The World Health Organization 2030 goals for onchocerciasis: Insights and perspectives from mathematical modelling

The World Health Organization (WHO) has embarked on a consultation process to refine the 2030 goals for priority neglected tropical diseases (NTDs), onchocerciasis among them. Current goals include elimination of transmission (EOT) by 2020 in Latin America, Yemen and selected African countries. The new goals propose that, by 2030, EOT be verified in 10 countries; mass drug administration (MDA) with ivermectin be stopped in at least one focus in 34 countries; and that the proportion of the population no longer in need of MDA be equal or greater than 25%, 50%, 75% and 100% in at least 16, 14, 12, and 10 countries, respectively. The NTD Modelling Consortium onchocerciasis teams have used EPIONCHO and ONCHOSIM to provide modelling insights into these goals. EOT appears feasible in low-moderate endemic areas with long-term MDA at high coverage (≥75%), but uncertain in areas of higher endemicity, poor coverage and adherence, and where MDA has not yet, or only recently, started. Countries will have different proportions of their endemic areas classified according to these categories, and this distribution of pre-intervention prevalence and MDA duration and programmatic success will determine the feasibility of achieving the proposed MDA cessation goals. Highly endemic areas would benefit from switching to biannual or quarterly MDA and implementing vector control where possible (determining optimal frequency and duration of anti-vectorial interventions requires more research). Areas without loiasis that have not yet initiated MDA should implement biannual (preferably with moxidectin) or quarterly MDA from the start. Areas with loiasis not previously treated would benefit from implementing test-and(not)-treat-based interventions, vector control, and anti-Wolbachia therapies, but their success will depend on the levels of screening and coverage achieved and sustained. The diagnostic performance of IgG4 Ov16 serology for assessing EOT is currently uncertain. Verification of EOT requires novel diagnostics at the individual- and population-levels

Designing antifilarial drug trials using clinical trial simulators

Lymphatic filariasis and onchocerciasis are neglected tropical diseases (NTDs) targeted for elimination by mass (antifilarial) drug administration. These drugs are predominantly active against the microfilarial progeny of adult worms. New drugs or combinations are needed to improve patient therapy and to enhance the effectiveness of interventions in persistent hotspots of transmission. Several therapies and regimens are currently in (pre-)clinical testing. Clinical trial simulators (CTSs) project patient outcomes to inform the design of clinical trials but have not been widely applied to NTDs, where their resource-saving payoffs could be highly beneficial. We demonstrate the utility of CTSs using our individual-based onchocerciasis transmission model (EPIONCHO-IBM) that projects trial outcomes of a hypothetical macrofilaricidal drug. We identify key design decisions that influence the power of clinical trials, including participant eligibility criteria and post-treatment follow-up times for measuring infection indicators. We discuss how CTSs help to inform target product profiles