Associations between Aminoquinoline Resistance Genotypes and Clinical Presentations of Plasmodium falciparum Infection in Uganda

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dc.contributor.authorCuu, Gloria
dc.contributor.authorAsua, Victor
dc.contributor.authorTukwasibwe, Stephen
dc.contributor.authorNsobya, Sam L.
dc.contributor.authorNanteza, Ann
dc.contributor.authorKimuda, Magambo Phillip
dc.contributor.authorMpimbaza, Arthur
dc.contributor.authorRosenthal, Philip J.
dc.date.accessioned2023-03-06T19:57:20Z
dc.date.available2023-03-06T19:57:20Z
dc.date.issued2020
dc.description.abstractMutations that mediate resistance of Plasmodium falciparum to aminoquinoline antimalarials are selected by prior drug use and may alter parasite fitness, but associations with clinical presentations are uncertain. We evaluated genotypes in samples from a case-control study of determinants of severe malaria in Ugandan children 4 months to 10 years of age. We studied 274 cases with severe malaria matched by age and geography to 275 uncomplicated malaria controls and 179 asymptomatic parasitemic controls. The overall prevalence of mutations of interest (considering mixed results as mutant) was 67.0% for PfCRT K76T, 8.5% for PfMDR1 N86Y, 71.5% for PfMDR1 Y184F, and 14.7% for PfMDR1 D1246Y. Compared to asymptomatic controls, the odds of mutant PfCRT 76T were lower for uncomplicated (odds ratio, 0.42 [95% confidence interval, 0.24 to 0.72]; P < 0.001) or severe (0.56 [0.32 to 0.97]; P = 0.031) malaria; the odds of mutant PfMDR1 86Y were lower for uncomplicated (0.33 [0.16 to 0.65]; P < 0.001) or severe (0.21 [0.09 to 0.45]; P < 0.001) malaria; and the odds of mutant PfMDR1 1246Y were higher for uncomplicated (1.83 [0.90 to 3.98]; P = 0.076) or severe (2.06 [1.01 to 4.55]; P = 0.033) malaria. The odds of mutant PfMDR1 184F were lower in severe than asymptomatic (0.59 [0.37 to 0.92]; P = 0.016) or uncomplicated (0.61 [0.41 to 0.90]; P = 0.009) malaria. Overall, the PfCRT 76T and PfMDR1 86Y mutations were associated with decreased risk of symptomatic malaria, PfMDR1 1246Y was associated with increased risk of symptomatic malaria, and PfMDR1 184F was associated with decreased risk of severe malaria. These results offer insights into parasite genotypes in children with different presentations, although the basis for the identified associations is likely complex.en_US
dc.identifier.citationCuu, G., Asua, V., Tukwasibwe, S., Nsobya, S. L., Nanteza, A., Kimuda, M. P., ... & Rosenthal, P. J. (2020). Associations between aminoquinoline resistance genotypes and clinical presentations of Plasmodium falciparum infection in Uganda. Antimicrobial Agents and Chemotherapy, 64(10), e00721-20.https://doi.org/10.1128/AAC.00721-20en_US
dc.identifier.urihttps://nru.uncst.go.ug/handle/123456789/8092
dc.language.isoenen_US
dc.publisherAntimicrobial Agents and Chemotherapyen_US
dc.subjectmalariaen_US
dc.subjectPlasmodium falciparumen_US
dc.subjectdrug resistanceen_US
dc.subjectgenotypeen_US
dc.subjectdrug resistance mechanismsen_US
dc.subjectAminoquinolineen_US
dc.titleAssociations between Aminoquinoline Resistance Genotypes and Clinical Presentations of Plasmodium falciparum Infection in Ugandaen_US
dc.typeArticleen_US
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