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Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria

Author

Listed:
  • Qi Zhan

    (The University of Chicago)

  • Qixin He

    (Purdue University)

  • Kathryn E. Tiedje

    (The University of Melbourne)

  • Karen P. Day

    (The University of Melbourne)

  • Mercedes Pascual

    (New York University
    New York University
    Santa Fe Institute)

Abstract

Intervention efforts against falciparum malaria in high-transmission regions remain challenging, with rapid resurgence typically following their relaxation. Such resilience co-occurs with incomplete immunity and a large transmission reservoir from high asymptomatic prevalence. Incomplete immunity relates to the large antigenic variation of the parasite, with the major surface antigen of the blood stage of infection encoded by the multigene and recombinant family known as var. With a stochastic agent-based model, we investigate the existence of a sharp transition in resurgence ability with intervention intensity and identify molecular indicators informative of its proximity. Their application to survey data with deep sampling of var sequences from individual isolates in northern Ghana suggests that the transmission system was brought close to transition by intervention with indoor residual spraying. These results indicate that sustaining and intensifying intervention would have pushed malaria dynamics to a slow-rebound regime with an increased probability of local parasite extinction.

Suggested Citation

  • Qi Zhan & Qixin He & Kathryn E. Tiedje & Karen P. Day & Mercedes Pascual, 2024. "Hyper-diverse antigenic variation and resilience to transmission-reducing intervention in falciparum malaria," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51468-6
    DOI: 10.1038/s41467-024-51468-6
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    References listed on IDEAS

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    1. Lúcio H. Freitas-Junior & Emmanuel Bottius & Lindsay A. Pirrit & Kirk W. Deitsch & Christine Scheidig & Francoise Guinet & Ulf Nehrbass & Thomas E. Wellems & Artur Scherf, 2000. "Frequent ectopic recombination of virulence factor genes in telomeric chromosome clusters of P. falciparum," Nature, Nature, vol. 407(6807), pages 1018-1022, October.
    2. Kelsey M. Sumner & Elizabeth Freedman & Lucy Abel & Andrew Obala & Brian W. Pence & Amy Wesolowski & Steven R. Meshnick & Wendy Prudhomme-O’Meara & Steve M. Taylor, 2021. "Genotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Qixin He & Shai Pilosof & Kathryn E. Tiedje & Shazia Ruybal-Pesántez & Yael Artzy-Randrup & Edward B. Baskerville & Karen P. Day & Mercedes Pascual, 2018. "Networks of genetic similarity reveal non-neutral processes shape strain structure in Plasmodium falciparum," Nature Communications, Nature, vol. 9(1), pages 1-12, December.
    4. Marvin Chew & Weijian Ye & Radoslaw Igor Omelianczyk & Charisse Flerida Pasaje & Regina Hoo & Qingfeng Chen & Jacquin C. Niles & Jianzhu Chen & Peter Preiser, 2022. "Selective expression of variant surface antigens enables Plasmodium falciparum to evade immune clearance in vivo," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
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