• 1.

    Schenone F, Hugo, Andrea Olea N, Antonio Rojas S, Nolberto García D, 2002. Malaria en Chile: 1913–2001. Revista Médica de Chile 130: 11701176.

    • Search Google Scholar
    • Export Citation
  • 2.

    Escobar DF, Lucchi NW, Abdallah R, Valenzuela MT, Udhayakumar V, Jercic MI, Chenet SM, 2020. Molecular and epidemiological characterization of imported malaria cases in Chile. Malar J 19: 289.

    • Search Google Scholar
    • Export Citation
  • 3.

    World Health Organization, 2015. Guidelines for the Treatment of Malaria. Geneva, Switzerland: WHO. Available at: https://www.who.int/malaria/publications/atoz/9789241549127/en/. Accessed May 4, 2020.

    • Search Google Scholar
    • Export Citation
  • 4.

    MINSAL, 2019. Orientaciones técnicas para el diagnóstico y tratamiento de la malaria en Chile Santiago. Available at: https://diprece.minsal.cl/wrdprss_minsal/wp-content/uploads/2016/06/Orientaciones-t%C3%A9cnicas-para-el-diagn%C3%B3stico-y-tratamiento-de-la-Malaria.pdf. Accessed March 3, 2020.

    • Search Google Scholar
    • Export Citation
  • 5.

    World Health Organization, 2016. World Malaria Report. Geneva, Switzerland: WHO. Available at: www.who.int/malaria. Accessed March 3, 2020.

    • Search Google Scholar
    • Export Citation
  • 6.

    Musset L, Le Bras J, Clain J, 2007. Parallel evolution of adaptive mutations in Plasmodium falciparum mitochondrial DNA during atovaquone-proguanil treatment. Mol Biol Evol 24: 15821585.

    • Search Google Scholar
    • Export Citation
  • 7.

    Plucinski M 2014. Novel mutation in cytochrome B of Plasmodium falciparum in one of two atovaquone-proguanil treatment failures in travelers returning from same site in Nigeria. Open Forum Infect Dis 1: ofu059.

    • Search Google Scholar
    • Export Citation
  • 8.

    Parzy D, Doerig C, Pradines B, Rico A, Fusai T, Doury C, 1997. Proguanil resistance in Plasmodium falciparum African isolates: assessment by mutation-specific polymerase chain reaction and in vitro susceptibility testing. Am J Trop Med Hyg 57: 646650.

    • Search Google Scholar
    • Export Citation
  • 9.

    Massamba L 2020. Late clinical failure associated with cytochrome b codon 268 mutation during treatment of falciparum malaria with atovaquone–proguanil in traveller returning from Congo. Malar J 19: 37.

    • Search Google Scholar
    • Export Citation
  • 10.

    Ekala MT 2007. Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic sites. Malar J 6: 164.

  • 11.

    Wichmann O 2004. Screening for mutations related to atovaquone/proguanil resistance in treatment failures and other imported isolates of Plasmodium falciparum in Europe. J Infect Dis 190: 15411546.

    • Search Google Scholar
    • Export Citation
  • 12.

    Goodman CD 2016. Parasites resistant to the antimalarial atovaquone fail to transmit by mosquitoes. Science 352: 349353.

  • 13.

    Rougemont M, Van Saanen M, Sahli R, Hinrikson HP, Bille J, Jaton K, 2004. Detection of four Plasmodium species in blood from humans by 18S RRNA gene subunit-based and species-specific real-time PCR assays. J Clin Microbiol 42: 56365643.

    • Search Google Scholar
    • Export Citation
  • 14.

    Chenet SM 2016. Independent emergence of the Plasmodium falciparum kelch propeller domain mutant allele C580Y in Guyana. J Infect Dis 213: 14721475.

    • Search Google Scholar
    • Export Citation
  • 15.

    Staines HM, Burrow R, Huei-Yi B, Ster IC, Kremsner PG, Krishna S, 2018. Clinical implications of Plasmodium resistance to atovaquone/proguanil: a systematic review and meta-analysis. J Antimicrob Chemoth 73: 581595.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Atovaquone/Proguanil Resistance in an Imported Malaria Case in Chile

View More View Less
  • 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), Madrid, Spain;
  • 6 Malaria Branch, Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, Georgia

ABSTRACT

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, Instituto de Enfermedades Tropicales, Universidad Nacional Toribio Rodriguez de Mendoza de Amazonas, Chachapoyas, Peru. 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.

Save