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

Lawrence Lubyayi,Elson Abayo,Samuel Kiwanuka,James Kaweesa,Prossy Kabuubi,Jacent Nassuuna,John Vianney Tushabe,Joel Sserubanja,William Ssenyonga,Richard E Sanya ,Alison M Elliott ,Govert J Van Dam ,Edridah M Tukahebwa ,Emily L Webb ,Narcis B Kabatereine ,Paul L A M Corstjens ,Laviiswa Trial Team

doi:10.1093/ofid/ofaa091

Abstract

BackgroundPraziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas. Animal models demonstrate Schistosoma parasite resistance to praziquantel after repeated exposure.MethodsWe conducted a parasitological survey in 26 fishing communities in Uganda after 4 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 test and 3-sample Kato-Katz. We calculated cure rates (CRs) and egg reduction rates (ERRs) based on 3-sample Kato-Katz and infection intensity using worm-specific circulating anodic antigen (CAA) in blood, comparing these between quarterly and annually treated participants.ResultsSingle-sample Kato-Katz Schistosoma mansoni prevalence was 22% in 1,056 quarterly treated participants and 34% in 1,030 annually treated participants (risk ratio, 0.62; 95% confidence interval [CI], 0.40 to 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 to 1.58); ERRs were 94% and 81% (difference, –13%; 95% CI, –48% to 2%). There was no impact of quarterly vs annual praziquantel on S. mansoni by CAA.ConclusionsIn 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.

Highlights

Praziquantel mass drug administration (MDA) is recommended in schistosomiasis-endemic areas
Among 110 test-of-cure participants, cure rates (CRs) were 65% and 51% in annually and quarterly treated villages, respectively; egg reduction rate (ERR) were 94% and 81%
Praziquantel is the only drug that is widely available for the treatment of Schistosoma mansoni [3]

Summary

Methods

We conducted a parasitological survey in 26 fishing communities in Uganda after 4 years of quarterly (13 communities) or annual (13 communities) praziquantel MDA, with Schistosoma infection detected by single-stool-sample Kato-Katz. We anticipated that sampling 70 households per village would give >80% power to detect a 25% relative reduction in S. mansoni prevalence in the intensive trial arm compared with standard, assuming a coefficient of variation of 0.2 and standard arm S. mansoni prevalence of 35%. We anticipated that this would give >80% power to detect an absolute increase of 10% in S. mansoni prevalence in the 13 intensively treated study villages between years 3 and 4, assuming a coefficient of variation of 0.1 for this analysis. For the test-ofcure substudy, we anticipated that screening 220 individuals in each arm would yield 70 Kato-Katz-positive participants in the standard arm and 55 in the intensive arm Following up these individuals after treatment would give ~80% power to detect a difference in cure rate of 70% in the standard arm [21] vs 40% in the intensive arm. The prevalence of S. mansoni infection was compared between time points using paired t tests of cluster-level proportions

Results

Discussion

Conclusion