Does Intensive Treatment Select for Praziquantel Resistance in High-Transmission Settings? Parasitological Trends and Treatment Efficacy Within a Cluster-Randomized Trial

Abstract

Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel following repeated exposure. We conducted a parasitological survey in 26 fishing communities, Uganda, following four years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. A test-of-cure was done in participants who were positive on both urine circulating cathodic antigen (CCA) test and three-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on three-sample Kato-Katz, and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants. Single-sample Kato-Katz S. mansoni prevalence was 22% in 1,056 quarterly-treated participants and 34% in 1,030 annually-treated participants (risk ratio 0.62, 95%CI: 0.40,0.94). Among 110 test-of-cure participants, CRs were 65% and 51% in annually and quarterly treated villages, respectively (odds ratio 0.65, 95%CI: 0.27,1.58); ERRs were 94% and 81% (difference -13%, 95%CI:-48%,2%). There was no impact of quarterly versus annual praziquantel on S. mansoni by CAA. In this schistosomiasis hot-spot, there was little evidence of decreased praziquantel efficacy. However, in the absence of alternative therapies, there remains a need for continued vigilance of praziquantel efficacy in the MDA era.