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

Taylor, Mark, Makunde, W. H., McGarry, Helen F., Turner, Joseph, Mand, S. and Hoerauf, A. (2005) 'Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-control led trial'. Lancet, Vol 365, Issue 9477, pp. 2116-2121.

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Abstract

Background Wolbachia endosymbionts of filarial nematodes are vital for larval development and adult-worm fertility and viability. This essential dependency on the bacterium for survival of the parasites has provided a new approach to treat filariasis with antibiotics. We used this strategy to investigate the effects of doxycycline treatment on the major cause of lymphatic filariasis, Wuchereria bancrofti.
Methods We undertook a double-blind, randomised, placebo-controlled field trial of doxycycline (200 mg per day) for 8 weeks in 72 individuals infected with W bancrofti from Kimang'a village, Pangani, Tanzania. Participants were randomly assigned by block randomisation to receive capsules of doxycycline (n=34) or placebo (n=38). We assessed treatment efficacy by monitoring microfilaraemia, antigenaemia, and ultrasound detection of adult worms. Followup assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol.
Findings One person from the doxycycline group died from HIV infection. Five (doxycycline) and 11 (placebo) individuals were absent at the time of ultrasound analysis. Doxycycline treatment almost completely eliminated microfilaraemia at 8-14 months' follow-up (for all timepoints p<0.001). Ultrasonography detected adult worms in only six (22%) of 27 individuals treated with doxycycline compared with 24 (88%) of 27 with placebo at 14 months after the start of treatment (p<0.0001). At the same timepoint, filarial antigenaemia in the doxycycline group fell to about half of that before treatment (p=0.015). Adverse events were few and mild.
Interpretation An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.

Item Type: Article
Uncontrolled Keywords: endosymbiotic wolbachia-bacteria filarial nematodes lymphatic filariasis brugia-malayi onchocerca-volvulus antibiotics worms diethylcarbamazine chemotherapy tetracycline
Subjects: QV Pharmacology > QV 38 Drug action.
QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs
WB Practice of Medicine > Medical Climatology > WB 710 Diseases of geographic areas
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 850 Nematode infections (General)
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 880 Filariasis and related conditions (General)
Faculty: Department: Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI): https://doi.org/10.1016/S0140-6736(05)66591-9
Depositing User: Sarah Lewis-Newton
Date Deposited: 10 Oct 2011 14:47
Last Modified: 06 Feb 2018 13:03
URI: https://archive.lstmed.ac.uk/id/eprint/1932

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