In a randomized, placebo-controlled trial in Ghana, 67 onchocerciasis patients received 200-mg/day doxycycline for 4–6 weeks, followed by ivermectin (IVM) after 6 months. After 6–27 months, efficacy was evaluated by onchocercoma histology, PCR and microfilariae determination. Administration of doxycycline resulted in endobacteria depletion and female worm sterilization. The 6-week treatment was macrofilaricidal, with >60% of the female worms found dead, despite the presence of new, Wolbachia-containing worms acquired after the administration of doxycycline. Doxycycline may be developed as second-line drug for onchocerciasis, to be administered in areas without transmission, in foci with IVM resistance and in areas with Loa co-infections.

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The effects of 5-week doxycycline treatment on the depletion of Wolbachia endobacteria from Onchocerca volvulus, on the interruption of embryogenesis and on microfilariae production, and with regard to macrofilaricidal activity were studied. In 2003, in an endemic area in Ghana, 22 onchocerciasis patients received 100 mg/day doxycycline for 5 weeks. Two years after the start of the study, 20 treated and ten untreated patients were nodulectomized and skin microfilariae were counted. The onchocercomas were examined by immunohistology for the presence of Wolbachia, embryogenesis, and vitality of adult filariae. The latter two parameters were further assessed by alternating logistic regression analysis, taking into account the dependency of worms and nodules in patients. Doxycycline resulted in depletion of Wolbachia and in complete interruption of embryogenesis in all worms that were assumed to have been present during treatment. In the treated patients, only 51% of the female worms were alive, compared to 84% in the untreated patients, indicating a moderate but distinct macrofilaricidal activity of doxycycline at this dose. It is concluded that, in areas with ongoing transmission, doxycycline cannot replace regular ivermectin mass treatment because new infections would require repeated rounds of doxycycline. However, doxycycline can be used for the treatment of individuals outside transmission areas, in foci where ivermectin resistance may occur, and in countries where onchocerciasis and loiasis are co-endemic. Abbreviations

Summaryobjective To evaluate the efficacy of doxycycline as a macrofilaricidal agent against Wuchereria bancrofti.method In the Western Region of Ghana, 18 patients infected with W. bancrofti were recruited and treated with 200 mg doxycycline per day for 4 weeks. Seven untreated patients served as controls. Four months after doxycycline treatment, all patients received 150 lg ⁄ kg ivermectin. Patients were monitored for Wolbachia and microfilaria loads, antigenaemia and filarial dance sign (FDS).results Four months after doxycycline treatment, cases had a significantly lower Wolbachia load than controls; and 24 months after treatment, microfilaraemia, antigenaemia and frequency of FDS were significantly lower in cases than controls. Most importantly, 4 weeks of doxycycline killed 80% of macrofilariae, which is comparable with the results of a 6-week regimen. Circulating filarial antigenaemia and FDS were strongly correlated.conclusion A 4-week regimen of doxycycline seems sufficient to kill adult W. bancrofti and could be advantageous for the treatment of individual patients, e.g. in outpatient clinics.

Sub-optimal responses to ivermectin (IVM) have emerged. Targeting the Onchocerca volvulus Wolbachia endosymbionts with doxycycline is effective in clearing microfilariae in onchocerciasis patients with persistent microfilaridermia and in enhanced killing of adult worms after repeated standard IVM treatment.