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Therapeutic Efficacy of Artemisinin-Based Combination Therapies in Democratic Republic of the Congo and Investigation of Molecular Markers of Antimalarial Resistance

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  • 1 Malaria Branch, Centers for Disease Control and Prevention, Atlanta, Georgia;
  • | 2 President’s Malaria Initiative, Atlanta, Georgia;
  • | 3 Georgia State University School of Public Health, Atlanta, Georgia;
  • | 4 National Institute of Biomedical Research, Kinshasa, Democratic Republic of the Congo;
  • | 5 Faculty of Medicine, University of Kisangani, Kisangani, Democratic Republic of the Congo;
  • | 6 Tropical Medicine Department, University of Kinshasa, Kinshasa, Democratic Republic of the Congo;
  • | 7 National Malaria Control Program, Ministry of Health, Kinshasa, Democratic Republic of the Congo;
  • | 8 Faculty of Medicine University of Lubumbashi, Lubumbashi, Democratic Republic of the Congo;
  • | 9 Liverpool School of Tropical Medicine and Hygiene Pembroke Place, Liverpool, United Kingdom;
  • | 10 Unit of Clinical Pharmacology and Pharmacovigilance University of Kinshasa, Kinshasa, Democratic Republic of the Congo;
  • | 11 President’s Malaria Initiative, Kampala, Uganda;
  • | 12 United States Agency for International Development, President’s Malaria Initiative, Kinshasa, Democratic Republic of the Congo;
  • | 13 Biomedical Department, University of Kinshasa, Kinshasa, Democratic Republic of the Congo;
  • | 14 Association of Public Health Laboratories, Silver Spring, Maryland;
  • | 15 Department of Pharmacology and Therapeutics, University of Kinshasa, Kinshasa, Democratic Republic of the Congo

ABSTRACT.

Routine assessment of the efficacy of artemisinin-based combination therapies (ACTs) is critical for the early detection of antimalarial resistance. We evaluated the efficacy of ACTs recommended for treatment of uncomplicated malaria in five sites in Democratic Republic of the Congo (DRC): artemether-lumefantrine (AL), artesunate-amodiaquine (ASAQ), and dihydroartemisinin-piperaquine (DP). Children aged 6–59 months with confirmed Plasmodium falciparum malaria were treated with one of the three ACTs and monitored. The primary endpoints were uncorrected and polymerase chain reaction (PCR)-corrected 28-day (AL and ASAQ) or 42-day (DP) cumulative efficacy. Molecular markers of resistance were investigated. Across the sites, uncorrected efficacy estimates ranged from 63% to 88% for AL, 73% to 100% for ASAQ, and 56% to 91% for DP. PCR-corrected efficacy estimates ranged from 86% to 98% for AL, 91% to 100% for ASAQ, and 84% to 100% for DP. No pfk13 mutations previously found to be associated with ACT resistance were observed. Statistically significant associations were found between certain pfmdr1 and pfcrt genotypes and treatment outcome. There is evidence of efficacy below the 90% cutoff recommended by WHO to consider a change in first-line treatment recommendations of two ACTs in one site not far from a monitoring site in Angola that has shown similar reduced efficacy for AL. Confirmation of these findings in future therapeutic efficacy monitoring in DRC is warranted.

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Author Notes

Address correspondence to Leah F. Moriarty, Centers for Disease Control and Prevention, 1600 Clifton Rd. NE, MS V18-2, Atlanta, GA 30330. E-mail: lmoriarty@cdc.gov

Financial support: This study was partially funded by the U.S. President’s Malaria Initiative, the Global Fund to Fight AIDS, Tuberculosis and Malaria, the Department for International Development, World Health Organization. The Centers for Disease Control and Prevention provided staff support to the study.

Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the U.S. Centers for Disease Control and Prevention or USAID.

Disclosure: All data generated or analyzed during this study are available from the corresponding author upon reasonable request.

Authors’ addresses: Leah F. Moriarty, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, President’s Malaria Initiative, Atlanta, GA, and Georgia State University School of Public Health, Atlanta, GA, E-mail: lmoriarty@cdc.gov. Papy Mandoko Nkoli, National Institute of Biomedical Research, Kinshasa, DRC, E-mail: drpmandoko@yahoo.fr. Joris Losimba Likwela, Faculty of Medicine, University of Kisangani, Kisangani, DRC, E-mail: jorislikwela@gmail.com. Patrick Mitashi Mulopo, Junior Matangila Rika, and Hypolite Muhindo Mavoko, Tropical Medicine Department, University of Kinshasa, Kinshasa, DRC, E-mails: patrick.mitashi@unikin.ac.cd, matangilaj@yahoo.fr, and hypolite.muhindo@unikin.ac.cd. Eric Mukomena Sompwe, National Malaria Control Program, Ministry of Health, Kinshasa, DRC, and Faculty of Medicine University of Lubumbashi, Lubumbashi, DRC, E-mail: ericsompwe27867@gmail.com. Samaly S. Svigel, Naomi Lucchi, and Gireesh Subramaniam, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, E-mails: ynp4@cdc.gov, frd9@cdc.gov, and gireeshsubramaniam@gmail.com. Sam Jones, Liverpool School of Tropical Medicine and Hygiene, Pembroke Place, Liverpool, United Kingdom, E-mail: joness@mmv.org. Nsengi Y. Ntamabyaliro, Unit of Clinical Pharmacology and Pharmacovigilance, University of Kinshasa, Kinshasa, DRC, E-mail: nsengi.ntama@unikin.ac.cd. Albert Kutekemeni Kaputu, National Malaria Control Program, Ministry of Health, Kinshasa, DRC, E-mail: alkutek@gmail.com. Mame Niang, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, and President’s Malaria Initiative, Kampala, Uganda, E-mail: mwz5@cdc.gov. Aboubacar Sadou, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, and United States Agency for International Development, President’s Malaria Initiative, Kinshasa, DRC, E-mail: asadou@usaid.gov. Dieudonné Mumba Ngoyi, National Institute of Biomedical Research, Kinshasa, DRC, and Tropical Medicine Department, University of Kinshasa, Kinshasa, DRC, E-mail: mumbadieudonne@yahoo.fr. Jean Jacques Muyembe Tamfum, National Institute of Biomedical Research, Kinshasa, DRC, and Biomedical Department, University of Kinshasa, Kinshasa, DRC, E-mail: jjmuyembet@gmail.com. Sarah E. Schmedes, Malaria Branch, Centers for Disease Control & Prevention, Atlanta, GA, and Association of Public Health Laboratories, Silver Spring, MD, E-mail: sarahschmedes@gmail.com. Mateusz M. Plucinski and Eric S. Halsey, Malaria Branch, Centers for Disease Control and Prevention, Atlanta, GA, and President’s Malaria Initiative, Atlanta, GA, E-mails: wif7@cdc.gov and ycw8@cdc.gov. Gerardo Chowell-Puente, Georgia State University School of Public Health, Atlanta, GA, E-mail: gchowell@gsu.edu. Gauthier Mesia Kahunu, Unit of Clinical Pharmacology and Pharmacovigilance University of Kinshasa, Kinshasa, DRC, and Department of Pharmacology and Therapeutics, University of Kinshasa, Kinshasa, DRC, E-mail: mesia.kahunu@unikin.ac.cd.

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