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Despite successful mass drug administration and vector control programs, the nematode Onchocerca volvulus is far from being eradicated. Therefore, new long-term sterilizing or macrofilaricidal drugs are needed. The depletion of Wolbachia endobacteria using doxycycline leads to long-term sterilizing effects and macrofilaricidal activity against female filariae of more than 60%. The worms die or degenerate 18–27 months after doxycycline. However, during this time patients may be exposed to new infections. We evaluated these newly acquired worms in onchocercomas of doxycycline-treated patients in relation to transmission using morphology, histochemistry, and immunohistology. On an average, 10% of the female filariae had been newly acquired per year in the treated groups. Our observations showed: (a) Sixty-three of 68 newly acquired worms harbored many intact Wolbachia, whereas none of the other surviving worms contained many bacteria. (b) Higher percentages of dead filariae than originally reported were calculated, when the new worms were excluded, indicating a stronger macrofilaricidal activity than previously reported. The difference was significant for female filariae after doxycycline treatment for 6 weeks. (c) Only newly acquired worms presented normal embryogenesis and microfilariae production after sufficient treatment. We conclude that newly acquired filariae have to be considered when evaluating drug efficacy in onchocerciasis. [ABSTRACT FROM AUTHOR]

Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is a neglected bacterial infection of the poor in remote rural areas, mostly affecting children. BUD is a mutilating disease leading to severe disability; it is the third most common mycobacterial infection in immunocompetent people after tuberculosis and leprosy. It is most endemic in West Africa, but cases have been reported from more than 30 countries. Treatment with antibiotics is possible, long-lasting and requires injections; there are cases of treatment failures, and the disease is prone to resistance. A vaccine against M. ulcerans would protect persons at risk in highly endemic areas, and could be used as a therapeutic vaccine to shorten the duration of treatment and prevent relapses. There is considerable evidence supporting the notion that generation of a vaccine is feasible. This article reviews the present state of the art with special emphasis on the immunology of the infection and the prospects for development of a vaccine. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chemotherapy of onchocerciasis by doxycycline, which targets symbiotic Wolbachia endobacteria, has been shown to result in a long-term sterility of adult female worms and corresponding absence of microfilariae. It represents an additional chemotherapeutic approach. The aim of this study was to determine whether a similar regimen would also show efficacy against Wuchereria bancrofti. Ghanaian individuals (n=93) with lymphatic filariasis and a minimum microfilaremia of 40 microfilariae/ml were included in a treatment study consisting of four arms: (1) doxycycline 200 mg/day for 6 weeks; (2) doxycycline as in (1), followed by a single dose of ivermectin after 4 months; (3) ivermectin only; or (4) no treatment during observation period of 1 year (ivermectin at the end of the study). Doxycycline treatment resulted in a 96% loss of Wolbachia, as determined by real time PCR from microfilariae. After 12 months, doxycycline had led to a 99% reduction of microfilaremia when given alone, and to a complete amicrofilaremia together with ivermectin. In contrast, after ivermectin treatment alone a significant presence of microfilariae remained (9% compared to pretreatment), as known from other studies. This study shows that doxycycline is also effective in depleting Wolbachia from W. bancrofti. It is likely that the mechanism of doxycycline is similar to that in other filarial species, i.e., a predominant blockade of embryogenesis, leading to a decline of microfilariae according to their half-life. This could render doxycycline treatment an additional tool for the treatment of microfilaria-associated diseases in bancroftian filariasis, such as tropical pulmonary eosinophilia and microfiluria. [ABSTRACT FROM AUTHOR]