Infection with the filarial nematode Wuchereria bancrofti can lead to lymphedema, hydrocele, and elephantiasis. Since adult worms cause pathology in lymphatic filariasis (LF), it is imperative to discover macrofilaricidal drugs for the treatment of the infection. Endosymbiotic Wolbachia in filariae have emerged as a new target for antibiotics which can lead to macrofilaricidal effects. In Ghana, a pilot study was carried out with 39 LF-infected men; 12 were treated with 200？mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200？mg doxycycline/day + 10？mg/kg/day rifampicin for 2 weeks, and 11 patients received placebo. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia, and filarial dance sign (FDS). Both 4-week doxycycline and the 2-week combination treatment reduced Wolbachia load significantly. At 18 months posttreatment, four-week doxycycline resulted in 100% adult worm loss, and the 2-week combination treatment resulted in a 50% adult worm loss. In conclusion, this pilot study with a combination of 2-week doxycycline and rifampicin demonstrates moderate macrofilaricidal activity against W. bancrofti. 1. Introduction Approximately 120 million people in Africa, Asia, and America are infected with the filarial nematodes Wuchereria bancrofti or Brugia malayi, resulting in lymphatic filariasis (LF), of which more than 40 million suffer from the debilitating lymphatic pathologies such as lymphedema, elephantiasis, and hydrocele. LF is one of the most common causes of global disability [1]. The classical drugs diethylcarbamazine (DEC), ivermectin (IVM), and albendazole (ALB) have been used for the last two decades as the major mode of intervention for filarial infection in successful mass drug administration (MDA) programmes [2–4]. However, these drugs are mainly microfilaricidal [5–10], that is, killing the first larval stage, the microfilariae (Mf). The currently available regimes have been optimised to obtain a decrease in transmission by reducing the Mf load in a given population at both low cost and logistical effort. Because ivermectin does not, and DEC plus albendazole only partially kill adult worms that are the causes of pathology in LF (urogenital disorders and lymphedema), research is ongoing to discover novel antifilarial drugs with strong macrofilaricidal activity. A macrofilaricidal drug would help to prevent excruciating sequela and ensure elimination of the disease as a public health problem. One promising area is the use of antibiotics to deplete the Wolbachia endosymbionts found in most filarial
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