The Death to Onchocerciasis and Lymphatic Filariasis (DOLF) project: Accomplishments and ongoing research.

The Death to Onchocerciasis and Lymphatic Filariasis (DOLF) project conducts clinical and translational research to accelerate the global elimination of lymphatic filariasis (LF) and onchocerciasis (river blindness). Research needs were identified during several meetings of experts and helped study design. Over the last 15 years the project has conducted mass drug administration (MDA) studies and clinical trials with outstanding research teams in 11 countries that have led to many important discoveries. For example, DOLF studies showed that annual MDA was as effective as semiannual MDA for LF elimination and that semiannual MDA with albendazole alone can eliminate LF in areas where ivermectin cannot be safely used. Multiple studies showed that a single dose of the triple-drug combination ivermectin plus diethylcarbamazine and albendazole (IDA) was well tolerated and more effective than previously recommended treatments for LF. Results of these studies led the World Health Organization (WHO) to endorse IDA for LF elimination programs in countries without coendemic onchocerciasis or loiasis. More recently, we have shown that single-dose treatment with moxidectin plus albendazole is superior to the ivermectin plus albendazole regimen currently recommended for LF elimination in Africa. Safety and efficacy studies of combination treatments for onchocerciasis have shown that IDA is more effective against adult Onchocerca volvulus worms than ivermectin plus albendazole, although the effect was modest. We are currently testing the macrofilaricidal efficacy of other drug combinations and treatment schedules. DOLF researchers have also conducted important studies that are not clinical trials. For example, we discovered that some people with high Loa loa microfilaria (Mf, first-stage larvae) densities have cross-reactive filarial antigen tests. DOLF has also addressed the issue of MDA compliance, because improved treatments cannot be effective if people do not swallow the tablets. We highlight here some of DOLF's important discoveries that support the control and elimination of neglected tropical diseases caused by helminths.