Dataset Information

Increased hepatotoxicity among HIV-infected adults co-infected with Schistosoma mansoni in Tanzania: A cross-sectional study.

ABSTRACT:

Introduction

Little is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without.

Methodology/principal findings

We determined the presence and grade of hepatotoxicity among 305 HIV-infected outpatients who had been on medium-term (3-6 months) and long-term (>36 months) antiretroviral therapy in a region of northwest Tanzania where S. mansoni is hyperendemic. We used the AIDS Clinical Trial Group definition to define mild to moderate hepatotoxicity as alanine aminotransferase, alanine aminotransferase, and/or bilirubin elevations of grade 1 or 2, and severe hepatotoxicity as any elevation of grade 3 or 4. We determined schistosome infection status using the serum circulating cathodic antigen rapid test and used logistic regression to determine factors associated with hepatotoxicity. The prevalence of mild-moderate and severe hepatotoxicity was 29.6% (45/152) and 2.0% (3/152) in patients on medium-term antiretroviral therapy and 19.6% (30/153) and 3.3% (5/153) in the patients on long-term antiretroviral therapy. S. mansoni infection was significantly associated with hepatotoxicity on univariable analysis and after controlling for other factors associated with hepatotoxicity including hepatitis B or C and anti-tuberculosis medication use (adjusted odds ratio = 3.0 [1.6-5.8], p = 0.001).

Conclusions/significance

Our work demonstrates a strong association between S. mansoni infection and hepatotoxicity among HIV-infected patients on antiretroviral therapy. Our study highlights the importance of schistosome screening and treatment for patients starting antiretroviral therapy in schistosome-endemic settings. Additional studies to determine the effects of schistosome-HIV co-infections are warranted.

SUBMITTER: Marti AI

PROVIDER: S-EPMC5574610 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

Increased hepatotoxicity among HIV-infected adults co-infected with Schistosoma mansoni in Tanzania: A cross-sectional study.

Marti Amon I AI Colombe Soledad S Masikini Peter J PJ Kalluvya Samuel E SE Smart Luke R LR Wajanga Bahati M BM Jaka Hyasinta H Peck Robert N RN Downs Jennifer A JA

PLoS neglected tropical diseases 20170817 8

<h4>Introduction</h4>Little is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without.<h4>Methodology/principal findings</h4>We determined the presence and grade of hepatotoxicity among 305 HIV-infec ...[more]

PMID: 28817570

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Project description:BackgroundAnimal studies have demonstrated that functional immune responses, as determined by the levels of CD4(+) cell counts and anti-schistosome antibodies responses, determine the efficacy of praziquantel. Based on this evidence, it has been hypothesised that the immunodeficiency effects of the human immunodeficiency virus (HIV)-1 infection may affect the efficacy of praziquantel in co-infected human hosts. Thus, the present study assessed the efficacy of praziquantel by comparing parasitological cure rates and the reduction in infection intensity in HIV-1 seronegative individuals infected with S. mansoni and HIV-1 seropositive individuals co-infected with S. mansoni, following treatment with a single oral dose of praziquantel.MethodsThis was a prospective longitudinal study which included, at baseline, 555 S. mansoni infected adults aged 21-55 years, who were either co-infected or not with HIV-1 and who lived in fishing villages along Lake Victoria in Northwest Tanzania. These individuals were treated with a single oral dose of praziquantel (40 mg/kg) and, at 12 weeks, single stool samples were obtained and examined for S. mansoni eggs using the Kato-Katz technique. Finger prick and venous blood samples were collected for HIV-1 screening and CD4(+) cell quantification.ResultsThe parasitological cure rate did not differ significantly from the HIV-1 serostatus (P = 0.12): among the co-infected individuals, the cure rate was 48.3% (14/29), and among the individuals infected only with S. mansoni, the cure rate was 62.6% (329/526). The egg reduction rate did not vary with the HIV-1 serostatus (P = 0.22): 77.22% for HIV-1 seronegative and 75% for HIV-1 seropositive individuals. The level of CD4(+) cell counts (median 228 cells/?L: range 202-380 cells) did not influence the cure rate (P = 0.23) or the reduction in the intensity of the infection (P = 0.37).ConclusionThe HIV-1 infection per se or its moderate immunodeficiency effects, demonstrated by the range of CD4(+) cell counts observed in co-infected individuals, did not affect praziquantel efficacy, as measured by the parasitological cure rate and the reduction in intensity of infection in the present study cohort.

Project description:Mycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth Schistosoma mansoni (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM+ and SM- individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM+ LTBI individuals had higher frequencies of IFN?+ Mtb-specific CD4 T cells than SM- LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM+ and SM- individuals with LTBI. However, SM+ individuals with active TB had significantly higher frequencies of GATA3+ CCR4+ TH1 cytokine+ Mtb-specific CD4 T cells, compared with SM- TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine+ CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses.

Project description:Schistosomiasis is a leading cause of morbidity in Africa. Understanding the disease ecology and environmental factors that influence its distribution is important to guide control efforts. Geographic information systems have increasingly been used in the field of schistosomiasis environmental epidemiology. This study reports prevalences of Schistosoma haematobium infection and uses remotely sensed and questionnaire data from over 17000 participants to identify environmental and socio-demographic factors that are associated with this parasitic infection. Data regarding socio-demographic status and S. haematobium infection were obtained between May 2006 and May 2007 from 17280 participants (53% females, median age = 17 years) in the Mbeya Region, Tanzania. Combined with remotely sensed environmental data (vegetation cover, altitude, rainfall etc.) this data was analyzed to identify environmental and socio-demographic factors associated with S. haematobium infection, using mixed effects logistic regression and geostatistical modelling. The overall prevalence of S. haematobium infection was 5.3% (95% confidence interval (CI): 5.0-5.6%). Multivariable analysis revealed increased odds of infection for school-aged children (5-15 years, odds ratio (OR) = 7.8, CI: 5.9-10.4) and the age groups 15-25 and 25-35 years (15-25 years: OR = 5.8, CI: 4.3-8.0, 25-35 years: OR = 1.6, CI: 1.1-2.4) compared to persons above 35 years of age, for increasing distance to water courses (OR = 1.4, CI: 1.2-1.6 per km) and for proximity to Lake Nyasa (<1 km, OR = 4.5, CI: 1.8-11.4; 1-2 km, OR = 3.5, CI: 1.7-7.5; 2-4 km; OR = 3.3, CI: 1.7-6.6), when compared to distances >4 km. Odds of infection decreased with higher altitude (OR = 0.7, CI: 0.6-0.8 per 100 m increase) and with increasing enhanced vegetation index EVI (OR = 0.2, CI: 0.1-0.4 per 0.1 units). When additionally adjusting for spatial correlation population density became a significant predictor of schistosomiasis infection (OR = 1.3, CI: 1.1-1.5 per 1000 persons/km2) and altitude turned non-significant. We found highly focal geographical patterns of S. haematobium infection in Mbeya Region in Southwestern Tanzania. Despite low overall prevalence our spatially heterogeneous results show that some of the study sites suffer from a considerable burden of S. haematobium infection, which is related to various socio-demographic and environmental factors. Our results could help to design more effective control strategies in the future, especially targeting school-aged children living in low altitude sites and/or crowded areas as the persons at highest need for preventive chemotherapy.

Project description:BackgroundSchistosomiasis (bilharzia) is a chronic and potentially deadly parasitic disease that affects millions of people in (sub)tropical areas. An important partial immunity to Schistosoma infections does develop in disease endemic areas, but this takes many years of exposure and maturation of the immune system. Therefore, children are far more susceptible to re-infection after treatment than older children and adults. This age-dependent immunity or susceptibility to re-infection has been shown to be associated with specific antibody and T cell responses. Many antibodies generated during Schistosoma infection are directed against the numerous glycans expressed by Schistosoma. The nature of glycan epitopes recognized by antibodies in natural schistosomiasis infection serum is largely unknown.Methodology/principal findingsThe binding of serum antibodies to glycans can be analyzed efficiently and quantitatively using glycan microarray approaches. Very small amounts of a large number of glycans are presented on a solid surface allowing binding properties of various glycan binding proteins to be tested. We have generated a so-called shotgun glycan microarray containing natural N-glycan and lipid-glycan fractions derived from 4 different life stages of S. mansoni and applied this array to the analysis of IgG and IgM antibodies in sera from children and adults living in an endemic area. This resulted in the identification of differential glycan recognition profiles characteristic for the two different age groups, possibly reflecting differences in age or differences in length of exposure or infection.Conclusions/significanceUsing the shotgun glycan microarray approach to study antibody response profiles against schistosome-derived glycan elements, we have defined groups of infected individuals as well as glycan element clusters to which antibody responses are directed in S. mansoni infections. These findings are significant for further exploration of Schistosoma glycan antigens in relation to immunity.

Project description:BackgroundInfection with Schistosoma mansoni negatively impact children's physical health and may influence their general well-being. The aim of this study was to investigate the effect of S. mansoni infections on a panel of morbidity indicators with emphasis on quality of life (PedsQL; measured in four different dimensions) and physical fitness (measured as VO2 max) among 572 schoolchildren aged 7-8 years.Methodology/principal findingsPrevalence of S. mansoni infections was 58.7%, with an arithmetic mean (95% CI) among positives of 207.3 (169.2-245.4) eggs per gram (epg). Most infections were light (56.5%), while 16.4% had heavy infections. Girls had significantly higher arithmetic mean intensities (95% CI) than boys (247.4 (189.2-305.6) vs. 153.2 (110.6-195.8); P = 0.004). A total of 30.1% were anaemic with no sex difference. Stunting and wasting was found in less than 10% of the population. There was no association between S. mansoni prevalence or intensities and the following parameters: anthropometry, anaemia, liver or spleen pathology in neither univariable nor multivariable linear regression analyses. However, in univariable analyses children with S. mansoni infection had a significantly lower score in emotional PedsQL (95% CI) than uninfected (77.3 (74.5-80.1) vs. 82.7 (79.9-85.5); P = 0.033) and infected children had a higher VO2 max (95% CI) compared to uninfected (51.4 (51.0-51.8) vs. 50.8 (50.3-51.3); P = 0.042). In multivariable linear regression analyses, age, S. mansoni infection, haemoglobin and VO2 max were significant predictors for emotional PedsQL while significant predictors for VO2 max were physical PedsQL, height, age and haemoglobin. S. mansoni infection was thus not retained in the multivariable regression analyses on VO2 max.Conclusions/significanceOf the measured morbidity parameters, S. mansoni infection had a significant effect on the emotional dimension of quality of life, but not on physical fitness. If PedsQL should be a useful tool to measure schistosome related morbidity, more in depth studies are needed in order to refine the tool so it focuses more on aspects of quality of life that may be affected by schistosome infections.

Dataset Information

Increased hepatotoxicity among HIV-infected adults co-infected with Schistosoma mansoni in Tanzania: A cross-sectional study.

Introduction

Methodology/principal findings

Conclusions/significance

Publications

Increased hepatotoxicity among HIV-infected adults co-infected with Schistosoma mansoni in Tanzania: A cross-sectional study.

Similar Datasets

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