Doxycycline in the treatment of human onchocerciasis: kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms

Hoerauf, Achim; Mand, Sabine; Volkmann, Lars; Büttner, Marcelle; Marfo-Debrekyei, Yeboah; Taylor, Mark J.; Adjei, Ohene; Büttner, Dietrich W.

doi:10.1016/s1286-4579(03)00026-1

Cited by 185 publications

(200 citation statements)

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“…Previously, we had studied the efficacy of 100 mg/day doxycycline administered for 6 weeks (Hoerauf et al 2000(Hoerauf et al , 2003. The aim of the present study was to investigate the effects of a shortened regimen of only 5 weeks doxycycline treatment on the depletion of Wolbachia endobacteria from O. volvulus, on interruption of embryogenesis and mf production, and to detect macrofilaricidal activity.…”

Section: Objectivesmentioning

confidence: 97%

“…The aim of the present study was to investigate the effects of a shortened regimen of only 5 weeks doxycycline treatment on the depletion of Wolbachia endobacteria from O. volvulus, on interruption of embryogenesis and mf production, and to detect macrofilaricidal activity. We deliberately chose to nodulectomize the patients after a longer period of observation than in the preceding study, namely at 21 and 27 months, since we knew from this previous study as well as from unpublished studies (Hoerauf et al 2003;in preparation) that the depletion of Wolbachia and the interruption of embryogenesis could still be observed up to 27 months but macrofilaricidal activity would become detectable only later than 11 months, e.g., at 18, 21, or 27 months.…”

Section: Objectivesmentioning

confidence: 99%

“…The sample size was planned on the basis of previous histological analyses: accordingly, 50-100 female worms should be available per treatment arm to detect significant differences in embryogenesis and vitality of female worms (Albiez et al 1988b, Awadzi et al 1995a, b, 1999Büttner et al 1988;Hoerauf et al 2003). These worm numbers were obtained for both the doxycycline and the untreated group.…”

Section: Sample Sizementioning

confidence: 99%

“…Doxycycline has been introduced as a novel chemotherapeutic principle, targeting Wolbachia endobacteria in the worms (Hoerauf et al 2000(Hoerauf et al , 2001(Hoerauf et al , 2003. Given for 6 weeks at 100 mg/day, doxycycline led to Wolbachia depletion and sterilization of female filariae up to 18 months.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, the present study was conducted focusing on the assessment of a macrofilaricidal and long-term sterilizing activities after the longer observation time of 21 and 27 months compared to the earlier study (Hoerauf et al 2000(Hoerauf et al , 2001(Hoerauf et al , 2003. Second, since we knew that a doxycycline treatment shorter than 6 weeks also depletes Wolbachia (Debrah et al 2006a), the regimen was reduced to 5 weeks at only 100 mg/day of doxycycline.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus

et al. 2008

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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

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Section: Objectivesmentioning

confidence: 97%

Section: Objectivesmentioning

confidence: 99%

Section: Sample Sizementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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