Paediatric Schistosomiasis: diagnosis, morbidity and treatment

Abstract

Schistosomiasis is a major parasitic disease caused by parasitic helminths of the genus Schistosoma which affects children in Africa, with negative impacts on general health, growth and cognitive development. Infection and morbidity are controlled by treatment with the antihelminthic drug praziquantel. Preschool children (aged ≤5 years old) have been neglected both in terms of research and control, and it is only recently that the World Health Organization (WHO) recommended praziquantel treatment and the inclusion of preschool children in control programmes. However, the burden of disease in this age group still remains poorly understood, and the performance of the currently available tools for detecting infection and morbidity is still yet to be systematically evaluated. The aim of this thesis was to compare the utility of currently available tools for diagnosing S. haematobium infection and related morbidity. The initial study cohort consisted of 438 Zimbabwean children (age range: 1-10 years) who were endemically exposed. Point-of-care schistosome-related morbidity markers applicable in the field, as well as serological biomarkers (CHI3L1, CRP, ferritin, resistin and SLPI) and inflammatory cytokines (IL-4, IL-5, IL-10, IL-13 and IFN-γ) that could predict early stages of immune-mediated pathology due to schistosomiasis were measured. Using a combination of applied statistical methods, the effect of treatment on factors associated with S. haematobium exposure, infection and morbidity in children aged 1-5 years was determined and the findings compared with those observed in children aged between 6-10 years old, who are the current targets of the schistosome control programmes. In this thesis, I able to demonstrate that preschool children carried significant infection, further reiterating the need for their inclusion in control programmes. Furthermore, this study demonstrated the importance of using additional sensitive diagnostic methods as this has implications on the required intervention strategies for the targeted populations. This study further revealed that preschool children can be effectively screened for schistosome-related morbidity using the same currently available diagnostic tools applicable to older children. Urinalysis markers microhaematuria, proteinuria and albuminuria are recommended in this thesis as the best choice for rapid assessment of morbidity attributed to S. haematobium infection in the field. Additionally, it was shown that the praziquantel treatment regimens aimed at controlling schistosome infection and morbidity currently designated for primary school-aged children and older populations are applicable to preschool-aged children. The involvement of serum biomarkers and immune correlates in the biological processes of inflammation suggests that these markers can be potential early predictors of schistosome-related pathology. Further research efforts are required to establish the relationship between these biomarkers and presence of schistosome-related morbidity as measured using point-of-care indicators in larger cohorts of populations chronically exposed to schistosome infections. In summary, the findings of this thesis highlight the need for the refinement of existing diagnostic methods for accurate detection of infection and morbidity in children. This will enable appropriate and timely intervention strategies, aimed at improving the current and future health of preschool aged-children to be implemented. The findings presented here will aid researchers and other stakeholders in making informed choices about intervention tools for control programmes targeting young children.