Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial

Taylor, Mark J.; Makunde, Williams H.; McGarry, Helen F.; Turner, Joseph D.; Mand, Sabine; Hoerauf, Achim

doi:10.1016/s0140-6736(05)66591-9

Cited by 253 publications

(172 citation statements)

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“…Human and animal studies also suggest that tribendimidine will prove effective against food-borne flukes (166) and the drug moxidectin might become an alternative to ivermectin for the treatment of filarial infections (167). Finally, based on the observation that the filarial parasites Wuchereria bancrofti and Onchocerca volvulus harbor bacterial endosymbionts of the genus Wolbachia and depend on these endosymbionts for normal metabolic and reproductive activities, there is excitement about the development and use of antibiotics to target adult filarial worms (168). This is of particular importance because to date there is no effective drug that targets the adult stage of these parasitic worms.…”

Section: Global Control Of Helminthiases and Clinical Research Imperamentioning

confidence: 99%

“…Such a vaccine could be used together with a hookworm vaccine. At the same time, the recently revealed importance of Wolbachia endosymbionts is helping to launch new drug discovery efforts for the treatment of LF and onchocerciasis as well as treatment programs based on either existing or new antibiotics (168). The recent completion of the filarial genome might soon yield additional drug targets (105).…”

Section: Concluding Commentsmentioning

confidence: 99%

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Helminth infections: the great neglected tropical diseases

et al. 2008

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Helminths are parasitic worms. They are the most common infectious agents of humans in developing countries and produce a global burden of disease that exceeds better-known conditions, including malaria and tuberculosis. As we discuss here, new insights into fundamental helminth biology are accumulating through newly completed genome projects and the nascent application of transgenesis and RNA interference technologies. At the same time, our understanding of the dynamics of the transmission of helminths and the mechanisms of the Th2-type immune responses that are induced by infection with these parasitic worms has increased markedly. Ultimately, these advances in molecular and medical helminth biology should one day translate into a new and robust pipeline of drugs, diagnostics, and vaccines for targeting parasitic worms that infect humans.

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Section: Global Control Of Helminthiases and Clinical Research Imperamentioning

confidence: 99%

Section: Concluding Commentsmentioning

confidence: 99%

Helminth infections: the great neglected tropical diseases

et al. 2008

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“…There was also a reduction in the proportion of living female and male worms at this point of time, but the number of extirpated worms was too small to allow the definite conclusion of a macrofilaricidal effect. However, a macrofilaricidal activity of doxycycline was demonstrated against Wuchereria bancrofti (Taylor et al 2005;Debrah et al 2006b), and recently also against O. volvulus, albeit at a higher daily dose of 200 mg/day, also after a longer observation period .…”

Section: Introductionmentioning

confidence: 98%

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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“…Studies using doxycycline with anti-wolbachial activity: A study in Tanzania, where doxycycline at a daily dose of 200 mg/day was administered for 8 weeks without other antifilarial drugs, showed a 78% macrofilaricidal effect 15 months after treatment. 18 In Ghana, a 6-week doxycycline treatment followed by a single dose of ivermectin (150 μg/kg) and albendazole (400 mg) 4 months later showed a 77% macrofilaricidal effect at the 12-month follow-up and 92% after 2 years. 9 The 4-week doxycycline (200 mg/day) regimen in Ghanaian participants resulted in a macrofilaricidal effect of 71% after 12 months and in 83% after 24 months.…”

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confidence: 98%

Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine

Mand

Pfarr²,

Sahoo³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. In a placebo controlled trial, the effects of 21-and 10-day doxycycline treatments (200 mg/day) followed by single dose diethylcarbamazine (administered 4 months post treatment) on depletion of Wolbachia endobacteria from Wuchereria bancrofti , filaricidal activity, and amerlioration of scrotal lymph vessel dilation were studied in 57 men from Orissa, India. The 21-day doxycycline course reduced Wolbachia in W. bancrofti by 94% before diethylcarbamazine administration. After 12 months, all patients with this treatment were amicrofilaremic and different from the 10-day doxycycline (42.9%) and placebo (37.5%) groups, and significantly fewer were positive for scrotal worm nests (6.7%) compared with 10-day doxycycline (60%) and placebo (66.7%). Average scrotal lymph vessel diameters were reduced from 0.7 cm pre-treatment to 0.02 cm in patients after 21 days of treatment, while no significant changes were seen in the other groups. This latter feature confirms the beneficial effects of doxycycline on lymphatic dilation and thus adds to the existing evidence that doxycycline, in addition to being macrofilaricidal, may be used to prevent or reverse lymphatic pathology.

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Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial

Cited by 253 publications

References 25 publications

Helminth infections: the great neglected tropical diseases

Helminth infections: the great neglected tropical diseases

Efficacy of 5-week doxycycline treatment on adult Onchocerca volvulus

Macrofilaricidal Activity and Amelioration of Lymphatic Pathology in Bancroftian Filariasis after 3 Weeks of Doxycycline Followed by Single-Dose Diethylcarbamazine

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