Authors

MG Basáñez¹; P Milton¹; K Kura¹; J Hamley¹; M Walker²;  ¹ Imperial College London, UK;  ² Royal Veterinary College, University of London, UK

Discussion

The World Health Organization’s 2021–2030 Roadmap on Neglected Tropical Diseases has proposed that elimination (interruption) of transmission (EoT) be achieved and verified in 12 onchocerciasis-endemic countries by 2030. In Africa, epidemiological and modelling studies have suggested that EoT may not be achieved with annual mass drug administration (MDA) of ivermectin alone, particularly in areas of high initial endemicity (characterised by high vector biting rates). Phase II and III clinical trials demonstrated moxidectin’s superiority to ivermectin regarding clearance of Onchocerca volvulus skin microfilariae. Not only was the amicrofilaridermic period following moxidectin treatment longer, but also there was less inter-individual variation in treatment responses compared to ivermectin. In 2018, moxidectin was approved by the US FDA for treatment of O. volvulus infection in those aged ≥12 years. We used the stochastic EPIONCHO-IBM model to compare the probabilities of reaching EoT between ivermectin and moxidectin MDA for a range of (from hypo- to hyper-) endemicity levels, treatment frequency and adherence, with and without inter-individual response variation. We examined assumptions regarding: a) the modelling of vector biting rates to simulate pre-intervention endemicity levels; b) drugs’ efficacy and their effects on O. volvulus reproductive biology; c) starting with moxidectin from the outset vs. switching to moxidectin during current ivermectin MDA programmes; d) treating the population aged ≥5 years with moxidectin vs. treating the 5–11-year olds with ivermectin and those aged ≥12 years with moxidectin; and e) random vs. systematic variation in inter-individual treatment responses. EPIONCHO-IBM’s projections indicated that annual moxidectin MDA would be roughly equivalent to 6-monthly ivermectin MDA, but 6-monthly moxidectin was the best strategy, leading to substantial reductions in the number of years necessary to achieve EoT, and the only strategy that would help achieve EoT in highly endemic areas. To improve modelling projections, it is crucial to collect further data on: i) patterns of treatment adherence in endemic communities; i) the effect of moxidectin on adult O. volvulus worms; iii) the potential prophylactic effect of moxidectin; and iv) patterns of inter-individual variation in treatment responses over subsequent treatment rounds.