More than 120 million people in approximately 80 countries are infected with the mosquito‐transmitted filarial nematodes, Wuchereria bancrofti or Brugia species. Furthermore, it is estimated that >40 million people have chronic, disabling disease manifestations, including lymphedema, hydrocele, and elephantiasis. Despite successful elimination programs in some countries, transmission of lymphatic filariasis remains a problem in many regions of the world. This is particularly true in resource‐poor areas of Africa, including Mali, where sustaining the World Health Organization–approved mass treatment regimen of single‐dose albendazole (400 mg) and ivermectin (150–200 μg/kg) annually for 4–6 years poses a significant financial burden. Because microfilarial levels in the blood are directly responsible for continued transmission by the mosquito vectors, a more effective suppressive regimen could accelerate the interruption of transmission and shorten the overall duration of the mass treatment program.
Currently available antifilarial drugs with activity against W. bancrofti, the agent of lymphatic filariasis in Africa, include ivermectin, diethylcarbamazine, albendazole, and doxycycline. Of these, ivermectin and diethylcarbamazine have each been shown to be effective in clearing microfilariae from the circulation after single‐dose therapy, although diethylcarbamazine is contraindicated in most of Africa because of the risk of severe (and possibly life‐threatening) posttreatment reactions in patients with concomitant onchocerciasis. The demonstration that the addition of albendazole (400 mg) to annual, single‐dose therapy with ivermectin (200 μg/kg) prolonged the suppression of microfilaremia without any noticeable increase in adverse effects or posttreatment reactions provided the basis for the current World Health Organization recommendation of annual single‐dose ivermectin‐albendazole for lymphatic filariasis elimination in Africa.
Although early studies in French Polynesia suggested that increased dosage (400 μg/kg) or twice‐yearly administration of ivermectin alone was more effective than standard annual therapy in reducing W. bancrofti microfilaremia, the effects of these parameters in the setting of combination therapy are unknown. The current study was designed to assess whether twice‐yearly administration of albendazole‐ivermectin at an increased dosage (800 mg and 400 μg/kg, respectively) is more effective in suppressing microfilarial levels than the current World Health Organization–approved regimen. The effects of this regimen on adult worm burden, as assessed by serum levels of circulating filarial antigen and ultrasonography, were also explored.
Study population. The study was conducted in the villages of Tienekebougou and Bougoudiana, 105 km northwest of Bamako, Mali. Prior studies in these villages had demonstrated a high prevalence of W. bancrofti microfilaremia. This region is outside the area of endemicity for onchocerciasis. Patients had received a single dose of albendazole and ivermectin as part of the National Program to Eliminate Lymphatic Filariasis 1 year before the start of the study. The study (NCT00339417) was approved by the ethical review committees of the Faculty of Medicine, Pharmacy, and Dentistry at the University of Bamako (Bamako, Mali) and of the National Institutes of Allergy and Infectious Diseases (Bethesda, Maryland). Community permission for the study was obtained from village elders, and individual oral or written informed consent was obtained from all participants in French or Bambara, the local language.