Genetic epidemiology of human schistosomiasis in Brazil

Bethony, Jeffrey M.; Quinnell, Rupert J.

doi:10.1016/j.actatropica.2007.11.008

Cited by 16 publications

(15 citation statements)

References 60 publications

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“…Those living within ∼100 m of the major water contact site (Figure 4B) were at least six times more likely to develop advanced hepatic fibrosis (liver image pattern D–F) than those living further away. However, other factors cannot be excluded such as genetic predisposition [74], diet or nutritional status [75], or co-infections, which may have put those living in close vicinity of the water at a higher risk of developing hepatic morbidity than the rest of the community.…”

Section: Discussionmentioning

confidence: 99%

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

et al. 2013

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Background Schistosoma mansoni and S. haematobium are co-endemic in many areas in Africa. Yet, little is known about the micro-geographical distribution of these two infections or associated disease within such foci. Such knowledge could give important insights into the drivers of infection and disease and as such better tailor schistosomiasis control and elimination efforts.MethodologyIn a co-endemic farming community in northern Senegal (346 children (0–19 y) and 253 adults (20–85 y); n = 599 in total), we studied the spatial distribution of S. mansoni and S. haematobium single and mixed infections (by microscopy), S. mansoni-specific hepatic fibrosis, S. haematobium-specific urinary tract morbidity (by ultrasound) and water contact behavior (by questionnaire). The Kulldorff's scan statistic was used to detect spatial clusters of infection and morbidity, adjusted for the spatial distribution of gender and age.Principal Findings Schistosoma mansoni and S. haematobium infection densities clustered in different sections of the community (p = 0.002 and p = 0.023, respectively), possibly related to heterogeneities in the use of different water contact sites. While the distribution of urinary tract morbidity was homogeneous, a strong geospatial cluster was found for severe hepatic fibrosis (p = 0.001). Particularly those people living adjacent to the most frequently used water contact site were more at risk for more advanced morbidity (RR = 6.3; p = 0.043).Conclusions/Significance Schistosoma infection and associated disease showed important micro-geographical heterogeneities with divergent patterns for S. mansoni and S. haematobium in this Senegalese community. Further in depth investigations are needed to confirm and explain our observations. The present study indicates that local geospatial patterns should be taken into account in both research and control of schistosomiasis. The observed extreme focality of schistosomiasis even at community level, suggests that current strategies may not suffice to move from morbidity control to elimination of schistosomiasis, and calls for less uniform measures at a finer scale.

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Section: Discussionmentioning

confidence: 99%

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

et al. 2013

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“…[1] These obstacles have motivated research to better understand schistosomiasis host immunity to identify those individuals susceptible to greatest intensity of infection for targeted treatment and prevention. [3], [4].…”

Section: Introductionmentioning

confidence: 99%

Functional Polymorphisms in IL13 Are Protective against High Schistosoma mansoni Infection Intensity in a Brazilian Population

et al. 2012

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BackgroundIL-13 is a signature cytokine of the helper T cell type 2 (TH2) pathway which underlies host defense to helminthic infection and activates production of IgE in both parasitized populations and in urban settings after allergen exposure.Methodology/Principal FindingsTwo functional polymorphisms in IL13, rs1800925 (or c.1-1111C>T) and rs20541 (or R130Q) were previously found to be associated with Schistosoma hematobium infection intensity. They have not been thoroughly explored in S. mansoni-endemic populations, however, and were selected along with 5 tagging SNPs for genotyping in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area of Conde, Bahia, in Brazil. Regression models using GEE to account for family membership and family-based quantitative transmission disequilibrium tests (QTDT) were used to evaluate associations with total serum IgE (tIgE) levels and S. mansoni fecal egg counts adjusted for non-genetic covariates. We identified a protective effect for the T allele at rs20541 (P = 0.005) against high S. mansoni egg counts, corroborated by QTDT (P = 0.014). Our findings also suggested evidence for protective effects for the T allele at rs1800925 and A allele at rs2066960 after GEE analysis only (P = 0.050, 0.0002).Conclusions/SignificanceThe two functional variants in IL13 are protective against high S. mansoni egg counts. These markers showed no evidence of association with tIgE levels, unlike tIgE levels previously studied in non-parasitized or atopic study populations.

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“…16 The impact of IL10 genetic variation on schistosomiasis has not been studied, however. 2,17 In vitro functional studies have shown individuals with the 'GCC' haplotype at promoter polymorphic sites rs1800896, rs1800871 and rs1800872 produced high levels of IL-10 in peripheral blood mononuclear cell culture, whereas individuals with the 'ATA' haplotype had a lower rate of transcription, producing lower levels of IL-10. 18 Differential levels of IL-10 production may also impact outcomes in a population endemic for schistosomiasis.…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population

et al. 2010

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Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopyrelated IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P ¼ 0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P ¼ 0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.

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Genetic epidemiology of human schistosomiasis in Brazil

Cited by 16 publications

References 60 publications

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

Micro-Geographical Heterogeneity in Schistosoma mansoni and S. haematobium Infection and Morbidity in a Co-Endemic Community in Northern Senegal

Functional Polymorphisms in IL13 Are Protective against High Schistosoma mansoni Infection Intensity in a Brazilian Population

Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population

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