Potential Value of Triple Drug Therapy with Ivermectin, Diethylcarbamazine, and Albendazole (IDA) to Accelerate Elimination of Lymphatic Filariasis and Onchocerciasis in Africa.

Abstract

The Global Program to Eliminate Lymphatic Filariasis (GPELF) has made significant progress in many countries. GPELF has delivered 5,600 million treatments to more than 763 million people living in 61 countries between the years 2000 and 2014, and it was estimated to have prevented 36 million clinical cases and saved 175 million disability adjusted life years (DALYs) [1]. Although elimination of LF is a major goal of the London Declaration on Neglected Tropical Diseases (NTDs), it is unlikely that LF will be eliminated by the target year of 2020 [2]. The key strategy of the elimination program comprises repeated annual rounds of mass drug administration (MDA) to populations at risk of acquiring the infection with diethylcarbamazine (DEC) plus albendazole outside of Africa and with ivermectin plus albendazole in Africa [3]. MDA reduces microfilariae (Mf) in human blood that are necessary for transmission by mosquito vectors, and one aim of the program is to interrupt transmission. Repeated rounds of MDA are required because current regimens fail to kill all adult worms and completely clear Mf following single-dose treatments. Successful programs have sustained annual MDA with high compliance for several years. Seventy-three countries were considered to be endemic for LF in 2015, and 55 of them still required MDA [4]. The GPELF has lagged in sub-Saharan Africa, where only 2 of 35 LF-endemic countries have stopped MDA and started post-MDA surveillance. Many countries in this region have either not started MDA or have less than 65% geographical coverage. Hence, a more effective treatment strategy could have a major impact on LF elimination in Africa. The goal of onchocerciasis intervention in Africa has also shifted in recent years from control towards elimination [5, 6]. As with LF, the key strategy for onchocerciasis intervention is MDA. In most countries, this is accomplished with annual community-directed treatment with ivermectin (CDTi). Modeling studies predict that current strategies will permit many countries to reach targets for stopping MDA for onchocerciasis by 2028, but intervention is likely to be required for a much longer period in some areas (especially in Central Africa) [7]. While annual or semiannual CDTi for 15 to 17 years eliminated the infection in some areas, it was not sufficient to stop transmission in others [8, 9]. Therefore, extensive research is currently ongoing to identify drugs that are more effective than ivermectin. Drug development studies are time and resource intensive, and it is unlikely that a novel drug for onchocerciasis will be registered to significantly advance the progress of onchocerciasis elimination within the next 5 years. In this paper, we discuss the potential value of combination therapy with three currently approved drugs (ivermectin, DEC, and albendazole, or IDA) for advancing LF and onchocerciasis elimination programs in Africa. Because DEC treatment can cause ocular adverse events in persons with heavy Onchocerca volvulus infections, studies of the new combination will have to be conducted with proper precautions. Therefore, this paper also discusses prior experience with DEC in onchocerciasis patients and a strategy for studying the effects of IDA in patients with onchocerciasis.