Identifying sub-optimal responses to ivermectin in the treatment of River Blindness.
Identification of drug resistance before it becomes a public health concern requires a clear distinction between what constitutes a normal and a suboptimal treatment response. A novel method of analyzing drug efficacy studies in human helminthiases is proposed and used to investigate recent claims of atypical responses to ivermectin in the treatment of River Blindness. The variability in the rate at which Onchocerca volvulus microfilariae repopulate host's skin following ivermectin treatment is quantified using an individual-based onchocerciasis mathematical model. The model estimates a single skin repopulation rate for every host sampled, allowing reports of suboptimal responses to be statistically compared with responses from populations with no prior exposure to ivermectin. Statistically faster rates of skin repopulation were observed in 3 Ghanaian villages (treated 12-17 times), despite the wide variability in repopulation rates observed in ivermectin-naïve populations. Another village previously thought to have high rates of skin repopulation was shown to be indistinguishable from the normal treatment response. The model is used to generate testable hypotheses to identify whether atypical rates of skin repopulation by microfilariae could result from low treatment coverage alone or provide evidence of decreased ivermectin efficacy. Further work linking phenotypic poor responses to treatment with parasite molecular genetics markers will be required to confirm drug resistance. Limitations of the skin-snipping method for estimating parasite load indicates that changes in the distribution of microfilarial repopulation rates, rather than their absolute values, maybe a more sensitive indicator of emerging ivermectin resistance.
Churcher
Thomas S
TS
Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London, United Kingdom.
Pion
Sébastien D S
SD
Osei-Atweneboana
Mike Y
MY
Prichard
Roger K
RK
Awadzi
Kwablah
K
Boussinesq
Michel
M
Collins
Richard C
RC
Whitworth
James A
JA
Basáñez
María-Gloria
MG
D000818:Animals; D005369:Filaricides / Q000627:therapeutic use*; D006790:Host-Parasite Interactions; D006801:Humans; D007559:Ivermectin / Q000627:therapeutic use*; D008962:Models, Theoretical; D017181:Onchocerca volvulus / Q000378:metabolism; D015827:Onchocerciasis, Ocular / Q000188:drug therapy*; D012867:Skin / Q000469:parasitology
D005369:Filaricides; D007559:Ivermectin