A new powerful drug to combat river blindness

www.thelancet.com Published online January 17, 2018 http://dx.doi.org/10.1016/S0140-6736(18)30101-6 1 Onchocerciasis, which is a disease caused by the filarial worm Onchocerca volvulus, is transmitted from individual to individual by Simulium black flies that breed in fast flowing rivers. The millions of larvae (microfilariae) released by the adult parasites invade skin and eyes where they can cause severe manifestations, including blindness. International control programmes for onchocerciasis have been implemented since the 1970s. Insecticide spraying to eliminate the vector was supplemented by, and ultimately replaced from the 1990s by, mass administration of ivermectin, a drug which kills microfilariae and prevents their release by the adult worms for several months. This mass treatment was made possible by the decision of Merck & Co to donate ivermectin for the control of onchocerciasis. Since ivermectin does not kill adult O volvulus, annual treatments are required to keep microfilarial densities low. To ensure distribution of the drug is sustained in the long term, the African Programme for Onchocerciasis Control implemented community-directed treatment with ivermectin. The programme has had an impressive impact; in most endemic foci, onchocerciasis is no longer a public health problem and transmission might have been interrupted in some foci. However, the focus is now global elimination of onchocerciasis, which requires treatment in areas of low endemicity that are not covered by community-directed treatment with ivermectin, use of new diagnostic and therapeutic tools, and alternative treatment strategies. In The Lancet, Nicholas Opoku and colleagues present the results of a multicentre trial including about 1500 participants that compared the effect over 18 months of single doses of ivermectin and a structurally similar new drug, moxidectin, on O volvulus microfilariae. Skin microfilarial densities (geometric mean about 30 microfilariae per mg skin pretreatment) decreased rapidly in both groups within the first month. 12 months after treatment, adjusted geometric mean densities were 7·5-times lower in the moxidectin than in the ivermectin group (moxidectin 0·6 per mg, ivermectin 4·5 per mg). Additionally, and maybe more notably, the proportion of participants with undetectable skin microfilariae at all three examinations from 1 month to 12 months post treatment was 38·4% in the moxidectin compared with only 1·5% in the ivermectin group. This longer lasting effect of moxidectin, probably because of its long half-life (moxidectin 20–43 days, ivermectin <1 day), would have a much greater impact on transmission intensity. Programmatically speaking, moxidectin has two main advantages: annual treatment could affect onchocerciasis transmission to a similar extent to that of biannual ivermectin treatment, and the effect on transmission will not be as dependent on time of distribution relative to peak transmission season as that of ivermectin is. As a single dose of moxidectin does not kill adult O volvulus, the effect of repeated treatment needs to be assessed urgently to evaluate the long-term effects of moxidectin-based elimination programmes. Further, given moxidectin’s microfilaricidal effect, it is likely to induce—like ivermectin does—serious adverse events in patients with high microfilarial densities of Loa loa, which is another filarial parasite that is common in Central Africa. Such adverse events would restrict or complicate its use in countries with the highest need for increased efforts, such as the Democratic Republic of the Congo. Moxidectin dose-escalating and Loa loa microfilarial density-escalating safety trials are needed. Finally, the relative effect of moxidectin and ivermectin on symptoms of onchocerciasis, particularly itching, needs to be quantified. A better clinical effect of moxidectin would probably improve participation in mass drug administration, particularly for systematic non-compliers who never participate in ivermectin distribution programmes. They can represent greater than 10% of A new powerful drug to combat river blindness