Reduced Efficacy of Praziquantel Against Schistosoma mansoni Is Associated With Multiple Rounds of Mass Drug Administration

Abstract

Background: Mass drug administration (MDA) with praziquantel is the cornerstone of schistosomiasis control in sub-Saharan Africa. The effectiveness of this strategy is dependent on the continued high efficacy of praziquantel; however, drug efficacy is rarely monitored using appropriate statistical approaches that can detect early signs of wane.

Methods: We conducted a repeated cross-sectional study, examining children infected with Schistosoma mansoni from 6 schools in Uganda that had previously received between 1 and 9 rounds of MDA with praziquantel. We collected up to 12 S. mansoni egg counts from 414 children aged 6-12 years before and 25-27 days after treatment with praziquantel. We estimated individual patient egg reduction rates (ERRs) using a statistical model to explore the influence of covariates, including the number of prior MDA rounds.

Results: The average ERR among children within schools that had received 8 or 9 previous rounds of MDA (95% Bayesian credible interval [BCI], 88.23%-93.64%) was statistically significantly lower than the average in schools that had received 5 rounds (95% BCI, 96.13%-99.08%) or 1 round (95% BCI, 95.51%-98.96%) of MDA. We estimate that 5.11%, 4.55%, and 16.42% of children from schools that had received 1, 5, and 8-9 rounds of MDA, respectively, had ERRs below the 90% threshold of optimal praziquantel efficacy set by the World Health Organization.

Conclusions: The reduced efficacy of praziquantel in schools with a higher exposure to MDA may pose a threat to the effectiveness of schistosomiasis control programs. We call for the efficacy of anthelmintic drugs used in MDA to be closely monitored.

Keywords: anthelmintic efficacy; generalized linear mixed model; parasite; praziquantel; schistosomiasis.

Figure 1.

Maps of study sites. A, Map of Uganda in an East African context with Mayuge and Tororo districts highlighted. B, Location of the schools (triangles) surveyed in Mayuge district. C, Location of the school (triangle) surveyed in Tororo district.

Figure 2.

Flow diagram of patient recruitment and exclusion criteria for egg reduction rate analysis after treatment with praziquantel (PZQ) and albendazole (ALB).

Figure 3.

Estimated egg reduction rates of Schistosoma mansoni from 414 children in eastern Uganda treated with praziquantel. Individual estimates are stratified by school (A) and by mass drug administration (MDA) exposure category (B). Black points indicate the mean of the posterior distribution, and the gray bars indicate 95% Bayesian credible intervals (BCIs). The hashed lines correspond to the nominal reference threshold of 90% suggested by the World Health Organization. Note that the BCIs have been truncated at 1% and 99%. Category of MDA reflects the previous number of rounds of treatment with praziquantel the schools have received (high is 8 or 9; medium is 5; low is 1).

Figure 4.

Posterior distribution of average egg reduction rates (ERRs) of Schistosoma mansoni in 414 children from 6 primary schools in eastern Uganda treated with praziquantel. The average ERRs are stratified by school (A) and by mass drug administration (MDA) exposure category (B). The posteriors were constructed by marginalizing over the fixed- and random-effects coefficients estimated from the generalized linear mixed model. The colored hashed lines indicate the mean of the posterior. Category of MDA reflects the previous number of rounds with praziquantel the schools have received (high is 8 or 9; medium is 5; low is 1).