de Moira, Angela Pinot and Fulford, Anthony J.C. and Kabatereine, Narcis B. and Ouma, John H. and Booth, Mark and Dunne, David W. (2010) 'Analysis of complex patterns of human exposure and immunity to schistosomiasis mansoni : the influence of age, sex, ethnicity and IgE.', PLoS neglected tropical diseases., 4 (9). e820.
Background: Numerous factors may influence Schistosoma infection intensity and prevalence within endemic communities, including exposure-related factors such as local environment and behaviour, and factors relating to susceptibility to infection such as immunology and genetics. While animal studies performed in the laboratory can be tightly controlled, human populations are highly heterogeneous, varying according to demographic characteristics, genetic background and exposure to infection. The heterogeneous nature of human water contact behaviour in particular makes it difficult to distinguish between a lack of cercarial exposure and reduced susceptibility to infection as the cause for low levels of infection in the field. Methods and Principal Findings: In this study we investigate risk factors for Schistosoma mansoni infection in a rural Ugandan fishing community receiving treatment as part of a multi-disciplinary longitudinal reinfection study. More specifically, we examine the influence that age, sex and ethnic background have on susceptibility to reinfection after anti-helminth drug treatment, but use individual estimates of cercarial exposure and multivariable methods in an attempt to remove noise created by environmental and behavioural heterogeneities. We then investigate whether schistosome-specific IgE immune responses could account for any remaining variations in susceptibility to reinfection. Our findings suggest that observed ethnic- and sex-related variations in S. mansoni reinfection were due to variations in cercarial exposure, as opposed to biological differences in susceptibility to infection. Age-related differences in reinfection were not explained by exposure, however, and appeared linked to the balance of IgE and IgG4 to the tegumental antigen SmTAL1 (formerly Sm22.6), which itself was significantly related to resistance to reinfection. Conclusions: This study highlights the benefit of taking a multidisciplinary approach in complex field settings; it allows the ecology of a population to be understood and thus more robust conclusions to be made.
|Additional Information:||Author Summary: Human schistosomiasis is a chronic parasitic disease affecting around 200 million people worldwide. Infection occurs when cercariae penetrate the skin during water contact. Although there is effective treatment for schistosomiasis, individuals remain susceptible to reinfection after treatment; some individuals, however, appear more susceptible to reinfection than others. The highly heterogeneous nature of human water contact behaviour makes it difficult to identify whether low levels of reinfection are caused by immunity or a simple lack of cercarial exposure; this complicates the characterisation of risk factors for infection and immune correlates of protection. Here, we take a multidisciplinary approach using individual estimates of cercarial exposure and multivariable analysis to allow for environmental and behavioural heterogeneities. We examine the influence of demographic factors and antibody responses on susceptibility to reinfection. While observed ethnic- and sex-related variations in Schistosoma mansoni reinfection could be explained by differences in exposure, age-related differences appeared linked to the balance of specific IgE and IgG4 antibodies, themselves related to resistance to reinfection. Our study highlights the benefits of a multidisciplinary approach in complex field settings: it improves our understanding of a population's ecology and therefore the biology of disease.|
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|Publisher Web site:||http://dx.doi.org/10.1371/journal.pntd.0000820|
|Publisher statement:||Copyright: © 2010 Pinot de Moira et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
|Record Created:||24 Jan 2012 11:50|
|Last Modified:||25 Jan 2012 14:34|
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