Review 1: "Current Schistosoma Mansoni Exposure and Infection have Distinct Determinants: A Data-driven Population-Based Study in Rural Uganda"

RR:C19 Evidence Scale rating by reviewer:

• Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

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Review: This paper reports on the results of a large and well-conducted study of water contact and Schistosomiasis Mansoni infection in rural Uganda. The results contribute to a series of reports extending over the past 20 to 30 years showing either no or no strong relationship between water contact and schistosomiasis infection. This is not surprising since the environmental determinant of schistosomiasis infection is exposure to schistosome cercariae in water, not to water itself which is the medium in which these cercariae exist and are transported. (See figure 2 of this paper’s reference 42, for example.) The authors are well aware of this distinction despite the fact that, in environmental health generally, exposure refers to contact with the infectious or toxic agent, not the medium in which these agents exist. Hence, the title of the paper is misleading to many readers in that it seems to imply that exposure, conventionally defined as cercarial exposure, is not a determinant of schistosomiasis infection which it unquestionably is. Throughout the text this confusing and non-standard use of the word exposure is continued. The study reports no effort to address the presence of cercariae in water, e.g. the presence of infected snails, or even the desirability of having such data.  Therefore, the study simply confirms the existing strong evidence that the risk of S. Mansoni infection among a population with well documented and widespread infection cannot be based on careful and thorough water contact estimates alone.

With the foregoing caveat in mind, the results of this study are based on an array of data that include a combination of questionnaire and environmental data that represent most of the accessible predictors of water contact likely to be available in rural areas of the developing world. The statistical analysis is thorough, perhaps excessively so, and well documented.  Again, the paper makes the case that water contact estimates based on currently available data are inadequate to inform the risk of schistosomiasis infection in any useful way. Indeed, the results contribute to the already strong case for the continued development of practical methods of assessing the presence of cercariae in water in common with many other infectious waterborne agents (e.g. Sengupta et al, www.pnas.org/cgi/doi/10.1073/pnas.1815046116).