Macrofilaricidal activity after doxycycline treatment of Wuchereria bancrofti: a double-blind, randomised placebo-controlled trial.
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. Follow-up assessments were done at 5, 8, 11, and 14 months after the start of treatment. Analysis was per protocol.


RESULTS
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.


CONCLUSIONS
An 8-week course of doxycycline is a safe and well-tolerated treatment for lymphatic filariasis with significant activity against adult worms and microfilaraemia.
Taylor
Mark J
MJ
Filariasis Research Group, Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Liverpool, UK. mark.taylor@liv.ac.uk
Makunde
Williams H
WH
McGarry
Helen F
HF
Turner
Joseph D
JD
Mand
Sabine
S
Hoerauf
Achim
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D004311:Double-Blind Method; D004318:Doxycycline / Q000627:therapeutic use*; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000469:parasitology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020577:Wolbachia / Q000187:drug effects*; D014958:Wuchereria bancrofti / Q000187:drug effects / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D004318:Doxycycline