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Whole-Genome Sequencing to Evaluate the Resistance Landscape Following Antimalarial Treatment Failure With Fosmidomycin-Clindamycin

Year: 2016
Type: article
Abstract: Novel antimalarial therapies are needed in the face of emerging resistance to artemisinin combination therapies. A previous study found a high cure rate in Mozambican children with uncomplicated Plasmodium falciparum malaria 7 days after combination treatment with fosmidomycin-clindamycin. However, 28-day cure rates were low (45.9%), owing to parasite recrudescence. We sought to identify any genetic changes underlying parasite recrudescence. To this end, we used a selective whole-genome amplification method to amplify parasite genomes from blood spot DNA samples. Parasite genomes from pretreatment and postrecrudescence samples were subjected to whole-genome sequencing to identify nucleotide variants. Our data did not support the existence of a genetic change responsible for recrudescence following fosmidomycin-clindamycin treatment. Additionally, we found that previously described resistance alleles for these drugs do not represent biomarkers of recrudescence. Future studies should continue to optimize fosmidomycin combinations for use as antimalarial therapies.
DOI: 10.1093/infdis/jiw304
Authors: Ann M. Guggisberg, Sesh A. Sundararaman, Miguel Lanaspa, Cinta Moraleda, Raquel González, Alfredo Mayor, Pau Cisteró, David Hutchinson, Peter G. Kremsner, Beatrice H. Hahn, Quique Bassat, Audrey R. Odom
Institutions: University of Pennsylvania, Hospital Clínic de Barcelona, Manhiça Health Research Centre, Barcelona Institute for Global Health, Universitat de Barcelona, Centre de Recherche Médicales de Lambaréné, University of Tübingen, Washington University in St. Louis
Language: English
Field: Medicine
Open Access status: bronze
Funders: March of Dimes Foundation, National Institutes of Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences
Awards: G1388710674, G1781501939, G2202404319, G4762734956, Training Program in Cellular and Molecular Biology, TARGETING ISPC TO TREAT MALARIA, Molecular Epidemiology and Natural History of SIVcpz, Great Ape Reservoirs of Human Malaria, Washington University Institute of Clinical and Translational Sciences, G9000026982, G9000042340, G9000148241, Cancer Center Support Grant
OpenAlex ID: W2476499393
FWCI: 3.018
Cites: 49
Cited by: 27
Related to: 10