For the last 30 years, control and treatment of onchocerciasis has relied on mass drug administration (MDA) using ivermectin (Mectizan, donated by Merck & Co through the Mectizan Donation Programme (https://mectizan.org). This drug rapidly kills microfilariae but does not kill adult parasites. Repeated annual or biannual treatment leads to a reduction in morbidity (eye and skin disease) associated with the death and destruction of the microfilariae. Furthermore, removal of microfilariae from the skin blocks transmission of the infection and this has resulted in eradication of the disease from isolated foci in Colombia, Ecuador, Mexico and Guatemala. However, in areas of Africa with high initial prevalence of infection, transmission continues even after 25 years of annual treatment (https://doi.org/10.1371/journal.pntd.0004392). Mathematical models have shown that elimination of onchocerciasis using ivermectin alone, if at all possible, would require at least another 25 years of MDA (https://doi.org/10.1371/journal.pntd.0003664).
The prospects for elimination of onchocerciasis through MDA alone are severely reduced because ivermectin cannot be used across large areas of central Africa where onchocerciasis and loiasis are co-endemic (Figure 9). Loiasis, another filarial disease, is caused by the eye worm Loa loa, which is closely related to O volvulus and similarly gives birth to large numbers of microfilariae. However, L loa microfilaria live in the blood and their rapid death following ivermectin treatment can be associated with severe adverse and sometimes fatal inflammatory responses. It has been estimated that 10 million (2015) [rising to 17 million in 2025, https://doi.org/10.1093/cid/ciz647] people live in such high-risk areas and are potentially affected by this contraindication. In these areas, communities often do not receive supportive treatment; onchocerciasis transmission rates remain high; and they provide a reservoir for reintroduction of the infection to neighbouring communities from which the disease has been eliminated.
Additionally, the potential emergence of drug-resistant O volvulus poses a threat to the long-term effectiveness of using ivermectin alone in all areas (https://doi.org/10.1371/journal.pntd.0000998; https://doi.org/10.1371/journal.pntd.0005816). In some foci, microfilariae are reappearing in the skin following ivermectin treatment at a faster rate than anticipated, and this may be indicative of development of drug resistance, which is widespread amongst parasites of veterinary importance.