Repeated praziquantel treatments remodel the genetic and spatial landscape of schistosomiasis risk and transmission

Abstract

Repeated treatments with praziquantel reduce schistosomiasis prevalence and morbidity, but transmission persists and populations often recover within a few years. To identify factors associated with persistence, we surveyed and treated all identified Schistosoma mansoni infections in two rural Brazilian communities (Jenipapo and Volta do Rio) in 2009, 2012 and 2013. Eggs were collected from all infected individuals and genotyped with 11 microsatellite markers to evaluate parasite differentiation and diversity. After successive rounds of community-wide treatment, prevalence decreased from 45% to 24% then 16%. Intensity of infection decreased by 57% over this period, and the number of eggs transmitted to the environment decreased by 92%. During all time periods the majority of eggs were excreted by those >15years of age. The incidence was 23% in 2012 and 15% in 2013, consistent with a decrease in transmission. There was little immigration or gene flow over a distance of 6km. On reinfection, infrapopulations were moderately differentiated indicating that pretreatment multilocus genotypes were not fully reacquired. The effective population size responded to census population decline more rapidly than differentiation. Reinfection was concentrated in the downstream portion of Jenipapo, consistent with the observed increased human fecal contamination. At this scale and in this area S. mansoni infections exist on a fragmented landscape with a highly focal pattern of transmission that may facilitate future elimination.

Keywords: Brazil; Effective population size; Extinction; Genetic differentiation; Praziquantel; Reinfection; Spatial analysis.

Fig. 1

Map of Ubaíra and Santa Inês areas in Brazil. Jenipapo and Volta do Rio are discrete communities 6 km apart, and each is 9 km distant from urbanized centres.

Fig. 2

Study Design. Demographic and parasitologic surveys were conducted in 2009, 2012 and 2013. Those with stools positive for Schistosoma mansoni eggs were treated with praziquantel and re-examined after 4 – 6 weeks. Those with persistent infections were retreated. In 2012 and 2013 there were two and zero persistent infections, respectively.

Fig. 3

Estimated total per day Schistosoma mansoni egg production (millions/day), 2009 – 2013. Data points represent the sum of eggs produced by all infected individuals in each community based on stool weight and mean stool egg concentration.

Fig. 4

Age-specific prevalence and intensity of Schistosoma mansoni infections, 2009 – 2013. epg, eggs per gram of feces.

Fig. 5

Spatial distribution of Schistosoma mansoni infection/reinfection in Jenipapo, Brazil, 2009 – 2013. The spatial kernel density estimation of numbers of S. mansoni-infected individuals by household in each year. Detectable infections were zero at the end of 2009 and 2012. Inset shows the distribution of homes which changed little during this period.