten years after the discovery of Lyme disease. Their pathological synergism can exacerbate Lyme disease or induce similar disease manifestations. Co-infecting agents can be transmitted together with Borrelia burgdorferi by tick bite resulting in multiple infections but a fraction of co-infections occur independently of tick bite. Clinically relevant co-infections are caused by Bartonella species, Yersinia enterocolitica, Chlamydophila pneumoniae, Chlamydia trachomatis, and Mycoplasma pneumoniae. In contrast to the USA, human granulocytic anaplasmosis (HGA) and babesiosis are not of major importance in Europe. Infections caused by these pathogens in patients not infected by Borrelia burgdorferi can result in clinical symptoms similar to those occurring in Lyme disease. This applies particularly to infections caused by Bartonella henselae, Yersinia enterocolitica, and Mycoplasma pneumoniae. Chlamydia trachomatis primarily causes polyarthritis. Chlamydophila pneumoniae not only causes arthritis but also affects the nervous system and the heart, which renders the differential diagnosis difficult. The diagnosis is even more complex when co-infections occur in association with Lyme disease. Treatment recommendations are based on individual expert opinions. In antibiotic therapy, the use of third generation cephalosporins should only be considered in cases of Lyme disease. The same applies to carbapenems, which however are used occasionally in infections caused by Yersinia enterocolitica. For the remaining infections predominantly tetracyclines and macrolides are used. Quinolones are for alternative treatment, particularly gemifloxacin. For Bartonella henselae, Chlamydia trachomatis, and Chlamydophila pneumoniae the combination with rifampicin is recommended. Erythromycin is the drug of choice for

  12. Chronic Ulcerative Herpes Simplex Virus Infection of the Vulva

    Directory of Open Access Journals (Sweden)

    Kelly Griffith-Bauer

    2012-09-01

    Full Text Available Herpes simplex virus infections in HIV-infected individuals can be clinically unusual and difficult to treat due to underlying problems with cell-mediated immunity and the occurrence of antiviral resistance. Additionally, partial or incomplete restoration of immune function may result in chronic ulcerations that require rotational treatments. In this report, we describe the case of a 38-year-old HIV-positive woman who developed the ulcerative form of chronic herpes simplex infection despite highly active antiretroviral therapy and valacyclovir prophylaxis. Repeated intravenous courses of foscarnet and topical cidofovir finally controlled her erosions as her cell-mediated immunity was slowly restored. This case highlights the challenges that still exist in diagnosing and managing this rare presentation of herpes simplex virus

  13. Chronic Mycobacterium marinum Infection Acts as a Tumor Promoter in Japanese Medaka (Oryzias latipes)

    Science.gov (United States)

    An accumulating body of research indicates there is an increased cancer risk associated with chronic infections. The genus Mycobacterium contains a number of species, including M tuberculosis, which mount chronic infections and have been implicated in higher cancer risk. Several ...

  14. Female hepatology: Favorable role of estrogen in chronic liver disease with hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Chronic hepatitis B virus (HBV) infection is the most common cause of hepatic fibrosis and hepatocellular carcinoma (HCC), mainly as a result of chronic necroinflammatory liver disease. A characteristic feature of chronic hepatitis B infection, alcoholic liver disease and nonalcoholic fatty liver disease (NAFLD) is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which, in turn, activates hepatic stellate cells (HSCs). HSCs are the primary target cells for inflammatory and oxidative stimuli, and these cells produce extracellular matrix components.Chronic hepatitis B appears to progress more rapidly in males than in females, and NAFLD, cirrhosis and HCC are predominately diseases that tend to occur in men and postmenopausal women. Premenopausal women have lower hepatic iron stores and a decreased production of proinflammatory cytokines. Hepatic steatosis has been observed in aromatase-deficient mice, and has been shown to decrease in animals after estradiol treatment. Estradiol is a potent endogenous antioxidant which suppresses hepatic fibrosis in animal models, and attenuates induction of redox sensitive transcription factors, hepatocyte apoptosis and HSC activation by inhibiting a generation of reactive oxygen species in primary cultures. Variant estrogen receptors are expressed to a greater extent in male patients with chronic liver disease than in females. These lines of evidence suggest that the greater progression of hepatic fibrosis and HCC in men and postmenopausal women may be due, at least in part, to lower production of estradiol and a reduced response to the action of estradiol. A better understanding of the basic mechanisms underlying the sex-associated differences in hepatic fibrogenesis and carciogenesis may open up new avenues for the prevention and treatment of chronic liver disease.

  15. Comparing Once- versus Twice-Weekly Yoga Classes for Chronic Low Back Pain in Predominantly Low Income Minorities: A Randomized Dosing Trial.

    Science.gov (United States)

    Saper, Robert B; Boah, Ama R; Keosaian, Julia; Cerrada, Christian; Weinberg, Janice; Sherman, Karen J

    2013-01-01

    Background. Previous studies have demonstrated that once-weekly yoga classes are effective for chronic low back pain (cLBP) in white adults with high socioeconomic status. The comparative effectiveness of twice-weekly classes and generalizability to racially diverse low income populations are unknown. Methods. We conducted a 12-week randomized, parallel-group, dosing trial for 95 adults recruited from an urban safety-net hospital and five community health centers comparing once-weekly (n = 49) versus twice-weekly (n = 46) standardized yoga classes supplemented by home practice. Primary outcomes were change from baseline to 12 weeks in pain (11-point scale) and back-related function (23-point modified Roland-Morris Disability Questionnaire). Results. 82% of participants were nonwhite; 77% had annual household incomes back pain and impairment. Pain and back-related function improved within both groups (P yoga classes were similarly effective for predominantly low income minority adults with moderate to severe chronic low back pain. This trial is registered with ClinicalTrials.gov NCT01761617.

  16. Transmammary infection in BALB/c mice with chronic toxocariasis.

    Science.gov (United States)

    de Souza Aguiar, Patricia; Furtado, Raquel Dutra; de Avila, Luciana Farias da Costa; de Lima Telmo, Paula; Martins, Lourdes Helena Rodrigues; Berne, Maria Elisabeth Aires; da Silva, Pedro Eduardo Almeida; Scaini, Carlos James

    2015-04-01

    Human toxocariasis is a neglected public health problem. Infection of humans generally results from the accidental ingestion of embryonated Toxocara canis eggs, but it is important to broaden knowledge about other forms of transmission. This study aimed to demonstrate the prevalence of transmammary transmission in mice with chronic toxocariasis. BALB/c mice in groups 1 (G1) and 3 (G3) were inoculated with 1200 T. canis eggs 60days before mating, whereas those of group 2 (G2) were not infected. After delivery, the G1 neonates were transferred to G2 females to be nursed, and vice versa. Thus, the mice generated by G2 females and breastfed by G1 females could be infected only during lactation. In the G3 group, offspring were not exchanged. The search for T. canis larvae in the bodies of the lactating females and their offspring was performed after weaning and at 60days old, respectively. The frequency of transmammary infection in the mice generated by G2 uninfected females and breastfed by G1 infected females was 19.8%, which was similar to that observed (19.6%) in the mice bred and fed by G3 females. The frequency of infection in the mice generated by G1 females and breastfed by G2 females was only 4.2%, which was lower than that of G1 (p=0.0064) and G3 (p=0.0062) groups. Transmammary infection by mice with chronic toxocariasis was found to be more prevalent than congenital infection.

  17. THE CYTOKINE IP-10 IN CHRONIC HBV AND HCV INFECTION

    Directory of Open Access Journals (Sweden)

    Nina S. Nikolova

    2013-08-01

    Full Text Available Introduction: IP-10 it has been studied as a predictor of treatment response in chronic HCV infected patients. The data for the HBV infection are not enough.Aim: To compare IP-10 levels in patients with chronic HBV /CHB/ and HCV infection /CHC/ and their relation to liver disease and treatment response. Material and methods: 20 patients - with CHC genotype 1 infection /on standard bi-therapy/ and 32 patients with CHB /21 pts - NUC; 11 pts - IFN/. Results: The IP-10 did not correlate with sex, age, ALT and liver fibrosis. The basal IP-10 were lower in patients with CHB (p=0,017. There was a difference in IP-10 baseline levels among the HCV patients with or without RVR (p=0,007. A negative correlation was found between basal IP-10 and RVR (r= -0,508; p=0,008. Conclusion: IP-10 could predict virological response in patients with CHC on standard bi-therapy, but not in HBV infected patients on standard therapy.

  18. Chronic West Nile virus infection in kea (Nestor notabilis).

    Science.gov (United States)

    Bakonyi, Tamás; Gajdon, Gyula K; Schwing, Raoul; Vogl, Wolfgang; Häbich, Annett-Carolin; Thaller, Denise; Weissenböck, Herbert; Rudolf, Ivo; Hubálek, Zdenek; Nowotny, Norbert

    2016-02-01

    Six kea (Nestor notabilis) in human care, naturally infected with West Nile virus (WNV) lineage 2 in Vienna, Austria, in 2008, developed mild to fatal neurological signs. WNV RNA persisted and the virus evolved in the birds' brains, as demonstrated by (phylo)genetic analyses of the complete viral genomes detected in kea euthanized between 2009 and 2014. WNV antibodies persisted in the birds, too. Chronic WNV infection in the brain might contribute to the circulation of the virus through oral transmission to predatory birds.

  19. ANA testing in the presence of acute and chronic infections.

    Science.gov (United States)

    Litwin, Christine M; Binder, Steven R

    2016-01-01

    Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings.

  20. Features of direct implantation in chronic foci of odontogenic infection

    Directory of Open Access Journals (Sweden)

    Gudaryan А.А.

    2016-12-01

    Full Text Available The article presents the results of the developed therapeutic and prophylactic complex and efficacy of immediate implantation in 66 patients with chronic foci of odontogenic infection in the periapical region. Objective: to increase preventive measures of inflammatory and infectious complications and optimization of osteo-integrative processes in immediate implantation after tooth extraction, with periapical foci of chronic infection. It was found that the use of the developed medical complex of following up direct implantation includes the use of local photodynamic therapy, platelet, rich in fibrin as a injection and membranes; this allowed to create a favorable background for the prevention of inflammatory and infectious complications in the peri-implant area and created a favorable background for the osseo-integration of implants in 97.1% of the investigated.

  1. Chronic infection drives expression of the inhibitory receptor CD200R, and its ligand CD200, by mouse and human CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Stefano Caserta

    Full Text Available Certain parasites have evolved to evade the immune response and establish chronic infections that may persist for many years. T cell responses in these conditions become muted despite ongoing infection. Upregulation of surface receptors with inhibitory properties provides an immune cell-intrinsic mechanism that, under conditions of chronic infection, regulates immune responses and limits cellular activation and associated pathology. The negative regulator, CD200 receptor, and its ligand, CD200, have been shown to regulate macrophage activation and reduce pathology following infection. We show that CD4 T cells also increase expression of inhibitory CD200 receptors (CD200R in response to chronic infection. CD200R was upregulated on murine effector T cells in response to infection with bacterial, Salmonella enterica, or helminth, Schistosoma mansoni, pathogens that respectively drive predominant Th1- or Th2-responses. In vitro chronic and prolonged stimuli were required for the sustained upregulation of CD200R, and its expression coincided with loss of multifunctional potential in T effector cells during infection. Importantly, we show an association between IL-4 production and CD200R expression on T effector cells from humans infected with Schistosoma haematobium that correlated effectively with egg burden and, thus infection intensity. Our results indicate a role of CD200R:CD200 in T cell responses to helminths which has diagnostic and prognostic relevance as a marker of infection for chronic schistosomiasis in mouse and man.

  2. Breastfeeding and chronic HBV infection: Clinical and social implications

    Institute of Scientific and Technical Information of China (English)

    Mihaela; Petrova; Victor; Kamburov

    2010-01-01

    Mother-to-child transmission of hepatitis B virus (HBV) is among the most important causes of chronic HBV infection and is the commonest mode of transmission worldwide. Currently, the presence of HBsAg, HBeAg and HBV DNA in breast milk is confirmed. Several studies have reported that breastfeeding carries no additional risk that might lead to vertical transmission. Beyond some limitations, the surveys have not demonstrated any differences in HBV transmission rate regarding feeding practices in early childho...

  3. Biofilms in chronic infections - a matter of opportunity - monospecies biofilms in multispecies infections

    DEFF Research Database (Denmark)

    Burmølle, Mette; Thomsen, Trine Rolighed; Fazli, Mustafa

    2010-01-01

    to permanent tissue fillers and chronic wounds) both as to distribution (such as where in the wound bed) and organization (monospecies or multispecies microcolonies). We correlate these biofilm observations to observations of commensal biofilms (dental and intestine) and biofilms in natural ecosystems (soil......). The observations of the chronic biofilm infections point toward a trend of low bacterial diversity and sovereign monospecies biofilm aggregates even though the infection in which they reside are multispecies. In contrast to this, commensal and natural biofilm aggregates contain multiple species that are believed...

  4. Agglutination of Trypanosoma cruzi in infected cells treated with serum from chronically infected mice.

    Science.gov (United States)

    Wendelken, Jennifer L; Rowland, Edwin C

    2009-04-01

    The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease. The chronic stage of infection is characterized by a production of neutralizing antibodies in the vertebrate host. A polyclonal antibody, anti-egressin, has been found to inhibit egress of parasites from the host cell late in the intracellular cycle, after the parasites have transformed from the replicative amastigote into the trypomastigote. It has also been found that BALB/c mouse fibroblasts in the late stages of parasite infection become permeable to molecules as large as antibodies, leading to the possibility that anti-egressin affects the intracellular parasites. This project addresses the fate of the intracellular trypomastigotes that have been inhibited from egressing the host cell. Extended cultures of infected fibroblasts treated with chronic mouse serum reduced parasite egress at all time points measured. Parasites released from infected fibroblasts treated with chronic serum had a reduced ability to infect fibroblasts in culture, yet did not lose infectivity entirely. Absorption of chronic serum with living trypomastigotes removed the anti-egressin effect. The possibility that the target of anti-egressin is a parasite surface component is further indicated by the agglutination of extracellular trypomastigotes by chronic serum. The possibility that cross-linking by antibody occurs intracellularly, thus inhibiting egress, was reinforced by cleaving purified IgG into Fab fragments, which did not inhibit egress when added to infected cultures. From this work, it is proposed that the current, best explanation of the mechanism of egress inhibition by anti-egressin is intracellular agglutination, preventing normal parasite-driven egress.

  5. [The diagnostic of chronic infection Helicobacter pylori in children].

    Science.gov (United States)

    Tereschenko, S Yu; Olkhovskiy, I A

    2014-02-01

    The epidemiological studies testify an extremely high prevalence of chronic infection of children with Helicobacter pylori in Russia. The affection consists from 50% to 80% depending on region and age of examined children. The currently in force recommendations "Maastricht IV" concerning diagnostic and treatment of Helicobacter pylori infection adult patients are applied not in its fullness to children adolescent population. At the same time recently published joint conciliatory document of the European and North American associations of pediatric gastroenterologists is oriented to populations with low prevalence of Helicobacter pylori infection and particular profile of drug resistance. Hence, an urgent need exists to develop modern local algorithm concerning diagnostic, treatment and control of eradication of Helicobacter pylori infection among children and adolescents in Russia. The review presents analysis of admissibility of application in Russia's conditions of the international conciliatory documents concerning diagnostic of Helicobacter pylori infection in children. The data from conciliatory document of the European (ESPGHAN) and North American (NASPGHAN) associations of pediatric gastroenterologists, particular orginal research studies and one's own clinical experience were used. The advantages and shortcomings of actual methods of laboratory diagnostic of Helicobacter pylori infection are discussed. The approaches to application of particular diagnostic methods are considered. The enhanced indications to detection of infection and implementation of eradication therapy are proposed.

  6. Chronic experimental infection by Trypanosoma cruzi in Cebus apella monkeys

    Directory of Open Access Journals (Sweden)

    A. Riarte

    1995-12-01

    Full Text Available Twenty young male Cebus apella monkeys were infected with CAl Trypanosoma cruzi strain and reinfected with CA l or Tulahuen T.cruzi strains, with different doses and parasite source. Subpatent parasitemia was usually demonstrated in acute and chronic phases. Patent parasitemia was evident in one monkey in the acute phase and in four of them in the chronic phase after re-inoculations with high doses of CAl strain. Serological conversion was observed in all monkeys; titers were low, regardless of the methods used to investigate anti-T. cruzi specific antibodies. Higher titers were induced only when re-inoculations were perfomed with the virulent Tulahuén strain or high doses of CAl strain. Clinical electrocardiographic and ajmaline test evaluations did not reveal changes between infected and control monkeys. Histopathologically, cardiac lesions were always characterized by focal or multifocal mononuclear infiltrates and/or isolated fibrosis, as seen during the acute and chronic phases; neither amastigote nests nor active inflammation and fibrogenic processes characteristic of human acute and chronic myocarditis respectively, were observed. These morphological aspects more closely resemble those found in the "indeterminate phase" and contrast with the more diffuse and progressive pattern of the human chagasic myocarditis. All monkeys survived and no mortality was observed.

  7. A DESCRIPTIVE STUDY OF FUNGAL INFECTIONS IN CHRONICALLY DISCHARGING EARS

    Directory of Open Access Journals (Sweden)

    Sujatha

    2015-08-01

    Full Text Available BACKGROUND : Chronic Suppurative Otitis Media (CSOM is a disease of multiple aetiology and well known for its persis tence and recurrence inspite of treatment and are the bearbug of otologist, paediatrician and general practitioner. One of the reason s for the refractoriness to treatment and chronicity is coexist ing fungal infection of the ear. OBJECTIVES: Are to find out the prevalence of fungal infections in chronic discharging ears and to identify and isolate the type of fungus prevalent in these ears . MATERIALS AND METHOD S: Tertiary care hospital level descrip tive study was conducted in 50 cases of CSOM with actively discharging ears for a period of one year starting from February 2013. For all the cases aural swabs were collected from the diseased ear and were used for direct microscopic examination in potassi um hydroxide wet mount. Ear swab was cultured on Sabouraud’s dextrose agar plate for fungal cultures. The patient characteristics were prospectively recorded and results were analysed. CONCLUSION : There is high prevalence of coexisting fungal infection in actively discharging ears of CSOM patients

  8. Characterization of HIV-1 Gag-specific T cell responses in chronically infected Indian population

    Science.gov (United States)

    Kaushik, S; Vajpayee, M; Wig, N; Seth, P

    2005-01-01

    India is at the epicentre of the global HIV/AIDS epidemic in South-east Asia, predominated by subtype C infections. It is important to characterize HIV-1-specific T cell responses in this particular population with the aim of identifying protective correlates of immunity to control HIV-1 infection. In this study, we performed a comprehensive analysis of the breadth and magnitude of T cell responses directed at HIV-1 subtype C Gag, one of the most conserved HIV-1 proteins. The study population consisted of antiretroviral naive, chronic HIV-1 subtype C-infected individuals at various stages of infection. We used recent advanced techniques such as enzyme-linked immunospot (ELISPOT) assay and intracellular cytokine staining to quantify the total CD4+ and CD8+ T cell response to HIV-1 gag at single peptide level, regardless of HLA haplotype of the infected individual. The p24-Gag was identified as the most frequently recognized subunit protein with the greatest magnitude of CD4+ and CD8+ T cell responses. Stronger and broader CD8 T cell responses were recognized, contrasting with the weaker and narrower CD4 T cell responses with regard to Gag protein subunits. The magnitude of the HIV-specific interferon (IFN)-γ responses was observed to be higher than the corresponding interleukin (IL)-2 response, indicating the persistence of antigenic load in chronically infected Indian population due to the probable dysfunction of HIV-specific, IFN-γ-secreting CD8 T cells in absence of IL-2 help. PMID:16232229

  9. Predominance of hepatitis C virus genotype 4 infection and rapid transmission between 1935 and 1965 in the Central African Republic.

    Science.gov (United States)

    Njouom, Richard; Frost, Eric; Deslandes, Sylvie; Mamadou-Yaya, Fleurie; Labbé, Annie-Claude; Pouillot, Régis; Mbélesso, Pascal; Mbadingai, Sylvestre; Rousset, Dominique; Pépin, Jacques

    2009-10-01

    The molecular epidemiology of hepatitis C virus (HCV) in the Central African Republic (CAR) is poorly documented. Thus, we conducted phylogenetic analyses of NS5B gene sequences from 58 HCV-infected inhabitants of a remote area of south-west CAR, which indicated that 48 (82.8%) were infected with genotype 4 (HCV-4), five (8.6%) with genotype 2 and five (8.6%) with genotype 1. HCV-4 strains were highly heterogeneous, containing previously described subtypes 4k (48%), 4c (27%), 4r (4%), 4f (4%) and unclassified subtypes (17%). To estimate the epidemic history of these HCV-4 strains, an evolutionary analysis using the coalescent approach was used. The estimated date of the most recent common ancestor of the CAR HCV-4 strains was 1539 (95% confidence intervals, 1317-1697). They exhibited a rapid, exponential spread from 1935 to 1965, simultaneously with what was recently reported in neighbouring Cameroon and Gabon. The hypothesis of a massive iatrogenic transmission during interventions for the control of endemic tropical diseases is discussed.

  10. Acute neurological signs as the predominant clinical manifestation in four dogs with Angiostrongylus vasorum infections in Denmark

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    Pors Susanne E

    2011-06-01

    Full Text Available Abstract Four dogs with acute neurological signs caused by haemorrhages in the central nervous system were diagnosed with Angiostrongylus vasorum infection as the underlying aetiology. Two dogs presented with brain lesions, one dog with spinal cord lesions and one with lesions in both the brain and spinal cord. Only one dog presented with concurrent signs of classical pulmonary angiostrongylosis (respiratory distress, cough, and only two dogs displayed overt clinical signs of haemorrhages. Results of coagulation assays were inconsistent. Neurological signs reflected the site of pathology and included seizures, various cranial nerve deficits, vestibular signs, proprioceptive deficits, ataxia and paraplegia. One dog died and three were euthanised due to lack of improvement despite medical treatment. This emphasises canine angiostrongylosis as a potential cause of fatal lesions of the central nervous system and the importance of including A. vasorum as a differential diagnosis in young dogs with acute neurological signs in Denmark.

  11. Predominance of Trypanosoma rangeli infection in children from a Chagas disease endemic area in the west-shore of the Panama canal

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    Azael Saldaña

    2005-11-01

    Full Text Available A total of 206 serum samples from children (3-14 years old living in the Amador County (La Chorrera District, Province of Panama were screened by indirect immunofluorescence antibody test (IFAT for the presence of antibodies against Trypanosoma cruzi. Positive sera were confirmed by recombinant enzyme-linked immunosorbent assay (ELISA and Western blot analysis. The presence of blood trypanosomes was investigated by hemoculture and subsequently identify by a duplex polymerase chain reaction (PCR followed by dot blot hybridization. The results indicated a prevalence of 9.7% for trypanosome infections, a seroprevalence of 2.9% against T. cruzi and a predominance of T. rangeli infection (6.8%. The immunological and clinical implications of these findings are discussed.

  12. Extrahepatic manifestations of chronic hepatitis C virus infection.

    Science.gov (United States)

    Cacoub, Patrice; Gragnani, Laura; Comarmond, Cloe; Zignego, Anna Linda

    2014-12-15

    Hepatitis C virus (HCV) infected patients are known to be at risk of developing liver complications i.e. cirrhosis and liver cancer. However, the risks of morbidity and mortality are underestimated because they do not take into account non-liver consequences of chronic hepatitis C virus infection. Numerous extrahepatic manifestations have been reported in up to 74% of patients, from perceived to disabling conditions. The majority of data concern hepatitis C virus-related autoimmune and/or lymphoproliferative disorders, from mixed cryoglobulinaemia vasculitis to frank lymphomas. More recently, other hepatitis C virus-associated disorders have been reported including cardiovascular, renal, metabolic, and central nervous system diseases. This review aims to outline most of the extrahepatic manifestations that are currently being investigated, including some of autoimmune and/or lymphoproliferative nature, and others in which the role of immune mechanisms appears less clear. Beyond the liver, hepatitis C virus chronic infection should be analyzed as a multifaceted systemic disease leading to heavy direct and indirect costs. The accurate consideration of extrahepatic consequences of such a systemic infection significantly increases the weight of its pathological burden. The need for effective viral eradication measures is underlined.

  13. Comparing Once- versus Twice-Weekly Yoga Classes for Chronic Low Back Pain in Predominantly Low Income Minorities: A Randomized Dosing Trial

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    Robert B. Saper

    2013-01-01

    Full Text Available Background. Previous studies have demonstrated that once-weekly yoga classes are effective for chronic low back pain (cLBP in white adults with high socioeconomic status. The comparative effectiveness of twice-weekly classes and generalizability to racially diverse low income populations are unknown. Methods. We conducted a 12-week randomized, parallel-group, dosing trial for 95 adults recruited from an urban safety-net hospital and five community health centers comparing once-weekly (n=49 versus twice-weekly (n=46 standardized yoga classes supplemented by home practice. Primary outcomes were change from baseline to 12 weeks in pain (11-point scale and back-related function (23-point modified Roland-Morris Disability Questionnaire. Results. 82% of participants were nonwhite; 77% had annual household incomes <$40,000. The sample’s baseline mean pain intensity [6.9 (SD 1.6] and function [13.7 (SD 5.0] reflected moderate to severe back pain and impairment. Pain and back-related function improved within both groups (P<0.001. However, there were no differences between once-weekly and twice-weekly groups for pain reduction [-2.1 (95% CI -2.9, -1.3 versus −2.4 (95% CI -3.1, -1.8, P=0.62] or back-related function [-5.1 (95% CI -7.0, -3.2 versus −4.9 (95% CI -6.5, -3.3, P=0.83]. Conclusions. Twelve weeks of once-weekly or twice-weekly yoga classes were similarly effective for predominantly low income minority adults with moderate to severe chronic low back pain. This trial is registered with ClinicalTrials.gov NCT01761617.

  14. Expression of NKp46 Splice Variants in Nasal Lavage Following Respiratory Viral Infection: Domain 1-Negative Isoforms Predominate and Manifest Higher Activity

    Science.gov (United States)

    Shemer-Avni, Yonat; Kundu, Kiran; Shemesh, Avishai; Brusilovsky, Michael; Yossef, Rami; Meshesha, Mesfin; Solomon-Alemayehu, Semaria; Levin, Shai; Gershoni-Yahalom, Orly; Campbell, Kerry S.; Porgador, Angel

    2017-01-01

    The natural killer (NK) cell activating receptor NKp46/NCR1 plays a critical role in elimination of virus-infected and tumor cells. The NCR1 gene can be transcribed into five different splice variants, but the functional importance and physiological distribution of NKp46 isoforms are not yet fully understood. Here, we shed light on differential expression of NKp46 splice variants in viral respiratory tract infections and their functional difference at the cellular level. NKp46 was the most predominantly expressed natural cytotoxicity receptor in the nasal lavage of patients infected with four respiratory viruses: respiratory syncytia virus, adenovirus, human metapneumovirus, or influenza A. Expression of NKp30 was far lower and NKp44 was absent in all patients. Domain 1-negative NKp46 splice variants (i.e., NKp46 isoform d) were the predominantly expressed isoform in nasal lavage following viral infections. Using our unique anti-NKp46 mAb, D2-9A5, which recognizes the D2 extracellular domain, and a commercial anti-NKp46 mAb, 9E2, which recognizes D1 domain, allowed us to identify a small subset of NKp46 D1-negative splice variant-expressing cells within cultured human primary NK cells. This NKp46 D1-negative subset also showed higher degranulation efficiency in term of CD107a surface expression. NK-92 cell lines expressing NKp46 D1-negative and NKp46 D1-positive splice variants also showed functional differences when interacting with targets. A NKp46 D1-negative isoform-expressing NK-92 cell line showed enhanced degranulation activity. To our knowledge, we provide the first evidence showing the physiological distribution and functional importance of human NKp46 splice variants under pathological conditions. PMID:28261217

  15. Determinants of survival among HIV-infected chronic dialysis patients.

    Science.gov (United States)

    Rodriguez, Rudolph A; Mendelson, Michael; O'Hare, Ann M; Hsu, Ling Chin; Schoenfeld, Patricia

    2003-05-01

    Over 100 HIV-infected patients have initiated chronic dialysis at San Francisco General Hospital (SFGH) since 1985. This study employed retrospective analysis to identify determinants of and trends in survival among HIV-infected patients who have initiated chronic dialysis at SFGH from January 1, 1985 to November 1, 2002 (n = 115). Cohort patient survival was compared with survival after an AIDS-opportunistic illness in all HIV-infected patients in San Francisco during the study period. Higher CD4 count (hazard ratio [HR], 0.86 per 50 cells/mm(3) increase; 95% confidence interval [CI], 0.80 to 0.93) and serum albumin (HR, 0.53 per 1 g/dl increase; CI, 0.36 to 0.78) at initiation of dialysis were strongly associated with lower mortality. Survival for those initiating dialysis during the era of highly active antiretroviral therapy (HAART) was 16.1 mo versus 9.4 mo for those initiating dialysis before this time, but this difference was not statistically significant. In adjusted analysis, only a non-statistically significant trend toward improved survival during the HAART era was noted (HR, 0.59; CI, 0.34 to 1.04). By comparison, survival for all HIV-infected patients after an AIDS-opportunistic illness in San Francisco increased from 16 mo in 1994 to 81 mo in 1996. The dramatic improvement in survival that has occurred since the mid-1990s for patients with HIV appears to be greatly attenuated in the sub-group undergoing dialysis. Although this may partly reflect confounding by race, injection drug use and HCV co-infection, future attempts to improve survival among HIV-infected dialysis patients should focus on barriers to the effective use of HAART in this group.

  16. Effect of chronic FIV infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection.

    Science.gov (United States)

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-10-31

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on Mycoplasma haemofelis infection. Six cats chronically infected with FIV-Glasgow8 (Group X) and six FIV-free cats (Group Y) were infected with M. haemofelis on Day 0 by intravenous blood inoculation. From Day 0 until Day 86 post-infection (pi), blood samples were collected for M. haemofelis and FIV provirus quantitative real-time PCR and haematology. Three of the six cats in each of Groups X and Y were randomly selected to receive marbofloxacin treatment (2 mg/kg PO q24 h) from Day 16 to 43 pi, with the remaining cats being untreated controls with no antibiotic treatment. The M. haemofelis copy numbers and haematological data were compared between Groups X and Y, and between marbofloxacin-treated and control cats using a Mann-Whitney U-test. M. haemofelis infection was associated with development of macrocytic hypochromic anaemia. In some cats, marked variation in M. haemofelis copy number over time (>100,000-fold difference within 48 h in some cats) and/or cycling of copy number was seen. No correlation was found between FIV provirus copy number and M. haemofelis copy number or haematological variables. No significant effect of chronic FIV infection on M. haemofelis copy number kinetics or haematological changes due to M. haemofelis infection was found, other than MCHC (P=0.03). Marbofloxacin treatment was associated with a significant decrease in M. haemofelis copy number (P=0.002), although consistent clearance of infection was not demonstrated. This study reveals the presence of marked fluctuations in M. haemofelis copy number kinetics in vivo and a significant response to marbofloxacin antibiotic treatment.

  17. The treatment of chronic hepatitis C virus infection in HIV co-infection

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    Vogel Martin

    2009-12-01

    Full Text Available Abstract Chronic HCV co-infection is present in up to one third of HIV-positive patients in Europe. In recent years, apart from the traditional transmission route of intravenous drug abuse, outbreaks of sexually transmitted acute HCV infections, mainly among HIV-positive men who have sex with men, have contributed to the overall disease burden. Because the natural course of HCV infection is substantially accelerated in HIV-co-infection, end-stage liver disease has become the most frequent cause of non-AIDS related death in this population. Therefore every HIV/HCV co-infected patient should be evaluated for possible anti-HCV therapy with the goal of reaching a sustained virological response and thus cure of hepatitis C infection. The standard of care for the treatment of chronic HCV infection in HIV-infected remains a pegylated interferon in combination with weight-adapted ribavirin. HAART should not be withheld from HCV co-infected patients due to concerns of drug related hepatotoxicity and in patients with reduced CD4-cell counts HAART should be started first. Under pegylated interferon and ribavirin combination therapy drug to drug interactions and cumulated toxicity between nucleoside analogues and anti-HCV therapy may be observed and concomitant didanosine use is contraindicated and zidovudine and stavudine should be avoided if possible. The development of new drugs for the treatment of chronic hepatitis C represents a promising perspective also for HIV positive patients. However, these substances will probably reach clinical routine for HIV patients later than HCV monoinfected patients. Therefore at present waiting for new drugs is not an alternative to a modern pegylated interferon/ribavirin therapy.

  18. High-resolution computed tomography to differentiate chronic diffuse interstitial lung diseases with predominant ground-glass pattern using logical analysis of data

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Sophie Grivaud; Brauner, Michel W.; Rety, Frederique [Universite Paris 13, Assistance Publique-Hopitaux de Paris, Hopital Avicenne, UPRES EA 2363, Department of Radiology, Bobigny (France); Kronek, Louis-Philippe; Brauner, Nadia [Universite Joseph Fourier, Laboratoire G-SCOP, Grenoble (France); Valeyre, Dominique; Nunes, Hilario [Universite Paris 13, Assistance Publique-Hopitaux de Paris, Hopital Avicenne, UPRES EA 2363, Department of Pneumology, Bobigny (France); Brillet, Pierre-Yves [Universite Paris 13, Assistance Publique-Hopitaux de Paris, Hopital Avicenne, UPRES EA 2363, Department of Radiology, Bobigny (France); Hopital Avicenne, Service de Radiologie, Bobigny Cedex (France)

    2010-06-15

    We evaluated the performance of high-resolution computed tomography (HRCT) to differentiate chronic diffuse interstitial lung diseases (CDILD) with predominant ground-glass pattern by using logical analysis of data (LAD). A total of 162 patients were classified into seven categories: sarcoidosis (n = 38), connective tissue disease (n = 32), hypersensitivity pneumonitis (n = 18), drug-induced lung disease (n = 15), alveolar proteinosis (n = 12), idiopathic non-specific interstitial pneumonia (n = 10) and miscellaneous (n = 37). First, 40 CT attributes were investigated by the LAD to build up patterns characterising a category. From the association of patterns, LAD determined models specific to each CDILD. Second, data were recomputed by adding eight clinical attributes to the analysis. The 20 x 5 cross-folding method was used for validation. Models could be individualised for sarcoidosis, hypersensitivity pneumonitis, connective tissue disease and alveolar proteinosis. An additional model was individualised for drug-induced lung disease by adding clinical data. No model was demonstrated for idiopathic non-specific interstitial pneumonia and the miscellaneous category. The results showed that HRCT had a good sensitivity ({>=}64%) and specificity ({>=}78%) and a high negative predictive value ({>=}93%) for diseases with a model. Higher sensitivity ({>=}78%) and specificity ({>=}89%) were achieved by adding clinical data. The diagnostic performance of HRCT is high and can be increased by adding clinical data. (orig.)

  19. Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents

    Directory of Open Access Journals (Sweden)

    Yvonne Tse

    2017-01-01

    Full Text Available Background. Chronic idiopathic constipation (CIC and constipation-predominant irritable bowel syndrome (IBS-C are common functional lower gastrointestinal disorders that impair patients’ quality of life. In a national survey, we aimed to evaluate (1 Canadian physician practice patterns in the utilization of therapeutic agents listed in the new ACG and AGA guidelines; (2 physicians satisfaction with these agents for their CIC and IBS-C patients; and (3 the usefulness of these new guidelines in their clinical practice. Methods. A 9-item questionnaire was sent to 350 Canadian specialists to evaluate their clinical practice for the management of CIC and IBS-C. Results. The response rate to the survey was 16% (n=55. Almost all (96% respondents followed a standard, stepwise approach for management while they believed that only 24% of referring physicians followed the same approach. Respondents found guanylyl cyclase C (GCC agonist most satisfying when treating their patients. Among the 69% of respondents who were aware of published guidelines, only 50% found them helpful in prioritizing treatment choices and 69% of respondents indicated that a treatment algorithm, applicable to Canadian practice, would be valuable. Conclusion. Based on this needs assessment, a treatment algorithm was developed to provide clinical guidance in the management of IBS-C and CIC in Canada.

  20. Inverse association between hepatic stellate cell apoptosis and fibrosis in chronic hepatitis C virus infection.

    Science.gov (United States)

    Gonzalez, S A; Fiel, M I; Sauk, J; Canchis, P W; Liu, R-C; Chiriboga, L; Yee, H T; Jacobson, I M; Talal, A H

    2009-02-01

    Perisinusoidal hepatic stellate cells (HSC) are the principal fibrogenic cells in the liver. In animal models, HSC apoptosis is the predominant clearance mechanism of activated HSC, although data evaluating whether the same processes occur in humans are limited. We conducted a cross-sectional study to evaluate the association between HSC apoptosis and fibrosis stage in subjects with chronic hepatitis C virus (HCV) infection (n = 44) and HCV-negative controls with normal liver histology (n = 9). We used immunohistochemical techniques to identify activated (alpha-smooth muscle actin+), proliferative (Ki-67+) and apoptotic (terminal deoxynucleotidyl transferase [TdT]-mediated dUTP nick end-labelling+) HSC in liver biopsy specimens from all subjects. The same pathologist enumerated positive cells per high-power field (HPF, x 200) in 20 periportal/lobular areas. HSC apoptosis was decreased in HCV-positive subjects compared with controls (median 0.4, range 0.0-3.1 vs 1.1, 0.2-3.5 cells/HPF, P = 0.02). Among HCV-positive subjects, HSC apoptosis was decreased in those with moderate to advanced fibrosis (P = 0.04) compared with those with mild fibrosis. By multivariate analysis, HSC apoptosis decreased by an average of 0.14 cells/HPF (95% confidence interval 0.01-0.28 cells/HPF) per increase in fibrosis stage (P = 0.04). While the number of activated and proliferative HSC was significantly increased in HCV-infected subjects compared with that in uninfected controls, the numbers of these cells did not differ between HCV-infected subjects with mild vs moderate/advanced fibrosis. In conclusion, the number of apoptotic HSC was significantly decreased in HCV-infected subjects with advanced fibrosis. In chronic HCV infection, inhibition of HSC apoptosis may be one mechanism by which fibrosis progresses.

  1. Actinomyces and Nocardia infections in chronic granulomatous disease

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    Shahindokht Bassiri-Jahromi

    2011-01-01

    Full Text Available Objective : Chronic granulomatous disease (CGD is an inherited disorder of the Nicotinamide adenine dinucleotide phosphate reduced oxidase complex characterized by recurrent bacterial and fungal infections. Disseminated infection by combination of opportunistic agents is being increasingly reported in CGD patients. We presented in the retrospective review of medical records, the etiology, presentation, clinical characteristics the infections detected, predisposing condition and outcome of nocardiosis and actinomycosis involved in a group of pediatric patients diagnosed with CGD. Materials and Methods: The clinical presentation of CGD-related infections was reviewed retrospectively from the medical records of all 12 patients with CGD. We studied respectively 12 patients between 2001 and 2008, and we analyzed two pediatric patients with CGD who acquired Nocardia and Actinomyces infections, and their clinical and microbiological characteristics were described. The material for investigations was collected from scrapings, crusts, pus from subcutaneous abscesses or exudation from sinus tracts, surgical debridement, and biopsy specimens. The microbiological diagnosis was determined by biochemical tests, histology, microscopy, and culture of clinical samples. Results: The medical records of 12 diagnosed CGD patients with suspected nocardiosis or actinomycosis were reviewed. One patient was diagnosed with actinomycosis and one patient with nocardiosis. Patients consisted of seven males and five females with ranging ages of 3 to 18 years. Nocardiosis and actinomycosis isolated in the two patients were confirmed by histology and culture methods. Neutrophil oxidative burst were absent (NBT=0 in both patients. The most common manifestations of CGD due to fungal infections, actinomycosis, and nocardiosis were osteomyelitis (42.8%, pulmonary infections (28.6%, lymphadenopathy (14.3%, and skin involvement (14.3% during their illness. Conclusion: Nocardiosis

  2. Variability of the preC/C region of hepatitis B virus genotype A from a South African cohort predominantly infected with HIV.

    Science.gov (United States)

    Mayaphi, Simnikiwe H; Martin, Desmond J; Mphahlele, M Jeffrey; Blackard, Jason T; Bowyer, Sheila M

    2013-11-01

    Hepatitis B virus (HBV) is a serious global health problem, and HBV genotype is an important determinant of disease progression and treatment outcome. The aim of this study was to assess variations of the precore/core (preC/C) region in HBV genotype A. Sequencing of the preC/C and surface (S) genes of HBV was performed on plasma samples from 20 HBV/HIV co-infected and 5 HBV mono-infected individuals. All preC/C study sequences clustered with subgenotype A1, except for two which clustered with subgenotype D4 reference strains. The nucleotide and amino acid variability was far higher in the preC/C region than in the S region. Mutations associated with reduction or failure of HBV e-antigen (HBeAg) production were observed, with a preC start codon mutation being common (24%). Other mutations (e.g., P5H/L and I97L) associated with severe liver disease were also noticed, some of which were located in the major histocompatibility restricted sites. PreC/C intergenotype nucleotide divergence was >7%, while subgenotypes differed by 2.5-7%. Several study sequences were highly divergent from other African subgenotype A1 strains. This study showed that HBeAg-negative chronic hepatitis B is underestimated in subgenotype A1, and also highlighted the variant South African A1 strains. The major advantage of preC/C sequencing is that it informs patient management as HBeAg-negative chronic hepatitis B responds poorly to conventional interferon-α therapy, and some guidelines treat HBeAg-negative chronic hepatitis B differently from HBeAg-positive chronic hepatitis B. These data suggest that subgenotype A1 may be more involved in severe HBV-related diseases.

  3. 77 FR 30293 - Recommendations for the Identification of Hepatitis C Virus (HCV) Chronic Infection

    Science.gov (United States)

    2012-05-22

    ... Hepatitis C Virus (HCV) Chronic Infection AGENCY: Centers for Disease Control and Prevention (CDC...) announces draft recommendations for identification of persons with HCV chronic infection, available for public comment. The recommendations are intended to increase the proportion of persons with chronic...

  4. Atypical streptococcal infection of gingiva associated with chronic mouth breathing.

    Science.gov (United States)

    Haytac, M Cenk; Oz, I Attila

    2007-01-01

    Streptococcal infections of oral tissues are mainly seen in young children who experience a variety of upper respiratory tract infections. The disease is characterized by fever, lymphadenopathy, and ulcers on the gingiva, lips, and tonsils. This case report presents an atypical streptococcal infection of the gingiva in an 18-year-old man. The patient was referred to the periodontology department complaining of a 2-month history of gingival enlargement. He had persistent fever (39.5 degrees C) and general malaise for 2 weeks. Intraoral examination revealed extremely inflamed and enlarged gingiva with spontaneous bleeding and suppuration. Based on the otolaryngologic consultation and the hematologic, immunologic, and microbiologic tests, the final diagnosis was an atypical streptococcal gingivitis with chronic adenoid-related mouth breathing and oral hygiene neglect as contributing factors. Treatment consisted of a broad-spectrum antibiotic regimen, supragingival and subgingival debridement, adenoidectomy, and scaling and root planing. A good response to nonsurgical therapy was achieved despite poor patient compliance, and no recurrence of gingival enlargement was observed after 1 year. Streptococcal gingivitis should be included in the differential diagnosis of suppurative gingival enlargements. Furthermore, chronic mouth breathing may initiate and/or contribute to this disease.

  5. Chronic cutaneous varicella zoster virus infection complicating dermatomyositis.

    Science.gov (United States)

    Hoesly, Fridolin J; Sluzevich, Jason C

    2014-04-01

    Chronic cutaneous varicella zoster virus (VZV) infection has not been previously reported or characterized as a complication of dermatomyositis. Two patients with non-malignancy-associated dermatomyositis, treated with long-term prednisone and methotrexate, developed persistent, painless ulcers ultimately established to be secondary to chronic VZV. The absence of pain or a history suggestive of acute VZV, and the lack of characteristic histopathology, resulted in a lengthy delay in diagnosis. Polymerase chain reaction and tissue immunohistochemistry were positive for VZV, and treatment with valacyclovir resulted in complete clearance. Diagnostic testing for VZV should thus be considered in the evaluation of ulcerative lesions in patients with dermatomyositis. The increased incidence of acute VZV in combination with the nature and duration of immunosuppressive treatment in this patient population may be contributory.

  6. Chronic active Epstein-Barr virus infection in an adult with no detectable immune deficiency.

    NARCIS (Netherlands)

    Boer, M. de; Mol, M.J.T.M.; Bogman, M.J.J.T.; Galama, J.M.D.; Raymakers, R.A.P.

    2003-01-01

    INTRODUCTION: Epstein-Barr virus (EBV) establishes lifelong latent infection. In some patients the host-virus balance is disturbed, resulting in a chronic active EBV infection. The following case illustrates the difficulty in diagnosing and treating chronic EBV infection. CASE: A 30-year-old woman w

  7. Aureobasidium pullulans infection in a patient with chronic lymphocytic leukemia

    Directory of Open Access Journals (Sweden)

    Leonardo Rodrigues de Oliveira

    2013-09-01

    Full Text Available Saprophytic fungi are being increasingly recognized as etiologic agents of mycoses in immunosuppressed patients. We report a case of subcutaneous infiltration by Aureobasidium pullulans, likely due to traumatic inoculation, in a neutropenic patient during chemotherapy for chronic lymphocytic leukemia. The patient was treated with amphotericin B deoxycholate but was subsequently switched to itraconazole, which improved the lesion. This case highlights the importance of considering unusual fungal infections in critically ill patients such as those who are immunosuppressed due to chemotherapy. Diagnostic techniques and effective antifungal therapy have improved the prognosis of these cases.

  8. Chronic Hepatitis B and C Virus Infection and Risk for Non-Hodgkin Lymphoma in HIV-Infected Patients

    DEFF Research Database (Denmark)

    Wang, Qing; De Luca, Andrea; Smith, Colette

    2017-01-01

    Background: Non-Hodgkin lymphoma (NHL) is the most common AIDS-defining condition in the era of antiretroviral therapy (ART). Whether chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection promote NHL in HIV-infected patients is unclear. Objective: To investigate whether chronic HB...

  9. Chronic obstructive pulmonary disease and infection. Disruption of the microbiome?

    Science.gov (United States)

    Sethi, Sanjay

    2014-01-01

    The dynamics of infection in chronic obstructive pulmonary disease (COPD) are complex, and microbiome technology has provided us with a new research tool for its better understanding. There is compartmentalization of the microbiota in the various parts of the lung. Studies of the lower airway lumen microbiota in COPD have yielded confusing results, and additional studies with scrupulous attention to prevent and account for upper airway contamination of bronchoalveolar lavage samples are required. Lung tissue microbiota has been examined in three studies, which also demonstrate varied results based on the site of sampling (bronchial mucosa, lung parenchyma), and this variation extends to sampling sites within a lobe of the lung. The Vicious Circle Hypothesis embodies how an altered lung microbiome could contribute to COPD progression. Relating microbiota composition to airway and systemic inflammation and clinical outcomes are important research questions. Although various obstacles need to be surmounted, ultimately lung microbiome studies will provide new insights into how infection contributes to COPD.

  10. Manifestations of chronic hepatitis C virus infection beyond the liver.

    Science.gov (United States)

    Jacobson, Ira M; Cacoub, Patrice; Dal Maso, Luigino; Harrison, Stephen A; Younossi, Zobair M

    2010-12-01

    In addition to its effects in the liver, chronic hepatitis C virus (HCV) infection can have serious consequences for other organ systems. Extrahepatic manifestations include mixed cryoglobulinemia (MC) vasculitis, lymphoproliferative disorders, renal disease, insulin resistance, type 2 diabetes, sicca syndrome, rheumatoid arthritis-like polyarthritis, and autoantibody production; reductions in quality of life involve fatigue, depression, and cognitive impairment. MC vasculitis, certain types of lymphoma, insulin resistance, and cognitive function appear to respond to anti-HCV therapy. However, treatments for HCV and other biopsychosocial factors can reduce quality of life and complicate management. HCV treatment has a high overall cost that increases when extrahepatic manifestations are considered. HCV appears to have a role in the pathogenesis of MC vasculitis, certain types of lymphoma, and insulin resistance. Clinicians who treat patients with HCV infections should be aware of potential extrahepatic manifestations and how these can impact and alter management of their patients.

  11. Antiviral treatment for chronic hepatitis B virus infection--immune modulation or viral suppression?

    NARCIS (Netherlands)

    E.H.C.J. Buster (Erik); H.L.A. Janssen (Harry)

    2006-01-01

    textabstractThe availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be

  12. Pathogenesis of occult chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Rocio Aller de la Fuente; María L Gutiérrez; Javier Garcia-Samaniego; Conrado Fernández-Rodriguez; Jose Luis Lledó; Gregorio Castellano

    2011-01-01

    Occult hepatitis B infection (OBI) is characterized by hepatitis B virus (HBV) DNA in serum in the absence of hepatitis B surface antigen (HBsAg) presenting HBsAg-negative and anti-HBc positive serological patterns. Occult HBV status is associated in some cases with mutant viruses undetectable by HBsAg assays; but more frequently it is due to a strong suppression of viral replication and gene expression. OBI is an entity with world-wide diffusion. The failure to detect HBsAg, despite the persistence of the viral DNA, is due in most cases to the strong suppression of viral replication and gene expression that characterizes this "occult" HBV infection; although the mechanisms responsible for suppression of HBV are not well understood. The majority of OBI cases are secondary to overt HBV infection and represent a residual low viremia level suppressed by a strong immune response together with histological derangements which occurred during acute or chronic HBV infection. Much evidence suggests that it can favour the progression of liver fibrosis and the development of hepatocellular carcinoma.

  13. Occult hepatitis B infection and its possible impact on chronic hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Habibollahi Peiman

    2009-01-01

    Full Text Available As a well-recognized clinical phenomenon, persistent detectable viral genome in liver or sera in the absence of other serological markers for active hepatitis B virus (HBV replication is called occult HBV infection. The main mechanism through which occult infection occurs is not completely understood and several possible explanations, such as integration into human genome and maintenance in peripheral mononuclear cells, exist. Occult HBV infection has been reported in different populations, especially among patients with Hepatitis C (HCV related liver disease. The probable impact of occult HBV in patients with chronic HCV infection has been previously investigated and the evidence suggests a possible correlation with lower response to anti-viral treatment, higher grades of liver histological changes, and also developing hepatocellular carcinoma. However, in the absence of conclusive results, further studies should be conducted to absolutely assess the impact of occult HBV contamination on the HCV related liver disease.

  14. Effect of chronic feline immunodeficiency infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection.

    Science.gov (United States)

    Tasker, Séverine; Caney, Sarah M A; Day, Michael J; Dean, Rachel S; Helps, Chris R; Knowles, Toby G; Lait, Philippa J P; Pinches, Mark D G; Gruffydd-Jones, Timothy J

    2006-03-01

    The purpose of this study was to investigate the effect of chronic feline immunodeficiency virus (FIV) infection, and efficacy of marbofloxacin treatment, on 'Candidatus Mycoplasma haemominutum' infection. Six cats chronically infected with FIV-Glasgow8 (group A) and six FIV-free cats (group B) were infected with 'Candidatus M. haemominutum' on day 0 by intravenous inoculation of blood. From day 0 to 105 post-infection (pi), blood samples were collected for 'Candidatus M. haemominutum' and FIV provirus quantitative real-time polymerase chain reaction (PCR) and haematological examination. Three of the six cats in each of the groups were randomly selected to receive marbofloxacin treatment (2mg/kg PO SID) from day 49 to day 76 pi, with the remaining cats being untreated controls. Maximum 'Candidatus M. haemominutum' copy number was reached around day 30 pi. No overt cycling or marked variation in copy number was observed. No significant effect of FIV infection on 'Candidatus M. haemominutum' copy number kinetics or anaemia indices was found. No correlation was found between FIV provirus copy number and 'Candidatus M. haemominutum' copy number or haematological variables. Although marbofloxacin treatment was associated with a significant decrease in 'Candidatus M. haemominutum' copy number, the copy number plateaued during treatment, with no negative PCR results. Additionally, after termination of marbofloxacin treatment the copy numbers of the treated cats increased to reach levels similar to those of the untreated cats within 7-10 days. This study documents, for the first time, the infection kinetics and antibiotic responsiveness of 'Candidatus M. haemominutum' infection.

  15. Serial observations of chronic rotavirus infection in an immunodeficient child.

    Science.gov (United States)

    Oishi, I; Kimura, T; Murakami, T; Haruki, K; Yamazaki, K; Seto, Y; Minekawa, Y; Funamoto, H

    1991-01-01

    Chronic rotavirus infection of an infant with severe combined immunodeficiency (SCID) was studied by virological examinations in association with long-term observation of his symptoms and immune status. During eleven months of hospitalization, the patient was suffering from incurable severe diarrhea with persisting excretion of rotaviruses detected by electron microscopy and the reversed-passive hemagglutination (R-PHA) test and had transient hepatitis symptom despite multiple administrations of human gammaglobulin and high calorie fluids. The detected viruses were morphologically recognized as rotavirus with double capsid structure. Polyacrylamide gel electrophoretic (PAGE) analysis of their genomic RNAs showed the long electropherotype of group A virus with abnormal migration profiles changing considerably from the early to the late phase of illness: (1) The 11th segment became undetectable; (2) the molecular weight of the 6th segment slightly increased; (3) seven to fourteen extra segments appeared; and (4) PAGE patterns of viral genomic RNAs changed every three or four months. These findings suggest that chronic infection with rotavirus accompanied the generation of extra viral genomic segments and their unusual assortments in an immunodeficient host.

  16. [Extrahepatic manifestations of chronic hepatitis C virus infection].

    Science.gov (United States)

    Puchner, K P; Berg, T

    2009-05-01

    Current data suggest that HCV infection should be regarded as a systemic infectious disease with multiorgan involvement. More than 50 % of HCV-positive patients develop during the course of the disease at least one extrahepatic manifestation (EHM). The EHMs are often the first and only clinical signs of a chronic hepatitis C. Evidence of HCV infection should always be sought out in cases of unspecific chronic fatigue and/or rheumatic, haematological, endocrine or dermatological disorders. Key pathogenetic factors for the development of EHM are undisputably the HCV lymphotropism and cryoglobulinaemia. Nevertheless, the exact pathogenesis of many EHM still remains unclear. The therapeutic approach to EHM should concentrate on the eradication of HCV. Antiviral therapy in the form of peg-interferon and ribavirin should be regarded as the first-line therapy. Viral response leads mostly to a consecutive clinical response. However, in the case of HCV-related cytopaenias or neuropathies, antiviral therapy may trigger an aggravation of these conditions. Thus, organ-involvement, severity and course of the EHM should be always taken into account when choosing the appropriate therapeutic strategy. Immunosuppressive drugs, plasmapheresis and lately rituximab are counted among therapies that can be applied complementarly or alternatively to the antiviral therapy.

  17. Antibody producing B lineage cells invade the central nervous system predominantly at the time of and triggered by acute Epstein-Barr virus infection: A hypothesis on the origin of intrathecal immunoglobulin synthesis in multiple sclerosis.

    Science.gov (United States)

    Otto, Carolin; Hofmann, Jörg; Ruprecht, Klemens

    2016-06-01

    Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%. However, intriguingly, despite of the universal EBV seroprevalence, the frequency of intrathecally produced IgG to EBV in patients with MS is much lower than that of intrathecally produced IgG to other common viruses. The acute phase of primary EBV infection is characterized by a strong polyclonal B cell activation. As typical for humoral immune responses against viruses, EBV specific IgG is produced only with a temporal delay after acute EBV infection. Aiming to put the above facts into a logical structure, we here propose the hypothesis that in individuals going on to develop MS antibody producing B lineage cells invade the CNS predominantly at the time of and triggered by acute primary EBV infection. Because at the time of acute EBV infection EBV IgG producing B lineage cells have not yet occurred, the hypothesis could explain the universal EBV seroprevalence and the low frequency of intrathecally produced IgG to EBV in patients with MS. Evidence supporting the hypothesis could be provided by large prospective follow-up studies of individuals with symptomatic primary EBV infection (infectious mononucleosis). Furthermore, the clarification of the molecular mechanism underlying an EBV induced invasion of B lineage cells into the CNS of individuals going on to develop MS could corroborate it, too. If true, our

  18. Diagnosis and Treatment of Infective Endocarditis in Chronic Hemodialysis Patients

    Institute of Scientific and Technical Information of China (English)

    Jian-ling Tao; Xue-mei Li; Xue-wang Li; Jie Ma; Guang-li Ge; Li-meng Chen; Hang Li; Bao-tong Zhou; Yang Sun; Wen-ling Ye; Qi Miao

    2010-01-01

    Objective To analyze the clinical features of hemodialysis patients complicated by infective endo-carditis.Methods The clinical features of six such patients admitted to Peking Union Medical College Hos-pital during the year 1990 to 2009 were analyzed. All of them were diagnosed based on Chinese Children Diagnostic Criteria for Infective Endocarditis.Results The average age of the six patients was 52.3±19.3 years old. Four were males. Vascular ac-cesses at the onset of infective endocarditis were as follows: permanent catheters in three, temporary cathe-ters in two, and arteriovenous fistula in one. Three were found with mitral valve involvement, two with aor-tic valve involvement, and one with both. Five vegetations were found by transthoraeic echocardiography, and one by transesophageal echocardiography. Four had positive blood culture results. The catheters were all removed. Four of the patients were improved by antibiotics treatment, in which two were still on hemodialy-sis in the following 14-24 months and the other two were lost to follow-up. One patient received surgery, but died of heart failure after further hemodialysis for three months. One was well on maintenance hemodi-alysis for three months after surgery.Conclusions Infective endocarditis should be suspected when hemodialysis patients suffer from long-term fever, for which prompt blood culture and transthoracic echocardiography confirmation could be performed. Transesophageal echocardiography could be considered even when transthoracic echocardiogra-phy produces negative findings. With catheters removed, full course of appropriate sensitive antibiotics and surgery if indicated could improve the outcome of chronic hemodialysis patients complicated by infective endocarditis.

  19. Causative Role of Sexually Transmitted Infections in the Development of Chronic Cystitis Complicated with Leukoplakia of the Bladder

    Directory of Open Access Journals (Sweden)

    Alexander I. Neymark, PhD, ScD

    2012-09-01

    Full Text Available The objective of this study was the investigation of the influence of chlamydial, mycoplasmal and trichomonas infection on the development of urinary bladder leukoplakia. The article presents the results of the examination of women with chronic cystitis complicated with leukoplakia of the bladder, and associated with concomitant sexually transmitted infections, including the results of culture analysis of the cervical canal content and urinary bladder biopsy samples, as well as molecular-biological analyses confirming the presence of sexually transmitted infections, pathomorphological characteristics of tissue samples from leukoplakia foci typical for different types of infectious agents. In this study, 60 women with chronic cystitis, complicated with leukoplakia of the bladder and associated with concomitant sexually transmitted infections were examined. Using PCR diagnostics, Mycoplasma hominis and Chlamydia albicans were found to be the most frequently occurring agents, followed by Ureaplasma urealyticum, Chlamydia trachomatis and Trichomonas vaginalis. The results of culture analyses demonstrated that M. hominis and U. urealyticum were prevalent in patients with chronic urinary tract inflammatory processes, followed by Tr. vaginalis. Candida fungi show practically the same frequency of occurrence. The pathomorphological examination of the foci of leukoplakia in the urinary bladder (in 30 subjects demonstrated metaplasia of the transitional epithelium to the stratified pavement squamous epithelium with inflammatory cellular infiltration of the lamina propria in all types of infections. The intensity of the urothelial transformation and stromal inflammatory processes were determined by the type of predominant infection. Pathomorphological characteristics of the foci of leukoplakia correlate with the etiology of chronic inflammation and are relevant for etiological diagnosis and treatment.

  20. Relationship Between Helicobacter Pylori Infection and Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Mohammad-Ali Seif-Rabiei

    2011-11-01

    Full Text Available There is some evidence indicating the role of Helicobacter pylori infection in pathogenesis of extragastrointestinal diseases including skin, vascular, and autoimmune disorders, as well as some respiratory diseases. The aim of this study was to investigate the association between H. pylori and chronic obstructive pulmonary disease (COPD. In a case-control study, 90 patients with COPD and 90 age- and sex- matched control subjects were included. Serum samples were tested for anti-H. pylori and anti-CagA IgG by ELISA. A physician completed a questionnaire including demographic characteristics, habitual history, and spirometric findings for each patient. Of 90 patients with COPD 66 (51% had mild, 31 (34.4% moderate, and 13 (14.4% sever disease. There was no significant association between H. pylori IgG seropositivity and COPD. Serum levels of anti-CagA IgG were significantly higher in patients with COPD than in the control subjects (P < 0.001. No association was observed between H. pylori infection and severity of COPD. The results suggest that there is an association between CagA-positive H. pylori infections and COPD. Further studies should be planned to investigate the potential pathogenic mechanisms that might underlie these associations.

  1. Changes in HIV RNA and CD4 cell count after acute HCV infection in chronically HIV-infected individuals

    NARCIS (Netherlands)

    Gras, L.; Wolf, F. de; Smit, C.; Prins, M.; Meer, J.T. van der; Vanhommerig, J.W.; Zwinderman, A.H.; Schinkel, J.; Geskus, R.B.; Warris, A.

    2015-01-01

    OBJECTIVE: Little is known about the impact of acute hepatitis C virus (HCV) co-infection on HIV-1 disease progression. We investigated CD4 cell count and HIV RNA concentration changes after HCV infection in individuals chronically infected with HIV-1. METHODS: We selected individuals that had the l

  2. Chronic hepatitis c genotype-4 infection: role of insulin resistance in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    M Hashem Abdel

    2011-11-01

    Full Text Available Abstract Background Hepatitis C virus (HCV is a major cause of chronic hepatitis and hepatocellular carcinoma (HCC and different HCV genotypes show characteristic variations in their pathological properties. Insulin resistance (IR occurs early in HCV infection and may synergize with viral hepatitis in HCC development. Egypt has the highest reported rates of HCV infection (predominantly genotype 4 in the world; this study investigated effects of HCV genotype-4 (HCV-4 on prevalence of insulin resistance in chronic hepatitis C (CHC and HCC in Egyptian patients. Methods Fifty CHC patients, 50 HCC patients and 20 normal subjects were studied. IR was estimated using HOMA-IR index and HCV-4 load determined using real-time polymerase chain reaction. Hepatitis B virus was excluded by enzyme-linked immunosorbent assay. Standard laboratory and histopathological investigations were undertaken to characterize liver function and for grading and staging of CHC; HCC staging was undertaken using intraoperative samples. Results HCC patients showed higher IR frequency but without significant difference from CHC (52% vs 40%, p = 0.23. Multivariate logistic regression analysis showed HOMA-IR index and International Normalization Ratio independently associated with fibrosis in CHC; in HCC, HbA1c, cholesterol and bilirubin were independently associated with fibrosis. Fasting insulin and cholesterol levels were independently associated with obesity in both CHC and HCC groups. Moderate and high viral load was associated with high HOMA-IR in CHC and HCC (p Conclusions IR is induced by HCV-4 irrespective of severity of liver disease. IR starts early in infection and facilitates progression of hepatic fibrosis and HCC development.

  3. Chronic hepatitis B infection presenting with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS): a case report

    OpenAIRE

    Weng, Ching-Fu; Chan, Ding-Cheng; Chen, Ya-Fang; Liu, Fei-Chih; Liou, Horng-Huei

    2015-01-01

    Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids is a brainstem disorder characterized by perivascular pathologic reaction with lymphocyte infiltration and leading to diplopia, facial palsy, dysarthria, and gait ataxia. It was thought to be an autoimmune disorder without distinct pathogenesis. Chronic hepatitis B virus infection has been proposed in correlation with autoimmune diseases, including central nervous system demyelinating di...

  4. Function of monocytes in chronic HCV infection: Role for IL-10 and interferon

    NARCIS (Netherlands)

    B. Liu (Bi Sheng)

    2011-01-01

    textabstractHepatitis C virus (HCV) establishes persistent infection in about 80% of the infected individuals. The symptoms are initially mild in those persistently infected patients, and it may take decades before the serious consequences of chronic HCV infection become apparent. Up to 20% of infec

  5. Dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection.

    Science.gov (United States)

    Tang, L; Ward, H; Kattakuzhy, S; Wilson, E; Kottilil, S

    2016-01-01

    Sofosbuvir is the first pan-genotypic direct acting antiviral agent to be approved. This article provides an overview of the pharmacology of sofosbuvir and ribavirin and a comprehensive summary of the phase 2 and 3 studies supporting dual sofosbuvir and ribavirin therapy for chronic hepatitis C infection. With the production of generic formulations of sofosbuvir, we anticipate this regimen leading the first wave for widespread, IFN-free treatment and becoming first line for all genotypes (including genotype 1) for much of the world-in particular in developing and middle income countries. We discuss the continued challenges with this regimen including among patients with decompensated liver disease and post-liver transplant, and renal failure. We address concerns of emerging resistance. We also discuss the future prospects including the global uptake of sofosbuvir and ribavirin for the treatment of all genotypes.

  6. Interleukin-17 and innate immunity in infections and chronic inflammation.

    Science.gov (United States)

    Isailovic, Natasa; Daigo, Kenji; Mantovani, Alberto; Selmi, Carlo

    2015-06-01

    Interleukin 17 (IL-17) includes several cytokines among which IL-17A is considered as one of the major pro-inflammatory cytokine being central to the innate and adaptive immune responses. IL-17 is produced by unconventional T cells, members of innate lymphoid cells (ILCs), mast cells, as well as typical innate immune cells, such as neutrophils and macrophages located in the epithelial barriers and characterised by a rapid response to infectious agents by recruiting neutrophils as first line of defence and inducing the production of antimicrobial peptides. Th17 responses appear pivotal in chronic and acute infections by bacteria, parasites, and fungi, as well as in autoimmune and chronic inflammatory diseases, including rheumatoid arthritis, psoriasis, and psoriatic arthritis. The data discussed in this review cumulatively indicate that innate-derived IL-17 constitutes a major element in the altered immune response against self antigens or the perpetuation of inflammation, particularly at mucosal sites. New drugs targeting the IL17 pathway include brodalumab, ixekizumab, and secukinumab and their use in psoriatic disease is expected to dramatically impact our approach to this systemic condition.

  7. Chronic lymphoedema caused by recurrent infections in a patient with allergic hand eczema

    DEFF Research Database (Denmark)

    Dyring-Andersen, Beatrice; Skov, Lone; Jensen, Peter

    2011-01-01

    Allergic contact dermatitis is very common and may be complicated by secondary infections. Chronic lymphoedema is a potentially debilitating condition, which may occur due to secondary infections or the dermatitis itself. The problem of chronic lymphoedema following allergic contact dermatitis ha...

  8. Chronic pulmonary infection with Stenotrophomonas maltophilia and lung function in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Dalbøge, C S; Hansen, C R; Pressler, T;

    2011-01-01

    Background The clinical consequences of chronic Stenotrophomonas maltophilia infection in cystic fibrosis (CF) patient are still unclear. Method All patients treated in the Copenhagen CF centre (N=278) from 1 January 2008 to 31 December 2009 were included. Each patient chronically infected with S...

  9. Chronic lymphoedema caused by recurrent infections in a patient with allergic hand eczema

    Directory of Open Access Journals (Sweden)

    Beatrice Dyring-Andersen

    2011-07-01

    Full Text Available Allergic contact dermatitis is very common and may be complicated by secondary infections. Chronic lymphoedema is a potentially debilitating condition, which may occur due to secondary infections or the dermatitis itself. The problem of chronic lymphoedema following allergic contact dermatitis has been infrequently reported. We report a case of a 47-year-old woman with severe allergic contact dermatitis complicated by chronic, intractable lymphoedema of the hands and forearms. This case report reminds us that allergic hand dermatitis may be complicated by a chronic and debilitating state of lymphoedema. Also, it underlines the importance of fast and adequate treatment of both the dermatitis and the secondary infections.

  10. Immune therapy including dendritic cell based therapy in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Sk Md Fazle Akbar; Norio Horiike; Morikazu Onji

    2006-01-01

    Hepatitis B virus (HBV) infection is a global public health problem. Of the approximately 2 billion people who have been infected worldwide, more than 400 million are chronic carriers of HBV. Considerable numbers of chronic HBV carriers suffer from progressive liver diseases. In addition, all HBV carriers are permanent source of this virus. There is no curative therapy for chronic HBV carriers. Antiviral drugs are recommended for about 10% patients, however, these drugs are costly, have limited efficacy, and possess considerable side effects.Recent studies have shown that immune responses of the host to the HBV are critically involved at every stage of chronic HBV infection: (1) These influence acquisition of chronic HBV carrier state, (2) They are important in the context of liver damages, (3) Recovery from chronic HBV-related liver diseases is dependent on nature and extent of HBV-specific immune responses.However, induction of adequate levels of HBV-specific immune responses in chronic HBV carriers is difficult.During the last one decade, hepatitis B vaccine has been administered to chronic HBV carriers as a therapeutic approach (vaccine therapy). The present regimen of vaccine therapy is safe and cheap, but not so effective.A dendritic cell-based therapeutic vaccine has recently been developed for treating chronic HBV infection. In this review, we will discuss about the concept, scientific logics, strategies and techniques of development of HBV-specific immune therapies including vaccine therapy and dendritic cell-based vaccine therapy for treating chronic HBV infection.

  11. Deep dermatophyte infection with chronic draining nodules in an immunocompromised patient.

    Science.gov (United States)

    Demidovich, C W; Kornfeld, B W; Gentry, R H; Fitzpatrick, J E

    1995-04-01

    Chronic superficial dermatophyte infection may predispose the immunocompromised patient to invasive or disseminated involvement. We report a case of deep dermatophyte infection in a patient treated with long-term corticosteroid therapy for lung disease. The patient responded well to oral griseofulvin. Previously reported cases are reviewed along with recent investigative findings in the pathogenesis of chronic dermatophyte infections. Recommendations are made for diagnosis and therapy.

  12. Role of chemokines and their receptors in viral persistence and liver damage during chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Chemokines produced in the liver during hepatitis C virus (HCV) infection induce migration of activated T cells from the periphery to infected parenchyma. The milieu of chemokines secreted by infected hepatocytes is predominantly associated with the T-helper cell/Tc1 T cell (Th1/Tc1) response. These chemokines consist of CCL3 (macrophage inflammatory protein-1α; MIP-1α), CCL4 (MIP-1β), CCL5 (regulated on activation normal T cell expressed and secreted; RANTES), CXCL10 (interferon-γ-inducible protein-10; IP-10),CXCL11 (interferon-inducible T-cell α chemoattractant; I-TAC), and CXCL9 (monokine induced by interferon γ; Mig) and they recruit T cells expressing either CCR5 or CXCR3 chemokine receptors. Intrahepatic and peripheral blood levels of these chemokines are increased during chronic hepatitis C. The interaction between chemokines and their receptors is essential in recruiting HCV-specific T cells to control the infection. When the adaptive immune response fails in this task, non-specific T cells without the capacity to control the infection are also recruited to the liver, and these are ultimately responsible for the persistent hepatic damage. The modulation of chemokine receptor expression and chemokine secretion could be a viral escape mechanism to avoid specific T cell migration to the liver during the early phase of infection, and to maintain liver viability during the chronic phase, by impairing non-specific T cell migration. Some chemokines and their receptors correlate with liver damage, and CXCL10 (IP-10) and CXCR3 levels have shown a clinical utility as predictors of treatment response outcome. The regulation of chemokines and their receptors could be a future potential therapeutic target to decrease liver inflammation and to increase specific T cell migration to the infected liver.

  13. Hepatitis E virus genotype three infection of human liver chimeric mice as a model for chronic HEV infection

    NARCIS (Netherlands)

    M.D.B. van de Garde (Martijn); S.D. Pas (Suzan); G. van der Net (Guido); R.A. de Man (Robert); A.D.M.E. Osterhaus (Albert); B.L. Haagmans (Bart); A. Boonstra (Andre); T. Vanwolleghem (Thomas)

    2016-01-01

    textabstractGenotype (gt) 3 hepatitis E virus (HEV) infections are emerging in Western countries. Immunosuppressed patients are at risk of chronic HEV infection and progressive liver damage, but no adequate model system currently mimics this disease course. Here we explore the possibilities of in vi

  14. Endothelial Dysfunction Correlates with Liver Fibrosis in Chronic HCV Infection

    Directory of Open Access Journals (Sweden)

    Michele Barone

    2015-01-01

    Full Text Available Background. Hepatitis C virus (HCV infection can exert proatherogenic activities due to its direct action on vessel walls and/or via the chronic inflammatory process involving the liver. Aims. To clarify the role of HCV in atherosclerosis development in monoinfected HCV patients at different degrees of liver fibrosis and with no risk factors for coronary artery disease. Methods. Forty-five patients were included. Clinical, serological, and anthropometric parameters, liver fibrosis (transient liver elastometry (fibroscan and aspartate aminotransferase to platelet ratio index (APRI, carotid intima-media thickness (c-IMT, and brachial artery flow-mediated vasodilatation (FMD were assessed. Patients were divided into 3 tertiles according to fibroscan values. Results. Patients in the third tertile (fibroscan value >11.5 KPa showed FMD values were significantly lower than second and first tertiles (4.7±1.7% versus 7.1±2.8%, p=0.03. FMD values were inversely related to liver elastomeric values. c-IMT values were normal. The risk for endothelial dysfunction development in the third tertile (p=0.02 was 6.9 higher than the first tertile. A fibroscan value >11.5 KPa had a positive predictive power equal to 79% for endothelial dysfunction. Conclusions. HCV advanced liver fibrosis promotes atherosclerosis by inducing endothelial dysfunction independently of common cardiovascular risk factors.

  15. The woodchuck as an animal model for pathogenesis and therapy of chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This review describes the woodchuck and the woodchuck hepatitis virus (WHV) as an animal model for pathogenesis and therapy of chronic hepatitis B virus (HBV) infection and disease in humans. The establishment of woodchuck breeding colonies, and use of laboratory-reared woodchucks infected with defined WHV inocula, have enhanced our understanding of the virology and immunology of HBV infection and disease pathogenesis, including major sequelae like chronic hepatitis and hepatocellular carcinoma. The role of persistent WHV infection and of viral load on the natural history of infection and disease progression has been firmly established along the way. More recently, the model has shed new light on the role of host immune responses in these natural processes,and on how the immune system of the chronic carrier can be manipulated therapeutically to reduce or delay serious disease sequelae through induction of the recovery phenotype. The woodchuck is an outbred species and is not well defined immunologically due to a limitation of available host markers. However, the recent development of several key host response assays for woodchucks provides experimental opportunities for further mechanistic studies of outcome predictors in neonatal- and adult-acquired infections. Understanding the virological and immunological mechanisms responsible for resolution of self-limited infection, and for the onset and maintenance of chronic infection, will greatly facilitate the development of successful strategies for the therapeutic eradication of established chronic HBV infection. Likewise, the results of drug efficacy and toxicity studies in the chronic carrier woodchucks are predictive for responses of patients chronically infected with HBV. Therefore, chronic WHV carrier woodchucks provide a well-characterized mammalian model for preclinical evaluation of the safety and efficacy of drug candidates, experimental therapeutic vaccines, and immunomodulators for the treatment and

  16. Nutritional status in chronically hospitalized stroke patients complicated with pulmonary infection

    Institute of Scientific and Technical Information of China (English)

    Yue Chen; Lufang Chen; Yiqing Tao; Maomao Han; Chunlan Cui; Shichao Liu

    2011-01-01

    Complicated pulmonary infection following stroke has traditionally been considered an aspirated infection by many physicians, and little attention has been paid to concomitant protein-energy malnutrition. In the present study, we hypothesized that protein-energy malnutrition may be present in hospitalized chronic stroke patients complicated with pulmonary infection. The results revealed that body protein and fat stores were significantly depleted in stroke patients with pulmonary infection. Protein-energy malnutrition was present in 12 of 27 patients with pulmonary infection. In comparison, only eight of 42 stroke patients without pulmonary infection exhibited protein-energy malnutrition. A significantly higher prevalence of protein-energy malnutrition was found in the pulmonary infection group, suggesting that protein-energy malnutrition is more likely to be present in hospitalized chronic stroke patients with pulmonary infection.

  17. Early severe inflammatory responses to uropathogenic E. coli predispose to chronic and recurrent urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Thomas J Hannan

    Full Text Available Chronic infections are an increasing problem due to the aging population and the increase in antibiotic resistant organisms. Therefore, understanding the host-pathogen interactions that result in chronic infection is of great importance. Here, we investigate the molecular basis of chronic bacterial cystitis. We establish that introduction of uropathogenic E. coli (UPEC into the bladders of C3H mice results in two distinct disease outcomes: resolution of acute infection or development of chronic cystitis lasting months. The incidence of chronic cystitis is both host strain and infectious dose-dependent. Further, development of chronic cystitis is preceded by biomarkers of local and systemic acute inflammation at 24 hours post-infection, including severe pyuria and bladder inflammation with mucosal injury, and a distinct serum cytokine signature consisting of elevated IL-5, IL-6, G-CSF, and the IL-8 analog KC. Mice deficient in TLR4 signaling or lymphocytes lack these innate responses and are resistant, to varying degrees, to developing chronic cystitis. Treatment of C3H mice with the glucocorticoid anti-inflammatory drug dexamethasone prior to UPEC infection also suppresses the development of chronic cystitis. Finally, individuals with a history of chronic cystitis, lasting at least 14 days, are significantly more susceptible to redeveloping severe, chronic cystitis upon bacterial challenge. Thus, we have discovered that the development of chronic cystitis in C3H mice by UPEC is facilitated by severe acute inflammatory responses early in infection, which subsequently are predisposing to recurrent cystitis, an insidious problem in women. Overall, these results have significant implications for our understanding of how early host-pathogen interactions at the mucosal surface determines the fate of disease.

  18. Hepatitis B core-related antigen (HBcrAg) levels in the natural history of hepatitis B virus infection in a large European cohort predominantly infected with genotypes A and D.

    Science.gov (United States)

    Maasoumy, B; Wiegand, S B; Jaroszewicz, J; Bremer, B; Lehmann, P; Deterding, K; Taranta, A; Manns, M P; Wedemeyer, H; Glebe, D; Cornberg, M

    2015-06-01

    Hepatitis B core-related antigen (HBcrAg) has been suggested as an additional marker of hepatitis B virus (HBV) infection. HBcrAg combines the antigenic reactivity resulting from denatured hepatitis B e antigen (HBeAg), HBV core antigen and an artificial core-related protein (p22cr). In Asian patients, high levels of HBcrAg have been suggested to be an independent risk factor for hepatocellular carcinoma, while low levels could guide safe cessation of treatment with nucleos(t)ide analogues. We here studied HBcrAg levels in different phases of HBV infection in a large European cohort predominantly infected with genotypes A and D: HBeAg-positive immune tolerance (n = 30), HBeAg-positive immune clearance (IC) (n = 60), HBeAg-negative hepatitis (ENH) (n = 50), HBeAg-negative inactive/quiescent carrier phase (c) (n = 109) and acute hepatitis B (n = 8). Median HBcrAg levels were high in the immune tolerance and immune clearance phases (8.41 and 8.11 log U/mL, respectively), lower in ENH subjects (4.82 log U/mL) but only 2.00 log U/mL in ENQ subjects. Correlation between HBcrAg and HBV DNA varied among the different phases of HBV infection, while HBcrAg moderately correlated with hepatitis B surface antigen in all phases. ENQ patients had HBcrAg levels HBcrAg levels vary significantly during the different phases of HBV infection. HBcrAg may serve as valuable marker for virus replication and reflect the transcriptional activity of intrahepatic cccDNA. In HBeAg-negative patients, HBcrAg may help to distinguish between inactive carriers (ENQ) and those with active disease (ENH).

  19. Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.

    Science.gov (United States)

    Ferns, R Bridget; Tarr, Alexander W; Hue, Stephane; Urbanowicz, Richard A; McClure, C Patrick; Gilson, Richard; Ball, Jonathan K; Nastouli, Eleni; Garson, Jeremy A; Pillay, Deenan

    2016-05-01

    HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.

  20. Chronic hepatitis C virus infection and post-liver transplantation diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Yun Ma; Wen-Wei Yan

    2005-01-01

    Patients with chronic hepatitis C virus (HCV) infection have a significantly increased prevalence of type 2 diabetes mellitus compared to controls or HBV-infected patients.Moreover, the incidence rate of post-liver transplantation diabetes mellitus (PTDM) also appears to be higher among patients with HCV infection. PTDM is often associated with direct viral infection, autoimmune disorders, and immunosuppressive regimen. Activation of tumor necrosis factor-α may be the link between HCV infection and diabetes. In this article, we reviewed the epidemiologic association between HCV infection and PTDM, highlighting the most recent pathophysiologic insights into the mechanisms underlying this association.

  1. Metabolic Manifestations and Complications Associated With Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Wong, Robert J; Gish, Robert G

    2016-05-01

    Chronic hepatitis C virus (HCV) infection is associated with many extrahepatic manifestations that contribute to morbidity and mortality. It is especially important to be aware of metabolic manifestations and serious complications that affect other organs and cancer risks. Chronic HCV infection itself contributes to de novo development of insulin resistance and hepatic steatosis, both of which increase the risk of cardiovascular diseases. Through these metabolic pathways (as well as through other hypothesized mechanisms that involve lipid metabolism, systemic inflammatory signals, and endothelial dysfunction), chronic HCV infection also contributes to significant systemic cardiovascular morbidity and mortality. While chronic HCV infection contributes to incident development of metabolic complications, the presence of concurrent metabolic diseases also contributes to disease progression, such as higher risks of hepatocellular carcinoma and progression to advanced fibrosis, among patients with chronic HCV infection. The implications of these observations are particularly important given the rising prevalence of obesity and metabolic syndrome in the United States and worldwide. Furthermore, concurrent nonalcoholic fatty liver disease, either as a result of underlying metabolic syndrome or as a direct result of HCV-induced fatty liver disease, further complicates the management of chronic HCV-infected patients. Greater awareness is needed toward the systemic manifestations of chronic HCV infection, with focused attention on the associated metabolic manifestations and complications. Successful treatment and cure of chronic HCV infection with the currently available, highly effective antiviral therapies will significantly improve long-term outcomes among these patients. It is also important to recognize and address the associated metabolic manifestations and complications to reduce cardiovascular-related morbidity and mortality.

  2. Mortality in patients with chronic and cleared hepatitis C viral infection: a nationwide cohort study

    DEFF Research Database (Denmark)

    Omland, Lars Haukali; Krarup, Henrik; Jepsen, Peter;

    2010-01-01

    It is unknown whether mortality differs between patients with chronic hepatitis C virus (HCV) replication and those who cleared the virus after infection. We examined the impact of chronic HCV replication on mortality among Danish patients testing positive for HCV antibodies....

  3. Phyllanthus species versus antiviral drugs for chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Yun, Xia; Luo, Hui; Liu, Jian Ping

    2013-01-01

    Phyllanthus species for patients with chronic hepatitis B virus (HBV) infection have been assessed in clinical trials, but no consensus regarding their usefulness exists. When compared with placebo or no intervention, we were unable to identify convincing evidence that phyllanthus species...... are beneficial in patients with chronic hepatitis B. Some randomised clinical trials have compared phyllanthus species versus antiviral drugs....

  4. STIM1 controls T cell-mediated immune regulation and inflammation in chronic infection.

    Science.gov (United States)

    Desvignes, Ludovic; Weidinger, Carl; Shaw, Patrick; Vaeth, Martin; Ribierre, Theo; Liu, Menghan; Fergus, Tawania; Kozhaya, Lina; McVoy, Lauren; Unutmaz, Derya; Ernst, Joel D; Feske, Stefan

    2015-06-01

    Chronic infections induce a complex immune response that controls pathogen replication, but also causes pathology due to sustained inflammation. Ca2+ influx mediates T cell function and immunity to infection, and patients with inherited mutations in the gene encoding the Ca2+ channel ORAI1 or its activator stromal interaction molecule 1 (STIM1) are immunodeficient and prone to chronic infection by various pathogens, including Mycobacterium tuberculosis (Mtb). Here, we demonstrate that STIM1 is required for T cell-mediated immune regulation during chronic Mtb infection. Compared with WT animals, mice with T cell-specific Stim1 deletion died prematurely during the chronic phase of infection and had increased bacterial burdens and severe pulmonary inflammation, with increased myeloid and lymphoid cell infiltration. Although STIM1-deficient T cells exhibited markedly reduced IFN-γ production during the early phase of Mtb infection, bacterial growth was not immediately exacerbated. During the chronic phase, however, STIM1-deficient T cells displayed enhanced IFN-γ production in response to elevated levels of IL-12 and IL-18. The lack of STIM1 in T cells was associated with impaired activation-induced cell death upon repeated TCR engagement and pulmonary lymphocytosis and hyperinflammation in Mtb-infected mice. Chronically Mtb-infected, STIM1-deficient mice had reduced levels of inducible regulatory T cells (iTregs) due to a T cell-intrinsic requirement for STIM1 in iTreg differentiation and excessive production of IFN-γ and IL-12, which suppress iTreg differentiation and maintenance. Thus, STIM1 controls multiple aspects of T cell-mediated immune regulation to limit injurious inflammation during chronic infection.

  5. Comparative study between occult hepatitis C virus infection and chronic hepatitis C.

    Science.gov (United States)

    Pardo, M; López-Alcorocho, J M; Rodríguez-Iñigo, E; Castillo, I; Carreño, V

    2007-01-01

    We have recently described the presence of occult hepatitis C virus (HCV) infection (HCV-RNA in liver in the absence of anti-HCV and serum HCV-RNA) in patients with persistently abnormal liver function tests of unknown aetiology. The aim of this study was to compare the characteristics of patients with occult HCV infection vs those of patients with chronic hepatitis C. We compared clinical features of 68 patients with occult HCV infection and 69 untreated chronic HCV patients (anti-HCV and serum HCV-RNA positive), matched for age, gender, duration of abnormal liver function tests and body mass index. Aspartate aminotransferase and alanine aminotransferase were higher (P HCV, but cholesterol and triglycerides were significantly higher in patients with occult HCV infection (P HCV patients had higher gamma-globulin (P = 0.005), alpha-foetoprotein (P HCV than in occult HCV infection. Mean percentage of infected hepatocytes was higher (P = 0.001) in chronic HCV (10.1%) than in occult HCV infection (5.3%). This occult HCV infection is a milder disease than chronic HCV, and this could be related to the significantly lower number of infected hepatocytes observed in occult HCV.

  6. Innate immunity and chronic immune activation in HCV/HIV-1 co-infection.

    Science.gov (United States)

    Gonzalez, Veronica D; Landay, Alan L; Sandberg, Johan K

    2010-04-01

    Innate immune responses are critical in the defense against viral infections. NK cells, myeloid and plasmacytoid dendritic cells, and invariant CD1d-restricted NKT cells mediate both effector and regulatory functions in this early immune response. In chronic uncontrolled viral infections such as HCV and HIV-1, these essential immune functions are compromised and can become a double edged sword contributing to the immunopathogenesis of viral disease. In particular, recent findings indicate that innate immune responses play a central role in the chronic immune activation which is a primary driver of HIV-1 disease progression. HCV/HIV-1 co-infection is affecting millions of people and is associated with faster viral disease progression. Here, we review the role of innate immunity and chronic immune activation in HCV and HIV-1 infection, and discuss how mechanisms of innate immunity may influence protection as well as immunopathogenesis in the HCV/HIV-1 co-infected human host.

  7. Phenotypes selected during chronic lung infection in cystic fibrosis patients: implications for the treatment of Pseudomonas aeruginosa biofilm infections.

    Science.gov (United States)

    Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang; Høiby, Niels

    2012-07-01

    During chronic lung infection of patients with cystic fibrosis, Pseudomonas aeruginosa can survive for long periods of time under the challenging selective pressure imposed by the immune system and antibiotic treatment as a result of its biofilm mode of growth and adaptive evolution mediated by genetic variation. Mucoidy, hypermutability and acquirement of mutational antibiotic resistance are important adaptive phenotypes that are selected during chronic P. aeruginosa infection. This review dicsusses the role played by these phenotypes for the tolerance of biofilms to antibiotics and show that mucoidy and hypermutability change the architecture of in vitro formed biofilms and lead to increase tolerance to antibiotics. Production of high levels of beta-lactamase impairs penetration of beta-lactam antibiotics due to inactivation of the antibiotic. In conclusion, these data underline the importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis.

  8. Neospora caninum: Chronic and congenital infection in consecutive pregnancies of mice.

    Science.gov (United States)

    Mazuz, Monica L; Shkap, Varda; Wollkomirsky, Ricardo; Leibovich, Benjamin; Savitsky, Igor; Fleiderovitz, Ludmila; Noam, Sugar; Elena, Blinder; Molad, Thea; Golenser, Jacob

    2016-03-30

    Neospora caninum, the causative agent of bovine neosporosis is the major cause of abortion in cattle worldwide. The principal route of transmission is via in utero infection of the offspring. Congenitally-infected dams remain persistently infected for life and might undergo abortions in consecutive pregnancies. In the present study, the effect of N. caninum in chronic and congenital infection was examined. CD1 mice were infected intra-peritoneally with live tachyzoites of the NcIs491 isolate, while non-infected mice served as a control. There were no clinical signs of infection observed following inoculation, but high titers of specific anti- N. caninum antibodies were detected. A month after infection, when chronic-infection was established, mice were mated. Fertility, litter size and mortality rate were monitored within two generations of four consecutive pregnancies. During a nine months period of the study all females maintained high level of antibodies, while the non- infected control mice remained seronegative. There was no difference in the fertility rate of the dams, or in the litter size of infected and control mice. Mortality of offspring of the first and second generations of the infected dams was observed within the two first weeks of life. The vertical transmission was analyzed by PCR assay of offspring brains. PCR positive results were found in all 13 litters of the first generation tested during four consecutive pregnancies. The rate of vertical transmission slightly decreased in successive pregnancies being 74.2%, 59.5%, 48.1% and 40% for the first to fourth pregnancies respectively. In the second generation 21 out of 28 litters were found positive and the overall rate of vertical transmission was 28.5%. In chronically and congenitally infected dams N. caninum infection was maintained during all successive pregnancies for about 9 months. The results show that CD-1 outbred mice are a suitable model for studying chronic and congenital neosporosis.

  9. Invasive Aspergillus infections in hospitalized patients with chronic lung disease

    Directory of Open Access Journals (Sweden)

    Wessolossky M

    2013-05-01

    Full Text Available Mireya Wessolossky,1 Verna L Welch,2 Ajanta Sen,1 Tara M Babu,1 David R Luke21Division of Infectious Diseases, University of Massachusetts Medical School, Worcester, MA, USA; 2Medical Affairs, Pfizer Inc, Collegeville, PA, USABackground: Although invasive pulmonary aspergillosis (IPA is more prevalent in immunocompromised patients, critical care clinicians need to be aware of the occurrence of IPA in the nontraditional host, such as a patient with chronic lung disease. The purpose of this study was to describe the IPA patient with chronic lung disease and compare the data with that of immunocompromised patients.Methods: The records of 351 patients with Aspergillus were evaluated in this single-center, retrospective study for evidence and outcomes of IPA. The outcomes of 57 patients with chronic lung disease and 56 immunocompromised patients were compared. Patients with chronic lung disease were defined by one of the following descriptive terms: emphysema, asthma, idiopathic lung disease, bronchitis, bronchiectasis, sarcoid, or pulmonary leukostasis.Results: Baseline demographics were similar between the two groups. Patients with chronic lung disease were primarily defined by emphysema (61% and asthma (18%, and immunocompromised patients primarily had malignancies (27% and bone marrow transplants (14%. A higher proportion of patients with chronic lung disease had a diagnosis of IPA by bronchoalveolar lavage versus the immunocompromised group (P < 0.03. The major risk factors for IPA were found to be steroid use in the chronic lung disease group and neutropenia and prior surgical procedures in the immunocompromised group. Overall, 53% and 69% of chronic lung disease and immunocompromised patients were cured (P = 0.14; 55% of chronic lung patients and 47% of immunocompromised patients survived one month (P = 0.75.Conclusion: Nontraditional patients with IPA, such as those with chronic lung disease, have outcomes and mortality similar to that in the

  10. 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

    2016-01-01

    AIM 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. METHODS 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. RESULTS 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. CONCLUSION The prevalence of OBI in chronic HCV patients was 18.4%, and OBI was not associated with disease progression in South Koreans. PMID:27895431

  11. Quasispecies composition and diversity do not reveal any predictors for chronic classical swine fever virus infection.

    Science.gov (United States)

    Jenckel, Maria; Blome, Sandra; Beer, Martin; Höper, Dirk

    2017-03-01

    Classical swine fever (CSF) can run acute, chronic, and prenatal courses in both domestic pigs and wild boar. Although chronic infections are rare events, their epidemiological impact is very high due to the long-term shedding of virus. So far, little is known about the factors that influence disease course and outcome from either the host or virus's perspective. To elucidate the viral determinants, we analyzed the role of the viral populations for the development of chronic CSF virus (CSFV) infections. Three different animal trials that had led to both chronic and acute infections were chosen for a detailed analysis by deep sequencing. The three inocula represented sub-genogroups 2.1 and 2.3, and two viruses were wild-type CSFV, one derived from an infectious cDNA clone. These viruses and samples derived from acutely and chronically infected animals were subjected to next-generation sequencing. Subsequently, the derived full-length genomes were compared at both the consensus and the quasispecies level. At consensus level, no differences were observed between the parental viruses and the viruses obtained from chronically infected animals. Despite a considerable level of variability at the quasispecies level, no indications were found for any predictive pattern with regard to the chronicity of the CSFV infections. While there might be no direct marker for chronicity, moderate virulence of some CSFV strains in itself seems to be a crucial prerequisite for the establishment of long-term infections which does not need further genetic adaption. Thus, general host and virus factors need further investigation.

  12. Novel PI3Kγ Mutation in a 44-Year-Old Man with Chronic Infections and Chronic Pelvic Pain

    Science.gov (United States)

    Hoischen, Alexander; Veltman, Joris; Allsop, Stephen A.; Granadillo, Victor J. Anciano; William, Arsani; Netea, Mihai G.; Dimitrakoff, Jordan

    2013-01-01

    A 44-year-old man is presented here with 14 years of chronic purulent sinusitis, a chronic fungal rash of the scrotum, and chronic pelvic pain. Treatment with antifungal therapy resulted in symptom improvement, however he was unable to establish an effective long-term treatment regimen, resulting in debilitating symptoms. He had undergone extensive work-up without identifying a clear underlying etiology, although Candida species were cultured from the prostatic fluid. 100 genes involved in the cellular immune response were sequenced and a missense mutation was identified in the Ras-binding domain of PI3Kγ. PI3Kγ is a crucial signaling element in leukotaxis and other leukocyte functions. We hypothesize that his mutation led to his chronic infections and pelvic pain. PMID:23861857

  13. Bone SPECT/CT detection of a sequestrum in chronic-infected nonunion of the tibia

    DEFF Research Database (Denmark)

    Madsen, Jan L

    2008-01-01

    Abstract: Sequestra are dead pieces of bone most often seen in long bones affected with prior or current infection. In addition to antibiotic therapy, chronic osteomyelitis with sequestration requires surgical debridement for cure. The author presents a case of tibial fracture associated with chr......Abstract: Sequestra are dead pieces of bone most often seen in long bones affected with prior or current infection. In addition to antibiotic therapy, chronic osteomyelitis with sequestration requires surgical debridement for cure. The author presents a case of tibial fracture associated...... with chronic osteomyelitis, nonunion, and the presence of a sequestrum that was detected by bone SPECT/CT.  ...

  14. Is chronic hepatitis C virus infection a risk factor for breast cancer?

    Institute of Scientific and Technical Information of China (English)

    Dominique; Larrey; Marie-Cécile; Bozonnat; Ihab; Kain; Georges-Philippe; Pageaux; Eric; Assenat

    2010-01-01

    AIM:To evaluate the prevalence of breast tumors in adult females with chronic hepatitis C virus(HCV) infection.METHODS:Prospective,single-center study,based on female outpatients consulting in a liver unit,for 1 year.The study group included females with present and/or past history of chronic infection by HCV.Patients with spontaneous recovery were excluded.Chronic hepatitis had been proved by liver biopsy in the majority of cases and/or biological markers of inflammation and fibrosis.The control group incl...

  15. Sofosbuvir and Simeprevir Treatment of a Stem Cell Transplanted Teenager With Chronic Hepatitis C Infection.

    Science.gov (United States)

    Fischler, Björn; Priftakis, Peter; Sundin, Mikael

    2016-06-01

    There have been no previous reports on the use of interferon-free combinations in pediatric patients with chronic hepatitis C infection. An infected adolescent with severe sickle cell disease underwent stem cell transplantation and subsequent treatment with sofosbuvir and simeprevir during ongoing immunosuppression. Despite the emergence of peripheral edema as a side effect, treatment was continued with sustained antiviral response.

  16. Case Report: Chronic Recurrent Unilateral Pulmonary Infection: Result of Congenital Unilateral Agenesis of Pulmonary Artery.

    Science.gov (United States)

    Al Jabbari, Odeaa; Abu Saleh, Walid K; Ramchandani, Mahesh; Scheinin, Scott

    2016-01-01

    Unilateral agenesis of the pulmonary artery (UAPA) is a rare congenital anomaly. This report describes a 52-year-old female who gave a long history of chronic, recurrent, left-sided pulmonary infections related to UAPA. For many years, she was managed medically but the infection continued to recur. She eventually underwent left pneumonectomy and made a good recovery.

  17. Chronic infection with Helicobacter pylori does not provoke major systemic inflammation in healthy adults

    DEFF Research Database (Denmark)

    Brenner, H; Berg, Gabriele; Fröhlich, M

    1999-01-01

    It has been suggested that chronic infection with Helicobacter pylori (H. pylori), in particular infection with virulent strains producing the cytotoxin-associated protein CagA, may increase the risk of coronary heart disease by generation of a persistent low-grade inflammatory stimulus. We...

  18. Shared immune and repair markers during experimental toxoplasma chronic brain infection and schizophrenia

    NARCIS (Netherlands)

    J.J. Tomasik (Jakub); T.L. Schultz (Tracey L.); W. Kluge (Wolfgang); R.H. Yolken (Robert H.); S. Bahn (Sabine); V.B. Carruthers (Vern B.)

    2016-01-01

    textabstractChronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse m

  19. Immune recovery in acute and chronic HIV infection and the impact of thymic stromal lymphopoietin

    DEFF Research Database (Denmark)

    Gelpi, Marco; Hartling, Hans J; Thorsteinsson, Kristina

    2016-01-01

    that promotes CD4+ T cells homeostatic polyclonal proliferation and regulates Th17/regulatory T-cell balance, immunological functions known to be affected during primary HIV infection. The aim of this study was to describe immune recovery in primary and chronic HIV infection and possible impact of TSLP. METHODS...

  20. Pattern recognition receptor responses in children with chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Heiberg, Ida Louise; Winther, Thilde Nordmann; Paludan, Søren Riis

    2012-01-01

    Several studies have demonstrated that hepatitis B virus (HBV) affects the expression and function of Toll like receptors (TLRs), but data on TLR function in HBV infection are mainly from adult patients. The natural history of chronic hepatitis B (CHB) infection is distinctly different in children...

  1. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections

    DEFF Research Database (Denmark)

    Yang, L.; Haagensen, J.A.; Jelsbak, L.

    2008-01-01

    The growth dynamics of bacterial pathogens within infected hosts are a fundamental but poorly understood feature of most infections. We have focused on the in situ distribution and growth characteristics of two prevailing and transmissible Pseudomonas aeruginosa clones that have caused chronic lu...

  2. Current progress in the development of therapeutic vaccines for chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Faezeh Ghasemi

    2016-07-01

    Full Text Available Chronic hepatitis B is still a major public health issue despite the successful prophylactic vaccination attempts. Chronicity of hepatitis B virus(HBV is mainly due to its ability to debilitate host's immune system. Therefore, major measures have been taken to stop this process and help patients with chronic hepatitis B infection recover from their illness. While satisfactory results have been achieved using preventive HBV vaccines, a reliable and effective therapeutic treatment is still in need of extensive studies. Current treatments for chronic hepatitis B include direct antiviral agents and nucleoside/nucleotide analogs, which are not always effective and are also costly. In addition, due to the fact that chronic HBV is responsible for debilitation of the immune system, studies have focused on developing therapeutic vaccines to help host's immune system recover and limit the infection. Several approaches including but not restricted to recombinant peptide-based, DNA-based, viral vector-based, and cell-based approaches are currently in use to develop therapeutic vaccines against the chronic form of HBV infection. In the current review, the authors will first discuss the role of the immune system in chronic hepatitis B infection and will then focus on latest advancements in therapeutic vaccination of HBV especially the clinical trials that have been carried out so far.

  3. Mycobacterium ulcerans infection as a cause of chronic diarrhea in an AIDS patient: A case report

    Institute of Scientific and Technical Information of China (English)

    Jin-Gook Huh; Myoung-Don Oh; You-Sun Kim; Jong-Sung Lee; Tae-Yeob Jeong; Soo-Hyung Ryu; Jung-Hwan Lee; Jeong-Seop Moon; Yun-Kyung Kang; Myung-Shup Shim

    2008-01-01

    Chronic diarrhea is one of the most frequent gastro-intestinal manifestations in acquired immunodeficiency syndrome (AIDS).Protozoa and nontuberculous mycobacteria (NTM) are opportunistic pathogens that can easily infect these patients.Among the NTM,Mycobacterium avium complex (MAC) is the most frequently observed pathogen in HIV-infected patients.However,NTMs other than MAC have not been reported as a gastrointestinal pathogen as yet.We present a case of chronic diarrhea in an AIDS patient in whom Mycobacterium ulcerans and cryptosporidium co-infection is evidenced from colonic tissue.

  4. Clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV

    Directory of Open Access Journals (Sweden)

    Braga Eduardo Lorens

    2006-02-01

    Full Text Available Co-infection with hepatitis C virus (HCV and human immunodeficiency virus (HIV is increasingly common and affects the clinical course of chronic hepatitis C. Highly active antiretroviral therapy has improved the life expectancy of HIV infected patients, but, by extending survival, it permits the development of HCV cirrhosis. This study tried to evaluate clinical and epidemiological features of patients with chronic hepatitis C co-infected with HIV. We evaluated 134 HCV-infected patients: i group A - 65 co-infected HCV/HIV patients, ii group B - 69 mono-infected HCV patients. The impact of HIV infection on HCV liver disease was analyzed using Child's score, ultrasound findings and liver histology. Patients were subjected to HCV genotyping and anti-HBs dosage. Patients mean age was 42.4 years (±9.1 and 97 (72.4% were males. Injected drug use and homo/bisexual practice were more frequently encountered in the co-infected group: 68.3% and 78.0%, respectively. Antibodies against hepatitis B virus (anti-HBs were found in only 38.1% of the patients (66.7% group A x 33.3% group B. Ten out of 14 individuals (71.4% who had liver disease (Child B or C and 25 out of 34 (73.5% who showed ultrasound evidence of chronic liver disease were in the co-infection group. HCV genotype-2/3 was more frequently encountered in co-infected patients (36.9% group A vs. 21.8% group B. Conclusions: a HIV infection seems to adversely affect the clinical course of chronic hepatitis C, b injected drug use, bi/homosexual practice and genotype-2/3 were more frequently encountered in co-infected patients, c immunization against HBV should be encouraged in these patients.

  5. Spiritual well-being, intrinsic religiosity, and suicidal behavior in predominantly Catholic Croatian war veterans with chronic posttraumatic stress disorder: a case control study.

    Science.gov (United States)

    Nad, Sanea; Marcinko, Darko; Vuksan-Aeusa, Bjanka; Jakovljević, Miro; Jakovljevic, Gordana

    2008-01-01

    We investigated relationships between spiritual well-being (SWB), intrinsic religiosity (IR), and suicidal behavior in 45 Croatian war veterans with chronic posttraumatic stress disorder and 32 healthy volunteers. Compared with the volunteers, the veterans had significantly lower SWB scores (p = 0.000) and existential well-being (EWB) scores (p = 0.000). Scores on the religious well-being (RWB) subscale (p = 0.108) and the IR scale did not differ significantly between the groups (p = 0.803). Veterans' suicidality inversely correlated with SWB (p = 0.000), EWB (p = 0.000), RWB (p = 0.026), and IR (p = 0.041), with the association being stronger for the EWB subscale than for the RWB subscale. Veterans who had attempted suicide at least once in their lifetime had significantly higher Suicidal Assessment Scale scores and lower EWB scores than veterans who never attempted suicide. Low EWB scores may imply an increased risk of suicidality. Some religious activities were more frequent among the veterans than among the healthy volunteers, possibly reflecting the veterans' increased help-seeking behavior due to poor EWB.

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

    Science.gov (United States)

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

    2011-05-12

    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 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) 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 target condition through considerations of the pathogenesis, and specification of a practical case definition, which can subsequently be used in the DTE for the specific purpose. The process is illustrated by two examples of Mycobacterium avium subsp. paratuberculosis (MAP) infections in cattle. MAP infections are chronic and can result in different adverse effects at different time points during the incubation period. The description provides input on the process and deductive reasoning which are integral parts to develop a high-quality design of a DTE for chronic infectious diseases.

  7. Therapeutic strategies for a functional cure of chronic hepatitis B virus infection

    Directory of Open Access Journals (Sweden)

    Jinhong Chang

    2014-08-01

    Full Text Available Treatment of chronic hepatitis B virus (HBV infection with the viral DNA polymerase inhibitors or pegylated alpha-interferon has led to a significant retardation in HBV-related disease progression and reduction in mortality related to chronic hepatitis B associated liver decompensation and hepatocellular carcinoma. However, chronic HBV infection remains not cured. The reasons for the failure to eradicate HBV infection by long-term antiviral therapy are not completely understood. However, clinical studies suggest that the intrinsic stability of the nuclear form of viral genome, the covalently closed circular (ccc DNA, sustained low level viral replication under antiviral therapy and homeostatic proliferation of hepatocytes are the critical virological and pathophysiological factors that affect the persistence and therapeutic outcomes of HBV infection. More importantly, despite potent suppression of HBV replication in livers of the treated patients, the dysfunction of HBV-specific antiviral immunity persists. The inability of the immune system to recognize cells harboring HBV infection and to cure or eliminate cells actively producing virus is the biggest challenge to finding a cure. Unraveling the complex virus–host interactions that lead to persistent infection should facilitate the rational design of antivirals and immunotherapeutics to cure chronic HBV infection.

  8. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    patients, the lungs of susceptible BALB/c mice were re-infected with P. aeruginosa 14 days after the initial infection. Singly-infected BALB/c mice, as well as non-infected mice, were used as controls. Decreased mortality and milder lung inflammation in re-infected BALB/c mice, as well as a tendency......Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF...... production, in chronic P. aeruginosa lung infection in CF....

  9. Methamphetamine mediates immune dysregulation in a murine model of chronic viral infection.

    Directory of Open Access Journals (Sweden)

    Uma eSriram

    2015-08-01

    Full Text Available Methamphetamine (METH is a highly addictive psychostimulant that not only affects the brain and cognitive functions but also greatly impacts the host immune system, rendering the body susceptible to infections and exacerbating the severity of disease. Although there is gathering evidence about METH abuse and increased incidence of HIV and other viral infections, not much is known about the effects on the immune system in a chronic viral infection setting. We have used the lymphocytic choriomeningitis virus (LCMV chronic mouse model of viral infection in a chronic METH environment and demonstrate that METH significantly increases CD3 marker on splenocytes and programmed death -1 (PD-1 expression on T cells, a cell surface signaling molecule known to inhibit T cell function and cause exhaustion in a lymphoid organ. Many of these METH effects were more pronounced during early stage of infection, which are gradually attenuated during later stages of infection. An essential cytokine for T-lymphocyte homeostasis, Interleukin-2 (IL-2 in serum was prominently reduced in METH-exposed infected mice. In addition, the serum pro-inflammatory (TNF, IL12 p70, IL1β, IL-6 and KC-GRO and Th2 (IL-2, IL-10 and IL-4 cytokine profiles were also altered in the presence of METH. Interestingly CXCR3, an inflammatory chemokine receptor, showed significant increase in the METH treated LCMV infected mice. Similarly, compared to only infected mice, epidermal growth factor receptor (EGFR in METH exposed LCMV infected mice were up regulated. Collectively, our data suggest that METH alters systemic, peripheral immune responses and modulates key markers on T cells involved in pathogenesis of chronic viral infection.

  10. Occult hepatitis B virus infection and cryptogenic chronic hepatitis in an area with intermediate prevalence of HBV infection

    Institute of Scientific and Technical Information of China (English)

    Mohammad Javad Kaviani; Behzad Behbahani; Mohammad Jafar Mosallaii; Fatemeh Sari-Aslani; Seyed Alireza Taghavi

    2006-01-01

    AIM: To assess the possible role of occult HBV infection in the pathogenesis of chronic hepatitis in Iranian patients.METHODS: After exclusion of autoimmune, metabolic and viral etiologies, 104 consecutive adult patients with histologic and biochemical features of chronic hepatitis and negative HBsAg were enrolled in the study.Qualitative PCR with a sensitivity of 150 × 103 copies/L,using two primers for Pre-S and core regions was applied to measure presence of HBV DNA in serum of the patients.RESULTS: All 104 patients completed the study.Qualitative HBV DNA was positive in two patients (1.9%).CONCLUSION: Occult HBV infection has negligible role in the pathogenesis of cryptogenic chronic hepatitis in Iranian patients.

  11. Prevalence of rheumatologic manifestations of chronic hepatitis C virus infection among Egyptians.

    Science.gov (United States)

    Mohammed, Reem Hamdy Abdellatif; ElMakhzangy, Hesham Ibrahim; Gamal, Amira; Mekky, Fatma; El Kassas, Mohammed; Mohammed, Nabil; Abdel Hamid, Mohammed; Esmat, Gamal

    2010-12-01

    Chronic hepatitis C virus (HCV) viremia has been known to provoke a plethora of autoimmune syndromes referred to as extrahepatic manifestations of chronic HCV infection. Aim of the current study was to assess the prevalence of rheumatologic manifestations among Egyptians with hepatitis C infection and its' association with cryoglobulin profile. The current research represents a cross-sectional study where patients with chronic HCV infection attending the outpatient clinic of the National Hepatology and Tropical Medicine Research Institute over a period of 1 year were interviewed. Patients with decompensated liver disease, on interferon therapy, having end-stage renal disease or coexisting viral infection like hepatitis B surface antibody positive patients were all excluded from the research. Laboratory investigations as well as serological assay including cryoglobulin profile, rheumatoid factor, antinuclear antibody, HCV-PCR were performed. Three hundred and six patients having chronic HCV infection were interviewed in this research. The overall estimated prevalence of rheumatologic manifestations in the current research was 16.39%, chronic fatigue syndrome 9.5%, sicca symptoms 8.8%, arthralgia 6.5%, fibromyalgia 1.9%, myalgia 1.3%, arthritis 0.7%, cryoglobulinemic vasculitis 0.7%, autoimmune hemolytic anemia 0.7%, thrombocytopenia 0.7%. Xerophthalmia was significantly present in male population (p = 0.04), whereas fibromyalgia, cryoglobulinemic vasculitis, arthritis, and autoimmune hemolytic anemia were significantly present in female population under study (p chronic HCV genotype 4 infection, the prevalence of rheumatologic manifestations was 16.3% with chronic fatigue syndrome and sicca symptoms being the most common with no significant correlation to the degree of elevation of liver disease or viral load.

  12. ATM facilitates mouse gammaherpesvirus reactivation from myeloid cells during chronic infection.

    Science.gov (United States)

    Kulinski, Joseph M; Darrah, Eric J; Broniowska, Katarzyna A; Mboko, Wadzanai P; Mounce, Bryan C; Malherbe, Laurent P; Corbett, John A; Gauld, Stephen B; Tarakanova, Vera L

    2015-09-01

    Gammaherpesviruses are cancer-associated pathogens that establish life-long infection in most adults. Insufficiency of Ataxia-Telangiectasia mutated (ATM) kinase leads to a poor control of chronic gammaherpesvirus infection via an unknown mechanism that likely involves a suboptimal antiviral response. In contrast to the phenotype in the intact host, ATM facilitates gammaherpesvirus reactivation and replication in vitro. We hypothesized that ATM mediates both pro- and antiviral activities to regulate chronic gammaherpesvirus infection in an immunocompetent host. To test the proposed proviral activity of ATM in vivo, we generated mice with ATM deficiency limited to myeloid cells. Myeloid-specific ATM deficiency attenuated gammaherpesvirus infection during the establishment of viral latency. The results of our study uncover a proviral role of ATM in the context of gammaherpesvirus infection in vivo and support a model where ATM combines pro- and antiviral functions to facilitate both gammaherpesvirus-specific T cell immune response and viral reactivation in vivo.

  13. 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...

  14. Clinical features of vascular disorders associated with chronic hepatitis virus infection.

    Science.gov (United States)

    Nishida, Naoshi; Kudo, Masatoshi

    2014-01-01

    Hepatitis virus infections can be accompanied by extrahepatic manifestations that may be caused by the host's immune reaction to the viral infection. Vascular involvement is one of these manifestations and is occasionally associated with life-threatening conditions due to systemic organ failure. The unique profile of hepatitis-related vascular involvement is associated with infection by different types of hepatitis viruses. For example, polyarteritis nodosa is more frequently reported in patients with chronic hepatitis B than those with chronic hepatitis C. Similarly, membranous nephropathy is a notable manifestation among hepatitis B virus-positive patients. In contrast, patients infected with hepatitis C virus are at risk for cryoglobulinemia and membranoproliferative glomerulonephritis. Antiviral therapy is necessary to control these kinds of vasculitis related to hepatitis virus infections; however, immunosuppressive agents may be required to treat severe cases. New antiviral drugs for viral hepatitis could improve the prognosis of vascular and renal involvement.

  15. Immune complexed (IC) hepatitis C virus (HCV) in chronically and acutely HCV-infected patients.

    Science.gov (United States)

    Riva, E; Maggi, F; Abbruzzese, F; Bellomi, F; Giannelli, G; Picardi, A; Scagnolari, C; Folgori, A; Spada, E; Piccolella, E; Dianzani, F; Antonelli, G

    2009-02-01

    In infected individuals, hepatitis C virus (HCV) exists in various forms of circulating particles which role in virus persistence and in HCV resistance to IFN therapy is still debated. Here, the proportion of HCV bound to immunoglobulin was determined in plasma of 107 chronically infected patients harbouring different HCV genotypes and, for comparison, of six patients with acute HCV infection. The results showed that, in spite of wide individual variability, chronically HCV-infected patients exhibited an extremely high proportion of immune complexed (IC) virus regardless of plasma HCV load and infecting genotype. Moreover, no significant association was found between baseline proportion of IC HCV and response to IFN treatment. Plasma samples collected within 2 weeks of treatment from 20 patients revealed a significant decline of mean IC HCV values relative to baseline that clearly paralleled the decay of total HCV load. In acutely infected patients, circulating HCV was not IC or IC at very low levels only in patients developing chronic HCV infection. Collectively, these findings strengthen the possibility that IC virus could play a critical role in the pathogenesis of HCV infection.

  16. The Emerging Extrahepatic Manifestations of Hepatitis C Virus Infection in Chronic Hepatitis and Mixed Cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    Poupak Fallahi

    2008-08-01

    Full Text Available Hepatitis C virus (HCV is known to be responsible for both hepatic and extrahepatic diseases. Mixed cryoglobulinemia, Sjögren syndrome, and chronic polyarthritis are the most documented rheumatologic extrahepatic manifestations of HCV infection. The most frequent and clinically important extrahepatic endocrine manifestations of chronic HCV infection are thyroid disorders and type 2 diabetes mellitus. From a meta-analysis of the literature, a significant association between HCV infection and thyroid autoimmunity and/or hypothyroidism as well as a high prevalence of thyroid cancer have been reported. The pattern of thyroid disorders observed in HCV infected patients is characterized by the presence of elevated circulating anti-thyroid peroxidase antibodies with increased risk of hypothyroidism. Several clinical epidemiologic studies have reported that HCV infection is a risk factor for type 2 diabetes. The type of diabetes manifested by subjects with chronic HCV infection is not of the classical type 2 diabetes; in fact, HCV-related diabetic patients are leaner than the classical diabetic patients, and have a significantly lower LDL-cholesterol, and both systolic and diastolic blood pressure. Furthermore, patients with mixed cryoglobulinemia (mixed cryoglobulinemia and chronic HCV infection with type 2 diabetes have more frequently non-organ-specific-autoantibodies than non-diabetic patients with mixed cryoglobulinemia and those with chronic HCV infection. Based on the above-mentioned findings, it has been hypothesized that diabetes in HCV infection may have an immune-mediated pathogenesis. In patients with chronic HCV infection, we found an increased risk of carotid artery plaque and carotid intima-media thickening. These findings suggested a possible role for chronic hepatitis C in the pathogenesis of carotid artery remodelling. Recently, high prevalence rates of anti-HCV antibodies were shown in patients with hypertrophic cardiomyopathy or

  17. Extrahepatic immune related manifestations in chronic hepatitis C virus infection.

    Science.gov (United States)

    Tampaki, Maria; Koskinas, John

    2014-09-21

    The association of chronic hepatitis C with immune related syndromes has been frequently reported. There is a great range of clinical manifestations affecting various systems and organs such as the skin, the kidneys, the central and peripheral nervous system, the musculoskeletal system and the endocrine glands. Despite the high prevalence of immune related syndromes in patients with chronic hepatitis C, the exact pathogenesis is not always clear. They have been often associated with mixed cryoglobulinemia, a common finding in chronic hepatitis C, cross reaction with viral antigens, or the direct effect of virus on the affected tissues. The aim of this review is to analyze the reported hepatitis C virus immune mediated syndromes, their prevalence and clinical manifestations and to discuss the most supported theories regarding their pathogenesis.

  18. Association between Helicobacter pylori Infection and Chronic Urticaria: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Huiyuan Gu

    2015-01-01

    Full Text Available Background. Some studies have shown the possible involvement of Helicobacter pylori (H. pylori infection in chronic urticaria, but the relationship remains controversial. The aim of this meta-analysis was to quantitatively assess the association between H. pylori infection and chronic urticaria. Methods. Observational studies comparing the prevalence of H. pylori infection in patients with chronic urticaria and control subjects were identified through a systematic search in MEDLINE and EMBASE up to July 2014. H. pylori infection was confirmed by serological or nonserological tests. For subgroup analyses, studies were separated by region, publication year, and H. pylori detection method to screen the potential factors resulting in heterogeneity. Results. 16 studies involving 965 CU cases and 1235 controls were included. Overall, the prevalence of H. pylori infection was higher in urticarial patients than in controls (OR = 1.66; 95% CI: 1.12–2.45; P=0.01. This result persisted in subanalysis of nine high-quality studies (OR = 1.36; 95% CI: 1.03–1.80; P=0.03. Subgroup analysis showed that detection method of H. pylori is also a potential influential factor for the overall results. Conclusions. Our present meta-analysis suggests that H. pylori infection is significantly, though weakly, associated with an increased risk of chronic urticaria.

  19. Chronically infected wild boar can transmit genotype 3 hepatitis E virus to domestic pigs.

    Science.gov (United States)

    Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin

    2015-10-22

    Hepatitis E virus (HEV) causes acute hepatitis E in humans in developing countries, but sporadic and autochthonous cases do also occur in industrialized nations. In Europe, food-borne zoonotic transmission of genotype 3 (gt3) has been associated with the consumption of raw and undercooked products from domestic pig and wild boar. As shown recently, naturally acquired HEV gt3 replicates efficiently in experimentally infected wild boar and is transmissible from a wild boar to domestic pigs. Generally, following an acute infection swine suffer from a transient febrile illness and viremia in connection with fecal virus shedding. However, little is known about sub-acute or chronic HEV infections in swine, and how and where HEV survives the immune response. In this paper, we describe the incidental finding of a chronic HEVgt3 infection in two naturally infected European wild boar which were raised and housed at FLI over years. The wild boar displayed fecal HEV RNA excretion and viremia over nearly the whole observation period of more than five months. The animal had mounted a substantial antibody response, yet without initial clearance of the virus by the immune system. Further analysis indicated a subclinical course of HEV with no evidence of chronic hepatitis. Additionally, we could demonstrate that this chronic wild boar infection was still transmissible to domestic pigs, which were housed together with this animal. Sentinel pigs developed fecal virus shedding accompanied by seroconversion. Wild boar should therefore be considered as an important reservoir for transmission of HEV gt3 in Europe.

  20. Health implications of chronic hepatosplenomegaly in Kenyan school-aged children chronically exposed to malarial infections and Schistosoma mansoni

    DEFF Research Database (Denmark)

    Wilson, Shona; Vennervald, Birgitte J; Kadzo, Hilda;

    2010-01-01

    with hepatosplenomegaly. Children who presented with hepatosplenomegaly had the lowest height-for-age Z-scores. This study shows that hepatosplenomegaly associated with chronic exposure to malaria and schistosomiasis is not a benign symptom amongst school-aged children but has potential long-term health consequences.......Hepatosplenomegaly among school-aged children in sub-Saharan Africa is highly prevalent. Two of the more common aetiological agents of hepatosplenomegaly, namely chronic exposure to malaria and Schistosoma mansoni infection, can result in similar clinical presentation, with the liver and spleen...... investigated in a study area where children were chronically exposed to malaria throughout while S. mansoni transmission was geographically restricted. Hepatosplenomegaly was associated with increased portal vein diameters, with enlargement of the spleen rather than the liver being more closely associated...

  1. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.

    Science.gov (United States)

    Kim, Edy Y; Battaile, John T; Patel, Anand C; You, Yingjian; Agapov, Eugene; Grayson, Mitchell H; Benoit, Loralyn A; Byers, Derek E; Alevy, Yael; Tucker, Jennifer; Swanson, Suzanne; Tidwell, Rose; Tyner, Jeffrey W; Morton, Jeffrey D; Castro, Mario; Polineni, Deepika; Patterson, G Alexander; Schwendener, Reto A; Allard, John D; Peltz, Gary; Holtzman, Michael J

    2008-06-01

    To understand the pathogenesis of chronic inflammatory disease, we analyzed an experimental mouse model of chronic lung disease with pathology that resembles asthma and chronic obstructive pulmonary disease (COPD) in humans. In this model, chronic lung disease develops after an infection with a common type of respiratory virus is cleared to only trace levels of noninfectious virus. Chronic inflammatory disease is generally thought to depend on an altered adaptive immune response. However, here we find that this type of disease arises independently of an adaptive immune response and is driven instead by interleukin-13 produced by macrophages that have been stimulated by CD1d-dependent T cell receptor-invariant natural killer T (NKT) cells. This innate immune axis is also activated in the lungs of humans with chronic airway disease due to asthma or COPD. These findings provide new insight into the pathogenesis of chronic inflammatory disease with the discovery that the transition from respiratory viral infection into chronic lung disease requires persistent activation of a previously undescribed NKT cell-macrophage innate immune axis.

  2. Macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.

    Directory of Open Access Journals (Sweden)

    Scott W Cousins

    Full Text Available The neovascular (wet form of age-related macular degeneration (AMD leads to vision loss due to choroidal neovascularization (CNV. Since macrophages are important in CNV development, and cytomegalovirus (CMV-specific IgG serum titers in patients with wet AMD are elevated, we hypothesized that chronic CMV infection contributes to wet AMD, possibly by pro-angiogenic macrophage activation. This hypothesis was tested using an established mouse model of experimental CNV. At 6 days, 6 weeks, or 12 weeks after infection with murine CMV (MCMV, laser-induced CNV was performed, and CNV severity was determined 4 weeks later by analysis of choroidal flatmounts. Although all MCMV-infected mice exhibited more severe CNV when compared with control mice, the most severe CNV developed in mice with chronic infection, a time when MCMV-specific gene sequences could not be detected within choroidal tissues. Splenic macrophages collected from mice with chronic MCMV infection, however, expressed significantly greater levels of TNF-α, COX-2, MMP-9, and, most significantly, VEGF transcripts by quantitative RT-PCR assay when compared to splenic macrophages from control mice. Direct MCMV infection of monolayers of IC-21 mouse macrophages confirmed significant stimulation of VEGF mRNA and VEGF protein as determined by quantitative RT-PCR assay, ELISA, and immunostaining. Stimulation of VEGF production in vivo and in vitro was sensitive to the antiviral ganciclovir. These studies suggest that chronic CMV infection may serve as a heretofore unrecognized risk factor in the pathogenesis of wet AMD. One mechanism by which chronic CMV infection might promote increased CNV severity is via stimulation of macrophages to make pro-angiogenic factors (VEGF, an outcome that requires active virus replication.

  3. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

    Science.gov (United States)

    Ma, Yue; Sun, Xiaolong; Li, Wen; Li, Yi; Kang, Tao; Yang, Xiai; Jiang, Wen

    2016-01-01

    Abstract Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as the white matter and spinal cord were very recently reported as involved regions in CLIPPERS. In this study, we report a case of CLIPPERS presenting with intracranial Epstein–Barr virus (EBV) infection and diffuse white matter involvement. Case summary: A 37-year-old male was diagnosed with mediastinal Hodgkin's lymphoma (lymphocyte predominance type) at the age of 26, and then obtained complete remission after treatment and remained free of relapse for 11 years. He was admitted with 7 months’ history of mental disorder, and 20 days’ history of gait and limb ataxia, dysphagia, and cough. The diagnosis of CLIPPERS was established based on the findings of punctate and nodular enhancing lesions in the bilateral pons, the basal ganglia, the mid-brain, the pontine brachium, and diffuse white matter in magnetic resonance imaging (MRI), together with CD3+ T-lymphocytic inflammatory infiltration in perivascular and parenchymal area revealed by bilateral parietal lobe brain biopsy. Also, our patient exhibited a good response to steroid therapy and remained free of relapse for 5 months. Importantly, we found intracranial Epstein–Barr virus infection in this patient. Conclusion: CLIPPERS might be an autoimmune disorder, and intracranial EBV-infection raises the possibility that EBV-associated autoimmunity is associated with CLIPPERS pathogenesis. PMID:27861371

  4. Blastocystis hominis and Endolimax nana Co-Infection Resulting in Chronic Diarrhea in an Immunocompetent Male.

    Science.gov (United States)

    Shah, Mitanshu; Tan, Christopher Bryan; Rajan, Dhyan; Ahmed, Shadab; Subramani, Krishnaiyer; Rizvon, Kaleem; Mustacchia, Paul

    2012-05-01

    Blastocystis hominis and Endolimax nana exist as two separate parasitic organisms; however co-infection with the two individual parasites has been well documented. Although often symptomatic in immunocompromised individuals, the pathogenicity of the organisms in immunocompetent subjects causing gastrointestinal symptoms has been debated, with studies revealing mixed results. Clinically, both B. hominis and E. nana infection may result in acute or chronic diarrhea, generalized abdominal pain, nausea, vomiting, flatulence and anorexia. We report the case of a 24-year-old immunocompetent male presenting with chronic diarrhea and abdominal pain secondary to B. hominis and E. nana treated with metronidazole, resulting in symptom resolution and eradication of the organisms. Our case illustrates that clinicians should be cognizant of both B. hominis and E. nana infection as a cause of chronic diarrhea in an immunocompetent host. Such awareness will aid in a timely diagnosis and possible parasitic eradication with resolution of gastrointestinal symptoms.

  5. Risk of Infections in Patients with Chronic Diseases

    DEFF Research Database (Denmark)

    Mor, Anil; Thomsen, Reimar W.

    2013-01-01

    of pyelonephritis may be 2 to 4 times increased. Treatment of asymptomatic bacteriuria in diabetes is generally not recommended. Diabetes duration and chronic complications including cystopathy appear to be more important risk factors than current glycemic control, but further evidence is needed. Modifiable risk...

  6. Clinical identification of bacteria in human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing

    OpenAIRE

    Rhoads Daniel D; Cox Stephen B; Rees Eric J; Sun Yan; Wolcott Randall D

    2012-01-01

    Abstract Background Chronic wounds affect millions of people and cost billions of dollars in the United States each year. These wounds harbor polymicrobial biofilm communities, which can be difficult to elucidate using culturing methods. Clinical molecular microbiological methods are increasingly being employed to investigate the microbiota of chronic infections, including wounds, as part of standard patient care. However, molecular testing is more sensitive than culturing, which results in m...

  7. Aging aggravates ischemic stroke-induced brain damage in mice with chronic peripheral infection.

    Science.gov (United States)

    Dhungana, Hiramani; Malm, Tarja; Denes, Adam; Valonen, Piia; Wojciechowski, Sara; Magga, Johanna; Savchenko, Ekaterina; Humphreys, Neil; Grencis, Richard; Rothwell, Nancy; Koistinaho, Jari

    2013-10-01

    Ischemic stroke is confounded by conditions such as atherosclerosis, diabetes, and infection, all of which alter peripheral inflammatory processes with concomitant impact on stroke outcome. The majority of the stroke patients are elderly, but the impact of interactions between aging and inflammation on stroke remains unknown. We thus investigated the influence of age on the outcome of stroke in animals predisposed to systemic chronic infection. Th1-polarized chronic systemic infection was induced in 18-22 month and 4-month-old C57BL/6j mice by administration of Trichuris muris (gut parasite). One month after infection, mice underwent permanent middle cerebral artery occlusion and infarct size, brain gliosis, and brain and plasma cytokine profiles were analyzed. Chronic infection increased the infarct size in aged but not in young mice at 24 h. Aged, ischemic mice showed altered plasma and brain cytokine responses, while the lesion size correlated with plasma prestroke levels of RANTES. Moreover, the old, infected mice exhibited significantly increased neutrophil recruitment and upregulation of both plasma interleukin-17α and tumor necrosis factor-α levels. Neither age nor infection status alone or in combination altered the ischemia-induced brain microgliosis. Our results show that chronic peripheral infection in aged animals renders the brain more vulnerable to ischemic insults, possibly by increasing the invasion of neutrophils and altering the inflammation status in the blood and brain. Understanding the interactions between age and infections is crucial for developing a better therapeutic regimen for ischemic stroke and when modeling it as a disease of the elderly.

  8. Development of chronic and acute golden Syrian hamster infection models with Leptospira borgpetersenii serovar Hardjo.

    Science.gov (United States)

    Zuerner, R L; Alt, D P; Palmer, M V

    2012-03-01

    The golden Syrian hamster (Mesocricetus auratus) is frequently used as a model to study virulence for several Leptospira species. Onset of an acute lethal infection following inoculation with several pathogenic Leptospira species has been widely adopted for pathogenesis studies. An important exception is the outcome following inoculation of hamsters with live L. borgpetersenii serovar Hardjo, the primary cause of bovine leptospirosis and a cause of human infections. Typically, inoculation of hamsters with L. borgpetersenii serovar Hardjo fails to induce clinical signs of infection. In this study, the authors defined LD(50) and ID(50) for 2 strains of L. borgpetersenii serovar Hardjo: JB197 and 203. Both strains infected hamsters with ID(50) values of approximately 1.5 × 10(2) bacteria yet differed in tissue invasion and interaction with leukocytes, resulting in widely divergent clinical outcomes. Hamsters infected with strain 203 established renal colonization within 4 days postinfection and remained asymptomatic with chronic renal infections similar to cattle infected with serovar Hardjo. In contrast, hamsters infected with strain JB197 developed a rapidly debilitating disease typical of acute leptospirosis common in accidental hosts (eg, humans) with an LD(50) of 3.6 × 10(4) bacteria. Evidence that strain JB197 resides in both extracellular and intracellular environments during hamster infection was obtained. Development of models that result in chronic and acute forms of leptospirosis provides a platform to study L. borgpetersenii pathogenesis and to test vaccines for the prevention of leptospirosis.

  9. Hepatocellular carcinoma in patients with chronic hepatitis C virus infection without cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Kathryn; L; Nash; Tracy; Woodall; Ashley; SM; Brown; Susan; E; Davies; Graeme; JM; Alexander

    2010-01-01

    AIM:To investigate and characterise patients with chronic hepatitis C virus(HCV) infection presenting with hepatocellular carcinoma(HCC) in the absence of cirrhosis.METHODS:Patients with chronic hepatitis C infection without cirrhosis presenting with HCC over a 2-year period were identified.The clinical case notes,blood test results and histological specimens were reviewed to identify whether additional risk factors for the development of HCC were present.RESULTS:Six patients(five male,one female) with chro...

  10. A case of multiple extrahepatic manifestations in a patient with untreated, chronic hepatitis C virus infection.

    Science.gov (United States)

    Meillier, Andrew; McGee, Jean; Kartan, Saritha; Baskin, Stuart

    2014-02-01

    Chronic hepatitis C virus (HCV) infection is a complex, multi-organ disorder, not just limited to the liver. Mixed cryoglobulinemia (MC) type 2 is a common extrahepatic complication, in which immunoglobulin complexes deposit in vascular endothelium. This in turn creates a diffuse inflammatory reaction, leading to a variety of disorders involving multiple systems. We report the rare case of a patient with cryoglobulinemia, cutaneous vasculitis, membroproliferative glomerulonephritis, and B cell lymphoma with a variant t(6;10) translocation in the setting of an untreated, chronic HCV infection. This case highlights the challenge associated with diagnosing and managing such a complex presentation.

  11. Co-infection with Cyclospora cayetanensis and Salmonella typhi in a patient with HIV infection and chronic diarrhoea.

    Science.gov (United States)

    Llanes, Rafael; Velázquez, Beltran; Reyes, Zoila; Somarriba, Lorenzo

    2013-01-01

    A 45-year-old-Haitian male patient with fever, abdominal cramping, chronic diarrhoea and weight loss of about 3 kg was investigated. Stool examination revealed Salmonella typhi and Cyclospora cayetanensis. The HIV test was positive with a CD4 count of 130 cells/mm(3). We provided the first report of co-infection Cyclospora cayetanensis and Salmonella typhi in a HIV patient with chronic diarrhoea. The patient was treated with oral ciprofloxacin, 500 mg, twice daily for two weeks, with a good clinical outcome.

  12. Chronic kidney disease of uncertain etiology in Sri Lanka: Are leptospirosis and Hantaviral infection likely causes?

    Science.gov (United States)

    Gamage, Chandika Damesh; Sarathkumara, Yomani Dilukshi

    2016-06-01

    Chronic kidney disease of uncertain etiology (CKDu) has been a severe burden and a public health crisis in Sri Lanka over the past two decades. Many studies have established hypotheses to identify potential risk factors although causative agents, risk factors and etiology of this disease are still uncertain. Several studies have postulated that fungal and bacterial nephrotoxins are a possible etiological factor; however, the precise link between hypothesized risk factors and the pathogenesis of chronic kidney disease has yet to be proven in prior studies. Leptospirosis and Hantavirus infections are important zoonotic diseases that are naturally maintained and transmitted via infected rodent populations and which present similar clinical and epidemiological features. Both infections are known to be a cause of acute kidney damage that can proceed into chronic renal failure. Several studies have reported presence of both infections in Sri Lanka. Therefore, we hypothesized that pathogenic Leptospira or Hantavirus are possible causative agents of acute kidney damage which eventually progresses to chronic kidney disease in Sri Lanka. The proposed hypothesis will be evaluated by means of an observational study design. Past infection will be assessed by a cross-sectional study to detect the presence of IgG antibodies with further confirmatory testing among chronic kidney disease patients and individuals from the community in selected endemic areas compared to low prevalence areas. Identification of possible risk factors for these infections will be followed by a case-control study and causality will be further determined with a cohort study. If the current hypothesis is true, affected communities will be subjected for medical interventions related to the disease for patient management while considering supportive therapies. Furthermore and possibly enhance their preventive and control measures to improve vector control to decrease the risk of infection.

  13. Type-I Interferon responses: From Friend to Foe in the Battle against Chronic Viral Infection

    Directory of Open Access Journals (Sweden)

    Armstrong Murira

    2016-12-01

    Full Text Available Type I interferons (IFN-I have long been heralded as key contributors to effective antiviral responses. More widely understood in the context of acute viral infection, the role of this pleiotropic cytokine has been characterized as triggering antiviral states in cells and potentiating adaptive immune responses. Upon induction in the innate immune response, IFN-I triggers the expression of interferon-stimulated genes (ISGs, which upregulate the effector function of immune cells (e.g., dendritic cells, B cells and T cells towards successful resolution of infections. However, emerging lines of evidence reveal that viral persistence in the course of chronic infections could be driven by deleterious immunomodulatory effects upon sustained IFN-I expression. In this setting, elevation of IFN-I and ISGs is directly correlated to viral persistence and elevated viral loads. It is important to note that the correlation among IFN-I expression, ISGs and viral persistence may be a cause or effect of chronic infection and this is an important distinction to make towards establishing the dichotomous nature of IFN-I responses. The aim of this mini-review is to (i summarize the interaction between IFN-I and downstream effector responses and therefore (ii delineate the function of this cytokine on positive and negative immunoregulation in chronic infection. This is a significant consideration given the current therapeutic administration of IFN-I in chronic viral infections whose therapeutic significance is projected to continue despite emergence of increasingly efficacious antiviral regimens. Furthermore, elucidation of the interplay between virus and the antiviral response in the context of IFN-I will elucidate avenues towards more effective therapeutic and prophylactic measures against chronic viral infections.

  14. Antibodies from women urogenitally infected with C. trachomatis predominantly recognized the plasmid protein pgp3 in a conformation-dependent manner

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    Wu Yimou

    2008-06-01

    Full Text Available Abstract Background C. trachomatis organisms carry a cryptic plasmid that encodes 8 open reading frames designated as pORF1 to 8. It is not clear whether all 8 pORFs are expressed during C. trachomatis infection in humans and information on the functionality of the plasmid proteins is also very limited. Results When antibodies from women urogenitally infected with C. trachomatis were reacted with the plasmid proteins, all 8 pORFs were positively recognized by one or more human antibody samples with the recognition of pORF5 protein (known as pgp3 by most antibodies and with the highest titers. The antibody recognition of the pORFs was blocked by C. trachomatis-infected HeLa but not normal HeLa cell lysates. The pgp3 fusion protein-purified human IgG detected the endogenous pgp3 in the cytosol of C. trachomatis-infected cells with an intracellular distribution pattern similar to that of CPAF, a chlamydial genome-encoded protease factor. However, the human antibodies no longer recognized pgp3 but maintained recognition of CPAF when both antigens were linearized or heat-denatured. The pgp3 conformation is likely maintained by the C-terminal 75% amino acid sequence since further deletion blocked the binding by the human antibodies and two conformation-dependent mouse monoclonal antibodies. Conclusion The plasmid-encoded 8 proteins are both expressed and immunogenic with pgp3 as the most immunodominant antigen during chlamydial infection in humans. More importantly, the human anti-pgp3 antibodies are highly conformation-dependent. These observations have provided important information for further understanding the function of the plasmid-encoded proteins and exploring the utility of pgp3 in chlamydial diagnosis and vaccination.

  15. Telbivudine (Sebivo in patients with hepatitis B virus (HBV chronic infection

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    Viola Sacchi

    2008-12-01

    Full Text Available Hepatitis B is the most common serious liver infection in the world, with about 350 million people who are infected with the hepatitis B virus (HBV and about 1 million deaths annually.Hepatitis B is characterized by an acute and a chronic phase, if the subject fails to produce adequate immune response.About 5-10% of adults infected with HBV go on to develop chronic infection and become chronic carriers (CHB; moreover, the liver damage, if not stopped, continues until cirrhosis or hepatocellular carcinoma. In the natural history of HBV infection, the most important event is HBeAg seroconversion, characterized by loss of HBeAg (a specific antigen of the virus and development of anti-HBe antibodies (HBeAg-positive patients. If the seroconversion has occurred early (when liver damage is not already significant and is maintained, long-term prognosis is excellent. The disease can follow a more aggressive course if active viral replication persists despite anti-HBe positivity. This state, characterized by continuing viral replication, has been termed as HBeAg-negative CHB, and is the most prevalent form in Italy. At the moment, there are 4 approved antiviral drug classes, with different antiviral efficacy, for the treatment of chronic hepatitis B: interferons, nucleoside analogues, nucleotide analogues, and cyclopents.The primary target of the treatment is a prolonged suppression of viral replication, in order to avoid long term complications and increase survival.

  16. Differential diagnosis of infections in a patient with Chronic Obstructive Pulmonary Disease

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    Paolo Ghiringhelli

    2008-12-01

    Full Text Available We describe a case of a 65-years-old patient with Chronic Obstructive Pulmonary Disease (COPD, receiving oxygen therapy and resistant to antibiotic therapy. He was admitted with high fever, productive cough, marked leukocytosis, and chest X-ray findings of infiltration and fluid levels within lung cysts. A differential diagnosis was essential to start an adequate treatment and avoid the rapid worsening of patients respiratory status. In patients with chronic pulmonary diseases under immunotherapy, micotic infections should be considered. Aspergillus fumigatus was cultured from bronchial washing fluid and we diagnosed chronic necrotizing pulmonary aspergillosis (CNPA. Oral itraconazole was started and his symptoms and laboratory data markedly improved.

  17. T cell immunopathogenesis and immunotherapeutic strategies for chronic hepatitis B virus infection

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    Yukihiro Shimizu

    2012-01-01

    Hepatitis B is caused by the host immune response and T cells play a major role in the immunopathogenesis.More importantly,T cells not only destroy hepatocytes infected by hepatitis B virus (HBV),but also control HBV replication or eradicate HBV in a noncytolytic manner.Therefore,analysis of T cell immune response during acute and chronic HBV infection is important to develop a strategy for successful viral control,which could lead to immunotherapy for terminating persistent HBV infection.There have been many attempts at immunotherapy for chronic HBV infection,and some have shown promising results.High viral load has been shown to suppress antiviral immune responses and immunoinhibitory signals have been recently elucidated,therefore,viral suppression by nucleos(t)ide analogs,stimulation of antiviral immune response,and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.

  18. Cost-Effective Interventions in The Control of Chronic Hepatitis B (CHB Infection

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    Mehlika Toy

    2014-05-01

    Full Text Available The hepatitis B virus (HBV causes infection in the liver that can lead to cirrhosis, liver cancer, and premature death. The disease is not widely recognised as a serious public health problem, and as a result, inadequate resources are being allocated to hepatitis B prevention and control. Vaccination against HBV has been a great success and has resulted in a reduction in the rate of chronic infection; however, the vaccine is of no help for those already infected. The big challenge is how to deliver effective and affordable care to those who are carriers and who are eligible for treatment, and affordable diagnostics to detect those who are not yet aware of their infection, to prevent the spread to susceptible individuals. This review intends to give the reader a brief overview of the types of control strategies that have been examined in recent cost-effectiveness studies on the control of chronic hepatitis B.

  19. Management of chronic diarrhea in HIV-infected patients: current treatment options, challenges and future directions

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    Lidia Elfstrand

    2010-11-01

    Full Text Available Lidia Elfstrand, Claes-Henrik FlorénDepartment of Medicine, Division of Clinical Sciences, Skåne University Hospital, Lund University, Lund, SwedenAbstract: Diarrhea is a common clinical manifestation of HIV infection regardless of whether the patients have AIDS. HIV and malnutrition tend to occur in the same populations, the underprivileged and resource-poor. Malnutrition increases severity and mortality of infection. Occurrence of chronic diarrhea in HIV-infected patients, gut status and pathogenic agents, nutritional status and the crucial role of nutrition are reviewed. Bovine colostrum-based food can be useful for managing chronic diarrhea in HIV-infected patients, enhancing both nutritional and immunological status.Keywords: HIV, diarrhea, nutrition, bovine colostrum, CD4+ 

  20. Autoantibodies in patients with chronic hepatitis C virus infection: pitfalls for the diagnosis of rheumatic diseases.

    Science.gov (United States)

    Palazzi, Carlo; Buskila, Dan; D'Angelo, Salvatore; D'Amico, Emilio; Olivieri, Ignazio

    2012-07-01

    Hepatitis C virus infection (HCV) is one of the best mimes in medicine. About 40-70% of patients suffering from this disorder develop at least one extra-hepatic disorder that can have a rheumatic nature (arthralgias, arthritis, vasculitis and sicca syndrome) and must be differentiated from the primitive rheumatic diseases. In addition, HCV infection can also alter the laboratory tests. Several alterations of first line laboratory tests can be usually found in both chronic HCV infection and chronic inflammatory rheumatic disorders. In the present review we analyze the interference of HCV in tests more specifically used in rheumatology: rheumatoid factor and other autoantibodies (ANA, anti-ENA, ANCA, anti-DNA, antiphospholipid, anti-CCP). In patients suffering from HCV infection, the diagnosis of connective tissue diseases (CTD) or rheumatoid arthritis (RA) should be made only when the detected symptoms or laboratory data are not inducible by HCV, otherwise only a diagnosis of "possible CTD" or "possible RA" should be considered.

  1. Recurrent paratyphoid fever A co-infected with hepatitis A reactivated chronic hepatitis B.

    Science.gov (United States)

    Liu, Yanling; Xiong, Yujiao; Huang, Wenxiang; Jia, Bei

    2014-05-12

    We report here a case of recurrent paratyphoid fever A with hepatitis A co-infection in a patient with chronic hepatitis B. A 26-year-old male patient, who was a hepatitis B virus carrier, was co-infected with Salmonella enterica serovar Paratyphi A and hepatitis A virus. The recurrence of the paratyphoid fever may be ascribed to the coexistence of hepatitis B, a course of ceftriaxone plus levofloxacin that was too short and the insensitivity of paratyphoid fever A to levofloxacin. We find that an adequate course and dose of ceftriaxone is a better strategy for treating paratyphoid fever. Furthermore, the co-infection of paratyphoid fever with hepatitis A may stimulate cellular immunity and break immunotolerance. Thus, the administration of the anti-viral agent entecavir may greatly improve the prognosis of this patient with chronic hepatitis B, and the episodes of paratyphoid fever and hepatitis A infection prompt the use of timely antiviral therapy.

  2. Chronic lyme disease: psychogenic fantasy or somatic infection?

    Science.gov (United States)

    Mervine, Phyllis

    2003-02-01

    Sigal and Hassett published an article about Lyme disease in the EHP Supplements (Sigal and Hassett 2002), suggesting that chronic Lyme disease is "psychogenic." I do not think that Sigal and Hassett, non-psychiatrists, are qualified to speak about psychiatric matters. I, however, actually have had the disease, which they characterize as "medically unexplained," for over 25 years and have 15 years of experience as a patient advocate and educator. I beg to differ.

  3. Health-related quality of life of Southern Chinese with chronic hepatitis B infection

    OpenAIRE

    Lam Elegance TP; Lam Cindy LK; Lai CL; Yuen MF; Fong Daniel YT; So Thomas MK

    2009-01-01

    Abstract Background Few studies have evaluated the health-related quality of life (HRQOL) of Southern Chinese with chronic hepatitis B (CHB) infection. Aim To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL. Methods 520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC) were interviewed with a structured questionnaire, ...

  4. As a Rare Site of Invasive Fungal Infection, Chronic Granulomatous Aspergillus Synovitis: A Case Report

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    Aylin Canbolat Ayhan

    2013-06-01

    Full Text Available Aspergillus can causes invasive disease of various organs especially in patients with weakened immune systems. Aspergillus synovitis and arthritis are uncommon types of involvement due to this infection. Approches to fungal osteoarticular infections are based on only case reports. This paper presents a rare case of chronic granulomatous Aspergillus synovitis in an immunocompromised 5-year old girl who was treated for acute lymphoblastic leukemia.

  5. Clinical and Pathologic Evaluation of Chronic Bartonella henselae or Bartonella clarridgeiae Infection in Cats

    OpenAIRE

    Kordick, Dorsey L.; Brown, Talmage T; Shin, KwangOk; Breitschwerdt, Edward B.

    1999-01-01

    Human Bartonella infections result in diverse medical presentations, whereas many cats appear to tolerate chronic bacteremia without obvious clinical abnormalities. Eighteen specific-pathogen-free cats were inoculated with Bartonella henselae- and/or Bartonella clarridgeiae-infected cat blood and monitored for 454 days. Relapsing bacteremia did not correlate with changes in protein profiles or differences in antigenic protein recognition. Intradermal skin testing did not induce a delayed type...

  6. Sinus surgery postpones chronic Gram-negative lung infection

    DEFF Research Database (Denmark)

    Alanin, M C; Aanaes, K; Høiby, N

    2016-01-01

    of pulmonary samples positive for GNB. We investigated whether the effect is sustained. METHODOLOGY: We report the effect of ESS and adjuvant therapy three years postoperatively in a CF cohort participating in this prospective clinical follow-up study. The primary endpoint was the lung infection status defined...

  7. Adiponectin serum level in chronic hepatitis C infection andtherapeutic profile

    Institute of Scientific and Technical Information of China (English)

    Valentina Peta; Carlo Torti; Natasa Milic; Alfredo Focà; Ludovico Abenavoli

    2015-01-01

    Hepatic steatosis is commonly seen in the patients withchronic hepatitis C virus (HCV) infection. HCV is closelyassociated with lipid metabolism, and viral steatosis ismore common in genotype 3 infection owing to a directcytopathic effect of HCV core protein. In non-genotype3 infection, hepatic steatosis is considered largely tobe the result of the alterations in host metabolism;metabolic steatosis is primarily linked with HCV genotype1. Adipose tissue secretes different hormonesinvolved in glucose and lipid metabolisms. It has beendemonstrated that adipocytokines are involved in thepathogenesis of non-alcoholic fatty liver disease, as thedecreased plasma adiponectin levels, a soluble matrixprotein expressed by adipoctyes and hepatocyte, areassociated with liver steatosis. Various studies haveshown that steatosis is strongly correlated negativelywith adiponectin in the patients with HCV infection.The role of adiponectin in hepatitis C virus inducedsteatosis is still not completely understood, but therelationship between adiponectin low levels and liversteatosis is probably due to the ability of adiponectinto protect hepatocytes from triglyceride accumulationby increasing β-oxidation of free fatty acid and thusdecreasing de novo free fatty acid production.

  8. Acanthamoeba polyphaga in rheumatoid arthritis: possibility for a chronic infection.

    Science.gov (United States)

    Jeansson, S; Kvien, T K

    2001-06-01

    Acanthamoeba polyphaga (AP) is ubiquitous in nature and frequently infects humans. AP has some features, such as persistence, which makes it an attractive candidate in studies of a possible infectious aetiology in rheumatoid arthritis (RA). In this study the occurrence of AP-specific antibodies was compared between RA patients and matched controls.

  9. 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 ...

  10. Oral mucosa alterations in chronic hepatitis and cirrhosis due to HBV or HCV infection.

    Science.gov (United States)

    Sulka, Agnieszka; Simon, Krzysztof; Piszko, Paweł; Kalecińska, Ewa; Dominiak, Marzena

    2006-03-01

    The aim of the study was to evaluate the character of lesions within oral mucosa in patients suffering from chronic hepatitis and cirrhosis of the liver due to either HBV or HCV infection. A total of 74 patients treated at the Clinic of Infectious Diseases in Wrocław for chronic hepatitis B (20 patients, group I) and for chronic hepatitis C (23 patients group III) and cirrhosis of the liver due to HBV (15 patients , group II) and HCV (16 patients, group IV) infection. The control group comprised 29 healthy subjects. Lesions within the oral mucosa found on clinical examinations were confirmed with a histopathological evaluation. Patients suffering from chronic hepatitis B revealed leukoplakia (1/20), melanoplakia (1/20), petechiae (1/20), 17 patients from this group did not show any changes. Patients suffering from chronic hepatitis C revealed leukoplakia (6/23), Delbanco's disease (2/23), melanoplakia (1/23), lichen planus (1/23), petechiae (1/23), 12 patients from this group did not show any changes. Patients suffering from cirrhosis of the liver due of HBV infection revealed leukoplakia (3/15) petechiae (2/15), Delbanco's disease (1/15), angular cheilitis (1/15), aphthae (1/15), 7 patients from this group did not reveal any changes. Patients suffering from cirrhosis of the liver due of HCV infection revealed petechiae (2/16), melanoplakia (1/16), candidosis (1/16), labial herpes (1/16), 11 patients from this group did not reveal any changes. In control group we observed leukoplakia (3/29), Delbanco's disease (1/29), labial herpes (1/29), petechiae (1/29), and 23 subjects did not present pathological lesions within the oral mucosa. Results indicate the lack of connection between chronic HBV and HCV infection as well as the stage of the disease with the incidence and character of oral lesions in oral mucosa.

  11. Exceptional Heterogeneity in Viral Evolutionary Dynamics Characterises Chronic Hepatitis C Virus Infection

    Science.gov (United States)

    Lemey, Philippe; Farci, Patrizia; Pybus, Oliver G.

    2016-01-01

    The treatment of HCV infection has seen significant progress, particularly since the approval of new direct-acting antiviral drugs. However these clinical achievements have been made despite an incomplete understanding of HCV replication and within-host evolution, especially compared with HIV-1. Here, we undertake a comprehensive analysis of HCV within-host evolution during chronic infection by investigating over 4000 viral sequences sampled longitudinally from 15 HCV-infected patients. We compare our HCV results to those from a well-studied HIV-1 cohort, revealing key differences in the evolutionary behaviour of these two chronic-infecting pathogens. Notably, we find an exceptional level of heterogeneity in the molecular evolution of HCV, both within and among infected individuals. Furthermore, these patterns are associated with the long-term maintenance of viral lineages within patients, which fluctuate in relative frequency in peripheral blood. Together, our findings demonstrate that HCV replication behavior is complex and likely comprises multiple viral subpopulations with distinct evolutionary dynamics. The presence of a structured viral population can explain apparent paradoxes in chronic HCV infection, such as rapid fluctuations in viral diversity and the reappearance of viral strains years after their initial detection. PMID:27631086

  12. Infective endocarditis in chronic hemodialysis patients: Experience from Morocco

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    Dina Montasser

    2011-01-01

    Full Text Available Since the 1960s, regular hemodialysis (HD was recognized as a risk factor for the development of infective endocarditis (IE, particularly at vascular access sites. The present report describes our experience at the Etat Major General Agadir, Morocco, of taking care of IE in patients on regular dialysis. A retrospective analysis was made of five cases of IE in patients receiving re-gular HD having arteriovenous fistula as vascular access. They were sent from four private centers and admitted in our formation between January 2004 and March 2009. Infective endocarditis was detected after 34.5 months following initiation of dialysis. The causative organisms included Sta-phylococcus and Enterococcus in two cases each and negative blood culture in one case. A recent history of infection (<3 months of the vascular access was found in three cases. Peripheric embolic phenomena were noted in two cases. A pre-existing heart disease was common and contributed to heart failure. Mortality was frequent due to valvular perforations and congestive heart failure, making the medical treatment alone unsatisfactory. Two patients survived and three of our patients received a prosthetic valve replacement, with a median survival after surgery of 10.3 months/person. The clinical diagnosis of infective endocarditis in regularly dialyzed patients remains difficult, with the presence of vascular calcification as a common risk factor. The vascular catheter infections are the cardinal gateway of pathogenic organisms, which are mainly Staphlococcus. The prognosis is bad and the mortality is significant, whereas medical and surgical treatments are often established in these patients who have many factors of comorbidity.

  13. Cyst infection in hospital-admitted autosomal dominant polycystic kidney disease patients is predominantly multifocal and associated with kidney and liver volume

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    Balbo, B.E.P. [Divisão de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Sapienza, M.T.; Ono, C.R. [Divisão de Medicina Nuclear, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Jayanthi, S.K. [Divisão de Radiologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Dettoni, J.B. [Divisão de Patologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil); Castro, I.; Onuchic, L.F. [Divisão de Nefrologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-06-13

    Positron-emission tomography/computed tomography (PET/CT) has improved cyst infection (CI) management in autosomal dominant polycystic kidney disease (ADPKD). The determinants of kidney and/or liver involvement, however, remain uncertain. In this study, we evaluated clinical and imaging factors associated with CI in kidney (KCI) and liver (LCI) in ADPKD. A retrospective cohort study was performed in hospital-admitted ADPKD patients with suspected CI. Clinical, imaging and surgical data were analyzed. Features of infected cysts were evaluated by PET/CT. Total kidney (TKV) and liver (TLV) volumes were measured by CT-derived multiplanar reconstruction. CI was detected in 18 patients who experienced 24 episodes during an interval of 30 months (LCI in 12, KCI in 10 and concomitant infection in 2). Sensitivities of CT, magnetic resonance imaging and PET/CT were 25.0, 71.4, and 95.0%. Dysuria (P<0.05), positive urine culture (P<0.01), and previous hematuria (P<0.05) were associated with KCI. Weight loss (P<0.01) and increased C-reactive protein levels (P<0.05) were associated with LCI. PET/CT revealed that three or more infected cysts were present in 70% of the episodes. TKV was higher in kidney-affected than in LCI patients (AUC=0.91, P<0.05), with a cut-off of 2502 mL (72.7% sensitivity, 100.0% specificity). TLV was higher in liver-affected than in KCI patients (AUC=0.89, P<0.01) with a cut-off of 2815 mL (80.0% sensitivity, 87.5% specificity). A greater need for invasive procedures was observed in LCI (P<0.01), and the overall mortality was 20.8%. This study supports PET/CT as the most sensitive imaging method for diagnosis of cyst infection, confirms the multifocal nature of most hospital-admitted episodes, and reveals an association of kidney and liver volumes with this complication.

  14. Multidrug-resistant Enterobacteriaceae including metallo-β-lactamase producers are predominant pathogens of healthcare-associated infections in an Indian teaching hospital

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    J B Sarma

    2011-01-01

    Full Text Available Purpose: A study was carried out in an Indian teaching hospital in 2009 to detect the rate of surgical site infections (SSI and peripheral vascular access site infections. Materials and Methods: The study was a point-prevalence study involving over 300 patients. The presence of infection was determined according to the CDC criteria. Swabs were taken from the infected sites and identification and sensitivity were carried out using VITEK® 2 automated system. Characterisation of β-lactamase was carried out at ARRML, Colindale, London. Results: The rate of SSI was 15% for the clean and clean-contaminated categories while that for the dirty contaminated category was 85% (NNIS risk index 0. Cultures yielded definite or probable pathogens from 64% (9/14 of the patients with SSI. In 1/3 rd of the cultures, Staphylococcus aureus was grown and the rest had Enterobacteriaceae, either extended-spectrum β-lactamase (ESBL producers or Amp-C hyperproducers and, alarmingly, three isolates were positive for newly recognised New Delhi metallo-β-lactamase-1 (NDM-1. In medicine, 87% (n = 99 of the patients had a peripheral IV access device, 55% developed associated phlebitis/infection and, in seven, probable pathogens were isolated (Candida species and Escherichia coli producing ESBL and NDM-1, respectively, Staphylococcus aureus and Enterococcus faecium. All ESBL and metallo-β-lactamase producers were resistant to multiple classes of antimicrobials, the latter being sensitive only to colistin and tigecycline. The study also found that all post-operative patients were on antibiotics, 92% on IV [213 defined daily doses (DDD/100 post-op patients] limited mainly to the third-generation cephalosporins (26% and aminoglycosides (24% and imidazole derivatives (30%. In medicine, 83% (n = 82 were on IV antibiotics (123 DDD/100 bed-days, limited mainly to the third-generation cephalosporins (74%. Conclusion: Indiscriminate use of antibiotics is a major problem

  15. EBV infection is common in gingival epithelial cells of the periodontium and worsens during chronic periodontitis.

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    Séverine Vincent-Bugnas

    Full Text Available An amplifying role for oral epithelial cells (ECs in Epstein-Barr Virus (EBV infection has been postulated to explain oral viral shedding. However, while lytic or latent EBV infections of oro/nasopharyngeal ECs are commonly detected under pathological conditions, detection of EBV-infected ECs in healthy conditions is very rare. In this study, a simple non-surgical tissue sampling procedure was used to investigate EBV infection in the periodontal epithelium that surrounds and attaches teeth to the gingiva. Surprisingly, we observed that the gingival ECs of the periodontium (pECs are commonly infected with EBV and may serve as an important oral reservoir of latently EBV-infected cells. We also found that the basal level of epithelial EBV-infection is significantly increased in chronic periodontitis, a common inflammatory disease that undermines the integrity of tooth-supporting tissues. Moreover, the level of EBV infection was found to correlate with disease severity. In inflamed tissues, EBV-infected pECs appear to be prone to apoptosis and to produce larger amounts of CCL20, a pivotal inflammatory chemokine that controls tissue infiltration by immune cells. Our discovery that the periodontal epithelium is a major site of latent EBV infection sheds a new light on EBV persistence in healthy carriers and on the role of this ubiquitous virus in periodontitis. Moreover, the identification of this easily accessible site of latent infection may encourage new approaches to investigate and monitor other EBV-associated disorders.

  16. Chronic diarrhea associated with Campylobacter jejuni infection in a cat.

    Science.gov (United States)

    Fox, J G; Claps, M; Beaucage, C M

    1986-08-15

    Campylobacter jejuni was isolated from a cat with chronic diarrhea. The diarrheic cat and another cat (which previously had diarrhea) in the same household had bactericidal antibody titers to the C jejuni. Clinical response to antibiotic therapy and not recovering Campylobacter sp from normal feces after treatment also supported the diagnosis of Campylobacter-associated diarrhea. Although the owner had a protracted episode of diarrhea, C jejuni was not isolated from the owner's feces, nor was a bactericidal antibody detected in the owner's serum.

  17. Factors Associated With Chronic Hepatitis in Patients With Hepatitis E Virus Infection Who Have Received Solid Organ Transplants

    NARCIS (Netherlands)

    Kamar, Nassim; Garrouste, Cyril; Haagsma, Elizabeth B.; Garrigue, Valerie; Pischke, Sven; Chauvet, Cecile; Dumortier, Jerome; Cannesson, Amelie; Cassuto-Viguier, Elisabeth; Thervet, Eric; Conti, Filomena; Lebray, Pascal; Dalton, Harry R.; Santella, Robert; Kanaan, Nada; Essig, Marie; Mousson, Christiane; Radenne, Sylvie; Roque-Afonso, Anne Marie; Izopet, Jacques; Rostaing, Lionel

    2011-01-01

    BACKGROUND & AIMS: Hepatitis E virus (HEV) infection can cause chronic hepatitis in recipients of solid organ transplants. However, the factors that contribute to chronic infection and the outcomes of these patients are incompletely understood. We performed a retrospective analysis of data from 17 c

  18. Impact of Helminth Infection on the Clinical and Microbiological Presentation of Chagas Diseases in Chronically Infected Patients.

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    Fernando Salvador

    2016-04-01

    Full Text Available Helminth infections are highly prevalent in tropical and subtropical countries, coexisting in Chagas disease endemic areas. Helminth infections in humans may modulate the host immune system, changing the Th1/Th2 polarization. This immunological disturbance could modify the immune response to other infections. The aim of this study is to evaluate the relationship between clinical, microbiological and epidemiological characteristics of Chagas disease patients, with the presence of helminth infection.A prospective observational study was conducted at Vall d'Hebron University Hospital (Barcelona, Spain. Inclusion criteria were: age over 18 years, diagnosis of Chagas disease, and not having received specific treatment for Chagas disease previously to the inclusion. The study protocol included Chagas disease assessment (cardiac and digestive evaluation, detection of T. cruzi DNA measured by PCR in peripheral blood, and helminth infection diagnosis (detection of IgG anti-Strongyloides stercoralis by ELISA, microscopic examination of stool samples from three different days, and specific faecal culture for S. stercoralis larvae.Overall, 65 patients were included, median age was 38 years, 75.4% were women and most of them came from Bolivia. Cardiac and digestive involvement was present in 18.5% and 27.7% of patients respectively. T. cruzi PCR was positive in 28 (43.1% patients. Helminth infection was diagnosed in 12 (18.5% patients. No differences were observed in clinical and epidemiological characteristics between patients with and without helminth infection. Nevertheless, the proportion of patients with positive T. cruzi PCR was higher among patients with helminth infection compared with patients without helminth infection (75% vs 35.8%, p = 0.021.We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated with significantly higher proportion of

  19. Sex influence on chronic intestinal inflammation in Helicobacter hepaticus-infected A/JCr mice.

    Science.gov (United States)

    Livingston, Robert S; Myles, Mathew H; Livingston, Beth A; Criley, Jennifer M; Franklin, Craig L

    2004-06-01

    Helicobacter hepaticus is a bacterial pathogen of mice that has been reported to cause chronic intestinal inflammation in A/JCr, germfree Swiss Webster, and immunodeficient mice. To the authors' knowledge, the influence of sex on development of chronic intestinal inflammation in H. hepaticus-infected mice has not been investigated. The purposes of the study reported here were to determine whether severity of intestinal inflammation differs between male and female A/JCr mice chronically infected with H. hepaticus and to characterize the mucosal immune response in these mice. The cecum of male and female A/JCr mice infected with H. hepaticus for 1 month and 3 months was objectively evaluated histologically for intestinal disease. Also, semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis was done to measure interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), IL-10, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-inducible protein of 10 kDa (IP-10), and monokine induced by gamma interferon (MIG) mRNA values in the cecal tissue of these mice. Significant differences in cecal lesion scores were not present at 1 month after infection. However, infected female mice had significantly up-regulated expression of cecal IL-10, MIP-1alpha, IP-10, and MIG mRNA compared with that in uninfected females, and expression of IL-10 and MIP-1alpha was significantly greater than that detected in infected male mice (P JCr mice, females develop more severe intestinal inflammation than do males, and the chronic mucosal inflammation is polarized toward a Th1 response that is not down-regulated by increased activity of IL-10. We propose that H. hepaticus-infected A/JCr mice will serve as a good animal model with which to study the influence of sex on bacterial-induced mucosal inflammation.

  20. Sofosbuvir: A novel treatment option for chronic hepatitis C infection

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    Harmeet Kaur Bhatia

    2014-01-01

    Full Text Available Hepatitis C currently infects more than 170 million people around the world, leading to significant morbidity and mortality. The current standard of care for HCV infection, including one of the two protease inhibitors, telaprevir or boceprevir, for 12-32 weeks, along with pegylated interferon alfa-2a (PEG-IFN-α and ribavirin for up to 48 weeks, is unsatisfactory in many cases, either because of lack of efficacy or because of treatment-related adverse effects. There is an urgent need of new drugs with improved efficacy as well as a safety profile. Sofosbuvir, a recently approved nucleotide analog, is a highly potent inhibitor of the NS5B polymerase in the Hepatitis C virus (HCV, and has shown high efficacy in combination with several other drugs, with and without PEG-INF, against HCV. It offers many advantages due to its high potency, low side effects, oral administration, and high barrier to resistance. The efficacy and safety were demonstrated in many large and well-designed phase 2 and phase 3 clinical trials like NEUTRINO, PROTON, ELECTRON, ATOMIC, COSMOS, FUSION, FISSION, NUCLEAR, POSITRON, and the like. It is generally well-tolerated. Adverse events that occurred include: Headache, insomnia, fatigue, nausea, dizziness, pruritis, upper respiratory tract infections, rash, back pain, grade 1 anemia, and grade 4 lymphopenia; however, the exact safety profile can only be judged when this drug is actually used on a large scale.

  1. Pseudomonas aeruginosa mutations in lasl and rhll quorum sensing systems result in milder chronic lung infection

    DEFF Research Database (Denmark)

    Wu, H.; Song, Z.J.; Givskov, Michael Christian;

    2001-01-01

    To understand the importance of quorum sensing in chronic Pseudomonas aeruginosa lung infection, the in vivo pathogenic effects of the wild-type P aeruginosa PAO1 and its double mutant, PAO1 lasI rhlI, in which the signal-generating parts of the quorum sensing systems are defective were compared....

  2. Recent advances in managing chronic HCV infection: Focus on therapy in patients with severe liver disease

    NARCIS (Netherlands)

    R. Maan (Raoel); A.J.P. van der Meer (Adriaan)

    2016-01-01

    textabstractChronic hepatitis C virus (HCV) infection still represents a major public health problem, as it is thought to be responsible for more than 350,000 deaths around the globe on a yearly basis. Fortunately, successful eradication of the virus has been associated with improved clinical outcom

  3. Strategies for Coping with Educational and Social Consequences of Chronic Ear Infections in Rural Communities.

    Science.gov (United States)

    Pillai, Patrick

    2000-01-01

    Children with chronic ear infections experience a lag time in understanding speech, which inhibits classroom participation and the ability to make friends, and ultimately reduces self-esteem. Difficulty in hearing affects speech and vocabulary development, reading and writing proficiency, and academic performance, and could lead to placement in…

  4. Melatonin and zinc treatment: distinctive modulation of cytokine production in chronic experimental Trypanosoma cruzi infection.

    Science.gov (United States)

    Brazão, Vânia; Del Vecchio Filipin, Marina; Santello, Fabricia Helena; Caetano, Leony Cristina; Abrahão, Ana Amélia Carraro; Toldo, Míriam Paula Alonso; do Prado, José Clóvis

    2011-12-01

    Melatonin by exhibiting antioxidant, anti-aging, and immunomodulatory properties favorably modulate the immune function, protecting the hosts from several infectious diseases. Zinc is an essential trace element important for the efficiency of the immune system in reason of its widespread role in the activity of enzymes, transcription factors and cytokines. The etiology of Chagas' disease, caused by a protozoan parasite Trypanosoma cruzi, has been the focus of considerable discussion, although chronic phase still remains not fully understood. This study showed that zinc and melatonin treatment did not affect the percentage of both CD4+ and CD8+ T lymphocytes subsets in chronically infected animals. Increased levels of IL-2 and IL-10, as well as, enhanced thymocyte proliferation in T. cruzi infected groups under zinc and melatonin therapy was observed as compared to untreated group. Conversely, during the chronic phase of infection, macrophages counts were reduced in melatonin and zinc-melatonin treated animals. The combined actions of zinc and melatonin have beneficial effects in counteracting parasite-induced immune dysregulation, protecting animals against the harmful actions of chronic T. cruzi infection. Furthermore, our results provide an experimental basis for further studies on the role of immunomodulatory therapies.

  5. Controlled trial of inhaled budesonide in patients with cystic fibrosis and chronic bronchopulmonary Psuedomonas aeruginosa infection

    DEFF Research Database (Denmark)

    Bisgaard, H; Pedersen, S S; Nielsen, K G;

    1997-01-01

    The efficacy and safety of anti-inflammatory treatment with inhaled glucocorticosteroids in patients with cystic fibrosis (CF) and complicating chronic Pseudomonas aeruginosa (P.a.) lung infection was studied in a placebo-controlled, parallel, double-blind single center trial. Active treatment...

  6. Isolated antibody to hepatitis B core antigen in patients with chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Ahmed Helmy; Mohammed Ibrahim Al-Sebayel

    2006-01-01

    AIM: To evaluate the prevalence of isolated anti-HBc in patients with chronic hepatitis C virus (HCV) infection,and its relation to disease severity.METHODS: We screened all patients with chronic HCV infection referred to King Faisal Specialist Hospital and Research Center for hepatitis B surface antigen (HBsAg), antibody to hepatitis B surface antigen (antiHBs), and anti-HBc. One hundred and sixty nine patients who tested negative for both HBsAg and anti-HBs were included in this study.RESULTS: Pathologically, 59 had biopsy-proven cirrhosis and 110 had chronic active hepatitis (CAH). Of these 169 patients, 85 (50.3%) tested positive for anti-HBc.Patients with CAH had significantly higher prevalence of isolated anti-HBc than patients with cirrhosis, 71 (64.5%)and 14 (23.7%) respectively (P < 0.001). Twenty-five patients were tested for HBV DNA by qualitative PCR.The test was positive in 3 of them (12%; occult HBV infection).CONCLUSION: Isolated anti-HBc alone is common in Saudi patients with chronic HCV infection, and is significantly more common in those with CAH than those with cirrhosis. Therefore, a screening strategy that only tests for HBsAg and anti-HBs in these patients will miss a large number of individuals with isolated anti-HBc, who may be potentially infectious.

  7. The microorganisms in chronically infected end-stage and non-end-stage cystic fibrosis patients

    DEFF Research Database (Denmark)

    Rudkjøbing, Vibeke Børsholt; Thomsen, Trine Rolighed; Alhede, Morten;

    2012-01-01

    Patients suffering from cystic fibrosis (CF) develop chronic lung infections because of highly viscous mucus, where bacteria can form biofilms. In this study, we investigated the microorganisms present in the lungs of end-stage and non-end-stage patients using standard culturing techniques and mo...

  8. RESPIRATORY VIRAL-INFECTIONS AGGRAVATE AIRWAY DAMAGE CAUSED BY CHRONIC REJECTION IN RAT LUNG ALLOGRAFTS

    NARCIS (Netherlands)

    WINTER, JB; GOUW, ASH; GROEN, M; WILDEVUUR, C; PROP, J

    1994-01-01

    Airway damage resulting in bronchiolitis obliterans occurs frequently in patients after heart-lung and lung transplantation. Generally, chronic rejection is assumed to be the most important cause of bronchiolitis obliterans. However, viral infections might also be potential causes of airway damage a

  9. Giant cell arteritis associated with chronic active Epstein-Barr virus infection

    Directory of Open Access Journals (Sweden)

    A. Giardina

    2013-03-01

    Full Text Available Giant cell arteritis is an inflammatory vasculopathy that preferentially affects medium-sized and large arteries. A viral cause has been suspected but not confirmed in polymyalgia rheumatica and giant-cell arteritis. We report the case of a 81-year-old female who suffered from chronic active Epstein-Barr virus infection and developed giant cell temporal arteritis.

  10. Molecular epidemiology of chronic Pseudomonas aeruginosa airway infections in cystic fibrosis

    DEFF Research Database (Denmark)

    Cramer, Nina; Wiehlmann, Lutz; Ciofu, Oana

    2012-01-01

    The molecular epidemiology of the chronic airway infections with Pseudomonas aeruginosa in individuals with cystic fibrosis (CF) was investigated by cross-sectional analysis of bacterial isolates from 51 CF centers and by longitudinal analysis of serial isolates which had been collected at the CF...

  11. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Saeko; Cologne, John; Akahoshi, Masazumi [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, Shizuyo [Institute of Radiation Epidemiology, Radiation Effects Association, Tokyo (Japan); Kodama, Kazunori; Yoshizawa, Hiroshi [Hiroshima University School of Medicine, Hiroshima (Japan)

    2000-05-01

    Hepatitis C and B virus (HCV, HBV) infection plays a crucial role in the etiology of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have been reported to increase with radiation dose among the atomic bomb survivors. The purpose of this study is to investigate whether radiation exposure altered the prevalence of hepatitis virus infection or accelerated the progress toward chronic hepatitis after hepatitis virus infection. Levels of serum antibody to hepatitis C virus (anti-HCV), HBs antigen (HBsAg), and anti-HBs antibody (anti-HBs) were measured for 6,121 participants in the Adult Health Study of atomic bomb survivors in Hiroshima and Nagasaki. No relationship was found between anti-HCV prevalence and radiation dose, after adjusting for age, sex, city, history of blood transfusion, acupuncture, and family history, but prevalence of anti-HCV was significantly lower overall among the radiation-exposed people (relative prevalence 0.84, p=0.022) compared to people with estimated radiation dose 0 Gy. No significant interaction was found between any of the above mentioned risk factors and radiation dose. People with anti-HCV positive had 13 times higher prevalence of chronic liver disease than those without anti-HCV. However, the radiation dose response for chronic liver disease among anti-HCV positive survivors may be greater than that among anti-HCV negative survivors (slope ratio 20), but the difference was marginally significant (p=0.097). Prevalence of HBsAg increased with whole-body kerma. However, no trend with radiation dose was found in the anti-HBs prevalence. In the background, prevalence of chronic liver disease in people with HBsAg-positive was approximately three times higher that in those without HBsAg. No difference in slope of the dose was found among HBsAg positive and negative individuals (slope: HBsAg positive 0.91/Gy, HBsAg negative 0.11/Gy, difference p=0.66). In conclusion, no dose-response relationship was found between

  12. Clinical and morphological characteristics of chronic uretheroprostatitis associated with chlamydial and mycoplasmal infections

    Directory of Open Access Journals (Sweden)

    Yu. S. Kondratyeva

    2012-01-01

    Full Text Available The purpose of this study was to investigate the clinical symptoms, features of morphological structure of prostate in patients with chronic recurrent prostatitis associated with chlamydial and mycoplasmal infections. 60 male patients were examined. Anamnesis and interview data, results of laboratory and instrumental tests were analyzed. In 73.3% of cases cultural test and PCR allowed to identify M. hominis, U. urealiticum, M. genitalium, C. trachomatis in patients with chronic uretheroprostatitis. Out of 16 patients (26,6% of all examined with chronic recurrent uretheroprostatitis for whom neither chlamidial nor mycoplasmal infection was diagnosed by laboratory tests, for 14 patients (87,5% it was confirmed that patogenic urogenital infectious agents were localized intracellularly. Pathomorphological investigation of prostate bioptates allowed to estimate the type and degree of specific changes in the prostate tissue in cases of recurrent uretheroprostatitis resistant to the therapy and with frequent relapses.

  13. [THE ROLE OF SYSTEM QUORUM SENSING UNDER CHRONIC UROGENITAL CHLAMYDIA INFECTION].

    Science.gov (United States)

    2015-10-01

    It is established that system quorum sensing (QS) assure social behavior of bacteria in regulation of genes of virulence and generalization of inflectional inflammatory process under chronic urogenital chlamydia infection. The techniques of gas chromatography and mass-spectrometry were applied to detect molecular markers of generalization of infectious process under urogenital chlamydiasis--activators of QS microbes (lactones, quinolones, furan ethers). The developed diagnostic gas chromatography and mass-spectrometry criteria of indexation of molecular markers under chronic urogenital chlamydia infection have high level of diagnostic sensitivity, specificity and prognostic value of positive and negative result. The application of techniques of gas chromatography and mass-spectrometry permits enhancing effectiveness of diagnostic of chronic inflectional inflammatory diseases of urogenital system of chlamydia etiology with identification of prognostic criteria of generalization of infectious process and subsequent prescription of timely and appropriate therapy

  14. SPF rabbits infected with rabbit hepatitis E virus isolate experimentally showing the chronicity of hepatitis.

    Science.gov (United States)

    Han, Jian; Lei, Yaxin; Liu, Lin; Liu, Peng; Xia, Junke; Zhang, Yulin; Zeng, Hang; Wang, Lin; Wang, Ling; Zhuang, Hui

    2014-01-01

    This study focused on investigating the pathogenesis seen in specific-pathogen-free (SPF) rabbits following infection with a homologous rabbit HEV isolate (CHN-BJ-rb14) and comparing it to that seen following infection with a heterologous swine genotype 4 HEV isolate (CHN-XJ-SW13). Three of the four animals inoculated with the homologous rabbit HEV became infected, exhibiting an intermittent viremia, obvious fluctuations of liver function biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and persistent fecal virus shedding throughout the nine month study. In addition, liver histopathology showed both chronic inflammation and some degree of fibrosis. Both positive and negative-stranded HEV RNA and HEV antigen expression were detected in liver, brain, stomach, duodenum and kidney from the necropsied rabbits. Inflammation of extrahepatic tissue (duodenum and kidney) was also observed. Three of the four rabbits inoculated with the heterologous genotype 4 swine HEV also became infected, showing similar levels of anti-HEV antibody to that generated following infection with the homologous virus isolate. The duration of both viremia and fecal shedding of virus was however shorter following infection with the heterologous virus and there was no significant elevation of liver function biomarkers. These results suggest that rabbit HEV infection may cause more severe hepatitis and prolong the course of the disease, with a possible chronic trend of hepatitis in SPF rabbits.

  15. Chronic Schistosoma japonicum infection reduces immune response to vaccine against hepatitis B in mice.

    Directory of Open Access Journals (Sweden)

    Lin Chen

    Full Text Available BACKGROUND: Hepatitis B and schistosomiasis are most prevalent in Africa and Asia, and co-infections of both are frequent in these areas. The immunomodulation reported to be induced by schistosome infections might restrict immune control of hepatitis B virus (HBV leading to more severe viral infection. Vaccination is the most effective measure to control and prevent HBV infection, but there is evidence for a reduced immune response to the vaccine in patients with chronic schistosomiasis japonica. METHODOLOGY/PRINCIPAL FINDINGS: In this paper, we demonstrate in a mouse model that a chronic Schistosoma japonicum infection can inhibit the immune response to hepatitis B vaccine (HBV vaccine and lead to lower production of anti-HBs antibodies, interferon-γ (IFN-γ and interleukin-2 (IL-2. After deworming with Praziquantel (PZQ, the level of anti-HBs antibodies gradually increased and the Th2-biased profile slowly tapered. At 16 weeks after deworming, the levels of anti-HBs antibodies and Th1/Th2 cytokines returned to the normal levels. CONCLUSIONS/SIGNIFICANCE: The results suggest that the preexisting Th2-dominated immune profile in the host infected with the parasite may down-regulate levels of anti-HBs antibodies and Th1 cytokines. To improve the efficacy of HBV vaccination in schistosome infected humans it may be valuable to treat them with praziquantel (PZQ some time prior to HBV vaccination.

  16. Insulin resistance, steatosis, and fibrosis in Egyptian patients with chronic Hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Ahlam M Ahmed

    2011-01-01

    Full Text Available Background/Aim: Both nonalcoholic fatty liver disease (NAFLD and chronic hepatitis C virus (HCV infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC (necroinflammation and fibrosis and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection. Patients and Methods: Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. Results: Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST level were 42 ± 7.7 years (range 20-56 and 68 ± 41.7 U/L (range 16-214, respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4 and 5.9 ± 15.2 (range 0.9-136.2, respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis. Conclusions: Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.

  17. Therapy with bone marrow cells reduces liver alterations in mice chronically infected by Schistosoma mansoni

    Institute of Scientific and Technical Information of China (English)

    Sheilla Andrade Oliveira; Bruno Solano Freitas Souza; Cada Adriana Guimar(a)es-Ferreira; Elton Sá Barreto; Siane Campos Souza; Luiz Antonio Rodrigues Freitas; Ricardo Ribeiro-dos-Santos; Milena Botelho Pereira Soares

    2008-01-01

    AIM: To investigate the potential of bone marrow mononuclear cells (BM-MCs) in the regeneration of hepatic lesions induced by Schistosoma mansoni (S.mansoni) chronic infection.METHODS: Female mice chronically infected with S.mansoni were treated with BM-MCs obtained from male green fluorescent protein (GFP) transgenic mice by intravenous or intralobular injections. Control mice received injections of saline in similar conditions. Enzyme-linked immunosorbent assay (ELISA) assay for transforming growth factor-beta (TGF-β), polymerase chain reaction (PCR) for GFP DNA, immunofluorescence and morphometric studies were performed.RESULTS: Transplanted GFP+ cells migrated to granuloma areas and reduced the percentage of liver fibrosis. The presence of donor-derived cells was confirmed by Fluorescence in situ hybridization (FISH) analysis for detection of cells bearing Y chromosome and by PCR analysis for detection of GFP DNA. The levels of TGF-β, a cytokine associated with fibrosis deposition, in liver fragments of mice submitted to therapy were reduced. The number of oval cells in liver sections of S.rnansoni-infected mice increased 3-4 fold after transplantation. A partial recovery in albumin expression, which is decreased upon infection with S.mansoni, was found in livers of infected mice after cellular therapy.CONCLUSION: In conclusion, transplanted BMCs migrate to and reduce the damage of chronic fibrotic liver lesions caused by S.mansoni.

  18. Chronic hepatitis virus infection in patients with multiple myeloma: clinical characteristics and outcomes

    Directory of Open Access Journals (Sweden)

    Chung-Jen Teng

    2011-01-01

    Full Text Available OBJECTIVES: Cytotoxic agents and steroids are used to treat lymphoid malignancies, but these compounds may exacerbate chronic viral hepatitis. For patients with multiple myeloma, the impact of preexisting hepatitis virus infection is unclear. The aim of this study is to explore the characteristics and outcomes of myeloma patients with chronic hepatitis virus infection. METHODS: From 2003 to 2008, 155 myeloma patients were examined to determine their chronic hepatitis virus infection statuses using serologic tests for the hepatitis B (HBV and C viruses (HCV. Clinical parameters and outcome variables were retrieved via a medical chart review. RESULTS: The estimated prevalences of chronic HBV and HCV infections were 11.0% (n = 17 and 9.0% (n = 14, respectively. The characteristics of patients who were hepatitis virus carriers and those who were not were similar. However, carrier patients had a higher prevalence of conventional cytogenetic abnormalities (64.3% vs. 25.0%. The cumulative incidences of grade 3-4 elevation of the level of alanine transaminase, 30.0% vs. 12.0%, and hyperbilirubinemia, 20.0% vs. 1.6%, were higher in carriers as well. In a Kaplan-Meier analysis, carrier patients had worse overall survival (median: 16.0 vs. 42.4 months. The prognostic value of carrier status was not statistically significant in the multivariate analysis, but an age of more than 65 years old, the presence of cytogenetic abnormalities, a beta-2-microglobulin level of more than 3.5 mg/L, and a serum creatinine level of more than 2 mg/ dL were independent factors associated with poor prognosis. CONCLUSION: Myeloma patients with chronic hepatitis virus infections might be a distinct subgroup, and close monitoring of hepatic adverse events should be mandatory.

  19. Increased interleukin-18 in the gingival tissues evokes chronic periodontitis after bacterial infection.

    Science.gov (United States)

    Yoshinaka, Kotaro; Shoji, Noriaki; Nishioka, Takashi; Sugawara, Yumiko; Hoshino, Tomoaki; Sugawara, Shunji; Sasano, Takashi

    2014-01-01

    Periodontal disease is a chronic inflammatory disease that results in the breakdown of the tooth-supporting tissues, and can ultimately lead to resorption of the alveolar bone. Recently, several studies have shown a close relationship between increased interleukin-18 (IL-18) levels and the pathogenesis of chronic periodontitis, a major cause of tooth loss. However, it has yet to be shown whether chronic periodontitis results from or causes an increase in IL-18 after bacterial infection. In the present study, we investigated how IL-18 overexpression relates to periodontal disease using IL-18 transgenic (Tg) mice. IL-18Tg and wild-type mice were inoculated intraorally with Porphyromonas (P.) gingivalis, which has been implicated in the etiology of chronic periodontitis. Seventy days after P. gingivalis infection, alveolar bone loss and gingival cytokine levels were assessed using histo-morphological analysis and enzyme-linked immuno-absorbent assay, respectively. Periodontal bone loss was evoked in IL-18Tg mice, but not in wild-type mice. Interestingly, levels of bone-resorptive cytokines, including IL-1α, IL-1β, tumor necrosis factor-α, and IL-6, were unchanged in the gingival tissues of IL-18Tg mice infected with P. gingivalis, although levels of interferon γ (a proinflammatory T-helper 1 cytokine) decreased. RT-PCR analysis showed elevated expression of mRNAs for receptor activator of nuclear factor kappa-B ligand (a key stimulator of osteoclast development and activation) and CD40 ligand (a marker of T cell activation) in the gingiva of IL-18Tg mice infected with P. gingivalis. We conclude that increased IL-18 in the gingival tissues evokes chronic periodontitis after bacterial infection, presumably via a T cell-mediated pathway.

  20. Lack of indinavir-associated nephrological complications in HIV-infected adults (predominantly women) with high indinavir plasma concentration in Abidjan, Côte d'Ivoire.

    Science.gov (United States)

    Danel, Christine; Moh, Raoul; Peytavin, Gilles; Anzian, Amani; Minga, Albert; Gomis, Olivier Ba; Seri, Boga; Nzunettu, Gustave; Gabillard, Delphine; Salamon, Roger; Bissagnene, Emmanuel; Anglaret, Xavier

    2007-01-01

    To report the tolerance of indinavir combined with ritonavir (IDV/r 800/100 mg) twice daily (bid) in sub-Saharan African HIV-infected adults. HAART-naives patients started zidovudine plus lamivudine plus IDV/r 800/100 mg bid. Follow-up included standardized documentation of morbidity, CD4(+) cell count, creatininemia, plasma HIV-1 RNA, and IDV minimal plasma concentration (C(min)) measurements at month 1 (M1), M3, and M6. Seventy HIV-1-infected adults (68 women, median CD4 235/mm(3)) started HAART. At M6, 63% had undetectable viral load, and the median gain in CD4 since baseline was +128/mm(3). During the first 6 months, 21 patients experimented with 23 treatment modifications (reduction in IDV/r 400/100 mg bid, n = 11; switch to efavirenz, n = 11; zidovudine replaced by stavudine, n = 1), including 22 for digestive intolerance and 1 for severe anemia. At M1, M3, and M6, 67, 59, and 48 patients were still receiving IDV/r 800/100 mg bid, of whom 70%, 72%, and 60% had IDV Cmin above 5 ng/ml, respectively. In these patients, at M1, M3, and M6, the mean (+/- SD) IDV C(min) were 3431 +/- 3835 ng/ml, 2288 +/- 2116 ng/ml, and 1543 +/- 2398 ng/ml, respectively. There was no renal insufficiency of any grade, and no symptoms of urinary stones. The IDV/r 800/100 mg bid-containing regimen led to high IDV Cmin and a high rate of digestive intolerance. There was a surprising lack of nephrological side effects during the 6 months of follow-up, supporting the hypothesis that nephrological tolerance of IDV might be higher in sub-Saharan African individuals than in Americans or Europeans.

  1. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection.

    Science.gov (United States)

    Vitozzi, Susana; Lapierre, Pascal; Djilali-Saiah, Idriss; Marceau, Gabriel; Beland, Kathie; Alvarez, Fernando

    2004-05-01

    Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation.

  2. Comparison of antibody repertoires produced by HIV-1 infection, other chronic and acute infections, and systemic autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Felix Breden

    Full Text Available BACKGROUND: Antibodies (Abs produced during HIV-1 infection rarely neutralize a broad range of viral isolates; only eight broadly-neutralizing (bNt monoclonal (MAbs have been isolated. Yet, to be effective, an HIV-1 vaccine may have to elicit the essential features of these MAbs. The V genes of all of these bNt MAbs are highly somatically mutated, and the V(H genes of five of them encode a long (≥ 20 aa third complementarity-determining region (CDR-H3. This led us to question whether long CDR-H3s and high levels of somatic mutation (SM are a preferred feature of anti-HIV bNt MAbs, or if other adaptive immune responses elicit them in general. METHODOLOGY AND PRINCIPAL FINDINGS: We assembled a V(H-gene sequence database from over 700 human MAbs of known antigen specificity isolated from chronic (viral infections (ChI, acute (bacterial and viral infections (AcI, and systemic autoimmune diseases (SAD, and compared their CDR-H3 length, number of SMs and germline V(H-gene usage. We found that anti-HIV Abs, regardless of their neutralization breadth, tended to have long CDR-H3s and high numbers of SMs. However, these features were also common among Abs associated with other chronic viral infections. In contrast, Abs from acute viral infections (but not bacterial infections tended to have relatively short CDR-H3s and a low number of SMs, whereas SAD Abs were generally intermediate in CDR-H3 length and number of SMs. Analysis of V(H gene usage showed that ChI Abs also tended to favor distal germline V(H-genes (particularly V(H1-69, especially in Abs bearing long CDR-H3s. CONCLUSIONS AND SIGNIFICANCE: The striking difference between the Abs produced during chronic vs. acute viral infection suggests that Abs bearing long CDR-H3s, high levels of SM and V(H1-69 gene usage may be preferentially selected during persistent infection.

  3. Comparative genomics of isolates of a Pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients.

    Directory of Open Access Journals (Sweden)

    Julie Jeukens

    Full Text Available Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF. During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES from the United Kingdom and Canada representing different virulence characteristics in order to: (1 associate comparative genomics results with virulence factor variability and (2 identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung.

  4. Infections

    Science.gov (United States)

    ... Does My Child Need? How to Safely Give Acetaminophen Is It a Cold or the Flu? Is the Flu Vaccine a Good Idea for Your Family? Too Late for the Flu Vaccine? Common Childhood Infections Can Chronic Ear Infections Cause Long-Term Hearing Loss? Chickenpox Cold Sores Common Cold Diarrhea Fever and ...

  5. Sofosbuvir for the treatment of chronic hepatitis C virus infection.

    Science.gov (United States)

    Temesgen, Z; Talwani, R; Rizza, S A

    2014-06-01

    Sofosbuvir is a nucleotide analogue selective inhibitor of the RNA-directed RNA polymerase (NS5B) enzyme of the hepatitis C virus (HCV) genome. It has shown potent antiviral activity across all HCV genotypes and in a variety of patient populations, including treatment-naive patients; treatment-experienced patients who had failed previous standard therapy; patients with decompensated liver disease, including cirrhosis; and HIV co-infected patients. It is administered as a single, once-daily 400-mg tablet, has no food restrictions, has low potential for drug interactions, and requires no dose adjustment in mild to moderate kidney or liver impairment. When sofosbuvir is combined with pegylated interferon and/or ribavirin, its clinical and laboratory safety profile is similar to that which is expected from pegylated interferon or ribavirin alone. Rates of treatment discontinuation and dose reduction with sofosbuvir-containing regimens were lower than those commonly observed with pegylated interferon and ribavirin.

  6. Rare inborn errors associated with chronic hepatitis B virus infection

    DEFF Research Database (Denmark)

    Zhao, Qiang; Peng, Liang; Huang, Weijun

    2012-01-01

    Chronic hepatitis B (CHB) is a major global health issue. The role of rare genetic variants in CHB has not been elucidated. We aimed to identify rare allelic variants predisposing to CHB. We performed exome sequencing in 50 CHB patients who had no identifiable risk factors for CHB and 40 controls...... who were healthy and hepatitis B surface antibody-positive, but had never received hepatitis B vaccination. We selected six rare variant alleles and followed up their association with disease status by Sanger sequencing in a case-control study comprising 1,728 CHB patients and 1,636 healthy controls....... The latter had either not been immunized with hepatitis B vaccine or had uncertain vaccination status. Our results showed that transmembrane protein 2 p.Ser1254Asn, interferon alpha 2 p.Ala120Thr, its regulator NLR family member X1 p.Arg707Cys, and complement component 2 p.Glu318Asp were associated with CHB...

  7. Dendritic cells: The warriors upfront-turned defunct in chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Meenakshi; Sachdeva; Yogesh; K; Chawla; Sunil; K; Arora

    2015-01-01

    Hepatitis C virus(HCV) infection causes tremendousmorbidity and mortality with over 170 million people infected worldwide. HCV gives rise to a sustained, chronic disease in the majority of infected individuals owing to a failure of the host immune system to clear the virus. In general, an adequate immune response is elicited by an efficient antigen presentation by dendritic cells(DCs), the cells that connect innate and adaptive immune system to generate a specific immune response against a pathogen. However, HCV seems to dysregulate the activity of DCs, making them less proficient antigen presenting cells for the optimal stimulation of virusspecific T cells, hence interfering with an optimal antiviral immune response. There are discordant reports on the functional status of DCs in chronic HCV infection(CHC), from no phenotypic or functional defects to abnormal functions of DCs. Furthermore, the molecular mechanisms behind the impairment of DC function are even so not completely elucidated during CHC. Understanding the mechanisms of immune dysfunction would help in devising strategies for better management of the disease at the immunological level and help to predict the prognosis of the disease in the patients receiving antiviral therapy. In this review, we have discussed the outcomes of the interaction of DCs with HCV and the mechanisms of DC impairment during HCV infection with its adverse effects on the immune response in the infected host.

  8. Polymerase Chain Reaction: A Better Method for Diagnosing Chronic Schistosoma mansoni Infections.

    Science.gov (United States)

    Abdel-Hafeez, Ekhlas Hamed; Mohamed, Rabie M; Belal, Usama S; Abdel-Raheem, Ehab M; Naoi, Koji; Norose, Kazumi

    2015-12-01

    For more effective diagnosis of the acute and chronic stages of Schistosoma mansoni infection in humans, the polymerase chain reaction (PCR) technique was compared with the Kato-Katz method. A total of 150 stool samples were collected from inpatient and outpatient clinics at the Department of Tropical Medicine, Minia University Hospital, Egypt. Three groups of patients, 50 with acute intestinal schistosomiasis, 70 with chronic intestinal schistosomiasis and 30 normal healthy controls were studied. Stool samples were analyzed by PCR and the Kato-Katz method. The mean number of eggs per gram of feces was 4.6 when estimated by the Kato-Katz method in positive stool samples from acute schistosomiasis cases but only 1.7 in chronic cases. In acute intestinal schistosomiasis, 15 and 45 out of 50 cases were positive by Kato-Katz and PCR, respectively. In the chronic intestinal schistosomiasis cases, 6 and 68 out of 70 cases were positive by the Kato-Katz and PCR methods, respectively. We conclude that PCR appears to be an effective diagnostic technique for S. mansoni infection, especially where a low worm burden exists, such as in chronic cases.

  9. Cytokine profiles and hepatic injury in occult hepatitis C versus chronic hepatitis C virus infection.

    Science.gov (United States)

    Mousa, N; Eldars, W; Eldegla, H; Fouda, O; Gad, Y; Abousamra, N; Elmasry, E; Arafa, M

    2014-01-01

    Occult hepatitis C virus (HCV) infection is a new entity that should be considered when diagnosing patients with abnormal liver functions of unknown origin. This work was carried out to evaluate T-helper 1/T-helper 2 (Th1/Th2) cytokine profiles in patients with occult HCV infection versus chronic hepatitis C (CHC) infection, also to investigate any association between theses cytokines and liver histological features in both groups. Serum levels of Th1 cytokines (IL-2, IFN-gamma) and Th2 (IL-4 and IL-10) were measured in 35 patients with occult HCV infection compared to 50 patients with chronic hepatitis C infection and 30 healthy controls. We have found that Th1 cytokines were significantly increased in patients with CHC infection than in both occult HCV infection and control groups (p less than 0.001). On the other hand, serum IL-4 levels were higher in occult HCV infection than in CHC and control groups (p less than 0.001). Furthermore, serum IL-10 levels were higher in both patient groups vs control group (pless than 0.001), with no significant difference between CHC and occult HCV groups. Finally, only serum IL-10 levels were significantly higher among patients with high activity (A2-A3) than those with low activity (A0-A1) in both CHC and occult HCV groups (p=0.038, p=0.025, respectively). Patients with occult HCV infection exhibited a distinct immunoregulatory cytokine pattern that is shifted towards the Th2 arm.

  10. The presence of Chronic Bee Paralysis Virus infection in Honey bees (Apis mellifera L.) in the U.S.

    Science.gov (United States)

    The presence of Chronic bee paralysis virus (CBPV) infection in the U.S. is reported for the first time. Using molecular methods, the evidence of infection of honey bees with CBPV has been detected in both symptomatic and asymptomatic bees. While our seven year’s survey showed that the CBPV infect...

  11. CD58 expression of liver tissue in patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    WANG Ping; QI Bao-tai; CHEN Ping; HE Lin-jing; LI Jie; JI Yu-qiang; XIE Ming

    2008-01-01

    Background Several kinds of intercellular adhesion molecules closely relate to hepatitis B.The complex of CD2 and CD58 plays an important role in enhancing the adhesion of T lymphocytes to target cells,hyperplasia and activation of T lymphocytes.In this study,we explored the relationship between the expression of CD58 in liver tissue and chronic hepatitus B infection.Methods We determined the expression of the CD58 molecule on the surface of hepatocytes by using immunohistochemistry and the levels of serum HBV DNA from patients with HBV infection and from normal controls.The biochemical parameters of hepatic function were analyzed as well.Results CD58 expression in hepatocytes significantly increased with the severity progression of chronic HBV infection.The IOD levels(1og10)of CD58 in the control,mild,moderate,and severe chronic HBV infection groups were O,(7.20±4.64)×103,(25.63±7.41)x103 and(37.47±11.17)×103 respectively(P<0.05 compared with the control group,respectively)Conclusion CD58 probably increases cell mediated immunity to eliminate hepatitis B virus and leads to damage of hepatocytes.

  12. New horizon for radical cure of chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    Kazuto; Tajiri; Yukihiro; Shimizu

    2016-01-01

    About 250 to 350 million people worldwide are chronically infected with hepatitis B virus(HBV), and about 700000 patients per year die of HBV-related cirrhosis or hepatocellular carcinoma(HCC). Several anti-viral agents, such as interferon and nucleos(t)ide analogues(NAs), have been used to treat this disease. NAs especially have been shown to strongly suppress HBV replication, slowing the progression to cirrhosis and the development of HCC. However, reactivation of HBV replication often occurs after cessation of treatment, because NAs alone cannot completely remove covalentlyclosed circular DNA(ccc DNA), the template of HBV replication, from the nuclei of hepatocytes. Anti-HBV immune responses, in conjunction with interferon-γ and tumor necrosis factor-α, were found to eliminate ccc DNA, but complete eradication of ccc DNA by immune response alone is difficult, as shown in patients who recover from acute HBV infection but often show long-term persistence of small amounts of HBV-DNA in the blood. Several new drugs interfering with the life cycle of HBV in hepatocytes have been developed, with drugs targeting ccc DNA theoretically the most effective for radical cure of chronic HBV infection. However, the safety of these drugs should be extensively examined before application to patients, and combinations of several approaches may be necessary for radical cure of chronic HBV infection.

  13. Fibrosis assessment in patients with chronic hepatitis B virus (HBV) infection

    Science.gov (United States)

    Parikh, Pathik; Ryan, John D.

    2017-01-01

    Chronic hepatitis B virus (HBV) infection is a major cause of liver morbidity and mortality worldwide. While a proportion of the 250 million individuals chronically infected with HBV will not come to significant harm or require therapy, many others risk developing complications of the end-stage liver disease such as decompensated cirrhosis and hepatocellular carcinoma (HCC), without intervention. Due to the complex natural history of HBV infection, patients require an expert assessment to interpret biochemistry, viral serology and appropriately stage the disease, and to initiate monitoring and/or therapy where indicated. The detection and quantification of liver fibrosis is a key factor for disease management and prognostication for an individual with HBV. The reliance on invasive liver biopsy to stage disease is diminishing with the advent of robust non-invasive blood- and imaging-based algorithms which can reliably stage disease in many cases. These tests are now incorporated into International guidelines for HBV management and relied upon daily to inform clinical judgement. Both blood- and imaging-based approaches have advantages over liver biopsy, including minimal risks, lower cost, better patient acceptance and speed of results, while disadvantages include lower diagnostic accuracy in intermediate disease stages and variability with co-existing hepatic inflammation or steatosis. This review outlines the methods of fibrosis assessment in chronic HBV infection and focuses on the most commonly used blood- and imaging-based non-invasive tests, reviewing their diagnostic performance and applicability to patient care. PMID:28251119

  14. Risk Factors for Hepatitis C Virus Infection in Canadian Patients with Chronic Type C Hepatitis

    Directory of Open Access Journals (Sweden)

    GY Minuk

    1995-01-01

    Full Text Available Previous reports from the United States indicate that as many as 40% of patients with chronic hepatitis C virus (HCV have no identifiable risk factor for HCV infection. To determine whether the same is true of Canadian patients with chronic HCV the records of 89 anti-HCV positive patients referred to the authors' tertiary care centre for evaluation of liver disease were reviewed. Each patient had been specifically asked about the following risk factors: previous blood transfusions; intravenous drug abuse; homosexual activity; sexual promiscuity (multiple sexual partners or a history of sexually transmitted diseases; tattoos made with nonsterile techniques; and ear piercing using nonsterile techniques. The results of the study revealed that 76 of 89 patients (85% had at least one risk factor for HCV exposure, 38 (43% had only one risk factor, 19 (21% had two, 12 (14% had three and the remaining three patients (3% had four. The most common risk factor was a history of intravenous drug abuse (30 of 89 patients, 34% followed by sexual promiscuity (28, 32%, previous blood transfusions (21, 24%, tattoos (17, 19%, homosexual contacts (seven, 8% and ear piercing (five, 6%. Contrary to a recent report identifying sexual contact as an independent risk factor for HCV infection, only four cases (5% were found where sexual promiscuity was identified as the only risk factor. In conclusion, these findings indicate that a possible source of HCV infection can be identified in a large majority of Canadians referred to an urban centre with chronic HCV infection.

  15. 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.

  16. Chronic Opisthorchis viverrini Infection Changes the Liver Microbiome and Promotes Helicobacter Growth

    Science.gov (United States)

    Itthitaetrakool, Upsornsawan; Pinlaor, Porntip; Pinlaor, Somchai; Chomvarin, Chariya; Dangtakot, Rungtiwa; Chaidee, Apisit; Wilailuckana, Chotechana; Sangka, Arunnee; Lulitanond, Aroonlug; Yongvanit, Puangrat

    2016-01-01

    Adults of Opisthorchis viverrini reside in the biliary system, inducing inflammation of bile ducts and cholangitis, leading to hepatobiliary disease (HBD) including cholangiocarcinoma. O. viverrini infection also has major implications for the bacterial community in bile ducts and liver. To investigate this in chronic O. viverrini infection (≥ 8 months p.i.), bacterial genomic DNA from livers of hamsters and from worms was investigated using culture techniques, PCR for Helicobacter spp. and high-throughput next-generation sequencing targeting the V3-V4 hypervariable regions of prokaryotic 16S rRNA gene. Of a total of 855,046 DNA sequence reads, 417,953 were useable after filtering. Metagenomic analyses assigned these to 93 operational taxonomic units (OTUs) consisting of 80 OTUs of bacteria, including 6 phyla and 42 genera. In the chronic O. viverrini-infected group, bacterial community composition and diversity were significantly increased compared to controls. Sequences of Fusobacterium spp. were the most common (13.81%), followed by Streptococcus luteciae (10.76%), Escherichia coli (10.18%), and Bifidobacterium spp. (0.58%). In addition, Helicobacter pylori (0.17% of sequences) was also identified in the liver of chronic O. viverrini infections, but not in normal liver. The presence of H. pylori was confirmed by PCR and by use of an antibody against bacterial antigen, supporting the metagenomics data. The identities of bacteria cultured for enrichment suggested that chronic O. viverrini infection changes the liver microbiome and promotes Helicobacter spp. growth. There may be synergy between O. viverrini and the liver microbiome in enhancing immune response-mediated hepatobiliary diseases. PMID:27806126

  17. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

    DEFF Research Database (Denmark)

    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S....... In the current study genetic adaptation during experimental chronic S. Typhimurium infections of mice, an established model of chronic typhoid fever, was probed as an approach for studying the molecular mechanisms of host-adaptation during long-term host-association. Results Individually sequence-tagged wild...

  18. Hepatitis C virus infection in Argentina: Burden of chronic disease

    Institute of Scientific and Technical Information of China (English)

    Ezequiel; Ridruejo; Fernando; Bessone; Jorge; R; Daruich; Chris; Estes; Adrián; C; Gadano; Homie; Razavi; Federico; G; Villamil; Marcelo; O; Silva

    2016-01-01

    AIM: To estimate the progression of the hepatitis C virus(HCV) epidemic and measure the burden of HCVrelated morbidity and mortality. METHODS: Age- and gender-defined cohorts were used to follow the viremic population in Argentina and estimate HCV incidence, prevalence, hepatic complications, and mortality. The relative impact of two scenarios on HCV-related outcomes was assessed:(1) increased sustained virologic response(SVR); and(2) increased SVR and treatment.RESULTS: Under scenario 1, SVR raised to 85%-95% in 2016. Compared to the base case scenario, there was a 0.3% reduction in prevalent cases and liverrelated deaths by 2030. Given low treatment rates, cases of hepatocellular carcinoma and decompensated cirrhosis decreased < 1%, in contrast to the base case in 2030. Under scenario 2, the same increases in SVR were modeled, with gradual increases in the annual diagnosed and treated populations. This scenario decreased prevalent infections 45%, liver-related deaths 55%, liver cancer cases 60%, and decompensated cirrhosis 55%, as compared to the base case by 2030. CONCLUSION: In Argentina, cases of end stage liver disease and liver-related deaths due to HCV are still growing, while its prevalence is decreasing. Increasing in SVR rates is not enough, and increasing in the number of patients diagnosed and candidates for treatment is needed to reduce the HCV disease burden. Based on this scenario, strategies to increase diagnosis and treatment uptake must be developed to reduce HCV burden in Argentina.

  19. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Science.gov (United States)

    Beck, Zoltan; Jagodzinski, Linda L; Eller, Michael A; Thelian, Doris; Matyas, Gary R; Kunz, Anjali N; Alving, Carl R

    2013-01-01

    Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC) either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC), platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture) from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a) platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b) platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV-1; (c) DC

  20. Platelets and erythrocyte-bound platelets bind infectious HIV-1 in plasma of chronically infected patients.

    Directory of Open Access Journals (Sweden)

    Zoltan Beck

    Full Text Available Chronic HIV-1 infection is associated with persistent viremia in most patients, but it remains unclear how free virus may survive the potential hostile effects of plasma. We investigated whether sites might exist on the surfaces of circulating blood cells for protection of infectious HIV-1 particles. Red blood cells (RBC either from blood of uninfected normal individuals, or from blood obtained without EDTA from chronically infected HIV-1 patients, invariably contained a small number of RBC having attached platelets as determined by flow cytometry, light microscopy, and immunofluorescence microscopy. After mixing normal RBC with platelet-rich plasma, discrete populations of RBC, platelets, and complexes of platelets attached to RBC were purified by fluorescence-activated cell sorting. Upon incubation of purified cells or platelets with HIV-1 followed by washing and co-incubation with CD4-positive peripheral blood mononuclear cells (PBMC, platelets, and platelet-RBC complexes, but not platelet-free RBC, caused infection of PBMC. Infection was prevented by pre-treating the platelet-RBC complexes with EDTA. Plasma and RBC (comprising a RBC/platelet-RBC mixture from chronically infected patients with low viral loads were also co-incubated with PBMC ex vivo to determine the presence of infectious HIV-1. All freshly isolated plasmas from the HIV-1-infected donors, obtained in the absence of anticoagulant, were noninfectious. Interestingly, the RBC from most of the patients caused cell-cell infection of PBMC that was prevented by stripping the RBC with EDTA. A monoclonal antibody to DC-SIGN partially inhibited cell-cell HIV-1 infection of PBMC by normal RBC pre-incubated with platelets and HIV-1. We conclude: (a platelet-free EDTA-free plasma from chronically infected HIV-1 patients, although containing viral RNA, is an environment that lacks detectable infectious HIV-1; (b platelets and platelet-RBC complexes, but not purified RBC, bind infectious HIV

  1. Early diagnosis of bacterial and fungal infection in chronic cholestatic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Xiong-Zhi Wu; Dan Chen; Lian-San Zhao; Xiao-Hui Yu; Mei Wei; Yan Zhao; Qing Fang; Qian Xu

    2004-01-01

    AIM: To investigate the early diagnostic methods of bacterial and fungal infection in patients with chronic cholestatic hepatitis B.METHODS: One hundred and one adult in-patients with chronic hepatitis B were studied and divided into 3 groups:direct bilirubin (DBil)/total bilirubin (TBil)≥0.5, without bacterial and fungal infection (group A, n=38); DBil/TBil <0.5, without bacterial and fungal infection (group B, n=23);DBil/TBil≥0.5, with bacterial or fungal infection (group C,n=40). The serum biochemical index and pulse rate were analyzed.RESULTS: Level of TBil, DBil, alkaline phosphatase (ALP)and DBil/ALP in group A increased compared with that in group B. The level of ALP in group C decreased compared with that in group A, whereas the level of TBil, DBil and DBil/ALP increased (ALP: 156±43, 199±68, respectively,P<0.05; TBil: 370±227, 220±206, respectively, P<0.01;DBil: 214±143, 146±136, respectively, P<0.01; DBil/ALP:1.65±1.05, 0.78±0.70, respectively, P<0.001). The level of DBil and infection affected DBil/ALP. Independent of the effect of DBil, infection caused DBil/ALP to rise (P<0.05).The pulse rate in group A decreased compared with that in group B (63.7±6.4, 77.7±11.4, respectively, P<0.001),and the pulse rate in group C increased compared with that in group A (81.2±12.2, 63.7±6.4, respectively, P<0.001).The equation (infection=0.218 pusle rate +1.064 DBil/ALP -16.361), with total accuracy of 85.5%, was obtained from stepwise logistic regression. Pulse rate (≥80/min) and DBil/ALP (≥1.0) were used to screen infection. The sensitivity was 62.5% and 64.7% respectively, and the specificity was 100% and 82.8% respectively.CONCLUSION: Bacterial and fungal infection deteriorate jaundice and increase pulse rate, decrease serum ALP and increase DBil/ALP. Pulse rate, DBil/ALP and the equation (infection=0.218 pusle rate+1.064 DBil/ALP-16.361) are helpful to early diagnosis of bacterial and fungal infection in patients with chronic

  2. Exhaled breath analysis using electronic nose in cystic fibrosis and primary ciliary dyskinesia patients with chronic pulmonary infections

    DEFF Research Database (Denmark)

    Joensen, Odin; Paff, Tamara; Haarman, Eric G;

    2014-01-01

    The current diagnostic work-up and monitoring of pulmonary infections may be perceived as invasive, is time consuming and expensive. In this explorative study, we investigated whether or not a non-invasive exhaled breath analysis using an electronic nose would discriminate between cystic fibrosis...... (CF) and primary ciliary dyskinesia (PCD) with or without various well characterized chronic pulmonary infections. We recruited 64 patients with CF and 21 with PCD based on known chronic infection status. 21 healthy volunteers served as controls. An electronic nose was employed to analyze exhaled......, this method significantly discriminates CF patients suffering from a chronic pulmonary P. aeruginosa (PA) infection from CF patients without a chronic pulmonary infection. Further studies are needed for verification and to investigate the role of electronic nose technology in the very early diagnostic workup...

  3. Delayed gastric emptying and Helicobacter pylori infection in patients with chronic renal failure

    Energy Technology Data Exchange (ETDEWEB)

    Kao Chiahung [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan, Province of China)]|[Yang-Ming Univ., Taipei (Taiwan, Province of China); Hsu Yuehhan [Division of Nephrology, Taichung Veterans General Hospital, Taichung (Taiwan, Province of China); Wang Shyhjen [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung (Taiwan, Province of China)]|[Yang-Ming Univ., Taipei (Taiwan, Province of China)

    1995-11-01

    Forty patients with chronic renal failure (CRF) were enrolled in this study. Twelve of the 40 patients had upper gastrointestinal symptoms or signs (GI Sx). Twenty of the 40 patients had been receiving regular haemodialysis (HD) for at least 1 year prior to the study. Radionuclide-labelled solid metals were used to calculate gastric emptying times (GETs). The carbon-14 urea breath test ({sup 14}C4-UBT) was used to diagnose Helicobacter pylori (HP) infection. Among the 40 patients, 35 (88%) had an abnormal HP infection. There were no statistically significant differences in the incidence of abnormal GET among patients with HP infection and patients without HP infection. There were also no significant differences in the incidence of HP infection among patients with abnormal and normal GETs. In addition, the incidences of abnormal GET in patients with and without upper GI Sx were 83% and 89% respectively. The incidences of HP infection in patients with and without upper GI Sx were 58% and 54%, respectively. The incidences of abnormal GET in HD and non-HD patients were 95% and 80%, respectively. The incidences of HP infection in HD and non-HD patients were 45% and 65%, respectively. The differences in the incidences of abnormal GET and HP infection among HD and non-HD patients, as well as among patients with and without upper GI Sx, were not statistically significant. (orig.)

  4. HBV/D1: a major HBV subgenotype circulating in Uyghur patients with chronic HBV infection in Xinjiang, China.

    Science.gov (United States)

    Nie, Jingjing; Li, Jie; Sun, Kuixia; Sun, Mishu; Chen, Jie; Ma, Junfeng; Yan, Ling; Zhuang, Hui

    2012-08-01

    Each hepatitis B virus (HBV) genotype and subgenotype is associated with a particular geographic distribution, ethnicity, and anthropological history. The present study investigated the genomic characteristics of HBV from Uyghur patients with chronic HBV infection in Xinjiang, China. Among the 53 Uyghur patients enrolled, HBV/D was found to be the dominant strain, with 64.2 % (34/53), 60.4 % (32/53) with HBV/D1 and 3.8 % (2/53) with HBV/D3. In addition to these findings, 3.8 % HBV/B (2/53), 5.7 % HBV/C (3/53), 11.3 % C+D (6/53), 7.5 % B+D (4/53), 3.8 % B+C (2/53) and 3.8 % B+C+D (2/53) were also detected. The full-length genome of seven HBV/D1 isolates and 144 reference sequences retrieved from GenBank were compared and analyzed by biological information methods. These results demonstrate that the D1 isolates from Xinjiang and Central Asia show a close genetic proximity (0.013±0.0007). Furthermore, four unique amino acid substitutions (sp82(Asn), sp89(His), rt129(Leu), rt151(Leu)) representing background polymorphisms rather than drug resistance mutations or immune escape variants were found in the Uyghur patients of Xinjiang, but these were seldom found in HBV/D1 strains from other regions (0 %-14.3 %). This study indicates that in Xinjiang, unlike HBV-infected Han patients, HBV/D1 is the predominant strain among HBV-infected Uyghur people. Although genetic distance analysis suggests that the HBV/D1 isolates from Xinjiang are closely related to those from Central Asia, unique amino acid substitutions suggest independent evolution of HBV in the Uyghur patients of Xinjiang.

  5. Autosomal recessive chronic granulomatous disease presenting with cutaneous dermatoses and ocular infection.

    Science.gov (United States)

    Low, L C M; Manson, A L; Hardman, C; Carton, J; Seneviratne, S L; Ninis, N

    2013-04-01

    Dermatoses such as eczematous dermatitis and cutaneous infection are recognized presentations of primary immunodeficiency (PID). However, atopic dermatitis affects approximately 10% of infants, and cutaneous infections are not uncommon in children, therefore the challenge for the dermatologist is to distinguish the few patients that have PID from the many that do not. We report on a 6-year-old girl who was ultimately diagnosed with autosomal recessive chronic granulomatous disease (AR-CGD) after presenting to various hospitals with dermatitis, scalp plaques recalcitrant to treatment, and recurrent infections over a 3-year period, and describe some aspects of her diagnosis and management. This report highlights the importance of considering rare disorders such as AR-CGD in the differential diagnosis of recurrent or recalcitrant dermatological infections in children.

  6. Mechanistic insights on immunosenescence and chronic immune activation in HIV-tuberculosis co-infection

    Science.gov (United States)

    Shankar, Esaki M; Velu, Vijayakumar; Kamarulzaman, Adeeba; Larsson, Marie

    2015-01-01

    Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus (HIV) disease progression, and functional T-cell responses in HIV-tuberculosis (HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB co-infection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis. PMID:25674514

  7. Chronic hepatitis C virus infection: Prevalence of extrahepatic manifestations and association with cryoglobulinemia in Bulgarian patients

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To assess the prevalence of extrahepatic manifestations in Bulgarian patients with chronic hepatitis C virus (HCV) infection and identify the clinical and biological manifestations associated with cryoglobulinemia.METHODS: The medical records of 136 chronically infected HCV patients were reviewed to assess the prevalence of extrahepatic manifestations. Association between cryoglobulin-positivity and other manifestations were identified using χ2 and Fisher's exact test. Risk factors for the presence of extrahepatic manifestations were assessed by logistic regression analysis.RESULTS: Seventy six percent (104/136) of the patients had at least one extrahepatic manifestation.Clinical manifestations included fatigue (59.6%),kidney impairment (25.0%), type 2 diabetes (22.8%),paresthesia (19.9%), arthralgia (18.4%), palpable purpura (17.6%), lymphadenopathy (16.2%), pulmonary fibrosis (15.4%), thyroid dysfunction (14.7%), Raynaud's phenomenon (11.8%), B-cell lymphoma (8.8%),sicca syndrome (6.6%), and lichen planus (5.9%).The biological manifestations included cryoglobulin production (37.5%), thrombocytopenia (31.6%), and autoantibodies: anti-nuclear (18.4%), anti-smooth muscle (16.9%), anti-neutrophil cytoplasm (13.2%) and anti-cardiolipin (8.8%). All extrahepatic manifestations showed an association with cryoglobulin-positivity, with the exception of thyroid dysfunction, sicca syndrome,and lichen planus. Risks factors for the presence of extrahepatic manifestations (univariate analysis) were:age ≥ 60 years, female gender, virus transmission by blood transfusions, longstanding infection (≥ 20 years), and extensive liver fibrosis. The most significant risks factors (multivariate analysis) were longstanding infection and extensive liver fibrosis.CONCLUSION: We observed a high prevalence of extrahepatic manifestations in patients with chronic HCV infection. Most of these manifestations were associated with impaired lymphoproliferation and cryoglobulin production

  8. Benign and malignant hematological manifestations of chronic Hepatitis C virus infection

    Directory of Open Access Journals (Sweden)

    Shiksha Kedia

    2014-01-01

    Full Text Available Chronic hepatitis C virus (HCV infection, that affects 3% of world′s population, is associated with several hematological manifestations mainly benign cytopenias, coagulopathy and lymphoproliferative diseases. Immune or non-immune-mediated thrombocytopenia is a major challenge in chronic HCV infected patients especially in the setting of an advanced liver disease, with average prevalence of nearly 24%. Although several treatment modalities such as steroids, intravenous immunoglobulin, splenectomy and immunosuppresants have been tried with some success, their efficacy is not impressive and can result in an increase in viral load or other thrombotic complications. Even though a recent phase 2 study has shown promising role of a platelet growth factor, eltrombopag, in boosting platelets counts prior to antiviral treatment, its use in pre-operative setting had unexpected complications. Unlike thrombocytopenia, anemia and neutropenia are more frequently seen in treated patients and are often the result of antiviral therapy. HCV infection also pre-disposes to lymphoproliferative diseases, mainly non-Hodking′s lymphomas, likely as a result of chronic antigenic stimulation and mutation of several genes involved in carcinogenesis. Understanding of the role of HCV infection in these conditions has therapeutic implications. Whereas antiviral therapy has shown therapeutic role in HCV-associated indolent lymphomas, monitoring of hepatic function and viral load is important in the management of diffuse large B-cell lymphoma in HCV-infected patients. Although our knowledge about the HCV infection and hematological manifestations has substantially grown in last few decades, further studies are important to advance our therapeutic approach.

  9. Hepatitis C virus infection among chronic dialysis patients in the south of France: a collaborative study.

    Science.gov (United States)

    Dussol, B; Berthezène, P; Brunet, P; Roubicek, C; Berland, Y

    1995-03-01

    During the last quarter of 1992, 984 patients from 13 dialysis centers in the Provence-Alpes-Côte-d'Azur region in France participated in a multicenter cross-sectional study to determine the prevalence, the risk factors, and the clinical consequences of infection by the hepatitis C virus (HCV). Serum samples were tested for anti-HCV antibodies using second-generation enzyme-linked immunosorbent assay (ELISA). In the case of a positive result, a combination test was performed using second-generation recombinant immunoblot (RIBA) or direct detection of HCV-RNA by nested polymerase chain reaction (PCR). Collected data included the patient's age, gender, cause of the kidney disease, type of dialysis treatment, number of years on dialysis, weekly dialysis time, drug addiction, co-infection with hepatitis B virus and human immunodeficiency virus (HIV), number of kidney transplants, number of blood transfusions, and history of acute or chronic hepatitis. Chronic HCV infection was detected in 232 (23.6%) patients, whereas only 71 (7.2%) were infected by HBV. Logistic-regression analysis showed that HCV infection was associated with dialysis over a long period, numerous blood transfusions, female gender, kidney grafts, HBV infection, hemodialysis, and acute as well as chronic hepatitis. Multiple-correspondence analysis confirmed that the contamination was both transfusional and nosocomial. These results underscore the need for a strict compliance with "universal precautions" (Centers for Disease Control [CDC], Atlanta) in dialysis units and raise the question as to whether anti-HCV-positive patients should be isolated.

  10. Effect of chronic hepatitis C virus infection on bone disease in postmenopausal women.

    LENUS (Irish Health Repository)

    Nanda, Kavinderjit S

    2012-02-01

    BACKGROUND & AIMS: Limited data are available on the contribution of chronic HCV infection to the development of bone disease in postmenopausal women. We studied whether women who acquired HCV infection through administration of HCV genotype 1b-contaminated anti-D immunoglobulin from a single source had decreased bone mineral density (BMD) or altered levels of bone turnover markers (BTMs), compared with women who spontaneously resolved infection or age-matched healthy controls. METHODS: From a cohort of postmenopausal Irish women, we compared BMD, determined by dual-energy x-ray absorptiometry, and a panel of BTMs in 20 women chronically infected with HCV (PCR(+)), 21 women who had spontaneously resolved infection (PCR(-)), and 23 age-matched healthy controls. RESULTS: Levels of BTMs and BMD were similar in PCR(+) and PCR(-) women and healthy age-matched controls. However, there was an increased frequency of fractures in PCR(+) (n = 6) compared with PCR(-) women (n = 0, P = .007). PCR(+) women with fractures were postmenopausal for a longer time (median, 15.5, range, 5-20 years vs 4.5, range, 1-20 years in PCR(+) women without fractures; P = .033), had lower BMD at the hip (0.79, range, 0.77-0.9 g\\/cm(2) vs 0.96, range, 0.81-1.10 g\\/cm(2); P = .007), and had a lower body mass index (23.7, range 21.2-28.5 kg\\/m(2) vs 25.6, range 22.1-36.6 kg\\/m(2); P = .035). There was no difference in liver disease severity or BTMs in PCR(+) women with or without fractures. CONCLUSIONS: Chronic HCV infection did not lead to discernable metabolic bone disease in postmenopausal women, but it might be a risk factor for bone fractures, so preventive measures should be introduced. To view this article\\'s video abstract, go to the AGA\\'s YouTube Channel.

  11. Chronic Opisthorchis viverrini infection and associated hepatobiliary disease is associated with iron loaded M2-like macrophages.

    Science.gov (United States)

    Bility, Moses T; Sripa, Banchob

    2014-12-01

    Chronic Opisthorchis viverrini-induced hepatobiliary disease is associated with significant leukocyte infiltration, including activated macrophages; however, the polarization of infiltrating macrophages remains to be fully characterized. In this study, we characterized macrophage polarization and phenotype in chronic O. viverrini-induced hepatobiliary disease in humans and hamsters using gene expression and histochemical analysis. Chronic O. viverrini infection and associated hepatobiliary diseases were associated with iron loaded M2-like macrophages in both humans and hamsters. This study provides suggestive evidence that iron loaded M2-like macrophages promote hepatobiliary disease in chronic O. viverrini infection.

  12. Murine Model Imitating Chronic Wound Infections for Evaluation of Antimicrobial Photodynamic Therapy Efficacy

    Science.gov (United States)

    Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar

    2016-01-01

    It is generally acknowledged that the age of antibiotics could come to an end, due to their widespread, and inappropriate use. Particularly for chronic wounds alternatives are being thought. Antimicrobial Photodynamic Therapy (APDT) is a potential candidate, and while approved for some indications, such as periodontitis, chronic sinusitis and other niche indications, its use in chronic wounds is not established. To further facilitate the development of APDT in chronic wounds we present an easy to use animal model exhibiting the key hallmarks of chronic wounds, based on full-thickness skin wounds paired with an optically transparent cover. The moisture-retaining wound exhibited rapid expansion of pathogen colonies up to 8 days while not jeopardizing the host survival. Use of two bioluminescent pathogens; methicillin resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa permits real time monitoring of the pathogens. The murine model was employed to evaluate the performance of four different photosensitizers as mediators in Photodynamic Therapy. While all four photosensitizers, Rose Bengal, porphyrin TMPyP, New Methylene Blue, and TLD1411 demonstrated good to excellent antimicrobial efficacy in planktonic solutions at 1 to 50 μM concentrations, whereas in in vivo the growth delay was limited with 24–48 h delay in pathogen expansion for MRSA, and we noticed longer growth suppression of P. aeruginosa with TLD1411 mediated Photodynamic Therapy. The murine model will enable developing new strategies for enhancement of APDT for chronic wound infections. PMID:27555843

  13. Rhinovirus genome variation during chronic upper and lower respiratory tract infections.

    Directory of Open Access Journals (Sweden)

    Caroline Tapparel

    Full Text Available Routine screening of lung transplant recipients and hospital patients for respiratory virus infections allowed to identify human rhinovirus (HRV in the upper and lower respiratory tracts, including immunocompromised hosts chronically infected with the same strain over weeks or months. Phylogenetic analysis of 144 HRV-positive samples showed no apparent correlation between a given viral genotype or species and their ability to invade the lower respiratory tract or lead to protracted infection. By contrast, protracted infections were found almost exclusively in immunocompromised patients, thus suggesting that host factors rather than the virus genotype modulate disease outcome, in particular the immune response. Complete genome sequencing of five chronic cases to study rhinovirus genome adaptation showed that the calculated mutation frequency was in the range observed during acute human infections. Analysis of mutation hot spot regions between specimens collected at different times or in different body sites revealed that non-synonymous changes were mostly concentrated in the viral capsid genes VP1, VP2 and VP3, independent of the HRV type. In an immunosuppressed lung transplant recipient infected with the same HRV strain for more than two years, both classical and ultra-deep sequencing of samples collected at different time points in the upper and lower respiratory tracts showed that these virus populations were phylogenetically indistinguishable over the course of infection, except for the last month. Specific signatures were found in the last two lower respiratory tract populations, including changes in the 5'UTR polypyrimidine tract and the VP2 immunogenic site 2. These results highlight for the first time the ability of a given rhinovirus to evolve in the course of a natural infection in immunocompromised patients and complement data obtained from previous experimental inoculation studies in immunocompetent volunteers.

  14. Manipulation of Regulatory Cells’ Responses to Treatments for Chronic Hepatitis B Virus Infection

    Science.gov (United States)

    Tavakolpour, Soheil; Alavian, Seyed Moayed; Sali, Shahnaz

    2016-01-01

    Background Identification of effective treatments in hepatitis B virus (HBV) infection remains a controversial topic. Although the currently approved drugs for HBV control the disease’s progression and also limit associated outcomes, these drugs may not fully eradicate HBV infection. In addition to better managing patients with chronic hepatitis B (CHB) infection, the induction of seroclearance by these drugs has been a commonly discussed topic in recent years. Objectives In this study, we focused on treating CHB infection via the manipulation of T cells’ responses to identify possible approaches to cure CHB. Materials and Methods All studies relevant to the role of cellular and humoral responses in HBV infection (especially regulatory cells) were investigated via a systematic search of different databases, including PubMed, Scopus, and Google Scholar. Considering extracted data and also our unpublished data regarding the association between regulatory cytokines and CHB, we introduced a novel approach for the induction of seroclearance. Results Considering the increased levels of regulatory cytokines and also regulatory T cells (Tregs) during CHB, it seems that these cells are deeply involved in CHB infection. The inhibition of regulatory T cells may reverse the dysfunction of effector T cells in patients with CHB infection. In order to inhibit Tregs’ responses, different types of approaches could be employed to restore the impaired function of effector T cells. The blockade of IL-10, IL-35, CTLA-4, PD-1, and TIM-3 were discussed throughout this study. Regardless of the efficacy of these methods, CHB patients may experience serious liver injuries due to the cytotoxic action of CD8+ T cells. Antiviral therapy and a decrease in HBV DNA to undetectable levels could also significantly reduce the risk of the hepatitis B flare. Conclusions The inhibition of Tregs is a novel therapeutic approach to cure chronically HBV infected patients. However, further studies are

  15. Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

    Science.gov (United States)

    Serra, Raffaele; Grande, Raffaele; Buffone, Gianluca; Molinari, Vincenzo; Perri, Paolo; Perri, Aldina; Amato, Bruno; Colosimo, Manuela; de Franciscis, Stefano

    2016-02-01

    Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.

  16. 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.

  17. Is hepcidin the bridge linking Helicobacter pylori and anemia of chronic infection? A research proposal.

    Science.gov (United States)

    Pellicano, R; Rizzetto, M

    2004-09-01

    Since the last decade, several studies have reported on the link between chronic Helicobacter pylori (H. pylori) or Helicobacter species (H. species) infection and a variety of extragastric manifestations, comprising iron-deficiency anemia. A crucial question concerns which possible pathogenic mechanism of H. pylori infection may be involved in chronic anemia. Recent findings support the hypothesis that in subjects with H. pylori-positive gastritis, concomitant changes in intragastric pH and ascorbic acid are present that might play a role in impairing alimentary iron absorption with consequent sideropenic anemia. It has also been speculated that H. pylori infected antrum could act as a sequestering focus for iron. The bacterium enhances gastric lactoferrin, which captures iron from transferrin. The iron thus bound to lactoferrin is in turn picked up by the bacterium, by means of its outer membrane receptors, for its own growth. These models, however, are not able to answer why iron-deficiency anemia does not develop in all infected subjects. Recently, a new anti-microbial liver-made peptide, namely hepcidin, has been characterised. The link between hepcidin induction, inflammation and anemia both in humans and in animal models supports its key role as mediator of anemia of inflammation. In the present paper, we highlight the data available on the association between H. pylori and iron-deficiency anemia and, we propose to evaluate a possible mechanism involving hepcidin in a bridging role linking the infection to the anemia.

  18. Successful interferon desensitization in a patient with chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Seyed Alireza Taghavi; Ahad Eshraghian

    2009-01-01

    Treatment of hepatitis C, even when absolutely necessary, is almost impossible when interferon cannot be administered for any reason. We report a 65-year-old patient with chronic hepatitis C virus (HCV) infection and fibrosis, who was unable to receive interferon because of systemic hypersensitivity. The patient was desensitized successfully through gradual incremental exposure to interferon, and HCV infection was eradicated after a complete course of treatment,with no further allergic reactions. This case report that describes successful eradication of hepatitis C in a patient with advanced liver disease after desensitization to interferon revealed that desensitization may not necessarily damage the therapeutic efficacy of the drug.

  19. ETHNIC AND POPULATION-SPECIFIC FEATURES OF SOME IMMUNOLOGICAL PARAMETERS IN CHRONIC HELICOBACTER PYLORI INFECTION

    Directory of Open Access Journals (Sweden)

    E. S. Ageeva

    2012-01-01

    Full Text Available Abstract. Immunophenotype profile of lymphocytes (CD3+, CD4+ and CD8+ from peripheral blood in gastric ulcer associated with Helicobacter pylori, chronic gastritis and stomach cancer has been studied in Khakassian aboriginals and migrants. Apoptosis of peripheral blood lymphocytes was also evaluated. Some alterations of immunological indexes were revealed in patients infected with Helicobacter pylori, as compared to healthy donors and migrants. The changes were characterized by a more intense apoptotic death of lymphocytes in the patients, when compared with numbers of apoptotic cells in control group. Probable role of apoptotic events in regulation of local and system immunity in Helicobacter pylori infection is discussed.

  20. Chronic Plasmodium falciparum infections in an area of low intensity malaria transmission in the Sudan

    DEFF Research Database (Denmark)

    Hamad, A A; El Hassan, I M; El Khalifa, A A

    2000-01-01

    Chronic Plasmodium falciparum malaria infections in a Sudanese village, in an area of seasonal and unstable malaria transmission, were monitored and genetically characterized to study the influence of persistent infection on the immunology and epidemiology of low endemicity malaria. During...... the October-December malaria season of 1996, 51 individuals out of a population of 420 had confirmed and treated P. falciparum malaria in the village of Daraweesh in eastern Sudan. In a cross-sectional survey carried out in December 1996, an additional 6 individuals were found to harbour a microscopically...

  1. Salmonella Typhimurium undergoes distinct genetic adaption during chronic infections of mice

    DEFF Research Database (Denmark)

    Søndberg, Emilie; Jelsbak, Lotte

    2016-01-01

    Background Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) is a severe systemic human disease and endemic in regions of the world with poor drinking water quality and sewage treatment facilities. A significant number of patients become asymptomatic life-long carriers of S......, the kdgR-SNP was confirmed to confer selective advantage during chronic infections and constitute a true patho-adaptive mutation. Together, the results provide evidence for rapid genetic adaptation to the host of S. Typhimurium and validate experimental evolution in the context of host infection...

  2. [Extrahepatic manifestations in patients with chronic infections due to the hepatitis C virus].

    Science.gov (United States)

    Ramos-Casals, Manuel

    2009-01-01

    Autoimmunity and viral infections are closely related, and viruses have been proposed as possible etiologic or triggering agents of systemic autoimmune diseases (SAD). The hepatitis C virus (HCV), a linear, single-stranded RNA virus, identified in 1989, is recognized as one of the viruses most often associated with autoimmune features. The association between HCV and SAD has generated growing interest in recent years. The extrahepatic manifestations often observed in patients with chronic HCV infection (both clinical and immunological) may lead to the fulfilment of the current classification criteria for some SAD.

  3. Chronic eosinophilic dermatitis associated with persistent feline herpes virus infection in cheetahs (Acinonyx jubatus).

    Science.gov (United States)

    Munson, L; Wack, R; Duncan, M; Montali, R J; Boon, D; Stalis, I; Crawshaw, G J; Cameron, K N; Mortenson, J; Citino, S; Zuba, J; Junge, R E

    2004-03-01

    A chronic ulcerative and eosinophilic dermatitis occurred in 20 captive cheetahs (Acinonyx jubatus) with persistent feline herpes virus 1 (FHV1) infection. Affected animals had erythematous, ulcerated plaques primarily on the face and forelegs in sites of contact with lachrymal and salivary secretions. The dermatitis was characterized by dense infiltrates of eosinophils and plasma cells and pseudoepitheliomatous hyperplasia. Rare keratinocytes within the lesions had nuclei with marginated chromatin and small eosinophilic inclusions composed of herpes virus nucleocapsids. Virus isolated from lesions was confirmed to be FHV1. Lesions persisted and progressed unless removed by cryoexcision. The occurrence of this unusual reaction to FHV1 in approximately 5% of captive North American cheetahs suggests a species propensity for a Th2-dominant response to herpes virus infection. This atypical immune reaction may indicate a heritable trait or modulation of the immune response by other factors such as chronic stress.

  4. Effects of adding ribavirin to interferon to treat chronic hepatitis C infection

    DEFF Research Database (Denmark)

    Brok, Jesper; Gluud, Lise L; Gluud, Christian

    2005-01-01

    , EMBASE, manual searches of bibliographies and journals, and correspondence with experts (in May 2004). Data were extracted independently by 2 reviewers. The primary outcomes were morbidity plus mortality and viral clearance. Secondary outcomes included histologic response, quality of life, and adverse....... In conclusion, the effect of ribavirin plus interferon on viral clearance may lead to reduced mortality and morbidity in patients with chronic hepatitis C infection. However, combination therapy is associated with increased risk for adverse events.......Evidence shows that a combination therapy of ribavirin plus interferon clears hepatitis C virus from the blood in about 40% of patients with chronic hepatitis C infection, but the effects on clinical outcomes are unclear. We evaluated the beneficial and harmful effects of ribavirin plus interferon...

  5. Antigen-induced regulatory T cells in HBV chronically infected patients.

    Science.gov (United States)

    Barboza, Luisa; Salmen, Siham; Goncalves, Loredana; Colmenares, Melisa; Peterson, Darrell; Montes, Henry; Cartagirone, Raimondo; Gutiérrez, Maria del Carmen; Berrueta, Lisbeth

    2007-11-10

    T cell response against HBV is vigorous in patients with acute hepatitis who clear the virus, whereas it is weak and narrowly focused in patients with chronic disease. We report that following incubation with HBcAg, a population of CD4+FoxP3+ cells expressing phenotypic markers of both natural and induced Tregs, can be antigen-induced from peripheral mononuclear cells. Conversely, naive and naturally immune subjects did not increase CD4+FoxP3+ Tregs following stimulation with HBcAg, supporting the idea that natural Tregs are able to respond specifically to HBV antigen. Furthermore, increased frequencies of antigen-induced CD4+FoxP3+IL-10+ Tregs correlated with viral load, suggesting that antigen-induced Tregs could contribute to an inadequate response against the virus, leading to chronic infection and support the view that specific natural Tregs may be implicated in host immune tolerance during HBV infection.

  6. Chronic meningitis with intracranial hypertension and bilateral neuroretinitis following Mycoplasma pneumoniae infection.

    Science.gov (United States)

    Karampatsas, Konstantinos; Patel, Himanshu; Basheer, Sheikh N; Prendergast, Andrew J

    2014-12-23

    A previously well 12-year-old boy presented with a 2-week history of headache, nausea, vomiting and left-sided weakness. He subsequently developed meningism, right abducens nerve palsy, persistent papilloedema and reduced visual acuity in association with a bilateral macular star, consistent with neuroretinitis. Cerebrospinal fluid (CSF) examination indicated chronic meningitis and serological testing confirmed recent Mycoplasma pneumoniae infection, although PCR in CSF was negative. He was treated for aseptic meningitis with ceftriaxone, aciclovir, azithromycin and acetazolamide for intracranial hypertension, with gradual improvement in clinical condition and visual acuity over several weeks. This is the first report of M. pneumoniae chronic meningitis further complicated with bilateral neuroretinitis and intracranial hypertension. Evidence of central nervous system inflammation in the absence of direct infection suggests an immune-mediated pathophysiology. Although the use of macrolides with antibiotic and immunomodulatory activity might be beneficial, it was not possible to ascertain whether it influenced clinical recovery in this case.

  7. Microbial biofilms: impact on the pathogenesis of periodontitis, cystic fibrosis, chronic wounds and medical device-related infections.

    Science.gov (United States)

    Mihai, Mara Madalina; Holban, Alina Maria; Giurcaneanu, Calin; Popa, Liliana Gabriela; Oanea, Raluca Mihaela; Lazar, Veronica; Chifiriuc, Mariana Carmen; Popa, Marcela; Popa, Mircea Ioan

    2015-01-01

    The majority of chronic infections are associated with mono- or polymicrobial biofilms, having a significant impact on the patients' quality of life and survival rates. Although the use of medical devices revolutionized health care services and significantly improved patient outcomes, it also led to complications associated with biofilms and to the emergence of multidrug resistant bacteria. Immunocompromised patients, institutionalized or hospitalized individuals, elderly people are at greater risk due to life-threatening septic complications, but immunocompetent individuals with predisposing genetic or acquired diseases can also be affected, almost any body part being able to shelter persistent biofilms. Moreover, chronic biofilm-related infections can lead to the occurrence of systemic diseases, as in the case of chronic periodontitis, linked to atherosclerosis, cardiovascular disease and diabetes. The more researchers discover, new unknown issues add up to the complexity of biofilm infections, in which microbial species establish relationships of cooperation and competition, and elaborate phenotypic differentiation into functional, adapted communities. Their interaction with the host's immune system or with therapeutic agents contributes to the complex puzzle that still misses a lot of pieces. In this comprehensive review we aimed to highlight the microbial composition, developmental stages, architecture and properties of medical biofilms, as well as the diagnostic tools used in the management of biofilm related infections. Also, we present recently acquired knowledge on the etiopathogenesis, diagnosis and treatment of four chronic diseases associated with biofilm development in tissues (chronic periodontitis, chronic lung infection in cystic fibrosis, chronic wounds) and artificial substrata (medical devices-related infections).

  8. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    OpenAIRE

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained vir...

  9. Chronic Infections and Management Setting in Drug Addicts of MMT Program in Pinang, Malaysia

    OpenAIRE

    Syed Azhar Syed Sulaiman; Syed Wasif Gillani

    2009-01-01

    Background: The authors sought to identify the prevalence of blood-borne chronic infections and determine the appropriate management therapy setting among the drug addicts of methadone maintenance treatment (MMT) program. The purpose to identify such factor is to know the quality of health of respondents active to MMT program and possibly predict the risk reduction of relapse during the treatment. Methodology: As it was known that government of Malaysia allowed MMT on large scale at 2005, so ...

  10. Viral suppression and immune restoration in the gastrointestinal mucosa of human immunodeficiency virus type 1-infected patients initiating therapy during primary or chronic infection.

    Science.gov (United States)

    Guadalupe, Moraima; Sankaran, Sumathi; George, Michael D; Reay, Elizabeth; Verhoeven, David; Shacklett, Barbara L; Flamm, Jason; Wegelin, Jacob; Prindiville, Thomas; Dandekar, Satya

    2006-08-01

    Although the gut-associated lymphoid tissue (GALT) is an important early site for human immunodeficiency virus (HIV) replication and severe CD4+ T-cell depletion, our understanding is limited about the restoration of the gut mucosal immune system during highly active antiretroviral therapy (HAART). We evaluated the kinetics of viral suppression, CD4+ T-cell restoration, gene expression, and HIV-specific CD8+ T-cell responses in longitudinal gastrointestinal biopsy and peripheral blood samples from patients initiating HAART during primary HIV infection (PHI) or chronic HIV infection (CHI) using flow cytometry, real-time PCR, and DNA microarray analysis. Viral suppression was more effective in GALT of PHI patients than CHI patients during HAART. Mucosal CD4+ T-cell restoration was delayed compared to peripheral blood and independent of the time of HAART initiation. Immunophenotypic analysis showed that repopulating mucosal CD4+ T cells were predominantly of a memory phenotype and expressed CD11 alpha, alpha(E)beta 7, CCR5, and CXCR4. Incomplete suppression of viral replication in GALT during HAART correlated with increased HIV-specific CD8+ T-cell responses. DNA microarray analysis revealed that genes involved in inflammation and cell activation were up regulated in patients who did not replenish mucosal CD4+ T cells efficiently, while expression of genes involved in growth and repair was increased in patients with efficient mucosal CD4+ T-cell restoration. Our findings suggest that the discordance in CD4+ T-cell restoration between GALT and peripheral blood during therapy can be attributed to the incomplete viral suppression and increased immune activation and inflammation that may prevent restoration of CD4+ T cells and the gut microenvironment.

  11. Pathogenesis, prophylaxis and treatment of infections in patients with chronic lymphocytic leukemia 

    Directory of Open Access Journals (Sweden)

    Piotr Stelmach

    2013-06-01

    Full Text Available Chronic lymphocytic leukemia (CLL patients are at high risk for infections. The pathogenesis of infection in patients with this leukemia is complex and multifactorial. Patients with CLL have a number of immune system defects, including disordered B-cell function with decreased production of normal B-cells and abnormal production of immunoglobulins, suppressed Tcell function and neutropenia. Other immune abnormalities present in CLL patients include neutrophil dysfunction, and complement deficiencies. In addition, further perturbations in immune function are related to the antileukemic therapies. Immune disturbance might be common prior to CLL diagnosis and infectious agents could trigger CLL development. Current chemotherapy-based regimens are not curative and often worsen this immune suppression. The introduction of new effective therapeutic agents such as the purine analogues and monoclonal antibodies has influenced the spectrum of infections diagnosed in CLL patients. Some conditions increase the risk for the development of infections including advanced age, decreased levels of immunoglobulins, advanced Binet stage, neutropenia and treatment with more than one line of chemotherapy. Until now it is debatable whether and when antibacterial prophylaxis could be useful in CLL patients. The prevention of infection includes antimicrobial prophylaxis, as well as immunoglobulin replacement and vaccination. Antibacterial prophylaxis should be given to CLL patients with previous severe and/or relapsing bacterial infections. This article reviews the immune defects in CLL and discusses strategies aimed at prophylaxis and treatment of infections in patients with CLL. 

  12. Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Doaa Salah Hegab

    2015-01-01

    Full Text Available Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC shows a striking association with hepatitis C virus (HCV infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169% were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg’s disease. Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients’ demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management.

  13. Cryoglobulinaemia in Egyptian Patients with Extrahepatic Cutaneous Manifestations of Chronic Hepatitis C Virus Infection.

    Science.gov (United States)

    Hegab, Doaa Salah; Sweilam, Mohammed Abd El Rahman

    2015-01-01

    Background. Hepatitis C is a global major health problem with extremely variable extrahepatic manifestations. Mixed cryoglobulinaemia (MC) shows a striking association with hepatitis C virus (HCV) infection, and it is sometimes asymptomatic. The skin is a frequently involved target organ in MC. Objective. To investigate the prevalence of cryoglobulinaemia in a sample of Egyptian patients with cutaneous manifestations of chronic HCV infection and to correlate its presence with clinical criteria and liver function tests. Methods. One hundred and eighteen patients with skin manifestations of chronic compensated hepatitis C were included. Venous blood was tested for liver function tests and serum cryoglobulins. Results. Twelve patients (10.169%) were positive for serum cryoglobulins (2 with pruritus, 4 with vasculitic lesions, 3 with livedo reticularis, one with oral lichen, one with chronic urticaria, and another with Schamberg's disease). Vasculitic lesions and livedo reticularis of the legs showed higher prevalence in cryoglobulin-positive than in cryoglobulin-negative patients. Presence of serum cryoglobulins did not relate to patients' demographic or laboratory findings. Conclusions. Fortunately, MC is not markedly prevalent among Egyptians with cutaneous lesions of chronic hepatitis C, and cryopositivity was commonly, but not exclusively, detected with cutaneous vasculitis and livedo reticularis. Laboratory testing for cryoglobulins in every HCV patient is advisable for earlier MC detection and management.

  14. Evaluation of viral load in saliva from patients with chronic hepatitis C infection.

    Science.gov (United States)

    Xavier Santos, Renata L; de Deus, Dayse M V; de Almeida Lopes, Edmundo P; Duarte Coêlho, Maria R C; de Castro, Jurema F L

    2015-01-01

    Hepatitis C virus can be detected in blood and other bodily fluids, such as saliva. The aim of this study was to detect and quantify the HCV-RNA in saliva and plasma from patients with chronic hepatitis C infections, as well as check the level of viral load in sex groups (age, ethnicity and virus subtypes). Whole saliva and blood from 70 patients with chronic hepatitis C infections attended at the department of gastroenterology from University Hospital. The HCV-RNA load was performed by qRT-PCR using Sybr Green I master mix. HCV-RNA was detected in 80% (56/70) of patients in saliva and 92.85% (65/70) in plasma. The median of the viral load in the plasma was of 4.87 log10, and in saliva, it was 3.32log10, (p = 0.0005). Female patients and black patients exhibited a negative correlation between the HCV-RNA load in saliva vs. the HCV-RNA load in plasma (r = -0.3172, CI95% -0.6240 to -0.03736, p = 0.0491) and (r = -0.3141; IC95% -0.6069 to -0.05926; p = 0.0209), respectively. HCV-RNA was detected and quantified in saliva samples, and according to the quantification levels, saliva may be a possible transmission source of HCV, particularly in women and people of black ethnicity who develop chronic HCV infections.

  15. Maximum growth rate of Mycobacterium avium in continuous culture or chronically infected BALB/c mice.

    Science.gov (United States)

    McCarthy, C M; Taylor, M A; Dennis, M W

    1987-01-01

    Mycobacterium avium is a human pathogen which may cause either chronic or disseminated disease and the organism exhibits a slow rate of growth. This study provides information on the growth rate of the organism in chronically infected mice and its maximal growth rate in vitro. M. avium was grown in continuous culture, limited for nitrogen with 0.5 mM ammonium chloride and dilution rates that ranged from 0.054 to 0.153 h-1. The steady-state concentration of ammonia nitrogen and M. avium cells for each dilution rate were determined. The bacterial saturation constant for growth-limiting ammonia was 0.29 mM (4 micrograms nitrogen/ml) and, from this, the maximal growth rate for M. avium was estimated to be 0.206 h-1 or a doubling time of 3.4 h. BALB/c mice were infected intravenously with 3 x 10(6) colony-forming units and a chronic infection resulted, typical of virulent M. avium strains. During a period of 3 months, the number of mycobacteria remained constant in the lungs, but increased 30-fold and 8,900-fold, respectively, in the spleen and mesenteric lymph nodes. The latter increase appeared to be due to proliferation in situ. The generation time of M. avium in the mesenteric lymph nodes was estimated to be 7 days.

  16. PFGE and antibiotic susceptibility phenotype analysis of Pseudomonas aeruginosa strain chronically infecting Cystic Fibrosis patients

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    Giovanna Pulcrano

    2008-09-01

    Full Text Available Pseudomonas aeruginosa is the leading cause of chronic lung infection and following pulmonary worsening of cystic fibrosis patients. To verify whether bacterial modifications regarding motility, mucoidy, and serum susceptibility proceeded from an adaptation to chronic infection or a replacement with a new strain, sequential P. aeruginosa isolates of known phenotype collected from 5 cystic fibrosis patients were typed by pulsed-field gel electophoresis (PFGE. Antimicrobial susceptibility testing of all isolates was performed by the disc diffusion method. PFGE typing demonstrated that strains dissimilar in colony morphotype and of different antibiotic susceptibility patterns could be of the same genotype. Some patients were colonized with a rather constant P. aeruginosa flora, with strains of different phenotypes but of one genotype. Instead, some patients may be colonized by more than one genotype. Secretion of mucoid exopolysaccharide and acquisition of a new antibiotic susceptibility phenotype in these strain appear to evolve during chronic colonization in cystic fibrosis patients from specific adaptation to infection rather than from acquisition of new bacterial strains.

  17. Progression of chronic hepatitis and preneoplasia in Helicobacter hepaticus-infected A/JCr mice.

    Science.gov (United States)

    Rogers, Arlin B; Boutin, Samuel R; Whary, Mark T; Sundina, Nataliya; Ge, Zhongming; Cormier, Kathleen; Fox, James G

    2004-01-01

    Helicobacter hepaticus infection induces sustained inflammation and carcinoma of the liver in A/JCr mice, and serves as a model of human cancers associated with viral hepatitis and H. pylorichronic gastritis. Here we describe the pathogenesis of premalignant disease in A/JCr mice infected with H. hepaticus. We inoculated dams intragestationally and/or pups postnatally, and evaluated offspring at 3, 6, or 12 months. Mice infected at or before 3 weeks of age, but not at 12 weeks, developed disease. Male mice were most affected, but expressed a bimodal pattern of susceptibility. Males exhibited lobular necrogranulomatous and interface (chronic active) hepatitis, while females usually developed intraportal (chronic persistent) hepatitis. Portal inflammation was slowly progressive, with tertiary lymphoid nodule development by 12 months. Hepatic bacterial load and preneoplastic lesions, including clear and tigroid cell foci of cellular alteration, were correlated with lobular hepatitis severity. No extrahepatic surrogate disease marker reliably predicted individual hepatitis grade. In conclusion, gender and bacterial exposure timing are key determinants of H. hepaticus disease outcomes. Intrahepatic inflammation is driven by local signals characterized by a vigorous but nonsterilizing immune response. Continued study of chronic hepatitis progression may reveal therapeutic targets to reduce the risk of hepatocellular carcinoma.

  18. Chronic filarial infection provides protection against bacterial sepsis by functionally reprogramming macrophages.

    Directory of Open Access Journals (Sweden)

    Fabian Gondorf

    2015-01-01

    Full Text Available Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode Litomosoides sigmodontis (L.s. and the outcome of acute systemic inflammation caused by i.p. Escherichia coli injection was determined. L.s. infection significantly improved E. coli-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in L.s.-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as L.s., signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from L.s.-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with L.s. extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a Wolbachia- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from L.s.-infected wild type, but not TLR2-deficient animals. In association, L.s. infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated E. coli-induced hypothermia and sepsis survival. These results indicate that chronic L.s. infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases

  19. Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

    Directory of Open Access Journals (Sweden)

    Ming V Lin

    Full Text Available The prevalence of Hepatitis C Virus (HCV infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79% with a median age of 60 years (range 34-70 years, median creatinine of 1.2 mg/dL (0.66-1.76, and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%. All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin, ledipasvir (7 patients without and 1 patient with ribavirin or ribavirin alone (4 patients. The overall sustained virologic response (SVR12 was 91% (21 out of 23 patients. One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46% and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective

  20. Peripheral whole blood FOXP3 TSDR methylation: a potential marker in severity assessment of autoimmune diseases and chronic infections.

    Science.gov (United States)

    Ngalamika, Owen; Liang, Gongping; Zhao, Ming; Yu, Xinhai; Yang, Yang; Yin, Heng; Liu, Yu; Yung, Susan; Chan, Tak Mao; Lu, Qianjin

    2015-01-01

    Immune dysregulation is a cardinal feature of autoimmune diseases and chronic microbial infections. In particular, regulatory T cells are downregulated in autoimmune diseases while upregulated in chronic microbial infections. FOXP3 is the master regulator of Treg development. Treg-specific demethylated region (TSDR) is a highly conserved locus on the FOXP3 gene that is fully demethylated in natural Tregs but methylated in effector T cells. In our study, we used high resolution melt-polymerase chain reaction (HRM-PCR) to determine the FOXP3 TSDR methylation status in autoimmune diseases and chronic microbial infections. We found that FOXP3 TSDR to have the highest mean melting temperature (highly methylated) in active SLE patients compared to all the other groups (p autoimmune diseases and chronic microbial infections.

  1. Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus

    DEFF Research Database (Denmark)

    Bartholdy, C; Christensen, Jan Pravsgaard; Wodarz, D;

    2000-01-01

    ). While wild-type mice rapidly cleared the infection, IFN-gamma -/- mice became chronically infected. Virus persistence in the latter mice did not reflect failure to generate cytotoxic T-lymphocyte (CTL) effectors, as an unimpaired primary CTL response was observed. Furthermore, while ex vivo CTL activity...

  2. Immunological aspects of antiviral therapy of chronic hepatitis B virus and hepatitis C virus infections.

    Science.gov (United States)

    Rehermann, Barbara; Bertoletti, Antonio

    2015-02-01

    Hepatitis B virus (HBV) and hepatitis C virus (HCV) cause a large proportion of acute and chronic liver disease worldwide. Over the past decades many immunological studies defined host immune responses that mediate spontaneous clearance of acute HBV and HCV infection. However, host immune responses are also relevant in the context of treatment-induced clearance of chronic HBV and HCV infection. First, the pretreatment level of interferon-stimulated genes as well as genetic determinants of innate immune responses, such as single nucleotide polymorphisms near the IFNL3 gene, are strong predictors of the response to interferon-alpha (IFN-α)-based therapy. Second, IFN-α, which has been a mainstay of HBV and HCV therapy over decades, and ribavirin, which has also been included in interferon-free direct antiviral therapy for HCV, modulate host immune responses. Third, both IFN-α-based and IFN-α-free treatment regimens of HBV and HCV infection alter the short-term and long-term adaptive immune response against these viruses. Finally, treatment studies have not just improved the clinical outcomes, but also provided opportunities to study virus-host interaction. This review summarizes our current knowledge on how a patient's immune response affects the treatment outcome of HBV and HCV infection and how innate and adaptive immune responses themselves are altered by the different treatment regimens.

  3. PCR for diagnosis of male Trichomonas vaginalis infection with chronic prostatitis and urethritis.

    Science.gov (United States)

    Lee, Jong Jin; Moon, Hong Sang; Lee, Tchun Yong; Hwang, Hwan Sik; Ahn, Myoung-Hee; Ryu, Jae-Sook

    2012-06-01

    The aim of this study was to assess the usefulness of PCR for diagnosis of Trichomonas vaginalis infection among male patients with chronic recurrent prostatitis and urethritis. Between June 2001 and December 2003, a total of 33 patients visited the Department of Urology, Hanyang University Guri Hospital and were examined for T. vaginalis infection by PCR and culture in TYM medium. For the PCR, we used primers based on a repetitive sequence cloned from T. vaginalis (TV-E650). Voided bladder urine (VB1 and VB3) was sampled from 33 men with symptoms of lower urinary tract infection (urethral charge, residual urine sensation, and frequency). Culture failed to detect any T. vaginalis infection whereas PCR identified 7 cases of trichomoniasis (21.2%). Five of the 7 cases had been diagnosed with prostatitis and 2 with urethritis. PCR for the 5 prostatitis cases yielded a positive 330 bp band from bothVB1 and VB3, whereas positive results were only obtained from VB1 for the 2 urethritis patients. We showed that the PCR method could detect T. vaginalis when there was only 1 T. vaginalis cell per PCR mixture. Our results strongly support the usefulness of PCR on urine samples for detecting T. vaginalis in chronic prostatitis and urethritis patients.

  4. Molecular identification of chronic bee paralysis virus infection in Apis mellifera colonies in Japan.

    Science.gov (United States)

    Morimoto, Tomomi; Kojima, Yuriko; Yoshiyama, Mikio; Kimura, Kiyoshi; Yang, Bu; Kadowaki, Tatsuhiko

    2012-07-01

    Chronic bee paralysis virus (CBPV) infection causes chronic paralysis and loss of workers in honey bee colonies around the world. Although CBPV shows a worldwide distribution, it had not been molecularly detected in Japan. Our investigation of Apis mellifera and Apis cerana japonica colonies with RT-PCR has revealed CBPV infection in A. mellifera but not A. c. japonica colonies in Japan. The prevalence of CBPV is low compared with that of other viruses: deformed wing virus (DWV), black queen cell virus (BQCV), Israel acute paralysis virus (IAPV), and sac brood virus (SBV), previously reported in Japan. Because of its low prevalence (5.6%) in A. mellifera colonies, the incidence of colony losses by CBPV infection must be sporadic in Japan. The presence of the (-) strand RNA in dying workers suggests that CBPV infection and replication may contribute to their symptoms. Phylogenetic analysis demonstrates a geographic separation of Japanese isolates from European, Uruguayan, and mainland US isolates. The lack of major exchange of honey bees between Europe/mainland US and Japan for the recent 26 years (1985-2010) may have resulted in the geographic separation of Japanese CBPV isolates.

  5. [Opportunistic lung infections in patients with chronic obstructive lung disease; a side effect of inhalation corticosteroids?].

    Science.gov (United States)

    Smeenk, F W; Klinkhamer, P J; Breed, W; Jansz, A R; Jansveld, C A

    1996-01-13

    In four patients, men of 64, 66 and 69 years old and a woman of 65 years, who suffered from chronic obstructive pulmonary disease (COPD) and used inhalation corticosteroids in a relatively high dose (800-1600 micrograms of budesonide per day), a pulmonary infection was diagnosed caused by Mycobacterium malmoense (the first two patients) and Aspergillus (the other two) respectively. Inhalation corticosteroids are of great importance in the treatment of asthmatic patients. Their place in the treatment of patients with COPD is much less clear. The patients did not have an immunological deficiency or anatomical pulmonary or bronchial deformation which could have explained the occurrence of these infections. The high dosages of inhalation corticosteroids may have been involved in the cause of these infections by suppressing the T-cell response locally. In view of this, longterm inhalation corticosteroid treatment should be prescribed in COPD patients only if the efficacy of the medication has been proved in the individual patient involved.

  6. Influence of occult hepatitis B virus infection in chronic hepatitis C outcomes

    Institute of Scientific and Technical Information of China (English)

    Conrado M Fernandez-Rodriguez; Maria Luisa Gutierrez; José Luis Lledó; Maria Luisa Casas

    2011-01-01

    Persistence of hepatitis B virus-DNA in the sera, peripheral blood mononuclear cells or in the liver of hepatitis B surface antigen (HBsAg)-negative patients with or without serological markers of previous exposure (antibodies to HBsAg and/or to HB-core antigen) defines the entity called occult hepatitis B infection (OBI). Co-infection with hepatitis B and hepatitis C viruses is frequent in highly endemic areas. While this co-infection increases the risk of liver disease progression, development of cirrhosis and hepatocellular carcinoma and also increases the rate of therapeutic failure to interferon-based treatments than either virus alone, a potentially negative effect of OBI on clinical outcomes and of therapeutic response to current antiviral regimes of patients with chronic hepatitis C remains inconclusive.

  7. Post-epizootic chronic dolphin morbillivirus infection in Mediterranean striped dolphins Stenella coeruleoalba.

    Science.gov (United States)

    Soto, Sara; Alba, Ana; Ganges, Llilianne; Vidal, Enric; Raga, Juan Antonio; Alegre, Ferrán; González, Beatriz; Medina, Pascual; Zorrilla, Irene; Martínez, Jorge; Marco, Alberto; Pérez, Mónica; Pérez, Blanca; Pérez de Vargas Mesas, Ana; Martínez Valverde, Rosa; Domingo, Mariano

    2011-10-06

    Dolphin morbillivirus (DMV) has caused 2 epizootics with high mortality rates on the Spanish Mediterranean coast, in 1990 and 2006-07, mainly affecting striped dolphins Stenella coeruleoalba. Following the first epizootic unusual DMV infections affecting only the central nervous system of striped dolphins were found, with histological features similar to subacute sclerosing panencephalitis and old dog encephalitis, the chronic latent localised infections caused by defective forms of measles virus and canine distemper virus, respectively. Between 2008 and 2010, monitoring by microscopic and immunohistochemical (IHC) studies of 118 striped dolphins stranded along Catalonia, the Valencia Region and Andalusia showed similar localised DMV nervous system infections in 25.0, 28.6 and 27.4% of cases, respectively, with no significant differences among regions or sex. The body length of DMV-infected dolphins was statistically greater than that of non-infected dolphins (196.5 vs. 160.5 cm; p dolphins with positive IHC-DMV had positive PCR results. All 6 cases were positive with the 78 bp RT-PCR. These findings contraindicate the use of the 429 bp RT-PCR protocol based on the P gene to detect this specific form of DMV. DMV localised nervous infection constitutes the most relevant single cause of stranding and death in Mediterranean striped dolphins in the years following a DMV epizootic, and it might even overwhelm the effects of the epizootic itself, at least in 2007.

  8. Is laparoscopy an advantage in the diagnosis of cirrhosis in chronic hepatitis C virus infection?

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Felix Braun; Peter Schott; Giuliano Ramadori

    2003-01-01

    AIM: To evaluate the potential of laparoscopy in the diagnosis of cirrhosis and outcome of interferon treatment in HCV-infected patients.METHODS: In this retrospective study, diagnostic laparoscopy with laparoscopic liver biopsy was performed in 72 consecutive patients with chronic HCV infection. The presence or absence of cirrhosis was analyzed macroscopically by laparoscopy and microscopically by liver biopsy specimens. Clinical and laboratory data and outcome of interferon-alfa treatment were compared between cirrhotic and noncirrhotic patients.RESULTS: Laparoscopically, cirrhosis was seen in 29.2%(21/72) and non-cirrhosis in 70.8% (51/72) of patients.Cirrhotic patients were significantly older with a significant longer duration of HCV infection than noncirrhotic patients.Laboratory parameters (AST, y-GT, y-globulin fraction) were measured significantly higher as well as significantly lower (prothrombin index, platelet count) in cirrhotic patients than in non-cirrhotic patients. Histologically, cirrhosis was confirmed in 11.1% (8/72) and non cirrhosis in 88.9% (64/72). Patients with macroscopically confirmed cirrhosis (n=21) showed histologically cirrhosis in 38.1% (8/21) and histologically noncirrhosis in 61.9% (13/21). In contrast, patients with macroscopically non-cirrhosis (n=51) showed histologically non cirrhosis in all cases (51/51). Thirty-nine of 72 patients were treated with interferon-alfa, resulting in 35.9% (14/39)patients with sustained response and 64.1% (25/39) with non response. Non-responders showed significantly more macroscopically cirrhosis than sustained responders. In contrast, there were no significant histological differences between non-responders and sustained responders.CONCLUSION: Diagnostic laparoscopy is more accurate than liver biopsy in recognizing cirrhosis in patients with chronic HCV infection. Liver biopsy is the best way to assess inflammatory grade and fibrotic stage. The invasive marker for staging, prognosis and

  9. Pathogenesis and management of virus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

    Science.gov (United States)

    Yamaya, Metstuo

    2002-06-01

    The number of senile patients with therapy resistant bronchial asthma, chronic pulmonary emphysema increases due to the habit of smoking and increased number of older people, and these inflammatory pulmonary diseases are the leading causes of death worldwide. Rhinoviruses cause the majority of common colds, and provoke exacerbations of bronchial asthma and chronic pulmonary emphysema. Here, I review the pathogenesis and management of rhinovirus infection-induced exacerbation of senile bronchial asthma and chronic pulmonary emphysema.

  10. A Comparative Study of Clinicopathological Features between Chronic Cholecystitis Patients with and without Helicobacter pylori Infection in Gallbladder Mucosa

    OpenAIRE

    Zhou, Di; Guan, Wen-bin; Wang, Jian-Dong; Zhang, Yong,; Gong, Wei; Quan, Zhi-wei

    2013-01-01

    Background Helicobacter pylori has been isolated from 10%–20% of human chronic cholecystitis specimens but the characteristics of “Helicobacter pylori positive cholecystitis” remains unclear. This study aims to compare the clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infection in gallbladder mucosa. Methods Three hundred and twenty-six chronic cholecystitis patients were divided into two groups according to whether Helicobacter pylor...

  11. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Esteban R Fernández

    Full Text Available Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  12. Altered distribution of peripheral blood memory B cells in humans chronically infected with Trypanosoma cruzi.

    Science.gov (United States)

    Fernández, Esteban R; Olivera, Gabriela C; Quebrada Palacio, Luz P; González, Mariela N; Hernandez-Vasquez, Yolanda; Sirena, Natalia María; Morán, María L; Ledesma Patiño, Oscar S; Postan, Miriam

    2014-01-01

    Numerous abnormalities of the peripheral blood T cell compartment have been reported in human chronic Trypanosoma cruzi infection and related to prolonged antigenic stimulation by persisting parasites. Herein, we measured circulating lymphocytes of various phenotypes based on the differential expression of CD19, CD4, CD27, CD10, IgD, IgM, IgG and CD138 in a total of 48 T. cruzi-infected individuals and 24 healthy controls. Infected individuals had decreased frequencies of CD19+CD27+ cells, which positively correlated with the frequencies of CD4+CD27+ cells. The contraction of CD19+CD27+ cells was comprised of IgG+IgD-, IgM+IgD- and isotype switched IgM-IgD- memory B cells, CD19+CD10+CD27+ B cell precursors and terminally differentiated CD19+CD27+CD138+ plasma cells. Conversely, infected individuals had increased proportions of CD19+IgG+CD27-IgD- memory and CD19+IgM+CD27-IgD+ transitional/naïve B cells. These observations prompted us to assess soluble CD27, a molecule generated by the cleavage of membrane-bound CD27 and used to monitor systemic immune activation. Elevated levels of serum soluble CD27 were observed in infected individuals with Chagas cardiomyopathy, indicating its potentiality as an immunological marker for disease progression in endemic areas. In conclusion, our results demonstrate that chronic T. cruzi infection alters the distribution of various peripheral blood B cell subsets, probably related to the CD4+ T cell deregulation process provoked by the parasite in humans.

  13. Antibodies against beta-lactamase can improve ceftazidime treatment of lung infection with beta-lactam-resistant Pseudomonas aeruginosa in a rat model of chronic lung infection

    DEFF Research Database (Denmark)

    Ciofu, Oana; Bagge, Niels; Høiby, Niels

    2002-01-01

    To test the hypothesis that antibodies against the chromosomal beta-lactamase of Pseudomonas aeruginosa (a beta ab) might act as beta-lactamase inhibitors in patients with cystic fibrosis and chronic lung infection with P. aeruginosa, we compared in a rat model of chronic lung infection...... the efficacy of treatment with ceftazidime in beta-lactamase-immunized (group I) and non-immunized (group II) rats. Chronic lung infection was established with alginate-embedded P. aeruginosa producing high amounts of beta-lactamase in 133 Lewis rats. Prior to infection, group I (66 rats) was immunized three...... times at 2-week intervals with purified beta-lactamase in incomplete Freund's adjuvant (IFA) and group II (67 rats) received IFA. Ceftazidime treatment was initiated after challenge and continued for 10 days, after which the rats were sacrificed and the lung bacteriology and pathology were analysed. Rat...

  14. Immunoregulatory actions of melatonin and zinc during chronic Trypanosoma cruzi infection.

    Science.gov (United States)

    Brazão, Vânia; Santello, Fabricia Helena; Filipin, Marina Del Vecchio; Azevedo, Angela Palamin; Toldo, Míriam Paula Alonso; de Morais, Fabiana Rossetto; do Prado, José Clóvis

    2015-03-01

    After one century of the discovery of Chagas' disease and the development of an efficient drug with amplitude of actions both in the acute and chronic phase is still a challenge. Alternative immune modulators have been exhaustively used. For that purpose, melatonin and zinc were administered during chronic Trypanosoma cruzi-infected Wistar rats and several endpoints were assessed. Melatonin has a remarkable functional versatility, being associated with important antioxidant, anti-inflammatory, and anti-apoptotic effects. The cross-talk between zinc and the immune system includes its ability to influence the production and signaling of numerous inflammatory cytokines in a variety of cell types. Our study showed that zinc triggered a decrease in the generation of IFN-γ for TCD4(+) cells. Reduced percentage of CD4(+) T cells producing TNF-α was observed in control melatonin or zinc-and-melatonin-treated animals as compared with untreated rats. On the other hand, a significant increase in the percentage of IL-4 from CD4(+) and CD8(+) T lymphocytes producers was observed 60 days after infection, for all zinc-treated animals, whether infected or not. Melatonin and zinc therapies increased the percentages of CD4(+) and CD8(+) T lymphocytes IL-10 producers. CD4(+) CD25(high) Foxp3(+) T cells were also elevated in zinc- and melatonin-treated animals. The modulation of the immune system influenced by these molecules affected cytokine production and the inflammatory process during chronic T. cruzi infection. Elucidation of the interplay between cytokine balance and the pathogenesis of Chagas' disease is extremely relevant not only for the comprehension of the immune mechanisms and clinical forms but, most importantly, also for the implementation of efficient and adequate therapies.

  15. Cellular immune responses and occult infection in seronegative heterosexual partners of chronic hepatitis C patients.

    Science.gov (United States)

    Roque-Cuéllar, M C; Sánchez, B; García-Lozano, J R; Praena-Fernández, J M; Núñez-Roldán, A; Aguilar-Reina, J

    2011-10-01

    It is unknown whether hepatitis C virus (HCV)-specific cellular immune responses can develop in seronegative sexual partners of chronically HCV-infected patients and whether they have occult infection. Thirty-one heterosexual partners of patients with chronic HCV were studied, fifteen of them with HCV transmission risks. Ten healthy individuals and 17 anti-HCV seropositive patients, without viremia, were used as controls. Virus-specific CD4+ and CD8+ T-cell responses were measured by flow cytometry against six HCV peptides, situated within the nonstructural (NS) proteins NS3, NS4 and NS5, through intracellular detection of gamma interferon (IFN-γ) or interleukin 4 (IL-4) production and CD69 expression. Sexual partners had a higher production of IFN-γ and IL-4 by CD4+ cells against NS3-p124 (P = 0.003), NS5b-p257 (P = 0.005) and NS5b-p294 (P = 0.012), and CD8+ cells against NS3-p124 (P = 0.002), NS4b-p177 (P = 0.001) and NS3-p294 (P = 0.004) as compared with healthy controls. We observed elevated IFN-γ production by CD4+ T cells against NS5b-p257 (P = 0.042) and NS5b-p294 (P = 0.009) in the sexual partners with HCV transmission risks (sexual, professional and familial altogether) than in those without risks. RNA was extracted from peripheral blood mononuclear cells (PBMC), and detection of HCV-RNA positive and replicative (negative) strands was performed by strand-specific real-time PCR. In four sexual partners, the presence of positive and negative HCV- RNA strands in PBMC was confirmed. Hence, we found an HCV-specific cellular immune response as well as occult HCV infection in seronegative and aviremic sexual partners of chronically HCV-infected patients.

  16. Acute hepatitis C in a chronically HIV-infected patient: Evolution of different viral genomic regions

    Institute of Scientific and Technical Information of China (English)

    Diego Flichman; Veronica Kott; Silvia Sookoian; Rodolfo Campos

    2003-01-01

    AIM: To analyze the molecular evolution of different viral genomic regions of HCV in an acute HCV infected patient chronically infected with HIV through a 42-month follow-up.METHODS: Serum samples of a chronically HIV infected patient that seroconverted to anti HCV antibodies were sequenced, from the event of superinfection through a period of 17 months and in a late sample (42nd month). Hypervariable genomic regions of HIV (V3 loop of the gp120) and HCV (HVR-1 on the E2 glycoprotein gene) were studied. In order to analyze genomic regions involved in different biological functions and with the cellular immune response, HCV core and NS5A were also chosen to be sequenced. Amplification of the different regions was done by RT-PCR and directly sequenced. Confirmation of sequences was done on reamplified material. Nucleotide sequences of the different time points were aligned with CLUSTAL W 1.5, and the corresponding amino acid ones were deduced.RESULTS: Hypervariable genomic regions of both viruses (HVR1 and gp120 V3 loop) presented several nonsynonymous changes but, while in the gp120 V3 loop mutations were detected in the sample obtained right after HCV superinfection and maintained throughout, they occurred following a sequential and cumulative pattern in the HVR1. In the NS5A region of HCV, two amino acid changes were detected during the follow-up period, whereas the core region presented several amino acid replacements, once the HCV chronic infection had been established.CONCLUSION: During the HIV-HCV superinfection, each genomic region analyzed shows a different evolutionary pattem.Most of the nucleotide substitutions observed are nonsynonymous and clustered in previously described epitopes,thus suggesting an immune-driven evolutionary process.

  17. Immune activation response in chronic HIV-infected patients: influence of Hepatitis C virus coinfection.

    Directory of Open Access Journals (Sweden)

    Mercedes Márquez

    Full Text Available We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated.Seventy HIV-infected patients [monoinfected by HIV (n = 20, HCV-coinfected (with (n = 25 and without (n = 25 liver cirrhosis] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months.Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase.In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients.

  18. Immune Activation Response in Chronic HIV-Infected Patients: Influence of Hepatitis C Virus Coinfection

    Science.gov (United States)

    Márquez, Mercedes; Romero-Cores, Paula; Montes-Oca, Monserrat; Martín-Aspas, Andrés; Soto-Cárdenas, María-José; Guerrero, Francisca; Fernández-Gutiérrez, Clotilde; Girón-González, José-Antonio

    2015-01-01

    Objectives We have analyzed the parameters (bacterial translocation, immune activation and regulation, presence of HCV coinfection) which could be implicated in an inappropriate immune response from individuals with chronic HIV infection. The influence of them on the evolution of CD4+ T cell count has been investigated. Patients and methods Seventy HIV-infected patients [monoinfected by HIV (n = 20), HCV-coinfected (with (n = 25) and without (n = 25) liver cirrhosis)] and 25 healthy controls were included. Median duration of HIV infection was 20 years. HIV- and HCV-related parameters, as well as markers relative to bacterial translocation, monocyte and lymphocyte activation and regulation were considered as independent variables. Dependent variables were the increase of CD4+ T cell count during the follow-up (12 months). Results Increased values of bacterial translocation, measured by lipopolysaccharide-binding protein, monocyte and lymphocyte activation markers and T regulatory lymphocytes were detected in HIV-monoinfected and HIV/HCV coinfected patients. Serum sCD14 and IL-6 were increased in HIV/HCV-coinfected patients with liver cirrhosis in comparison with those with chronic hepatitis or HIV-monoinfected individuals. Time with undetectable HIV load was not related with these parameters. The presence of cirrhosis was negatively associated with a CD4+ T cell count increase. Conclusion In patients with a chronic HIV infection, a persistent increase of lipopolysaccharide-binding protein and monocyte and lymphocyte modifications are present. HCV-related cirrhosis is associated with more elevated serum concentrations of monocyte-derived markers. Cirrhosis influences the continued immune reconstitution of these patients. PMID:25775475

  19. Mupirocin in the Treatment of Staphylococcal Infections in Chronic Rhinosinusitis: A Meta-Analysis

    Science.gov (United States)

    2016-01-01

    Background Saline irrigation of the nasal cavity is a classic and effective treatment for acute or chronic rhinosinusitis. Topical antibiotics such as mupirocin have been widely used for recalcitrant chronic rhinosinusitis. Therefore, the purpose of this study was to evaluate the effect of saline irrigation using mupirocin. Methods A systematic literature review and meta-analysis of mupirocin saline irrigation were performed using EMBASE, MEDLINE, and Cochrane library through December 2015. Data were analyzed with R 3.2.2 software. A random effects model was used because of the diversity of included studies. Sensitivity analysis of particular tested groups and single proportion tests were also performed. The main outcome measure was residual staphylococcal infection, as confirmed by culture or PCR. Results Two RCTs, two prospective studies and two retrospective studies were included. A random effects model meta-analysis of the pooled data identified a relative risk of residual infection of 0.13 (95% CI: 0.06–0.26, prhinosinusitis. Although there is currently a lack of clear evidence, future studies with well-designed inclusion criteria and randomized controlled trials are needed to examine mupirocin’s long-term effect on chronic rhinosinusitis. PMID:27907108

  20. Prevalence of occult HBV infection in haemodialysis patients with chronic HCV

    Institute of Scientific and Technical Information of China (English)

    Vedat Goral; Hamza Ozkul; Selahattin Tekes; Dede Sit; Ali Kemal Kadiroglu

    2006-01-01

    AIM: To study the prevalence and clinical effects of occult HBV infection in haemodialysis patients with chronic HCV.METHODS: Fifty chronic hemodialysis patients with negative HbsAg, and positive anti-HCV were included in the study. These patients were divided into two groups:HCV-RNA positive and HCV-RNA negative, based on the results of HCV-RNA PCR. HBV-DNA was studied using the PCR method in both groups.RESULTS: None of the 22 HCV-RNA positive patients and 28 HCV-RNA negative patients revealed HBV-DNA in serum by PCR method. The average age was 47.2 ± 17.0 in the HCV-RNA positive group and 39.6 ± 15.6 in the HCV-RNA negative group.CONCLUSION: The prevalence of occult HBV infection is not high in haemodialysis patients with chronic HCV in our region. This result of our study has to be evaluated in consideration of the interaction between HBsAg positivity (8%-10%) and frequency of HBV mutants in our region.

  1. Proifle, spectrum and signiifcance of hepatitis B virus genotypes in chronic HBV-infected patients in Yunnan, China

    Institute of Scientific and Technical Information of China (English)

    Jing You; Bao-Zhang Tang; Hutcha Sriplung; Virasakdi Chongsuvivatwong; Alan Geater; Lin Zhuang; Jun-Hua Huang; Hong-Ying Chen; Lan Yu

    2008-01-01

    BACKGROUND:There are signiifcant variations in the geographical distribution of hepatitis B virus (HBV) genotypes throughout the world, and some genotypes are associated with different clinical outcomes. Eight genotypes of human HBV (designated A-H) have been reported. The present study was designed to examine the distribution of HBV genotypes among patients at various stages of chronic type B liver disease in Yunnan Province, China, and to explore its signiifcance and the relationship of HBV genotype with gender and age, clinical spectrum of chronic HBV infection, and viral replicative activity. METHODS:Serum samples from 126 patients with chronic HBV infection from Yunnan Province, including 26 chronic asymptomatic HBV carriers (ASC), 61 patients with chronic hepatitis B (CHB) (21 mild, 30 moderate and 10 severe), 20 patients with chronic fulminant hepatic failure (CFHF), 12 patients with HBV-related liver cirrhosis (LC) and 7 patients with HBV-related hepatocellular carcinoma (HCC) were analyzed using reverse dot blot (RDB) methodology, which is based on the reverse hybridization principle for HBV genotyping. The relations of HBV genotype with gender and age, clinical patterns, and serological data of the patients were analyzed. RESULTS: In this series, genotypes A, B, C, and D were found. 38.1%patients (48/126) belonged to B, 54.8%(69/126) to C, 0.8%(1/126) to D, 1.6%(2/126) to a mixture of B and C, and 1.6%(2/126) to a mixture of A and C. 3.2%patients (4/126) had unknown genotypes. No other genotypes (E, F, G, and H) were found. Genotypes B and C were predominant. There was a statistically signiifcant difference in the distributions of genotypes C and B (χ2=7.04, P=0.008), and C was the dominant genotype in all patient categories. The rate of genotype B in the mild CHB group was signiifcantly higher than that in the moderate and severe groups (χ2=12.16, P=0.0001; χ2=11.98, P=0.001, respectively), the ASC group (χ2=5.46, P=0.02), the CFHF group (χ2

  2. Improved outcome of chronic Pseudomonas aeruginosa lung infection is associated with induction of a Th1-dominated cytokine response

    DEFF Research Database (Denmark)

    Moser, C; Jensen, P O; Kobayashi, O;

    2002-01-01

    Repeated challenge with antigen is involved in the pathogenesis of a variety of pulmonary diseases. Patients with cystic fibrosis (CF) experience recurrent pulmonary colonization with Pseudomonas aeruginosa before establishment of chronic lung infection. To mimic recurrent lung infections in CF p...

  3. Disposition of mefloquine and enpiroline is highly influenced by a chronic Schistosoma mansoni infection.

    Science.gov (United States)

    Ingram, Katrin; Duthaler, Urs; Vargas, Mireille; Ellis, William; Keiser, Jennifer

    2013-09-01

    Chronic Schistosoma mansoni infections lead to severe tissue destruction of the gut wall and liver and can influence drug disposition. This study aimed to investigate the impact of a chronic S. mansoni infection on the pharmacokinetic (PK) parameters of two promising antischistosomal lead candidates (mefloquine and enpiroline) in mice. Studies were conducted in two different mouse cohorts (S. mansoni-infected and uninfected mice) for both drugs. Plasma samples were collected at various time points after oral treatment (200 mg/kg of body weight) with study drugs. A high-performance liquid chromatography (HPLC) method was validated to analyze enpiroline and mefloquine in plasma. Livers and intestines were collected from infected animals to determine the onset of action, hepatic shift, and worm burden reduction. Following mefloquine administration, hepatic shifting and significant worm burden reductions (79.2%) were observed after 72 h. At 1 week posttreatment with enpiroline, the majority of worms had migrated to the liver and significant worm burden reductions were observed (93.1%). The HPLC method was selective, accurate (87.8 to 111.4%), and precise (mefloquine, with a 5-fold increase of t1/2 (182.7 h versus 33.6 h) and 2-fold increase of AUC (1,116,517.8 ng · h/ml versus 522,409.1 ng · h/ml). S. mansoni infections in mice influence the PK profiles of enpiroline and mefloquine, leading to delayed clearance. Our data confirm that drug disposition should be carefully studied in schistosomiasis patients.

  4. Activated ClpP kills persisters and eradicates a chronic biofilm infection.

    Energy Technology Data Exchange (ETDEWEB)

    Conlon, Brian P.; Nakayasu, Ernesto S.; Fleck, Laura E.; LaFleur, Michael D.; Isabella, Vincent M.; Coleman, K.; Leonard, Steve N.; Smith, Richard D.; Adkins, Joshua N.; Lewis, Kim

    2013-11-21

    The current antibiotic crisis stems from two distinct phenomena-drug resistance, and drug tolerance. Resistance mechanisms such as drug efflux or modification prevent antibiotics from binding to their targets 1, allowing pathogens to grow. Antibiotic tolerance is the property of persister cells, phenotypic variants of regular bacteria 2. Antibiotics kill by corrupting targets, but these are inactive in dormant persisters, leading to tolerance. Persisters were first identified by Joseph Bigger in 1944, when he discovered a surviving sub-population of Staphylococcus following treatment with penicillin3. Persisters are largely responsible for recalcitrance of chronic diseases such as tuberculosis, and various infections associated with biofilms - endocarditis, osteomyelitis, infections of catheters and indwelling devices, and deep-seated infections of soft tissues 4. There are a number of redundant pathways involved in persister formation5,6 precluding development of drugs inhibiting their formation. The acyldepsipeptide antibiotic (ADEP 4) has been shown to activate the ClpP protease resulting in death of growing cells 7. Here we show that ADEP4 activated ClpP becomes a fairly non-specific protease and kills persister cells by degradation of over 400 intracellular targets. clpP mutants are resistant to ADEP4 7, but we find that they display increased susceptibility to killing by a range of conventional antibiotics. Combining ADEP4 with rifampicin leads to eradication of persisters, stationary and biofilm populations of Staphylococcus aureus in vitro and in a deep-seated murine infection. Target corruption/activation provides an approach to killing persisters and eradicating chronic infections.

  5. IL-22 Defect During Streptococcus pneumoniae Infection Triggers Exacerbation of Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Muriel Pichavant

    2015-11-01

    Full Text Available Progression of chronic obstructive pulmonary disease (COPD is linked to episodes of exacerbations caused by bacterial infections due to Streptococcus pneumoniae. Our objective was to identify during COPD, factors of susceptibility to bacterial infections among cytokine network and their role in COPD exacerbations. S. pneumoniae was used to sub-lethally challenge mice chronically exposed to air or cigarette smoke (CS and to stimulate peripheral blood mononuclear cells (PBMC from non-smokers, smokers and COPD patients. The immune response and the cytokine production were evaluated. Delayed clearance of the bacteria and stronger lung inflammation observed in infected CS-exposed mice were associated with an altered production of IL-17 and IL-22 by innate immune cells. This defect was related to a reduced production of IL-1β and IL-23 by antigen presenting cells. Importantly, supplementation with recombinant IL-22 restored bacterial clearance in CS-exposed mice and limited lung alteration. In contrast with non-smokers, blood NK and NKT cells from COPD patients failed to increase IL-17 and IL-22 levels in response to S. pneumoniae, in association with a defect in IL-1β and IL-23 secretion. This study identified IL-17 and IL-22 as susceptibility factors in COPD exacerbation. Therefore targeting such cytokines could represent a potent strategy to control COPD exacerbation.

  6. Chronic inhibition of cyclooxygenase-2 attenuates antibody responses against vaccinia infection.

    Science.gov (United States)

    Bernard, Matthew P; Bancos, Simona; Chapman, Timothy J; Ryan, Elizabeth P; Treanor, John J; Rose, Robert C; Topham, David J; Phipps, Richard P

    2010-02-01

    Generation of optimal humoral immunity to vaccination is essential to protect against devastating infectious agents such as the variola virus that causes smallpox. Vaccinia virus (VV), employed as a vaccine against smallpox, provides an important model of infection. Herein, we evaluated the importance cyclooxygenase-2 (Cox-2) in immunity to VV using Cox-2 deficient mice and Cox-2 selective inhibitory drugs. The effects of Cox-2 inhibition on antibody responses to live viruses such as vaccinia have not been previously described. Here, we used VV infection in Cox-2 deficient mice and in mice chronically treated with Cox-2 selective inhibitors and show that the frequency of VV-specific B cells was reduced, as well as the production of neutralizing IgG. VV titers were approximately 70 times higher in mice treated with a Cox-2 selective inhibitor. Interestingly, Cox-2 inhibition also reduced the frequency of IFN-gamma producing CD4(+) T helper cells, important for class switching. The significance of these results is that the chronic use of non-steroidal anti-inflammatory drugs (NSAIDs), and other drugs that inhibit Cox-2 activity or expression, blunt the ability of B cells to produce anti-viral antibodies, thereby making vaccines less effective and possibly increasing susceptibility to viral infection. These new findings support an essential role for Cox-2 in regulating humoral immunity.

  7. HLA DRB1 alleles and hepatitis C virus infection in chronic kidney disease patients.

    Science.gov (United States)

    Shaheen, Noha Mohamed Hosni; Soliman, Amin Roshdy; El-Khashab, Sahier Omar; Hanna, Mariam Onsy Farag

    2013-01-01

    T cell responses against HCV are regulated by the host's human leukocyte antigen (HLA) alleles, which thus are ideal candidate genes to investigate for associations with HCV susceptibility. We aimed to identify associations of HLA DRB1* alleles with HCV infection in a high risk of exposure population, chronic kidney disease (CKD) patients on dialysis, and to study any possible relationships with allele zygosity. The study population comprised 110 HCV infected and 143 HCV uninfected CKD patients undergoing regular hemodialysis. HLA DRB1* alleles were determined using polymerase chain reaction followed by hybridization with sequence-specific oligonucleotide probes. We found a significant negative association between HLA DRB1*03 and HCV infection, but the association did not retain significance after adjustment for multiple comparisons. HLA DRB1*03 was found at reduced frequency in HCV antibody positive compared to HCV antibody negative CKD patients on regular dialysis (corrected p was not significant). No significant association between HCV infection and HLA DRB1* zygosity was observed. Our results suggest that there is minimal evidence for a significant role of a particular HLA DRB1* allele or allele zygosity in the susceptibility or protection to HCV in high-risk hemodialysis patients with similar exposure to infection.

  8. Spatial and Temporal Shifts in Bacterial Biogeography and Gland Occupation during the Development of a Chronic Infection

    Science.gov (United States)

    Zavros, Yana; Shepherd, Benjamin; Salama, Nina R.

    2016-01-01

    ABSTRACT Gland colonization may be one crucial route for bacteria to maintain chronic gastrointestinal infection. We developed a quantitative gland isolation method to allow robust bacterial population analysis and applied it to the gastric pathobiont Helicobacter pylori. After infections in the murine model system, H. pylori populations multiply both inside and outside glands in a manner that requires the bacteria to be motile and chemotactic. H. pylori is able to achieve gland densities averaging 25 to 40 bacteria/gland after 2 to 4 weeks of infection. After 2 to 4 weeks of infection, a primary infection leads to colonization resistance for a secondary infection. Nonetheless, about ~50% of the glands remained unoccupied, suggesting there are as-yet unappreciated parameters that prevent gastric gland colonization. During chronic infections, H. pylori populations collapsed to nearly exclusive gland localization, to an average of <8 bacteria/gland, and only 10% of glands occupied. We analyzed an H. pylori chemotaxis mutant (Che−) to gain mechanistic insight into gland colonization. Che− strains had a severe inability to spread to new glands and did not protect from a secondary infection but nonetheless achieved a chronic gland colonization state numerically similar to that of the wild type. Overall, our analysis shows that bacteria undergo substantial population dynamics on the route to chronic colonization, that bacterial gland populations are maintained at a low level during chronic infection, and that established gland populations inhibit subsequent colonization. Understanding the parameters that promote chronic colonization will allow the future successful design of beneficial microbial therapeutics that are able to maintain long-term mammalian colonization. PMID:27729513

  9. A comparison between previous and present histologic assessments of chronic hepatitis C viral infections in humans

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    AIM To compare the previously employed classification of liver histology (minimal, chronic persistent hepatitis, chronic active hepatitis and cirrhosis) with a new classification recently described by Sheuer et al (activity grade and fibrosis stage) in percutaneous liver biopsies from patients with chronic hepatitis C viral infections.METHODS Liver biopsies from 79 untreated patients were reviewed. Anti-HCV testing had been performed by ELISA and confirmed by a recombinant immunoblot assay. With respect to the new classification, all the specimens were evaluated using the Knodell score for activity.RESULTS A good correlation was revealed between the previous and more recent histologic classifications in patients with abnormal liver enzyme tests. However, in 13/ 15 (87%) of patients with normal aminotransferase values, changes were consistent with chronic persistent hepatitis whereas normal activity and no fibrosis were demonstrated by the Sheuer classification.CONCLUSION The old classification is more often misleading but correlates well with the new classification and thereby permits comparisons between historically clinical studies.

  10. Improvement of complex therapy of patients with pathology of scrotal organs formed by chronic brucellosis infection

    Directory of Open Access Journals (Sweden)

    Glybochko Р. V.

    2013-06-01

    Full Text Available The aim of the study is to improve the treatment of patients with male reproductive organs pathology, formed by chronic brucellosis infection. Material and methods: We have analyzed the dynamics of the clinical manifestations of diseases of the scrotal organs, data of physical and ultrasound studies, semen parameters, the quality of life in 22 patients with chronic brucellosis and the presence of orchitis / orchiepididymitis against conventional therapy (10 patients, and combined treatment with the inclusion of cycloferon (i/m, 2 injection rate from 5 (0.25g with a break 10 days — 12. Results: We have proved ability of cycloferon to reduce the severity of the inflammatory process in the testis and epididymis, with improving of spermatogenesis and the quality of life for patients. We have marked the reduction in the number of exacerbations of chronic orchitis / orchiepididymitis 2.4 times after the course of cycloferon, its good tolerability of patients, no side effects. Conclusion: Using these results, the presence of anti-inflammatory and immunomodulatory potencies, cycloferon can be recommended in treatment of inflammatory lesions of the scrotal organs in patients with chronic brucellosis.

  11. Does chronic hepatitis B infection affect the clinical course of acute hepatitis A?

    Science.gov (United States)

    Shin, Su Rin; Moh, In Ho; Jung, Sung Won; Kim, Jin Bae; Park, Sang Hoon; Kim, Hyoung Su; Jang, Myung Kuk; Lee, Myung Seok

    2013-01-01

    The impact of chronic hepatitis B on the clinical outcome of acute hepatitis A remains controversial. The aim of present study was to evaluate the clinical characteristics of acute hepatitis A in cases with underlying chronic hepatitis B compared to cases of acute hepatitis A alone. Data on 758 patients with acute hepatitis A admitted at two university-affiliated hospitals were reviewed. Patients were classified into three groups: group A, patients with both acute hepatitis A and underlying chronic hepatitis B (n = 27); group B, patients infected by acute hepatitis A alone whose sexes and ages were matched with patients in group A (n  = 54); and group C, patients with acute hepatitis A alone (n = 731). None of the demographic features of group A were significantly different from those of group B or C, except for the proportion of males and body weight, which differed from group C. When comparing to group B, clinical symptoms were more frequent, and higher total bilirubin and lower albumin levels were observed in group A. When comparing to group C, the albumin levels were lower in group A. There were no differences in the duration of hospital stay, occurrence of acute kidney injury, acute liver failure, prolonged cholestasis, or relapsing hepatitis. This study revealed that clinical symptoms and laboratory findings were less favorable for patients with acute hepatitis A and chronic hepatitis B compared to those with acute hepatitis A alone. However, there were no differences in fatal outcomes or serious complications.

  12. Intestinal parasitic infection in patients with chronic human immunodeficiency virus infection%慢性HIV感染者的肠道寄生虫感染

    Institute of Scientific and Technical Information of China (English)

    温少芳; 王玉光; 成军

    2011-01-01

    慢性HIV感染者易合并多种感染,其中合并肠道寄生虫感染可造成体内HIV复制增加、慢性腹泻、消瘦及营养不良而加快病情发展.此文就慢性HIV感染者合并的肠道寄生虫感染进行了综述.%Patients with chronic HIV infection may be complicated by varied infection.Intestinal parasitic infection may raise the replication of HIV,chronic diarrhea,emaciation and malnutrition,which could enhance the development of the disease.In this article,intestinal parasitic infection in patients infected with HIV are reviewed.

  13. PREVALENCE OF DIABETES MELLITUS TYPE 2 IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION

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    Ranjeet

    2015-01-01

    Full Text Available BACKGROUND: There is a growing body of literature on the relationship of Hepatitis C Virus (HCV infection and diabetes mellitus type 2 as its unique extrahepatic manifestation. This association was for the first time made by Allison et al. in 1994 . [1] Since then a number of observational studies have been published on the prevalence of diabetes in HCV infection and also the link between association of cirrhosis with diabetes mellitus. AIMS : To study the prevalence of diabetes mellitus type 2 in patients diagnosed to have chronic hepatitis C virus infection. To compare it with the prevalence of diabetes mellitus type 2 in general population. SETTINGS AND DESIGN : A case control study. Participants were the subjects attending the OPD / indoor of Sri Guru Ramdas Institute of Medical Sciences and Research, Amritsar. PATIENTS AND METHODS : 50 patients older than 18 years, with chronic HCV infection confirmed by ELISA, were investigated for their blood counts, LFTs, prothrombin time , serum proteins, glycosylated hemoglobin levels and abdominal ultrasonography after applying the exclusion criteria. Detailed clinical examination was done to assess for signs of encephalopathy and ascites. An equal number of age and sex matched , HCV seronegative patients with normal liver function tests were taken as controls. The prevalence of diabetes mellitus was then determined among the two groups. A relationship between HCV and Diabetes mellitus type 2 was then established. STATISTICAL ANALYSIS USED: Data was expressed as mean + SD. For categorical variables a chi square test was applied and p value was calculated. For the comparison of continuous data, the student t – test was used. Probability levels less than 0.05 were considered significant. RESULTS : 50% ( 25 out of 50 patients with chronic hepatitis C infection were diabetic while 30% (15 out of 50 of the controls were diabetic. The difference was statistically significant ( p=0.041 . Further , of the

  14. Autoantibody production in chronic idiopathic urticaria is not associated with Helicobacter pylori infection

    Directory of Open Access Journals (Sweden)

    Atta A.M.

    2004-01-01

    Full Text Available Chronic idiopathic urticaria (CIU is a dermatological syndrome, characterized by raised erythematous skin lesions, that affects 20% of the general population and has been associated with autoimmunity. However, some reports have also suggested a close relationship between CIU and Helicobacter pylori infection, which is endemic in developing countries and associated with chronic gastritis, peptic ulcer disease, and gastric carcinoma. In the present study, we investigated the occurrence of autoantibodies in sera from 23 CIU subjects infected with H. pylori and from 23 CIU subjects without this infection. The presence of anti-thyroid antibodies was determined by indirect hemagglutination assay and the presence of autoantibodies to IgE and C1INH was determined by ELISA. Antibodies to thyroid antigens were detected at low titers from 100 to 400 in three of 23 (13% CIU-infected subjects and in four of 23 (17% CIU-noninfected subjects. The titers of anti-IgE autoantibodies were similar in these CIU groups, presenting absorbances of 1.16 ± 0.09 and 1.07 ± 0.16, respectively, while a titer of 1.14 ± 0.15 was detected in the healthy control group. The concentration of anti-C1INH autoantibodies was the same in the CIU-infected and -noninfected subjects (7.28 ± 1.31 and 7.91 ± 2.45 ng/ml, respectively, and was 7.20 ± 2.25 ng/ml in the healthy control group. However, the serum levels of complexed anti-C1INH antibodies were increased in CIU-infected subjects compared to CIU-noninfected subjects and healthy controls with an absorbance of 1.51 ± 0.21 vs 1.36 ± 0.16 and 1.26 ± 0.23, respectively (P < 0.05, indicating an impaired clearance of immune complexes in CIU-infected patients. In conclusion, no correlation was observed between H. pylori infection and autoantibody production in CIU patients consistent with reports of clinical studies.

  15. Оptimization of periodontitis treatment in patients with chronic brucellosis infection

    Directory of Open Access Journals (Sweden)

    L.A. Soboleva

    2010-06-01

    Full Text Available For the purpose to determine the clinical pathogenetic efficacy of Cycloferon liniment in the combined therapy of parodontitis in patients with chronic brucellosis medical examination and treatment of 50 patients was carried out. It was established that use of liniment Cycloferon in the combined treatment of patients with pariodontitis against chronic brucellosis allowed to accelerate process of normalization of parameters of lipid peroxidation and antioxidant potential of blood, to decrease infection load (herpes symplex virus I, candida albicans, staphylococcus aureus in parodontal recess and evidence of local inflammation with reduction of activity of tumour necrosis and interleukin 1b, that provided acceleration of recovery processes, lowering in frequency of pariodontitis recurrences

  16. Treatment of extrahepatic manifestations of chronic hepatitis C viral infection--a challenge.

    Science.gov (United States)

    Tănăsescu, C; Ionescu, R

    2010-01-01

    Often, chronic hepatitis C infection is clinically manifested as extra hepatic disease. Therapy of the extra hepatic manifestations (EHM) is always difficult and based on the optimal and individual association of antiviral treatment, immunosuppressant and plasma cleaning techniques. We observed for 4 years 246 patients admitted to "Colentina" Internal Medicine Clinic, of whom 168 were diagnosed as chronic C hepatitis. 130 of those patients have had at least one EHM. In our experience, the presence of an EHM is significantly correlated with lack of early viral response and sustained viral response, as well. Cryoglobulinemic vasculitis needs to be treated with oral or pulse corticotherapy associated to plasmapheresis. When present, peripheral neuropathy and cryocrit greater than 10% are indicators of need of more than 3 plasmapheresis sessions.

  17. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper;

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared......-lung transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...... the paranasal sinuses and the lungs occurs in chronically infected patients and extensive sinus surgery before the lung transplantation might prevent infection of the new lung....

  18. Extrahepatic manifestations of chronic hepatitis C virus infection:297 cases from a tertiary medical center in Beijing, China

    Institute of Scientific and Technical Information of China (English)

    Cheng Zhaojing; Zhou Baotong; Shi Xiaochun; Zhang Yao; Zhang Lifan; Chen Limeng; Liu Xiaoqing

    2014-01-01

    Background Chronic hepatitis C virus (HCV) infection can affect multiple organ systems and cause a variety of extrahepatic manifestations (EMs).We sought to assess the constituent ratio of EMs in Chinese patients with chronic HCV infection and identify the clinical and biological factors associated with EM.Methods The medical records of 297 patients with chronic HCV infection were analyzed and demographic and epidemiological information was collected.The diagnosis of chronic HCV infection was based on positive anti-HCV combined with a positive HCV-RNA or at least two times of elevated aminotransferases attributable to HCV infection.Patients with HBV and/or HIV coinfection,autoimmune hepatitis,and history of alcohol abuse were excluded.Results Sixty-two percent (184/297) of the patients had at least one EM,including fatigue (29.4%),type 2 diabetes mellitus (28.2%),renal involvement (12.5%),lymphadenopathy (9.6%),fever (9.4%),thyroid dysfunction (8.1%),and arthralgia (7.4%).Neuropathy,sicca syndrome,B-cell lymphoma,Raynaud's phenomenon,and lichen planus were rare.The mean age of patients with EM was older compared with those without EM.Conclusions EMs were common in Chinese patients with chronic HCV infection,particularly fatigue,type 2 diabetes,renal impairment,lymphadenophy,fever,and thyroid dysfunction.Older age was associated with EMs.

  19. MONITORING OF CASES WITH A CHRONIC PERSISTENT INFECTION WITH HELICOBACTER PYLORI

    Directory of Open Access Journals (Sweden)

    Miglena Stamboliyska

    2014-09-01

    Full Text Available Introduction: The patients with persistent forms of Helicobacter pylori (HP infection are refractory to eradication treatment. They receive unsuccessful therapies, experience frequent recurrences and re-infections. One of the main reasons for the development of persistent forms is an inadequate and insufficient treatment. The persistent forms of HP infection create conditions for the maintenance of activity and for the progression of the induced chronic gastritis. In this aspect these cases will be at a higher risk for the development of gastric cancer. The aim of this study is: to monitor and analyze the cases with persistent HP infection and to establish an approach for their management. Clinical material and methods: The study includes 12 patients (8 female and 4 male at a middle age of 63,7, with a persistent HP infection, who have been observed for a period of five years. Two methods for the detection of HP infection are used – one invasive and one non-invasive. Upper endoscopy with morphological examination was performed. Results: In 9/12 patients HP was unsuccessfully treated for three times, in 2 patients – four times, and in 1 patient – five times. In all patients the initial treatment consisted of a standard triple therapy (STT. In 5 of them STT was conducted twice, with the same regimen for a period of seven days. Two patients received three courses of STT. In four patients an antibiotic resistance was established by means of a cultured assessment. In three cases an HP resistance to Clarithromycine and Metronidazole was demonstrated. Significant gastro-duodenal pathology with atrophic gastritis, intestinal metaplasia, and hyperplastic polyposis was found in all patients. The persistent clinical symptoms had 9 patients. Conclusion: We believe that a devised and proposed step strategy which covers early detection of infection, reliable diagnosis, adequate and successful treatment, and dispensary monitoring, contributes to the

  20. Is chronic HIV infection associated with venous thrombotic disease? A systematic review.

    Science.gov (United States)

    Klein, S K; Slim, E J; de Kruif, M D; Keller, T T; ten Cate, H; van Gorp, E C M; Brandjes, D P M

    2005-04-01

    Infection with the human immunodeficiency virus (HIV) is still a major health problem world-wide. HIV infection has changed into a chronic infection with the chance of developing long-term complications. Vascular complications are frequently reported in the current literature. HIV and treatment by highly active antiretroviral therapy (HAART) are associated with many cardiovascular risk factors. An increased risk of arterial cardiovascular complications was found in a number of studies. However, data about the risk of venous thrombotic disease (VTE), including potentially fatal conditions as pulmonary embolism, were limited. In a systematic review of the literature, ten relevant epidemiological studies were identified that investigated the risk of venous thrombotic disease in HIV-infected patients. The incidence was increased two- to tenfold in comparison with a healthy population of the same age. However, these studies were mainly retrospective cohort studies that were prone to selection bias, confounding factors were not always mentioned and in all but three control populations were missing. An increased risk of venous thrombotic disease in HIV-infected patients could be explained by the presence of a hypercoagulable state, characterised by an increase in procoagulant factors, such as endothelial TF expression and thrombogenic properties of microparticles, and a decrease in anticoagulant factors, including AT III, HC II and the protein C pathway. Furthermore, the risk of VTE was associated with an increased risk of infections and autoimmune haemolytic anaemia, and was weakly associated with HAART. All together, quite some evidence pointed towards a relationship between HIV infection and venous thrombotic disease, but the association still needs to be established in properly designed epidemiological studies.

  1. Cationic antimicrobial peptides promote microbial mutagenesis and pathoadaptation in chronic infections.

    Directory of Open Access Journals (Sweden)

    Dominique H Limoli

    2014-04-01

    Full Text Available Acquisition of adaptive mutations is essential for microbial persistence during chronic infections. This is particularly evident during chronic Pseudomonas aeruginosa lung infections in cystic fibrosis (CF patients. Thus far, mutagenesis has been attributed to the generation of reactive species by polymorphonucleocytes (PMN and antibiotic treatment. However, our current studies of mutagenesis leading to P. aeruginosa mucoid conversion have revealed a potential new mutagen. Our findings confirmed the current view that reactive oxygen species can promote mucoidy in vitro, but revealed PMNs are proficient at inducing mucoid conversion in the absence of an oxidative burst. This led to the discovery that cationic antimicrobial peptides can be mutagenic and promote mucoidy. Of specific interest was the human cathelicidin LL-37, canonically known to disrupt bacterial membranes leading to cell death. An alternative role was revealed at sub-inhibitory concentrations, where LL-37 was found to induce mutations within the mucA gene encoding a negative regulator of mucoidy and to promote rifampin resistance in both P. aeruginosa and Escherichia coli. The mechanism of mutagenesis was found to be dependent upon sub-inhibitory concentrations of LL-37 entering the bacterial cytosol and binding to DNA. LL-37/DNA interactions then promote translesion DNA synthesis by the polymerase DinB, whose error-prone replication potentiates the mutations. A model of LL-37 bound to DNA was generated, which reveals amino termini α-helices of dimerized LL-37 bind the major groove of DNA, with numerous DNA contacts made by LL-37 basic residues. This demonstrates a mutagenic role for antimicrobials previously thought to be insusceptible to resistance by mutation, highlighting a need to further investigate their role in evolution and pathoadaptation in chronic infections.

  2. Enterococcus faecalis subverts and invades the host urothelium in patients with chronic urinary tract infection.

    Directory of Open Access Journals (Sweden)

    Harry Horsley

    Full Text Available Bacterial urinary tract infections (UTI are a major growing concern worldwide. Uropathogenic Escherichia coli has been shown to invade the urothelium during acute UTI in mice and humans, forming intracellular reservoirs that can evade antibiotics and the immune response, allowing recurrence at a later date. Other bacterial species, such as Staphylococcus saprophyticus, Klebsiella pneumonia and Salmonella enterica have also been shown to be invasive in acute UTI. However, the role of intracellular infection in chronic UTI causing more subtle lower urinary tract symptoms (LUTS, a particular problem in the elderly population, is poorly understood. Moreover, the species of bacteria involved remains largely unknown. A previous study of a large cohort of non-acute LUTS patients found that Enterococcus faecalis was frequently found in urine specimens. E. faecalis accounts for a significant proportion of chronic bladder infections worldwide, although the invasive lifestyle of this uropathogen has yet to be reported. Here, we wanted to explore this question in more detail. We harvested urothelial cells shed in response to inflammation and, using advanced imaging techniques, inspected them for signs of bacterial pathology and invasion. We found strong evidence of intracellular E. faecalis harboured within urothelial cells shed from the bladder of LUTS patients. Furthermore, using a culture model system, these patient-isolated strains of E. faecalis were able to invade a transitional carcinoma cell line. In contrast, we found no evidence of cellular invasion by E. coli in the patient cells or the culture model system. Our data show that E. faecalis is highly competent to invade in this context; therefore, these results have implications for both the diagnosis and treatment of chronic LUTS.

  3. Infección crónica por el VHC Chronic Hepatitis C virus infection

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    M. Iñarrairaegui

    2004-01-01

    Full Text Available Tras la infección aguda por el virus de la hepatitis C (VHC, un porcentaje importante de pacientes no aclara el virus y desarrollan una hepatitis crónica C. Los síntomas, cuando existen, suelen ser inespecíficos. Aproximadamente un tercio de los pacientes presentan además manifestaciones extrahepáticas de la infección, debidas fundamentalmente al linfotropismo del virus C. De éstas destacan, por su clara asociación con el VHC, la crioglobulinemia mixta y la producción de autoanticuerpos (autoAc. Otras enfermedades como el linfoma no Hodgkin (LNH o la tiroiditis autoinmune no tienen una asociación claramente establecida. Aunque la mayoría de los pacientes con hepatitis crónica C tienen niveles ligeros o moderadamente elevados y fluctuantes de transaminasas, hasta un tercio de los infectados pueden presentar niveles persistentemente normales de transaminasas. El diagnóstico de la infección crónica por el VHC se basa en pruebas serológicas, que detectan la presencia de anticuerpos frente al VHC, y en pruebas virológicas que detectan RNA del VHC, que confirman la existencia de infección activa. Por último, un aspecto importante en la infección crónica por el VHC, tras el diagnóstico, es establecer el estadio de fibrosis y el grado de inflamación, ya que ambas características son muy importantes para predecir la evolución natural y la necesidad de tratamiento. Hoy en día esta información sólo puede obtenerse mediante biopsia hepática, que está indicada en pacientes con infección crónica por el VHC y transaminasas elevadas. Su indicación en pacientes con transaminasas normales permanece todavía controvertida.Following acute hepatitis C virus infection (HCV, a significant percentage of patients do not clear the virus and develop a chronic hepatitis C. The symptoms, when they exist, are usually unspecific. Besides, approximately one third of the patients present extrahepatic manifestations of the infection, basically

  4. Association between Interleukin-12 Receptor B1 Gene Polymorphism (rs401502 C/G and Chronic Hepatitis B Virus Infection

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    M Salehi

    2016-06-01

    Full Text Available Introduction: Hepatitis B virus (HBV infection is a major health problem worldwide and may lead to serious clinical complications, including chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The host’s genetic background in immune system genes is a crucial etiologic factor in progression of HBV infection to chronic disease or clearance of the virus from the body. Interleukin 12 and its receptor (IL12 Receptor play an important role in the clearance of viral infections, especially HBV. The aim of this study is to investigate the association between interleukin 12 receptor B1 gene single nucleotide polymorphism (rs401502 C/G and chronic HBV infection. Methods: In this case control study, genomic DNA of 105 chronically HBV infected patients and 105 healthy controls was extracted. Genotype of (rs401502 C/G single nucleotide polymorphism was determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP method. Results: The frequency of (rs401502 C/G SNP for GG, GC, CC genotypes and G, C alleles was %53.3, %41, %5.7 and %73.3, %26.7 in the chronic patients and %51.4, %41, %7.6 %71.9 , and %28.1 in the control group, respectively. Statistical analysis of the results showed that there was not any significant difference between the case and control groups (p=0.851. Conclusion: In this study, no association was found between (rs401502 C/G single nucleotide polymorphism within IL12RB1 gene and chronic hepatitis B virus infection. It seems that this SNP does not play a crucial role in susceptibility to HBV chronic infection

  5. Distribution specificity of polarized populations of T helper cells in patients with chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    JIANG Rong-long; FENG Xiao-rong; LU Qiao-sheng; LUO Kang-xian; FU Ning

    2001-01-01

    Objective: To investigate the roles of the polarized populations of T helper cells isolated from the peripheral blood mononuclear cells (PBMCs) of individuals with chronic hepatitis B virus (HBV) infection. Methods: PBMCs from patients with chronic HBV infection were separated routinely, stimulated by PMA, ionomycin and monensin, and the production of IL-4, IFN-γ and TGF-β by CD4+ T cells was observed by flow cytometry(FACS). Results: The percentages of the T cells producing IFN-γ, IL-4 or TGF-β ranged from 2.3% to 18.6%, 1.1% to 8.7% and 0.7% to 7.1% respectively among CD4+ cells from non-infected individuals. The majority of CD4+ T cells in PBMCs from individuals with chronic HBV infection were Th0 cells. The proportion of Th1 cells in patients with active chronic hepatitis B was higher than that in patients at inactive stage of the disease (P<0.05), indicating a significant elevation of Thl cells with the hepatic inflammation activity. The percentage of Th2 cells in individuals with HBV infection was higher than that in controls (P<0.05),but showed no difference between different patients (P>0.05). The percentage of Th3 cells was higher in asymptomatic HBV carriers than that in patients with chronic hepatitis B and in healthy controls (P<0.05). Conclusions: Th1-type cytokines are related with hepatic inflammation activity of chronic hepatitis B, and Th2 cells may be associated with the persistence of HBV infection. Th3 cells cooperating with Th2 cells are likely to function as negative immunoregulator, and may be responsible for the immune tolerance state of chronic HBV infection.

  6. The Distribution of Hepatitis C Virus Genotypes in Patients with Chronic Hepatitis C Infection

    Directory of Open Access Journals (Sweden)

    Sevin Kırdar

    2015-12-01

    Full Text Available Objective: Hepatitis C virus (HCV infection represents a major public health problem worldwide. HCV can cause chronic hepatitis infection which may ultimately result in cirrhosis and hepatocellular carcinoma. Seven major genotypes and more than 100 subtypes of HCV are shown by sequence analysis. Genotype 1 is associated with more severity of liver disease than genotypes 2 and 3 and sustained response totreatment is known to be less. In this study, we aimed to determine the HCV genotype distribution in chronic hepatitis C patients. Materials and Methods: A total of 50 patients with chronic HCV infection who attended the Microbiology Laboratory at Adnan Menderes University Hospital between August 2007 and December 2010 found to be positive for anti-HCV and HCV-RNA were included in the study. Anti-HCV testing was performed using microparticle Enzyme-Linked immunosorbent assay test kit (Murex Anti-HCV version 4, UK with autoanalyser (Grifols Triturus, Spain. The quantification of serum HCV-RNA was carried out by a realtime polymerase chain reaction method with two different systems (Cobas TaqMan HCV, Roche Diagnostics, Germany and RotorGene 6000,Corbett Research, USA. HCV genotype analysis was performed by using a kit (HCV-TS; AB Analitica, Italy based on the reverse hybridization of 5’-untranslated region and amplified products with genotype-specific probes. Results: The mean age of the 50 chronic hepatitis C patients [27 (54% female, and 23 (46% male] was 57.1±14.3 years. Genotype 1b was found in 36 (72% subjects, genotype 1a in nine (18%, genotype 2b in one (2%, genotype 3 in one (2%, and genotype 1a/1b was found in three (6% patients. No statistically significant difference was detected in HCV-RNA quantities and anti-HCV index between HCV genotypes (p>0.05. Conclusion: Compatible with the previous data obtained in Turkey, genotype 1b was found to be the most common HCV genotype in patients with chronic hepatitis C followed in our hospital.

  7. Hepatitis virus infection and chronic liver disease among atomic-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, S.; Cologne, J.; Akahoshi, M. [Radiation Effects Research Foundation, Hiroshima (Japan); Kusumi, S.; Kodama, K.; Yoshizawa, H.

    2000-05-01

    The purpose of this study is to analyze various laboratory indicators of inflammation measured in atomic bomb survivors. Subjects are 6304 survivors who underwent inflammatory tests at RERF between 1998 and 1992 and whose radiation doses (DS86) are available. Inflammatory tests include leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha 1 globulin, alpha 2 globulin, and sialic acid. Adjusting for age, sex, smoking, and city of residence, regression analysis was conducted. Regression analysis, adjusted for age, sex, smoking, and city of residence showed statistically significant associations with radiation dose for leukocyte counts (71.0 /mm{sup 3}/Gy, p=0.00151), erythrocyte sedimentation rate (1.58 mm/hour/Gy, p=0.0001), corrected erythrocyte sedimentation rate (1.14 mm/hour/Gy, p=0.0001), alpha 1 globulin (0.0057 g/dl/Gy, p=0.0001), alpha 2 globulin (0.0128 g/dl/Gy, p=0.0001), and sialic acid (1.2711 mg/dl/Gy, p=0.0001), but not for neutrophil counts (29.9 /mm{sup 3}/Gy, p=0.1729). Standardized scores combining results from these seven inflammatory tests showed significant associations with radiation dose both for persons with and without inflammatory disease, and for two inflammatory conditions in particular, chronic thyroiditis and chronic liver disease. In analyses of data from 403 AHS patients, in whom both inflammation indicators and T-cell ratios were measured, increased inflammation correlates with decreases in CD4 T-cells. Since the laboratory indicators of inflammation that we studied are not specific for particular clinical diseases, the implication of their dose-response-pattern is hard to interpret. The general occurrence of infectious diseases in survivors is not related to radiation dose. Such a relationship does exist, however, for other diseases in which infection may play an etiologic role. Virologic studies in A-bomb survivors have suggested dose-response alterations in immune

  8. Treatment of genotype 2 and 3 chronic hepatitis C virus-infected patients

    Institute of Scientific and Technical Information of China (English)

    Perdita Wietzke-Braun; Volker Meier; Katrin Neubauer-Saile; Sabine Mihm; Giuliano Ramadori

    2005-01-01

    AIM: Before pegylated interferon alpha (IFN) was introduced for the therapy of chronic hepatitis C virus(HCV)-induced hepatitis, conventional thrice weekly IFN therapy was supplemented by ribavirin. Also, at that time,higher and more frequent doses of IFN were expected to be more effective than the standard regimen of 3 MU thrice weekly. As ribavirin significantly increases side effects and negatively influences the quality of life particularly in young patients, we started a prospective non-randomized study with a daily IFN-2a monotherapy as an initial treatment for chronic hepatitis C.METHODS: Forty-six consecutive chronic HCV-infected patients received 3 MU IFN-2a per day as an initial treatment. Patients with genotype 2 or 3 (n = 12) were treated for 24 wk, and patients with genotypes other than 2 or 3 (n = 34) for 48 wk. Treatment outcome was followed up for 48 wk after the end of treatment (EOT).Virological response was defined as the absence of detectable serum HCV-RNA. Patients without virological response at 12 wk after the start of treatment received RESULTS: During treatment, three genotype 3 patients were excluded from the study due to incompliance. The remaining patients (n = 9) infected with genotype 2 or 3showed an initial virological response rate of 100%. Six patients (66.7%) were still found to be virus-free at the end of follow-up period. In these patients, initial virological response was evident already after 2 wk of treatment. In contrast, initial virological response occurred first after 4 wk of treatment in the three patients who relapsed(33.3%). In comparison, patients infected with genotypes other than 2 or 3 (n = 34) showed an initial virological response rate of only 23.5% (n = 8), and even in combination with ribavirin a sustained virological response(SVR) rate of only 11.8% (n = 4) could be achieved.CONCLUSION: In chronic HCV-infected patients with genotype 2 or 3, a SVR can be expected after 24 wk of daily dose IFN-2a treatment

  9. Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection

    Institute of Scientific and Technical Information of China (English)

    Chao-Hung; Hung; Jing-Houng; Wang; Tsung-Hui; Hu; Chien-Hung; Chen; Kuo-Chin; Chang; Yi-Hao; Yen; YuanHung; Kuo; Ming-Chao; Tsai; Chuan-Mo; Lee

    2010-01-01

    AIM:To elucidate the role of insulin resistance(IR) and serum adiponectin level in hepatocellular carcinoma(HCC) associated with chronic hepatitis C.METHODS:Clinical and biochemical characteristics were collected from 165 consecutive patients with newly diagnosed HCC.Homeostasis model assessment of IR(HOMA-IR) and serum adiponectin level were investigated in 188 patients with different stages of hepatitis C virus(HCV) infection.RESULTS:Among HCC patients,type 2 diabetics(DM) was more prevalent in HCV subjec...

  10. Soluble CD163 Predicts Incident Chronic Lung, Kidney and Liver Disease in HIV Infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M.; Mejer, Niels; Knudsen, Troels Bygum

    2017-01-01

    OBJECTIVE:: To examine if monocyte and macrophage activity may be on the mechanistic pathway to non-AIDS comorbidity by investigating the associations between plasma soluble CD163 (sCD163) and incident non-AIDS comorbidities in well-treated HIV-infected individuals. DESIGN:: Prospective single......-center cohort study. METHODS:: Plasma sCD163 was quantified by ELISA technique at study entry in 2004/05 and non-AIDS comorbidity was identified by International Classification of Disease Tenth revision (ICD-10) diagnosis codes and registry linkage in 2014/2015. Associations between sCD163 and incident...... comorbidity was examined using multivariable Cox proportional hazards models adjusted for pertinent covariates. RESULTS:: In HIV-1 infected individuals (n=799), the highest quartile of plasma sCD163 was associated with incident chronic lung disease (adjusted hazard ratio (aHR), 3.2; 95% confidence interval...

  11. In situ growth rates and biofilm development of Pseudomonas aeruginosa populations in chronic lung infections

    DEFF Research Database (Denmark)

    Yang, Lei; Haagensen, Janus Anders Juul; Jelsbak, Lars;

    2008-01-01

    The growth dynamics of bacterial pathogens within infected hosts are a fundamental but poorly understood feature of most infections. We have focused on the in situ distribution and growth characteristics of two prevailing and transmissible Pseudomonas aeruginosa clones that have caused chronic lung...... matrix, whereas nonmucoid variants were present mainly as dispersed cells. To obtain estimates of the growth rates of P. aeruginosa in CF lungs, we used quantitative FISH to indirectly measure growth rates of bacteria in sputum samples (reflecting the in vivo lung conditions). The concentration of r......RNA in bacteria isolated from sputa was measured and correlated with the rRNA contents of the same bacteria growing in vitro at defined rates. The results showed that most cells were actively growing with doubling times of between 100 and 200 min, with some growing even faster. Only a small stationary...

  12. Toxoplasma gondii infection among chronic hepatitis C patients:A case-control study

    Institute of Scientific and Technical Information of China (English)

    Hala A El-Nahas; Nora L El-Tantawy; Raghda E Farag; Argaya MA Alsalem

    2014-01-01

    Objective:To determine the detection rate of anti-Toxoplasma gondii(T. gondii)IgG and IgM in chronicHCV patients attending theDepartment ofTropicalMedicineMansoura University hospital inEgypt.Methods:This study included120 adult chronicHCV patients,81 decompensate cirrhosis(late-stage) and39 chronicHCV non cirrhotic patients(early-stage) and 40 healthy blood donors as controls.Serum samples were examined for anti-ToxoplasmaIgM and anti-ToxoplasmaIgG antibodies byELISA.Real-timeRT-polymerase chain reaction assay was done for quantitation of hepatitisC virus.Results:Anti-T. gondiiIgG antibodies were detected in75(92.6%) of81 late-stage cirrhotic patients,30(76.9%) of the39 chronicHCV non cirrhotic patients(early-stage) and in6(15%) of40 controls with statistically significant difference(P<0.001). Anti-T. gondiiIgM antibodies were found in11(13.6%) in late stage patients,5(12.8%) in early stage and in3(7.5%) of controls with no statistical significant difference(P=0.610).There was no correlation between stage of fibrosis andIgM orIgG antibodies positivity in our studied groups (P=0.526).HighIgG levels significantly correlated with high viral load(P=0.026).Conclusions:Our findings suggest that the serious opportunisticT. gondii infection represent a potential significant risk for chronicHCV patients.So, toxoplasmosis should be considered in their investigations and follow-up.

  13. Current treatment indications and strategies in chronic hepatitis B virus infection

    Institute of Scientific and Technical Information of China (English)

    George V Papatheodoridis; Spilios Manolakopoulos; Athanasios J Archimandritis

    2008-01-01

    The optimal approach to the management of several marginal cases with chronic hepatitis B virus (HBV)infection is controversial. Serum HBV DNA and aminotransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase (>twice the upper limit of normal) and serum HBV DNA above 20000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B: standard and pegylated interferon-alpha, lamivudine, adefovir,entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained offtherapy remission in 30%-32% of patients with HBeAgpositive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B.Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients' outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and entecavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but after only 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used,compliance should always be ascertained and HBV DNA levels should be regularly tested.

  14. Occult hepatitis B virus infection among chronic hemodialysis patients in Alexandria, Egypt.

    Science.gov (United States)

    Helaly, Ghada F; El Ghazzawi, Ebtisam F; Shawky, Sherine M; Farag, Farag M

    2015-01-01

    The prevalence of end-stage renal disease has increased dramatically in developing countries. Hepatitis B virus (HBV) infection is a global health problem that represents a significant co-morbidity event that has led to outbreaks of hepatitis B. There are inadequate data concerning occult HBV infection among Egyptian chronic hemodialysis patients. This study aimed to detect occult HBV infection among chronic hemodialysis patients in Alexandria, Egypt. A cross-sectional study was performed on 100 patients with end-stage renal disease that received maintenance hemodialysis and had tested negative for HBV surface antigen. Blood samples were collected before the initiation of hemodialysis. Sera were tested for hepatitis C virus (HCV) and hepatitis B core (HBc) antibodies using ELISA, and HBV DNA was detected by SYBR Green real-time PCR using specific primers for the s and c genes and by nested PCR using pol gene-specific primers. The serum activity of alanine and aspartate aminotransferase (ALT and AST) were also measured. Anti-HCV and anti-HBc antibodies were detected in 34% and 48% of patients, respectively, and 70.6% of anti-HCV positive patients were also positive for anti-HBc antibodies. This association was statistically significant (p=0.001). HBV DNA was detected in 32% of the hemodialysis patients. A significant association was determined between the presence of HBV DNA and anti-HCV positivity (p=0.021). Aminotransferases were elevated in 21% of the studied patients, more often in patients with positive anti-HCV profiles than in patients negative for anti-HCV (poccult infections, especially among anti-HBc-positive hemodialysis patients, to improve our understanding of their clinical, laboratory, and epidemiological characteristics.

  15. TNF-α基因多态性与慢性HBV感染研究进展%Tumour necrosis factor-α gene polymorphism and chronic HBV infection

    Institute of Scientific and Technical Information of China (English)

    邱冰; 李庆华; 李东复

    2011-01-01

    肿瘤坏死因子-α(TNF-α)是人体重要的免疫调节因子,在炎症反应和免疫应答中起重要作用.研究发现,TNF-α基因启动子单核苷酸多态性影响TNF-α的表达.在HBV感染中,TNF-α主要是通过直接抑制病毒复制和间接调节宿主免疫应答发挥作用.TNF-α启动子区基因多态性必然导致不同HBV感染者外周血单个核细胞和肝组织TNF-α表达水平间的差异,从而与HBV的慢性持续感染相关.%TNF-α (tumour necrosis factor-α) plays a pivotal role in inflammation and immune response as an important human immune regulator. Some studies indicated that the capacity for the TNF-α production in individuals largely depends on promoter genetic polymorphisms. TNF-α participates in the defense against hepatitis B viral infection, directly through inhibition of viral replication, and indirectly through determination of the predominant pattern of the host response. The promoter genetic polymorphisms surely lead to different TNF-α expression level in peripherial blood and liver tissues of HBV infection individuals, thus are associated with the chronic HBV infection. Here, the structure, function, and gene polymorphism of TNF-α, and its relationship with HBV chronic infection will be reviewed.

  16. Pathway analysis in blood cells of pigs infected with classical swine fever virus: comparison of pigs that develop a chronic form of infection or recover.

    Science.gov (United States)

    Hulst, Marcel; Loeffen, Willie; Weesendorp, Eefke

    2013-02-01

    Infection of pigs with CSFV can lead to either acute disease, resulting in death or recovery, or chronic disease. The mechanisms by which CSFV manipulates the pig's first line of defence to establish a chronic infection are poorly understood. Therefore, pigs were infected with moderately virulent CSFV, and whole blood was collected on a regular basis during a period of 18 days. Using whole-genome microarrays, time-dependent changes in gene expression were recorded in blood cells of chronically diseased pigs and pigs that recovered. Bioinformatics analysis of regulated genes indicated that different immunological pathways were regulated in chronically diseased pigs compared to recovered pigs. In recovered pigs, antiviral defence mechanisms were rapidly activated, whereas in chronically diseased pigs, several genes with the potential to inhibit NF-κB- and IRF3/7-mediated transcription of type I interferons were up-regulated. Compared to recovered pigs, chronically diseased pigs failed to activate NK or cytotoxic T-cell pathways, and they showed decreased gene activity in antigen-presenting monocytes/macrophages. Remarkably, in chronically diseased pigs, genes related to the human autoimmune disease systemic lupus erythematosus (SLE) were up-regulated during the whole period of 18 days. CSFV pathology in kidney and skin resembles that of SLE. Furthermore, enzymes involved in the degradation of 1,25-dihydroxyvitamin D3 and of tryptophan to kynurenines were expressed at different levels in chronically diseased and recovered pigs. Both of these chemical processes may affect the functions of T helper/regulatory cells that are crucial for tempering the inflammatory response after a viral infection.

  17. Direct infection of dendritic cells during chronic viral infection suppresses antiviral T cell proliferation and induces IL-10 expression in CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Carmen Baca Jones

    Full Text Available Elevated levels of systemic IL-10 have been associated with several chronic viral infections, including HCV, EBV, HCMV and LCMV. In the chronic LCMV infection model, both elevated IL-10 and enhanced infection of dendritic cells (DCs are important for viral persistence. This report highlights the relationship between enhanced viral tropism for DCs and the induction of IL-10 in CD4 T cells, which we identify as the most frequent IL-10-expressing cell type in chronic LCMV infection. Here we report that infected CD8αneg DCs express elevated IL-10, induce IL-10 expression in LCMV specific CD4 T cells, and suppress LCMV-specific T cell proliferation. DCs exposed in vivo to persistent LCMV retain the capacity to stimulate CD4 T cell proliferation but induce IL-10 production by both polyclonal and LCMV-specific CD4 T cells. Our study delineates the unique effects of direct infection versus viral exposure on DCs. Collectively these data point to enhanced infection of DCs as a key trigger of the IL-10 induction cascade resulting in maintenance of elevated IL-10 expression in CD4 T cells and inhibition of LCMV-specific CD4 and CD8 T cell proliferation.

  18. Constraints on Viral Evolution during Chronic Hepatitis C Virus Infection Arising from a Common-Source Exposure

    Science.gov (United States)

    Bailey, Justin R.; Laskey, Sarah; Wasilewski, Lisa N.; Munshaw, Supriya; Fanning, Liam J.; Kenny-Walsh, Elizabeth

    2012-01-01

    Extraordinary viral sequence diversity and rapid viral genetic evolution are hallmarks of hepatitis C virus (HCV) infection. Viral sequence evolution has previously been shown to mediate escape from cytotoxic T-lymphocyte (CTL) and neutralizing antibody responses in acute HCV infection. HCV evolution continues during chronic infection, but the pressures driving these changes are poorly defined. We analyzed plasma virus sequence evolution in 5.2-kb hemigenomes from multiple longitudinal time points isolated from individuals in the Irish anti-D cohort, who were infected with HCV from a common source in 1977 to 1978. We found phylogenetically distinct quasispecies populations at different plasma time points isolated late in chronic infection, suggesting ongoing viral evolution and quasispecies replacement over time. We saw evidence of early pressure driving net evolution away from a computationally reconstructed common ancestor, known as Bole1b, in predicted CTL epitopes and E1E2, with balanced evolution toward and away from the Bole1b amino acid sequence in the remainder of the genome. Late in chronic infection, the rate of evolution toward the Bole1b sequence increased, resulting in net neutral evolution relative to Bole1b across the entire 5.2-kb hemigenome. Surprisingly, even late in chronic infection, net amino acid evolution away from the infecting inoculum sequence still could be observed. These data suggest that, late in chronic infection, ongoing HCV evolution is not random genetic drift but rather the product of strong pressure toward a common ancestor and concurrent net ongoing evolution away from the inoculum virus sequence, likely balancing replicative fitness and ongoing immune escape. PMID:22973048

  19. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

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    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  20. Chronic Subdural Hematoma Associated with Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection in Cameroon

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    Clovis Nkoke

    2017-01-01

    Full Text Available Hematological abnormalities including thrombocytopenia are common in patients living with HIV infection. Patients with HIV infection related thrombocytopenia present generally with only minor bleeding problems. But cases of subdural hematoma are very rare. A 61-year-old female with a history of HIV infection of 9 years’ duration presented with a 3-month history of generalized headache associated with visual blurring and anterograde amnesia. There was no history of trauma or fever. She was treated empirically for cerebral toxoplasmosis for 6 weeks without any improvement of the symptoms. One week prior to admission, she developed weakness of the left side of the body. Clinical examination revealed left-sided hemiparesis. Computed tomography scan of the brain showed a 25 mm chronic right frontoparietotemporal subdural hematoma compressing the lateral ventricle with midline shift. There was no appreciable cerebral atrophy. A complete blood count showed leucopenia and thrombocytopenia at 92,000 cells/mm3. Her CD4-positive cell count was 48 cells/mm3 despite receiving combination antiretroviral therapy for 9 years. A complete blood count analysis suggestive of thrombocytopenia should raise suspicion of possibilities of noninfectious focal brain lesions like subdural hematoma amongst HIV infected patients presenting with nonspecific neurological symptoms. This will enable prompt diagnosis and allow early appropriate intervention.

  1. Reversible Reprogramming of Circulating Memory T Follicular Helper Cell Function during Chronic HIV Infection.

    Science.gov (United States)

    Cubas, Rafael; van Grevenynghe, Julien; Wills, Saintedym; Kardava, Lela; Santich, Brian H; Buckner, Clarisa M; Muir, Roshell; Tardif, Virginie; Nichols, Carmen; Procopio, Francesco; He, Zhong; Metcalf, Talibah; Ghneim, Khader; Locci, Michela; Ancuta, Petronella; Routy, Jean-Pierre; Trautmann, Lydie; Li, Yuxing; McDermott, Adrian B; Koup, Rick A; Petrovas, Constantinos; Migueles, Steven A; Connors, Mark; Tomaras, Georgia D; Moir, Susan; Crotty, Shane; Haddad, Elias K

    2015-12-15

    Despite the overwhelming benefits of antiretroviral therapy (ART) in curtailing viral load in HIV-infected individuals, ART does not fully restore cellular and humoral immunity. HIV-infected individuals under ART show reduced responses to vaccination and infections and are unable to mount an effective antiviral immune response upon ART cessation. Many factors contribute to these defects, including persistent inflammation, especially in lymphoid tissues, where T follicular helper (Tfh) cells instruct and help B cells launch an effective humoral immune response. In this study we investigated the phenotype and function of circulating memory Tfh cells as a surrogate of Tfh cells in lymph nodes and found significant impairment of this cell population in chronically HIV-infected individuals, leading to reduced B cell responses. We further show that these aberrant memory Tfh cells exhibit an IL-2-responsive gene signature and are more polarized toward a Th1 phenotype. Treatment of functional memory Tfh cells with IL-2 was able to recapitulate the detrimental reprogramming. Importantly, this defect was reversible, as interfering with the IL-2 signaling pathway helped reverse the abnormal differentiation and improved Ab responses. Thus, reversible reprogramming of memory Tfh cells in HIV-infected individuals could be used to enhance Ab responses. Altered microenvironmental conditions in lymphoid tissues leading to altered Tfh cell differentiation could provide one explanation for the poor responsiveness of HIV-infected individuals to new Ags. This explanation has important implications for the development of therapeutic interventions to enhance HIV- and vaccine-mediated Ab responses in patients under ART.

  2. Chronic ethanol feeding increases the severity of Staphylococcus aureus skin infections by altering local host defenses

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    Parlet, Corey P.; Kavanaugh, Jeffrey S.; Horswill, Alexander R.; Schlueter, Annette J.

    2015-01-01

    Alcoholics are at increased risk of Staphylococcus aureus skin infection and serious sequelae, such as bacteremia and death. Despite the association between alcoholism and severe S. aureus skin infection, the impact of EtOH on anti-S. aureus cutaneous immunity has not been investigated in a model of chronic EtOH exposure. To test the hypothesis that EtOH enhances the severity of S. aureus skin infection, mice were fed EtOH for ≥12 weeks via the Meadows-Cook model of alcoholism and inoculated with S. aureus following epidermal abrasion. Evidence of exacerbated staphylococcal disease in EtOH-fed mice included: skin lesions that were larger and contained more organisms, greater weight loss, and increased bacterial dissemination. Infected EtOH-fed mice demonstrated poor maintenance and induction of PMN responses in skin and draining LNs, respectively. Additionally, altered PMN dynamics in the skin of these mice corresponded with reduced production of IL-23 and IL-1β by CD11b+ myeloid cells and IL-17 production by γδ T cells, with the latter defect occurring in the draining LNs as well. In addition, IL-17 restoration attenuated S. aureus-induced dermatopathology and improved bacterial clearance defects in EtOH-fed mice. Taken together, the findings show, in a novel model system, that the EtOH-induced increase in S. aureus-related injury/illness corresponds with defects in the IL-23/IL-17 inflammatory axis and poor PMN accumulation at the site of infection and draining LNs. These findings offer new information about the impact of EtOH on cutaneous host-defense pathways and provide a potential mechanism explaining why alcoholics are predisposed to S. aureus skin infection. PMID:25605871

  3. Prevalence of hepatitis B virus precore stop codon mutations in chronically infected children

    Institute of Scientific and Technical Information of China (English)

    Philip Wintermeyer; Patrick Gerner; Stephan Gehring; Afshin Karimi; Stefan Wirth

    2006-01-01

    AIM: To find out whether there is a significant difference in the prevalence of the precore stop codon mutation between HBeAg positive and anti-HBe positive children.METHODS: We investigated a large pediatric population of 155 European children (mean age 10.9 years) with chronic hepatitis B by PCR and direct sequencing. Ninety were HBeAg positive and 65 had seroconversion to antiHBe. Additionally genotyping was performed.RESULTS: Seventy-four (48%) of the sequenced HBV strains were attributed to genotype D and 81 (52%) to genotype A. In the group of 90 HBeAg positive patients,2 (2.2%) 1896-G-to-A transitions leading to precore stop codon mutation were found, and in the group of 65 antiHBe positive children, 5 (7.7%) were identified harbouring HBeAg-minus mutants. The difference was not statistically significant (P= 0.13).CONCLUSIONS: HBeAg minus variants as predominant viral HB strains play a minor role in the course of chronic hepatitis B in European children.

  4. Occult hepatitis B infection in egyptian chronic hepatitis C patients: prevalence, impact on pegylated interferon/ribavirin therapy

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    Mohamed Lamiaa A

    2010-11-01

    Full Text Available Abstract Background Chronic HCV infection combined with occult hepatitis B infection has been associated with liver enzymes flare, advanced hepatic fibrosis and cirrhosis, poor response to standard interferon-α, and increased risk of HCC. This study aimed to elucidate the prevalence of occult hepatitis B infection in Egyptian chronic HCV patients, and to clarify its role in non-response of those patients to pegylated interferon/ribavirin therapy. This study enrolled 155 consecutive chronic HCV patients under pegylated interferon/ribavirin therapy. All patients were exposed to clinical assessment, biochemical, histological and virological examinations. HBV parameters (HBV DNA, anti-HBc, anti-HBs and patients' response status to the combination therapy were determined. Results In this study, occult hepatitis B infection occurs in 3.9% of Egyptian chronic HCV patients; tends to affect younger age patients, associated with higher base line HCV viral load, less hepatic fibrosis than monoinfected patients. This occult hepatitis B infection is not a statistically significant cause of non-response to pegylated interferon/ribavirin therapy. Anti-HBs was not associated with any biochemical, histological or virological abnormalities in those patients, contrary to low response rate to therapy and higher HCV viral load that was observed with anti-HBc. Conclusions Detection of HBV DNA in HBsAg negative chronic HCV patients plays a non significant role in non-response of Egyptian patients to pegylated interferon/ribavirin therapy.

  5. Limited Ability of Posaconazole To Cure both Acute and Chronic Trypanosoma cruzi Infections Revealed by Highly Sensitive In Vivo Imaging.

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    Francisco, Amanda Fortes; Lewis, Michael D; Jayawardhana, Shiromani; Taylor, Martin C; Chatelain, Eric; Kelly, John M

    2015-08-01

    The antifungal drug posaconazole has shown significant activity against Trypanosoma cruzi in vitro and in experimental murine models. Despite this, in a recent clinical trial it displayed limited curative potential. Drug testing is problematic in experimental Chagas disease because of difficulties in demonstrating sterile cure, particularly during the chronic stage of infection when parasite burden is extremely low and tissue distribution is ill defined. To better assess posaconazole efficacy against acute and chronic Chagas disease, we have exploited a highly sensitive bioluminescence imaging system which generates data with greater accuracy than other methods, including PCR-based approaches. Mice inoculated with bioluminescent T. cruzi were assessed by in vivo and ex vivo imaging, with cyclophosphamide-induced immunosuppression used to enhance the detection of relapse. Posaconazole was found to be significantly inferior to benznidazole as a treatment for both acute and chronic T. cruzi infections. Whereas 20 days treatment with benznidazole was 100% successful in achieving sterile cure, posaconazole failed in almost all cases. Treatment of chronic infections with posaconazole did however significantly reduce infection-induced splenomegaly, even in the absence of parasitological cure. The imaging-based screening system also revealed that adipose tissue is a major site of recrudescence in mice treated with posaconazole in the acute, but not the chronic stage of infection. This in vivo screening model for Chagas disease is predictive, reproducible and adaptable to diverse treatment schedules. It should provide greater assurance that drugs are not advanced prematurely into clinical trial.

  6. Massive Trichuris trichiura infection as a cause of chronic bloody diarrhea in a child.

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    Diniz-Santos, Daniel R; Jambeiro, Jamile; Mascarenhas, Ramiro R; Silva, Luciana R

    2006-02-01

    The differential diagnosis of chronic diarrhea is extensive and requires the investigation of several diseases, such as celiac disease, inflammatory bowel disease and irritable bowel syndrome. A few patients infected by Trichuris trichiura may present a chronic dysentery-like syndrome in the context of a massive infestation of the colon leading to anemia and growth retardation, but the rarity of that finding demands a high level of suspicion. Herein we report the case of an 8-year-old boy from the rural zone who had suffered diarrhea without blood or mucus for 4 years and was taken to our Service because his mother had noticed the presence of blood on the feces on the 3 previous months. The diagnosis of a massive Trichuris trichiura infestation as the cause of the process was only reached by colonoscopy. We stress that Trichuris trichiura infection can mimic other forms of inflammatory bowel disease and lead to physical growth retardation and that prolonged regimens of albendazole may be required to the effective treatment of massive infestations.

  7. Chronic hepatitis C infection in a patient with bone marrow hypoplasia

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Chronic hepatitis C virus (HCV) infection is associated with multifarious extra-hepatic manifestations; the most described and discussed being mixed cryoglob- ulinemia which is strongly related to B-cell lympho- proliferative disorders (LPDs). We present a case of chronic HCV infection and mixed cryoglobulinemia, with minimal liver involvement. The case is a 53-year- old patient who was diagnosed as having bone marrow hypoplasia at the age of three. She received several blood transfusions to normalize her haemoglobin. At the age of 31, she was diagnosed with rheumatoid ar- thritis on account of her diffuse joint pain and inflam- mation, elevated rheumatoid factor (RF) and Raynaud's phenomenon. Twenty years later, monoclonal gam- mopathy of IgG Lambda (one year later, changed to IgM Kappa) was detected during a routine examina- tion. A bone marrow biopsy showed hypoplasia, Kappa positive B-lymphocytes and low-grade malignant lym- phoma cells. PCR of the bone marrow aspirate was not contributory. No treatment was initiated owing to her poor bone marrow function and she is under regular follow-up.

  8. Superficially, longer, intermittent ozone theraphy in the treatment of the chronic, infected wounds.

    Science.gov (United States)

    Białoszewski, Dariusz; Kowalewski, Michał

    2003-10-30

    Background. Ozone therapy - i.e. the treatment of patients by a mixture of oxygen and ozone - has been used for many years as a method ancillary to basic treatment, especially in those cases in which traditional treatment methods do not give satisfactory results, e.g. skin loss in non-healing wounds, ulcers, pressure sores, fistulae, etc. Material and methods. In the Department of Phisiotherapy of the Medical Faculty and the Department of the Orthopedics and Traumatology of the Locomotor System at the Medical University of Warsaw in the period from January 2001 until November 2002, 23 patients with heavy,chronic, antibiotic resistants septic complications after trauma, surgical procedures and secundary skin infetions were treated with ozone. The ozone therapy was administered using an authorial technique of superficially, longer, intermittent ozone application. Results. In the wounds of the all experienced patients the inhibition of septic processes and wound healing was much faster than normal. Conclusions. Our data confirm the advantages wich result from the technique of superficially, longer, intermittent ozone theraphy in combined treatment for septic complications in the soft tissue, especially in the locomotor system. These technique makes posttraumatic infections and promotes quicker healing of post-surgical and post-traumal complications - chronic septic infections. This method also lowers the cost of antibiotic therapy and is sometimes the only available auxiliary technique to support surgical procedures.

  9. Transplacental transmission of Anaplasma marginale in beef cattle chronically infected in southern Brazil

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    Hermann Eduardo Gonzalez Grau

    Full Text Available In this study, we have investigated the incidence of transplacental transmission of Anaplasma marginale in chronically infected cows with no history of acute anaplasmosis during gestation. In addition, we evaluated various techniques for detection of transplacental transmission ofA. marginale. Blood samples were collected from 30 cows at three different periods: at the time of artificial insemination, at gestational diagnosis, and after calving. Also, blood was collected from the newborn calves, including one sample before colostrum intake, and another three days after birth. A. marginale-specific antibodies were detected in 100% of the cows with an indirect fluorescent antibody test (IFAT, and in 97% of them, using an indirect enzyme-linked immunosorbent assay (ELISA. Also, we observed that all of the three-day-old newborn calves were seropositive by IFAT. According to polymerase chain reaction, 63.3% of the cows were carriers of A. marginale, as well as 6.7% of the newborn calves. This represented a transplacental transmission rate of 10.5%. Furthermore, a correlation of 93.3% was observed between the two serodiagnostic techniques, demonstrating that both ELISA and IFAT can be used in epidemiological surveys of A. marginale. These results confirm the occurrence of transplacental transmission of A. marginale in chronically infected cows and suggest the importance of this transmission route in areas of enzootic instability.

  10. [Clinical study of astromicin administered by intravenous drip infusion against chronic complicated urinary tract infections].

    Science.gov (United States)

    Suzuki, K; Takanashi, K; Nagakubo, I; Kiyosaki, H; Naide, Y

    1987-07-01

    Astromicin (ASTM) was administered by intravenous drip infusion (i.v.d.) to 22 patients with chronic complicated urinary tract infections and the clinical efficacy and safety of this drug were evaluated. The overall clinical efficacy rate obtained was 71.4% (excellent 6; moderate 9) of 21 evaluable cases by the UTI committee's criteria. Concerning the response on clinical isolates, the drug was highly effective especially against strains of Escherichia coli, indole positive Proteus and Serratia marcescens. It was not effective, however, against 2 strains of Pseudomonas aeruginosa. As for adverse reactions, there was one case which complained of headache on the 3rd day after starting treatment. In this case the drug administration was discontinued at the 5th day. The symptom disappeared within 24 hours without any treatment. No any other adverse reactions were noted. With regard to clinical test values for peripheral blood, liver and renal functions, no abnormality was observed in any of the cases treated with the drug. In conclusion, ASTM was found to be a highly effective and safe drug when administered by intravenous drip infusion in the treatment of chronic complicated urinary tract infections.

  11. HIV type 1 integrase polymorphisms in treatment-naive and treatment-experienced HIV type 1-infected patients in Thailand where HIV type 1 subtype A/E predominates.

    Science.gov (United States)

    Phuphuakrat, Angsana; Pasomsub, Ekawat; Kiertiburanakul, Sasisopin; Chantratita, Wasun; Sungkanuparph, Somnuek

    2012-08-01

    Integrase inhibitor (INI) is a novel antiretroviral drug recommended for both treatment-naive and treatment-experienced HIV-1-infected patients. Limited data are available on INI resistance in Thailand, where HIV-1 subtype A/E predominates. We aimed to investigate INI resistance-associated mutations (RAMs) among treatment-naive patients and patients who experienced treatment failure with NNRTI-based or PI-based antiretroviral therapy (ART) in Thailand. One hundred and eight plasma samples of 58 treatment-naive and 50 treatment-experienced HIV-1-infected individuals were collected. The HIV-1 integrase coding region was sequenced. Polymorphisms were compared between subtype A/E and B circulating in Thailand and between treatment-naive and treatment-experienced groups. Resulting amino acids were interpreted for drug resistance according to Stanford algorithms. Ninety-seven samples were HIV-1 subtype A/E, 10 were subtype B, and one was subtype C. Age, gender, and CD4 cell counts were similar between treatment-naive and treatment-experienced groups, while the treatment-failure group showed a statistically significant longer awareness time of HIV-1 infection and lower viral load than the treatment-naive group. Major INI-RAM was not found in this study, but some minor INI-RAMs, such asV54I, L68I, L74M, T97A, and S230N, were found. Comparing INI-RAMs between subtype A/E and B, the prevalence of V54I and V72I was higher in subtype B than subtype E, while V201I was found in all sequences of subtype A/E. In subtype A/E, integrase polymorphisms were not different between treatment-naive and treatment-experienced groups. However, the number of amino acid substitutions was significantly higher in the treatment-experienced group (p=0.009). One NNRTI-based ART-treated patient was found to have potential low-level INI-RAMs. INI-RAMs are rare in both treatment-naive and treatment-experienced patients in Thailand. This suggested that INI should be active in patients who are naive to

  12. Epidemiology of acute and chronic hepatitis B virus infection in Norway, 1992-2009

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    Blystad Hans

    2011-05-01

    Full Text Available Abstract Background Norway is classified as a low prevalence country for hepatitis B virus infection. Vaccination is only recommended for risk groups (intravenous drug users (IDUs, Men who have Sex with Men (MSM, immigrants and contacts of known carriers. We describe the epidemiology of reported cases of hepatitis B in Norway, during the years 1992-2009 in order to assess the validity of current risk groups and recommend preventive measures. Methods We used case based data from the national surveillance system on acute and chronic hepatitis B. The Norwegian Statistics Bureau provided population and migration data and the Norwegian Institute for Alcohol and Drug Research the estimated number of active IDUs between 2002-2007. Incidence rates (IR and incidence rate ratios (IRR for acute hepatitis B and notification rates (NR and notification rate ratios (NRR for chronic hepatitis B with 95% confidence intervals were calculated. Results The annual IR of acute hepatitis B ranged from 0.7/100,000 (1992 to 10.6/100,000 (1999. Transmission occurred mainly among IDUs (64% or through sexual contact (24%. The risk of acquiring acute hepatitis B was highest in people aged 20-29 (IRR = 6.6 [3.3-13.3], and in males (IRR = 2.4 [1.7-3.3]. We observed two peaks of newly reported chronic hepatitis B cases in 2003 and 2009 (NR = 17.6/100,000 and 17.4/100,000, respectively. Chronic hepatitis B was more likely to be diagnosed among immigrants than among Norwegians (NRR = 93 [71.9-120.6], and among those 20-29 compared to those 50-59 (NRR = 5.2 [3.5-7.9]. Conclusions IDUs remain the largest risk group for acute hepatitis B. The observed peaks of chronic hepatitis B are related to increased immigration from high endemic countries and screening and vaccination of these groups is important to prevent further spread of infection. Universal screening of pregnant women should be introduced. A universal vaccination strategy should be considered, given the high cost of

  13. Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas' disease in rats.

    Science.gov (United States)

    Caetano, Leony Cristina; Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado, José Clóvis

    2009-03-01

    The effect of repetitive stress during acute infection with Trypanosoma cruzi (T. cruzi) on the chronic phase of ensuing Chagas' disease was the focus of this investigation. The aim of this study was to evaluate in Wistar rats the influence of repetitive stress during the acute phase of infection (7 days) with the Y strain of T. cruzi on the chronic phase of the infection (at 180 days). Exposure to ether vapor for 1 min twice a day was used as a stressor. Repetitive stress enhanced the number of circulating parasites and cardiac tissue disorganization, from a moderate to a severe diffuse mononuclear inflammatory process and the presence of amastigote burden in the cardiac fibers. Immunological parameters revealed that repetitive stress triggered a reduced concanavalin A induced splenocyte proliferation in vitro with major effects on the late chronic phase. Serum interleukin-12 concentration decreased in both stressed and infected rats in the early phase of infection although it was higher on 180 days post-infection. These results suggest that repetitive stress can markedly impair the host's immune system and enhance the pathological process during the chronic phase of Chagas' disease.

  14. Evaluation of immunological indices in HIV-infected patients with chronic hepatitis C in Kazakhstan

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    Sarsekeyeva N

    2016-05-01

    Full Text Available Nazgul Sarsekeyeva,1,2 Bakhyt Kosherova3 1Department of Infectious Diseases and Dermatovenerology, Karaganda State Medical University, 2Karaganda Regional Center for the AIDS Prevention and Control, 3Rectorate of Karaganda State Medical University, Karaganda, Kazakhstan Aim: To evaluate immunological indices in HIV-infected patients with chronic hepatitis C (CHC who are injecting drug users. Materials and methods: The study examined 38 patients coinfected with HIV and CHC who were injecting drug users and 36 patients with HIV/CHC who were not injecting drug users. In the study of immune status, the relative and absolute numbers of CD3+, CD4+, CD8+, CD16+, and CD20+ cells were determined by means of flow cytofluorometry of “FACSCount” using monoclonal antibodies of the company Becton Dickinson. The level of circulating immune complexes in blood serum was determined by means of precipitation in polyethylene glycol solution. Results: It was found that T-cell immunodeficiency was developing in patients coinfected with HIV and CHC. T-cell immunodeficiency was characterized by a decrease in the number of T-helpers, mainly for injecting drug users. At the same time, patients coinfected with HIV and CHC experienced markedly elevated levels of circulating immune complexes, mainly among injecting drug users. The evaluation of immunogram indices in injecting drug users coinfected with HIV and CHC, depending on the stage of HIV infection, revealed a greater degree of immune-suppression of T-helper cells in clinical stage III. Conclusion: Our comprehensive immunological study of patients coinfected with HIV and CHC revealed a pronounced dysfunction of the immune system. The comparison of the immune system indices in patients with HIV/CHC showed a more pronounced T-cell suppression in injecting drug users than in patients with HIV/CHC but who were not injecting drug users. Keywords: HIV infection, chronic hepatitis C, immunological indices, injecting drug

  15. Health-related quality of life of Southern Chinese with chronic hepatitis B infection

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    Lam Elegance TP

    2009-06-01

    Full Text Available Abstract Background Few studies have evaluated the health-related quality of life (HRQOL of Southern Chinese with chronic hepatitis B (CHB infection. Aim To evaluate the HRQOL of Chinese patients at different stages of CHB infection and to find out factors associated with HRQOL. Methods 520 Chinese adult CHB patients of whom 156 were uncomplicated, 102 had impaired liver function, 139 had cirrhosis and 123 had hepatocellular carcinoma (HCC were interviewed with a structured questionnaire, the SF-36 Health Survey version 2 (SF-36v2, and the Chronic Liver Disease Questionnaire (CLDQ. The differences in SF-6D health preference values and SF-36v2 scores between each CHB group and Hong Kong population norms were assessed by t-test. ANOVA was used to compare the mean SF-6D health preference, SF-36v2 scores, and CLDQ scores among CHB groups. Multiple linear regressions were performed to identify determinants of HRQOL. Results CHB patients had significantly lower SF-36v2 scores than the population norm. The SF-6D values of CHB patients with uncomplicated disease, impaired liver function, HCC and cirrhosis were 0.755, 0.745, 0.720 and 0.701, respectively, all significantly lower than the population norm of 0.787. Advanced stage of CHB illness, anti-viral treatment, bilirubin level, psychological co-morbidity, younger age and female were associated with poorer HRQOL. Conclusion CHB infection had a negative impact on HRQOL. There was a progressive decrease in health preference values with CHB disease progression. The results can be used for the estimation of quality adjusted life years (QALYs for CHB patients in cost effectiveness or cost utility studies. Trial Registration http://www.hkclinicaltrials.com; HKCTR-151.

  16. Tenofovir therapy in chronic hepatitis B infection: 48-week results from Izmir Province, Turkey

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    Şükran Köse

    2012-09-01

    Full Text Available Objectives: The goal of therapy in chronic hepatitis B infection (CHB is to impede liver injury by suppressing viral replication.The study was aimed to determine the efficacy of tenofovir (TDF in CHB infection for 48 weeks.Materials and methods: We retrospectively analyzed the data of 45 CHB patients treated by tenofovir. The patientswere divided into two groups based on their hepatitis B e antigen status (HBeAg. Those who were eligible to therapyreceived TDF 300 mg once daily for 48 weeks. Serum alanine aminotransferase levels (ALT, hepatitis B virus DNA (HBVDNA, and viral serological markers were checked at three-month intervals. Liver biopsy scores were determined in allpatients.Results: The mean age ± standard deviation (SD was 35.8 ± 17.0 years, 26 (57.8 % were male, and seven patients(15.5% were treatment-experienced by a nucleos(tide analogue before TDF. HBeAg was positive in 17 (37.8% patients.At week 48 among HBeAg positive (HBeAg + patients’ biochemical and virological response rates at month-3, -6 and-12 were 64.7%, and 100%, 70.6%, and 94.1%, and 88.2%, and 64.7%, respectively. The serological response in HBeAg+ patients was 29.4%. For HBeAg negative (HBeAg - patients; biochemical, and virological response rates were 64.3%,and 96.4% at month 3; 82.1%, and 96.4% at month 6; and 100%, and 85.7% at month 12, respectively. At week 48 bothgroups had significant virological response (p<0.001.Conclusion: Treatment in CHB with TDF leads to HBV DNA suppression without evident resistance for 48-week, and iswell tolerated. J Microbiol Infect Dis 2012; 2(3: 87-92Key words: Hepatitis B, chronic, tenofovir disoproxil

  17. Factors Associated with Hepatitis C Infection among Chronic HCV Egyptian Patients.

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    Ekram W Abd El-Wahab

    2014-11-01

    Full Text Available Identification of risk factors of acute hepatitis C virus (HCV infection in Egypt is crucial for developing appropriate prevention strategies. There are few community-based studies on the epidemiology and risk factors of hepatitis C infection in Egypt, which could not provide enough information. Clear identification of past and current risk factors for infection is of utmost importance so that intervention programs can be appropriately focused. This study aims to provide up-to-date information about changes in the incidence of individual risk factors for HCV infection transmission in Egypt.A total of 396 chronic HCV patients on follow-up treatment at liver center in El-Qabbary General Hospital in Alexandria were evaluated retrospectively regarding the potential iatrogenic, community acquired and behavioral HCV risk factors. Risk factors for HCV transmission were found in all study populations.At least three identifiable risk factors were reported by each participant. Some behavioral and community-acquired exposures that entail several risky behaviors particularly, unsafe sexual practices were exclusively established among males. We report a significant decline in prevalence of HCV transmission through blood transfusion, parenteral treatment, hospitalization, surgery, non medicalized circumcision, Hijiama done by informal practitioner, tattooing, folk body piercing and threading, sharing hygiene and sharp items, and the use of communal barber or manicure sets among younger age cluster.The pattern of risk differed among older patients compared to younger age group suggesting improved medical care and infection control measures and raised public health awareness regarding the different modes of viral transmission.

  18. High Programmed Death-1 levels on HCV specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection1

    Science.gov (United States)

    Rutebemberwa, Alleluiah; Ray, Stuart C.; Astemborski, Jacquie; Levine, Jordana; Liu, Lin; Dowd, Kimberly A.; Clute, Shalyn; Wang, Changyu; Korman, Alan; Sette, Alessandro; Sidney, John; Pardoll, Drew M.; Cox, Andrea L.

    2009-01-01

    HCV is an important human pathogen that represents a model for chronic infection since the majority of infected individuals fail to clear the infection despite generation of virus-specific T cell responses during the period of acute infection. While viral sequence evolution at targeted MHC class I restricted epitopes represents one mechanism for immune escape in HCV, many targeted epitopes remain intact under circumstances of viral persistence. In order to explore alternative mechanisms of HCV immune evasion, we analyzed patterns of expression of a major inhibitory receptor on T cells, programmed death-1 (PD-1), from the time of initial infection and correlated these with HCV RNA levels, outcome of infection, and sequence escape within the targeted epitope. We show that the level of PD-1 expression in early HCV infection is significantly higher on HCV-specific T cells from those who progress to chronic HCV infection compared to those who clear infection. This correlation is independent of HCV RNA levels, compatible with the notion that high PD-1 expression on HCV-specific CD8 T cells during acute infection inhibits viral clearance. Viral escape during persistent infection is associated with reduction in PD-1 levels on the surface of HCV specific T cells, supporting the necessity of ongoing antigenic stimulation of T cells for maintenance of PD-1 expression. These results support the idea that PD-1 expression on T cells specific for nonescaped epitopes contributes to viral persistence and suggest that PD-1 blockade may alter the outcome of HCV infection. PMID:19050238

  19. Evolution and diversification of Pseudomonas aeruginosa in the paranasal sinuses of cystic fibrosis children have implications for chronic lung infection

    DEFF Research Database (Denmark)

    Hansen, Susse Kirkelund; Rau, Martin Holm; Johansen, Helle Krogh

    2012-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is a frequent colonizer of the airways of patients suffering from cystic fibrosis (CF). Depending on early treatment regimens, the colonization will, with high probability, develop into chronic infections sooner or later, and it is important to es...... sinuses potentially constitute a protected niche of adapted clones of P. aeruginosa, which can intermittently seed the lungs and pave the way for subsequent chronic lung infections....... and evolution take place in the sinuses. Importantly, before the onset of chronic lung infection, lineages with mutations conferring a large fitness benefit in CF airways such as mucA and lasR as well as small colony variants and antibiotic-resistant clones are part of the sinus populations. Thus, the paranasal...

  20. Neutralizing antibodies in patients with chronic hepatitis C and correlation to liver cirrhosis and estimated duration of infection

    DEFF Research Database (Denmark)

    Pedersen, Jannie; Lundbo, Lene Fogt; Krarup, Henrik;

    2016-01-01

    Although chronic hepatitis C virus (HCV) infection accounts for 30% of individuals with cirrhotic livers worldwide, factors influencing disease progression are far from elucidated. The aim of this study was to determine whether the level of neutralizing antibodies (NAbs) correlated...... with the development of cirrhosis in patients with chronic HCV infection, genotype 1, when adjusting for estimated duration of infection. Thirty-nine patients with chronic hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were enrolled from two university hospitals in Denmark. Duration of HCV......% neutralization (NAb50-titer). A significant difference in HCV NAb50-titers among the six genotype 1a/1b recombinants was found. In patients with cirrhosis, a tendency for higher level of NAbs was observed compared to patients with no/mild fibrosis, although not statistical significant. Stratifying the two groups...

  1. 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.

  2. Early immune response in susceptible and resistant mice strains with chronic Pseudomonas aeruginosa lung infection determines the type of T-helper cell response

    DEFF Research Database (Denmark)

    Moser, C; Hougen, H P; Song, Z;

    1999-01-01

    Most cystic fibrosis (CF) patients become chronically infected with Pseudomonas aeruginosa in the lungs. The infection is characterized by a pronounced antibody response and a persistant inflammation dominated by polymorphonuclear neutrophils. Moreover a high antibody response correlates with a p...

  3. Broad Anti-Hepatitis C Virus (HCV) Antibody Responses Are Associated with Improved Clinical Disease Parameters in Chronic HCV Infection

    Science.gov (United States)

    Swann, Rachael E.; Cowton, Vanessa M.; Robinson, Mark W.; Cole, Sarah J.; Barclay, Stephen T.; Mills, Peter R.; Thomson, Emma C.; McLauchlan, John

    2016-01-01

    ABSTRACT During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection. In this study, we investigated whether bNAb responses in individuals with chronic infection were associated with differences in clinical presentation. Patient-derived purified serum IgG was used to assess the breadth of HCV E1E2 binding and the neutralization activity of HCV pseudoparticles. The binding and neutralization activity results for two panels bearing viral envelope proteins representing either an intergenotype or an intragenotype 1 group were compared. We found that the HCV load was negatively associated with strong cross-genotypic E1E2 binding (P = 0.03). Overall, we observed only a modest correlation between total E1E2 binding and neutralization ability. The breadth of intergenotype neutralization did not correlate with any clinical parameters; however, analysis of individuals with genotype 1 (gt1) HCV infection (n = 20), using an intragenotype pseudoparticle panel, found a strong association between neutralization breadth and reduced liver fibrosis (P = 0.006). A broad bNAb response in our cohort with chronic infection was associated with a single nucleotide polymorphism (SNP) in the HLA-DQB1 gene (P = 0.038), as previously reported in a cohort with acute disease. Furthermore, the bNAbs in these individuals targeted more than one region of E2-neutralizing epitopes, as assessed through cross-competition of patient bNAbs with well-characterized E2 antibodies. We conclude that the bNAb responses in patients with chronic gt1 infection are associated with lower rates of fibrosis and host genetics may play a role in the ability to raise such responses. IMPORTANCE Globally, there are 130 million to 150 million people with chronic HCV infection. Typically, the disease is progressive and is a

  4. Study of T-lymphocyte subsets, nitric oxide, hexosamine and Helicobacter pylori infection in patients with chronic gastric diseases

    Institute of Scientific and Technical Information of China (English)

    Hui Zhang; Shu Lin Jiang; Xi Xian Yao

    2000-01-01

    Chronic gastritis ( CG ) and peptic ulcer ( PU ) are frequently-occurring diseases. It is now well recognized that Helicobacter pylori (Hp) is a major factor that leads to CG and PU[1-8] In order to study the relationship among T lymphocyte subsets, NO, Hexosamine and Hp infection in patients with chronic gastric diseases, the levelsof blood T lymphocyte subsets, plasma NO and hexosamine in gastric mucosa were measured respectively in 30 patients with CG and 32 patients of PU + CG.

  5. Randomized pilot trial of a synbiotic dietary supplement in chronic HIV-1 infection

    Directory of Open Access Journals (Sweden)

    Schunter Marco

    2012-06-01

    Synbiotic treatment for 4 weeks can successfully augment the levels of probiotic species in the gut during chronic HIV-1 infection. Associated changes in microbial translocation appear to be absent, and markers of systemic immune activation appear largely unchanged. These findings may help inform future studies aimed at testing pre- and probiotic approaches to improve gut function and mucosal immunity in chronic HIV-1 infection. Trial registration Clinical Trials.gov: NCT00688311

  6. Increased frequency of micronuclei in the lymphocytes of patients chronically infected with hepatitis B or hepatitis C virus

    Directory of Open Access Journals (Sweden)

    Samantha Therezinha Almeida Pereira Leite

    2014-02-01

    Full Text Available In this study, we analysed the frequency of micronuclei (MN, nucleoplasmic bridges (NPBs and nuclear buds (NBUDs and evaluated mutagen-induced sensitivity in the lymphocytes of patients chronically infected with hepatitis B virus (HBV or hepatitis C virus (HCV. In total, 49 patients with chronic viral hepatitis (28 HBV-infected and 21 HCV-infected patients and 33 healthy, non-infected blood donor controls were investigated. The frequencies (‰ of MN, NPBs and NBUDs in the controls were 4.41 ± 2.15, 1.15 ± 0.97 and 2.98 ± 1.31, respectively. The frequencies of MN and NPBs were significantly increased (p < 0.0001 in the patient group (7.01 ± 3.23 and 2.76 ± 2.08, respectively compared with the control group. When considered separately, the HBV-infected patients (7.18 ± 3.57 and HCV-infected patients (3.27 ± 2.40 each had greater numbers of MN than did the controls (p < 0.0001. The HCV-infected patients displayed high numbers of NPBs (2.09 ± 1.33 and NBUDs (4.38 ± 3.28, but only the HBV-infected patients exhibited a significant difference (NPBs = 3.27 ± 2.40, p < 0.0001 and NBUDs = 4.71 ± 2.79, p = 0.03 in comparison with the controls. Similar results were obtained for males, but not for females, when all patients or the HBV-infected group was compared with the controls. The lymphocytes of the infected patients did not exhibit sensitivity to mutagen in comparison with the lymphocytes of the controls (p = 0.06. These results showed that the lymphocytes of patients who were chronically infected with HBV or HCV presented greater chromosomal instability.

  7. Murine Models for Trypanosoma brucei gambiense disease progression--from silent to chronic infections and early brain tropism.

    Directory of Open Access Journals (Sweden)

    Christiane Giroud

    Full Text Available Human African trypanosomiasis (HAT caused by Trypanosoma brucei gambiense remains highly prevalent in west and central Africa and is lethal if left untreated. The major problem is that the disease often evolves toward chronic or asymptomatic forms with low and fluctuating parasitaemia producing apparently aparasitaemic serological suspects who remain untreated because of the toxicity of the chemotherapy. Whether the different types of infections are due to host or parasite factors has been difficult to address, since T. b. gambiense isolated from patients is often not infectious in rodents thus limiting the variety of isolates.T. b. gambiense parasites were outgrown directly from the cerebrospinal fluid of infected patients by in vitro culture and analyzed for their molecular polymorphisms. Experimental murine infections showed that these isolates could be clustered into three groups with different characteristics regarding their in vivo infection properties, immune response and capacity for brain invasion. The first isolate induced a classical chronic infection with a fluctuating blood parasitaemia, an invasion of the central nervous system (CNS, a trypanosome specific-antibody response and death of the animals within 6-8 months. The second group induced a sub-chronic infection resulting in a single wave of parasitaemia after infection, followed by a low parasitaemia with no parasites detected by microscope observations of blood but detected by PCR, and the presence of a specific antibody response. The third isolate induced a silent infection characterised by the absence of microscopically detectable parasites throughout, but infection was detectable by PCR during the whole course of infection. Additionally, specific antibodies were barely detectable when mice were infected with a low number of this group of parasites. In both sub-chronic and chronic infections, most of the mice survived more than one year without major clinical symptoms

  8. Evolution of Hepatitis B Virus in a Chronic HBV-Infected Patient over 2 Years

    Directory of Open Access Journals (Sweden)

    Tao Shen

    2011-01-01

    Full Text Available Mutations in full-length HBV isolates obtained from a chronic HBV-infected patient were evaluated at three time points: 1 day, 6 months, and 31 months. While 5 nucleotides variation, and an 18 bp deletion of preS1 have been kept in during at least the first two years, C339T mutation occurring in the hydrophilic region of HBsAg and T770C that caused polymerase V560A substitution were the new point mutations found existing in sequenced clones of the 3rd time point. Internal deletion of coding region obviously appeared in the 3rd time point. The splicers included two new 5′-splice donors and three new 3′-splice acceptors besides the reported donors and acceptors and may have produced presumptive HBV-spliced proteins or truncated preS proteins. ALT, HBeAg and viral DNA load varied during the follow-up years. These data demonstrated the diversity of genomes in HBV-infected patient during evolution. Combined with clinical data, the HBV variants discovered in this patient may contribute to viral persistence of infection or liver pathogenesis.

  9. Progress With Developing Use of Gene Editing To Cure Chronic Infection With Hepatitis B Virus.

    Science.gov (United States)

    Ely, Abdullah; Moyo, Buhle; Arbuthnot, Patrick

    2016-04-01

    Chronic infection with hepatitis B virus (HBV) occurs in approximately 6% of the world's population. Carriers of the virus are at risk for life-threatening complications, and developing curative treatment remains a priority. The main shortcoming of licensed therapies is that they do not affect viral covalently closed circular DNA (cccDNA), a stable intermediate of replication. Harnessing gene editing to mutate cccDNA provides the means to inactivate HBV gene expression permanently. Reports have described use of engineered zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR) with CRISPR-associated (Cas) nucleases. Although inhibition of viral replication has been demonstrated, reliably detecting mutations in cccDNA has been difficult. Also, the dearth of murine models that mimic cccDNA formation has hampered analysis in vivo. To reach a stage of clinical use, efficient delivery of the editors to HBV-infected hepatocytes and limiting unintended off-target effects will be important. Investigating therapeutic efficacy in combination with other treatment strategies, such as immunotherapies, may be useful to augment antiviral effects. Advancing gene editing as a mode of treating HBV infection is now at an interesting stage and significant progress is likely to be made in the immediate future.

  10. Elimination of oral focal infection: a new solution in chronic fatigue syndrome management?

    Directory of Open Access Journals (Sweden)

    Haryono Utomo

    2005-12-01

    Full Text Available Chronic fatigue syndrome (CFS is an illness whose primary symptoms are debilitating fatigue and cognitive dysfunction. Substantial symptom overlaping with fibromyalgia, depression, allergic diseases, and many other illnesses, and the absence of a universally applicable diagnostic test, makes the diagnosis of CFS complex and challenging. The pathophysiology of CFS is also complex, and not clearly understood. Formerly, CFS was believed to be a variant form of depression, but due to an increasing body of evidence, CFS is now considered primarily as a biochemical derangement of the functioning of the neuroimmune and neuroendocrine systems. Recently, most treatments still primarily emphasize analgesics, anti inflammatory and psychiatric treatment which correlates to psychosomatic disorders. One of the symptoms that is poorly understood is allergy, but according to the neurogenic switching hypothesis the correlation can be explained nowadays. The role of oral focal infection as one of the possible etiology has still rarely been discussed. The goal of this article is to explain the possible pathophysiology of CFS which could be elicited by oral focal infection, especially endotoxin (lipopolysaccharide from gram negative bacteria. This case report discusses the history of illness, previous treatments, diagnosis, case management and treatment result. Periodontal treatment of a patient with symptom mimicking CFSs undergoing periodontal treatment has a remarkable result. The conclusion is that the elimination of oral focal infection could be a new solution in CFS management.

  11. MicroRNAs may solve the mystery of chronic hepatitis B virus infection.

    Science.gov (United States)

    Wei, Ying-Feng; Cui, Guang-Ying; Ye, Ping; Chen, Jia-Ning; Diao, Hong-Yan

    2013-08-14

    Hepatitis B virus (HBV) infection is a global public health problem that causes persistent liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. A large amount of people die annually from HBV infection. However, the pathogenesises of the HBV-related diseases are ill defined and the therapeutic strategies for the diseases are less than optimum. The recently discovered microRNAs (miRNAs) are tiny noncoding RNAs that regulate gene expression primarily at the post-transcriptional level by binding to mRNAs. miRNAs contribute to a variety of physiological and pathological processes. A number of miRNAs have been found to play a pivotal role in the host-virus interaction including host-HBV interaction. Numerous studies have indicated that HBV infection could change the cellular miRNA expression patterns and different stages of HBV associated disease have displayed distinctive miRNA profiles. Furthermore, the differential expressed miRNAs have been found involved in the progression of HBV-related diseases, for instance some miRNAs are involved in liver tumorigenesis and tumor metastasis. Studies have also shown that the circulating miRNA in serum or plasma might be a very useful biomarker for the diagnosis and prognosis of HBV-related diseases. In addition, miRNA-based therapy strategies have attracted increasing attention, indicating a promising future in the treatment of HBV-related diseases.

  12. Infección crónica por el VHB Chronic Hepatitis B Virus infection

    Directory of Open Access Journals (Sweden)

    C. Carretero

    2004-01-01

    Full Text Available Existen muchos factores implicados en la patogénesis de la infección crónica por el virus de la hepatitis B (VHB, como por ejemplo características del virus, la ingesta de etanol, la coinfección con otros virus (VHC, VIH, VHD, e intervenciones terapéuticas como el uso de fármacos citotóxicos o inmunosupresores, o agentes antivirales específicos. Las características clínicas, patológicas y serológicas de la hepatitis crónica por VHB, además, son muy heterogéneas. Se puede reconocer la infección crónica por VHB ante la persistencia del antígeno Australia (HBsAg durante más de seis meses. La presencia de HBeAg se suele asociar a la replicación viral activa y puede ser medida por la cantidad de DNA-VHB presente en el suero o bien por la expresión hepática de HBcAg. El daño hepático que se produce en la hepatitis crónica por VHB no es tanto por el efecto del virus sobre los hepatocitos sino por la reacción inmune que éste provoca en el huésped. Por ello puede verse cierta correlación inversamente proporcional entre la intensidad de la replicación viral y el grado de inflamación hepática. La presencia de hepatitis crónica activa en la biopsia inicial no se ha asociado al desarrollo de cirrosis así como tampoco el diagnóstico histológico de hepatitis crónica persistente puede asegurar que se vaya a desarrollar cirrosis en un futuro.Many factors are involved in the pathogenesis of chronic hepatitis B virus infection (HBV, such as, for example, characteristics of the virus, ethanol intake, coinfection with other viruses (HCV, HIV, HDV, and therapeutic interventions such as the use of cytotoxic drugs or immunosuppressors, or specific antiviral agents. The clinical, pathological and serological characteristics of chronic hepatitis B virus infection are besides very heterogeneous. Chronic HBV infection can be recognised facing persistence of the Australia antigen (HBsAg for more than six months. The presence of HBeAg is

  13. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) with intracranial Epstein–Barr virus infection

    OpenAIRE

    Ma, Yue; Sun, Xiaolong; Li, Wen; Li, Yi; Kang, Tao; Yang, Xiai; Jiang, Wen

    2016-01-01

    Abstract Background: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological features. The pathophysiology of CLIPPERS still remains unclear and the reports are quite few. Although the radiological lesions were reported to be located predominantly in the pons, brachium pontis, and cerebellum, other adjacent structures such as t...

  14. Influence of supplementary immunization activities for adults dynamics of chronic disease HBV-infection and its outcomes

    Directory of Open Access Journals (Sweden)

    S. V. Baramzina

    2014-01-01

    Full Text Available Purpose: to evaluate the effect of additional vaccination of adult HBV- infection years 2007–2010 on the incidence of chronic hepatitis B and its outcomes on the example of the Kirov region.Materials and Methods: the evaluation of epidemiological features process in patients with chronic HBV infection in adults, depending on the vaccination carried out on the basis of official data Rospotrebnadzora in Russia and Kirov region on incidence of infectious disease for the period 1999–2012. Diagnosis of chronic hepatitis B was based on clinical and biochemical, instrumental, virological data. Structure outcomes of chronic hepatitis B was studied in 295 patients aged 18–75 years who were hospitalized in the department of viral hepatitis Kirov infectious diseases hospital in 2006–2010.Results: In the Kirov region tended to decrease the incidence of chronic hepatitis B in adults. Additional adult vaccination against hepatitis B has not led to the expected significant decrease of the number of patients with chronic forms. One reason for this is the low (20,3–64% of the adult population immunization coverage. Chronic HBV- monoinfected was observed in 17.1% , cirrhosis in the outcome of chronic hepatitis B in 5,4% of cases, in hospital mortality from complications of HBV- cirrhosis was 0,7%. Association virus C and D have increased the total cohort, compared to a mono- infection by 3,8% and 0,5% lethality.Conclusion: Additional adult vaccination against hepatitis B in the area has led to a slight decrease in the overall incidence of chronic hepatitis B, but has not reduced the incidence of adverse events – cirrhosis and liver- mediated lethality.

  15. Soluble egg antigen of Schistosoma Haematobium induces HCV replication in PBMC from patients with chronic HCV infection

    OpenAIRE

    2006-01-01

    Abstract Background This study was conducted to examine, in vitro , the effect of soluble egg antigen (SEA) of S. haematobium on intracellular HCV RNA load in peripheral mononuclear cells (PBMC) as well as on cell proliferation in patients with chronic HCV infection. Methods PBMC from 26 patients with chronic HCV infection were cultured for 72 hours in presence and absence of 50 μg SEA/ml medium. Intracellular HCV RNA quantification of plus and minus strands was assessed before and after stim...

  16. Analysis of HIV-1- and CMV-specific memory CD4 T-cell responses during primary and chronic infection.

    Science.gov (United States)

    Harari, Alexandre; Rizzardi, G Paolo; Ellefsen, Kim; Ciuffreda, Donatella; Champagne, Patrick; Bart, Pierre-Alexandre; Kaufmann, Daniel; Telenti, Amalio; Sahli, Roland; Tambussi, Giuseppe; Kaiser, Laurent; Lazzarin, Adriano; Perrin, Luc; Pantaleo, Giuseppe

    2002-08-15

    CD4 T-cell-specific memory antiviral responses to human immunodeficiency virus type 1 (HIV-1) and cytomegalovirus (CMV) were investigated in 16 patients with documented primary HIV-1 infection (4 of the 16 subjects also had primary CMV infection) and compared with those observed in patients with chronic HIV-1 and CMV coinfection. Virus-specific memory CD4 T cells were characterized on the basis of the expression of the chemokine receptor CCR7. HIV-1- and CMV-specific interferon-gamma-secreting CD4 T cells were detected in patients with primary and chronic HIV-1 and CMV coinfection and were mostly contained in the cell population lacking expression of CCR7. The magnitude of the primary CMV-specific CD4 T-cell response was significantly greater than that of chronic CMV infection, whereas there were no differences between primary and chronic HIV-1-specific CD4 T-cell responses. A substantial proportion of CD4(+)CCR7(-) T cells were infected with HIV-1. These results advance the characterization of antiviral memory CD4 T-cell response and the delineation of the potential mechanisms that likely prevent the generation of a robust CD4 T-cell immune response during primary infection.

  17. Chronic oral infections of cats and their relationship to persistent oral carriage of feline calici-, immunodeficiency, or leukemia viruses.

    Science.gov (United States)

    Tenorio, A P; Franti, C E; Madewell, B R; Pedersen, N C

    1991-08-01

    Two hundred and twenty-six cats from the Veterinary Medical Teaching Hospital (VMTH), a cat shelter, and a purebred cattery were tested for chronic feline calicivirus (FCV), feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) infections. Chronic oral carriage of FCV was present in about one-fifth of the cats in each of the groups. FIV infection was not present in the purebred cattery, was moderately prevalent (8%) in the pet population of cats examined at the VMTH for various complaints and was rampant in the cat shelter (21%). Unexpectedly high FeLV infection rates were found in the hospital cat population (28%) and in the purebred cattery (36%), but not in the cat shelter (1.4%). FCV and FeLV infections tended to occur early in life, whereas FIV infections tended to occur in older animals. From 43 to 100% of the cats in these environments had oral cavity disease ranging from mild gingivitis (23-46%), proliferative gingivitis (18-20%), periodontitis (3-32%) and periodontitis with involvement of extra-gingival tissues (7-27%). Cats infected solely with FCV did not have a greater likelihood of oral lesions, or more severe oral disease, than cats that were totally virus free. This was also true for cats infected solely with FeLV, or for cats dually infected with FeLV and FCV. Cats infected solely with FIV appeared to have a greater prevalence of oral cavity infections and their oral cavity disease tended to be more severe than cats without FIV infection. FIV-infected cats that were coinfected with either FCV, or with FCV and FeLV, had the highest prevalence of oral cavity infections and the most severe oral lesions.

  18. Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells.

    Science.gov (United States)

    Snyder, Christopher M; Cho, Kathy S; Bonnett, Elizabeth L; van Dommelen, Serani; Shellam, Geoffrey R; Hill, Ann B

    2008-10-17

    During persistent murine cytomegalovirus (MCMV) infection, the T cell response is maintained at extremely high intensity for the life of the host. These cells closely resemble human CMV-specific cells, which compose a major component of the peripheral T cell compartment in most people. Despite a phenotype that suggests extensive antigen-driven differentiation, MCMV-specific T cells remain functional and respond vigorously to viral challenge. We hypothesized that a low rate of antigen-driven proliferation would account for the maintenance of this population. Instead, we found that most of these cells divided only sporadically in chronically infected hosts and had a short half-life in circulation. The overall population was supported, at least in part, by memory T cells primed early in infection, as well as by recruitment of naive T cells at late times. Thus, these data show that memory inflation is maintained by a continuous replacement of short-lived, functional cells during chronic MCMV infection.

  19. Durability of first antiretroviral treatment in HIV chronically infected patients: why change and what are the outcomes?

    Directory of Open Access Journals (Sweden)

    Patricia Moniz

    2014-11-01

    Full Text Available Introduction: First antiretroviral therapy (ART is often switched to simpler, more potent or better tolerated regimens (1, 2. Although discontinuation rates are frequently studied, the durability of regimens is rarely approached. Materials and Methods: Retrospective study with the following objectives: analyze first ART schemes and their durability in naive patients with chronic HIV-1 and 2 infections, evaluate factors influencing ART change, second-line ART and consequent virologic and immunologic responses. Patients had follow-ups in a Central University Hospital, started ART between January 2007 and December 2012 and changed first regimens. Clinical data was obtained from medical records and analyzed using the Statistical Package for the Social Sciences (version 20. Results: Of the 652 naive patients who started ART, 164 changed regimens. The majority had HIV-1 infection (n=158. The mean age was 43.9 years (standard deviation±14.3, with a male predominance of 57.9%. Regimens with efavirenz were the most common amongst HIV-1 patients (50% followed by lopinavir/r (22%. In HIV-2 patients, lopinavir/r (n=3 regimens were most prevalent. First ART regimens had a mean duration of 12.1 months. There was no difference between NNRTI (59.8% and protease inhibitor (40.2% schemes regarding durability. Adverse reactions were the major cause of ART switching (55.5% followed by therapy resistance (12.1%. Age was inversely related to durability (p=0.007 Mann-Whitney, Phi coefficient −0.161 and associated with the appearance of adverse reactions (p=0.04, Chi-square. Younger patients had a reduced risk of adverse reactions by 27%. Adverse reactions increased the risk of inferior durability by 40%. Psychiatric symptoms (28.4% were the most prevalent, all attributed to efavirenz. The year of ART initiation was associated with different durability rates (p=0.005, Mann-Whitney. Patients started on ART before the year 2010 reduced the probability of inferior ART

  20. Recurrent signature patterns in HIV-1 B clade envelope glycoproteins associated with either early or chronic infections.

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    S Gnanakaran

    2011-09-01

    Full Text Available Here we have identified HIV-1 B clade Envelope (Env amino acid signatures from early in infection that may be favored at transmission, as well as patterns of recurrent mutation in chronic infection that may reflect common pathways of immune evasion. To accomplish this, we compared thousands of sequences derived by single genome amplification from several hundred individuals that were sampled either early in infection or were chronically infected. Samples were divided at the outset into hypothesis-forming and validation sets, and we used phylogenetically corrected statistical strategies to identify signatures, systematically scanning all of Env. Signatures included single amino acids, glycosylation motifs, and multi-site patterns based on functional or structural groupings of amino acids. We identified signatures near the CCR5 co-receptor-binding region, near the CD4 binding site, and in the signal peptide and cytoplasmic domain, which may influence Env expression and processing. Two signatures patterns associated with transmission were particularly interesting. The first was the most statistically robust signature, located in position 12 in the signal peptide. The second was the loss of an N-linked glycosylation site at positions 413-415; the presence of this site has been recently found to be associated with escape from potent and broad neutralizing antibodies, consistent with enabling a common pathway for immune escape during chronic infection. Its recurrent loss in early infection suggests it may impact fitness at the time of transmission or during early viral expansion. The signature patterns we identified implicate Env expression levels in selection at viral transmission or in early expansion, and suggest that immune evasion patterns that recur in many individuals during chronic infection when antibodies are present can be selected against when the infection is being established prior to the adaptive immune response.

  1. Autoimmunity and Extrahepatic Manifestations in Treatment-Naïve Children with Chronic Hepatitis C Virus Infection

    OpenAIRE

    Giuseppe Indolfi; Elisa Bartolini; Biagio Olivito; Chiara Azzari; Massimo Resti

    2012-01-01

    Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significan...

  2. Chlamydophila spp. infection in horses with recurrent airway obstruction: similarities to human chronic obstructive disease

    Directory of Open Access Journals (Sweden)

    Hotzel Helmut

    2008-01-01

    Full Text Available Abstract Background Recurrent airway obstruction (RAO in horses is a naturally occurring dust-induced disease mainly characterized by bronchiolitis which shows histological and pathophysiological similarities to human chronic obstructive pulmonary disease (COPD. In human COPD previous investigations indicated an association with Chlamydophila psittaci infection. The present study was designed (1 to clarify a possible role of this infectious agent in RAO and (2 to investigate the suitability of this equine disorder as a model for human COPD. Methods Clinico-pathological parameters of a total of 45 horses (25 horses with clinical signs of RAO and 20 clinically healthy controls were compared to histological findings in lung tissue samples and infection by Chlamydiaceae using light microscopy, immunohistochemistry, and PCR. Results Horses with clinical signs of RAO vs. controls revealed more inflammatory changes in histology (p = 0.01, and a higher detection rate of Chlamydia psittaci antigens in all cells (p OmpA sequencing identified Chlamydophila psittaci (n = 9 and Chlamydophila abortus (n = 13 in both groups with no significant differences. Within the group of clinically healthy horses subgroups with no changes (n = 15 and slight inflammation of the small airways (n = 5 were identified. Also in the group of animals with RAO subgroups with slight (n = 16 and severe (n = 9 bronchiolitis could be formed. These four subgroups can be separated in parts by the number of cells positive for Chlamydia psittaci antigens. Conclusion Chlamydophila psittaci or abortus were present in the lung of both clinically healthy horses and those with RAO. Immunohistochemistry revealed acute chlamydial infections with inflammation in RAO horses, whereas in clinically healthy animals mostly persistent chlamydial infection and no inflammatory reactions were seen. Stable dust as the known fundamental abiotic factor in RAO is comparable to smoking in human disease. These

  3. Multiple immune factors are involved in controlling acute and chronic chikungunya virus infection.

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    Yee Suan Poo

    2014-12-01

    Full Text Available The recent epidemic of the arthritogenic alphavirus, chikungunya virus (CHIKV has prompted a quest to understand the correlates of protection against virus and disease in order to inform development of new interventions. Herein we highlight the propensity of CHIKV infections to persist long term, both as persistent, steady-state, viraemias in multiple B cell deficient mouse strains, and as persistent RNA (including negative-strand RNA in wild-type mice. The knockout mouse studies provided evidence for a role for T cells (but not NK cells in viraemia suppression, and confirmed the role of T cells in arthritis promotion, with vaccine-induced T cells also shown to be arthritogenic in the absence of antibody responses. However, MHC class II-restricted T cells were not required for production of anti-viral IgG2c responses post CHIKV infection. The anti-viral cytokines, TNF and IFNγ, were persistently elevated in persistently infected B and T cell deficient mice, with adoptive transfer of anti-CHIKV antibodies unable to clear permanently the viraemia from these, or B cell deficient, mice. The NOD background increased viraemia and promoted arthritis, with B, T and NK deficient NOD mice showing high-levels of persistent viraemia and ultimately succumbing to encephalitic disease. In wild-type mice persistent CHIKV RNA and negative strand RNA (detected for up to 100 days post infection was associated with persistence of cellular infiltrates, CHIKV antigen and stimulation of IFNα/β and T cell responses. These studies highlight that, secondary to antibodies, several factors are involved in virus control, and suggest that chronic arthritic disease is a consequence of persistent, replicating and transcriptionally active CHIKV RNA.

  4. NKT cells prevent chronic joint inflammation after infection with Borrelia burgdorferi.

    Science.gov (United States)

    Tupin, Emmanuel; Benhnia, Mohammed Rafii-El-Idrissi; Kinjo, Yuki; Patsey, Rebeca; Lena, Christopher J; Haller, Matthew C; Caimano, Melissa J; Imamura, Masakazu; Wong, Chi-Huey; Crotty, Shane; Radolf, Justin D; Sellati, Timothy J; Kronenberg, Mitchell

    2008-12-16

    Borrelia burgdorferi is the etiologic agent of Lyme disease, a multisystem inflammatory disorder that principally targets the skin, joints, heart, and nervous system. The role of T lymphocytes in the development of chronic inflammation resulting from B. burgdorferi infection has been controversial. We previously showed that natural killer T (NKT) cells with an invariant (i) TCR alpha chain (iNKT cells) recognize glycolipids from B. burgdorferi, but did not establish an in vivo role for iNKT cells in Lyme disease pathogenesis. Here, we evaluate the importance of iNKT cells for host defense against these pathogenic spirochetes by using Valpha14i NKT cell-deficient (Jalpha18(-/-)) BALB/c mice. On tick inoculation with B. burgdorferi, Jalpha18(-/-) mice exhibited more severe and prolonged arthritis as well as a reduced ability to clear spirochetes from infected tissues. Valpha14i NKT cell deficiency also resulted in increased production of antibodies directed against both B. burgdorferi protein antigens and borrelial diacylglycerols; the latter finding demonstrates that anti-glycolipid antibody production does not require cognate help from Valpha14i NKT cells. Valpha14i NKT cells in infected wild-type mice expressed surface activation markers and produced IFNgamma in vivo after infection, suggesting a participatory role for this unique population in cellular immunity. Our data are consistent with the hypothesis that the antigen-specific activation of Valpha14i NKT cells is important for the prevention of persistent joint inflammation and spirochete clearance, and they counter the long-standing notion that humoral rather than cellular immunity is sufficient to facilitate Lyme disease resolution.

  5. Demographic patterns and harvest vulnerability of chronic wasting disease infected white-tailed deer in Wisconsin

    Science.gov (United States)

    Grear, D.A.; Samuel, M.D.; Langenberg, J.A.; Keane, D.

    2006-01-01

    Chronic wasting disease (CWD) is a fatal disease of white-tailed deer (Odocoileus virginianus) caused by transmissible protease-resistant prions. Since the discovery of CWD in southern Wisconsin in 2001, more than 20,000 deer have been removed from a >2,500-km2 disease eradication zone surrounding the three initial cases. Nearly all deer removed were tested for CWD infection and sex, age, and harvest location were recorded. Our analysis used data from a 310-km2 core study area where disease prevalence was higher than surrounding areas. We found no difference in harvest rates between CWD infected and noninfected deer. Our results show that the probability of infection increased with age and that adult males were more likely to be infected than adult females. Six fawns tested positive for CWD, five fawns from the core study area, including the youngest (5 months) free-ranging cervid to test positive. The increase in male prevalence with age is nearly twice the increase found in females. We concluded that CWD is not randomly distributed among deer and that differential transmission among sex and age classes is likely driving the observed patterns in disease prevalence. We discuss alternative hypotheses for CWD transmission and spread and, in addition, discuss several possible nonlinear relationships between prevalence and age. Understanding CWD transmission in free-ranging cervid populations will be essential to the development of strategies to manage this disease in areas where CWD is found, as well as for surveillance strategies in areas where CWD threatens to spread.

  6. Side effects of antiviral therapy in patients with chronic hepatitis C infection

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    Kostić Velimir

    2012-01-01

    Full Text Available Introduction. Chronic hepatitis C currently represents a global health problem, which is expected to be reduced by pegylated-interferon and ribavirin therapy. Material and Methods. We examined 88 patients with chronic hepatitis C, divided into three groups according to their comorbidity: the patients without comorbidity were in group I, group II included the patients on dialysis, and group III included the patients with hemophilia. Results. A significant difference was found in the percentage of achieved sustained virological response between the patients on dialysis and other patients, p<0.05. Having analyzed the therapy adverse effects, we observed a significantly higher decrease of erythrocytes count, hemoglobin and hematocrit levels in dialysis patients compared to others (p<0.01. The patients on hemodialysis predominantly had anemia and leukopenia, while thrombocytopenia was equally present in all groups. The dominant clinical side effect was flu-like syndrome, present in more than a half of patients. Discussion. The therapy positive effect is usually accompanied with adverse effects. The lowest therapeutic response was recorded in group II, due to the virus genotype 1. A significant decrease in hematological parameters was determined in all patients. The most common clinical adverse effect was flu-like syndrome, later manifestations included: weight loss, alopecia, insomnia and irritability. Side effects like psychosis, thyroid gland dysfunction or psoriasis were not recorded. Conclusion. A significant decrease in the value of all these hematological parameters was found in all groups of patients. Clinical side effects were present in 60% of patients. Side effects did not lead to discontinuation of therapy, but only to modification of drug doses.

  7. Chronic oral infection with major periodontal bacteria Tannerella forsythia modulates systemic atherosclerosis risk factors and inflammatory markers.

    Science.gov (United States)

    Chukkapalli, Sasanka S; Rivera-Kweh, Mercedes F; Velsko, Irina M; Chen, Hao; Zheng, Donghang; Bhattacharyya, Indraneel; Gangula, Pandu R; Lucas, Alexandra R; Kesavalu, Lakshmyya

    2015-04-01

    Tannerella forsythia is a Gram-negative anaerobic organism that inhabits the subgingival cavity and initiates connective tissue destruction and alveolar bone resorption in periodontal disease (PD). PD is a chronic immunoinflammatory disease and has been linked to several systemic diseases including atherosclerosis. This study evaluated the effects of a chronic oral infection with T. forsythia ATCC 43037 on the induction of PD, inflammatory markers and atherosclerosis risk factors in hyperlipidemic ApoE(null) mice. Mice were orally infected for 12 and 24 weeks prior to euthanasia. Bacterial colonization of the oral cavity and bacteremia was confirmed via isolation of genomic DNA from oral plaque and tissues. Oral infection elicited significantly elevated levels of serum IgG and IgM antibodies and alveolar bone resorption compared to control mice. Tannerella forsythia-infected mice had increased serum amyloid A, and significantly reduced serum nitric oxide when compared to controls. Tannerella forsythia chronic infection also significantly increased serum lipoproteins suggesting altered cholesterol metabolism and potential for aortic inflammation. Despite enhanced acute phase reactants and altered lipid profiles, T. forsythia infection was associated with decreased aortic plaque. This study investigates the potential of a known periodontal bacterial pathogen found in atherosclerotic plaque in humans to accelerate atherosclerosis in hyperlipdemic mice.

  8. Impact of Chronic Hepatitis C Virus Genotype 1b Infection on Triglyceride Concentration in Serum Lipoprotein Fractions

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    Tomohisa Nagano

    2015-08-01

    Full Text Available Reduced low-density lipoprotein (LDL cholesterol level is a characteristic feature of dyslipidemia in chronic hepatitis C virus (HCV infection. However, abnormality in serum triglyceride (TG has not been fully investigated. To clarify the impact of HCV genotype 1b (G1b infection and advanced fibrosis on serum TG profiles, TG concentrations in lipoprotein fractions were examined in fasting sera from 185 subjects with active or cleared HCV infection by high-performance liquid chromatography. Serum lipoproteins were fractionated into four classes: chylomicron, very low-density lipoprotein (VLDL, LDL, and high-density lipoprotein (HDL. Then, the significance of HCV G1b infection on TG levels in each lipoprotein fraction was determined using multiple regression models. We found that active HCV G1b infection was positively associated with high HDL-TG levels and low VLDL-TG levels, independent of other factors included in the regression model. In VLDL sub-fractions, active HCV infection was only found to be associated with low levels of large VLDL-TG. Similarly, advanced liver fibrosis in chronic HCV G1b infection was associated with high levels of LDL-TG, HDL-TG, and small VLDL-TG, independent of other clinical factors. These findings indicate that active HCV G1b infection and advanced fibrosis are closely associated with abnormal serum TG profiles.

  9. Chronic parasitic infection maintains high frequencies of short-lived Ly6C+CD4+ effector T cells that are required for protection against re-infection.

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    Nathan C Peters

    2014-12-01

    Full Text Available In contrast to the ability of long-lived CD8(+ memory T cells to mediate protection against systemic viral infections, the relationship between CD4(+ T cell memory and acquired resistance against infectious pathogens remains poorly defined. This is especially true for T helper 1 (Th1 concomitant immunity, in which protection against reinfection coincides with a persisting primary infection. In these situations, pre-existing effector CD4 T cells generated by ongoing chronic infection, not memory cells, may be essential for protection against reinfection. We present a systematic study of the tissue homing properties, functionality, and life span of subsets of memory and effector CD4 T cells activated in the setting of chronic Leishmania major infection in resistant C57Bl/6 mice. We found that pre-existing, CD44(+CD62L(-T-bet(+Ly6C+ effector (T(EFF cells that are short-lived in the absence of infection and are not derived from memory cells reactivated by secondary challenge, mediate concomitant immunity. Upon adoptive transfer and challenge, non-dividing Ly6C(+ T(EFF cells preferentially homed to the skin, released IFN-γ, and conferred protection as compared to CD44(+CD62L(-Ly6C(- effector memory or CD44(+CD62L(+Ly6C(- central memory cells. During chronic infection, Ly6C(+ T(EFF cells were maintained at high frequencies via reactivation of T(CM and the T(EFF themselves. The lack of effective vaccines for many chronic diseases may be because protection against infectious challenge requires the maintenance of pre-existing T(EFF cells, and is therefore not amenable to conventional, memory inducing, vaccination strategies.

  10. Hierarchies of Predominantly Connected Communities

    CERN Document Server

    Hamann, Michael; Wagner, Dorothea

    2013-01-01

    We consider communities whose vertices are predominantly connected, i.e., the vertices in each community are stronger connected to other community members of the same community than to vertices outside the community. Flake et al. introduced a hierarchical clustering algorithm that finds such predominantly connected communities of different coarseness depending on an input parameter. We present a simple and efficient method for constructing a clustering hierarchy according to Flake et al. that supersedes the necessity of choosing feasible parameter values and guarantees the completeness of the resulting hierarchy, i.e., the hierarchy contains all clusterings that can be constructed by the original algorithm for any parameter value. However, predominantly connected communities are not organized in a single hierarchy. Thus, we develop a framework that, after precomputing at most $2(n-1)$ maximum flows, admits a linear time construction of a clustering $\\C(S)$ of predominantly connected communities that contains ...

  11. Interleukin-6 (IL-6) haplotypes and the response to therapy of chronic hepatitis C virus infection

    Science.gov (United States)

    Yee, Leland J.; Im, KyungAh; Borg, Brian; Yang, Huiying; Liang, T. Jake

    2009-01-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-α-2a is successful in eradicating virus from only 30%–80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) (RR=0.80; 95%C.I.: 0.66– 0.98; p=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95%C.I.: 0.66–0.94; p=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95%C.I.: 0.66–0.94; p=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% C.I.: 0.62–1.0; p=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy. PMID:19387461

  12. Interleukin-6 haplotypes and the response to therapy of chronic hepatitis C virus infection.

    Science.gov (United States)

    Yee, L J; Im, K; Borg, B; Yang, H; Liang, T J

    2009-06-01

    Chronic hepatitis C virus (HCV) infection affects nearly 170 million individuals worldwide. Treatment of HCV with pegylated interferon-alpha-2a is successful in eradicating virus from only 30 to 80% of those treated. Interleukin-6 (IL-6) is an important cytokine involved in the immune response to infectious agents and in vitro studies suggest that host genetic variation, particularly haplotypes, may affect IL-6 expression. We examined the contribution of haplotypes in the IL-6 gene on sustained viral response (SVR) to the therapy for chronic HCV infection. We observed the IL-6 T-T-G-G-G-G-C-A-G-A haplotype to be associated with a lower risk of achieving SVR among Caucasian Americans (CAs) ((relative risk) RR=0.80; 95% CI: 0.66-0.98; P=0.0261). Using a sliding window approach, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was associated with a reduced chance of SVR (RR=0.79; 95% CI: 0.66-0.94; P=0.0081), as was the rs1800796-(G)-rs1800795-(G)-rs2069830-(C) haplotype (RR=0.78; 95% CI: 0.66-0.94; P=0.0065) among CAs. Overall, the rs1800797-(G)-rs1800796-(G)-rs1800795-(G) haplotype was independently associated with a reduced chance of SVR (RR=0.78; 95% CI: 0.62-1.0; P=0.0489) after adjustment for potential confounding factors. Our findings further illustrate the complexity of IL-6 genetic regulation and the potential importance of haplotypes on IL-6 expression. Our findings provide additional support for the potential importance of genetic variation in the IL-6 gene and the response to HCV therapy.

  13. Persistent Coxiella burnetii infection in mice overexpressing IL-10: an efficient model for chronic Q fever pathogenesis.

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    Soraya Meghari

    2008-02-01

    Full Text Available Interleukin (IL-10 increases host susceptibility to microorganisms and is involved in intracellular persistence of bacterial pathogens. IL-10 is associated with chronic Q fever, an infectious disease due to the intracellular bacterium Coxiella burnetii. Nevertheless, accurate animal models of chronic C. burnetii infection are lacking. Transgenic mice constitutively expressing IL-10 in macrophages were infected with C. burnetti by intraperitoneal and intratracheal routes and infection was analyzed through real-time PCR and antibody production. Transgenic mice exhibited sustained tissue infection and strong antibody response in contrast to wild-type mice; thus, bacterial persistence was IL-10-dependent as in chronic Q fever. The number of granulomas was low in spleen and liver of transgenic mice infected through the intraperitoneal route, as in patients with chronic Q fever. Macrophages from transgenic mice were unable to kill C. burnetii. C. burnetii-stimulated macrophages were characterized by non-microbicidal transcriptional program consisting of increased expression of arginase-1, mannose receptor, and Ym1/2, in contrast to wild-type macrophages in which expression of inducible NO synthase and inflammatory cytokines was increased. In vivo results emphasized macrophage data. In spleen and liver of transgenic mice infected with C. burnetii by the intraperitoneal route, the expression of arginase-1 was increased while microbicidal pathway consisting of IL-12p40, IL-23p19, and inducible NO synthase was depressed. The overexpression of IL-10 in macrophages prevents anti-infectious competence of host, including the ability to mount granulomatous response and microbicidal pathway in tissues. To our knowledge, this is the first efficient model for chronic Q fever pathogenesis.

  14. The conduction system of the heart in mice chronically infected with Trypanosoma cruzi: histopathological lesions and electrocardiographic correlations

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    Sonia G. Andrade

    1987-03-01

    Full Text Available Chronic focal and diffuse myiocarditis with interstitial fibrosis developed in Swiss outbred mice and in the inbred AKR and A/J strains of mice which were chronically infected with several Trypanosoma cruzi strains belonging to three biological types (Type I, II and III. High incidence of electrocardiographic changes with predominance of intraventricular conduction disturbances, 1st. and 2nd. degree AV block, arrhythmias, comparable with those found in human Chagas' disease, were also present. Morphological study of the conduction tissue of the heart revealed inflammatory and fibrotic changes. The presence of inflammation in the inter-atrial septum almost always coincided with the inflammatory involvement of the ventricular conduction system. Focal inflammation was associated with vacuolization and focal necrosis of the specific fibers. Most of the lesions were seen affecting the His bundel (76.3% of the cases, the right bundle branch (73.3%, AV node (43.9% and left bundle branch (37.5%. Correlation between morphological changes in the conduction tissue and electrocardiographic alteration occured in 53.0 to 62.5% of the cases, according to the experimental groups.Em camundongos suiços não isogênicos e em camundongos isogênicos das linhagens AKR e A/J, cronicamente infectados com cepas do Trypanosoma cruzi representativas de três tipos biológicos (Tipos I, II e III foi observada uma miocardite crônica difusa e focal com graus variáveis de fibrose intersticial. Observou-se alta incidência de alterações eletrocardiográficas com predominância de distúrbios da condução intraventricular, bloqueios A-V de 1º e 2º graus e arritmias, comparáveis às encontradas na doença de Chagas humana. O estudo histopatológico do sistema de condução do coração mostrou alterações inflamatórias e fibróticas. A presença de inflamação no septo inter-atrial em geral coincidiu com o envolvimento do sistema de condução pelo processo inflamat

  15. Gastric Ollulanus tricuspis infection identified in captive cheetahs (Acinonyx jubatus with chronic vomiting : case report

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    M.G. Collett

    2000-07-01

    Full Text Available Gastritis, vomition and weight loss are common in captive cheetahs (Acinonyx jubatus. Gastric spiral bacteria (Helicobacter spp. and the very small, viviparous nematode Ollulanus tricuspis, a stomach worm of cats, are believed to be important causes. Three sibling cheetahs at Wellington Zoo, New Zealand, developed chronic vomiting, diarrhoea and debility. Their parents were both South African-born. Response to antibacterial treatment was poor. Endoscopic examinations revealed chronic lymphoplasmacytic gastritis and Ollulanus infection. Treatment with oxfendazole and pyrantel embonate resulted in clinical improvement; however, 1 cheetah, which died 7 months later as a result of a ruptured liver due to hepatic amyloidosis, still had Ollulanus worms present in her stomach. Ollulanus tricuspis is a significant cause of gastritis and vomiting in captive cheetahs, lions and tigers, as well as wild cougars and tigers. The parasite has not yet been found in sub-Saharan Africa. Because of the unusual characteristics of this parasite, the literature on its life history and techniques for diagnosis is reviewed.

  16. Effects of Toxoplasma gondii Infection in Level of Serum Testosterone in Males with Chronic Toxoplasmosis.

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    Zahra Eslamirad

    2013-12-01

    Full Text Available Toxoplasma gondii is an intracellular protozoan parasite that infects human and animals. Toxoplasma parasites are isolated from different parts of animals even from semen but there are little information about the effect of toxoplasmosis on fertility in animals and humans. In present study, the effect of chronic toxoplasmosis on serum levels of testosterone in men was studied.In this case-control study, 1026 men referred to Arak Post Marriage Center were selected. Three ml of blood samples were collected and sera separated by centrifugation at room temperature. These sera were analyzed for detection of anti-T. gondii IgG antibody. Next 365 positive sera were selected as cases and also the same number of negative sera (365 as controls. Finally the level of testosterone was analyzed for the cases and controls samples.Serological tests on the sera of 1,026 men in Arak City showed that 365 of them had anti-Toxoplasma antibody. Comparison of testosterone concentration in case and control groups showed that testosterone concentration in case group was less than control group and this difference was statistically significant (P<0.05.The chronic toxoplasmosis could affect reproductive parameters in men.

  17. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases.

    Science.gov (United States)

    Stefenelli, N; Klotz, H; Engel, A; Bauer, P

    1985-01-01

    The total serum sialic acid concentration was determined in 2,264 persons with various malignant tumors, bacterial infections, rheumatic diseases, and chronic liver diseases, and in a control group. The thiobarbiturate method according to Warren was used. The upper limit (95% percentile) in the control group was 2.23 mumol/ml. Higher values were found in the groups with neoplasms (mean: 3.04 mumol/ml), inflammatory diseases (e.g., pneumonia: 3.02 mumol/ml), and active rheumatoid arthritis (3.05 mumol/ml). In the group with malignant diseases, the sialic acid concentration at the time of diagnosis was highest for bronchial carcinoma (3.29 mumol/ml) and lowest for breast cancer (2.58 mumol/ml). In chronic liver diseases the mean sialic acid level was lower than in a heterogeneous group of noninflammatory and nonneoplastic diseases. The estimation of the serum sialic acid concentration could be useful in the detection of tumor burden and metastases, and in the evaluation of the later course and prognosis of malignant neoplasms if bacterial/inflammatory and active rheumatoid processes can be excluded.

  18. Clinical identification of bacteria in human chronic wound infections: culturing vs. 16S ribosomal DNA sequencing

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    Rhoads Daniel D

    2012-11-01

    Full Text Available Abstract Background Chronic wounds affect millions of people and cost billions of dollars in the United States each year. These wounds harbor polymicrobial biofilm communities, which can be difficult to elucidate using culturing methods. Clinical molecular microbiological methods are increasingly being employed to investigate the microbiota of chronic infections, including wounds, as part of standard patient care. However, molecular testing is more sensitive than culturing, which results in markedly different results being reported to clinicians. This study compares the results of aerobic culturing and molecular testing (culture-free 16S ribosomal DNA sequencing, and it examines the relative abundance score that is generated by the molecular test and the usefulness of the relative abundance score in predicting the likelihood that the same organism would be detected by culture. Methods Parallel samples from 51 chronic wounds were studied using aerobic culturing and 16S DNA sequencing for the identification of bacteria. Results One hundred forty-five (145 unique genera were identified using molecular methods, and 68 of these genera were aerotolerant. Fourteen (14 unique genera were identified using aerobic culture methods. One-third (31/92 of the cultures were determined to be Staphylococcus aureus, Pseudomonas aeruginosa, and Enterococcus faecalis with higher relative abundance scores were more likely to be detected by culture as demonstrated with regression modeling. Conclusion Discordance between molecular and culture testing is often observed. However, culture-free 16S ribosomal DNA sequencing and its relative abundance score can provide clinicians with insight into which bacteria are most abundant in a sample and which are most likely to be detected by culture.

  19. Association between risk factors, basal viral load, virus genotype and the degree of liver fibrosis with the response to the therapy in patients with chronic hepatitis C virus infection

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    Vuković Vuk R.

    2015-01-01

    Full Text Available Background/Aim. Hepatitis C is an important sociomedical problem worldwide due to frequent progression to chronic disease, occurrence of liver cirrhosis and hepatocellular carcinoma. Standard pegylated interferon alfa 2a plus ribavirin therapy results in resolution of infection only in 50% of patients. The aim of this study was to determine the association of various factors with response to the therapy in patients with chronic hepatitis C virus (HCV infection. Age and sex of patients, inoculation risk factors, histopathological changes in the liver, viral load and HCV genotype were analyzed. Methods. The study included a group of 121 patients with chronic HCV infection. The treatment was carried out 24 weeks for virus genotype 2 and 3, and 48 weeks for genotype 1 and 4. The degree of histopathological changes in the liver was determined by hematoxylin and eosin staining, whereas polimerase chain reaction was used for HCV genotyping. Results. In the group of non-responding patients genotype 1 was represented with 100%, while in the other groups, although predominantly present, its percentage was lower. Unresponsiveness to therapy and relapse of disease were associated with higher viral load and advanced fibrosis. Intravenous use of psychoactive substances, as a risk factor, was present in a high percentage in the group of patients with sustained response, while blood transfusion and dialysis were leading risk factors in the group of relapse responders and non-responders. Conclusion. The results of our study showed that the treatment outcome of chronic HCV infection was associated with baseline HCV ribonucleic acid, HCV genotype, route of infection and the degree of histopathological changes in the liver. [Projekat Ministarstva nauke Republike Srbije, br. III41010

  20. Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.

    Science.gov (United States)

    Holm, Jacob Bak; Sorobetea, Daniel; Kiilerich, Pia; Ramayo-Caldas, Yuliaxis; Estellé, Jordi; Ma, Tao; Madsen, Lise; Kristiansen, Karsten; Svensson-Frej, Marcus

    2015-01-01

    The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.

  1. Chronic Trichuris muris Infection Decreases Diversity of the Intestinal Microbiota and Concomitantly Increases the Abundance of Lactobacilli.

    Directory of Open Access Journals (Sweden)

    Jacob Bak Holm

    Full Text Available The intestinal microbiota is vital for shaping the local intestinal environment as well as host immunity and metabolism. At the same time, epidemiological and experimental evidence suggest an important role for parasitic worm infections in maintaining the inflammatory and regulatory balance of the immune system. In line with this, the prevalence of persistent worm infections is inversely correlated with the incidence of immune-associated diseases, prompting the use of controlled parasite infections for therapeutic purposes. Despite this, the impact of parasite infection on the intestinal microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal microbiota by 16S ribosomal-RNA gene-based sequencing. Our results demonstrate that persistent T. muris infection dramatically affects the large-intestinal microbiota, most notably with a drop in the diversity of bacterial communities, as well as a marked increase in the relative abundance of the Lactobacillus genus. In parallel, chronic T. muris infection resulted in a significant shift in the balance between regulatory and inflammatory T cells in the intestinal adaptive immune system, in favour of inflammatory cells. Together, these data demonstrate that chronic parasite infection strongly influences the intestinal microbiota and the adaptive immune system. Our results illustrate the complex interactions between these factors in the intestinal tract, and contribute to furthering the understanding of this interplay, which is of crucial importance considering that 500 million people globally are suffering from these infections and their potential use for therapeutic purposes.

  2. Chronic granulomatous disease of childhood: an unusual cause of recurrent uncommon infections in a 61-year-old man

    NARCIS (Netherlands)

    G. Isman-Nelkenbaum; B. Wolach; R. Gavrieli; D. Roos; E. Sprecher; E. Bash; A. Gat; H. Sprecher; R. Ben-Ami; T. Zeeli

    2011-01-01

    Chronic granulomatous disease (CGD) is a rare congenital immunodeficiency that affects 1 : 250 000 of the population, which is characterized by recurrent bacterial and fungal infections and by granuloma formation. We investigated a 61-year-old man presented with a 20-year history of a relapsing skin

  3. Poor outcomes of chronic active Epstein-Barr virus infection and hemophagocytic lymphohistiocytosis in non-Japanese adult patients

    NARCIS (Netherlands)

    G.S. Sonke (Gabe); I. Ludwig (Inge); H. van Oosten (Hannah); J.W. Baars (Joke); E. Meijer (Ellen); A.P. Kater (Arnon); D. de Jong (Daphne)

    2008-01-01

    textabstractChronic active Epstein-Barr virus infection manifests as a combination of persistent infectious mononucleosis-like symptoms and high viral load in apparently immunocompetent patients. It is closely related to Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis. These 2 abnor

  4. Chronic Trichuris muris infection decreases diversity of the intestinal microbiota and concomitantly increases the abundance of lactobacilli

    DEFF Research Database (Denmark)

    Holm, Jacob Bak; Sorobetea, Daniel; Kiilerich, Pia;

    2015-01-01

    microbiota, as well as potential downstream effects on the immune system, remain largely unknown. We have assessed the influence of chronic infection with the large-intestinal nematode Trichuris muris, a close relative of the human pathogen Trichuris trichiura, on the composition of the murine intestinal...

  5. Plasminogen Activator Inhibitor -1 (PAI-1) Predicts Negative Alterations in Whole Body Insulin Sensitivity in Chronic HIV Infection.

    Science.gov (United States)

    Wirunsawanya, Kamonkiat; Belyea, Loni; Shikuma, Cecilia; Watanabe, Richard; Kohorn, Lindsay; Shiramizu, Bruce; Mitchell, Brooks; Souza, Scott A; Keating, Sheila; Norris, Philip J; Ndhlovu, Lishomwa; Chow, Dominic

    2017-03-21

    Plasminogen activator inhibitor type 1 (PAI-1), a key negative regulator of fibrinolysis, has been investigated to be a potential predictor of the development of insulin resistance and diabetes mellitus. Because chronically stable HIV-infected individuals frequently develop abnormal glucose metabolism including insulin resistance and diabetes mellitus, we postulated PAI-1 could be one of multifactorial pathogenic roles in the development of insulin resistance among chronic HIV-infected individuals. From our longitudinal cohort study, we selectively recruited chronically stable HIV-infected individuals without diagnosis of diabetes mellitus at baseline (N = 62) to analyze the correlation of baseline inflammatory cytokines including PAI-1 and whole body insulin sensitivity with two-year follow-up, as measured by Matsuda Index. We found a negative correlation between baseline PAI-1 and Matsuda Index (r = -.435 , p = .001) and a negative correlation with PAI-1 at baseline and Matsuda Index at two years (r = -.377 , p = .005). In a linear regression model that included age, total body fat mass percentage, serum amyloid A and family history of diabetes mellitus, PAI-1 still remained significantly associated with Matsuda Index at two-year follow-up (β = -.397, p = .002). Our longitudinal study suggests PAI-1 is an independent predictor of insulin resistance among chronic HIV-infected individuals.

  6. Bacterial sinusitis can be a focus for initial lung colonisation and chronic lung infection in patients with cystic fibrosis

    DEFF Research Database (Denmark)

    Aanæs, Kasper

    2013-01-01

    A major purpose of treating patients with cystic fibrosis (CF) is to prevent or delay chronic lung infections with CF-pathogenic Gram-negative bacteria. In the intermittent stage, bacteria can usually be eradicated from the lungs with antibiotics, but following eradication, the next lung colonisa...... therapy, e.g. saline and antibiotic irrigations....

  7. Interleukin-16 Gene Polymorphisms Are Considerable Host Genetic Factors for Patients’ Susceptibility to Chronic Hepatitis B Infection

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    Sara Romani

    2014-01-01

    Full Text Available Host genetic background is known as an important factor in patients’ susceptibility to infectious diseases such as viral hepatitis. The aim of this study was to determine the effect of genetic polymorphisms of interleukin-16 (IL-16 cytokine on susceptibility of hepatitis B virus (HBV infected patients to develop chronic HBV infection. Genotyping was conducted using PCR followed by enzymatic digestion and RFLP (restriction fragment length polymorphism analysis. We genotyped three single nucleotide polymorphisms (SNPs in the Il-16 gene (rs11556218 T>G, rs4778889 T>C, and rs4072111 C>T to test for relationship between variation at these loci and patients’ susceptibility to chronic HBV infection. Allele frequency of Il-16 gene rs4072111 and rs11556218 was significantly different between chronic HBV patients and healthy blood donors. Genotype frequency of rs4778889 polymorphism of Il-16 gene was significantly different when chronic HBV patients and HBV clearance subjects were compared. Our results showed that Il-16 gene polymorphisms are considerable host genetic factors when we chase biomarkers for prognosis of HBV infected patients.

  8. Inhibition of protease-resistant prion protein formation in a transformed deer cell line infected with chronic wasting disease

    NARCIS (Netherlands)

    Raymond, G.J.; Olsen, E.A.; Lee, K.S.; Raymond, L.D.; Bryant, P.K.; Baron, G.S.; Caughey, W.S.; Kocisko, D.A.; McHolland, L.E.; Favara, C.; Langeveld, J.P.M.; Zijderveld, van F.G.; Mayer, R.T.; Miller, M.W.; Williams, E.S.; Caughey, B.

    2006-01-01

    Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti). To facilitate in vitro studies of CWD, we have developed a transformed deer cell line that is persistently infected wi

  9. Production of N-acyl-L-homoserine lactones by P. aeruginosa isolates from chronic lung infections associated with cystic fibrosis

    DEFF Research Database (Denmark)

    Geisenberger, O; Givskov, M; Riedel, K;

    2000-01-01

    The N-acyl-L-homoserine lactones (AHLs) produced by sequential Pseudomonas aeruginosa isolates from chronically infected patients with cystic fibrosis were analyzed by thin-layer chromatography. It is demonstrated that both the amounts and the types of molecules synthesized by isolates from...

  10. Case-term Adverse Outcomes of Chronic Hepatitis C, Extrahepatic Manifestations of a Young Man Infected in Early Childhood

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    S. V. Baramzina

    2015-01-01

    Full Text Available In the present article discusses the clinical case of unfavorable course of chronic hepatitis C with the outcome of cirrhosis and development of extrahepatic manifestations of a young man of 20 years as a result of infection in early childhood.

  11. Chronic bee paralysis virus and Nosema ceranae experimental co-infection of winter honey bee workers (Apis mellifera L.)

    Science.gov (United States)

    Chronic bee paralysis virus (CBPV) is an important viral disease of adult bees which induces significant losses in honey bee colonies. In this study winter worker bees were experimentally infected using three different experiments. Bees were inoculated orally or topically with CBPV to evaluate the l...

  12. Hepatitis B virus genotypes and mutations in the basal core promoter and pre-core/core in chronically infected patients in southern Brazil: a cross-sectional study of HBV genotypes and mutations in chronic carriers

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    Flávia Miryan Martins Almeida de Mello

    2014-12-01

    Full Text Available Introduction In Brazil, little data exist regarding the distribution of genotypes in relation to basal core promoter (BCP and precore/core mutations among chronic hepatitis B virus (HBV carriers from different regions of the country. The aim of this study was to identify HBV genotypes and the frequency of mutations at the BCP and precore/core region among the prevalent genotypes in chronic carriers from southern Brazil. Methods Nested-polymerase chain reaction (nested-PCR products amplified from the S-polymerase gene, BCP and precore/core region from 54 samples were sequenced and analyzed. Results Phylogenetic analysis of the S-polymerase gene sequences showed that 66.7% (36/54 of the patients were infected with genotype D (D1, D2, D3, 25.9% (14/54 with genotype A (A1, A2, 5.6% (3/54 with subgenotype C2, and 2% (1/54 with genotype E. A comparison of virological characteristics showed significant differences between genotypes A, C and D. The comparison between HBeAg status and the G1896A stop codon mutation in patients with genotype D revealed a relationship between HBV G1896A precore mutants and genotype D and hepatitis B e antigen (HBeAg seroconversion. Genotype D had a higher prevalence of the G1896A mutation and the presence of a thymine at position 1858. Genotype A was associated with a higher prevalence of the G1862T mutation and the presence of a cytosine at position 1858. Conclusions HBV genotype D (D3 is predominant in HBV chronic carriers from southern Brazil. The presence of mutations in the BCP and precore/core region was correlated with the HBV genotype and HBeAg negative status.

  13. In vitro-induced antibody production in chronic hepatitis C virus infection

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    Oliveira Jr. E.B.

    2003-01-01

    Full Text Available The objectives of the present study were to assess the in vitro-induced anti-hepatitis C virus (HCV antibody production (IVIAP in relation to the clinical, biochemical, virologic and histologic variables of patients with HCV infection. The study included 57 patients (60% males with HCV infection (anti-HCV and HCV-RNA positive. Alanine aminotransferase (ALT was elevated in 89% of the patients. Mean viral load was 542,241 copies/ml and histology of the liver showed chronic hepatitis in 27/52 (52% and cirrhosis in 11/52 (21% patients. IVIAP levels were determined by immunoenzymatic assay at median absorbance of 0.781 at 450 nm. IVIAP was negative in 14% of the patients. When groups with IVIAP levels above and below the median were compared, high IVIAP levels were associated with the male sex, elevated ALT levels and more advanced disease stage. After logistic regression analysis, advanced histologic damage to the liver remained as the only independent variable associated with elevated IVIAP levels. Using a receiver operator characteristic curve, the best cut-off level for IVIAP was established (= 1.540, with 71% sensitivity and 94% specificity for the detection of more advanced disease stages (grades 3 and 4. These findings are consistent with the participation of immunological mechanisms in the genesis of the hepatic lesions induced by HCV and indicate that the IVIAP test may be useful as a noninvasive marker of liver damage either alone or in combination with other markers.

  14. Enhanced binding of antibodies generated during chronic HIV infection to mucus component MUC16

    Science.gov (United States)

    Bastian, Arangassery Rosemary; Fahrbach, Kelly; Smith, Archer; Mahan, Alison; Karim, Marcus; Licht, Anna; Zvonar, Ivan; Tedesco, Jacquelynn; Anderson, Meegan; Chapel, Anais; Suscovich, Todd; Malaspina, David; Streeck, Hendrik; Walker, Bruce D.; Kim, Arthur; Lauer, Georg; Altfeld, Marcus; Pillai, Shiv; Szleifer, Igal; Kelleher, Neil L.; Kiser, Patrick F.; Hope, Thomas J.; Alter, Galit

    2016-01-01

    Transmission of HIV across mucosal barriers accounts for the majority of HIV infections worldwide. Thus, efforts aimed at enhancing protective immunity at these sites are a top priority, including increasing virus-specific antibodies (Abs) and antiviral activity at mucosal sites. Mucin proteins, including the largest cell-associated mucin, MUC16, help form mucus to provide a physical barrier to incoming pathogens. Here we describe a natural interaction between Abs and MUC16 that is enhanced in specific disease settings such as chronic HIV infection. Binding to MUC16 was independent of IgG subclass, but strongly associated with shorter Ab glycan profiles, with agalactosylated (G0) Abs demonstrating the highest binding to MUC16. Binding of Abs to epithelial cells was diminished following MUC16-knockdown, and the MUC16 N-linked glycans were critical for binding. Further, agalactosylated VRC01 captured HIV more efficiently in MUC16. These data point to a novel opportunity to enrich Abs at mucosal sites by targeting Abs to MUC16 through changes in Fc-glycosylation, potentially blocking viral movement and sequestering the virus far from the epithelial border. Thus, next-generation vaccines or monoclonal therapeutics may enhance protective immunity by tuning Ab glycosylation to promote the enrichment of Abs at mucosal barriers. PMID:26960182

  15. Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections.

    Science.gov (United States)

    Nourmohammad, Armita; Otwinowski, Jakub; Plotkin, Joshua B

    2016-07-01

    The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics between antibodies and antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may have relevance to vaccine design against HIV.

  16. Host-Pathogen Coevolution and the Emergence of Broadly Neutralizing Antibodies in Chronic Infections.

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    Armita Nourmohammad

    2016-07-01

    Full Text Available The vertebrate adaptive immune system provides a flexible and diverse set of molecules to neutralize pathogens. Yet, viruses such as HIV can cause chronic infections by evolving as quickly as the adaptive immune system, forming an evolutionary arms race. Here we introduce a mathematical framework to study the coevolutionary dynamics between antibodies and antigens within a host. We focus on changes in the binding interactions between the antibody and antigen populations, which result from the underlying stochastic evolution of genotype frequencies driven by mutation, selection, and drift. We identify the critical viral and immune parameters that determine the distribution of antibody-antigen binding affinities. We also identify definitive signatures of coevolution that measure the reciprocal response between antibodies and viruses, and we introduce experimentally measurable quantities that quantify the extent of adaptation during continual coevolution of the two opposing populations. Using this analytical framework, we infer rates of viral and immune adaptation based on time-shifted neutralization assays in two HIV-infected patients. Finally, we analyze competition between clonal lineages of antibodies and characterize the fate of a given lineage in terms of the state of the antibody and viral populations. In particular, we derive the conditions that favor the emergence of broadly neutralizing antibodies, which may have relevance to vaccine design against HIV.

  17. Recrudescence induced by cyclophosphamide of chronic Trypanosoma cruzi infection in mice is influenced by the parasite strain

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    Maria Elizabeth S Pereira

    1996-02-01

    Full Text Available Reactivation of chronic chagasic patients may occur upon use of immunosuppressive drugs related to kidney or heart transplantation or when they are affected by concomitant HIV infection. This recrudescence, however, does not occur in all chagasic patients exposed to immunosuppressive agents. We therefore investigated the influence of Trypanosoma cruzi strains in the recrudescence of the parasitism in mice at the chronic phase treated with cyclophosphamide, an immunosuppressor that blocks lymphocytes DNA synthesis and therefore controls B cells response. A large variation was detected in the percentages of newly established acute phases in the groups of mice inoculated with the different strains. We suggest that reactivation of chronic T. cruzi infections is influenced by the parasite intrinsic characteristics, a phenomenon that might occur in the human disease.

  18. Polymicrobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP.

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    Scot E Dowd

    Full Text Available BACKGROUND: Diabetic extremity ulcers are associated with chronic infections. Such ulcer infections are too often followed by amputation because there is little or no understanding of the ecology of such infections or how to control or eliminate this type of chronic infection. A primary impediment to the healing of chronic wounds is biofilm phenotype infections. Diabetic foot ulcers are the most common, disabling, and costly complications of diabetes. Here we seek to derive a better understanding of the polymicrobial nature of chronic diabetic extremity ulcer infections. METHODS AND FINDINGS: Using a new bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP approach we have evaluated the bacterial diversity of 40 chronic diabetic foot ulcers from different patients. The most prevalent bacterial genus associated with diabetic chronic wounds was Corynebacterium spp. Findings also show that obligate anaerobes including Bacteroides, Peptoniphilus, Fingoldia, Anaerococcus, and Peptostreptococcus spp. are ubiquitous in diabetic ulcers, comprising a significant portion of the wound biofilm communities. Other major components of the bacterial communities included commonly cultured genera such as Streptococcus, Serratia, Staphylococcus and Enterococcus spp. CONCLUSIONS: In this article, we highlight the patterns of population diversity observed in the samples and introduce preliminary evidence to support the concept of functional equivalent pathogroups (FEP. Here we introduce FEP as consortia of genotypically distinct bacteria that symbiotically produce a pathogenic community. According to this hypothesis, individual members of these communities when they occur alone may not cause disease but when they coaggregate or consort together into a FEP the synergistic effect provides the functional equivalence of well-known pathogens, such as Staphylococcus aureus, giving the biofilm community the factors necessary to maintain chronic biofilm infections

  19. Naturally acquired bovine besnoitiosis: Differential distribution of parasites in the skin of chronically infected cattle.

    Science.gov (United States)

    Schares, G; Langenmayer, M C; Majzoub-Altweck, M; Scharr, J C; Gentile, A; Maksimov, A; Schares, S; Conraths, F J; Gollnick, N S

    2016-01-30

    Bovine besnoitiosis is caused by Besnoitia besnoiti, an apicomplexan parasite closely related to Toxoplasma gondii and Neospora caninum. In the acute stage of besnoitiosis, cattle suffer from pyrexia, swollen lymph nodes, anorexia and subcutaneous edema. In the chronic stage, tissue cysts are formed in a variety of tissues including the skin. Knowledge about the distribution of tissue cysts of different parts of the skin of infected animals is scarce. Four chronically infected cattle were euthanized and skin samples were taken from a total of 77 standardized cutaneous locations per animal. Portions of the dermis were taken, from which DNA was extracted and examined by real-time PCR. Cycle of transition (Ct) values reflecting the amount of parasite DNA in the samples were determined. For statistical analysis, samples were attributed to 11 larger skin regions ('OuterHindlegDistal', 'Rump, ForelegMiddle', 'NoseFrontEars', 'CheekEye', 'SideLowerPart', 'ForelegDistal', 'SideUpperPart', 'LegsInner', 'VentralHeadNeck', 'DorsalNeckWithersBackTail'). While all samples revealed a positive result in three female cattle, only 63.6% (49/77) of the samples of a bull showed positive results. For statistical analysis, a Ct value of 45 was assumed for samples with a negative result. The dams showed median Ct values of 16.1, 17.5 and 19.4, while in skin samples of the bull a median Ct value of 37.6 was observed. To determine the differences in DNA concentrations between different locations of the skin of the animals, a relative Ct (relCt) was determined by subtracting for each animal indv the MedianCtindv from each sample Ct. Analyses of the relCt values showed that the highest relative parasite DNA concentrations were observed in the categories 'OuterHindlegDistal', 'Rump', 'ForelegMiddle' and 'NoseFrontEars'. The relCt values in these categories differed statistically significantly from those determined for the categories 'VentralHeadNeck' and 'DorsalNeckWithersBackTail'. The

  20. Randomized, controlled trial of therapy interruption in chronic HIV-1 infection.

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    Emmanouil Papasavvas

    2004-12-01

    Full Text Available BACKGROUND: Approaches to limiting exposure to antiretroviral therapy (ART drugs are an active area of HIV therapy research. Here we present longitudinal follow-up of a randomized, open-label, single-center study of the immune, viral, and safety outcomes of structured therapy interruptions (TIs in patients with chronically suppressed HIV-1 infection as compared to equal follow-up of patients on continuous therapy and including a final therapy interruption in both arms. METHODS AND FINDINGS: Forty-two chronically HIV-infected patients on suppressive ART with CD4 counts higher than 400 were randomized 1:1 to either (1 three successive fixed TIs of 2, 4, and 6 wk, with intervening resumption of therapy with resuppression for 4 wk before subsequent interruption, or (2 40 wk of continuous therapy, with a final open-ended TI in both treatment groups. Main outcome was analysis of the time to viral rebound (>5,000 copies/ml during the open-ended TI. Secondary outcomes included study-defined safety criteria, viral resistance, therapy failure, and retention of immune reconstitution. There was no difference between the groups in time to viral rebound during the open-ended TI (continuous therapy/single TI, median [interquartile range] = 4 [1-8] wk, n = 21; repeated TI, median [interquartile range] = 5 [4-8] wk, n = 21; p = 0.36. No differences in study-related adverse events, viral set point at 12 or 20 wk of open-ended interruption, viral resistance or therapy failure, retention of CD4 T cell numbers on ART, or retention of lymphoproliferative recall antigen responses were noted between groups. Importantly, resistance detected shortly after initial viremia following the open-ended TI did not result in a lack of resuppression to less than 50 copies/ml after reinitiation of the same drug regimen. CONCLUSION: Cycles of 2- to 6-wk time-fixed TIs in patients with suppressed HIV infection failed to confer a clinically significant benefit with regard to viral

  1. Pseudomonas aeruginosa AES-1 exhibits increased virulence gene expression during chronic infection of cystic fibrosis lung.

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    Sharna Naughton

    Full Text Available Pseudomonas aeruginosa, the leading cause of morbidity and mortality in people with cystic fibrosis (CF, adapts for survival in the CF lung through both mutation and gene expression changes. Frequent clonal strains such as the Australian Epidemic Strain-1 (AES-1, have increased ability to establish infection in the CF lung and to superimpose and replace infrequent clonal strains. Little is known about the factors underpinning these properties. Analysis has been hampered by lack of expression array templates containing CF-strain specific genes. We sequenced the genome of an acute infection AES-1 isolate from a CF infant (AES-1R and constructed a non-redundant micro-array (PANarray comprising AES-1R and seven other sequenced P. aeruginosa genomes. The unclosed AES-1R genome comprised 6.254Mbp and contained 6957 putative genes, including 338 not found in the other seven genomes. The PANarray contained 12,543 gene probe spots; comprising 12,147 P. aeruginosa gene probes, 326 quality-control probes and 70 probes for non-P. aeruginosa genes, including phage and plant genes. We grew AES-1R and its isogenic pair AES-1M, taken from the same patient 10.5 years later and not eradicated in the intervening period, in our validated artificial sputum medium (ASMDM and used the PANarray to compare gene expression of both in duplicate. 675 genes were differentially expressed between the isogenic pairs, including upregulation of alginate, biofilm, persistence genes and virulence-related genes such as dihydroorotase, uridylate kinase and cardiolipin synthase, in AES-1M. Non-PAO1 genes upregulated in AES-1M included pathogenesis-related (PAGI-5 genes present in strains PACS2 and PA7, and numerous phage genes. Elucidation of these genes' roles could lead to targeted treatment strategies for chronically infected CF patients.

  2. Interleukin-1 gene polymorphisms in chronic gastritis patients infected with Helicobacter pylori as risk factors of gastric cancer development.

    Science.gov (United States)

    Hnatyszyn, Andrzej; Wielgus, Karolina; Kaczmarek-Rys, Marta; Skrzypczak-Zielinska, Marzena; Szalata, Marlena; Mikolajczyk-Stecyna, Joanna; Stanczyk, Jerzy; Dziuba, Ireneusz; Mikstacki, Adam; Slomski, Ryszard

    2013-12-01

    Epidemiological investigations indicated association of the Helicobacter pylori infections with the occurrence of inflammatory conditions of the gastric mucosa and development of chronic gastritis and intestinal type of gastric cancer. IL1A and IL1B genes have been proposed as key factors in determining risk of gastritis and malignant transformation. The aim of this paper was to evaluate association of interleukin-1 gene polymorphisms with chronic gastritis, atrophy, intestinal metaplasia, dysplasia and intestinal type of gastric cancer in H. pylori-infected patients. Patients subjected to analysis represent group of 144 consecutive cases that suffered from dyspepsia with coexisting infection of H. pylori and chronic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia or gastric cancer. Molecular studies involved analysis of -889C>T polymorphism of IL1A gene and +3954C>T polymorphism of IL1B gene. Statistical analysis of association of polymorphism -889C>T of gene IL1A with changes in gastric mucosa showed lack of significance, whereas +3954C>T polymorphism of IL1B gene showed significant association. Frequency of allele T of +3954C>T polymorphism of IL1B gene was higher in group of patients with chronic gastritis, atrophy, intestinal metaplasia, dysplasia or intestinal type of gastric cancer (32.1 %) as compared with population group (23 %), χ(2) = 4.61 and p = 0.03. This corresponds to odds ratio: 1.58, 95 % CI: 1.04-2.4. Our results indicate that +3954C>T polymorphism of IL1B gene increase susceptibility to inflammatory response of gastric mucosa H. pylori-infected patients and plays a significant role in the development of chronic gastritis, atrophy, intestinal metaplasia, dysplasia and the initiation of carcinogenesis.

  3. Anti-HBs seroconversion during treatment with entecavir in a patient with chronic hepatitis B virus infection on hemodialysis.

    Science.gov (United States)

    Spaziante, Martina; Biliotti, Elisa; Grieco, Stefania; Palazzo, Donatella; Esvan, Rozenn; Taliani, Gloria

    2014-01-01

    Hepatitis B (HBV) virus infection is one of the most important causes of liver disease in patients with end-stage renal failure on hemodialysis. The natural history of chronic HBV infection acquired in childhood starts with an immune tolerant phase, followed by an immune clearance phase that may lead to the inactive carrier state or the development of chronic liver disease. Information on antiviral therapy administered very early during the immune clearance phase are lacking and no data exist on the treatment of early immune activation in the hemodialysis setting. This report describes the case of a patient affected by end-stage renal failure and HBeAg-positive chronic HBV virus infection treated very early during the immune clearance phase of HBV infection with an adjusted-dose of nucleoside analogue entecavir. The patient achieved a very rapid HBV-DNA undetectability, anti-HBe, and anti-HBs seroconversion. This is the first report of antiviral therapy with entecavir started during the immune reactive phase of HBV infection in a patient on hemodialysis and it suggests that antiviral treatment can enhance the effects of host immune activation resulting in biochemical, serological, and viral response, even in end-stage renal failure patients with partial immunodeficiency. Antiviral therapy with entecavir in the setting of hemodialysis was safe and well tolerated.

  4. Characterization of the specific CD4+ T cell response against the F protein during chronic hepatitis C virus infection.

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    De-Yong Gao

    Full Text Available BACKGROUND: The hepatitis C virus (HCV Alternate Reading Frame Protein (ARFP or F protein presents a double-frame shift product of the HCV core gene. We and others have previously reported that the specific antibodies against the F protein could be raised in the sera of HCV chronically infected patients. However, the specific CD4(+ T cell responses against the F protein during HCV infection and the pathological implications remained unclear. In the current study, we screened the MHC class II-presenting epitopes of the F protein through HLA-transgenic mouse models and eventually validated the specific CD4(+ T cell responses in HCV chronically infected patients. METHODOLOGY: DNA vaccination in HLA-DR1 and-DP4 transgenic mouse models, proliferation assay to test the F protein specific T cell response, genotyping of Chronic HCV patients and testing the F-peptide stimulated T cell response in the peripheral blood mononuclear cell (PBMC by in vitro expansion and interferon (IFN- γ intracellular staining. PRINCIPAL FINDINGS: At least three peptides within HCV F protein were identified as HLA-DR or HLA-DP4 presenting epitopes by the proliferation assays in mouse models. Further study with human PBMCs evidenced the specific CD4(+ T cell responses against HCV F protein as well in patients chronically infected with HCV. CONCLUSION: The current study provided the evidence for the first time that HCV F protein could elicit specific CD4(+ T cell response, which may provide an insight into the immunopathogenesis during HCV chronic infection.

  5. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

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    Abderaouf Damouche

    2015-09-01

    Full Text Available Two of the crucial aspects of human immunodeficiency virus (HIV infection are (i viral persistence in reservoirs (precluding viral eradication and (ii chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART-controlled HIV-infected patients. The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF; the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV. The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART. Data on the impact of HIV on the SVF (especially in individuals not receiving ART are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low

  6. Adipose Tissue Is a Neglected Viral Reservoir and an Inflammatory Site during Chronic HIV and SIV Infection.

    Science.gov (United States)

    Damouche, Abderaouf; Lazure, Thierry; Avettand-Fènoël, Véronique; Huot, Nicolas; Dejucq-Rainsford, Nathalie; Satie, Anne-Pascale; Mélard, Adeline; David, Ludivine; Gommet, Céline; Ghosn, Jade; Noel, Nicolas; Pourcher, Guillaume; Martinez, Valérie; Benoist, Stéphane; Béréziat, Véronique; Cosma, Antonio; Favier, Benoit; Vaslin, Bruno; Rouzioux, Christine; Capeau, Jacqueline; Müller-Trutwin, Michaela; Dereuddre-Bosquet, Nathalie; Le Grand, Roger; Lambotte, Olivier; Bourgeois, Christine

    2015-09-01

    Two of the crucial aspects of human immunodeficiency virus (HIV) infection are (i) viral persistence in reservoirs (precluding viral eradication) and (ii) chronic inflammation (directly associated with all-cause morbidities in antiretroviral therapy (ART)-controlled HIV-infected patients). The objective of the present study was to assess the potential involvement of adipose tissue in these two aspects. Adipose tissue is composed of adipocytes and the stromal vascular fraction (SVF); the latter comprises immune cells such as CD4+ T cells and macrophages (both of which are important target cells for HIV). The inflammatory potential of adipose tissue has been extensively described in the context of obesity. During HIV infection, the inflammatory profile of adipose tissue has been revealed by the occurrence of lipodystrophies (primarily related to ART). Data on the impact of HIV on the SVF (especially in individuals not receiving ART) are scarce. We first analyzed the impact of simian immunodeficiency virus (SIV) infection on abdominal subcutaneous and visceral adipose tissues in SIVmac251 infected macaques and found that both adipocytes and adipose tissue immune cells were affected. The adipocyte density was elevated, and adipose tissue immune cells presented enhanced immune activation and/or inflammatory profiles. We detected cell-associated SIV DNA and RNA in the SVF and in sorted CD4+ T cells and macrophages from adipose tissue. We demonstrated that SVF cells (including CD4+ T cells) are infected in ART-controlled HIV-infected patients. Importantly, the production of HIV RNA was detected by in situ hybridization, and after the in vitro reactivation of sorted CD4+ T cells from adipose tissue. We thus identified adipose tissue as a crucial cofactor in both viral persistence and chronic immune activation/inflammation during HIV infection. These observations open up new therapeutic strategies for limiting the size of the viral reservoir and decreasing low-grade chronic

  7. Neutralizing antibodies in patients with chronic hepatitis C and correlation to liver cirrhosis and estimated duration of infection.

    Science.gov (United States)

    Pedersen, Jannie; Lundbo, Lene Fogt; Krarup, Henrik; Bukh, Jens; Weis, Nina

    2016-10-01

    Although chronic hepatitis C virus (HCV) infection accounts for 30% of individuals with cirrhotic livers worldwide, factors influencing disease progression are far from elucidated. The aim of this study was to determine whether the level of neutralizing antibodies (NAbs) correlated with the development of cirrhosis in patients with chronic HCV infection, genotype 1, when adjusting for estimated duration of infection. Thirty-nine patients with chronic hepatitis C, with either no/mild fibrosis (n = 23) or cirrhosis (n = 16), were enrolled from two university hospitals in Denmark. Duration of HCV infection was estimated based on patient information and/or anti-HCV seroconversion. Serial dilutions of purified serum/plasma derived IgGs were tested for their ability to neutralize six HCV-genotype 1 cell-culture strains. The results were expressed as the lowest IgG concentration yielding ≥50% neutralization (NAb50 -titer). A significant difference in HCV NAb50 -titers among the six genotype 1a/1b recombinants was found. In patients with cirrhosis, a tendency for higher level of NAbs was observed compared to patients with no/mild fibrosis, although not statistical significant. Stratifying the two groups revealed that being infected >25 years resulted in higher levels of NAbs in both. Furthermore, by correlating estimated duration of HCV infection to NAb50 -titers a significant result was found against two recombinants. The NAb titer does not differ significantly between HCV patients with either no/mild fibrosis or cirrhosis but show a tendency for increasing level with increased duration of infection. NAbs might contribute as a biological marker to increase the accuracy of patient based information on duration of HCV infection. J. Med. Virol. 88:1791-1803, 2016. © 2016 Wiley Periodicals, Inc.

  8. Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

    OpenAIRE

    Lam, Elegance Ting Pui; Lam, Cindy Lo Kuen; Lai, Ching Lung; Yuen, Man Fung; Fong, Daniel Yee Tak

    2009-01-01

    Aim: To test the psychometric properties of a Chinese [(Hong Kong) HK] translation of the chronic liver disease questionnaire (CLDQ). Methods: A Chinese (HK) translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B (CHB) patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese (HK) SF-36 Health Survey Version 2 (SF-36v2). Results: Sc...

  9. Helicobacter pylori infection may increase the risk of progression of chronic hepatitis B disease among the Chinese population: a meta-analysis

    OpenAIRE

    Juan Wang; Ruo-Chan Chen; Yi-Xiang Zheng; Shu-Shan Zhao; Ning Li; Rong-Rong Zhou; Yan Huang; Ze-Bing Huang; Xue-Gong Fan

    2016-01-01

    Objectives: Helicobacter pylori is a bacterium that infects over 50% of the human population worldwide. An increasing number of studies have demonstrated that H. pylori may cause liver diseases, and the underlying relationship between H. pylori infection and chronic hepatitis B has attracted much attention. This study aimed to examine the association between H. pylori infection and the progression of chronic hepatitis B in the Chinese population. Methods: A search was performed of the PubM...

  10. TT virus and hepatitis G virus infections in Korean blood donors and patients with chronic liver disease

    Institute of Scientific and Technical Information of China (English)

    Mee Juhng Jeon; Jong Hee Shin; Soon Pal Suh; Yong Chai Lim; Dong Wook Ryang

    2003-01-01

    AIM: To determine the prevalences of TTV and HGV infections among blood donors and patients with chronic liver disease in Korea, to investigate the association of TTV and HGV infections with blood transfusion, and to assess the correlation between TTV and HGV viremia and hepatic damage.METHODS: A total of 391 serum samples were examined in this study. Samples were obtained from healthy blood donors (n= 110), hepatitis B surface antigen (HBsAg)-positive donors (n=112), anti-hepatitis C virus (anti-HCV)-positive donors (n=69), patients with type B chronic liver disease (n=81), and patients with type C chronic liver disease (n= 19).TTV DNA was detected using the hemi-nested PCR. HGV RNA was tested using RT-PCR. A history of blood transfusion and serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were also determined.RESULTS: TTV DNA was detected in 8.2 % of healthy blood donors, 16.1% of HBsAg-positive donors, 20.3 % of antiHCV-positive donors, 21.0 % of patients with type B chronic liver disease, and 21.1% of patients with type C chronic liver disease. HGV RNA was detected in 1.8 % of healthy blood donors, 1.8 % of HBsAg-positive donors, 17.4 % of anti-HCV-positive donors, 13.6% of patients with type B chronic liver disease, and 10.5% of patients with type C chronic liver disease. The prevalence of TTV and HGV infections in HBV- or HCV-positive donors and patients was significantly higher than in healthy blood donors (P<0.05),except for the detection rate of HGV in HBsAg-positive donors which was the same as for healthy donors. There was a history of transfusion in 66.7% of TTV DNA-positive patients and 76.9% of HGV RNA-positive patients (P<0.05). No significant increase in serum ALT and AST was detected in the TTV- or HGV-positive donors and patients.CONCLUSION: TTV and HGV infections are more frequently found in donors and patients infected with HBV or HCV than in healthy blood donors. However, there is no significant

  11. Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients

    Institute of Scientific and Technical Information of China (English)

    Xu-Dong Liu; Jian-Lin Wu; Jian Liang; Tao Zhang,; Qing-Shou Sheng

    2012-01-01

    AIM:To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.METHODS:We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals.Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis.A new fibrosis index [globulin/platelet (GP) model] was developed,including globulin (GLOB) and platelet count (PLT).GP model =GLOB (g/mL) x 100/PLT (x 109/L).We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.RESULTS:Thirteen clinical biochemical and hematological variables [sex,age,PLT,alanine aminotransferase,aspartate aminotransferase (AST),albumin,GLOB,total bilirubin (T.bil),direct bilirubin (D.bil),glutamyl transferase,alkaline phosphatase,HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1,F2-F3 and F4).Bivariate Spearman's rank correlation analysis showed that six variables,including age,PLT,T.bil,D.bil,GLOB and PT,were correlated with the three fibrosis stages (FS).Correlation coefficients were 0.23,-0.412,0.208,0.220,0.314 and 0.212; and P value was 0.014,< 0.001,0.026,0.018,0.001 and 0.024,respectively.Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT:F =11.772,P <0.001; GLOB:F =6.612,P =0.002).Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R2 =0.237).By Spearman's rank correlation analysis,GP model was significantly correlated with the three FS (r =0.466,P < 0.001).The median values in F0-F1,F2-F3 and F4 were 1.461,1.720 and 2.634.Compared with the six available models (fibrosis index,AST-platelet ratio,FIB-4,fibrosis-cirrhosis index and age-AST model and age-PLT ratio),GP model showed a highest correlation

  12. Increased urothelial cell apoptosis and chronic inflammation are associated with recurrent urinary tract infection in women.

    Directory of Open Access Journals (Sweden)

    Fei-Chi Chuang

    Full Text Available OBJECTIVE: This study was designed to investigate whether increased urothelial cell apoptosis and chronic inflammation might contribute to recurrent urinary tract infection (UTI in women. METHODS: The bladder biopsy specimens were collected from thirty women with recurrent UTI and ten controls. The bladder biopsies were performed at one to two months after UTI episode had been completely resolved and urine analysis and urine culture all showed negative. Immunofluorescence staining of the adhesive protein E-cadherin, mast cell and TUNEL were performed in all the bladder specimens. In addition, western blots were also performed to analyze the inflammatory proteins (phospho-p38, tryptase and apoptotic protein (Bax in the bladder mucosa specimens between patients with recurrent UTI and controls. RESULTS: Immunofluorescence staining showed significantly lower E-cadherin in the recurrent UTI bladder tissue compared with the controls (25.4±8.9 v 42.4±16.7, p<0.0001. The mast cell expression was significantly stronger in the recurrent UTI bladder tissue compared with the controls (2.5±1.8 v 1.3±1.2, p = 0.046. TUNEL staining revealed a significantly higher numbers of apoptotic cells in the recurrent UTI bladder tissue compared with the control bladder tissue (1.5±1.8 v 0.08±0.3, p<0.0001. Western blot analysis also showed that the expressions of tryptase and Bax increased in five recurrent UTI specimens compared with two normal control specimens. CONCLUSION: Chronic inflammation, urothelial cell apoptosis and impairment of barrier function of urothelial cells might contribute to recurrent UTI in women.

  13. Autoimmunity and extrahepatic manifestations in treatment-naïve children with chronic hepatitis C virus infection.

    Science.gov (United States)

    Indolfi, Giuseppe; Bartolini, Elisa; Olivito, Biagio; Azzari, Chiara; Resti, Massimo

    2012-01-01

    Hepatitis C virus (HCV) infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring.

  14. Autoimmunity and Extrahepatic Manifestations in Treatment-Naïve Children with Chronic Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Giuseppe Indolfi

    2012-01-01

    Full Text Available Hepatitis C virus (HCV infection has been associated with autoimmunity and extrahepatic manifestations in adults. Few data are available on these topics in children. Nonorgan specific auto-antibodies development is part of the natural course of chronic hepatitis C in children. Smooth muscle autoantibody is the most common autoantibody found, while liver-kidney microsomal type-1 antibody positivity is the most peculiar autoimmune feature of children with HCV infection. The clinical significance of non-organ specific autoantibodies in the course of paediatric chronic hepatitis C is still debated. Autoantibody positivity can be considered neutral for most patients, while it can be associated with negative connotations for others, especially those positive for liver-kidney microsomal type-1 autoantibody. Subclinical hypothyroidism but not autoimmune thyroiditis has been demonstrated in HCV infection in children, while only few cases of HCV-associated membranoproliferative glomerulonephritis have been described. Single reports are available in the literature reporting the anecdotal association between chronic hepatitis C and other extrahepatic manifestations such as myopathy and opsoclonus-myoclonus syndrome. Despite the low incidence of extrahepatic manifestations of chronic hepatitis C in children, overall, available data suggest a careful monitoring.

  15. Chronic asymptomatic pyuria precedes overt urinary tract infection and deterioration of renal function in autosomal dominant polycystic kidney disease

    Directory of Open Access Journals (Sweden)

    Hwang Jin Ho

    2013-01-01

    Full Text Available Abstract Background Urinary tract infection (UTI occurs in 30%-50% of individuals with autosomal dominant polycystic kidney disease (ADPKD. However, the clinical relevance of asymptomatic pyuria in ADPKD patients remains unknown. Methods We retrospectively reviewed medical records of 256 ADPKD patients who registered to the ADPKD clinic at Seoul National University Hospital from Aug 1999 to Aug 2010. We defined the asymptomatic pyuria as more than 5-9 white blood cells in high-power field with no related symptoms or signs of overt UTI. Patients were categorized into 2 groups depending on its duration and frequency: Group A included non-pyuria and transient pyuria patients; Group B included recurrent and persistent pyuria patients. The association between asymptomatic pyuria and both the development of overt UTI and the deterioration of renal function were examined. Results With a mean follow-up duration of 65.3 months, 176 (68.8% out of 256 patients experienced 681 episodes of asymptomatic pyuria and 50 episodes of UTI. The annual incidence of asymptomatic pyuria was 0.492 episodes/patient/year. The patients in group B showed female predominance (58.5% vs. 42.0%, P=0.01 and experienced an upper UTI more frequently (hazard ratio: 4.612, 95% confidence interval: 1.735-12.258; P=0.002, adjusted for gender and hypertension. The annual change in estimated glomerular filtration rate (ΔeGFR was significantly larger in magnitude in group B than in group A (-2.7��4.56 vs. -1.17±5.8, respectively; P=0.01. Age and Group B found to be the independent variables for ΔeGFR and developing end-stage renal disease (16.0% vs. 4.3%, respectively; P=0.001. Conclusions Chronic asymptomatic pyuria may increase the risk of developing overt UTI and may contribute to declining renal function in ADPKD.

  16. Assessment of immunological changes in Epstein-Barr virus co-infection in Egyptian chronic HCV patients

    Directory of Open Access Journals (Sweden)

    Sahar Shoman

    2014-09-01

    Full Text Available Epstein-Barr virus (EBV plays a major role in liver pathology. Similar to other members of the herpesvirus family, EBV establishes a persistent infection in more than 90% of adults. The aim of this study was to evaluate the impact of EBV and chronic hepatitis C co-infection (HCV on biochemical and immunological responses in patients. The study was conducted in 62 patients and 33 apparently healthy controls. Patients were divided into three groups: group I, consisting of 31 patients with chronic hepatitis C infection (CHC, group II, consisting of eight patients with EBV infection and without HCV infection and group III, consisting of 23 patients with EBV and chronic HCV. The percentage of CD3+ cells, helper CD4+ cells and CD19+ B-cells was measured by flow cytometry. Human interferon-γ (IFN-γ and interleukin (IL-15 levels were measured by an ELISA. The levels of liver alanine aminotransferase and aspartate aminotransferase enzymes were higher in EBV/HCV patients compared to that in EBV and HCV mono-infected patients. EBV/HCV patients had significantly reduced percentages of CD3+ and CD4+ cells compared to EBV patients. Serum IFN-γ levels were significantly reduced in EBV/HCV patients (3.86 pg/mL compared to CHC patients (6.76 pg/mL and normal controls (4.69 pg/mL. A significant increase in serum IL-15 levels was observed in EBV/HCV patients (67.7 pg/mL compared to EBV patients (29.3 pg/mL. Taken together, these observations suggest that HCV and EBV co-infection can potentiate immune response dampening in patients.

  17. Update on current management of chronic kidney disease in patients with HIV infection

    Directory of Open Access Journals (Sweden)

    Diana NE

    2016-09-01

    disease by screening of HIV-positive individuals for the presence of kidney disease is critical for the optimal management of these patients. Screening for the presence of kidney disease upon detection of HIV infection and annually thereafter in high-risk populations is recommended. Keywords: chronic kidney disease, HIV infection, current management

  18. Noninvasive assessment of hepatic fibrosis in Egyptian patients with chronic hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Shawky Abdelhamid Fouad; Serag Esmat; Dalia Omran; Laila Rashid; Mohamed H Kobaisi

    2012-01-01

    AIM:To evaluate the accuracy of specific biochemical markers for the assessment of hepatic fibrosis in patients with chronic hepatitis C virus (HCV) infection.METHODS:One hundred and fifty-four patients with chronic HCV infection were included in this study; 124patients were non-cirrhotic,and 30 were cirrhotic.The following measurements were obtained in all patients:serum alanine aminotransferase (ALT),aspartate aminotransferase (AST),albumin,total bilirubin,prothrombin time and concentration,complete blood count,hepatitis B surface antigen (HBsAg),HCVAb,HCV-RNA by quantitative polymerase chain reaction,abdominal ultrasound and ultrasonic-guided liver biopsy.The following ratios,scores and indices were calculated and compared with the results of the histopathological examination:AST/ALT ratio (AAR),age platelet index (API),AST to platelet ratio index (APRI),cirrhosis discriminating score (CDS),Pohl score,G(o)teborg University Cirrhosis Index (GUCI).RESULTS:AAR,APRI,API and GUCI demonstrated good diagnostic accuracy of liver cirrhosis (80.5%,79.2%,76.6% and 80.5%,respectively); P values were:< 0.01,< 0.05,< 0.001 and < 0.001,respectively.Among the studied parameters,AAR and GUCI gave the highest diagnostic accuracy (80.5%) with cutoff values of 1.2 and 1.5,respectively.APRI,API and GUCI were significantly correlated with the stage of fibrosis (P < 0.001) and the grade of activity (P <0.001,< 0.001 and < 0.005,respectively),while CDS only correlated significantly with the stage of fibrosis (P < 0.001) and not with the degree of activity (P >0.05).In addition,we found significant correlations for the AAR,APRI,API,GUCI and Pohl score between the non-cirrhotic (F0,F1,F2,F3) and cirrhotic (F4) groups (P values:< 0.001,< 0.05,< 0.001,< 0.001 and <0.005,respectively; CDS did not demonstrate significant correlation (P > 0.05).CONCLUSION:The use of AAR,APRI,API,GUCI and Pohl score measurements may decrease the need for liver biopsies

  19. Smarter vaccine design will circumvent regulatory T cell-mediated evasion in chronic HIV and HCV infection

    Directory of Open Access Journals (Sweden)

    Anne Searls De Groot

    2014-10-01

    Full Text Available Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic infection is suppression of viral-specific effector CD4+ and CD8+ T cells by stimulating regulatory T cells (Tregs educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a TCR-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses that cause acute infection. Furthermore, an HCV epitope that activates Tregs in chronically infected patients, but not clearers, shares a TCR-face with numerous human sequences. To boost weak CD4+ T cell responses associated with persistent infection, vaccines for HIV and HCV must circumvent potential Treg activation that can handicap efficacy. Epitope-driven approaches to vaccine design that involve careful consideration of the T cell subsets primed during immunization will advance HIV and HCV vaccine development.

  20. Chronic lung infection by Pseudomonas aeruginosa biofilm is cured by L-Methionine in combination with antibiotic therapy.

    Science.gov (United States)

    Gnanadhas, Divya Prakash; Elango, Monalisha; Datey, Akshay; Chakravortty, Dipshikha

    2015-11-02

    Bacterial biofilms are associated with 80-90% of infections. Within the biofilm, bacteria are refractile to antibiotics, requiring concentrations >1,000 times the minimum inhibitory concentration. Proteins, carbohydrates and DNA are the major components of biofilm matrix. Pseudomonas aeruginosa (PA) biofilms, which are majorly associated with chronic lung infection, contain extracellular DNA (eDNA) as a major component. Herein, we report for the first time that L-Methionine (L-Met) at 0.5 μM inhibits Pseudomonas aeruginosa (PA) biofilm formation and disassembles established PA biofilm by inducing DNase expression. Four DNase genes (sbcB, endA, eddB and recJ) were highly up-regulated upon L-Met treatment along with increased DNase activity in the culture supernatant. Since eDNA plays a major role in establishing and maintaining the PA biofilm, DNase activity is effective in disrupting the biofilm. Upon treatment with L-Met, the otherwise recalcitrant PA biofilm now shows susceptibility to ciprofloxacin. This was reflected in vivo, in the murine chronic PA lung infection model. Mice treated with L-Met responded better to antibiotic treatment, leading to enhanced survival as compared to mice treated with ciprofloxacin alone. These results clearly demonstrate that L-Met can be used along with antibiotic as an effective therapeutic against chronic PA biofilm infection.

  1. Efficacy of 1% acetic acid in the treatment of chronic wounds infected with Pseudomonas aeruginosa: prospective randomised controlled clinical trial.

    Science.gov (United States)

    Madhusudhan, V L

    2016-12-01

    Chronic wounds are those wounds that are persistent and do not respond to any sort of treatment. The concept of using topical antiseptics on open wounds is to prevent and treat infections. They also help to shorten the time taken to heal the wounds. The use of topical agents on wounds to prevent infection is a minimal ability to develop resistance to the microorganisms. Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen with innate resistance to many antibiotics. In places that are economically backward, these problems get compounded by the inability of patients to afford newer expensive drugs. Topically applied dilute acetic acid, which is cheap and easily available, has been found to be effective in such chronic wounds. In the present study, an attempt has been made to use 1% acetic acid as the sole antimicrobial agent for the treatment of pseudomonal wound infections. A control limb was used in which the wounds were treated with normal saline. Our objective was to evaluate the efficacy of acetic acid in low concentration of 1% in chronic wounds infected with P. aeruginosa. This was a prospective study conducted over a period of 6 months.

  2. Enalapril in Combination with Benznidazole Reduces Cardiac Inflammation and Creatine Kinases in Mice Chronically Infected with Trypanosoma cruzi

    Science.gov (United States)

    Penitente, Arlete Rita; Leite, Ana Luísa Junqueira; de Paula Costa, Guilherme; Shrestha, Deena; Horta, Aline Luciano; Natali, Antônio J.; Neves, Clóvis A.; Talvani, Andre

    2015-01-01

    The protozoan Trypanosoma cruzi triggers an inflammatory process in mammalian heart causing events such as fibrosis, changes in the architecture and functionality in this organ. Enalapril, an angiotensin II-converting enzyme inhibitor, is a drug prescribed to ameliorate this heart dysfunction, and appears to exert a potential role in immune system regulation. Our aim was to evaluate the chronic cardiac inflammatory parameters after therapeutic treatment with enalapril and benznidazole in C57BL/6 mice infected with the VL-10 strain of T. cruzi. After infection, animals were treated with oral doses of enalapril (25 mg/kg), benznidazole (100 mg/kg), or both during 30 days. Morphometric parameters and levels of chemokines (CCL2, CCL5), IL-10, creatine kinases (CKs), and C-reactive protein were evaluated in the heart and serum at the 120th day of infection. Enalapril alone or in combination with benznidazole did not change the number of circulating parasites, but reduced cardiac leukocyte recruitment and total collagen in the cardiac tissue. Interestingly, the combination therapy (enalapril/benznidazole) also reduced the levels of chemokines, CK and CK-MB, and C-reactive proteins in chronic phase. In conclusion, during the chronic experimental T. cruzi infection, the combination therapy using enalapril plus benznidazole potentiated their immunomodulatory effects, resulting in a low production of biomarkers of cardiac lesions. PMID:26350447

  3. Effect of interferon therapy on radionuclide imaging in chronic liver diseases due to HCV infection

    Energy Technology Data Exchange (ETDEWEB)

    Ghaffar, Y.; Dorgham, L.; Lotfy, N. [Ain Shams Univ., Imbaba, Giza (Egypt)]|[Menofia Unif., Shebin El Kom (Egypt)] [and others

    1995-09-01

    Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not received alpha-IFN. A {sup 99m}Tc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of the patients, compared to 8% in 20% of controls (p<0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p<0.001). Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon. 13 refs., 2 tabs.

  4. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Science.gov (United States)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-11-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  5. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Energy Technology Data Exchange (ETDEWEB)

    Jain-Gupta, Neeta [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Pothayee, Nipon; Pothayee, Nikorn [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Tyler, Ronald; Caudell, David L. [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Sriranganathan, Nammalwar, E-mail: nathans@vt.edu [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States)

    2013-11-15

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log{sub 10}), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log{sub 10}). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  6. Transmission of chronic wasting disease identifies a prion strain causing cachexia and heart infection in hamsters.

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    Richard A Bessen

    Full Text Available Chronic wasting disease (CWD is an emerging prion disease of free-ranging and captive cervids in North America. In this study we established a rodent model for CWD in Syrian golden hamsters that resemble key features of the disease in cervids including cachexia and infection of cardiac muscle. Following one to three serial passages of CWD from white-tailed deer into transgenic mice expressing the hamster prion protein gene, CWD was subsequently passaged into Syrian golden hamsters. In one passage line there were preclinical changes in locomotor activity and a loss of body mass prior to onset of subtle neurological symptoms around 340 days. The clinical symptoms included a prominent wasting disease, similar to cachexia, with a prolonged duration. Other features of CWD in hamsters that were similar to cervid CWD included the brain distribution of the disease-specific isoform of the prion protein, PrP(Sc, prion infection of the central and peripheral neuroendocrine system, and PrP(Sc deposition in cardiac muscle. There was also prominent PrP(Sc deposition in the nasal mucosa on the edge of the olfactory sensory epithelium with the lumen of the nasal airway that could have implications for CWD shedding into nasal secretions and disease transmission. Since the mechanism of wasting disease in prion diseases is unknown this hamster CWD model could provide a means to investigate the physiological basis of cachexia, which we propose is due to a prion-induced endocrinopathy. This prion disease phenotype has not been described in hamsters and we designate it as the 'wasting' or WST strain of hamster CWD.

  7. A comparative study of clinicopathological features between chronic cholecystitis patients with and without Helicobacter pylori infe