Effects of standard and high doses of ivermectin on adult worms of Onchocerca volvulus: a randomised controlled trial.
BACKGROUND
At present, control of onchocerciasis depends almost entirely on yearly treatments with 150 microg/kg ivermectin. We aimed to compare the effect of higher doses, more frequent doses, or both with the standard regimen on adult Onchocerca volvulus.


METHODS
We randomly allocated 657 patients who had onchocerciasis to 150 microg/kg ivermectin yearly (reference group), 150 microg/kg every 3 months, 400 then 800 microg/kg yearly, or 400 then 800 microg/kg every 3 months. We took skin snip samples from every patient before, and 3 years and 4 years after the first dose, and, at the same time excised one subcutaneous O volvulus nodule, which was examined histologically. The primary outcome was the vital status of the female worms. Analysis was done per protocol.


RESULTS
We obtained nodules from 511 patients. After 3 years of treatment, more female worms had died in the groups treated every 3 months than in the reference group (odds ratio=1.84 [95% CI 1.23-2.75], p=0.003 for 150 microg/kg; and 2.17 [1.42-3.31], p<0.001 for high doses). Female worms were also less fertile in these groups than in the reference group (0.24 [0.14-0.43], p<0.0001; and 0.14 [0.06-0.29], p<0.0001, respectively). No difference was recorded between groups treated yearly (p=0.83 for the proportion of dead females). Unexpected side-effects consisted of mild, temporary, subjective visual changes in patients on high-dose regimens.


CONCLUSIONS
Treatment with 3-monthly ivermectin could greatly reduce the number of female worms and acute itching and skin lesions; lower transmission of O volvulus; and change the duration of control programmes.
Gardon
Jacques
J
Institut Pasteur de la Guyane, Cayenne Cedex, Guyane Française, France.
Boussinesq
Michel
M
Kamgno
Joseph
J
Gardon-Wendel
Nathalie
N
Demanga-Ngangue
Duke
Brian O L
BO
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002163:Cameroon; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005369:Filaricides / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017181:Onchocerca volvulus / Q000187:drug effects*; D015827:Onchocerciasis, Ocular / Q000188:drug therapy*; D012867:Skin / Q000469:parasitology
D005369:Filaricides; D007559:Ivermectin