Host Determinants of Reinfection with Schistosomes in Humans: A Systematic Review and Meta-analysis

Background: Schistosomiasis is still a major public health burden in the tropics and subtropics. Although there is an effective chemotherapy (Praziquantel) for this disease, reinfection occurs rapidly after mass drug administration (MDA). Because the entire population do not get reinfected at the same rate, it is possible that host factors may play a dominant role in determining resistance or susceptibility to reinfection with schistosomes. Here, we systematically reviewed and meta-analyzed studies that reported associations between reinfection with the principal human-infecting species (S. mansoni, S. japonicum and S. haematobium) and host socio-demographic, epidemiological, immunological and genetic factors. Methodology/Principal Findings: PubMed, Scopus, Google Scholar, Cochrane Review Library and African Journals Online public databases were searched in October 2013 to retrieve studies assessing association of host factors with reinfection with schistosomes. Meta-analysis was performed to generate pooled odds ratios and standardized mean differences as overall effect estimates for dichotomous and continuous variables, respectively. Quality assessment of included studies, heterogeneity between studies and publication bias were also assessed. Out of the initial 2739 records, 109 studies were included in the analyses, of which only 32 studies with 37 data sets were eligible for quantitative data synthesis. Among several host factors identified, strong positive association was found with age and pre-treatment intensity, and only slightly for gender. These factors are major determinants of exposure and disease transmission. Significant positive association was found with anti-SWA IgG4 level, and a negative overall effect for association with IgE levels. This reconfirmed the concept that IgE/IgG4 balance is a major determinant of protective immunity against schistosomiasis. Other identified determinants were reported by a small number of studies to enable interpretation. Conclusions: Our data contribute to the understanding of host-parasite interaction as it affects reinfection, and is a potential tool to guide planning and tailoring of community interventions to target high-risk groups. Author Summary: One of the major challenges of schistosomiasis control is that disease prevalence reverts to baseline levels after mass drug administration due to high rate of reinfection. Host factors play a major role in determining resistance or susceptibility to reinfection with schistosomiasis and other diseases. We systematically searched and analyzed studies that identified potential host determinants of reinfection with schistosomes. Among demographic variables, age but not gender was strongly associated with reinfection with schistosomes. Pretreatment infection intensity was also identified as a major determinant of reinfection. Positive association with IgG4 levels and negative association with IgE levels reconfirmed the notion that IgE/IgG4 balance is the major factor controlling protective immunity against schistosomiasis. Other factors were reported by few studies to allow correct inferences. These results contribute to our understanding of host-parasite relationship as it affects reinfection, and will be useful for planning and targeting the limited resources for intervention on high-risk groups.