• 1.

    World Health Organization, 2019. World Malaria Report 2019. Geneva, Switzerland: WHO. Available at: https://www.who.int/publications/i/item/world-malaria-report-2019. Accessed August 8, 2020.

  • 2.

    Dondorp A, Nosten F, Stepniewska K, Day N, White N, South East Asian Quinine Artesunate Malaria Trial (SEAQUAMAT) Group, 2005. Artesunate versus quinine for treatment of severe falciparum malaria: a randomised trial. Lancet 366: 717725.

    • Search Google Scholar
    • Export Citation
  • 3.

    Dondorp AM 2010. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial. Lancet 376: 16471657.

    • Search Google Scholar
    • Export Citation
  • 4.

    Rehman K, Lötsch F, Kremsner PG, Ramharter M, 2014. Haemolysis associated with the treatment of malaria with artemisinin derivatives: a systematic review of current evidence. Int J Infect Dis 29: 268273.

    • Search Google Scholar
    • Export Citation
  • 5.

    Roussel C, Caumes E, Thellier M, Ndour PA, Buffet PA, Jauréguiberry S, 2017. Artesunate to treat severe malaria in travellers: review of efficacy and safety and practical implications. J Travel Med 24: 19.

    • Search Google Scholar
    • Export Citation
  • 6.

    Jauréguiberry S 2014. Postartesunate delayed hemolysis is a predictable event related to the lifesaving effect of artemisinins. Blood 124: 167175.

    • Search Google Scholar
    • Export Citation
  • 7.

    Rolling T 2014. Delayed hemolysis after treatment with parenteral artesunate in African children with severe malaria: a double-center prospective study. J Infect Dis 209: 19211928.

    • Search Google Scholar
    • Export Citation
  • 8.

    Scheu K 2019. Determinants of post-malarial anemia in African children treated with parenteral artesunate. Sci Rep 9: 18134.

  • 9.

    Hawkes MT 2020. Anemia and transfusion requirements among Ugandan children with severe malaria treated with intravenous artesunate. Pediatr Hematol Oncol 37: 140152.

    • Search Google Scholar
    • Export Citation
  • 10.

    Varo R 2020. Post-malarial anemia in Mozambican children treated with quinine or artesunate: a retrospective observational study. Int J Infect Dis 96: 655662.

    • Search Google Scholar
    • Export Citation
  • 11.

    Fanello C 2017. Post-treatment haemolysis in African children with hyperparasitaemic falciparum malaria: a randomized comparison of artesunate and quinine. BMC Infect Dis 17: 575.

    • Search Google Scholar
    • Export Citation
  • 12.

    World Health Organization, Regional Office for the Western Pacific, 2016. Malaria Microscopy Standard Operating Procedures. Available at: https://apps.who.int/iris/handle/10665/274382. Accessed April 2, 2021.

  • 13.

    Weimer A 2019. Blood transfusion safety in sub-Saharan Africa: a literature review of changes and challenges in the 21st century. Transfusion 59: 412427.

    • Search Google Scholar
    • Export Citation
  • 14.

    Kabaghe A 2017. Short-term changes in anemia and malaria parasite prevalence in children under 5 years during one year of repeated cross-sectional surveys in rural Malawi. Am J Trop Med Hyg 97: 1568–1575.

    • Search Google Scholar
    • Export Citation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Post-Malaria Anemia Is Rare in Malawian Children with Cerebral Malaria

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  • 1 Department of Pediatrics, Children’s National Medical Center, Washington, District of Columbia;
  • 2 Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi;
  • 3 Division of Biostatistics and Study Methodology, Children’s National Research Institute, Washington, District of Columbia;
  • 4 Division of Epidemiology, The George Washington University School of Public Health, Washington, District of Columbia;
  • 5 Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan;
  • 6 Division of Neurology, The George Washington University/Children’s National Medical Center, Washington, District of Columbia

Abstract.

Artesunate therapy for severe malaria syndromes has been associated with post-treatment hemolysis and anemia. We defined post-malaria anemia as any decrease in hematocrit between the index hospitalization for severe malaria and 1 month after. We determined the incidence and severity of post-malaria anemia in Malawian children surviving cerebral malaria (CM) by analyzing hospital and follow-up data from a long-standing study of CM pathogenesis. Children enrolled before 2014 and treated with quinine (N = 258) were compared with those admitted in 2014 and after, and treated with artesunate (N = 235). The last hematocrit value obtained during hospitalization was compared with the 1-month post-hospitalization hematocrit value. The overall rate of a post-hospitalization decrease in hematocrit in children surviving CM was 5.3% (11 of 235 or 4.7% for quinine, 15 of 258 or 5.8% for artesunate; odds ratio, 3.23 [0.88, 18.38]); no patients with a decrease in hematocrit were symptomatic, and none required transfusion after hospitalization. Of the 26 children who had a decrease in hematocrit 1 month after hospitalization, 23.1% had evidence of a new malaria infection. When children treated with quinine and artesunate were combined, a higher hematocrit level on admission, lower quantitative histidine-rich protein level, and splenomegaly were associated independently with post-malaria anemia. In African survivors of CM, post-malaria anemia is rare, mild, and unassociated with the anti-malarial treatment received.

Author Notes

Address correspondence to Douglas G. Postels, Division of Neurology, Children’s National Medical Center, 111 Michigan Ave. NW, Washington, DC 20010. E-mail: dpostels@childrensnational.org

Financial support: G. G.’s work was supported by the Robert H. Parrott Research, Education, Advocacy, and Child Health Care Program at Children’s National as well as by the Children’s National Global Health Initiative. R. I.’s work in the Division of Biostatistics and Study Methodology was supported by award number UL1TR001876 from the NIH National Center for Advancing Translational Sciences. Financial support for statistical analysis was provided by intramural funds from the Division of Neurology at Children’s National Medical Center.

Authors’ addresses: Geoffrey Guenther, Department of Pediatrics, Children’s National Medical Center, Washington, DC, E-mail: gguenther2@childrensnational.org. Alexuse M. Saidi, Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi, E-mail: alexmsaidi@gmail.com. Rima Izem, Division of Biostatistics and Study Methodology, Children’s National Research Institute, Washington, DC, and Division of Epidemiology, The George Washington University School of Public Health, Washington, DC, E-mail: izem.rima@gmail.com. Karl Seydel, Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi, and Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, E-mail: seydel@msu.edu. Douglas G. Postels, Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi, and Division of Neurology, The George Washington University/Children’s National Medical Center, Washington, DC, E-mail: dpostels@childrensnational.org.

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