Efficacy of ivermectin in the treatment of Wuchereria bancrofti infection: a model-based analysis of trial results.
Ivermectin is a promising drug for the treatment of lymphatic filariasis. A meta-analysis of trials investigating the effects of a single treatment suggested a dose-dependent effect on the production of microfilariae (mf) by adult Wuchereria bancrofti parasites. A mathematical model that describes the parasite dynamics in the human host and the impact of ivermectin treatment is presented and its outputs compared with these trials. The calculated trend in mf density after treatment appears to be particularly sensitive to the assumption about the mean life-span of mf. Adopting 0.5-2 years as a range of plausible values for this mf life-span, the model is used to estimate the impact of treatment on the parasite. It is found that irrespective of dosage, ivermectin eliminates 100% of the blood mf from a patient. Furthermore, at a dosage level of 400 micrograms/kg a single treatment irreversibly reduces the mf production of the adult parasites by at least 65%. For a dosage of 200 micrograms/kg this reduction is at least 35%. No such effect can be concluded from the results of trials using lower dosages.
Plaisier
A P
AP
Department of Public Health, Faculty of Medicine and Health Sciences, Erasmus University Rotterdam, The Netherlands. plaisier@mgz.fgg.eur.nl
Cao
W C
WC
van Oortmarssen
G J
GJ
Habbema
J D
JD
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005368:Filariasis / Q000188:drug therapy*; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D008842:Microfilariae / Q000187:drug effects; D008962:Models, Theoretical; D012680:Sensitivity and Specificity; D013997:Time Factors; D014958:Wuchereria bancrofti / Q000187:drug effects*
D007559:Ivermectin