Community Based Safety Study of 2-drug (Diethylcarbamazine and Albendazole) Versus 3-drug (Ivermectin, Diethylcarbamazine and Albendazole) Therapy for Lymphatic Filariasis

In 2000, the World Health Organization (WHO) launched the Global Programme to Eliminate Lymphatic Filariasis (GPELF) to eliminate lymphatic filariasis as a public health problem by 2020. To interrupt transmission, WHO recommends therapy using combinations of two medicines delivered to entire at-risk populations through a strategy known as mass drug administration. Ivermectin (IVM) and albendazole (ALB) are administered in areas where onchocerciasis is co-endemic; diethylcarbamazine (DEC) and albendazole (ALB) are administered in areas where onchocerciasis is not co-endemic.

Results of a pilot study in Papua New Guinea suggest that triple drug therapy (ivermectin, diethylcarbamazine and albendazole) is superior to the currently recommended two-drug regimen (DEC+ALB, DA). A single dose of the triple therapy (IVM+DEC+ALB, IDA) rapidly achieved complete clearance of Wuchereria bancrofti microfilariae from the blood of 12 individuals for at least one year post-treatment. All six individuals tested at 24 months were still amicrofilaremic, suggesting that the triple therapy might permanently sterilizes adult filarial worms. Many people treated in these studies experienced transient systemic adverse events commonly associated with diethylcarbamazine or ivermectin treatment of filariasis. Adverse events were more frequent after the triple therapy than after the usual combination of two drugs. However, no serious adverse events were observed. The dramatic reduction and sustained decrease of microfilaria along with the safety profile seen in the Papua New Guinea studies suggest that the triple drug therapy may be a useful tool to achieve the goal of eliminating lymphatic filariasis as a public health problem by 2020.

Although the study cited above has clearly demonstrated the superiority of the triple therapy for clearing W. bancrofti microfilaria from the blood, more safety and efficacy data are needed before triple therapy can be rolled out on a large scale as a mass drug administration regimen in lymphatic filariasis endemic countries. WHO recommends a best practice called "cohort event monitoring" for demonstrating safety of new drug regimens for public health program use. Establishing safety through such methodology requires pre and post treatment assessment from at least 10,000 people treated with the triple therapy across multiple settings.

It is therefore proposed to conduct a cohort event monitoring study to acquire safety data. Efficacy and acceptability components will also be included in the study. Similar studies will be conducted simultaneously in Haiti, India, Indonesia, Papua New Guinea and Sri Lanka to reach the 10,000 people necessary to assess the safety of this new drug combination.

This will be an open label, two-armed study. The two arms are (1) mass drug administration (MDA) with the currently used combination of two-drug regimen (DA) and (2) MDA with triple drug therapy (IDA).