Journal
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
Volume 83, Issue 1, Pages 28-32Publisher
AMER SOC TROP MED & HYGIENE
DOI: 10.4269/ajtmh.2010.09-0734
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Funding
- Canadian Institutes of Health
- Mectizan Donation Program
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Ivermectin (IVM) is exceptionally safe in humans, and is used for mass treatment of onchocerciasis and lymphatic filariasis. However, cases of encephalopathy, sometimes fatal, have been reported in a small number of individuals who harbored large numbers of Lou loa microfilariae (mf). A loss-of-function mutation in the mdr-1 gene in some dog breeds and in mice leads to accumulation of the drug in the brain, causing coma and death. This hypothesis was tested in four individuals from Cameroon who experienced a post-IVM serious adverse event (SAE) and in nine non-SAE matched controls. No loss-of-function mutation was detected in mdr-1 in any subject. However, haplotypes, associated with altered drug disposition, were present as homozygotes in two of the SAE patients (50%), but absent as homozygotes in the controls (0%). An association of high Lou mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs.
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