Asymptomatic Chronic Infection Research Articles

Whole-genome assembly of Babesia ovata and comparative genomics between closely related pathogens

BackgroundBabesia ovata, belonging to the phylum Apicomplexa, is an infectious parasite of bovids. It is not associated with the manifestation of severe symptoms, in contrast to other types of bovine babesiosis caused by B. bovis and B. bigemina; however, upon co-infection with Theileria orientalis, it occasionally induces exacerbated symptoms. Asymptomatic chronic infection in bovines is usually observed only for B. ovata. Comparative genomic analysis could potentially reveal factors involved in these distinguishing characteristics; however, the genomic and molecular basis of these phenotypes remains elusive, especially in B. ovata. From a technical perspective, the current development of a very long read sequencer, MinION, will facilitate the obtainment of highly integrated genome sequences. Therefore, we applied next-generation sequencing to acquire a high-quality genome of the parasite, which provides fundamental information for understanding apicomplexans.ResultsThe genome was assembled into 14,453,397 bp in size with 5031 protein-coding sequences (91 contigs and N50 = 2,090,503 bp). Gene family analysis revealed that ves1 alpha and beta, which belong to multigene families in B. bovis, were absent from B. ovata, the same as in B. bigemina. Instead, ves1a and ves1b, which were originally specified in B. bigemina, were present. The B. ovata and B. bigemina ves1a configure one cluster together even though they divided into two sub-clusters according to the spp. In contrast, the ves1b cluster was more dispersed and the overlap among B. ovata and B. bigemina was limited. The observed redundancy and rapid evolution in sequence might reflect the adaptive history of these parasites. Moreover, same candidate genes which potentially involved in the distinct phenotypes were specified by functional analysis. An anamorsin homolog is one of them. The human anamorsin is involved in hematopoiesis and the homolog was present in B. ovata but absent in B. bigemina which causes severe anemia.ConclusionsTaking these findings together, the differences demonstrated by comparative genomics potentially explain the evolutionary history of these parasites and the differences in their phenotypes. Besides, the draft genome provides fundamental information for further characterization and understanding of these parasites.

Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer.

Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention.

Duodenal strongyloidiasis infection mimicking lymphangiectasia

Strongyloides stercoralis infection usually causes a chronic asymptomatic intestinal infection or otherwise non-specific generalized complaints. The diagnosis of strongyloidiasis by routine stool examination is very limited. Endoscopic findings in strongyloidiasis range from mucosal granularity to friable edema to frank ulceration or Small bowel obstruction secondary to intense infestation. The pathological examination of tissue biopsy and aspirate can give the definitive diagnosis. We report a case of middle age patient who presented with the symptoms of weight loss and diarrhea. On evaluation, upper GI endoscopy (EGD) showed the findings of lymphangiectasia but biopsy findings were consistent with strongyloidiasis which was successfully treated with Ivermectin 200 μg/kg, given for two days.Asian Journal of Medical Sciences Vol.8(5) 2017 98-100

Lack of Geospatial Population Structure Yet Significant Linkage Disequilibrium in the Reservoir of Plasmodium falciparum in Bongo District, Ghana.

Malaria control in West Africa is impeded by the large reservoir of chronic asymptomatic Plasmodium falciparum infections in the human population. This study aimed to assess the extent of diversity in the P. falciparum reservoir in Bongo District (BD), Ghana, at the end of the dry season, the lowest point in malaria transmission over the course of the year. Analysis of the variation in 12 microsatellite loci was completed for 200 P. falciparum isolates collected from a cross-sectional survey of residents of all ages from two catchment areas in BD. Analysis of the multilocus haplotypes showed high levels of genetic diversity (He = 0.74), no population differentiation yet significant linkage disequilibrium (LD) (ISA = 0.0127, P = 0.006) in BD. Multilocus LD was significant between and within catchment areas even though every haplotype in the population was unique and the majority of individuals (84.0%) harbored multiple-clone infections. The linkage structure among multilocus haplotypes was not associated with sampling location. These data provide the first study with deep sampling of the P. falciparum reservoir in an area of seasonal malaria transmission in West Africa. The co-occurrence of high multiplicity of infection (multiple-clone infections) with significant multilocus LD is surprising given the likelihood of high recombination rates in BD. The results suggest that the linkage structure among multilocus haplotypes has not been shaped by geographic separation of parasite populations. Furthermore, the observed LD levels provide a baseline population genetic metric with putatively neutral markers to evaluate the effects of seasonality and malaria control efforts in BD.

Gram negative rod meningitis due to Strongyloides stercoralis

A 57-year-old male Mexican immigrant living in Dallas presented with altered mental status, progressive confusion, mild headache and fevers. He was diagnosed with embryonal liver sarcoma one year prior to admission and had recently started dexamethasone therapy for metastatic spinal lesions. Blood and cerebrospinal fluid cultures from a lumbar puncture were both positive for Escherichia coli. He was diagnosed with spontaneous gram negative rod (GNR) meningitis. Given his travel history, immunosuppression and GNR meningitis, a stool ova and parasite sample was obtained to screen for Strongyloides stercoralis. His stool was markedly positive for Strongyloides stercoralis larvae and he was further diagnosed with Strongyloides hyperinfection syndrome. Strongyloides is capable of chronically re-infecting human hosts without an external life cycle via autoinfection. In chronic infections, hyperinfection can be triggered with immunosuppressive medications, especially steroids. Disseminated Strongyloides should be considered as the source for unexplained GNR bacteremia or meningitis especially in immunosuppressed patients. Our patient likely had a chronic asymptomatic Strongyloides infection acquired in Mexico that became a hyperinfection resulting in GNR meningitis after starting high doses of dexamethasone.

Treatment of Chronic Asymptomatic Plasmodium falciparum Infection Does Not Increase the Risk of Clinical Malaria Upon Reinfection.

Chronic asymptomatic Plasmodium falciparum infections are common in endemic areas and are thought to contribute to the maintenance of malaria immunity. Whether treatment of these infections increases the subsequent risk of clinical episodes of malaria is unclear. In a 3-year study in Mali, asymptomatic individuals with or without P. falciparum infection at the end of the 6-month dry season were identified by polymerase chain reaction (PCR), and clinical malaria risk was compared during the ensuing 6-month malaria transmission season. At the end of the second dry season, 3 groups of asymptomatic children were identified: (1) children infected with P. falciparum as detected by rapid diagnostic testing (RDT) who were treated with antimalarials (n = 104), (2) RDT-negative children whose untreated P. falciparum infections were detected retrospectively by PCR (n = 55), and (3) uninfected children (RDT/PCR negative) (n = 434). Clinical malaria risk during 2 subsequent malaria seasons was compared. Plasmodium falciparum-specific antibody kinetics during the dry season were compared in children who did or did not harbor asymptomatic P. falciparum infections. Chronic asymptomatic P. falciparum infection predicted decreased clinical malaria risk during the subsequent malaria season(s); treatment of these infections did not alter this reduced risk. Plasmodium falciparum-specific antibodies declined similarly in children who did or did not harbor chronic asymptomatic P. falciparum infection during the dry season. These findings challenge the notion that chronic asymptomatic P. falciparum infection maintains malaria immunity and suggest that mass drug administration during the dry season should not increase the subsequent risk of clinical malaria.

In Vitro Variant Surface Antigen Expression in Plasmodium falciparum Parasites from a Semi-Immune Individual Is Not Correlated with Var Gene Transcription.

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is considered to be the main variant surface antigen (VSA) of Plasmodium falciparum and is mainly localized on electron-dense knobs in the membrane of the infected erythrocyte. Switches in PfEMP1 expression provide the basis for antigenic variation and are thought to be critical for parasite persistence during chronic infections. Recently, strain transcending anti-PfEMP1 immunity has been shown to develop early in life, challenging the role of PfEMP1 in antigenic variation during chronic infections. In this work we investigate how P. falciparum achieves persistence during a chronic asymptomatic infection. The infected individual (MOA) was parasitemic for 42 days and multilocus var gene genotyping showed persistence of the same parasite population throughout the infection. Parasites from the beginning of the infection were adapted to tissue culture and cloned by limiting dilution. Flow cytometry using convalescent serum detected a variable surface recognition signal on isogenic clonal parasites. Quantitative real-time PCR with a field isolate specific var gene primer set showed that the surface recognition signal was not correlated with transcription of individual var genes. Strain transcending anti-PfEMP1 immunity of the convalescent serum was demonstrated with CD36 selected and PfEMP1 knock-down NF54 clones. In contrast, knock-down of PfEMP1 did not have an effect on the antibody recognition signal in MOA clones. Trypsinisation of the membrane surface proteins abolished the surface recognition signal and immune electron microscopy revealed that antibodies from the convalescent serum bound to membrane areas without knobs and with knobs. Together the data indicate that PfEMP1 is not the main variable surface antigen during a chronic infection and suggest a role for trypsin sensitive non-PfEMP1 VSAs for parasite persistence in chronic infections.

Strongyloides and Dieulafoy on Steroids

Introduction:Strongyloides infection typically manifests with pulmonary, gastrointestinal (GI) or dermatological symptoms and can remain asymptomatic for decades. Steroid-induced immunosuppression increases the parasite's pathogenicity and may lead to superimposed infectious complications. We describe a patient with a history of extensive steroid treatment for COPD exacerbations who had three simultaneous disorders in his GI tract: Strongyloides, Herpes Simplex virus and Dieulafoy's lesion. This unusual case highlights the importance of including Strongyloides in the differential diagnosis of patients from tropical regions presenting with both respiratory and GI symptoms, especially in patients with previous steroid exposure. Case Presentation: A 64-year-old Bengali male, who had moved from India to the United States 4 months prior, presented with dyspnea and wheezing. His medical history included COPD (active smoker), CAD, heart failure, and hypertension. He was treated with prednisone for a suspected COPD exacerbation and discharged home. Soon after, he experienced odynophagia to solids, which progressed to intolerance of both solids and liquids, continuing dyspnea and, within one week, melena. He returned to the hospital septic with enterocolitis noted on CT. Hemoglobin dropped from 12.1 to 6.3 in 3 days. He was HIV negative and had no eosinophilia. EGD revealed multiple ulcers in the middle third of the esophagus, gastritis, duodenitis, and one medium-sized, oozing Dieulafoy's lesion in the distal duodenal bulb. Biopsies showed esophageal HSV and Strongyloides in the duodenum. The patient was treated with ivermectin for strongyloidiasis and with intravenous acyclovir for HSV esophagitis with resolution of his GI symptoms. Discussion: The degree to which Strongyloides contributed to this patient's dyspnea is unclear, as the patient is an active smoker with recurrent COPD exacerbations; however, we hypothesize that he was chronically infected. Prednisone-induced immunosuppression likely resulted in HSV esophagitis and triggered disseminated strongyloidiasis, which may have precipitated bleeding from his pre-existing Dieulafoy's lesion. Rapid diagnosis and prompt antiparasitic treatment prevent mortality, which can be as high as 50 - 80%. Our case highlights potential asymptomatic chronic helminth infections in patients from endemic areas and alerts clinicians to the ramifications of prednisone use in this population.

A Novel Model of Asymptomatic Plasmodium Parasitemia That Recapitulates Elements of the Human Immune Response to Chronic Infection.

In humans, immunity to Plasmodium sp. generally takes the form of protection from symptomatic malaria (i.e., 'clinical immunity') rather than infection ('sterilizing immunity'). In contrast, mice infected with Plasmodium develop sterilizing immunity, hindering progress in understanding the mechanistic basis of clinical immunity. Here we present a novel model in which mice persistently infected with P. chabaudi exhibit limited clinical symptoms despite sustaining patent parasite burdens for many months. Characterization of immune responses in persistently infected mice revealed development of CD4+ T cell exhaustion, increased production of IL-10, and expansion of B cells with an atypical surface phenotype. Additionally, persistently infected mice displayed a dramatic increase in circulating nonclassical monocytes, a phenomenon that we also observed in humans with both chronic Plasmodium exposure and asymptomatic infection. Following pharmacological clearance of infection, previously persistently infected mice could not control a secondary challenge, indicating that persistent infection disrupts the sterilizing immunity that typically develops in mouse models of acute infection. This study establishes an animal model of asymptomatic, persistent Plasmodium infection that recapitulates several central aspects of the immune response in chronically exposed humans. As such, it provides a novel tool for dissection of immune responses that may prevent development of sterilizing immunity and limit pathology during infection.

Interaction of Bovine Peripheral Blood Polymorphonuclear Cells and Leptospira Species; Innate Responses in the Natural Bovine Reservoir Host.

Cattle are the reservoir hosts of Leptospira borgpetersenii serovar Hardjo, and can also be reservoir hosts of other Leptospira species such as L. kirschneri, and Leptospira interrogans. As a reservoir host, cattle shed Leptospira, infecting other animals, including humans. Previous studies with human and murine neutrophils have shown activation of neutrophil extracellular trap or NET formation, and upregulation of inflammatory mediators by neutrophils in the presence of Leptospira. Humans, companion animals and most widely studied models of Leptospirosis are of acute infection, hallmarked by systemic inflammatory response, neutrophilia, and septicemia. In contrast, cattle exhibit chronic infection with few outward clinical signs aside from reproductive failure. Taking into consideration that there is host species variation in innate immunity, especially in pathogen recognition and response, the interaction of bovine peripheral blood polymorphonuclear cells (PMNs) and several Leptospira strains was evaluated. Studies including bovine-adapted strains, human pathogen strains, a saprophyte and inactivated organisms. Incubation of PMNs with Leptospira did induce slight activation of neutrophil NETs, greater than unstimulated cells but less than the quantity from E. coli P4 stimulated PMNs. Very low but significant from non-stimulated, levels of reactive oxygen peroxides were produced in the presence of all Leptospira strains and E. coli P4. Similarly, significant levels of reactive nitrogen intermediaries (NO2) was produced from PMNs when incubated with the Leptospira strains and greater quantities in the presence of E. coli P4. PMNs incubated with Leptospira induced RNA transcripts of IL-1β, MIP-1α, and TNF-α, with greater amounts induced by live organisms when compared to heat-inactivated leptospires. Transcript for inflammatory cytokine IL-8 was also induced, at similar levels regardless of Leptospira strain or viability. However, incubation of Leptospira strains with bovine PMNs did not affect Leptospira viability as measured by limiting dilution culture. This is in contrast to previously reported results of innate inflammatory activation by Leptospira in human and other animal models, or the activation and interaction of bovine PMNs with Escherichia coli and other bacterial pathogens. While it could be hypothesized that variations in innate receptor recognition, specifically variance in toll-like receptor 2, could underlie the observed reduction of activation in bovine PMNs, additional studies would be needed to explore this possibility. Reduction in neutrophil responses may help to establish nearly asymptomatic chronic Leptospira infection of cattle. This study emphasizes the importance of studying host-pathogen relationships in the appropriate species as extrapolation from other animal models may be incorrect and confounded by differences in the host responses.

Seroepidemiology of Sarcocystis neurona, Toxoplasma gondii and Neospora spp. among horses in the south of the state of Minas Gerais, Brazil.

The present study used the indirect fluorescent antibody test (IFAT) to determine the seroprevalence of Sarcocystis neurona, Toxoplasma gondii and Neospora spp., and evaluated the variables associated with these infections among 506 apparently healthy horses, reared in the south of the state of Minas Gerais, Brazil. This study was conducted between April 2012 and October 2013. Among the horses, the true prevalence of S. neurona was 26% (95% CI: 22.0-30.4%), T. gondii 19.9% (95% CI: 15.5-24.8%) and Neospora spp. 23.9% (95% CI: 19.9-28.1%); and among the farms, 88.3% (95% CI: 74.4-91.6%), 71.6% (95% CI: 41-92.8%) and 85% (95% CI: 70.7-96.1%), respectively. Regarding mixed infection, 17 horses (3.4%) were seropositive for both S. neurona and T. gondii, 16 (3.2%) for T. gondii and Neospora spp. and 14 (2.8%) for S. neurona and Neospora spp. The associations between seropositivity and variables relating to the structure of the farm, management and health were analyzed using the logistic regression analysis, through the generalized estimating equations (GEE). The results suggest that the south of Minas Gerais is an enzootic area for S. neurona, T. gondii and Neospora spp. among horses, with prevalence of asymptomatic subclinical or chronic infections.

Germinal Center T Follicular Helper Cells Are Highly Permissive to HIV-1 and Alter Their Phenotype during Virus Replication.

HIV-1 replication is concentrated within CD4(+) T cells in B cell follicles of secondary lymphoid tissues during asymptomatic disease. Limited data suggest that a subset of T follicular helper cells (TFH) within germinal centers (GC) is highly permissive to HIV-1. Whether GC TFH are the major HIV-1 virus-producing cells in vivo has not been established. In this study, we investigated TFH permissivity to HIV-1 ex vivo by spinoculating and culturing tonsil cells with HIV-1 GFP reporter viruses. Using flow cytometry, higher percentages of GC TFH (CXCR5(high)PD-1(high)) and CXCR5(+)programmed cell death-1 (PD-1)(low) cells were GFP(+) than non-GC TFH (CXCR5(+)PD-1(intermediate)) or extrafollicular (EF) (CXCR5(-)) cells. When sorted prior to spinoculation, however, GC TFH were substantially more permissive than CXCR5(+)PD-1(low) or EF cells, suggesting that many GC TFH transition to a CXCR5(+)PD-1(low) phenotype during productive infection. In situ hybridization on inguinal lymph node sections from untreated HIV-1-infected individuals without AIDS revealed higher frequencies of HIV-1 RNA(+) cells in GC than non-GC regions of follicle or EF regions. Superinfection of HIV-1-infected individuals' lymph node cells with GFP reporter virus confirmed the permissivity of follicular cells ex vivo. Lymph node immunostaining revealed 96% of CXCR5(+)CD4(+) cells were located in follicles. Within sorted lymph node cells from four HIV-infected individuals, CXCR5(+) subsets harbored 11-66-fold more HIV-1 RNA than CXCR5(-) subsets, as determined by RT PCR. Thus, GC TFH are highly permissive to HIV-1, but downregulate PD-1 and, to a lesser extent, CXCR5 during HIV-1 replication. These data further implicate GC TFH as the major HIV-1-producing cells in chronic asymptomatic HIV-1 infection.

Toxoplasmosis in HIV infection: An overview.

Toxoplasma gondii is an obligate intracellular protozoan parasite presenting as a zoonotic infection distributed worldwide. In HIV-positive individuals, it causes severe opportunistic infections, which is of major public health concern as it results in physical and psychological disabilities. In healthy immunocompetent individuals, it causes asymptomatic chronic persistent infections, but in immunosuppressed patients, there is reactivation of the parasite if the CD4 counts fall below 200 cells/μl. The seroprevalence rates are variable in different geographic areas. The tissue cyst or oocyst is the infective form which enters by ingestion of contaminated meat and transform into tachyzoites and disseminate into blood stream. In immunocompetent persons due to cell-mediated immunity the parasite is transformed into tissue cyst resulting in life long chronic infection. In HIV-infected people opportunistic infection by T. gondii occurs due to depletion of CD4 cells, decreased production of cytokines and interferon gamma and impaired cytotoxic T-lymphocyte activity resulting in reactivation of latent infection. The diagnosis can be done by clinical, serological, radiological, histological or molecular methods, or by the combination of these. There is various treatment regimen including acute treatment, maintenance therapy should be given as the current anti T. gondii therapy cannot eradicate tissue cysts. In HIV patients, CD4 counts <100; cotrimoxazole, alternately dapsone + pyrimethamine can be given for 6 months. Hence, early diagnosis of T. gondii antibodies is important in all HIV-positive individuals to prevent complications of cerebral toxoplasmosis.

Human Papillomaviruses; Epithelial Tropisms, and the Development of Neoplasia.

Papillomaviruses have evolved over many millions of years to propagate themselves at specific epithelial niches in a range of different host species. This has led to the great diversity of papillomaviruses that now exist, and to the appearance of distinct strategies for epithelial persistence. Many papillomaviruses minimise the risk of immune clearance by causing chronic asymptomatic infections, accompanied by long-term virion-production with only limited viral gene expression. Such lesions are typical of those caused by Beta HPV types in the general population, with viral activity being suppressed by host immunity. A second strategy requires the evolution of sophisticated immune evasion mechanisms, and allows some HPV types to cause prominent and persistent papillomas, even in immune competent individuals. Some Alphapapillomavirus types have evolved this strategy, including those that cause genital warts in young adults or common warts in children. These strategies reflect broad differences in virus protein function as well as differences in patterns of viral gene expression, with genotype-specific associations underlying the recent introduction of DNA testing, and also the introduction of vaccines to protect against cervical cancer. Interestingly, it appears that cellular environment and the site of infection affect viral pathogenicity by modulating viral gene expression. With the high-risk HPV gene products, changes in E6 and E7 expression are thought to account for the development of neoplasias at the endocervix, the anal and cervical transformation zones, and the tonsilar crypts and other oropharyngeal sites. A detailed analysis of site-specific patterns of gene expression and gene function is now prompted.

Management of Hepatitis C Post-liver Transplantation: a Comprehensive Review.

Infection with hepatitis C virus (HCV) is a common cause of chronic liver disease, and HCV-related cirrhosis and hepatocellular carcinoma are the leading causes for liver transplantation in the Western world. Recurrent infection of the transplanted liver allograft is universal in patients with detectable HCV viremia at the time of transplant and can cause a spectrum of disease, ranging from asymptomatic chronic infection to an aggressive fibrosing cholestatic hepatitis. Recurrent HCV is more aggressive in the post-transplant population and is a leading cause of allograft loss, morbidity, and mortality. Historically, treatment of recurrent HCV has been limited by low rates of treatment success and high side effect profiles. Over the past few years, promising new therapies have emerged for the treatment of HCV that have high rates of sustained virological response without the need for interferon based regimens. In addition to being highly effective, these treatments have higher rates of adherence and a lower side effect profile. The purpose of this review is to summarize current therapies in recurrent HCV infection, to review the recent advances in therapy, and to highlight areas of ongoing research.

Exposure to cows is not associated with diarrhoea or impaired child growth in rural Odisha, India: a cohort study.

Exposure to animal livestock has been linked to zoonotic transmission, especially of gastrointestinal pathogens. Exposure to animals may contribute to chronic asymptomatic intestinal infection, environmental enteropathy and child under-nutrition in low-income settings. We conducted a cohort study to explore the effect of exposure to cows on growth and endemic diarrhoea in children aged <5 years in a rural, low-income setting in the Indian state of Odisha. The study enrolled 1992 households with 2739 children. Height measurements were available for 824 children. Exposure to cows was measured as (1) the presence of a cowshed within or outside the compound, (2) the number of cows owned by a household, and (3) the number of cowsheds located within 50 m of a household. In a sub-study of 518 households, fly traps were used to count the number of synanthropic flies that may act as vectors for gastrointestinal pathogens. We found no evidence that environmental exposure to cows contributes to growth deficiency in children in rural India, neither directly by affecting growth, nor indirectly by increasing the risk of diarrhoea. We found no strong evidence that the presence of a cowshed increased the number synanthropic flies in households.

Increased Frequencies of Circulating IFN-γ-Producing Vδ1(+) and Vδ2(+) γδ T Cells in Patients with Asymptomatic Persistent Hepatitis B Virus Infection.

Hepatitis B virus (HBV) is a leading cause of liver cirrhosis and hepatocellular carcinoma. The outcome of HBV infection is largely determined by the host immune response, with virus-specific cytotoxic T cells being able to mediate immunity against HBV as well as causing liver pathology. γδ T cells are reported to be depleted in patients with HBV-associated liver disease. However, it is not known if these cells control HBV infection in patients with asymptomatic chronic HBV infection. In this study, the frequencies, phenotypes, and interferon-γ production were examined by circulating γδ T cell subsets in a group of asymptomatic HBV carriers with low viral loads and little evidence of liver disease. It is shown that γδ T cells expressing Vδ1 and Vδ2 T cell receptors and effector-memory phenotypes are found at higher frequencies in these patients compared to controls. Vδ2 T cells from the patients expressed interferon-γ significantly more frequently than Vδ2 T cells from healthy donors in the absence of ex vivo stimulation. These data suggest that effector-memory IFN-γ-producing Vδ2 T cells may contribute to the control of HBV in patients with asymptomatic infection, without mediating liver pathology.

Correlation between Liver Function Tests and Polymerase Chain Reaction in Chronic Hepatitis C Patients

Background: Hepatitis C virus infection is currently the most significant public health problem globally and particularly in Egypt. The outcomes of HCV infection range from asymptomatic chronic infection, with normal or nearly normal liver functions, to severe chronic hepatitis, evolving rapidly to cirrhosis and hepatocellular carcinoma. Our objective is to asses and evaluates the relationship between liver function tests, serum HCV-RNA positivity and the severity of liver damage in chronic HCV patients. Method: We studied 329 patients with chronic HCV, they were categorized into two groups according to the PCR results: first group were positive PCR (86 %), and second group were negative PCR (14 %). Liver transaminases, total and direct bilirubin, serum albumin, HCV RNA detection and viral load by real time PCR, and liver biopsy were done to all patients. Results: This study showed that the liver transaminases were significantly higher in HCV positive patients than in HCV negative patients (p value <0.0001). We also observed that the comparison between positive PCR group with negative PCR group revealed that, there were no statistically significant difference regarding albumin, alkaline phosphate, total bilirubin , direct bilirubin and prothrombin (p=0.35, p=0.80, p=0.26, p=0.86 and p=0.99 respectively). Conclusions: high results of liver function tests may be indicator for the severity of liver damage in chronic HCV patients but also PCR should be done as some cases show normal results while its PCR was high. There is no relationship between liver function tests and the grade of activity or fibrosis.

Worms and Humans: A Happy Divorce?

Chronic asymptomatic worm infection, often in combination with tuberculosis (TB), is common in low-income countries. Indeed, a life without worm infestation, as is now the case in most high-income countries, is a recent condition for humankind. Worms and Mycobacterium tuberculosis give rise to different immune response patterns (Th2 vs. Th1 driven), and we have studied whether chronic worm infection affects the susceptibility to and control of TB in the low income country of Ethiopia. Our results, as well of those in the general literature, are inconclusive, although we have some rather strong data in support of adult deworming in relation to vaccination with bacillus Calmette-Guérin (BCG) against TB. In addition, we discuss briefly the putative relationship between chronic worm infestation and autoimmunity/allergy.

Striking Divergence in Toxoplasma ROP16 Nucleotide Sequences From Human and Meat Samples.

ROP16 is a protein kinase of Toxoplasma gondii identified in the mouse model as a virulent marker, but it is unknown whether this finding is relevant in human toxoplasmosis. We obtained the Toxoplasma ROP16 locus DNA sequence in samples from 12 patients with ocular toxoplasmosis, 1 sample from a patient with congenital toxoplasmosis, 22 samples from soldiers operating in the jungle, 2 samples from urban soldiers, and 10 samples from meat for human consumption. An enzyme-linked immunosorbent assay specific for antibodies against the ROP16 mouse-virulent peptide was performed in 46 serum specimens from patients with ocular toxoplasmosis and in 28 serum specimens from patients with chronic asymptomatic infection, of whom 19 had congenital infection and 11 had toxoplasmic lymphadenitis. We found a striking divergence of the ROP16 nucleotide sequences. Ten of 12 sequences (83.3%) from patients with ocular toxoplasmosis clustered with those of mouse-virulent strains, whereas 7 of 7 ROP16 sequences (100%) from meat were clustered with those of mouse-avirulent strains. Only 11 of 104 serum specimens (10.5%) had specific antibodies against the mouse-virulent peptide, and there was no association between clinical forms and positive results of serological assays. The majority of ROP16 nucleotide sequences from Colombian patients with ocular toxoplasmosis belonged to the group of mouse-virulent strains.