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Background Kato-Katz examination of stool smears is the field-standard method for detecting Schistosoma mansoni infection. However, Kato-Katz misses many active infections, especially of light intensity. Point-of-care circulating cathodic antigen (CCA) is an alternative field diagnostic that is more sensitive than Kato-Katz when intensity is low, but interpretation of CCA-trace results is unclear. To evaluate trace results, we tested urine and stool specimens from 398 pupils from eight schools in Burundi using four approaches: two in Burundi and two in a laboratory in Leiden, the Netherlands. In Burundi, we used Kato-Katz and point-of-care CCA (CCAB). In Leiden, we repeated the CCA (CCAL) and also used Up-Converting Phosphor Circulating Anodic Antigen (CAA). Methods We applied Bayesian latent class analyses (LCA), first considering CCA traces as negative and then as positive. We used the LCA output to estimate validity of the prevalence estimates of each test in comparison to the population-level infection prevalence and estimated the proportion of trace results that were likely true positives. Results Kato-Katz yielded the lowest prevalence (6.8%), and CCAB with trace considered positive yielded the highest (53.5%). There were many more trace results recorded by CCA in Burundi (32.4%) than in Leiden (2.3%). Estimated prevalence with CAA was 46.5%. LCA indicated that Kato-Katz had the lowest sensitivity: 15.9% [Bayesian Credible Interval (BCI): 9.2–23.5%] with CCA-trace considered negative and 15.0% with trace as positive (BCI: 9.6–21.4%), implying that Kato-Katz missed approximately 85% of infections. CCAB underestimated disease prevalence when trace was considered negative and overestimated disease prevalence when trace was considered positive, by approximately 12 percentage points each way, and CAA overestimated prevalence in both models. Our results suggest that approximately 52.2% (BCI: 37.8–5.8%) of the CCAB trace readings were true infections. Conclusions Whether measured in the laboratory or the field, CCA outperformed Kato-Katz at the low infection intensities in Burundi. CCA with trace as negative likely missed many infections, whereas CCA with trace as positive overestimated prevalence. In the absence of a field-friendly gold standard diagnostic, the use of a variety of diagnostics with differing properties will become increasingly important as programs move towards elimination of schistosomiasis. It is clear that CCA is a valuable tool for the detection and mapping of S. mansoni infection in the field and CAA may be a valuable field tool in the future.

In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy. In this Personal View, we highlight recent advances that, taken together, support a call to revise the global strategy and guidelines for preventive chemotherapy and complementary interventions against schistosomiasis and soil-transmitted helminthiasis. These advances include the development of guidance that is specific to goals of morbidity control and elimination of transmission. We quantify the result of forgoing this opportunity by computing the yearly disease burden, mortality, and lost economic productivity associated with maintaining the status quo. Without change, we estimate that the population of sub-Saharan Africa will probably lose 2·3 million disability-adjusted life-years and US$3·5 billion of economic productivity every year, which is comparable to recent acute epidemics, including the 2014 Ebola and 2015 Zika epidemics. We propose that the time is now to strengthen the global strategy to address the substantial disease burden of schistosomiasis and soil-transmitted helminthiasis.

The susceptibility of coliform bacteria and bacterial pathogens to free chlorine residuals was determined before and after incubation with amoebae and ciliate protozoa. Viability of bacteria was quantified to determine their resistance to free chlorine residuals when ingested by laboratory strains of Acanthamoeba cestellanii and Tetrahymena pyriformis. Cocultures of bacteria and protozoa were incubated to facilitate ingestion of the bacteria and then were chlorinated, neutralized, and sonicated to release intracellular bacteria. Qualitative susceptibility of protozoan strains to free chlorine was also assessed. Protozoa were shown to survive and grow after exposure to levels of free chlorine residuals that killed free-living bacteria. Ingested coliforms Escherichia coli, Citrobacter freundii, Enterobacter agglomerans, Enterobacter cloacae, Klebsiella pneumoniae, and Klebsiella oxytoca and bacterial pathogens Salmonella typhimurium, Yersinia enterocolitica, Shigella sonnei, Legionella gormanii, and Campylobacter jejuni had increased resistance to free chlorine residuals. Bacteria could be cultured from within treated protozoans well after the time required for 99% inactivation of free-living cells. All bacterial pathogens were > 50-fold more resistant to free chlorine when ingested by T. pyriformis. Escherichia coli ingested by a Cyclidium sp., a ciliate isolated from a drinking water reservoir, were also shown to be more resistant to free chlorine. The mechanism that increased resistance appeared to be survival within protozoan cells. This study indicates that bacterial can survive ingestion by protozoa. This bacterium-protozoan association provides bacteria with increased resistance to free chlorine residuals which can lead to persistence of bacteria in chlorine-treated water. We propose that resistance to digestion by predatory protozoa was an evolutionary precursor of pathogenicity in bacteria and that today it is a mechanism for survival of fastidious bacteria in dilute and inhospitable aquatic environments.

Schistosomiasis is a parasitic disease that affects over 100 million children in the world living mostly in sub-Saharan Africa. This thesis explored several aspects of the disease affecting the health of children from two African endemic countries: Kenya and Uganda. Epidemiological work revealed a worrisome association between schistosomiasis and malnutrition (both acute and chronic) as well as anaemia. A novel paediatric quality of life assessment was performed in children with the disease with a significant decrease in their psychosocial functioning. Further work went into testing and validating novel morbidity detection tools to identify sub-clinical and overt disease; firstly in Kenya the 20-meter shuttle run test performed accurately in detecting anaemia associated with schistosomiasis, secondly in Uganda, point-of-care tests (faecal occult blood and calprotectin) correlated with severity of intestinal schistosomiasis. As a disease of poverty, schistosomiasis co-exists with other pandemic diseases such as HIV and the tandem HIV-schistosomiasis has not yet been explored in children. A review on the current knowledge on the subject to help delineate the very needed research agenda is presented. The final work in the thesis is the first pharmacokinetic/pharmacodynamics study of praziquantel in children, the only drug available for the treatment of schistosomiasis. The results of this study suggest that the current recommended dose for control programmes may be too low, particularly for preschool children. Overall, this work is an important contribution to paediatric schistosomiasis and opens up future research venues that need to be explored in order to fully understand this disabling disease. This can be done through better clinical staging, affordable morbidity detection tools and optimized treatment.