Article Category:
Research Article

Serologic and Cytokine Profiles of Children with Concurrent Cerebral Malaria and Severe Malarial Anemia Are Distinct from Other Subtypes of Severe Malaria

Rafal S. Sobota Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;
Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, Illinois;

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Abby R. Goron Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Andrea A. Berry Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Jason A. Bailey Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Drissa Coulibaly Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Matthew Adams Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Abdoulaye K. Kone Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Bourema Kouriba Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Ogobara K. Doumbo Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Marcelo B. Sztein Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Philip L. Felgner Division of Infectious Diseases, Department of Medicine, University of California, Irvine, California

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Christopher V. Plowe Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Kirsten E. Lyke Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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Mahamadou A. Thera Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali;

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Mark A. Travassos Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland;

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DOI:
https://doi.org/10.4269/ajtmh.22-0135
Volume/Issue:
Volume 107: Issue 2
Page(s):
315–319
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ABSTRACT.

We used a protein microarray featuring Plasmodium falciparum field variants of a merozoite surface antigen to examine malaria exposure in Malian children with different severe malaria syndromes. Unlike children with cerebral malaria alone or severe malarial anemia alone, those with concurrent cerebral malaria and severe malarial anemia had serologic responses demonstrating a broader prior parasite exposure pattern than matched controls with uncomplicated disease. Comparison of levels of malaria-related cytokines revealed that children with the concurrent phenotype had elevated levels of interleukin (IL)-6, IL-8, and IL-10. Our results suggest that the pathophysiology of this severe subtype is unique and merits further investigation.

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Author Notes

Address correspondence to Mark A. Travassos, Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 West Baltimore Street, Room 480, Baltimore, MD 21201. E-mail: mtravass@som.umaryland.edu

These authors contributed equally to this work.

Deceased.

These authors contributed equally to this work.

Financial support: This work was supported by National Institutes of Health (NIH) grants R01HL130750 and R01HL146377 (National Heart, Lung, and Blood Institute); cooperative agreement U19AI065683 (NIH National Institute of Allergy and Infectious Diseases ); NIH National Institute of Allergy and Infectious Diseases grant R01AI099628; a Burroughs Wellcome Fund/American Society of Tropical Medicine and Hygiene Postdoctoral Fellowship to M. A. T.; and an award to C. V. P. from the Howard Hughes Medical Institute. This research was supported by a subproject to R. S. S. on NIH R25NS070695.

Authors’ addresses: Rafal S. Sobota, Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, IL, E-mail: rafal4484@gmail.com. Abby R. Goron, Johns Hopkins University, Baltimore, MD, E-mail: agoron1@jhmi.edu. Andrea A. Berry, Jason A. Bailey, Matthew Adams, Marcelo B. Sztein, Christopher V. Plowe, Kirsten E. Lyke, and Mark A. Travassos, Malaria Research Program, Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, MD, E-mails: aberry@som.umaryland.edu, jason.bailey.719@gmail.com, madams@som.umaryland.edu, msztein@som.umaryland.edu, klyke@som.umaryland.edu, klyke@som.umaryland.edu, and mtravass@som.umaryland.edu. Drissa Coulibaly, Abdoulaye K. Kone, Bourema Kouriba, and Mahamadou A. Thera, Malaria Research and Training Center, University of Sciences, Techniques and Technologies, Bamako, Mali, E-mail: coulibalyd@icermali.org, akkone@yahoo.fr, kouriba@icermali.org, and mthera@icermali.org. Philip L. Felgner, Division of Infectious Diseases, Department of Medicine, University of California, Irvine, CA, E-mail: pfelgner@uci.edu.

Copyright:
© The American Society of Tropical Medicine and Hygiene 2022
Received:
17 Feb 2022
|
Accepted:
25 Mar 2022
|
Published Online:
13 Jun 2022
Cover The American Journal of Tropical Medicine and Hygiene
The American Journal of Tropical Medicine and Hygiene
Print ISSN:
0002-9637
Online ISSN:
1476-1645
  • 1.

    World Health Organization , 2020. WHO World Malaria Report. Geneva, Switzerland: WHO.

    • PubMed
    • Export Citation
  • 2.

    Murphy SC , Breman JG , 2001. Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy. Am J Trop Med Hyg 64: 57–67.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Lyke KE , Dicko A , Kone A , Coulibaly D , Guindo A , Cissoko Y , Traore K , Plowe CV , Doumbo OK , 2004. Incidence of severe Plasmodium falciparum malaria as a primary endpoint for vaccine efficacy trials in Bandiagara, Mali. Vaccine 22: 3169–3174.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Djimdé A et al., 2001. A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344: 257–263.

  • 5.

    Chan JA et al., 2012. Targets of antibodies against Plasmodium falciparum-infected erythrocytes in malaria immunity. J Clin Invest 122: 3227–3238.

  • 6.

    Travassos MA et al., 2018. Children with cerebral malaria or severe malarial anaemia lack immunity to distinct variant surface antigen subsets. Sci Rep 8: 6281.

  • 7.

    Bailey JA et al., 2020. Microarray analyses reveal strain-specific antibody responses to Plasmodium falciparum apical membrane antigen 1 variants following natural infection and vaccination. Sci Rep 10: 3952.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Lyke KE et al., 2004. Serum levels of the proinflammatory cytokines interleukin-1 beta (IL-1beta), IL-6, IL-8, IL-10, tumor necrosis factor alpha, and IL-12(p70) in Malian children with severe Plasmodium falciparum malaria and matched uncomplicated malaria or healthy controls. Infect Immun 72: 5630–5637.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Stucke EM et al., 2019. Serologic responses to the PfEMP1 DBL-CIDR head structure may be a better indicator of malaria exposure than those to the DBL-alpha tag. Malar J 18: 273.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Bailey JA et al., 2015. Seroreactivity to a large panel of field-derived Plasmodium falciparum apical membrane antigen 1 and merozoite surface protein 1 variants reflects seasonal and lifetime acquired responses to malaria. Am J Trop Med Hyg 92: 9–12.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Travassos MA et al., 2013. Seroreactivity to Plasmodium falciparum erythrocyte membrane protein 1 intracellular domain in malaria-exposed children and adults. J Infect Dis 208: 1514–1519.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Travassos MA et al., 2015. Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women. Am J Trop Med Hyg 92: 1190–1194.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Ventimiglia NT et al., 2021. Malian adults maintain serologic responses to virulent PfEMP1s amid seasonal patterns of fluctuation. Sci Rep 11: 14401.

  • 14.

    Hviid L , 2005. Naturally acquired immunity to Plasmodium falciparum malaria in Africa. Acta Trop 95: 270–275.

  • 15.

    Urquhart AD , 1994. Putative pathophysiological interactions of cytokines and phagocytic cells in severe human falciparum malaria. Clin Infect Dis 19: 117–131.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Friedland JS , Ho M , Remick DG , Bunnag D , White NJ , Griffin GE , 1993. Interleukin-8 and Plasmodium falciparum malaria in Thailand. Trans R Soc Trop Med Hyg 87: 54–55.

    • PubMed
    • Search Google Scholar
    • Export Citation

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First Report. World Health Organization Technical Report Series No. 62 (Available also in French). 26 pp. Geneva, W.H.O., Palais des Nations. March, 1953. Price 1/6, $0.20, Fr. fr. 65.-; Sw. fr. 0.80

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