Reduction in Onchocerca volvulus infection prevalence and intensity in Logo Health Zone in Ituri, Democratic Republic of the Congo, in the absence of interventions: Results of screening for clinical trials of moxidectin vs. ivermectin in 2010 and 2021-2023

Background: In Ituri province, 7576 and 1056 volunteers living in the Health Zone (ZdS) Logo and Nyarambe, respectively, were screened in 2021-2023 for two studies comparing efficacy and/or safety of moxidectin and ivermectin in individuals with or without detectable Onchocerca volvulus skin microfilariae densities (SmfD, microfilariae/mg skin). Site selection was based on the clinical trial capacity established for the Phase 3 study of moxidectin and SmfD measured among 1373 and 36 individuals screened in ZdS Logo and Nyarambe, respectively, in 2010. We are comparing the SmfD measured in 2010 and 2021-2023 in ZdS Logo where ivermectin mass administration was never implemented. Methods: Four skin snips from each consenting/assenting individual ≥12 years old were weighed and incubated in isotonic saline for ≥8 hours. Emerged microfilariae were counted and SmfD calculated as the mean of the number of microfilariae/mg skin of each snip. Other data collected included age, gender, village of residence and history of ivermectin treatment. Results: In 2010 and 2021-2023, respectively, adults (18-93 years old) represented 92.1% and 73.2%, and women 36.9% and 46.6% of the 1373 and 7547 volunteers from ZdS Logo without reported prior ivermectin treatment. Among these adults and adolescents (12-17 years), no microfilariae were detected in snips from 23.3% and 26.9% in 2010 and 89.8% and 96.8% in 2021-2023, respectively, with mean SmfD (± standard deviation) being 24.30±35.52 and 11.8±18.37 in 2010 and 1.1±6.44 and 0.3±2.62 in 2021-2023, respectively. Conclusions: Given that the reduction in infection prevalence and intensity cannot be attributed to ivermectin distribution, it has to be due to reduction in infective vector biting rates, possibly linked to a recently proposed change in vector species triggered by land-use changes. Because SmfD reflect transmission events approximately 2-15 years earlier, infective vector biting rate assessment is needed to determine current transmission rates. Reduced transmission shifts macrofilariae age distribution towards older macrofilariae with lower reproductive capacity. Comparison of the results from the Phase 3 and the ongoing efficacy study might help determine whether macrofilariae drug-susceptibility changes significantly with macrofilariae age. Should that be the case, transmission models evaluating the impact of mass drug administrations could be adjusted.