Review 1: "How does Treatment Coverage and Proportion Never Treated Influence the Success of Schistosoma Mansoni Elimination as a Public Health Problem by 2030?"

RR:C19 Evidence Scale rating by reviewer:

• Potentially informative. The main claims made are not strongly justified by the methods and data, but may yield some insight. The results and conclusions of the study may resemble those from the hypothetical ideal study, but there is substantial room for doubt. Decision-makers should consider this evidence only with a thorough understanding of its weaknesses, alongside other evidence and theory. Decision-makers should not consider this actionable, unless the weaknesses are clearly understood and there is other theory and evidence to further support it.

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Review: This manuscript addresses the impact of the proportion of the population never treated on school-based and community wide treatment efficacy by mass administration of praziquantel using two individually-based mathematical models to calculate the number of treatment rounds required to achieve elimination of S. mansoni as a public health problem. The models used and results achieved are straightforward and well-documented extensions of the many earlier studies carried out by these authors. The results are unsurprising.

However, there are at least two assumptions underlying the results that limit their significance from the perspective of this reviewer. The first is that the environmental and behavioral assumptions underlying the intensity of disease transmission are unaltered over the period of analysis which can range up to 10-15 years. This seems unlikely in Africa today which seems to require at least a caveat to be added to the report.

More importantly is that at least the SCHISTOX model seems not to acknowledge the probable effects of genetically differential susceptibility to infection, evidence of which was reported by Abel et al. for S. mansoni as long as 30 years ago. Differential susceptibility is a highly probable contributor to the 20/80 rule popularized for infectious diseases generally by Woolhouse et al. which, as they pointed out, has major implications for control programs such as those utilizing MDA. While the SCHISTOX model incorporates a gamma-distributed “level of predisposition”, this effect models the potentially genetically determined differences in larval uptake at a given exposure, but apparently produces some uptake at any exposure. 
Finally, one might speculate that a major reason for being among the never treated, NT, is the prolonged absence of symptoms which could include a substantial fraction of the uninfected and thereby diminish the importance of that group in being sources of ongoing disease transmission. Hence, it appears that the issue must be addressed in the present report.