{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T16:40:55Z","timestamp":1776184855583,"version":"3.50.1"},"reference-count":42,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2010,7]]},"abstract":"<jats:p>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 <jats:italic>Loa loa<\/jats:italic> microfilariae (mf). A loss-of-function mutation in the <jats:italic>mdr-1<\/jats:italic> 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 <jats:italic>mdr-1<\/jats:italic> 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 <jats:italic>Loa<\/jats:italic> mf load and a genetic predisposition to altered IVM distribution could be involved in IVM SAEs.<\/jats:p>","DOI":"10.4269\/ajtmh.2010.09-0734","type":"journal-article","created":{"date-parts":[[2010,7,1]],"date-time":"2010-07-01T16:25:01Z","timestamp":1278001501000},"page":"28-32","source":"Crossref","is-referenced-by-count":34,"title":["Analysis of the mdr-1 Gene in Patients Co-Infected with Onchocerca volvulus and Loa loa Who Experienced a Post-Ivermectin Serious Adverse Event"],"prefix":"10.4269","volume":"83","author":[{"given":"Catherine","family":"Bourguinat","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph","family":"Kamgno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel","family":"Boussinesq","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles D.","family":"Mackenzie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger K.","family":"Prichard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy G.","family":"Geary","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2795","reference":[{"key":"R1","series-title":"Ann Trop Med Parasitol","first-page":"69","article-title":"The Mectizan Donation Programme\u2013a 10-year report","volume":"92","author":"Dull","year":"1998"},{"issue":"(Suppl 1)","key":"R2","series-title":"Filaria J","first-page":"S4","article-title":"Clinical picture, epidemiology and outcome of Loa-associated serious adverse events related to mass ivermectin treatment of onchocerciasis in Cameroon","volume":"2","author":"Boussinesq","year":"2003"},{"issue":"(Suppl 1)","key":"R3","series-title":"Filaria J","first-page":"S7","article-title":"Loa loa encephalopathy temporally related to ivermectin administration reported from onchocerciasis mass treatment programs from 1989 to 2001: implications for the future","volume":"2","author":"Twum-Danso","year":"2003"},{"issue":"(Suppl 1)","key":"R4","series-title":"Filaria J","first-page":"S5","article-title":"Possible pathogenic pathways in the adverse clinical reactions seen following ivermectin administration to onchocerciasis patients","volume":"2","author":"Mackenzie","year":"2003"},{"key":"R5","series-title":"Trends Parasitol","first-page":"244","article-title":"What are the mechanisms associated with post-ivermectin serious adverse events?","volume":"22","author":"Boussinesq","year":"2006"},{"key":"R6","series-title":"Trends Parasitol","first-page":"237","article-title":"Where next with Loa loa encephalopathy? Data are badly needed","volume":"23","author":"Mackenzie","year":"2007"},{"key":"R7","series-title":"Lancet","first-page":"18","article-title":"Serious reactions after mass treatment of onchocerciasis with ivermectin in an area endemic for Loa loa infection","volume":"350","author":"Gardon","year":"1997"},{"key":"R8","series-title":"Ann Trop Med Parasitol","first-page":"495","article-title":"Relationships between the prevalence and intensity of Loa loa infection in the Central province of Cameroon","volume":"95","author":"Boussinesq","year":"2001"},{"key":"R9","series-title":"Parasitology","first-page":"101","article-title":"Microfilarial distribution of Loa loa in the human host: population dynamics and epidemiological implications","volume":"133","author":"Pion","year":"2006"},{"key":"R10","series-title":"Proc Natl Acad Sci U S A","first-page":"695","article-title":"Multidrug-resistance gene (P-glycoprotein) is expressed by endothelial cells at blood\u2013brain barrier sites","volume":"86","author":"Cordon-Cardo","year":"1989"},{"key":"R11","series-title":"Ann Emerg Med","first-page":"51","article-title":"Agricultural avermectins: an uncommon but potentially fatal cause of pesticide poisoning","volume":"34","author":"Chung","year":"1999"},{"key":"R12","series-title":"Vet Parasitol","first-page":"197","article-title":"The safety-net story about macrocyclic lactone heartworm preventives: a review, an update, and recommendations","volume":"133","author":"McCall","year":"2005"},{"key":"R13","series-title":"Am J Vet Res","first-page":"684","article-title":"Clinical observations in collies given ivermectin orally","volume":"48","author":"Paul","year":"1987"},{"key":"R14","series-title":"J Vet Pharmacol Ther","first-page":"257","article-title":"Therapeutic implications of the MDR-1 gene","volume":"27","author":"Mealey","year":"2004"},{"key":"R15","series-title":"Oncogene","first-page":"7468","article-title":"P-glycoprotein: from genomics to mechanism","volume":"22","author":"Ambudkar","year":"2003"},{"issue":"(Suppl 1)","key":"R16","series-title":"Filaria J","first-page":"S8","article-title":"Ivermectin: does P-glycoprotein play a role in neurotoxicity?","volume":"2","author":"Edwards","year":"2003"},{"key":"R17","series-title":"Parasitol Today","first-page":"226","article-title":"Pharmacology of ivermectin","volume":"4","author":"Bennett","year":"1988"},{"key":"R18","series-title":"J Neurol Neurosurg Psychiatry","first-page":"103","article-title":"Encephalitis in Loa-loa filariasis","volume":"18","author":"Van Bogaert","year":"1955"},{"key":"R19","series-title":"Blood","first-page":"2735","article-title":"Expression and activity of the multidrug resistance P-glycoprotein in human peripheral blood lymphocytes","volume":"80","author":"Chaudhary","year":"1992"},{"key":"R20","series-title":"Biochem Pharmacol","first-page":"949","article-title":"Expression of the drug transporters MDR1\/ABCB1, MRP1\/ABCC1, MRP2\/ABCC2, BCRP\/ABCG2, and PXR in peripheral blood mononuclear cells and their relationship with expression in intestine and liver","volume":"70","author":"Albermann","year":"2005"},{"key":"R21","series-title":"Pharmacogenomics J","first-page":"154","article-title":"ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research","volume":"7","author":"Leschziner","year":"2007"},{"key":"R22","series-title":"Proc Natl Acad Sci U S A","first-page":"265","article-title":"Expression of a multidrug-resistance gene in human tumors and tissues","volume":"84","author":"Fojo","year":"1987"},{"key":"R23","series-title":"Proc Natl Acad Sci USA","first-page":"7735","article-title":"Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues","volume":"84","author":"Thiebaut","year":"1987"},{"key":"R24","series-title":"Cancer Res","first-page":"1926","article-title":"Tissue distribution of P-glycoprotein encoded by a multidrug resistant gene as revealed by a monoclonal antibody, MRK 16","volume":"48","author":"Sugawara","year":"1988"},{"key":"R25","series-title":"Acta Genetica Sinica","first-page":"93","article-title":"MDRl Gene polymorphisms and clinical relevance","volume":"33","author":"Li","year":"2006"},{"key":"R26","series-title":"Eur J Clin Pharmacol","first-page":"97","article-title":"Single nucleotide polymorphisms of ABCB1 (MDR1) gene and distinct haplotype profile in a West Black African population","volume":"61","author":"Allabi","year":"2005"},{"key":"R27","series-title":"Pharmacogenetics J","first-page":"217","article-title":"MDRl pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity","volume":"11","author":"Ameyaw","year":"2001"},{"key":"R28","series-title":"Lancet","first-page":"383","article-title":"Frequency of C3435T polymorphism of MDR1 gene in African 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