A new powerful drug to combat river blindness
Authors: Michel Boussinesq
Journal: The Lancet (2018)

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.1Tekle AH Zouré HGM Noma M et al.Progress towards onchocerciasis elimination in the participating countries of the African Programme for Onchocerciasis Control: epidemiological evaluation results.Infect Dis Poverty. 2016; 5: 66Crossref PubMed Scopus (84) Google Scholar 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 colleagues2Opoku NO Bakajika DK Kanza EM et al.Efficacy and safety of a single dose of moxidectin in Onchocerca volvulus infection: a randomized, double-blind ivermectin-controlled trial in Ghana, Liberia, and the Democratic Republic of the Congo.Lancet. 2018; (published online Jan 17.)DOI:10.1016/S0140-6736(17)32844-1Summary Full Text Full Text PDF PubMed Scopus (64) Google Scholar 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.3Turner HC Walker M Attah SK et al.The potential impact of moxidectin on onchocerciasis elimination in Africa: an economic evaluation based on the phase II clinical trial data.Parasit Vectors. 2015; 8: 167Crossref PubMed Scopus (45) Google Scholar As a single dose of moxidectin does not kill adult O volvulus,4Awadzi K Opoku NO Attah SK Lazdins-Helds J Kuesel AC A randomized, single ascending-dose, ivermectin-controlled, double-blind study of moxidectin in Onchocerca volvulus infection.PLoS Negl Trop Dis. 2014; 8: e2953Crossref PubMed Scopus (57) Google Scholar 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 does5Gardon J Gardon-Wendel N Demanga-Ngangue Kamgno J Chippaux JP Boussinesq M Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection.Lancet. 1997; 350: 18-22Summary Full Text Full Text PDF PubMed Scopus (382) Google Scholar—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,6Whitworth JA Luty AJ Maude GH Morgan D Downham MD Taylor DW Ivermectin does not reduce the burden of itching in an onchocerciasis endemic community.Trans R Soc Trop Med Hyg. 1992; 86: 281-283Summary Full Text PDF PubMed Scopus (12) Google Scholar 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 the population7Wanji S Kengne-Ouafo JA Esum ME et al.Relationship between oral declaration on adherence to ivermectin treatment and parasitological indicators of onchocerciasis in an area of persistent transmission despite a decade of mass drug administration in Cameroon.Parasit Vectors. 2015; 8: 667Crossref PubMed Scopus (26) Google Scholar and maintain a parasite reservoir; thus a reduction in their numbers could accelerate elimination of onchocerciasis. As new diagnostics and treatments become available as a result of sustained and dynamic research efforts, alternative control strategies (including test-and-treat approaches)8Kamgno J Pion SD Chesnais CB et al.A test-and-not-treat strategy for onchocerciasis in Loa loa-endemic areas.N Engl J Med. 2017; 377: 2044-2052Crossref PubMed Scopus (73) Google Scholar that are adapted to the specific situation in a given focus (such as initial endemicity level, number of CDTI rounds applied, prevalence of Loa loa, and number of systematic non-compliers) can be considered. However, it is clear that mass treatment (ie, without individual diagnosis of onchocerciasis or loiasis) is the simplest strategy. Given its safety profile, mass treatment with moxidectin could be implemented rapidly in areas where Loa loa is not endemic. Moxidectin's effect on other neglected diseases, such as lymphatic filariasis, soil-transmitted helminthiases, or scabies, should be assessed in parallel. Ivermectin has been widely used for 30 years to combat onchocerciasis and is rightly considered a wonder drug.9Geary TG Ivermectin 20 years on: maturation of a wonder drug.Trends Parasitol. 2005; 21: 530-532Summary Full Text Full Text PDF PubMed Scopus (184) Google Scholar Moxidectin, which can be considered as a supercharged version of ivermectin, could help to accelerate elimination of onchocerciasis. Should moxidectin be registered (and donated), it should be deployed progressively with careful monitoring and appropriate pharmacovigilance, taking into account populations' expectations and familiarity with community-directed treatment with ivermectin. I declare no competing interests. Single dose moxidectin versus ivermectin for Onchocerca volvulus infection in Ghana, Liberia, and the Democratic Republic of the Congo: a randomised, controlled, double-blind phase 3 trialSkin microfilarial loads (ie, parasite transmission reservoir) are lower after moxidectin treatment than after ivermectin treatment. Moxidectin would therefore be expected to reduce parasite transmission between treatment rounds more than ivermectin could, thus accelerating progress towards elimination. Full-Text PDF Open Access