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Lymphatic filariasis (lympoedema and hydrocoele) and onchocerciasis (dermatitis and ocular inflammation) caused by the parasitic filarial nematodes , spp. and lead to severe morbidity in developing tropical countries. Mass drug administration (MDA) programmes use ivermectin or diethylcarbamazine, often combined with albendazole, with the aim to eliminate filarial diseases. However, these drugs primarily only kill the first stage larvae, the microfilariae. Removal of the parasites’ mutualistic endosymbionts of the genus using anti-rickettsial drugs results in permanent worm sterility and death of the adult worms. Since it is currently not compatible with mass drug administration due to the comparatively long treatment time of 4–6 weeks, doxycycline has been recommended for physician-monitored treatment of individuals. For individuals suffering from filarial pathology, the use of doxycycline is the first drug to have the additional advantage of improving lymphoedema. However, new drugs and regimes need to be in the pipeline in order to tackle the upcoming or already existing problem areas, such as those with ivermectin resistance, areas coendemic for loiasis, or end-game scenarios. Here, we summarize current treatment options and review current research approaches for optimization of anti-helminthic therapy, including the exploration of optimized delivery strategies of ivermectin and albendazole, the discovery and development of new antibiotics for anti-wolbachial chemotherapy and macrofilaricidal antihelminthics.

Infection with the filarial nematodeWuchereria 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 200mg doxycycline/day for 4 weeks, 16 were treated with a combination of 200 mg doxycycline/day + 10mg/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. [ABSTRACT FROM AUTHOR]

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.