Wong, Ambrose H.W.; Williams, Katie; Reddy, Sharon; Wilson, Douglas; Giddy, Janet; Alter, Galit; Ghebremichael, Musie; Carrington, Mary N; Ndung'u, Thumbi; Walker, Bruce D.; Altfeld, Marcus; Carr, William H.
Recent studies suggest that innate immune responses by natural killer (NK) cells play a significant role in restricting human immunodeficiency virus type-1 (HIV-1) pathogenesis. Our aim was to characterize changes in NK cells associated with HIV-1 clade C disease progression. Here we used multiparametric flow cytometry (LSRII) to quantify phenotype and function of NK cells in a cross-sectional analysis of cryopreserved blood samples from a cohort of 41 chronically HIV-1-infected, treatment-na...
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
Lange, Jeppe; Troelsen, Anders; Thomsen, Reimar W; Søballe, Kjeld
Two-stage revision is regarded by many as the best treatment of chronic infection in hip arthroplasties. Some international reports, however, have advocated one-stage revision. No systematic review or meta-analysis has ever compared the risk of reinfection following one-stage and two-stage revisi......Two-stage revision is regarded by many as the best treatment of chronic infection in hip arthroplasties. Some international reports, however, have advocated one-stage revision. No systematic review or meta-analysis has ever compared the risk of reinfection following one-stage and two......-stage revisions for chronic infection in hip arthroplasties....
Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice
Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.
Carr, Tara F; Kraft, Monica
Chronic bacterial infection is implicated in both the development and severity of asthma. The atypical bacteria Mycoplasma pneumoniae and Chlamydophila pneumoniae have been identified in the airways of asthmatics and correlated with clinical features such as adult onset, exacerbation risks, steroid sensitivity, and symptom control. Asthmatic patients with evidence of bacterial infection may benefit from antibiotic treatment directed towards these atypical organisms. Examination of the airway microbiome may identify microbial communities that confer risk for or protection from severe asthma. PMID:27401621
Full Text Available Abstract Nasopharyngeal carcinoma (NPC is a complex disease caused by a combination of Epstein-Barr virus chronic infection, the environment and host genes in a multi-step process of carcinogenesis. The identity of genetic factors involved in the development of chronic Epstein-Barr virus infection and NPC remains elusive, however. Here, we describe a two-phase, population-based, case-control study of Han Chinese from Guangxi province, where the NPC incidence rate rises to a high of 25-50 per 100,000 individuals. Phase I, powered to detect single gene associations, enrolled 984 subjects to determine feasibility, to develop infrastructure and logistics and to determine error rates in sample handling. A microsatellite screen of Phase I study participants, genotyped for 319 alleles from 34 microsatellites spanning an 18-megabase region of chromosome 4 (4p15.1-q12, previously implicated by a linkage analysis of familial NPC, found 14 alleles marginally associated with developing NPC or chronic immunoglobulin A production (p = 0.001-0.03. These associations lost significance after applying a correction for multiple tests. Although the present results await confirmation, the Phase II study population has tripled patient enrolment and has included environmental covariates, offering the potential to validate this and other genomic regions that influence the onset of NPC.
Kalager, T; Bøe, E; Digranes, A; Høisaether, P; Solberg, C O
Twenty-eight patients with chronic urinary tract infections were treated with 400 mg pivmecillinam orally three times daily for 10 to 15 days. The diagnosis was confirmed by a history of cystitis or cystopyelitis four to six times annually, microscopy of urine sediment, and growth of pathogens in urine specimens obtained by suprapubic bladder puncture. Three days, three and six weeks after completion of therapy the success rates were 24/28, 20/28 and 19/28 respectively. Pivmecillinam was well tolerated. Two patients developed nausea and vomiting. Other side-effects were not observed. Pivmecillinam is a useful drug in the treatment of chronic urinary tract infections. PMID:204581
Wilson, Eleanor M P; Tang, Lydia; Kottilil, Shyam
Chronic hepatitis B infection affects >300 million people worldwide and is a leading cause of liver failure and cancer. Current approaches to treatment for chronic hepatitis B involve suppression of hepatitis B virus (HBV) DNA with the use of nucleoside analogues. Chronic suppressive therapy rarely results in a "functional cure" or absence of detectable HBV DNA in plasma and loss of detectable hepatitis B surface antigen after cessation of therapy. The major obstacles to achieving a functional cure are the presence of covalently closed circular DNA and ineffective/exhaustive immune system. This review focuses on novel approaches to target viral life cycle and host immunity to achieve a functional cure. PMID:27190322
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; Barnes, Peter J; Adcock, Ian M.; Alberto Papi
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.
Minuk, G Y; Gutkin, A; Wong, S G; Kaita, K D E
Counselling of patients with chronic hepatitis C infections is often limited to discussions regarding how the virus is transmitted and what can be done to decrease the risk of transmission to others. The purpose of the present study was to document the principal concerns of newly diagnosed and follow-up patients with chronic hepatitis C, and thereby enhance counselling strategies and content. Seventy newly diagnosed and 115 follow-up patients with chronic hepatitis C virus (HCV) infection were initially asked in an open-ended manner (volunteered concerns) and then to prioritize from a prepared list of seven potential concerns (prioritized concerns), to identify those concerns that were of utmost importance to them. The most common volunteered concerns of newly diagnosed patients in decreasing order were: disease progression (27%), premature death (19%), infecting family members (13%), side-effects of treatment (11%) and miscellaneous others. In decreasing order, prioritized concerns included: infecting family members, development of liver cancer, infecting others, development of cirrhosis, social stigma of having liver disease, need for liver transplant and loss of employment. The principal volunteered and prioritized concerns of follow-up patients were similar to those of newly diagnosed patients. Volunteered and prioritized concerns were relatively consistent across the different genders, age groups, ethnic backgrounds, education level, marital status, employment, modes of viral acquisition and in the case of follow-up patients, duration of follow-up. These results indicate that health care providers who focus counselling efforts exclusively on viral transmission are unlikely to address other important concerns of newly diagnosed and follow-up patients with chronic HCV infection. PMID:15655048
Dickneite, G; Schorlemmer, H U; Sedlacek, H H
Models of chronic infections have been established to test the therapeutic and prophylactic potency of biological response modifiers (BRM). As an example for a BRM the immunostimulating drug Bestatin was tested. It is of dipeptide nature and was purified from culture supernatants of Streptomyces olivoreticuli. In two chronic bacterial infection models, induced by the inoculation of NRMI mice with Salmonella typhimurium or with a nephropathogenic strain of Escherichia coli, Bestatin acted prophylactically as well as therapeutically. This could be seen from the reduction of bacterial organ colonization and the inhibition of organ lesion formation. Bestatin could be shown to stimulate macrophage activity and to potentiate delayed type hypersensitivity, but not be effective on the humoral immune response. PMID:6383323
Ahmed, Waqas; Zheng, Ke; Liu, Zheng-Fei
Brucella is a facultative intracellular pathogen that causes zoonotic infection known as brucellosis which results in abortion and infertility in natural host. Humans, especially in low income countries, can acquire infection by direct contact with infected animal or by consumption of animal products and show high morbidity, severe economic losses and public health problems. However for survival, host cells develop complex immune mechanisms to defeat and battle against attacking pathogens and maintain a balance between host resistance and Brucella virulence. On the other hand as a successful intracellular pathogen, Brucella has evolved multiple strategies to evade immune response mechanisms to establish persistent infection and replication within host. In this review, we mainly summarize the "Stealth" strategies employed by Brucella to modulate innate and the adaptive immune systems, autophagy, apoptosis and possible role of small noncoding RNA in the establishment of chronic infection. The purpose of this review is to give an overview for recent understanding how this pathogen evades immune response mechanisms of host, which will facilitate to understanding the pathogenesis of brucellosis and the development of novel, more effective therapeutic approaches to treat brucellosis. PMID:27014640
Nicola Gillian Davis
Full Text Available Chronic wounds heal poorly and can have a huge impact on a sufferer’s life. They are caused by a number of factors, one of which is the presence of persistent infections. Many standard treatments are unsuccessful at destroying these infections as the bacteria form a biofilm. Biofilms encase the bacteria, preventing immune cells from destroying them. There are multiple bacterial species within a biofilm, sometimes with antibiotics resistance, and which species are present changes over time. The changing, multi-species nature of biofilms can make finding an effective antibiotic treatment difficult. Also, bacteria in biofilms genetically differ from planktonic bacteria, and are often less susceptible to antibiotics. Additionally, biofilms are thought to reduce the access of antibiotics to the bacteria within. These reasons are discussed in further detail in this review, along with some of the reasons why bacteria can prevent wound closure.
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...... 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...
Kang, Minah; Kim, Jaiyong; Bae, Sang-Soo; Choi, Yong-Jun; Shin, Dong-Soo
Objectives: Despite the recent emphasis on a patient-centered chronic care model, few studies have investigated its use in older adults in South Korea. We explored how older Korean adults perceive and cope with their chronic illness. Methods: We conducted focus group interviews in Seoul, Korea in January 2010. Focus groups were formed by disease type (hypertension and type 2 diabetes) and gender using purposive sampling. Inclusion criteria were patients aged 60 and over who had been diagnosed...
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
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. PMID:26886412
Shahindokht Bassiri-Jahromi; Aida Doostkam
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 no...
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.
Liu, J; Lin, Haili; McIntosh, H
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, ...
Ciofu, Oana; Mandsberg, Lotte F; Wang, Hengzhuang;
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...... importance of biofilm prevention strategies by early aggressive antibiotic prophylaxis or therapy before phenotypic diversification during chronic lung infection of patients with cystic fibrosis....
Nishiura, Hiroshi; Kinoshita, Ryo; Mizumoto, Kenji; Yasuda, Yohei; Nah, Kyeongah
Objectives: Zika virus has spread internationally through countries in the South Pacific and Americas. The present study aimed to estimate the basic reproduction number, R0, of Zika virus infection as a measurement of the transmission potential, reanalyzing past epidemic data from the South Pacific. Methods: Incidence data from two epidemics, one on Yap Island, Federal State of Micronesia in 2007 and the other in French Polynesia in 2013-2014, were reanalyzed. R0 of Zika virus infection was e...
Hiroshi Nishiura; Ryo Kinoshita; Kenji Mizumoto; Yohei Yasuda; Kyeongah Nah
Objectives: Zika virus has spread internationally through countries in the South Pacific and Americas. The present study aimed to estimate the basic reproduction number, R0, of Zika virus infection as a measurement of the transmission potential, reanalyzing past epidemic data from the South Pacific. Methods: Incidence data from two epidemics, one on Yap Island, Federal State of Micronesia in 2007 and the other in French Polynesia in 2013–2014, were reanalyzed. R0 of Zika virus infection wa...
Brok, Jesper; Gluud, Lise L; Gluud, Christian
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....
Henriet, S.S.V.; Verweij, P.E.; Holland, S.M.; Warris, A.
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
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.
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
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 inf...
Johansen, H K; Espersen, F; Pedersen, S S;
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 changes...
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 of...
Mogensen Trine H
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
Pretorius, Anne-Marié; Birtles, Richard J.
We report the first laboratory-confirmed case of Rickettsia mongolotimonae infection in Africa. The patient sought treatment for an eschar on his toe; lymphangitis, severe headaches, and fever subsequently developed. After a regimen of doxycycline, symptoms rapidly resolved. R. mongolotimonae infection was diagnosed retrospectively by serologic tests and molecular-based detection of the organism in biopsy specimens of eschar material.
Prescott, E; Lange, P; Vestbo, J
The association of chronic mucus hypersecretion and mortality is a matter of debate. We wished to determine whether the relationship between chronic mucus hypersecretion and chronic obstructive pulmonary disease (COPD)-related mortality could be explained by proneness to pulmonary infection. We...... followed 14,223 subjects of both sexes for 10-12 yrs. Cases where COPD was an underlying or contributory cause of death (n = 214) were included, and hospital records were obtained when possible (n = 101). From the presence of increased mucus, purulent mucus, fever, leucocytosis and infiltration on chest...... without chronic mucus hypersecretion. Controlling for covariates, in particular smoking habits, a Cox analysis showed a strong inverse relationship between ventilatory function and COPD-related mortality. Chronic mucus hypersecretion was found to be a significant predictor of COPD-related death with...
Greenberg, David E.; Shoffner, Adam R.; Zelazny, Adrian M.; Fenster, Michael E.; Zarember, Kol A.; Stock, Frida; Ding, Li; Marshall-Batty, Kimberly R.; Wasserman, Richard L.; Welch, David F.; Kanakabandi, Kishore; Sturdevant, Dan E.; Virtaneva, Kimmo; Porcella, Stephen F.; Murray, Patrick R.
Chronic granulomatous disease (CGD) is characterized by frequent infections, most of which are curable. Granulibacter bethesdensis is an emerging pathogen in patients with CGD that causes fever and necrotizing lymphadenitis. However, unlike typical CGD organisms, this organism can cause relapse after clinical quiescence. To better define whether infections were newly acquired or recrudesced, we use comparative bacterial genomic hybridization to characterize 11 isolates obtained from 5 patient...
Swords, W. Edward
Like many pathogens inhabiting mucosal surfaces, nontypeable Haemophilus influenzae (NTHi) forms multicellular biofilm communities both in vitro and in various infection models. In the past 15 years much has been learned about determinants of biofilm formation by this organism and potential roles in bacterial virulence, especially in the context of chronic and recurrent infections. However, this concept has not been without some degree of controversy, and in the past some have expressed doubt...
Following a coronary bypass surgery, a vein donor site became infected and failed to heal despite use of antibiotics and a variety of topical treatments. Octenilin Wound Gel not only helped to promote healing, but also increased the patient's ability to tolerate dressing changes. PMID:26949845
J.N. Stoop (Jeroen Nicolaas)
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
Khorramdelazad, Hossein; Hassanshahi, Gholamhossein; Nasiri Ahmadabadi, Behzad; Kazemi Arababadi, Mohammad
Background The transforming growth factor-β (TGF-β) is an important cytokine with anti-inflammatory properties. Objectives The main purpose of this study was to compare the serum levels of TGF-β in a group of chronic HBV infected (CHB) patients as well as healthy individuals from South-East of Iran. Patients and Methods Sixty patients with CHB as well as sixty healthy individuals were enrolled in the study. ELISA technique was applied to measure the serum levels of TGF-β in both groups. Resul...
Do, Danh Cong
Biofilm is the virulence factor that is responsible for chronic infection in diseases such as Cystic Fibrosis (CF) and chronic wounds. In this thesis, we examine the role of AlgX, a required protein for alginate biosynthesis in P. aeruginosa. We show that the absence of AlgX resulted in the loss of mucoidy and in silico studies demonstrated that AlgX binds alginate. Alanine mutations demonstrated that K396, T398, W400, and R406 are important for alginate binding. Alginate rescue assays confir...
Maldonado, Rita F; Sá-Correia, Isabel; Valvano, Miguel A
The Gram-negative bacterial lipopolysaccharide (LPS) is a major component of the outer membrane that plays a key role in host-pathogen interactions with the innate immune system. During infection, bacteria are exposed to a host environment that is typically dominated by inflammatory cells and soluble factors, including antibiotics, which provide cues about regulation of gene expression. Bacterial adaptive changes including modulation of LPS synthesis and structure are a conserved theme in infections, irrespective of the type or bacteria or the site of infection. In general, these changes result in immune system evasion, persisting inflammation and increased antimicrobial resistance. Here, we review the modifications of LPS structure and biosynthetic pathways that occur upon adaptation of model opportunistic pathogens (Pseudomonas aeruginosa, Burkholderia cepacia complex bacteria, Helicobacter pylori and Salmonella enterica) to chronic infection in respiratory and gastrointestinal sites. We also discuss the molecular mechanisms of these variations and their role in the host-pathogen interaction. PMID:27075488
Witte, M.; McNeill, G.; Crandall, C.; Case, T.; Witte, C.; Crandall, R.; Hall, J.; Williams, W.
Whole body lymphangioscintigraphy was performed after intradermal injection of /sup 99m/technetium human serum albumin or antimony colloid in the distal hindlimbs and forelimbs of ferrets chronically infected with Brugia malayi. The findings were compared with control ferrets and those with surgical interruption of the iliac lymphatics. While only one infected ferret manifested chronic hindlimb lymphedema, all exhibited delayed transport of radioisotope from the hindpaw with obstruction in the groin, poor or absent visualization of central lymphatic channels and regional lymph nodes, a picture similar to that following surgically induced lymphatic obstruction. In control ferrets, there was prompt visualization of peripheral lymphatic channels and regional lymph nodes with sharper and more extensive channel visualization after radiolabeled albumin and more intense sustained nodal visualization after radiolabeled antimony colloid. This noninvasive technique provides a readily repeatable investigative tool adaptable to small animals to study the evolution of lymphatic filariasis and other conditions associated with lymphatic obstruction.
Immunodeficient patients whose gut is chronically infected by vaccine-derived poliovirus (VDPV) may excrete large amounts of virus for years. To investigate how poliovirus (PV) establishes chronic infections in the gut, we tested whether it is possible to establish persistent VDPV infections in human intestinal Caco-2 cells. Four type 3 VDPV mutants, representative of the viral evolution in the gut of a hypogammaglobulinemic patient over almost 2 years [J. Virol. 74 (2000) 3001], were used to infect both undifferentiated, dividing cells, and differentiated, polarized enterocytes. A VDPV mutant excreted 36 days postvaccination by the patient was lytic in both types of intestinal cell cultures, like the parental Sabin 3 (S3) strain. In contrast, three VDPVs excreted 136, 442, and 637 days postvaccination, established persistent infections both in undifferentiated cells and in enterocytes. Thus, viral determinants selected between day 36 and 136 conferred on VDPV mutants the capacity to infect intestinal cells persistently. The percentage of persistently VDPV-infected cultures was higher in enterocytes than in undifferentiated cells, implicating cellular determinants involved in the differentiation of enterocytes in persistent VDPV infections. The establishment of persistent infections in enterocytes was not due to poor replication of VDPVs in these cells, but was associated with reduced viral adsorption to the cell surface
Garg, Ashish; Reddy, Chandrasekhar; Duseja, Ajay; Chawla, Yogesh; Radha K. Dhiman
Celiac disease affects the proximal small intestine and is caused by a local immune response to dietary gluten. Celiac disease usually presents with chronic diarrhea; however, presentations with elevated hepatic transaminase levels in blood or with iron-deficiency anemia have been described. Celiac disease has been reported to be associated with autoimmune liver diseases. Hepatitis C virus (HCV) can also initiate autoimmune disease process. Therefore, HCV infection and celiac disease may occu...
Hendricks, Kristy; Gorbach, Sherwood
Human immunodeficiency virus (HIV) infection and chronic drug abuse both compromise nutritional status. For individuals with both disorders, the combined effects on wasting, the nutritional consequence that is most closely linked to mortality, appear to be synergistic. Substance abuse clinicians can improve and extend patients’ lives by recommending healthy diets; observing and assessing for food insecurity, nutritional deficits, signs of weight loss and wasting, body composition changes, and...
Saddawi-Konefka, Robert; Crawford, John R.
Primary central nervous system (CNS) tumors cause significant morbidity and mortality in both adults and children. While some of the genetic and molecular mechanisms of neuro-oncogenesis are known, much less is known about possible epigenetic contributions to disease pathophysiology. Over the last several decades, chronic viral infections have been associated with a number of human malignancies. In primary CNS malignancies, two families of viruses, namely polyomavirus and herpesvirus, have be...
Michele Barone; Maria Teresa Viggiani; Annabianca Amoruso; Serafina Schiraldi; Annapaola Zito; Fiorella Devito; Francesca Cortese; Michele Gesualdo; Natale Brunetti; Alfredo Di Leo; Pietro Scicchitano; Marco Matteo Ciccone
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...
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.
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
Kamar, Fareed B; Hawkins, T Lee-Ann
While antineutrophil cytoplasmic antibody (ANCA) is often used as a diagnostic marker for certain vasculitides, ANCA induction in the setting of infection is much less common. In the case of infective endocarditis, patients may present with multisystem disturbances resembling an autoimmune process, cases that may be rendered even trickier to diagnose in the face of a positive ANCA. Though not always straightforward, distinguishing an infective from an inflammatory process is pivotal in order to guide appropriate therapy. We describe an encounter with a 43-year-old male with chronically untreated hepatitis C virus infection who featured ANCA positivity while hospitalized with acute bacterial endocarditis. His case serves as a reminder of two of the few infections known to uncommonly generate ANCA positivity. We also summarize previously reported cases of ANCA positivity in the context of endocarditis and hepatitis C infections. PMID:27366166
Cacoub, Patrice; Comarmond, Cloe; Domont, Fanny; Savey, Léa; Desbois, Anne C; Saadoun, David
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 therapeutic trials. More recently, other nonliver-related HCV disorders have been reported, including cardiovascular (i.e. stroke, ischemic heart disease), renal, metabolic and central nervous system diseases. For these manifestations, most evidence comes from large epidemiological studies; there is a need for mechanistic studies and therapeutic trials for confirmation. Beyond the risk of developing liver complications, that is, cirrhosis and liver cancer, patients with HCV infection have an increased risk of morbidity and mortality related to nonliver diseases. HCV chronic infection should be analyzed as a systemic disease in which extrahepatic consequences increase the weight of its pathological burden. The need for effective viral eradication measures is underlined. PMID:26862398
Schär, Fabian; Giardina, Federica; Khieu, Virak; Muth, Sinuon; Vounatsou, Penelope; Marti, Hanspeter; Odermatt, Peter
The soil-transmitted nematode, Strongyloides stercoralis is one of the most-neglected of all neglected tropical diseases. It is globally distributed, favouring the humid, wet climates of the tropics and subtropics. Inadequate sanitary conditions promote the spread of S. stercoralis infection. In South-East Asia, many countries provide the ideal ecological and economic setting for high S. stercoralis infection rates. Yet, in most of these countries, little is known about the actual prevalence and distribution of S. stercoralis. One reason for this lack of knowledge pertains to the time- and resource-intensive diagnostic methods used to detect S. stercoralis infection. The Koga Agar culture method and the Baermann method are considered to be the best coprological diagnostic methods for field settings today. Both detect the parasite with high sensitivity. This sensitivity can be increased further by examining stool samples for several consecutive days, thereby increasing the chances of detecting low-intensity chronic infections. Diagnostic challenges, however, lead to the omission of S. stercoralis in studies of soil-transmitted helminths and few studies focus on S. stercoralis, specifically. These factors lead to an underreporting of the nematode's prevalence, not only in South-East Asia but worldwide. We have reviewed the scientific literature of the last 25 years and estimated country-wide prevalence rates for South-East Asia. We aim to summarise what is known today about the prevalence of S. stercoralis in South-East Asia, as well as to ascertain the risk factors and diagnostic methods most commonly applied. PMID:25795619
Helicobacter pylori infection has been established as a major cause of chronic gastritis in adults, and it has been implicated in the genesis of gastric carcinomas and the development of gastric and duodenal ulcers. It is now postulated that neatly 90% of the adult population in developing countries may be affected with the infection since childhood. Earlier studies on Indians using serology and endoscopic biopsy have shown a high incidence of H. pylori infection in small numbers of patients. The 13C-urea breath test, which is simple, specific and non-invasive, is also increasingly being used to determine the presence of Helicobacter pylori infection. Preliminary data from India has shown a high prevalence in the urban Indian environment, and there is an urgent need to quantify the prevalence of H. pylori infections on an epidemiological basis in both urban and rural settings. It is also important to study the possible impact of this infection on growth in children, particularly in environments with low sanitation and high crowding. In this paper, we outline a proposal to study the prevalence of Helicobacter pylori infections in children from the following different environments: urban middle socio-economic class, urban slum, rural middle socio-economic class and rural village. (author)
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.
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
Deffert, Christine; Cachat, Julien; Krause, Karl-Heinz
Infection of humans with Mycobacterium tuberculosis remains frequent and may still lead to death. After primary infection, the immune system is often able to control M. tuberculosis infection over a prolonged latency period, but a decrease in immune function (from HIV to immunosenescence) leads to active disease. Available vaccines against tuberculosis are restricted to BCG, a live vaccine with an attenuated strain of M. bovis. Immunodeficiency may not only be associated with an increased risk of tuberculosis, but also with local or disseminated BCG infection. Genetic deficiency in the reactive oxygen species (ROS)-producing phagocyte NADPH oxidase NOX2 is called chronic granulomatous disease (CGD). CGD is among the most common primary immune deficiencies. Here we review our knowledge on the importance of NOX2-derived ROS in mycobacterial infection. A literature review suggests that human CGD patient frequently have an increased susceptibility to BCG and to M. tuberculosis. In vitro studies and experiments with CGD mice are incomplete and yielded - at least in part - contradictory results. Thus, although observations in human CGD patients leave little doubt about the role of NOX2 in the control of mycobacteria, further studies will be necessary to unequivocally define and understand the role of ROS. PMID:24916152
Full Text Available Upon infection with the obligate intracellular parasite Toxoplasma gondii, fast replicating tachyzoites infect a broad spectrum of host cells including neurons. Under the pressure of the immune response, tachyzoites convert into slow-replicating bradyzoites, which persist as cysts in neurons. Currently, it is unclear whether T. gondii alters the functional activity of neurons, which may contribute to altered behaviour of T. gondii-infected mice and men. In the present study we demonstrate that upon oral infection with T. gondii cysts, chronically infected BALB/c mice lost over time their natural fear against cat urine which was paralleled by the persistence of the parasite in brain regions affecting behaviour and odor perception. Detailed immunohistochemistry showed that in infected neurons not only parasitic cysts but also the host cell cytoplasm and some axons stained positive for Toxoplasma antigen suggesting that parasitic proteins might directly interfere with neuronal function. In fact, in vitro live cell calcium (Ca(2+ imaging studies revealed that tachyzoites actively manipulated Ca(2+ signalling upon glutamate stimulation leading either to hyper- or hypo-responsive neurons. Experiments with the endoplasmatic reticulum Ca(2+ uptake inhibitor thapsigargin indicate that tachyzoites deplete Ca(2+ stores in the endoplasmatic reticulum. Furthermore in vivo studies revealed that the activity-dependent uptake of the potassium analogue thallium was reduced in cyst harbouring neurons indicating their functional impairment. The percentage of non-functional neurons increased over time In conclusion, both bradyzoites and tachyzoites functionally silence infected neurons, which may significantly contribute to the altered behaviour of the host.
Full Text Available Research Objective: Evaluate the indicators of mineral metabolism in HIV-infected patients, patients with chronic hepatitis С and co-infection HIV/HCV. Material and Methods: The content of microelements (zinc (Zn, copper (Cu, iron (Fe in serum was determined by atomic absorption spectrophotometry. The study involved 99 patients: with chronic hepatitis С — 32 patients, with HIV infection — 34 and co-infection of HIV/HCV — 33 patients. Results: Microelements and metal-dependent proteins metabolic disorders as a reduction of the zinc, haptoglobin contents, and an increase of copper, iron, and ceruloplasmin contents were identified in patients with chronic hepatitis С In HIV-infected patients and patients with co-infection HIV/HCV were identified reducing zinc, copper, iron, haptoglobin, ceruloplasmin. in patients with co-infection HIV/HCV compared HIV-infected patients lower zinc, haptoglobin, ceruloplasmin contents (p<0,001 were detected. In patients with co-infected HIV/HCV, as compared with a group of chronic hepatitis С were set lower values of all parameters (p<0,001. Conclusion: Integrated assessment of the degree of deviation from the control of the trace element content and activity metal-dependent enzymes showed that its highest significance was typical for patients with co-infected HIV/HCV, which is higher than that of HIV-infected patients in the 1,2-fold and 2,2-fold in patients with chronic hepatitis С
Mangali, A; Sasabone, P; Syafruddin; Abadi, K; Hasegawa, H; Toma, T; Kamimura, K; Miyagi, I
Intestinal parasitic infections were surveyed in the inhabitants of 3 coastal and 2 inland villages of Campalagian District, South Sulawesi, Indonesia, in July 1992. A total of 398 fecal samples were examined by using Kato-Katz thick smear, Harada-Mori culture and agar-plate culture techniques. Protozoan cysts were examined by formalin ether concentration technique on 380 fecal samples. Soil-transmitted helminth infections were highly prevalent with the overall positive rates as follows: Ascaris lumbricoides 25.3%, Trichuris trichiura 59.3%, hookworm 68.3% and Strongyloides stercoralis 2.3%. Eight species of protozoan were detected with the overall prevalence as follows: Entamoeba histolytica 10.9%, E. hartmanni 16.3%, E. coli 31.9%, Endolimax nana 12.5%, Iodamoeba buetschlii 5.4%, Giardia lamblia 4.6%, Chilomastix mesnili 0.8% and Blastocystis hominis 18.0%. In the inland villages, prevalence of hookworm infection was higher than Ascaris and Trichuris infections, while in the coastal villages Trichuris infection was predominant. Egg count revealed that the infection level was light in most of the hookworm and Trichuris carriers. Prevalence of lavatories among houses appeared to be inversely proportional to the prevalence of hookworm infection. Meanwhile, the incomplete structure of the lavatories might result in contamination of environment with Ascaris and Trichuris eggs. Harada-Mori culture was the most efficient method in the detection of hookworm infection compared to other techniques. Both Necator americanus and Ancylostoma duodenale were found in all villages, but the former was the predominant species. An adult pinworm was detected by agar-plate culture of feces. Two types of pinworm males, corresponding to Enterobius vermicularis and E. gregorii, were observed. PMID:8266235
Leonardo Rodrigues de Oliveira
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.
Rocio Aller de la Fuente; María L Gutiérrez; Javier Garcia-Samaniego; Conrado Fernández-Rodriguez; Jose Luis Lledó; Gregorio Castellano
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.
Lorig, Kate; Ritter, Philip L.; Plant, Kathryn; Laurent, Diana D.; Kelly, Pauline; Rowe, Sally
Objectives: To evaluate the effectiveness of an online chronic disease self-management program for South Australia residents. Method: Data were collected online at baseline, 6 months, and 12 months. The intervention was an asynchronous 6-week chronic disease self-management program offered online. The authors measured eight health status measures,…
Omland, Lars Haukali; Krarup, Henrik; Jepsen, Peter; Georgsen, Jørgen; Harritshøj, Lene Holm; Riisom, Kirsten; Jacobsen, Svend Erik Hove; Schouenborg, Per; Christensen, Peer Brehm; Sørensen, Henrik Toft; Obel, Niels; Bangsborg, Jette Marie
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.......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....
Turner, Keith H.; Jake Everett; Urvish Trivedi; Rumbaugh, Kendra P.; Marvin Whiteley
Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in ...
Full Text Available Background: Infective endocarditis (IE is an infection of the endocardial surface of the heart. Despite recent advances in diagnosis and treatment, mortality rates remain high. Data on the prevalence, epidemiology and etiology of IE from India are sparse. Aims and Objectives: The aim of this study was to evaluate the clinical, laboratory, microbiological, and echocardiographic characteristics of IE patients in Chennai, south India. Materials and Methods: Patients were classified based on modified Duke criteria. Details of the clinical profile of the patients and laboratory data were recorded. Blood cultures were performed to establish the etiology. Results: Ninety six percent of patients had native valve endocarditis. Mitral valve was the most commonly affected valve. Conclusion: Rheumatic heart disease was the most common predisposing factor and fever was the most common clinical feature. Viridans group streptococci accounted of the culture positive cases.
Cornwell, William D; Wagner, Wendeline; Lewis, Mark G; Fan, Xiaoxuan; Rappaport, Jay; Rogers, Thomas J
We studied the effect of chronic morphine administration on the circulating dendritic cell population dynamics associated with SIV infection using rhesus macaques. Animals were either first infected with SIV and then given chronic morphine, or visa versa. SIV infection increased the numbers of myeloid DCs (mDCs), but morphine treatment attenuated this mDC expansion. In contrast, morphine increased the numbers of plasmacytoid DCs (pDCs) in SIV-infected animals. Finally, chronic morphine administration (no SIV) transiently increased the numbers of circulating pDCs. These results show that chronic morphine induces a significant alteration in the available circulating levels of critical antigen-presenting cells. PMID:27235346
Tarrant, Jeanne; Cilliers, Dirk; du Preez, Louis H.; Weldon, Ché
Chytridiomycosis has been identified as a major cause of global amphibian declines. Despite widespread evidence of Batrachochytrium dendrobatidis infection in South African frogs, sampling for this disease has not focused on threatened species, or whether this pathogen poses a disease risk to these species. This study assessed the occurrence of Bd-infection in South African Red List species. In addition, all known records of infection from South Africa were used to model the ecological niche ...
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
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.
... chronic infection, which places infected persons at risk for liver cirrhosis, liver cancer or...-viral therapies can clear HCV from the system (i.e., a virologic cure) and halt disease progression...
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.
Yoon, Hee Jung; Choi, Hwa Young; Kim, Young Kwon; Song, Yeong Jun; Ki, Moran
OBJECTIVES The symptoms of fungal infections vary from minor to severe. According to recent reports, fungal infection prevalence is increasing due to increases in the aging population and in patients with compromised immune systems. However, the total prevalence of fungal infections in South Korea is unknown. We investigated the recent 5-year prevalence of each type of fungal infection in South Korea across age, sex, and regional groups. METHODS Nationwide data from the National Health Insura...
Mocroft, Amanda; Kirk, Ole; Gatell, Jose;
BACKGROUND: The role of exposure to antiretrovirals in chronic renal failure (CRF) is not well understood. Glomerular filtration rates (GFR) are estimated using the Cockcroft-Gault (CG) or Modification of Diet in Renal Disease (MDRD) equations. METHODS: Baseline was arbitrarily defined as the first...... recorded GFR; patients with two consecutive GFR determine odds ratio (OR) of CRF at baseline. ART exposure (yes/no or cumulative exposure) prior to baseline was included in multivariate models (adjusted for region...... of Europe, age, prior AIDS, CD4 cell count nadir, viral load, hypertension and use of nephrotoxic anti-infective therapy). RESULTS: Using CG, the median GFR at baseline (n = 4474) was 94.4 (interquartile range, 80.5-109.3); 158 patients (3.5%) had CRF. Patients with CRF were older (median, 61.9 versus 43...
Dalbøge, C S; Hansen, C R; Pressler, T;
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...
Veldhuijzen, Irene K.; Toy, Mehlika; Hahne, Susan J. M.; de Wit, G. Ardine; Schalm, Solko W.; de Man, Robert A.; Richardus, Jan Hendrik
BACKGROUND & AIMS: Persons with chronic hepatitis B virus (HBV) infection are at risk of developing cirrhosis and hepatocellular carcinoma. Early detection of chronic HBV infection through screening and treatment of eligible patients has the potential to prevent these sequelae. We assessed the cost-
da Glória Sousa, Maria; Reid, Delyth M.; Schweighoffer, Edina; Tybulewicz, Victor; Ruland, Jürgen; Langhorne, Jean; Yamasaki, Sho; Taylor, Philip R.; Almeida, Sandro R.; Brown, Gordon D.
Summary Chromoblastomycosis is a chronic skin infection caused by the fungus Fonsecaea pedrosoi. Exploring the reasons underlying the chronic nature of F. pedrosoi infection in a murine model of chromoblastomycosis, we find that chronicity develops due to a lack of pattern recognition receptor (PRR) costimulation. F. pedrosoi was recognized primarily by C-type lectin receptors (CLRs), but not by Toll-like receptors (TLRs), which resulted in the defective induction of proinflammatory cytokines...
Rao Sambasiva R
Full Text Available Abstract Background Enterococci tend to be one of the leading causes of nosocomial infections, with E. faecalis and E. faecium accounting up to 90% of the clinical isolates. Nevertheless, the incidence of other species of enterococci from clinical sources shows an alarming increase with the properties of intrinsic resistance to several antibiotics including beta-lactams and glycopeptides. Thus proper identification of enterococci to species level is quintessential for management and prevention of these bacteria in any healthcare facility. Hence this work was undertaken to study the prevalence of unusual species of enterococci causing human infections, in a tertiary care hospital in South India. Methods The study was conducted in a tertiary care hospital in South India from July 2001 to June 2003. Isolates of enterococci were collected from various clinical specimens and speciated using extensive phenotypic and physiological tests. Antimicrobial susceptibility testing were performed and interpreted as per NCCLS guidelines. Whole cell protein (WCP fingerprinting of enterococci were done for species validation by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE and analyzed computationally. Results Our study showed the prevalence of unusual (non-faecalis and non-faecium enterococci and atypical (biochemical variant species of enterococci as 19% (46 isolates and 5% (12 isolates respectively. The 7 unusual species (46 isolates isolated and confirmed by phenotypic characterization includes: 15 E. gallinarum (6.2%, 10 E. avium (4.1%, 6 E. raffinosus (2.5%, 6 E. hirae (2.5%, 4 E. mundtii (1.7%, 3 E. casseliflavus-including the two atypical isolates (1.2% and 2 E. durans (0.8%. The 12 atypical enterococcal species (5% that showed aberrant sugar reactions in conventional phenotyping were confirmed as E. faecalis, E. faecium and E. casseliflavus respectively by WCP fingerprinting. The antimicrobial susceptibility testing depicted the
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.
Suzuki, Y.; Orellana, M A; Wong, S Y; Conley, F K; Remington, J S
Resistance against acute and chronic infection with Taxoplasma gondii in BALB/c and CBA/Ca mice was compared. Intraperitoneal inoculation of either 20, 40, or 80 cysts of the ME49 strain resulted in mortality rates in BALB/c mice of 12% (2 of 17), 50% (6 of 12), and 75% (9 of 12), respectively, within 3 weeks after infection (acute stage). There was no mortality in the CBA/Ca mice for any of the doses. In marked contrast, CBA/Ca mice were highly sensitive to chronic infection with developing ...
Keith H Turner
Full Text Available Opportunistic infections caused by Pseudomonas aeruginosa can be acute or chronic. While acute infections often spread rapidly and can cause tissue damage and sepsis with high mortality rates, chronic infections can persist for weeks, months, or years in the face of intensive clinical intervention. Remarkably, this diverse infectious capability is not accompanied by extensive variation in genomic content, suggesting that the genetic capacity to be an acute or a chronic pathogen is present in most P. aeruginosa strains. To investigate the genetic requirements for acute and chronic pathogenesis in P. aeruginosa infections, we combined high-throughput sequencing-mediated transcriptome profiling (RNA-seq and genome-wide insertion mutant fitness profiling (Tn-seq to characterize gene expression and fitness determinants in murine models of burn and non-diabetic chronic wound infection. Generally we discovered that expression of a gene in vivo is not correlated with its importance for fitness, with the exception of metabolic genes. By combining metabolic models generated from in vivo gene expression data with mutant fitness profiles, we determined the nutritional requirements for colonization and persistence in these infections. Specifically, we found that long-chain fatty acids represent a major carbon source in both chronic and acute wounds, and P. aeruginosa must biosynthesize purines, several amino acids, and most cofactors during infection. In addition, we determined that P. aeruginosa requires chemotactic flagellar motility for fitness and virulence in acute burn wound infections, but not in non-diabetic chronic wound infections. Our results provide novel insight into the genetic requirements for acute and chronic P. aeruginosa wound infections and demonstrate the power of using both gene expression and fitness profiling for probing bacterial virulence.
Amarapurkar, Deepak N; Madan, Kaushal; Kapoor, Dharmesh
Chronic hepatitis B (CHB) infection is a substantial global health problem with highest prevalence observed in the sub-Saharan Africa and East Asia. India lies in the intermediate endemicity zone with prevalence ranging from 0.1% to 11.7%. The predominant route of transmission is horizontal and the most commonly occurring genotypes are A and D. The high mortality and morbidity associated with CHB constitutes significant health and economic burden in developing countries like India. Antiviral agents decrease HBV DNA load and prevent disease progression. Several regional and country expert associations have developed treatment guidelines for appropriate management of CHB; however, various factors like prevalence, disease awareness, immunization status, cost implications, availability of resources, type of transmission and emerging significance of HBV genotypes have influenced the management of CHB in a country. This article focuses on expert's recommendations on CHB management including initiation, monitoring and termination of treatment with emphasis on borderline cases. The article also throws light on the challenges to optimum management and provides preferred therapeutic approaches in Indian perspective. PMID:27608783
Barone, Michele; Viggiani, Maria Teresa; Amoruso, Annabianca; Schiraldi, Serafina; Zito, Annapaola; Devito, Fiorella; Cortese, Francesca; Gesualdo, Michele; Brunetti, Natale; Di Leo, Alfredo; Scicchitano, Pietro; Ciccone, Marco Matteo
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. PMID:26000012
Bala Shashi; Tilahun Yaphet; Taha Odette; Alao Hawau; Kodys Karen; Catalano Donna; Szabo Gyongyi
Abstract Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined mi...
Moosa, Mohammed Rafique; Meyers, Anthony M; Gottlich, Errol; Naicker, Sarala
Very few patients with end-stage kidney disease in South Africa receive renal replacement treatment (RRT), despite the rapidly growing demand, because of resource constraints. Nephrologists who agonise daily about who to treat and who not to, and have been doing so since the inception of dialysis in this country, welcomed the opportunity to interact with the National Department of Health at a recent summit of stakeholders. The major challenges were identified and recommendations for short- to long-term solutions were made. While the renal community can still improve efficiencies, it is clear that much of the responsibility for improving access to RRT and reducing inequities must be borne by the national government. The summit marks the first step in a process that we hope will ultimately culminate in universal access to RRT for all South Africans. PMID:26821893
Viral loads were investigated in SIVmnd-1 chronically infected mandrills and the results were compared with those previously observed in other nonpathogenic natural SIV infections. Four naturally and 11 experimentally SIVmnd-1-infected mandrills from a semi-free-ranging colony were studied during the chronic phase of infection. Four SIVmnd-1-infected wild mandrills were also included for comparison. Twelve uninfected mandrills were used as controls. Viral loads in all chronically infected mandrills ranged from 105 to 9 x 105 copies/ml and antibody titers ranged from 200 to 14,400 and 200 to 12,800 for anti-V3 and anti-gp36, respectively. There were no differences between groups of wild and captive mandrills. Both parameters were stable during the follow-up, and no clinical signs of immune suppression were observed. Chronic SIVmnd-1-infected mandrills presented slight increases in CD20+ and CD28+ /CD8+ cell counts, and a slight decrease in CD4+ /CD3+ cell counts. A slight CD4+ /CD3+ cell depletion was also observed in old uninfected controls. Similar to other nonpathogenic models of lentiviral infection, these results show a persistent high level of SIVmnd-1 replication during chronic infection of mandrills, with minimal effects on T cell subpopulations
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.
Bacterial infection is a common complication in patients with liver cirrhosis, and acute-on-chronic liver failure due to bacterial infection has become a serious clinical problem. There are still many problems in the research on the pathogenesis and management of bacterial infection in liver cirrhosis, such as insidious onset, difficult early diagnosis, and increased multi-drug resistant bacteria. This article reviews the research progress in the causes and management of bacterial infection i...
Elfstrand, Lidia; Florén, Claes-Henrik
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. PMID:22096401
Objective: To determine the prevalence of H. pylori infection in patients with idiopathic chronic urticaria (ICU) and to see if eradication of the bacterium affects the course of the urticaria. Patients and Methods: One hundred patients with idiopathic chronic urticaria and 43 healthy subjects (matched for age and sex) underwent serological testing for H. pylori infection. All patients with idiopathic chronic urticaria were examined for Helicobacter pylori infection with the /sup 13/C-urea test as well as the serological testing. Gastric biopsy was obtained from 36 patients. Patients with proven Helicobacter pylori infection were given treatment for 2 weeks. Six weeks afterwards they were tested again for Helicobacter pylori infection, and their urticaria was clinically assessed. Results: There was no significant difference in the seroprevalence of H. pylori infection between : idiopathic chronic urticaria patients and healthy subjects. Helicobacter pylori was detected in 76% of patients and 69.8% of controls. Out of the 76 patients treated, only 24 showed complete remission of their urticaria after successfully eradicating Helicobacter pylori infection, the others only having some improvement in their symptoms. Conclusion: Patients with idiopathic chronic urticaria have similar high rates of H. pylori infection as healthy subjects. Bacterium eradication is associated with improvement of urticaria symptoms, suggesting a possible role of Helicobacter pylori in the pathogenesis of this skin disorder. (author)
Yun Ma; Wen-Wei Yan
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.
Maasoumy, Benjamin; Manns, Michael P
There are 160-170 million people with chronic hepatitis C virus (HCV) infection worldwide. The marketing of protease inhibitors (PIs) has been a milestone in the history of HCV therapy. In phase III studies, up to 75% of the patients achieved a sustained virological response (SVR) after triple therapy with pegylated-interferon (PEG-IFN)-α, ribavirin (RBV) and boceprevir (BOC). However, triple regimens are more expensive and associated with drug-drug interactions (DDIs) and more adverse events (AEs). According to results in 'real-world' settings, safety seems to be limited, in particular in patients with advanced liver disease. To optimize efficacy while minimizing AEs as well as costs, the optimal treatment strategy must be determined for BOC. Optimizing treatment is based on patient selection, the most efficient treatment design, management of side effects and the challenge of DDIs. Therapy-associated risks, treatment urgency and chances of SVR must all be considered for patient selection. In addition, certain differences between the two approved PIs may help identify the ideal candidates for each HCV PI. Optimal treatment design is based on the results of phase II and III studies, in which different approaches have been tested including 'lead-in' and response-guided strategies. Treatment regimens and stopping rules recommended by the FDA and EMA should normally be followed. Still, there are some cases in which more personalized strategies may be more promising. Management of side effects is a major challenge and plays a crucial role in ensuring safety and adherence. PMID:23286841
Madsen, Jan L
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. ...
Kiat-Hon Lim; Jason Pik-Eu Chang; Chee-Kiat Tan; Lynette Lin-Ean Oon; Boon-Huan Tan; Hoe-Nam Leong; Hui-Hui Tan
Hepatitis E, usually an acute hepatitis in the immunocompetent, has a chronic form described in immunocompromised hosts. We report the clinical course and outcome of an adult liver transplant recipient whose posttransplant period was complicated by chronic hepatitis E, Epstein-Barr virus infection, and cellular rejection of the graft.
Mazuz, Monica L; Shkap, Varda; Wollkomirsky, Ricardo; Leibovich, Benjamin; Savitsky, Igor; Fleiderovitz, Ludmila; Noam, Sugar; Elena, Blinder; Molad, Thea; Golenser, Jacob
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
The purpose of this thesis was to determine whether or not bacterial infection of the urinary bladder had a role in urinary bladder carcinogenesis. To investigate this proposition, four separate studies were conducted. The first study developed an experimental animal model where bacterial infection of the urinary bladder could be introduced and maintained for a period in excess of one year. The method of infection, inoculation of bacteria (Escherichia coli type 04) subserosally into the vesical wall, successfully caused persistent infection in the majority of animals. In the second study the temporal effects of bacterial infection on the induction of urothelial ornithine decarboxylase (ODC) and 3H-thymidine uptake and DNA synthesis were examined. Bacterial infection of the urinary bladder induced urothelial ODC with a peak in enzyme activity 6 hr after infection.3H-Thymidine uptake and DNA synthesis peaked 48 hr after infection and coincided with the urothelial hyperplasia that occurred in response to the infection. In the third study the specific bladder carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) was given to rats concurrent with the urinary bacterial infection. In the fourth study rats were administered sodium nitrate and either dibutylamine or piperazine in the drinking water. The infected group developed bladder tumors while none were detected in the non-infected rats. From these studies it may be concluded that bacterial infection may have a significant role in the process of urinary bladder carcinogenesis
Rafi, Wasiulla; Bhatt, Kamlesh; Gause, William C.
Previously we had reported that Nippostrongylus brasiliensis, a helminth with a lung migratory phase, affected host resistance against Mycobacterium tuberculosis infection through the induction of alternatively activated (M2) macrophages. Several helminth species do not have an obligatory lung migratory phase but establish chronic infections in the host that include potent immune downregulatory effects, in part mediated through induction of a FoxP3+ T regulatory cell (Treg) response. Treg cells exhibit duality in their functions in host defense against M. tuberculosis infection since their depletion leads to enhanced priming of T cells in the lymph nodes and attendant improved control of M. tuberculosis infection, while their presence in the lung granuloma protects against excessive inflammation. Heligmosomoides polygyrus is a strictly murine enteric nematode that induces a strong FoxP3 Treg response in the host. Therefore, in this study we investigated whether host immunity to M. tuberculosis infection would be modulated in mice with chronic H. polygyrus infection. We report that neither primary nor memory immunity conferred by Mycobacterium bovis BCG vaccination was affected in mice with chronic enteric helminth infection, despite a systemic increase in FoxP3+ T regulatory cells. The findings indicate that anti-M. tuberculosis immunity is not similarly affected by all helminth species and highlight the need to consider this inequality in human coinfection studies. PMID:25605766
Full Text Available This study evaluated the prevalence of HBV infection in a population of South American immigrants in Italy and to determine in patients with detectable serum HBV-DNA the HBVgenotypes. Between April 2005 and April 2006 a total of 130 South American immigrants were tested for HBsAg. In HBsAg positive patients the biochemical and virological activity of infection and the possible presence of co-infections (HCV, HDV, HIV were evaluated. In patients with detectable serum HBV DNA, the HBV genotype was determined by INNOLiPA. Among the 130 subjects tested, 14 (10.7% resulted HBsAg positive. All were men, with a mean age of 22 years (range 19-37 and 12 (85.7 % came from Brazil, while 2 (14.3% came from Ecuador. All patients infected by HBV had elevated alanine-aminotransferase serum levels (mean level was 127 IU/L, range 74-312 and serum HBV DNA detectable by PCR-Real Time (mean level 1,037,652 copies/mL, range 19,876-1,377,648. Genotype distribution was as follow: genotype D, 9 (64.2%, genotype A, 5 (35.8%. All patients infected by genotype D came from Brazil, while among the patients infected by genotype A, three came from Brazil and two from Ecuador. Our study evidences a moderate prevalence of HBV-infection in South American immigrants with the identification of two genotypes, D and A. These genotypes are not the most prevalent in the South America and this is probably the expression of a possible geographical redistribution of HBV genotypes.
Mor, Anil; Thomsen, Reimar W.
This review provides an update on the risk of several important community-acquired infections seen in patients with diabetes: respiratory tract infections, urinary tract infections, and bacteremia. Respiratory tract infections: Recent epidemiological evidence shows a modest (1.25 to 1.75-fold) risk...... tuberculosis. Limited data is available for diabetes and influenza, yet both influenza and pneumococcal vaccination is recommended in patients with diabetes. Urinary tract infections: The risk of asymptomatic bacteriuria and cystitis is 1.5 to 2 times increased in diabetes patients, while their risk of...... bacteremia. Conclusions: Increased infection surveillance and unmeasured confounding factors among diabetic patients may contribute to the observed increased infection risk, yet outcomes following infection are similar or worse in diabetes patients. In conclusion, there is epidemiological evidence that...
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
Christopher J Hoffmann
Full Text Available Introduction: Globally, hepatitis B virus (HBV infection is the leading cause of liver-related mortality. Newborn vaccination, maternal antiviral therapy and administering hepatitis B immune globulin shortly after birth can greatly reduce the risk of perinatal and infant infection. However, evidence-based policy regarding these interventions in Africa is hampered by gaps in knowledge of HBV epidemiology. We describe maternal chronic hepatitis B (CHB prevalence and infant infection during the first year of life within a cohort of women living with HIV. Methods: We recruited and prospectively followed pregnant women living with HIV and their infants from prenatal clinics in an urban area of South Africa. Hepatitis B surface antigen, anti-hepatitis B surface antibodies and HBV DNA were assessed in all women. Hepatitis B testing was also performed at 6 and 52 weeks for all infants born to mothers with either positive surface antigen or detectable HBV DNA. Results: We enrolled 189 women with a median age of 29 years and median CD4 count of 348 cells/mm3. Fourteen had a positive surface antigen (7.4%, of which six were positive for “e” antigen. An additional three had detectable HBV DNA without positive surface antigen. One infant developed CHB and three others had evidence of transmission based on positive HBV DNA assays. HBV vaccinations were delivered at six weeks of life to all infants. Conclusions: Our findings highlight the risk of peripartum HBV transmission in this setting. Approaches to reducing this transmission should be considered.
Dominique; Larrey; Marie-Cécile; Bozonnat; Ihab; Kain; Georges-Philippe; Pageaux; Eric; Assenat
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...
Esteban-Gil, A; Jacquiet, P; Florentin, S; Decaudin, A; Berthelot, X; Ronsin, P; Grisez, C; Prevot, F; Alzieu, J P; Marois, M; Corboz, N; Peglion, M; Vilardell, C; Liénard, E; Bouhsira, E; Castillo, J A; Franc, M; Picard-Hagen, N
Bovine besnoitiosis is a reemerging disease in Europe. The clinically Besnoitia besnoiti infection in bulls is characterized by fever, nasal discharge, and orchitis in the acute phase and by scleroderma in the chronic phase. However, in many bulls, B besnoiti infection remains at a subclinical stage. Bull infertility is an economically relevant consequence of besnoitiosis infection. It is not clear, however, if semen quality returns to normal levels when infected animals have clinically recovered. The aim of this study was to examine the relationship between chronic besnoitiosis and bull sexual function in a region of eastern France, where the disease is reemerging, by comparing semen quality and genital lesions in 11 uninfected, 17 subclinically infected, and 12 clinically infected bulls. The presence of anti-B besnoiti antibodies was detected by Western blot test. Semen was collected by electroejaculation. Bulls clinically infected with B besnoiti showed significantly more genital tract alterations than uninfected or subclinically infected bulls. No relationship was evidenced between besnoitiosis infectious status and semen quality, whereas a significant relationship was noted between genital lesions and semen score. This means that in the absence of moderate to severe genital lesions, chronic bovine besnoitiosis is unlikely to alter semen quality. However, as the presence of infected animals could lead to spread of the disease, culling or separation of clinically infected bulls from the remaining healthy animals is strongly recommended. PMID:27264738
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.)
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
Sun, Yang; Ma, Yingfei; Lin, Ping; Tang, Yi-Wei; Yang, Liying; Shen, Yinzhong; Zhang, Renfan; Liu, Li; Cheng, Jun; Shao, Jiashen; Qi, Tangkai; Tang, Yan; Cai, Rentian; Guan, Liqian; Luo, Bin; Sun, Meiyan; Li, Ben; Pei, Zhiheng; Lu, Hongzhou
The purpose of this study was to identify fecal bacterial microbiome changes in patients with chronic human immunodeficiency virus (HIV) infection in China. Bacterial 16S rRNA genes were amplified, sequenced (454 pyrosequencing), and clustered into operational taxonomic units using the QIIME software. Relative abundance at the phylum and genus levels were calculated. Alpha diversity was determined by Chao 1 and observed-species indices, and beta diversity was determined by double principal component analysis using the estimated phylogeny-based unweighted Unifrac distance matrices. Fecal samples of the patients with chronic HIV-infection tended to be enriched with bacteria of the phyla Firmicutes (47.20%±0.43 relative abundance) and Proteobacteria (37.21%±0.36) compared with those of the non-HIV infected controls (17.95%±0.06 and 3.81%±0.02, respectively). Members of the genus Bilophila were exclusively detected in samples of the non-HIV infected controls. Bacteroides and arabacteroides were more abundant in the chronic HIV-infected patients. Our study indicated that chronic HIV-infected patients in China have a fecal bacterial microbiome composition that is largely different from that found in non-HIV infected controls, and further study is needed to evaluate whether microbiome changes play a role in disease complications in the distal gut, including opportunistic infections. PMID:27048741
Heiberg, Ida Louise; Winther, Thilde Nordmann; Paludan, Søren Riis;
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 childre...
Fischler, Björn; Priftakis, Peter; Sundin, Mikael
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. PMID:26928522
Greenberg, David E.; Goldberg, Joanna B.; Stock, Frida; Murray, Patrick R.; Holland, Steven M.; LiPuma, John J.
The epidemiology of Burkholderia infection in persons with chronic granulomatous disease is poorly understood. We used species-specific polymerase chain reaction–based assays and genotyping analyses to identify 32 strains representing 9 Burkholderia species among 50 isolates recovered from 18 patients with chronic granulomatous disease. We found that recurrent pulmonary infection with distinct Burkholderia strains is common in chronic granulomatous disease.
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.
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
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.
Lacey, C. J.; Clarke, A. M.; Fraser, P; Metcalfe, T; Bonsor, G; Curry, A.
A case of chronic infection of the nasal mucosae, sinuses and conjunctivae with a microsporidian parasite in association with HIV infection and immune deficiency is reported. This microsporidian resembles both Encephalitozoon cuniculi and the newly described Encephalitozoon hellem by electron microscopy. This occurred in an adult male resident in the UK with no history of foreign travel. Although there are previous descriptions of conjunctival infections from the USA, this is the first descri...
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 patien...
Braga Eduardo Lorens
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.
Nally, Jarlath E.; Chow, Emilie; Fishbein, Michael C.; Blanco, David R.; Lovett, Michael A.
Leptospirosis is the most geographically widespread zoonotic disease in the world. A severe pulmonary form of leptospirosis (SPFL) is being recognized with increased frequency. We have reported that human SPFL isolates of Leptospira cause acute lethal infection with prominent pulmonary hemorrhage in guinea pigs. We have found that the same SPFL strains cause asymptomatic infection and chronic renal shedding in rats, where infection is restricted to the renal tubules. To address the antigenic ...
Mogueo, Amelie; Echouffo-Tcheugui, Justin B; Matsha, Tandi E.; Erasmus, Rajiv T; Kengne, Andre P.
Background Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. Methods Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as ‘estimated glomerular filtration rate (eGFR)
Çetinkaya, Erdoğan; Gül, Şule; Mert, Ali; Boyacı, Hilal; Çam, Ertan; Dincer, H. Erhan
Fungal infections of the lung are uncommon and mainly affect people with immune deficiency. There are crucial problems in the diagnosis and treatment of this condition. Invasive pulmonary aspergillosis and candidiasis are the most common opportunistic fungal infections. Aspergillus species (spp.) are saprophytes molds that exist in nature as spores and rarely cause disease in immunocompetent individuals. In patients with immune deficiency or chronic lung disease, such as cavitary lung disease or bronchiectasis, Aspergillus may cause a variety of aspergillosis infections. Here we present a case of a 57-year-old patient without immunodeficiency or chronic lung disease who was diagnosed with endotracheal fungus ball and chronic fungal infection, possibly due to Aspergillus. Bronchoscopic examination showed a paralyzed right vocal cord and vegetating mass that was yellow in color, at the posterior wall of tracheal lumen. After 3 months, both the parenchymal and tracheal lesions were completely resolved. PMID:27418930
Jacques, Christopher N; Jenks, Jonathan A; Grovenburg, Troy W; Klaver, Robert W; Dubay, Shelli A
The meningeal worm (Parelaphostrongylus tenuis) is a nematode parasite that commonly infects white-tailed deer (Odocoileus virginianus; WTD) throughout the deciduous forest biome and deciduous-coniferous ecotone of eastern and central North America; the species is not known to occur west of the grassland biome of central North America. We used county-specific prevalence data to evaluate potential effects of landscape and climatologic factors on the spatial distribution of meningeal worm infection in South Dakota, US. Probability of infection increased 4-fold between eastern and western South Dakota and 1.3-fold for each 1-cm increase in summer precipitation. Sixty-three percent of WTD had only a single worm in the cranium. Expansion of meningeal worm infection across western South Dakota may be inherently low due to the combined effects of arid climate and potential attributes of the Missouri River that limit regional movements by infected WTD. Use of landscape genetic analyses to identify potential relationships between landscape features and population genetic structure of infected deer and parasites may contribute to a greater understanding of regional heterogeneity in meningeal worm infection rates across South Dakota, particularly in counties adjacent to the Missouri River. Future research evaluating heterogeneity in prevalence and intensity of infection between fawn and yearling deer, and the potential role of yearling male deer as dispersal agents of meningeal worms across the Missouri River, also is warranted. PMID:25588013
Gut, A; Shiel, N; Kay, P M; Segal, I; Braganza, J M
Four indices of free radical activity were measured in fasting serum/plasma samples from 14 consecutive blacks with clinically quiescent chronic pancreatitis and 15 outwardly healthy hospital personnel at Soweto, the township near Johannesburg in South Africa. The patients had higher serum levels than did controls of lipid isomerisation (P radical activity is thus a common denominator in chronic pancreatitis irrespective of geography, or putative aetiological factors whether alcoholism or idiopathic, since that ratio was approximately 95:5 at Johannesburg and 50:50 at Manchester. The further finding of subclinical oxidative stress in Sowetan controls and the endemic nature of chronic pancreatitis in that area supports the hypothesis that oxidative stress may be involved in its pathogenesis. PMID:7834869
Mohammad Javad Kaviani; Behzad Behbahani; Mohammad Jafar Mosallaii; Fatemeh Sari-Aslani; Seyed Alireza Taghavi
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.
Hoffmann, Christopher J.; Fildah Mashabela; Silvia Cohn; Jennifer D Hoffmann; Sanjay Lala; Martinson, Neil A; Chaisson, Richard E.
Introduction: Globally, hepatitis B virus (HBV) infection is the leading cause of liver-related mortality. Newborn vaccination, maternal antiviral therapy and administering hepatitis B immune globulin shortly after birth can greatly reduce the risk of perinatal and infant infection. However, evidence-based policy regarding these interventions in Africa is hampered by gaps in knowledge of HBV epidemiology. We describe maternal chronic hepatitis B (CHB) prevalence and infant infection during th...
Full Text Available This study investigated the risk factors associated with recent and chronic HIV infections among individual attending a voluntary counseling and testing (VCT site in Rio de Janeiro, Brazil. In a cross-sectional study, recent HIV infections were detected by the sensitive/less-sensitive test, using Serologic Testing Algorithm for Recent HIV Seroconversion (STARHS strategy, and compared to chronic HIV infection and HIV negative individuals. Seroincidence was estimated and risk factors associated with recent and chronic infections were assessed using multinomial logistic regression. Among the 7,379 individuals tested between June 2006 and April 2007, the overall prevalence and incidence of HIV infection were 7.5%; and 1.39/100 PY, respectively. In multivariate analysis, having a HIV positive steady partner was a risk factor for recent and for chronic HIV infection for MSM, heterosexual male and women. No differences in risk factors for recent and chronic infections were found between MSM and heterosexual males. Among women, chronic infected individuals were more likely than HIV negatives to be older. Recently HIV infected women were more likely than HIV negatives to be less educated; and more likely than HIV negatives and chronically infected to report having more partners. Routinely used risk-based assessment in testing centers in Brazil lack sensitivity to distinguish between recent and chronic infections, particularly among MSM and heterosexual males. Steady relationships and serosorting may be playing a key role in maintaining the HIV epidemics in Brazil.
Lewis, Eric R G; Torres, Alfredo G
The Gram-negative proteobacteria genus Burkholderia encompasses multiple bacterial species that are pathogenic to humans and other vertebrates. Two pathogenic species of interest within this genus are Burkholderia pseudomallei (Bpm) and the B. cepacia complex (Bcc); the former is the causative agent of melioidosis in humans and other mammals, and the latter is associated with pneumonia in immunocompromised patients. One understudied and shared characteristic of these two pathogenic groups is their ability to persist and establish chronic infection within the host. In this review, we will explore the depth of knowledge about chronic infections caused by persistent Bpm and Bcc. We examine the host risk factors and immune responses associated with more severe chronic infections. We also discuss host adaptation and phenotypes associated with persistent Burkholderia species. Lastly, we survey how other intracellular bacteria associated with chronic infections are combatted and explore possible future applications to target Burkholderia Our goal is to highlight understudied areas that should be addressed for a more thorough understanding of chronic Burkholderia infections and how to combat them. PMID:27440810
Nielsen, Søren Saxmose; Toft, Nils; Gardner, Ian Andrew
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...... 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...... 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...
The global rise in antibiotic resistance is a significant problem facing healthcare professionals. In particular within the cystic fibrosis (CF) lung, bacteria can establish chronic infection and resistance to a wide array of antibiotic therapies. One of the principle pathogens associated with chronic infection in the CF lung is Pseudomonas aeruginosa. P. aeruginosa can establish chronic infection in the CF lung partly through the use of the biofilm mode of growth. This biofilm mode of growth...
Zhang, Chuan; Yamada, Nobutaka; Wu, Yun-Lin; Wen, Min; Matsuhisa, Takeshi; Matsukura, Norio
AIM: To compare Helicobacter pylori infection and gastric mucosal histological features of gastric ulcer patients with chronic gastritis patients in different age groups and from different biopsy sites.
Wilson, Shona; Vennervald, Birgitte J; Kadzo, Hilda; Ireri, Edmund; Amaganga, Clifford; Booth, Mark; Kariuki, H. Curtis; Mwatha, Joseph K.; Kimani, Gachuhi; Ouma, John H.; Muchiri, Eric; Dunne, David W.
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 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...
Price, Richard W; Spudich, Serena S; Peterson, Julia; Joseph, Sarah; Fuchs, Dietmar; Zetterberg, Henrik; Gisslén, Magnus; Swanstrom, Ronald
Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system (CNS) begins early in systemic infection and continues throughout its untreated course. Despite a common cerebrospinal fluid inflammatory response, it is usually neurologically asymptomatic for much of this course, but can evolve in some individuals to HIV-associated dementia (HAD), a severe encephalopathy with characteristic cognitive and motor dysfunction. While widespread use of combination antiretroviral therapy (ART) has led to a marked decline in both the CNS infection and its neurologic severe consequence, HAD continues to afflict individuals presenting with advanced systemic infection in the developed world and a larger number in resource-poor settings where ART is more restricted. Additionally, milder CNS injury and dysfunction have broader prevalence, including in those treated with ART. Here we review the history and evolving nomenclature of HAD, its viral pathogenesis, clinical presentation and diagnosis, and treatment. PMID:24715483
Søndberg, Emilie; Jelsbak, Lotte
type strains of S. Typhimurium 4/74 were used to establish chronic infections of 129X1/SvJ mice. Over the course of infections, S. Typhimurium bacteria were isolated from feces and from livers and spleens upon termination of the experiment. In all samples dominant clones were identified and select...... clones were subjected to whole genome sequencing. Dominant clones isolated from either systemic organs or fecal samples exhibited distinct single nucleotide polymorphisms (SNPs). One mouse appeared to have distinct adapted clones in the spleen and liver, respectively. Three mice were colonized 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...
Zhao, Qiang; Peng, Liang; Huang, Weijun;
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...
Reen, F Jerry; Flynn, Stephanie; Woods, David F; Dunphy, Niall; Chróinín, Muireann Ní; Mullane, David; Stick, Stephen; Adams, Claire; O'Gara, Fergal
Despite aggressive antimicrobial therapy, many respiratory pathogens persist in the lung, underpinning the chronic inflammation and eventual lung decline that are characteristic of respiratory disease. Recently, bile acid aspiration has emerged as a major comorbidity associated with a range of lung diseases, shaping the lung microbiome and promoting colonisation by Pseudomonas aeruginosa in Cystic Fibrosis (CF) patients. In order to uncover the molecular mechanism through which bile modulates the respiratory microbiome, a combination of global transcriptomic and phenotypic analyses of the P. aeruginosa response to bile was undertaken. Bile responsive pathways responsible for virulence, adaptive metabolism, and redox control were identified, with macrolide and polymyxin antibiotic tolerance increased significantly in the presence of bile. Bile acids, and chenodeoxycholic acid (CDCA) in particular, elicited chronic biofilm behaviour in P. aeruginosa, while induction of the pro-inflammatory cytokine Interleukin-6 (IL-6) in lung epithelial cells by CDCA was Farnesoid X Receptor (FXR) dependent. Microbiome analysis of paediatric CF sputum samples demonstrated increased colonisation by P. aeruginosa and other Proteobacterial pathogens in bile aspirating compared to non-aspirating patients. Together, these data suggest that bile acid signalling is a leading trigger for the development of chronic phenotypes underlying the pathophysiology of chronic respiratory disease. PMID:27432520
Sthoeger, Z; Fogel, M.; Smirov, A.; Ergas, D; Lurie, Y; Bass, D.; Geltner, D.; Malnick, S.
OBJECTIVE—Chronic hepatitis C virus (HCV) has been linked to extrahepatic autoimmune phenomena. In addition, a variety of autoantibodies are found in patients with HCV. The prevalence, nature, and clinical significance of anticardiolipin (aCL) autoantibodies in serum samples of patients with HCV were therefore investigated. PATIENTS AND METHODS—A prospective study of 48 consecutive patients with chronic HCV with no evidence of previous hepatitis B virus (HBV) infection or any other autoimmune...
Rautou, Pierre-Emmanuel; Cazals-Hatem, Dominique; Feldmann, Gérard; Mansouri, Abdellah; Grodet, Alain; Barge, Sandrine; Martinot-Peignoux, Michèle; Duces, Aurélie; Bièche, Ivan; Lebrec, Didier; Bedossa, Pierre; Paradis, Valérie; Marcellin, Patrick; Valla, Dominique; Asselah, Tarik
Autophagy is a regulated process that can be involved in the elimination of intracellular microorganisms and in antigen presentation. Some in vitro studies have shown an altered autophagic response in hepatitis C virus infected hepatocytes. The present study aimed at evaluating the autophagic process in the liver of chronic hepatitis C (CHC) patients. Fifty-six CHC patients and 47 control patients (8 with nonalcoholic steatohepatitis or alcoholic liver disease, 18 with chronic heptatitis B vi...
Tracy D Reynolds; Buonocore, Linda; Rose, Nina F.; Rose, John K.; Robek, Michael D.
More than 500,000 people die each year from the liver diseases that result from chronic hepatitis B virus (HBV) infection. Therapeutic vaccines, which aim to elicit an immune response capable of controlling the virus, offer a potential new treatment strategy for chronic hepatitis B. Recently, an evolved, high-titer vaccine platform consisting of Semliki Forest virus RNA replicons that express the vesicular stomatitis virus glycoprotein (VSV G) has been described. This platform generates virus...
Rhoads Daniel D; Cox Stephen B; Rees Eric J; Sun Yan; Wolcott Randall D
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...
Phull, P S; Price, A. B.; Stephens, J; Rathbone, B J; Jacyna, M R
AIM: To compare the histological characteristics of Helicobacter pylori positive chronic gastritis in patients with and without associated duodenitis. METHODS: Gastric mucosal biopsy specimens were obtained from patients undergoing endoscopy for dyspepsia. Severity of gastritis and density of H pylori infection were graded according to the Sydney system. RESULTS: Of the 69 patients studied, 15 had normal histology, 22 had chronic gastritis only (77.3% H pylori positive), 21 had duodenitis (90...
Shousha, S; Keen, C; Parkins, R A
Duodenal biopsy specimens from 80 patients with chronic renal failure, who were undergoing haemodialysis, were examined by light microscopy for evidence of inflammation, gastric metaplasia, and Campylobacter pylori infection. Chronic duodenitis was present in 47 (59%) of patients, of whom only seven (9%) showed evidence of active inflammation. Gastric metaplasia was present in 50 (62.5%) of patients, yet Campylobacter pylori was identified in only two patients (2.5%). It is suggested that the...
Barker, D J P; Osmond, Clive
The high mortality from chronic bronchitis in England and Wales and the excess of urban over rural mortality are unexplained. On dividing England and Wales into 212 local authority areas a strong geographical relation was found between death rates from chronic bronchitis and emphysema in 1959-78 and infant mortality from bronchitis and pneumonia during 1921-5. It was concluded that this relation provided strong evidence of a direct casual link between acute lower respiratory infection in earl...
Martin-Gandul, C; Mueller, N J; Pascual, M; Manuel, O
Infectious diseases after solid organ transplantation (SOT) are a significant cause of morbidity and reduced allograft and patient survival; however, the influence of infection on the development of chronic allograft dysfunction has not been completely delineated. Some viral infections appear to affect allograft function by both inducing direct tissue damage and immunologically related injury, including acute rejection. In particular, this has been observed for cytomegalovirus (CMV) infection in all SOT recipients and for BK virus infection in kidney transplant recipients, for community-acquired respiratory viruses in lung transplant recipients, and for hepatitis C virus in liver transplant recipients. The impact of bacterial and fungal infections is less clear, but bacterial urinary tract infections and respiratory tract colonization by Pseudomonas aeruginosa and Aspergillus spp appear to be correlated with higher rates of chronic allograft dysfunction in kidney and lung transplant recipients, respectively. Evidence supports the beneficial effects of the use of antiviral prophylaxis for CMV in improving allograft function and survival in SOT recipients. Nevertheless, there is still a need for prospective interventional trials assessing the potential effects of preventive and therapeutic strategies against bacterial and fungal infection for reducing or delaying the development of chronic allograft dysfunction. PMID:26474168
Bondarenko, A L; Baramzina, S V
Clinical, biochemical and immunological parameters depending on HLA-phenotypic features were examined in 107 patients aged 18-78 years with chronic hepatitis C virus (HCV) infection. Clinical and biochemical manifestations (asthenic, pain and cytolytic syndromes, hepatomegalia, hyperbilirubinemia, hypoprothrombin- and proteinemia), observed in hepatitis C, were more pronounced in patients having HLA-A30, B35, B41, Cw2, A1-B35, A9-B8. The carriers of B8 and B35 antigens were found to have inadequate immune response in HCV infection, manifested by progressive chronic process in the liver and the development of cirrhosis in patients with such specificity. PMID:12043154
Shih, C M; L. P. LIU; Spielman, A.
We determined whether the infectivity of the Lyme disease spirochete (Borrelia burgdorferi) to vector ticks varies with the duration of infection in laboratory mice. Thus, noninfected nymphal deer ticks were permitted to feed on two strains of early (2 months after infection) and late (8 months after infection) spirochete-infected mice. The attached ticks were removed from their hosts at specified time intervals and were thereafter examined for spirochetes by direct immunofluorescence microsc...
Gamage, Chandika Damesh; Sarathkumara, Yomani Dilukshi
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. PMID:27142134
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.
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.
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+
Full Text Available 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(tide analogs, stimulation of antiviral immune response, and suppression of the immunoinhibitory signals must be combined to achieve desirable antiviral effects.
Mahmoud, Motamed Elsayed; Ihara, Fumiaki; Fereig, Ragab M; Nishimura, Maki; Nishikawa, Yoshifumi
Although Toxoplasma gondii (T. gondii) infection is relevant to many psychiatric disorders, the fundamental mechanisms of its neurobiological correlation with depression are poorly understood. Here, we show that reactivation of chronic infection by an immunosuppressive regimen caused induction of depressive-like behaviors without obvious sickness symptoms. However, the depression-related behaviors in T. gondii-infected mice, specifically, reduced sucrose preference and increased immobility in the forced-swim test were observed at the reactivation stage, but not in the chronic infection. Interestingly, reactivation of T. gondii was associated with production of interferon-gamma and activation of brain indoleamine 2, 3-dioxygenase, which converts tryptophan to kynurenine and makes it unavailable for serotonin synthesis. Furthermore, serotonin turnover to its major metabolite, 5-hydroxyindoleacetic acid, was also enhanced at the reactivation stage. Thus, enhanced tryptophan catabolic shunt and serotonin turnover may be implicated in development of depressive-like behaviors in mice with reactivated T. gondii. PMID:26554725
Leonardo Rodrigues de Oliveira; Helio Moraes-Souza; Andre Luiz Maltos; Keila Cristina dos Santos; Rodrigo Juliano Molina; Cristina Hueb Barata
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 fung...
Khamid Karimov; Sevara Azimova; Bakhtiyor Iriskulov
Viral hepatitis B and C is a relevant issue because of high prevalence and degree of chronicity, late diagnosis and poor prognosis. Today, protein products of numerous genes are involved in the pathogenesis of viral pathology of the liver. In this review, the authors analyzed 42 literature sources on genetic basis of susceptibility to various infectious diseases. Study of the role of immunogenetic factors is of great practical importance to develop methods for predicting outcomes of viral hep...
We continue to study the implications of IR Cohen's theory of immune cognition, in the presence of both sudden and chronic pathogenic challenge, through a mathematical model derived from the Large Deviations Program of applied probability. The analysis makes explicit the linkage between an individual's 'immunocultural condensation' and embedding social or historical structures and processes, in particular power relations between groups. We use methods adapted from the theory of ecosystem...
Nedenskov-Sørensen, P; Aase, S; Bjørneklett, A; O. Fausa; Bukholm, G
The methods and sampling procedures used in the diagnosis of Helicobacter pylori infection and chronic active gastritis were evaluated. Five biopsy specimens for bacteriological cultivation and three specimens for histological examination were obtained endoscopically from a defined area of the gastric antral mucosae of 83 patients. An increase in the number of biopsy specimens for cultivation from one to five revealed only one more H. pylori-infected patient. H. pylori was isolated from 31 of...
Kordick, Dorsey L.; Brown, Talmage T.; Shin, KwangOk; Edward B Breitschwerdt
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...
Padhi, Sanghamitra; Dash, Muktikesh; Sahu, Rani; Panda, Pritilata
Paenibacilli, the Gram positive, aerobic spore bearing bacilli are found normally in the environment. Though these organisms were not known to cause human disease, until recently; few species of this genus have been reported to cause infections in humans. We report here, a case of urinary tract infection in a 60-year-old chronic kidney disease patient due to this rare bacterium. The patient presented with complains of fever, dysuria, and flank pain. Routine and microscopic examination of urin...
... infections that cause chronic diarrhea be prevented? Chronic Diarrhea What is chronic diarrhea? Diarrhea that lasts for more than 2-4 ... represent a life-threatening illness. What causes chronic diarrhea? Chronic diarrhea has many different causes; these causes ...
Full Text Available Abstract Background Hepatitis C Virus (HCV, a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA regulate inflammation (miR-155, -146a and -125b as well as hepatocyte function (miR-122. Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. Results We found that monocytes from chronic HCV infected treatment-naïve (cHCV but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. Conclusion In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate
Jensen, Trine Hammer; Chriél, Mariann; Hansen, Mette Sif
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 ...
Bakonyi, T.; Gaydon, G. K.; Schwing, R.; Vogl, W.; Häbich, A.-C.; Thaller, D.; Weissenböck, H.; Rudolf, Ivo; Hubálek, Zdeněk; Nowotny, N.
Roč. 183, February (2016), s. 135-139. ISSN 0378-1135 EU Projects: European Commission(XE) 261504 - EDENEXT; European Commission(XE) 261391 - EUROWESTNILE Institutional support: RVO:68081766 Keywords : West Nile virus * Lineage 2 * Kea * Nestor notabilis * Psittaciformes * Persistent infection * Austria Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.511, year: 2014
... all your household members see their physicians for hepatitis B testing and vaccination. Tell your healthcare professionals that you are infected ... of being protected from HBV! Learn more about hepatitis B so you can make the best decisions ... Action Coalition (651) 647-9009 www.immunize.org ...
Valentina Peta; Carlo Torti; Natasa Milic; Alfredo Focà; Ludovico Abenavoli
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.
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.
Full Text Available Introduction: Little is known about the prevalence and predictors of chronic non-communicable diseases (NCDs of older adults in South Africa. This study aims to investigate the self-reported prevalences of major chronic NCDs and their predictors among older South Africans. Methods: We conducted a national population-based cross-sectional survey with a sample of 3,840 individuals aged 50 years or above in South Africa in 2008. The outcome variable was the self-reported presence of chronic NCDs suffered, namely, arthritis, stroke, angina, diabetes, chronic lung disease, asthma, depression, and hypertension. The exposure variables were sociodemographic characteristics: age, gender, education, wealth status, race, marital status, and residence. Multivariate logistic regression was used to determine sociodemographic factors predictive of the presence of chronic NCDs. Results: The prevalence of chronic NCDs was 51.8%. The prevalence of multimorbidity (≥2 chronic conditions was 22.5%. Multivariate logistic regression analysis showed that being female, being in age groups 60–79 and 70–79, being Coloured or Asian, having no schooling, having greater wealth, and residing in an urban area were associated with the presence of NCDs. Conclusion: The rising burden of chronic NCDs affecting older people places a heavy burden on the healthcare system as a result of increased demand and access to healthcare services. Concerted effort is needed to develop strategies for the prevention and management of NCDs, especially among economically disadvantaged individuals who need these services the most.
Phaswana-Mafuya, Nancy; Peltzer, Karl; Chirinda, Witness; Musekiwa, Alfred; Kose, Zamakayise; Hoosain, Ebrahim; Davids, Adlai; Ramlagan, Shandir
Introduction Little is known about the prevalence and predictors of chronic non-communicable diseases (NCDs) of older adults in South Africa. This study aims to investigate the self-reported prevalences of major chronic NCDs and their predictors among older South Africans. Methods We conducted a national population-based cross-sectional survey with a sample of 3,840 individuals aged 50 years or above in South Africa in 2008. The outcome variable was the self-reported presence of chronic NCDs suffered, namely, arthritis, stroke, angina, diabetes, chronic lung disease, asthma, depression, and hypertension. The exposure variables were sociodemographic characteristics: age, gender, education, wealth status, race, marital status, and residence. Multivariate logistic regression was used to determine sociodemographic factors predictive of the presence of chronic NCDs. Results The prevalence of chronic NCDs was 51.8%. The prevalence of multimorbidity (≥2 chronic conditions) was 22.5%. Multivariate logistic regression analysis showed that being female, being in age groups 60–79 and 70–79, being Coloured or Asian, having no schooling, having greater wealth, and residing in an urban area were associated with the presence of NCDs. Conclusion The rising burden of chronic NCDs affecting older people places a heavy burden on the healthcare system as a result of increased demand and access to healthcare services. Concerted effort is needed to develop strategies for the prevention and management of NCDs, especially among economically disadvantaged individuals who need these services the most. PMID:24054088
Katz, Ivor; Schneider, Helen; Shezi, Zodwa; Mdleleni, Golebemang; Gerntholtz, Trevor; Butler, Omar; Manderson, Lenore; Naicker, Sarala
Diabetes (DM) and its resultant complications are a problem worldwide, and especially in developing countries like South Africa (SA). Risk factors associated with DM are potentially modifiable, but DM control is poor. Problems in SA include high prevalence of morbidity from DM and hypertension (HTN), lack of recognition of the importance of chronic kidney disease (CKD), late presentation to health care services, lack of education of health providers and patients, and poor quality of care in primary health care settings (PHC). In response, there has been growing advocacy for prevention strategies and improved support and education for primary health care nurses (PHCNs). A Chronic Disease Outreach Program (CDOP), based on the chronic care model was used to follow patients with DM and HTN, support PHCN, and improve health systems for management in Soweto. A group of 257 DM patients and 186 PHCN were followed over 2 years, with the study including the evaluation of 'functional' and clinical outcomes, diary recordings outlining program challenges, and a questionnaire assessing PHCNs' knowledge and education support, and the value of CDOP. CDOP was successful in supporting PHCNs, detecting patients with advanced disease, and ensuring early referral to a specialist center. It improved early detection and referral of high risk, poorly controlled patients and had an impact on PHCNs' knowledge. Its weaknesses include poor follow up due to poor existing health systems and the programs' inability to integrate into existing chronic disease services. The study also revealed an overworked, poorly supported, poorly educated and frustrated primary health care team. PMID:19640820
Candace K Mathiason; Hayes-Klug, Jeanette; Hays, Sheila A.; Powers, Jenny; Osborn, David A.; Dahmes, Sallie J.; Miller, Karl V.; Warren, Robert J., II; Mason, Gary L.; Telling, Glenn C.; Young, Alan J; Hoover, Edward A.
Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cervidized mice to determine (i) if chronic wasting disease (CWD) b...
Full Text Available Staphylococcus aureus is a major human pathogen that causes a range of infections from acute invasive to chronic and difficult-to-treat. Infection strategies associated with persisting S. aureus infections are bacterial host cell invasion and the bacterial ability to dynamically change phenotypes from the aggressive wild-type to small colony variants (SCVs, which are adapted for intracellular long-term persistence. The underlying mechanisms of the bacterial switching and adaptation mechanisms appear to be very dynamic, but are largely unknown. Here, we analyzed the role and the crosstalk of the global S. aureus regulators agr, sarA and SigB by generating single, double and triple mutants, and testing them with proteome analysis and in different in vitro and in vivo infection models. We were able to demonstrate that SigB is the crucial factor for adaptation in chronic infections. During acute infection, the bacteria require the simultaneous action of the agr and sarA loci to defend against invading immune cells by causing inflammation and cytotoxicity and to escape from phagosomes in their host cells that enable them to settle an infection at high bacterial density. To persist intracellularly the bacteria subsequently need to silence agr and sarA. Indeed agr and sarA deletion mutants expressed a much lower number of virulence factors and could persist at high numbers intracellularly. SigB plays a crucial function to promote bacterial intracellular persistence. In fact, ΔsigB-mutants did not generate SCVs and were completely cleared by the host cells within a few days. In this study we identified SigB as an essential factor that enables the bacteria to switch from the highly aggressive phenotype that settles an acute infection to a silent SCV-phenotype that allows for long-term intracellular persistence. Consequently, the SigB-operon represents a possible target to develop preventive and therapeutic strategies against chronic and therapy
Gastric colonization by Helicobacter pylori (H. pylori) and its association with gastritis and peptic ulcer has been strongly established in adults and children. H. pylori has also been implicated to cause gastric carcinomas. Many studies have suggested a supposed association between non-gastrointestinal tract disorders and H. pylori infection, however evidence is sparse and inconclusive. A recent review that looked into the evidence of association between H. pylori infection and non-gastrointestinal disorders has found inconclusive evidence of a causal relationship of this infection in coronary heart disease, hypertension, diabetes mellitus, thyroiditis, etc. H. pylori prevalence various across populations of children and ranges from about 10% to over 80%. Countries such as the U.S., Canada and countries in Western and Northern Europe have low prevalence. However, a high prevalence of H. pylori occurs in countries such as India, Africa, Latin America and Eastern Europe. Studies on Indians using serology and endoscopic biopsies have shown a high prevalence of H. pylori infection. An earlier study done by our centre studied 50 children (29 male and 21 female) from a lower socio-economic school in Bangalore. These children showed a high prevalence of 82% for H. pylori infection, which confirmed the high prevalence of H. pylori in Indians that was predicted by earlier serological studies
Salvador, Fernando; Sulleiro, Elena; Sánchez-Montalvá, Adrián; Martínez-Gallo, Mónica; Carrillo, Eugenia; Molina, Israel
Abstract Background 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. Methods 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). Results 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). Conclusions We observed a high prevalence of S. stercoralis infection among chronic Chagas disease patients attended in our tropical medicine unit. Strongyloidiasis was associated
textabstractThe function of the liver is to keep the human body in physiological equilibrium. This equilibrium is regulated by several metabolic pathways such as the production of plasma proteins and detoxification. Inflammation of the liver is known as hepatitis and as entity it has been recognized since the days of Hippocrates. The most important etiology of hepatitis is viral infection of the liver.
Nwolisa, Emeka; Mbanefo, Francis; Ezeogu, Joseph; Amadi, Paul
Introduction Hepatitis B infection impacts negatively on disease progression in HIV infected children thereby increasing morbidity and mortality. In spite of the foregoing, there is paucity of data on Hepatitis B co-infection in children living with HIV in Owerri, South Eastern Nigeria.This study set out to determine the prevalence of Hepatitis B Co- infection in HIV infected children attending the Paediatric HIV Care and Treatment clinic of the Federal Medical Centre Owerri. Methods The stud...
Wu, H.; Song, Z.J.; Givskov, Michael Christian;
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...
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.
Cramer, Nina; Wiehlmann, Lutz; Ciofu, Oana;
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...
Lanford, Robert E; Hildebrandt-Eriksen, Elisabeth S; Petri, Andreas; Persson, Robert; Lindow, Morten; Munk, Martin E; Kauppinen, Sakari; Ørum, Henrik
The liver-expressed microRNA-122 (miR-122) is essential for hepatitis C virus (HCV) RNA accumulation in cultured liver cells, but its potential as a target for antiviral intervention has not been assessed. We found that treatment of chronically infected chimpanzees with a locked nucleic acid (LNA...
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.
Brenner, H; Berg, Gabriele; Fröhlich, M; Boeing, H; Koenig, W
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...... with H. pylori was unrelated to C-reactive protein and the leukocyte count, regardless of CagA status. There was an inverse relation between H. pylori infection and serum albumin. The adjusted OR (95% CI) of an albumin level in the bottom versus the top third were 2.2 (1.5-3.1) and 2.0 (1.4-3.1) for...
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
Saadia Farid, Laila Rashid, Samya Swelam
Full Text Available Objective: Tumour necrosis factor (TNF-alpha, a prototype proinflammatory cytokine, has been implicated as an important pathogenic mediator in a variety of liver conditions. Some genetic polymorphisms in the human TNF-alpha promoter region, such as the G-A transitions -308 and – 238, have been shown to influence TNF-alpha expression in chronic hepatitis C virus infection.Aim of the work: The present study was to investigate the influence that the – 308 and – 238 TNF- alpha promoter polymorphisms have on the response to interferon and ribavirin therapy in chronic hepatitis C virus infection.Patients and methods: One hundred forty patients with chronic hepatitis C virus infection, their age ranges between (20-56 years, selected from the National Hepatology and Tropical Medicine Research Institute were included in this study, during interferon and ribavirin therapy and thirty five healthy individuals were included to serve as controls, the patients and controls were divided into two groups the first group forty patients and fifteen controls for the detection of TNF-alpha -308, -238 genotypes polymorphisms, the second group were one hundred patients and twenty healthy controls for the detection of serum levels of TNF-α. All the patients and controls were subjected to the following history, clinical examination, abdominal ultrasonography and collection of blood samples for routine laboratory investigation, CBCs and serological assay, genotyping of 308, 238 TNF-alpha promoter polymorphism and serum levels of TNF-α.Results: There was no statistically significant difference between chronic HCV patients and healthy controls as regarding TNF-alpha -238 different alleles.The frequencies of TNF-alpha gene polymorphism with A/G and G/G mutation at – 308 were significantly higher in chronic HCV patients than those in the controls. The serum level of TNF-alpha was markedly higher in the chronic HCV patients than in the healthy controls. There were
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)
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
Full Text Available Listeriosis is an under-diagnosed and under-reported infection; however, listeriosis is not a compulsorily notifiable disease in Brazil. We provide an overview of the rates of listeriosis in the United States of America (USA, Europe, Latin America, and Brazil during the past decade. We also report a case of miscarriage caused by listeriosis in which there was no suspicion of this infection. This overview and the case we report serve as reminders of the often-neglected threat of listeriosis and its potential to cause miscarriage while highlighting the necessity of recognizing listeriosis as a compulsorily notifiable disease in Brazil.
Listeriosis is an under-diagnosed and under-reported infection; however, listeriosis is not a compulsorily notifiable disease in Brazil. We provide an overview of the rates of listeriosis in the United States of America (USA), Europe, Latin America, and Brazil during the past decade. We also report a case of miscarriage caused by listeriosis in which there was no suspicion of this infection. This overview and the case we report serve as reminders of the often-neglected threat of listeriosis a...
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.
Conclusions: The transmissibility of Zika virus infection appears to be comparable to those of dengue and chikungunya viruses. Considering that Aedes species are a shared vector, this finding indicates that Zika virus replication within the vector is perhaps comparable to dengue and chikungunya.
Tomasik, Jakub; Schultz, Tracey L; Kluge, Wolfgang; Yolken, Robert H; Bahn, Sabine; Carruthers, Vern B
Chronic 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 model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis. PMID:26392628
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
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.
Alves de Medeiros, Ana Karina; Lodewick, Evelyn; Bogaert, Delfien J A; Haerynck, Filomeen; Van Daele, Sabine; Lambrecht, Bart; Bosma, Sara; Vanderdonckt, Laure; Lortholary, Olivier; Migaud, Mélanie; Casanova, Jean-Laurent; Puel, Anne; Lanternier, Fanny; Lambert, Jo; Brochez, Lieve; Dullaers, Melissa
Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp., dermatophytes (e.g., Trichophyton spp.) and phaeohyphomycetes (Exophiala spp., Phialophora verrucosa). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony-stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans. Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition. PMID:26961233
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.
Full Text Available Streptococcus pneumoniae is the commonest cause of bacteremic pneumonia among HIV-infected persons. As more countries with high HIV prevalence are implementing infant pneumococcal conjugate vaccine (PCV programs, we aimed to describe the baseline clinical characteristics of adult invasive pneumococcal disease (IPD in the pre-PCV era in South Africa in order to interpret potential indirect effects following vaccine use.National, active, laboratory-based surveillance for IPD was conducted in South Africa from 1 January 2003 through 31 December 2008. At 25 enhanced surveillance (ES hospital sites, clinical data, including HIV serostatus, were collected from IPD patients ≥ 5 years of age. We compared the clinical characteristics of individuals with IPD in those HIV-infected and -uninfected using multivariable analysis. PCV was introduced into the routine South African Expanded Program on Immunization (EPI in 2009.In South Africa, from 2003-2008, 17 604 cases of IPD occurred amongst persons ≥ 5 years of age, with an average incidence of 7 cases per 100 000 person-years. Against a national HIV-prevalence of 18%, 89% (4190/4734 of IPD patients from ES sites were HIV-infected. IPD incidence in HIV-infected individuals is 43 times higher than in HIV-uninfected persons (52 per 100 000 vs. 1.2 per 100 000, with a peak in the HIV-infected elderly population of 237 per 100 000 persons. Most HIV-infected individuals presented with bacteremia (74%, 3 091/4 190. HIV-uninfected individuals were older; and had more chronic conditions (excluding HIV than HIV-infected persons (39% (210/544 vs. 19% (790/4190, p<0.001. During the pre-PCV immunization era in South Africa, 71% of serotypes amongst HIV-infected persons were covered by PCV13 vs. 73% amongst HIV-uninfected persons, p = 0.4, OR 0.9 (CI 0.7-1.1.Seventy to eighty-five percent of adult IPD in the pre-PCV era were vaccine serotypes and 93% of cases had recognized risk factors (including HIV-infection for
Full Text Available An estimated 34 million people are living with HIV worldwide (UNAIDS, 2012, with the number of infected persons rising every year. Increases in HIV prevalence have resulted not only from new infections, but also from increases in the survival of HIV-infected persons produced by effective anti-retroviral therapies. Augmentation of anti-viral immune responses may be able to further increase the survival of HIV-infected persons. One strategy to augment these responses is to reinvigorate exhausted anti-HIV immune cells present in chronically infected persons. The PD-1-PD-L1 pathway has been implicated in the exhaustion of virus-specific T cells during chronic HIV infection. Inhibition of PD-1 signaling using blocking anti-PD-1 antibodies has been shown to reduce simian immunodeficiency virus (SIV loads in monkeys. We now show that PD-1 blockade can improve control of HIV replication in vivo in an animal model. BLT (Bone marrow-Liver-Thymus humanized mice chronically infected with HIV-1 were treated with an anti-PD-1 antibody over a 10-day period. The PD-1 blockade resulted in a very significant 45-fold reduction in HIV viral loads in humanized mice with high CD8(+ T cell expression of PD-1, compared to controls at 4 weeks post-treatment. The anti-PD-1 antibody treatment also resulted in a significant increase in CD8(+ T cells. PD-1 blockade did not affect T cell expression of other inhibitory receptors co-expressed with PD-1, including CD244, CD160 and LAG-3, and did not appear to affect virus-specific humoral immune responses. These data demonstrate that inhibiting PD-1 signaling can reduce HIV viral loads in vivo in the humanized BLT mouse model, suggesting that blockade of the PD-1-PD-L1 pathway may have therapeutic potential in the treatment of patients already infected with the AIDS virus.
Melvang, Heidi Mikkelsen; Grønbæk, Betina Chemnitz; Brogaard, Louise;
Mycobacterium avium subsp. paratuberculosis (Map) causes paratuberculosis, a chronic enteritis of ruminants. The aim of the study was to use high-throughput reverse transcriptase (RT) qPCR to describe intestinal gene expression patterns in response to different levels of Map infection with a large...... expected, leads to increased expression of local IFN-γ. Expression of IL-10 also increased as a result of Map infection, and this increase was more correlated to the amount of Map than IFN-γ, indicating a shift towards a regulatory environment as infection progress. Th17-mediated immune responses were...... suppressed at this stage. Gene expression of all other genes could not be interpreted in relation to infection status. High throughput RT qPCR can be used for exploring gene expression patterns in response to Map infection but larger study groups are needed to fully understand which are key mechanisms and...
Li, Xi; Wiesen, Eric; Diorditsa, Sergey; Toda, Kohei; Duong, Thi Hong; Nguyen, Lien Huong; Nguyen, Van Cuong; Nguyen, Tran Hien
Adverse Events Following Immunization in Viet Nam in 2013 led to substantial reductions in hepatitis B vaccination coverage (both the birth dose and the three-dose series). In order to estimate the impact of the reduction in vaccination coverage on hepatitis B transmission and future mortality, a widely-used mathematical model was applied to the data from Viet Nam. Using the model, we estimated the number of chronic infections and deaths that are expected to occur in the birth cohort in 2013 and the number of excessive infections and deaths attributable to the drop in immunization coverage in 2013. An excess of 90,137 chronic infections and 17,456 future deaths were estimated to occur in the 2013 birth cohort due to the drop in vaccination coverage. This analysis highlights the importance of maintaining high vaccination coverage and swiftly responding to reported Adverse Events Following Immunization in order to regain consumer confidence in the hepatitis B vaccine. PMID:26055296
Arabella K. M. Hayter
Full Text Available Background: Chronic diseases are now the leading cause of death and disability worldwide; this epidemic has been linked to rapid economic growth and urbanisation in developing countries. Understanding how characteristics of the physical, social, and economic environment affect behaviour in the light of these changes is key to identifying successful interventions to mitigate chronic disease risk. Design: We undertook a qualitative study consisting of nine focus group discussions (FGDs (n=57 in five villages in rural Andhra Pradesh, South India, to understand people's perceptions of community development and urbanisation in relation to chronic disease in rural transitional communities. Specifically, we sought to understand perceptions of change linked to diet, physical activity, and pollution (because these exposures are most relevant to chronic diseases, with the aim of defining future interventions. The transcripts were analysed thematically. Results: Participants believed their communities were currently less healthy, more polluted, less physically active, and had poorer access to nutritious food and shorter life expectancies than previously. There were contradictory perceptions of the effects of urbanisation on health within and between individuals; several of the participants felt their quality of life had been reduced. Conclusions: In the present study, residents viewed change and development within their villages as an inevitable and largely positive process but with some negative health consequences. Understanding how these changes are affecting populations in transitional rural areas and how people relate to their environment may be useful to guide community planning for health. Measures to educate and empower people to make healthy choices within their community may help reduce the spread of chronic disease risk factors in future years.
Full Text Available Chytridiomycosis has been identified as a major cause of global amphibian declines. Despite widespread evidence of Batrachochytrium dendrobatidis infection in South African frogs, sampling for this disease has not focused on threatened species, or whether this pathogen poses a disease risk to these species. This study assessed the occurrence of Bd-infection in South African Red List species. In addition, all known records of infection from South Africa were used to model the ecological niche of Bd to provide a better understanding of spatial patterns and associated disease risk. Presence and prevalence of Bd was determined through quantitative real-time PCR of 360 skin swab samples from 17 threatened species from 38 sites across the country. Average prevalence was 14.8% for threatened species, with pathogen load varying considerably between species. MaxEnt was used to model the predicted distribution of Bd based on 683 positive records for South Africa. The resultant probability threshold map indicated that Bd is largely restricted to the wet eastern and coastal regions of South Africa. A lack of observed adverse impacts on wild threatened populations supports the endemic pathogen hypothesis for southern Africa. However, all threatened species occur within the limits of the predicted distribution for Bd, exposing them to potential Bd-associated risk factors. Predicting pathogen distribution patterns and potential impact is increasingly important for prioritising research and guiding management decisions.
Oxidative stress as a contributor to neuronal death during prion infection is supported by the fact that various oxidative damage markers accumulate in the brain during the course of this disease. The normal cellular substrate of the causative agent, the prion protein, is also linked with protective functions against oxidative stress. Our previous work has found that, in chronic prion infection, an apoptotic subpopulation of cells exhibit oxidative stress and the accumulation of oxidised lipid and protein aggregates with caspase recruitment. Given the likely failure of antioxidant defence mechanisms within apoptotic prion-infected cells, we aimed to investigate the role of the crucial antioxidant pathway components, superoxide dismutases (SOD 1 and 2, in an in vitro model of chronic prion infection. Increased total SOD activity, attributable to SOD1, was found in the overall population coincident with a decrease in SOD2 protein levels. When apoptotic cells were separated from the total population, the induction of SOD activity in the infected apoptotic cells was lost, with activity reduced back to levels seen in mock-infected control cells. In addition, mitochondrial superoxide production was increased and mitochondrial numbers decreased in the infected apoptotic subpopulation. Furthermore, a pan-caspase probe colocalised with SOD2 outside of mitochondria within cytosolic aggregates in infected cells and inhibition of caspase activity was able to restore cellular levels of SOD2 in the whole unseparated infected population to those of mock-infected control cells. Our results suggest that prion propagation exacerbates an apoptotic pathway whereby mitochondrial dysfunction follows mislocalisation of SOD2 to cytosolic caspases, permitting its degradation. Eventually, cellular capacity to maintain oxidative homeostasis is overwhelmed, thus resulting in cell death.
C E Martin
Full Text Available The high burden of HIV and tuberculosis (TB among pregnant women in South Africa contributes to a high maternal mortality rate. Isoniazid preventive therapy (IPT is recommended for the prevention of active TB in HIV-infected individuals, including pregnant women. However, there are few data regarding IPT use in the latter, with concern regarding the concurrent use of IPT with nevirapine in pregnancy, as both treatments are hepatotoxic. The benefit and safety of IPT in HIV-infected pregnant women has not been established. We recommend a simplification of HIV and TB interventions by providing triple antiretroviral therapy to all HIV-infected pregnant women.
Schlosser, Josephine; Vina-Rodriguez, Ariel; Fast, Christine; Groschup, Martin H; Eiden, Martin
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. PMID:26344041
Youn, Jin-Won; Hu, Yu-Wen; Tricoche, Nancy; Pfahler, Wolfram; Shata, Mohamed Tarek; Dreux, Marlene; Cosset, François-Loic; Folgori, Antonella; Lee, Dong-Hun; Brotman, Betsy; Prince, Alfred M.
Given the failures of nonreplicating vaccines against chronic hepatitis C virus (HCV) infection, we hypothesized that a replicating viral vector may provide protective immunity. Four chimpanzees were immunized transdermally twice with recombinant vaccinia viruses (rVV) expressing HCV genes. After challenge with 24 50% chimpanzee infective doses of homologous HCV, the two control animals that had received only the parental VV developed chronic HCV infection. All four immunized animals resolved...
McDermott, S; Szwejbka, L; Mann, H; Durkin, M; Callaghan, W
This study presents evidence that over 20 percent of pregnant women with a UTI in South Carolina did not have an antibiotic pharmacy claim within 14 days of diagnosis. Untreated maternal UTI in pregnancy was associated with a 22 percent increased risk for MR/DD in the infant compared to the risk for women who had a UTI and a pharmacy claim for an antibiotic and 31 percent increased risk compared to women who did not have a UTI. The importance of medications compliance should be emphasized in the care of pregnant women. PMID:11381775
Christopher, Devasahayam J; Daley, Peter; Armstrong, Lois; James, Prince; Gupta, Richa; Premkumar, Beulah; Michael, Joy Sarojini; Radha, Vedha; Zwerling, Alice; Schiller, Ian; Dendukuri, Nandini; Pai, Madhukar
Background Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB) patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India. Methodology/Principal Findings Among 535 nursing students enrolled in 2007,...
Kallio, Eva R; Helle, Heikki; Koskela, Esa; Mappes, Tapio; Vapalahti, Olli
1. Pathogens often cause detrimental effects to their hosts and, consequently, may influence host population dynamics that may, in turn, feed back to pathogen transmission dynamics. Understanding fitness effects of pathogens upon animal host populations can help to predict the risks that zoonotic pathogens pose to humans. 2. Here we determine whether chronic infection by Puumala hantavirus (PUUV) affects important fitness-related traits, namely the probability of breeding, reproductive effort and mother and offspring condition, in the bank vole (Myodes glareolus). Using 9 years empirical data in a PUUV endemic area in Central Finland, we found differences between reproductive characteristics of PUUV-infected and uninfected female bank voles. 3. Young infected females had a significantly higher, and old individuals lower, likelihood of reproducing than uninfected animals during the middle of the breeding season. The implication is that PUUV infection may have long-term deleterious effects that are observed at old age, while in young individuals, the infection may enhance breeding probability by directing resources towards current breeding. 4. Moreover, PUUV infection was related with the mother's body condition. Infected mothers were in poorer condition than uninfected mothers in the early breeding season, but were in better condition than uninfected mothers during the middle of the breeding season. Offspring body condition was positively associated with mother's body condition, which, in turn, was related to the PUUV infection status of the mother. 5. Our findings indicate that chronic infection may affect the reproduction of female hosts, but the effect is dependent on the host age. The effect of chronic hantavirus infection was small and density-independent and hence unlikely to contribute to the cyclic population dynamics of the host. However, the effects on a female's reproductive output might affect the abundance of young susceptible individuals in the
Meenakshi; Sachdeva; Yogesh; K; Chawla; Sunil; K; Arora
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.
Steven K. Lundy
Full Text Available Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways.
Stypułkowska, Jadwiga; Lyszczarz, Robert; Błazowska, Katarzyna
Chronic dental infections, even of low intensity, may cause the development of atherosclerotic changes in arteries, that lead to coronary heart disease. There are many risk factors for atherosclerosis, but the most important are endothelium function disturbances, platelets activation and oxidative changes of plasmatic lipoproteins. Among factors that can induce the epithelium lesions bacterial factor may play an important role. In consequence of the bacterial cell breakdown place the release of endotoxins takes, that lead directly to the damage of endothelial cells. Apart from this direct effect endotoxins activate the fagocytes releasing superoxide reactive radicals, that cause lesions of endothelium. Probably the most widespread chronic bacterial infections in human are the diseases of periodontium and teeth and their inflammatory complications. Oral cavity is colonized by 300-400 bacterial species. In the case of dental bacterial infections bacteriemia occurs after such procedures as tooth extraction, endodontic treatment, therapeutic and hygienic interventions on periodontal tissues. The results of many investigations show the relationship between the oral status (dental and periodontal diseases as chronic oral infections) and disorders of cardiovascular system. PMID:17474623
Devasahayam J Christopher
Full Text Available BACKGROUND: Among healthcare workers in developing countries, nurses spend a large amount of time in direct contact with tuberculosis (TB patients, and are at high risk for acquisition of TB infection and disease. To better understand the epidemiology of nosocomial TB among nurses, we recruited a cohort of young nursing trainees at Christian Medical College, a large, tertiary medical school hospital in Southern India. METHODOLOGY/PRINCIPAL FINDINGS: Among 535 nursing students enrolled in 2007, 468 gave consent to participate, and 436 underwent two-step tuberculin skin testing (TST. A majority (95% were females, and almost 80% were under 22 years of age. Detailed TB exposure information was obtained using interviews and clinical log books. Prevalence of latent TB infection (LTBI was estimated using Bayesian latent class analyses (LCA. Logistic regression analyses were done to determine the association between LTBI prevalence and TB exposure and risk factors. 219 of 436 students (50.2%, 95% CI: 45.4-55.0 were TST positive using the 10 mm or greater cut-off. Based on the LCA, the prevalence of LTBI was 47.8% (95% credible interval 17.8% to 65.6%. In the multivariate analysis, TST positivity was strongly associated with time spent in health care, after adjusting for age at entry into healthcare. CONCLUSIONS: Our study showed a high prevalence of LTBI even in young nursing trainees. With the recent TB infection control (TBIC policy guidance from the World Health Organization as the reference, Indian healthcare providers and the Indian Revised National TB Control Programme will need to implement TBIC interventions, and enhance capacity for TBIC at the country level. Young trainees and nurses, in particular, will need to be targeted for TBIC interventions.
Xiong-Zhi Wu; Dan Chen; Lian-San Zhao; Xiao-Hui Yu; Mei Wei; Yan Zhao; Qing Fang; Qian Xu
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
Full Text Available Background: To counter the global increase in infection-related deaths, infection control has recently developed into an active area of research. Many diseases can be prevented by infection control. In the confines of the audiology clinic, cross-contamination by micro-organisms associated with opportunistic infections remains a real concern.Objective: The primary aim of the study was to ascertain the methods that audiologists in South Africa use to prevent and control the spread of infections during and after consultation with clients.Method: A survey study was conducted, using a self-administered questionnaire. Fifty currently practising audiologists participated in the study.Results: The majority (84%; n = 42 of respondents acknowledged the importance of hand hygiene for the purpose of infection control, with 76% (n = 38 making use of no-rinse hand sanitisers. Approximately a third of audiologists wear gloves during procedures such as otoscopy and immittance, and while handling hearing aids. Disinfecting audiological equipment seem to be the preferred choice of infection control, with only 60% (n = 30 of respondents sterilising audiological equipment after each individual patient consultation. Less than half of the respondents disinfected touch surfaces and toys in the reception area.Conclusions: Based on the results, further education and training should focus on measures implemented in infection control, awareness of possible risk factors at work settings, and vaccination as an effective means of infection control.
Ridruejo, Ezequiel; Bessone, Fernando; Daruich, Jorge R; Estes, Chris; Gadano, Adrián C; Razavi, Homie; Villamil, Federico G; Silva, Marcelo O
AIM: To estimate the progression of the hepatitis C virus (HCV) epidemic and measure the burden of HCV-related 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 liver-related 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.
Joensen, Odin; Paff, Tamara; Haarman, Eric G;
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...
Full Text Available Abstract Background Bladder cancer is a common malignancy in Egypt. A history of urinary tract infection can be considered as a risk factor for bladder cancer. Escherichia coli (E. coli infection is responsible for 70% of urinary tract infection. This study aimed to evaluate the role of chronic E. coli infection during bladder carcinogenesis. In order to achieve this aim, we investigated the histopathological changes in bladder tissue and measured the level of nuclear factor kappa p65 (NF-κBp65, Bcl-2 and interleukin 6 (IL-6 in four groups each consisting of 25 male albino rats except of control group consisting of 20 rats. The first group was normal control group, the second group was infected with E. coli, the third group was administered nitrosamine precursor, and the forth group was infected with E. coli and administered nitrosamine precursor. Results The histopathological examination revealed that E. coli infected group was able alone to produce some histopathological changes in bladder tissue and that nitrosamine precursor plus E. coli group showed highest incidences of urinary bladder lesions than the nitrosamine precursor group. NF-κBp65, Bcl-2 and IL-6 levels were significantly higher in nitrosamine precursor plus E. coli group than the other groups. Conclusion These findings suggested that urinary bladder infection by E. coli may play a major additive and synergistic role during bladder carcinogenesis.
Ewers, U; Weisser, L; Wegner, A
Suppression by lead of resistance to bacterial or viral infections has been reported by several authors. We have studied, if a decrease of resistance to bacterial infection could be evaluated at blood lead concentrations (PbB), which correspond to the upper levels of environmental or occupational lead exposure regarded as tolerable (PbB = 35 resp. 60 microgram/100 ml). NMRI mice were chronically exposed to lead by feeding with lead acetate containing diets and given a challenge with Salmonella typhimurium. No increase of susceptibility to bacterial infection could be demonstrated at PbB 100 microgram/100 g, however, an increase of lethality and a decrease of 50% survival times could be observed after bacterial infection. PMID:6999813
McGranahan, D A; Burgdorf, R; Kirkman, K P
Fungal endophytes have been documented in almost all terrestrial plant groups. Although the endophyte infection syndrome in agronomic cultivars is well studied, relatively little work addresses questions of spatial ecology and fire effects on epichloae endophyte infection in native grasses, and none, to our knowledge, in sub-Saharan Africa. We sampled seven populations of the native Festuca costata Nees along the spline of the Drakensberg range in South Africa at several spatial scales, including both recently burned and unburned stands. We tested epichloae presence and prevalence with immunoblot assays, PCR and genetic sequencing. We found epichloae endophytes were present and prevalent (38-98% infection rates depending on location). Variation in infection rates occurred primarily among locations, but also among bunches. There was little evidence that endophyte infection rates varied with fire. Novel evidence of epichloae infection of a native Festuca in South Africa opens the door to several new research questions, from the phylogenetic relationship between epichloae of sub-Saharan Africa and other continents to the ecological advantages or disadvantages that endophytes confer upon their hosts, especially in a fire-prone ecosystem vulnerable to global environmental change. PMID:25619128
Mathiason, Candace K; Hayes-Klug, Jeanette; Hays, Sheila A; Powers, Jenny; Osborn, David A; Dahmes, Sallie J; Miller, Karl V; Warren, Robert J; Mason, Gary L; Telling, Glenn C; Young, Alan J; Hoover, Edward A
Substantial evidence for prion transmission via blood transfusion exists for many transmissible spongiform encephalopathy (TSE) diseases. Determining which cell phenotype(s) is responsible for trafficking infectivity has important implications for our understanding of the dissemination of prions, as well as their detection and elimination from blood products. We used bioassay studies of native white-tailed deer and transgenic cervidized mice to determine (i) if chronic wasting disease (CWD) blood infectivity is associated with the cellular versus the cell-free/plasma fraction of blood and (ii) in particular if B-cell (MAb 2-104(+)), platelet (CD41/61(+)), or CD14(+) monocyte blood cell phenotypes harbor infectious prions. All four deer transfused with the blood mononuclear cell fraction from CWD(+) donor deer became PrP(CWD) positive by 19 months postinoculation, whereas none of the four deer inoculated with cell-free plasma from the same source developed prion infection. All four of the deer injected with B cells and three of four deer receiving platelets from CWD(+) donor deer became PrP(CWD) positive in as little as 6 months postinoculation, whereas none of the four deer receiving blood CD14(+) monocytes developed evidence of CWD infection (immunohistochemistry and Western blot analysis) after 19 months of observation. Results of the Tg(CerPrP) mouse bioassays mirrored those of the native cervid host. These results indicate that CWD blood infectivity is cell associated and suggest a significant role for B cells and platelets in trafficking CWD infectivity in vivo and support earlier tissue-based studies associating putative follicular B cells with PrP(CWD). Localization of CWD infectivity with leukocyte subpopulations may aid in enhancing the sensitivity of blood-based diagnostic assays for CWD and other TSEs. PMID:20219916
Damlund, Dina Silke Malling; Christophersen, Lars; Jensen, Peter Østrup; Alhede, Morten; Høiby, Niels; Moser, Claus
The majority of cystic fibrosis (CF) patients acquire chronic Pseudomonas aeruginosa lung infection, resulting in increased mortality and morbidity. The chronic P. aeruginosa lung infection is characterized by bacteria growing in biofilm surrounded by polymorphonuclear neutrophils (PMNs). However, the infection is not eradicated and the inflammatory response leads to gradual degradation of the lung tissue. In CF patients, a Th2-dominated adaptive immune response with a pronounced antibody response is correlated with poorer outcome. Dendritic cells (DCs) are crucial in bridging the innate immune system with the adaptive immune response. Once activated, the DCs deliver a set of signals to uncommitted T cells that induce development, such as expansion of regulatory T cells and polarization of Th1, Th2 or Th17 subsets. In this study, we characterized DCs in lungs and regional lymph nodes in BALB/c mice infected using intratracheal installation of P. aeruginosa embedded in seaweed alginate in the lungs. A significantly elevated concentration of DCs was detected earlier in the lungs than in the regional lymph nodes. To evaluate whether the chronic P. aeruginosa lung infection leads to activation of DCs, costimulatory molecules CD80 and CD86 were analyzed. During infection, the DCs showed significant elevation of CD80 and CD86 expression in both the lungs and the regional lymph nodes. Interestingly, the percentage of CD86-positive cells was significantly higher than the percentage of CD80-positive cells in the lymph nodes. In addition, cytokine production from Lipopolysaccharides (LPS)-stimulated DCs was analyzed demonstrating elevated production of IL-6, IL-10 and IL-12. However, production of IL-12 was suppressed earlier than IL-6 and IL-10. These results support that DCs are involved in skewing of the Th1/Th2 balance in CF and may be a possible treatment target. PMID:27009697
Nanda, Kavinderjit S
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.
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
Full Text Available Despite the production of neutralizing antibodies to hepatitis C virus (HCV, many patients fail to clear the virus and instead develop chronic infection and long-term complications. To understand how HCV infection perturbs the antibody repertoire and to identify molecular features of antibody genes associated with either viral clearance or chronic infection, we sequenced the V(DJ region of naïve and memory B cells of 6 persons who spontaneously resolved an HCV infection (SR, 9 patients with a newly diagnosed chronically evolving infection (CE, and 7 healthy donors. In both naïve and memory B cells, the frequency of use of particular antibody gene subfamilies and segments varied among the three clinical groups, especially between SR and CE. Compared to CE, SR antibody genes used fewer VH, D and JH gene segments in naïve B cells and fewer VH segments in memory B cells. SR and CE groups significantly differed in the frequency of use of 7 gene segments in naïve B cell clones and 3 gene segments in memory clones. The nucleotide mutation rates were similar among groups, but the pattern of replacement and silent mutations in memory B cell clones indicated greater antigen selection in SR than CE. Greater clonal evolution of SR than CE memory B cells was revealed by analysis of phylogenetic trees and CDR3 lengths. Pauciclonality of the peripheral memory B cell population is a distinguishing feature of persons who spontaneously resolved an HCV infection. This finding, previously considered characteristic only of patients with HCV-associated lymphoproliferative disorders, suggests that the B cell clones potentially involved in clearance of the virus may also be those susceptible to abnormal expansion.
Obieglo, Katja; Feng, Xiaogang; Bollampalli, Vishnu Priya; Dellacasa-Lindberg, Isabel; Classon, Cajsa; Österblad, Markus; Helmby, Helena; Hewitson, James P; Maizels, Rick M; Gigliotti Rothfuchs, Antonio; Nylén, Susanne
Helminth infections have been suggested to impair the development and outcome of Th1 responses to vaccines and intracellular microorganisms. However, there are limited data regarding the ability of intestinal nematodes to modulate Th1 responses at sites distal to the gut. In this study, we have investigated the effect of the intestinal nematode Heligmosomoides polygyrus bakeri on Th1 responses to Mycobacterium bovis bacillus Calmette-Guérin (BCG). We found that H. polygyrus infection localized to the gut can mute BCG-specific CD4(+) T cell priming in both the spleen and skin-draining lymph nodes. Furthermore, H. polygyrus infection reduced the magnitude of delayed-type hypersensitivity (DTH) to PPD in the skin. Consequently, H. polygyrus-infected mice challenged with BCG had a higher mycobacterial load in the liver compared with worm-free mice. The excretory-secretory product from H. polygyrus (HES) was found to dampen IFN-γ production by mycobacteria-specific CD4(+) T cells. This inhibition was dependent on the TGF-βR signaling activity of HES, suggesting that TGF-β signaling plays a role in the impaired Th1 responses observed coinfection with worms. Similar to results with mycobacteria, H. polygyrus-infected mice displayed an increase in skin parasite load upon secondary infection with Leishmania major as well as a reduction in DTH responses to Leishmania Ag. We show that a nematode confined to the gut can mute T cell responses to mycobacteria and impair control of secondary infections distal to the gut. The ability of intestinal helminths to reduce DTH responses may have clinical implications for the use of skin test-based diagnosis of microbial infections. PMID:26819205
Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P.; Lilge, Lothar
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
Fila, Grzegorz; Kasimova, Kamola; Arenas, Yaxal; Nakonieczna, Joanna; Grinholc, Mariusz; Bielawski, Krzysztof P; Lilge, Lothar
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
Kurihara, Takeshi; Yoshizumi, Tomoharu; Itoh, Shinji; Harimoto, Norifumi; Harada, Noboru; Ikegami, Toru; Inagaki, Yuki; Oshiro, Yukio; Ohkohchi, Nobuhiro; Okamoto, Hiroaki; Maehara, Yoshihiko
Although it occurs worldwide, hepatitis E virus (HEV) infection in developed countries is generally foodborne. HEV infection is subclinical in most individuals. Although fulminant liver failure may occur, progression to chronic hepatitis is rare. This study describes a 41-year-old man with liver cirrhosis caused by non-alcoholic steatohepatitis and hepatocellular carcinoma within the Milan criteria. His liver function was classified as Child-Pugh grade C. Living donor liver transplantation (LDLT) was performed, and he was discharged from the hospital on postoperative day (POD) 22. However, his alanine aminotransferase concentration began to increase on POD 60 and HEV infection was detected on POD 81. Retrospective assessments of stored blood samples showed that this patient became positive for HEV RNA on POD 3. The liver donor was negative for anti-HEV antibodies and HEV RNA. However, the platelet concentrate transfused into the liver recipient the day after LDLT was positive for HEV RNA. The patient remained positive for HEV infection for 10 months. Treatment with 800 mg/day ribavirin for 20 weeks reduced HEV RNA to an undetectable level. In conclusion, this report describes a patient infected with HEV through a blood transfusion after LDLT, who progressed to chronic hepatitis probably due to his immunosuppressed state and was treated well with ribavirin therapy. PMID:27059470
E. S. Ageeva
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.
Full Text Available Neutrophilic dermatosis of the dorsal hands, a localized form of Sweet′s syndrome, was recently described, and can be associated with several diseases including infections. Chronic hepatitis C virus infection has been proposed as a possible triggering factor. The authors present a case in which the clinical and laboratory workup diagnosis only revealed positive serology for hepatitis C virus. Although a cause-effect relation could not be proved, it might be advisable to include serology for this virus in the initial evaluation of patients with neutrophilic dermatosis.
Seyed Alireza Taghavi; Ahad Eshraghian
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.
Almushait, Mona A.; Dajem, Saad M. Bin; Elsherbiny, Nahla M.; Eskandar, Mamdoh A.; Al Azraqi, Tarik A.; Makhlouf, Laila M.
This study aimed to determine the seroprevalence of Toxoplasma gondii in pregnant women in the south western region of Saudi Arabia and to find out the possible risk factors that may lead to infection. This cross sectional hospital based study was carried out at three hospitals in the south western region of Saudi Arabia from January 2008 to August 2010. Blood samples from 487 pregnant women were collected and used to detect anti-T. gondii antibodies IgM and IgG by enzyme linked immunosorbent...
Boceprevir (Victrelis), from the oral α-ketoamide class of slow-binding reversible hepatitis C virus (HCV)-NS3 protease inhibitors, creates a new class of drugs: direct acting antivirals (DDAs). Boceprevir is highly selective against HCV serine protease. Its use is restricted to genotype 1 HCV infection and it must not be used as monotherapy. Boceprevir is given orally, rapidly absorbed, reaching plasma peak concentration within 1-2 h and is metabolized by aldo-ketoreductase and partly by the cytochrome P450 enzyme CYP3A4/5. Administration with drugs that induce or inhibit CYP3A4/5 could decrease or increase its plasma concentration. The optimal dosage is 800 mg three times daily; capsules should be taken with food. Boceprevir was approved by the US Food and Drug Administration and the European Medicines Agency and is indicated in combination with peginterferon plus ribavirin for the treatment of patients with genotype 1 HCV who have not received previous treatment or whose condition has failed to respond to previous therapy. In the Serine Protease Inhibitor Therapy 2 (SPRINT-2) trial (treatment-naïve patients) and RESPOND-2 trial (patients whose condition relapsed or did not respond to previous treatment), the boceprevir-containing regimen was always more effective than standard of care (SOC). Adverse events were similar in the treatment groups, but in the boceprevir treated group, anemia was more frequent, requiring erythropoietin in nearly 40% of cases. Discontinuation of therapy because of adverse events was identical in all treated groups. As for cost effectiveness, two studies showed that boceprevir plus SOC is cost effective with regard to the lifetime incidence of liver complications, quality of life years, and the incremental cost-effectiveness ratio. The management of this therapy is more complex than before for physicians and patients. The educational role of the physician is crucial for successful therapy and counseling should be carefully given
Bisgaard, H; Pedersen, S S; Nielsen, K G;
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......-trial histamine reactivity and the change in FEV1 in the first period in patients on budesonide. We conclude that inhaled glucocorticosteroids can be of short-term benefit in patients with CF and chronic P.a. infection and that those patients most likely to benefit from this treatment are patients with...... hyperreactive airways. Prolonged studies in larger number of patients are necessary to determine the long-term efficacy of this treatment....
Winstanley, Craig; O'Brien, Siobhan; Brockhurst, Michael A
Pseudomonas aeruginosa populations undergo a characteristic evolutionary adaptation during chronic infection of the cystic fibrosis (CF) lung, including reduced production of virulence factors, transition to a biofilm-associated lifestyle, and evolution of high-level antibiotic resistance. Populations of P. aeruginosa in chronic CF lung infections typically exhibit high phenotypic diversity, including for clinically important traits such as antibiotic resistance and toxin production, and this diversity is dynamic over time, making accurate diagnosis and treatment challenging. Population genomics studies reveal extensive genetic diversity within patients, including for transmissible strains the coexistence of highly divergent lineages acquired by patient-to-patient transmission. The inherent spatial structure and spatial heterogeneity of selection in the CF lung appears to play a key role in driving P. aeruginosa diversification. PMID:26946977
Rudkjøbing, Vibeke B; Thomsen, Trine R; Alhede, Morten; Kragh, Kasper N; Nielsen, Per H; Johansen, Ulla R; Givskov, Michael; Høiby, Niels; Bjarnsholt, Thomas
molecular methods. Tissue and sputum samples (n = 34) from explanted lungs of five end-stage patients were examined along with routine expectorates (n = 15) from 13 patients with non-end-stage CF, representing earlier stages of chronic lung infections. Previously, using peptide nucleic acid (PNA......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......RNA gene analysis (J Clin Microbiol 2011, 49: 4352). Conversely, the non-end-stage patients were found to harbor several species by culturing. PNA FISH confirmed heterogeneous microbiota and showed that the bacteria were located in monospecies aggregates with no apparent physical interaction between the...
Brok, Jesper; Gluud, Lise L; Gluud, Christian
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...... vs interferon alone for treatment of patients with chronic hepatitis C infection. Randomized trials were included irrespective of blinding, language, or publication status. Trials were identified through the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Library, MEDLINE...... events. Previous antiviral therapy (treatment-naive patients, relapsers, or nonresponders), patient characteristics, treatment regimen, methodological quality, and duration of follow-up were extracted. We included 72 trials with a total of 9991 enrolled patients. Treatment with ribavirin plus interferon...
E. S. Ageeva; V. M. Iptyshev; O. V. Stygasheva; N. V. Ryasantseva
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 intens...
Evrosimovska, Biljana; Dimova, Cena
Inflammation involved various genes. Gene polymorphisms are contributing factors in the pathogenesis of inflammation. The promontory region of some matrix metalloproteinase’s (MMP) detected polymorphisms of the DNA (those promontory regions controlled transcription of the gene). Identification of genetic factors which are of enormous meaning for establishing of different profile of patients who will develop chronic periapical lesion or acute odontogenic infection, as well as, calculation o...
Dimitra Peppa; Lorenzo Micco; Alia Javaid; Kennedy, Patrick T.F.; Anna Schurich; Claire Dunn; Celeste Pallant; Gidon Ellis; Pooja Khanna; Geoffrey Dusheiko; Gilson, Richard J.; Mala K Maini
NK cells are enriched in the liver, constituting around a third of intrahepatic lymphocytes. We have previously demonstrated that they upregulate the death ligand TRAIL in patients with chronic hepatitis B virus infection (CHB), allowing them to kill hepatocytes bearing TRAIL receptors. In this study we investigated whether, in addition to their pathogenic role, NK cells have antiviral potential in CHB. We characterised NK cell subsets and effector function in 64 patients with CHB compared to...
Aizawa, Naoko; Nakazawa, Toru; Shimura, Masahiko
Ocular complications of chronic active Epstein–Barr virus (EBV) infection have rarely been reported and are usually associated with systemic symptoms. We described a 17-year-old boy with unilateral optic disc swelling without any systemic symptoms at the initial onset. Antibody titers to EBV were markedly elevated. Treatment with immunosuppressants and corticosteroids dramatically relieved all his symptoms, including unilateral optic swelling and visual field abnormalities.
Fabrizi, Fabrizio; Messa, Piergiorgio
Recent evidence has been accumulated showing a negative impact of chronic hepatitis C virus infection on survival in patients with chronic kidney disease. Moreover, it appears that anti-HCV positive status has been associated with an increased risk of developing chronic kidney disease in the adult general population. These reports have emphasized the need for safe and effective therapies for hepatitis C virus infection in the chronic kidney disease population. Treatment of HCV has made considerable progress with the approval of interferon-free, direct-acting antiviral drug-based combination therapies among patients with intact kidneys; but a paucity of information exists regarding chronic kidney disease patients. The first published report on the antiviral treatment of hepatitis C among patients with chronic kidney disease (stage 4-5) and HCV genotype 1 concerns the combination of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor); excellent safety and efficacy (sustained viral response, 94.3% 115/122) have been reached. In another study, the 3-D regimen (ombitasvir/ paritaprevir/ ritonavir/ dasabuvir with or without ribavirin) has been administered to CKD (stage 4-5) patients with genotype 1 (n=20); the rate of sustained viral response was excellent (90%, 18/20) and no patients discontinued treatment due to adverse events. Preliminary data on the combined treatment of sofosbuvir (NS5B inhibitor) and simeprevir (NS3/4A inhibitor) has given a viral response of 89% (34/38), but the size of the study group (n=38 patients with end-stage renal disease) was small. Thus, the evidence in the medical literature concerning use of DAAs in CKD population is encouraging even if it has a preliminary nature. Also, several points need to be addressed regarding the use of DAAs in CKD population including their impact on survival, costs, and drug-drug interactions. PMID:27545640
Syed Azhar Syed Sulaiman
Full Text Available 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 a year retrospective with six months prospective study (from Jan 2007 to May 2008 was conducted in three methadone clinics of Pinang state, Malaysia. All the registered patients were included in the study and data was collected through special design data collection form by reviewing the medical profiles. Results: Findings showed HIV/AIDS was found in 2.3%, HCV 76.3%, HBV 3.3%, while 37.7% respondents were identified impaired liver function. The risk combination was HCV with impaired liver function identified in 39.5% respondents. None of them receives any supportive management treatment for the current chronic infectious condition. Conclusion: This study highly recommends producing necessary resources for the management treatment of Drug addicts for such chronic infection, as further delay can possibly increase the risk to transmit the infection in the society.
Kumar, G Aditya; Roy, Saptarshi; Jafurulla, Md; Mandal, Chitra; Chattopadhyay, Amitabha
Leishmania are obligate intracellular protozoan parasites that invade and survive within host macrophages leading to leishmaniasis, a major cause of mortality and morbidity worldwide, particularly among economically weaker sections in tropical and subtropical regions. Visceral leishmaniasis is a potent disease caused by Leishmania donovani. The detailed mechanism of internalization of Leishmania is poorly understood. A basic step in the entry of Leishmania involves interaction of the parasite with the host plasma membrane. In this work, we have explored the effect of chronic metabolic cholesterol depletion using lovastatin on the entry and survival of Leishmania donovani in host macrophages. We show here that chronic cholesterol depletion of host macrophages results in reduction in the attachment of Leishmania promastigotes, along with a concomitant reduction in the intracellular amastigote load. These results assume further relevance since chronic cholesterol depletion is believed to mimic physiological cholesterol modulation. Interestingly, the reduction in the ability of Leishmania to enter host macrophages could be reversed upon metabolic replenishment of cholesterol. Importantly, enrichment of host membrane cholesterol resulted in reduction in the entry and survival of Leishmania in host macrophages. As a control, the binding of Escherichia coli to host macrophages remained invariant under these conditions, thereby implying specificity of cholesterol requirement for effective leishmanial infection. To the best of our knowledge, these results constitute the first comprehensive demonstration that an optimum content of host membrane cholesterol is necessary for leishmanial infection. Our results assume relevance in the context of developing novel therapeutic strategies targeting cholesterol-mediated leishmanial infection. PMID:27319380
Roy, Abhik; Lichtiger, Simon
Background Prolonged antibiotic use is limited by several adverse effects, one of which is Clostridium difficile infection (CDI). The aim of this study was to determine the incidence of CDI in patients receiving chronic antibiotic treatment for Crohn’s disease (CD). Methods We conducted a retrospective review of 100 patients with CD for which ≥6 months of outpatient antibiotic therapy was prescribed. Data were collected regarding demographics, CD phenotype, treatment history, and CDI. The incidence of CDI in our patient population was calculated and compared with historical controls. Results 100 patients were studied—60% of men, mean age 23.9 years at CD diagnosis. Eighty-two percent had disease involving the ileum, and 33% had disease involving the colon. The mean duration of antibiotic therapy was 39.6 months (range, 6–217 months). The most commonly prescribed classes of antibiotics were fluoroquinolones (84%), penicillins (57%), and cephalosporins (32%). Forty-nine percent of patients were treated with concomitant thiopurines, 45% with budesonide, and 41% with biologics. The overall incidence of CDI was 2%. This incidence of CDI was lower than previously reported for non-CD patients receiving chronic antibiotics for continuous-flow left ventricular assist device infections (12.5%) and orthopedic prosthesis infections (22.2%). Conclusions The incidence of CDI is rare in patients receiving chronic antibiotic treatment for CD, and it seems significantly lower than for non-CD populations reported in the literature. PMID:26650148
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.
Gehring, Adam J; Ann D'Angelo, June
Therapeutic vaccines to boost endogenous T-cell immunity rely on the stimulatory capacity of dendritic cells (DCs). The functionality of DCs in chronic hepatitis B virus (HBV) infection has been a long-standing debate. Therefore, we have attempted to summarize multiple studies investigating DC function in chronic HBV patients to determine whether common observations can be drawn. We found that the frequency and function of ex vivo-tested myeloid and plasmacytoid DCs were largely intact in patients with HBV infection and similar to those of healthy donor DCs. The main exception was reduced IFN-α production by plasmacytoid DC from chronic HBV patients. This reduced IFN-α production correlated with liver inflammation in multiple studies but not with viral load, suggesting that viral antigens have little effect on DC function. The majority of the confusion about DC function arises from studies reporting the reduced function of healthy donor DCs exposed to various sources of HBV in vitro. These direct effects of viral antigens are in contrast to data from HBV-infected patients. The variations in the assays used and areas that require further investigation are also covered. PMID:25363524
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
Full Text Available The aim of the investigation is to prove the use of plazmapherez in pregnant women with combination of chronic placental insufficiency and urogenital infection. Materials and Methods. There were examined 190 pregnant women with chronic active urogenital infection and chronic placental insufficiency in whom current therapy was inefficient. The diagnostics included the clinical and laboratory methods. There was used polymerase chain reaction in real time, and enzyme-linked immunoassay. Results. Plasmapheresis was stated to improve significantly the blood flow in “mother–placenta–child” system by extraction of pathologic metabolites from liquid media, oxidation-reduction process activation, and hemostasis normalization. The use of plasmapheresis to treat chronic placental insufficiency in pregnant women with urogenital infection enables to increase the therapy efficiency. It leads to no allergization, and minimizes the infection negative effect on the organism of the mother and the fetus.
Hoenigl, Martin; Wagner, Jasmin; Raggam, Reinhard B.; Prueller, Florian; Prattes, Juergen; Eigl, Susanne; Leitner, Eva; Hönigl, Katharina; Valentin, Thomas; Zollner-Schwetz, Ines; Grisold, Andrea J.; Krause, Robert
Purpose The objective of this study was to compare epidemiology, causative pathogens, outcome, and levels of laboratory markers of inflammation of community-onset (i.e. community-acquired and healthcare-associated) and hospital-acquired bloodstream infection (BSI) in South-East Austria. Methods In this prospective cohort study, 672 patients fulfilling criteria of systemic inflammatory response syndrome with positive peripheral blood cultures (277 community-onset [192 community-acquired, 85 he...
Esteban-Gil, A; Grisez, C; Prevot, F; Florentin, S; Decaudin, A; Picard-Hagen, N; Berthelot, X; Ronsin, P; Alzieu, J P; Marois, M; Corboz, N; Peglion, M; Vilardell, C; Liénard, E; Bouhsira, E; Castillo, J A; Franc, M; Jacquiet, P
Bovine besnoitiosis is a chronic and debilitating disease observed in many European countries that may cause important economic losses in cattle. The recent widespread of the parasite in Europe had led the European Food Safety Authority to declare bovine besnoitiosis as a re-emerging disease in Europe. Many aspects of the epidemiology of bovine besnoitiosis such as the main routes of transmission are still unclear and need to be further studied. Among the different hypotheses, a sexual transmission has not yet been investigated. Therefore, the aim of this study was to evaluate the presence of Besnoitia besnoiti DNA in the semen of naturally infected bulls by using a highly sensitive method (real-time qPCR). Both pre-sperm and sperm fractions of 40 bulls, including seronegative (n = 11), seropositive subclinically (n = 17), and seropositive clinically (n = 12) infected animals, were collected by electroejaculation and analyzed by real-time qPCR. No B. besnoiti DNA was detected in 27 pre-sperm and 28 sperm fractions of the 40 examined bulls, suggesting that the transmission of B. besnoiti infection by the semen of chronically infected bulls is very unlikely. PMID:24802865
Bianconi, Irene; Milani, Andrea; Cigana, Cristina; Paroni, Moira; Levesque, Roger C.; Bertoni, Giovanni; Bragonzi, Alessandra
The opportunistic pathogen Pseudomonas aeruginosa can establish life-long chronic infections in the airways of cystic fibrosis (CF) patients. Persistent lifestyle is established with P. aeruginosa patho-adaptive variants, which are clonal with the initially-acquired strains. Several reports indicated that P. aeruginosa adapts by loss-of-function mutations which enhance fitness in CF airways and sustain its clonal expansion during chronic infection. To validate this model of P. aeruginosa adap...
Narayanan Kalyanaraman; Lakshmikanthan Thayumanavan; Mariakuttikan Jayalakshmi
The antiviral action of natural killer (NK) cells is regulated by a wide repertoire of germ-line encoded membrane receptors which recognize the expression of certain self-molecules on target cells. Among the receptors, killer cell immunoglobulinlikereceptor (KIR) which recognizes the expression of human leukocyte antigen (HLA) class I has a predominant role in regulating the effector functions of NK cells, particularly in viral infections. We studied a total of 128 hepatitis B virus (HBV)patients (15 acute, 43 asymptomatic, 27 chronic and 43 with other liver diseases) while attending the Department of Medical Gastroenterology, Government Rajaji Hospital, Madurai, India, and 128 ethnic matched control to find the association between the KIR : HLA genes and differential manifestations of HBV. KIR and its ligand HLA polymorphism were identified by DNAPCR methods. The activatory receptor KIR-2DS1 was significantly elevated in various disease categories, namely asymptomatic, chronic and other HBV, except acute HBV infection. Whereas, KIR 2DS3 in acute and chronic patients and KIR 2DS5 and 3DS1 in asymptomatic individuals. Among various KIR–HLA combinations, homozygous 2DS2:C1 and individuals with 3DSI:BW4 (OR = 3.23, CI = 1.55–6.7, Pc = 0.02) are associated with HBV asymptomatism, while most of the two domain inhibitory receptors with their ligands showed significant risk in other liver diseases. Further, KIR3DL1 : HLA Bw4Iso80 (OR = 3.89, 95% CI = 1.58–9.55, Pc = 0.004) is related with higher risk for asymptomatic infection when compared with chronic HBV. Thus, the select KIR : HLA alleles and combinations seem to direct the NK cell activities and immune response in different directions resulting in varied symptoms and manifestations in the subgroups of HBV-infected patientsstudied.
McPhillie, Martin; Zhou, Ying; El Bissati, Kamal; Dubey, Jitender; Lorenzi, Hernan; Capper, Michael; Lukens, Amanda K; Hickman, Mark; Muench, Stephen; Verma, Shiv Kumar; Weber, Christopher R; Wheeler, Kelsey; Gordon, James; Sanders, Justin; Moulton, Hong; Wang, Kai; Kim, Taek-Kyun; He, Yuqing; Santos, Tatiana; Woods, Stuart; Lee, Patty; Donkin, David; Kim, Eric; Fraczek, Laura; Lykins, Joseph; Esaa, Farida; Alibana-Clouser, Fatima; Dovgin, Sarah; Weiss, Louis; Brasseur, Gael; Wirth, Dyann; Kent, Michael; Hood, Leroy; Meunieur, Brigitte; Roberts, Craig W; Hasnain, S Samar; Antonyuk, Svetlana V; Fishwick, Colin; McLeod, Rima
Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites. PMID:27412848
Conrado M Fernandez-Rodriguez; Maria Luisa Gutierrez; José Luis Lledó; Maria Luisa Casas
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.
Mareli M Claassens
Full Text Available BACKGROUND: Challenges exist regarding TB infection control and TB in hospital-based healthcare workers in South Africa. However, few studies report on TB in non-hospital based healthcare workers such as primary or community healthcare workers. Our objectives were to investigate the implementation of TB infection control measures at primary healthcare facilities, the smear positive TB incidence rate amongst primary healthcare workers and the association between TB infection control measures and all types of TB in healthcare workers. METHODS: One hundred and thirty three primary healthcare facilities were visited in five provinces of South Africa in 2009. At each facility, a TB infection control audit and facility questionnaire were completed. The number of healthcare workers who had had TB during the past three years was obtained. RESULTS: The standardised incidence ratio of smear positive TB in primary healthcare workers indicated an incidence rate of more than double that of the general population. In a univariable logistic regression, the infection control audit score was significantly associated with reported cases of TB in healthcare workers (OR=1.04, 95%CI 1.01-1.08, p=0.02 as was the number of staff (OR=3.78, 95%CI 1.77-8.08. In the multivariable analysis, the number of staff remained significantly associated with TB in healthcare workers (OR=3.33, 95%CI 1.37-8.08. CONCLUSION: The high rate of TB in healthcare workers suggests a substantial nosocomial transmission risk, but the infection control audit tool which was used did not perform adequately as a measure of this risk. Infection control measures should be monitored by validated tools developed and tested locally. Different strategies, such as routine surveillance systems, could be used to evaluate the burden of TB in healthcare workers in order to calculate TB incidence, monitor trends and implement interventions to decrease occupational TB.
Perdita Wietzke-Braun; Felix Braun; Peter Schott; Giuliano Ramadori
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
Peters, Nathan C.; Pagán, Antonio J.; Lawyer, Phillip G.; Hand, Timothy W.; Henrique Roma, Eric; Stamper, Lisa W.; Romano, Audrey; Sacks, David L.
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 memor...
Zhou, Di; Guan, Wen-bin; Wang, Jian-Dong; Zhang, Yong; Gong, Wei; Quan, Zhi-wei
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...
Full Text Available Abstract Background Placental malaria (PM is associated with poor foetal development, but the pathophysiological processes involved are poorly understood. Cyclooxygenase (COX and lipoxygenase (LOX which convert fatty acids to prostaglandins and leukotrienes, play important roles in pregnancy and foetal development. COX-2, currently targeted by specific drugs, plays a dual role as it associates with both pre-eclampsia pathology and recovery during infection. The role of COX during PM was questioned by quantifying at delivery COX-1, COX-2, 15-LOX, and IL-10 expression in two groups of malaria infected and uninfected placenta. Methods Placental biopsies were collected at delivery for mRNA isolation and quantification, using real time PCR. Results COX-2 and IL-10 mRNAs increased mainly during chronic infections (nine- and five-times, respectively, whereas COX-1 transcripts remained constant. COX-2 over-expression was associated with a higher birth weight of the baby, but with a lower rate of haemoglobin of the mother. It was associated with a macrophage infiltration of the placenta and with a low haemozoin infiltration. In the opposite way, placental infection was associated with lower expression of 15-LOX mRNA. A high degree of haemozoin deposition correlates with low birth weight and decreased expression of COX-2. Conclusion These data provide evidence that COX-2 and IL-10 are highly induced during chronic infection of the placenta, but were not associated with preterm delivery or low birth weight. The data support the involvement of COX-2 in the recovery phase of the placental infection.
Charles Bitamazire Businge
Full Text Available Background: The prevalence of HIV among antenatal clients in South Africa has remained at a very high rate of about 29% despite substantial decline in several sub-Saharan countries. There is a paucity of data on risk factors for incident HIV infection among antenatal mothers and women within the reproductive age bracket in local settings in the Eastern Cape, South Africa. Objective: To establish the risk factors for incident HIV infection among antenatal clients aged 18–49 years attending public antenatal clinics in rural Eastern Cape, South Africa. Design: This was an unmatched case–control study carried out in public health antenatal clinics of King Sabata District Municipality between January and March 2014. The cases comprised 100 clients with recent HIV infection; the controls were 200 HIV-negative antenatal clients. Socio-demographic, sexual, and behavioral data were collected using interviewer-administered questionnaires adapted from the standard DHS5 women's questionnaire. Multivariate logistic regression models were used to identify the independent risk factors for HIV infection. A p<0.05 was considered statistically significant. Results: The independent risk factors for incident HIV infection were economic dependence on the partner, having older male partners especially among women aged ≤20 years, and sex under the influence of alcohol. Conclusions: Therefore, effective prevention of HIV among antenatal mothers in KSDM must target the improvement of the economic status of women, thereby reducing economic dependence on their sexual partners; address the prevalent phenomenon of cross-generation sex among women aged <20 years; and regulate the brewing, marketing, and consumption of alcohol.
Ciofu, Oana; Bagge, Niels; Høiby, Niels
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...
Full Text Available Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS. We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O, an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3(- and NO2(- in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4-157.9 µM N2O. The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3(- decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.
Diego Flichman; Veronica Kott; Silvia Sookoian; Rodolfo Campos
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.
Schulz, Claudia; Beer, Martin; Hoffmann, Bernd
During the first epizootic wave of the novel, teratogenic Schmallenberg virus (SBV, Orthobunyavirus) in ruminants in Northern Europe, serological evidence of a previous SBV-infection demonstrated that South American camelids (SAC) are also susceptible to SBV. However, their potential role in SBV spread remains unknown. To investigate the prevalence and course of SBV-infection in SAC, a German field study and an animal trial with three llamas and three alpacas were conducted. From September 2012 to December 2013, 313 of 502 SAC (62.35%) were found SBV seropositive, but negative for SBV-RNA. The estimated between-district (94.23% of 52) and median within-district (71.43%) and herd (73.13%) SBV seroprevalence in German SAC was similar to the seroprevalence reported in cattle herds and sheep flocks at the time. An age of >1 year was found a statistically significant risk factor for SBV-infection, which could be explained by the spatio-temporal spread of SBV in Germany during the study period. No clinical signs or an increase of abortion and congenital malformation associated with SBV-infection in SAC were reported by the study participants. Similar to SBV-infected ruminants, SBV-RNAemia in experimentally SBV-infected SAC was detected for a short time between days 3 and 7 after infection (dpi), and seroconversion occurred between 9 and 21 dpi. Despite the similar virological and serological results, the lack of clinical signs and congenital malformation associated with SBV-infection suggests that SBV causes subclinical infection in SAC. However, their role as reservoirs in the spread of SBV has to be further investigated. PMID:26361966