Associations Of Il13 Gene Polymorphisms And Immune Factors With Schistosoma Haematobium Infection In Schoolchildren In Four Schistosomiasis-Endemic Communities In Ghana

Author summary Schistosomiasis is a neglected tropical disease with an estimated morbidity of 2.54 million disability-adjusted life years (DALYS), ranking it third among the parasitic diseases after Malaria and Dengue fever (WHO, 2018). About a decade ago, the World Health Organization (WHO) and its partners committed to intensifying efforts at increasing coverage during annual mass chemotherapy programmes in affected countries. This has influenced the reduction of the estimated disease-associated morbidity from 4.5 million DALYs in 2002 (WHO, 2002) to the current rate. Despite these gains, there is still growing concern that the persistent and extensive use of Praziquantel (PZQ) (the only approved chemotherapeutic agent) in these campaigns may lead to the development of poorly-responding phenotypes of Schistosoma sp. Strategies therefore to mitigate such possibilities may prove very advantageous, while research efforts towards the development of an effective vaccine continues. There has been growing evidence in recent years that infection of inhabitants in endemic areas may be influenced not only by environmental, but also by genetic factors as well. Of particular interest in this regard, is the region in the human genome, 5q31-q33, which bears several genes associated with immune function. One such group within this region is the T-helper 2 (Th2) cluster of genes, which are responsible for the production interleukin-4 (IL-4), IL-5, and IL-13 during immune response. We focused on single-nucleotide polymorphisms (SNPs) occurring in the IL-13 promoter region, particularly IL13-1055C/T, IL13-591A/G, and IL13-1258A/G, where we observed interesting trends with regard to participants' infection status in association with the polymorphisms they presented with. Also, we assessed their immune profiles after stratifying by age, and herein indicate trends which reflect observed age-associated trends between S. haematobium infection and the IL-13 polymorphisms. The outcomes presented indicate a need for further work which challenges the current 'one size fits all' strategy in mass chemotherapy programmes and advocates for participant-specific/sub-group tailored programmes. This is more likely to minimize the likelihood for the development of resistant Schistosoma strains to PZQ.Background Schistosomiasis remains a major public health issue with over 90% of the prevalence rates recorded in Sub-Saharan Africa. In this study, the relationships between different interleukin gene polymorphisms (IL-13-591A/G, IL-13-1055C/T, IL-13-1258A/G) and Schistosoma haematobium infection levels were evaluated; as well as the host plasma antibodies and cytokine profiles associated with schistosomiasis infection. Methodology A total of 469 school children aged 6 to 19 years from four schistosomiasis-endemic communities in Ghana were involved. Single urine and stool samples were obtained from each pupil, processed via sedimentation and Kato-Katz, and examined via microscopy for Schistosoma and soil-transmitted helminth (STH) eggs. Next, venous blood samples were drawn from 350 healthy pupils, and used to measure antibody and plasma cytokine levels by ELISA. Single nucleotide polymorphisms in the IL-13 gene were genotyped on 71 selected blood samples using the Mass Array technique. Principal findings and conclusion The overall prevalence of urinary schistosomiasis was 21.11%. Community-level prevalences were 17.12%, 32.11%, 20.80%, and 15.32% for Asempaneye, Barikumah, Eyan Akotoguah, and Apewosika respectively. Generally, higher S. haematobium infection prevalence and intensity were recorded for participants with genotypes bearing the IL13-1055C allele, the IL13-591A, and the IL13-1258A alleles. Also, higher S. haematobium infection prevalence was observed among participants in the 12-14-year age group with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Interestingly, higher STH prevalence was also observed among participants with the IL13-1055C, IL13-591A, and IL13-1258A alleles. Furthermore, the age-associated trends of measured antibodies and cytokines of S. haematobium-infected school-children depicted a more pro-inflammatory immune profile for pupils aged up to 1l years, and an increasingly anti-inflammatory profile for pupils aged 12 years and above. This work provides insight into the influence of IL-13 gene polymorphisms on S. haematobium, and STH infections, in school-aged children (SAC).