Towards interruption of schistosomiasis transmission in sub-Saharan Africa: developing an appropriate environmental surveillance framework to guide and to support 'end game' interventions

Abstract

Schistosomiasis is a waterborne parasitic disease in sub-Saharan Africa, particularly common in rural populations living in impoverished conditions. With the scale-up of preventive chemotherapy, national campaigns will transition from morbidity- to transmission-focused interventions thus formal investigation of actual or expected declines in environmental transmission is needed as 'end game' scenarios arise. Surprisingly, there are no international or national guidelines to do so in sub-Saharan Africa. Our article therefore provides an introduction to key practicalities and pitfalls in the development of an appropriate environmental surveillance framework. In this context, we discuss how strategies need to be adapted and tailored to the local level to better guide and support future interventions through this transition. As detection of egg-patent infection in people becomes rare, careful sampling of schistosome larvae in freshwater and in aquatic snails with robust species-specific DNA assays will be required. Appropriate metrics, derived from observed prevalence(s) as compared with predetermined thresholds, could each provide a clearer insight into contamination- and exposure-related dynamics. Application could be twofold, first to certify areas currently free from schistosomiasis transmission or second to red-flag recalcitrant locations where extra effort or alternative interventions are needed.

Keywords: Environmental monitoring; Freshwater snails; WASH; Zoonosis; eDNA.

Fig. 1

Key environmental aspects in schistosome transmission as framed by contamination- and exposure- related behaviours. Schistosome eggs can be introduced to freshwater by any infected vertebrate host, in this instance a mother and her pre-school-aged child (who are not targetted in PC campaigns) are depicted. After maturation in keystone species of freshwater snail hosts, schistosome cercariae are released often in copious numbers, which have a potential to infect any demographic group, like the school-aged children in the image depicting exposure-related behaviours (who are the current target of PC campaigns). Each day the emergence, death and decay of the larval stages contributes to aquatic planktonic assemblage and environmental (e) DNA components. Only those aquatic habitats that contain snails patently shedding cercariae pose a potential or actual threat to human health

Fig. 2

Key environmental aspects in schistosome transmission as framed by contamination- and exposure- related behaviours. a Image of Barombi Mbo, South-West Cameroon a small linear village recently sampled in May 2016 during a conjoint parastiological and malacology survey, finding the prevalence of egg-patent S. haematobium infection < 10%. Snails were searched for at six collecting locations (sites 1–6), only B. forskalii and B. truncatus were found at sites 1 and 2, with an average daily collection at each site inspection of 11 and 57 snails over a three day period, respectively. The survey highlights the small-scale heterogenities typical of schistosomiasis. b A schematic of the three phased progress of interventions from morbidity to transmission control then interuption of transmission, as prevalence of egg-patent infection declines as indicated by the blue section. At the sametime the miracidial input will likely concomittantly decline into the local snail fauna, in host (H) or non-host (NH) snails, respectively. Contrary to host snails, non-host snails do not produce cercariae hence play no later role in exposure-related transmission. Measuring and comparing the prevalence of schistosome DNA in H and NH species could provide information in the context of contamination-related and exposure-related measures at different stages during this transition. Conceptually, there should always be additional H snails that are patently (stage II) or pre-patently (stage III) infected and carry schistosome infections. Note that as the human miracidial input declines zoonotic sources may be more obvious and the need for species- and population-specific schistosome probes becomes essential

Fig. 3

a Plot of sample size calculations for low prevalence (10% and less) settings, demonstrating the effect on sample size of reducing prevalence towards 1%, and of increasing the statistical significance (α). In principle, this hypothetical surface could derive from any diagnostic. However, as more sensitive diagnostics are each applied, the surface shape will remain similar only now with a raised offset, as previously ‘missed’ infections are subsequently detected. Note that even at assumed 10% prevalence of Schistosoma-infected snails, sample sizes for any level of significance of α = 0.05 or more are already between 140 and 240 snails; this increases as prevalence reduces and as more precision and statistical significance are applied, to levels that are laregly impractical (1500–2700 snails). Formula used is: $n={\left(Z_{\frac{a}{2}}\right)}^2\rho \left(1-\rho \right)/d^2$, where: n = sample size, p = estimated prevalence, d = precision of the estimate (with the assumption that d = 0.5*p given low prevalence setting), Zα/2 = the Z-statistic associated with the statistical significance α/2 (Z-statistic adjusted for each of α = 0.05 to α = 0.01) [94]. b Plot of prevalence of schistosomiasis across 100 schools (mean prevalence of 1.5%), ranked in ascending order according to the well-known pattern of overdispersion or focalisation. It may be proportionately easier to find infected snails in water contact sites surrounding those schools in red, while it will be harder around those schools in green. A flexible sample size criteria seems sensible where more geographical attention is given to those habitats in the vicinity of schools in red rather than around schools in green