Multivariable Regression Analysis in Schistosoma mansoni-Infected Individuals in the Sudan Reveals Unique Immunoepidemiological Profiles in Uninfected, egg+ and Non-egg+ Infected Individuals

Background: In the Sudan, Schistosoma mansoni infections are a major cause of morbidity in school-aged children and infection rates are associated with available clean water sources. During infection, immune responses pass through a Th1 followed by Th2 and Treg phases and patterns can relate to different stages of infection or immunity. Methodology: This retrospective study evaluated immunoepidemiological aspects in 234 individuals (range 4–85 years old) from Kassala and Khartoum states in 2011. Systemic immune profiles (cytokines and immunoglobulins) and epidemiological parameters were surveyed in n = 110 persons presenting patent S. mansoni infections (egg+), n = 63 individuals positive for S. mansoni via PCR in sera but egg negative (SmPCR+) and n = 61 people who were infection-free (Sm uninf). Immunoepidemiological findings were further investigated using two binary multivariable regression analysis. Principal Findings: Nearly all egg+ individuals had no access to latrines and over 90% obtained water via the canal stemming from the Atbara River. With regards to age, infection and an egg+ status was linked to young and adolescent groups. In terms of immunology, S. mansoni infection per se was strongly associated with increased SEA-specific IgG4 but not IgE levels. IL-6, IL-13 and IL-10 were significantly elevated in patently-infected individuals and positively correlated with egg load. In contrast, IL-2 and IL-1β were significantly lower in SmPCR+ individuals when compared to Sm uninf and egg+ groups which was further confirmed during multivariate regression analysis. Conclusions/Significance: Schistosomiasis remains an important public health problem in the Sudan with a high number of patent individuals. In addition, SmPCR diagnostics revealed another cohort of infected individuals with a unique immunological profile and provides an avenue for future studies on non-patent infection states. Future studies should investigate the downstream signalling pathways/mechanisms of IL-2 and IL-1β as potential diagnostic markers in order to distinguish patent from non-patent individuals. Author Summary: Schistosome infections are a major public health problem and currently 230 million people are infected with these blood-dwelling parasitic helminths. Schistosomiasis remains the most prevalent parasitic disease in the Sudan and control of the infection relies on large-scale administration of praziquantel. Although treatment is immediately effective, it is not a cure and therefore as soon as individuals re-enter freshwater sources with infected vectors, they are at risk of being re-infected. Therefore, increasing access to clean drinking water and adequate sanitation are important measures to reduce the risk of schistosome infection. During this study people from endemic areas in the Sudan were classified according to the presence of S. mansoni DNA in sera or eggs in stool samples and all analysed with regards to epidemiological and immunological parameters. In addition samples from S. mansoni infection-free individuals from the same endemic regions were used as controls. Our findings suggest that epidemiological factors and immune responses to schistosomes depend on the actual infection status (patent versus pre-patent/low egg producing). This improves our understanding of the biology of the disease which facilitates the development of techniques to identify early stages of pathology (fibrosis) which could help prevent further damage and morbidity.