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Hamilton, Elizabeth

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Hamilton

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Elizabeth

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Hamilton, Elizabeth
Author's Publications: search.filters.isAuthorOfPublication.3af16c34-cc39-4022-812d-9df7f64dd84d

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    Changes in drug sensitivity and anti-malarial drug resistance mutations over time among Plasmodium falciparum parasites in Senegal
    (BioMed Central, 2013) Van tyne, Daria; Dieye, Baba; Valim, Clarissa; Daniels, Rachel; Sène, Papa Diogoye; Lukens, Amanda; Ndiaye, Mouhamadou; Bei, Amy; Ndiaye, Yaye Die; Hamilton, Elizabeth; Ndir, Omar; Mboup, Souleymane; Volkman, Sarah K; Wirth, Dyann; Ndiaye, Daouda
    Background: Malaria treatment efforts are hindered by the rapid emergence and spread of drug resistant parasites. Simple assays to monitor parasite drug response in direct patient samples (ex vivo) can detect drug resistance before it becomes clinically apparent, and can inform changes in treatment policy to prevent the spread of resistance. Methods: Parasite drug responses to amodiaquine, artemisinin, chloroquine and mefloquine were tested in approximately 400 Plasmodium falciparum malaria infections in Thiès, Senegal between 2008 and 2011 using a DAPI-based ex vivo drug resistance assay. Drug resistance-associated mutations were also genotyped in pfcrt and pfmdr1. Results: Parasite drug responses changed between 2008 and 2011, as parasites became less sensitive to amodiaquine, artemisinin and chloroquine over time. The prevalence of known resistance-associated mutations also changed over time. Decreased amodiaquine sensitivity was associated with sustained, highly prevalent mutations in pfcrt, and one mutation in pfmdr1 – Y184F – was associated with decreased parasite sensitivity to artemisinin. Conclusions: Directly measuring ex vivo parasite drug response and resistance mutation genotyping over time are useful tools for monitoring parasite drug responses in field samples. Furthermore, these data suggest that the use of amodiaquine and artemisinin derivatives in combination therapies is selecting for increased drug tolerance within this population.
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    Genetic Surveillance Detects Both Clonal and Epidemic Transmission of Malaria following Enhanced Intervention in Senegal
    (Public Library of Science, 2013) Daniels, Rachel; Chang, Hsiao-Han; Séne, Papa Diogoye; Park, Danny C.; Neafsey, Daniel; Schaffner, Stephen; Hamilton, Elizabeth; Lukens, Amanda; Van tyne, Daria; Mboup, Souleymane; Sabeti, Pardis; Ndiaye, Daouda; Wirth, Dyann; Hartl, Daniel; Volkman, Sarah
    Using parasite genotyping tools, we screened patients with mild uncomplicated malaria seeking treatment at a clinic in Thiès, Senegal, from 2006 to 2011. We identified a growing frequency of infections caused by genetically identical parasite strains, coincident with increased deployment of malaria control interventions and decreased malaria deaths. Parasite genotypes in some cases persisted clonally across dry seasons. The increase in frequency of genetically identical parasite strains corresponded with decrease in the probability of multiple infections. Further, these observations support evidence of both clonal and epidemic population structures. These data provide the first evidence of a temporal correlation between the appearance of identical parasite types and increased malaria control efforts in Africa, which here included distribution of insecticide treated nets (ITNs), use of rapid diagnostic tests (RDTs) for malaria detection, and deployment of artemisinin combination therapy (ACT). Our results imply that genetic surveillance can be used to evaluate the effectiveness of disease control strategies and assist a rational global malaria eradication campaign.