Effect of schistosoma infection on malaria immune response: A systematic review

Background Worldwide an estimated 225 million cases and about 800, 000 deaths due to malaria were documented in 2009. Malaria vaccines have been developed as a malaria control strategy. Immune response to these vaccines might be affected by the blood fluke schistosoma which is often co-endemic with malaria in Sub-Saharan Africa where most of phase II and Phase III malaria vaccine trials were conducted.Objectives To systematically search, appraise and synthesize the best available evidence on the effect of schistosoma infection on the immune response to malaria antigens and provide direction to future malaria vaccination trials.Types of participants The review considered studies with above 5 year old individuals as participants.Phenomenon of interest The phenomenon of interest was the presence of schistosoma infectionTypes of outcomes Blood serum levels of Th1 and Th2 specific to Merozoite Surface Proteins 1, 2, and 3 of malaria were considered as primary outcomes. While blood serum levels of IgG1, IgG2, IgG3, IFN-γ, IL-10 and TGF-β directed against Merozoite Surface Proteins were considered as secondary outcomes.Types of studies Studies with any quantitative study designs were considered for inclusion.Search Strategy Any quantitative English language articles published between 1994 and April 2011 were sought using a comprehensive search strategy.Assessment of methodological quality It was done using Joanna Briggs Institutes' Meta Analysis of Statistical Assessment and Review Instrument critical appraisal tools.Data extraction Data extraction was carried out using the Joanna Briggs Institute Meta Analysis of Statistical Assessment and Review Instrument data extraction tool.Data synthesis Meta- analysis was conducted using random effects model with an inverse variance method with RevMan5 software. Heterogeneity between the studies was assessed using ξ test at a p-value of <0.1. Summary statistics were expressed as Standardized Mean Difference with 95% confidence intervals at a p-value of <0.05.Results From 3985 titles identified during the initial search, 3 cohort studies were included in the review following detailed examination and critical appraisal. Mean blood serum level of IgG1 directed against MSP of malaria was increased in S.hematobium positive individuals than in schistosoma negative individuals (0.478 and 0.181). This effect was small with no statistical significance, SMD (95% CI), 0.15 (-2.00, 2.31), p=0.89.Similarly a small and statistically not significant increase in mean blood serum levels of IgG3 and IFN-γ directed against MSP of malaria were found in schistosoma positive individuals than in schistosoma negative individuals with a SMD (95% CI) of 0.31 (-0.66, 1.29), p=0.52 and 0.16 (-0.27, 0.59), p=0.46, respectively.

Implications for Practice Concurrent schistosoma infection increases humoral immune response measures to malaria. This could confound an increase in humoral immune response measures after the administration of malaria vaccine. In addition, it might increase the incidence of malaria complication such as cerebral malaria by increasing IFN-γ levels.Implications for Research Further longitudinal studies aimed at determining the difference in long term response (cellular immunity) to malaria vaccine in individuals with and without schistosoma infection need to be undertaken.