Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile

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  • 1 Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodríguez de Mendoza (UNTRM), Chachapoyas, Perú;
  • 2 Instituto de Salud Pública de Chile (ISP), Santiago, Chile;
  • 3 Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile;
  • 4 Departamento de Biología Molecular e Ingeniería Bioquímica, Universidad Pablo de Olavide (UPO), Seville, Spain;
  • 5 Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM);
  • 6 Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia

In November 2018, we diagnosed a cluster of falciparum malaria cases in three Chilean travelers returning from Nigeria. Two patients were treated with sequential intravenous artesunate plus oral atovaquone/proguanil (AP) and one with oral AP. The third patient, a 23-year-old man, presented with fever on day 29 after oral AP treatment and was diagnosed with recrudescent falciparum malaria. The patient was then treated with oral mefloquine, followed by clinical recovery and resolution of parasitemia. Analysis of day 0 and follow-up blood samples, collected on days 9, 29, 34, 64, and 83, revealed that parasitemia had initially decreased but then increased on day 29. Sequencing confirmed Tyr268Cys mutation in the cytochrome b gene, associated with atovaquone resistance, in isolates collected on days 29 and 34 and P. falciparum dihydrofolate reductase mutation Asn51Ile, associated with proguanil resistance in all successfully sequenced samples. Molecular characterization of imported malaria contributes to clinical management in non-endemic countries, helps ascertain the appropriateness of antimalarial treatment policies, and contributes to the reporting of drug resistance patterns from endemic regions.

Author Notes

Address correspondence to Stella M. Chenet, 1600 Clifton Road Atlanta, Atlanta, GA 30329. E-mail: stella.chenet@untrm.edu.pe

Disclaimer: The opinions expressed herein are those of the authors and do not necessarily reflect the views of the CDC.

Financial support: S. M. C, J. R. T., and R. T.-L. are supported by the National University Toribio Rodríguez de Mendoza (Chachapoyas, Peru) (Grants: Contrato No 09-2019-FONDECYT-BM-INC.INV).

Authors’ addresses: Stella M. Chenet, Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, Peru, and Sección de Parasitología, Instituto de Salud Publica de Chile, Santiago, Chile, E-mail: schenet@asu.edu. Alan Oyarce and María Isabel Jercic, Sección de Parasitología, Instituto de Salud Publica de Chile, Santiago, Chile, E-mails: aoyarce@ispch.cl and majercic@ispch.cl. Jorge Fernandez, Subdepartamento de Genética Molecular, Instituto de Salud Pública de Chile (ISP), Santiago, Chile, E-mail: jfernand@ispch.cl. Rafael Tapia-Limonchi, Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, Peru, E-mail: rafael.tapia@untrm.edu.pe. Thomas Weitzel, Facultad de Medicina Clínica Alemana, Universidad del Desarrollo, Santiago, Chile, E-mail: thomas.weitzel@gmail.com. Juan R. Tejedo, Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, Peru, and Departamento de Biología Molecular e Ingeniería Bioquímica, Universidad Pablo de Olavide, Sevilla, Spain, E-mail: juan.tejedo@untrm.edu.pe. Venkatachalam Udhayakumar and Naomi W. Lucchi, Malaria Branch, CDC, Chamblee, GA, E-mails: vxu0@cdc.gov and frd9@cdc.gov.

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