Placebo-controlled community trial of four cycles of single-dose diethylcarbamazine or ivermectin against Wuchereria bancrofti infection and transmission in India

Abstract

A double-blind placebo-controlled trial was carried out in 1994–1998 to compare the effects of 4 cycles of single-dose diethylcarbamazine (DEC) or ivermectin on prevalence and geometric mean intensity (GMI) of microfilaraemia in the human population, infection rates in the vector population, and transmission intensity of Culex-transmitted Wuchereria bancrofti in rural areas in Tamil Nadu state, south India. Fifteen villages (population 26 800) were included in the study: 5 villages each were randomly assigned to community-wide treatment with DEC or ivermectin or placebo. People over 14 kg bodyweight received DEC 6 mg/kg, ivermectin 400 gmg/kg or a placebo, all identically packaged. After 2 cycles of treatment at a 6-month interval, the code was broken and the study continued as an open trial, with third and fourth cycles of treatment at a 12-month interval; 54–77% of eligible people (20 872) received treatment during the 4 cycles. Microfilaraemia prevalence and GMI fell by 48% and 65% with DEC and 60% and 80% with ivermectin respectively after 4 cycles of treatment. There was no change in the incidence of acute adenolymphangitis. Infection in resting mosquitoes fell significantly in all arms: 82%, 78% and 42% in the ivermectin, DEC and placebo arm, respectively. Landing mosquitoes also showed the same trend. The decline in infectivity was significant for resting ( P < 0·05) and landing mosquitoes ( P < 0·05) with ivermectin and DEC ( P < 0·05), and for neither in the placebo group ( P > 0·05). Transmission intensity was reduced by 68% with ivermectin and 63% with DEC. Transmission was apparently interrupted in 1 village with ivermectin, but infected resting mosquitoes were consistently found in this village. Single-dose community-level treatment with DEC or ivermectin is effective in reducing W. bancrofti infection in humans and mosquitoes, and may result in total interruption of transmission after several years of control. There is an immediate need to define the role of vector, parasite and community factors that influence the elimination of lymphatic filariasis, particularly the duration of treatment vis-à-vis efficacy of drugs, treatment compliance and efficiency of vectors.