Model-based analysis of trial data: microfilaria and worm-productivity loss after diethylcarbamazine-albendazole or ivermectin-albendazole combination therapy against Wuchereria bancrofti.
OBJECTIVE
To determine the efficacies of combinations of ivermectin or diethylcarbamazine and albendazole, which are recommended for use in mass treatment programmes against lymphatic filariasis.


METHODS
Review of published trends in microfilarial (mf) intensities after treatment with these combination therapies. By fitting a mathematical model of treatment effects to the trial data, we quantified the efficacy of treatment, distinguishing between the killing of mf (mf loss) and a reduction in mf production by adult worms (worm-productivity loss). After diethylcarbamazine-albendazole treatment mf density dropped immediately, then slowly but steadily decreased further (four trials). After ivermectin-albendazole treatment, mf densities immediately dropped to near-zero levels, followed by a small increase (five trials). For diethylcarbamazine-albendazole treatment the average mf loss was approximately 83% (ranging from 54% to 100% in the different studies) and worm-productivity loss was 100% (in all studies). For ivermectin-albendazole treatment, average mf loss was 100% (ranging from 98% to 100%) and worm productivity loss was 96% (ranging from 83% to 100%). The effects were dose-dependent. Sensitivity analysis showed that the estimates did not depend on assumptions on worm lifespan or premature period and little on assumptions on mf lifespan.


CONCLUSIONS
The two therapies differ with respect to their direct effect on mf, but both are highly effective against adult worms. If mass treatment with these combination therapies achieves high coverage, they can have a large impact on lymphatic filariasis transmission.
de Kraker
Marlieke E A
ME
Department of Public Health, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
Stolk
Wilma A
WA
van Oortmarssen
Gerrit J
GJ
Habbema
J Dik F
JD
D000293:Adolescent; D000328:Adult; D000368:Aged; D015766:Albendazole / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage / Q000627:therapeutic use; D000977:Antiparasitic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D002648:Child; D004049:Diethylcarbamazine / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004605:Elephantiasis, Filarial / Q000188:drug therapy*; D005369:Filaricides / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D007559:Ivermectin / Q000008:administration & dosage / Q000627:therapeutic use*; D008136:Longevity; D008842:Microfilariae / Q000187:drug effects / Q000254:growth & development; D008875:Middle Aged; D015233:Models, Statistical; D016032:Randomized Controlled Trials as Topic; D012107:Research Design; D016896:Treatment Outcome; D014958:Wuchereria bancrofti / Q000187:drug effects / Q000254:growth & development
D000871:Anthelmintics; D000977:Antiparasitic Agents; D005369:Filaricides; D007559:Ivermectin; D015766:Albendazole; D004049:Diethylcarbamazine