Published December 2, 2025 | Version v1
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Interactions Between the Frequency of the Duffy Antigen and the Dynamics of P. vivax Malaria Infections

Authors/Creators

  • 1. ROR icon University of Arizona
  • 2. Simon A. Levin Mathematical, Computational, and Modeling Sciences Center
  • 3. EDMO icon Rice University
  • 4. ROR icon Arizona State University

Description

The malarial parasite Plasmodium vivax has infected humans for millennia. As such, alleles like the FY*O allele in the Duffy Antigen Receptor for Chemokines (DARC) and
the sickle cell allele (HbS) have been naturally selected for in malaria-endemic regions because they confer resistance to malaria, thereby increasing the survival and reproductive success of individuals carrying these protective alleles. As resistance becomes more common in a population, malaria incidence is expected to decline, reducing the evolutionary pressure for additional resistance. In this work, we explore the interaction between these processes. We construct a model with seasonality that tracks the frequency of Duffy genotypes and leverages fast/slow dynamics to analyze the coupled dynamics of malaria transmission and changes in the gene frequency of the DARC genotype. Specifically, we investigate how the burden of malaria changes with the fractions of people with the various DARC genotypes. We derive the basic reproduction number as the threshold condition for the stability of the disease-free equilibrium and interpret the R_0 as a weighted sum of the cases generated by infected individuals of each genotype. Additionally, we calibrate our model using data from the Amazonas region in Brazil, which has a polymorphic population with respect to DARC, and still reports a substantial number of P. vivax cases. Analysis of our model determines the proportion of the population that must be Duffy-negative in order for the entire population to be protected against P. vivax without any further interventions. Furthermore, we assess how different proportions of Duffy-negative individuals influence the monthly incidence of P. vivax cases.

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References

  • Andargie Abate et al. "Differential transmissibility to Anopheles arabiensis of Plasmodium vivax gametocytes in patients with diverse Duffy blood group genotypes". In: Malaria Journal 22.1 (2023), p. 136.
  • FB Agusto, AB Gumel, and PE Parham. "Qualitative assessment of the role of temperature variations on malaria transmission dynamics". In: Journal of Biological Systems 23.04 (2015), p. 1550030.
  • Leon Arriola and James M Hyman. "Sensitivity analysis for uncertainty quantification in mathematical models". In: Mathematical and statistical estimation approaches in epidemiology. Springer, 2009, pp. 195–247.
  • Brazil. en. https://data.who.int/countries/076. Accessed: 2024-6-19.
  • Thomas S Churcher et al. "Probability of transmission of malaria from mosquito to human is regulated by mosquito parasite density in naive and vaccinated hosts". In: PLoS pathogens 13.1 (2017), e1006108.
  • Zhilan Feng and Carlos Castillo-Chavez. "The influence of infectious diseases on population genetics". In: Mathematical Biosciences & Engineering 3.3 (2006), pp. 467– 483.
  • Zhilan Feng et al. "Coupling ecology and evolution: malaria and the S-gene across time scales". In: Mathematical biosciences 189.1 (2004), pp. 1–19.
  • Renzo Galanello and Raffaella Origa. "Beta-thalassemia". In: Orphanet journal of rare diseases 5 (2010), pp. 1–15.
  • Klauss Kleydmann Sabino Garcia et al. "Is Brazil reaching malaria elimination? A time series analysis of malaria cases from 2011 to 2023". In: PLOS Global Public Health 4.1 (2024), e0002845.
  • Carlos A Guerra et al. "The international limits and population at risk of Plasmodium vivax transmission in 2009". In: PLoS neglected tropical diseases 4.8 (2010), e774.
  • Terence J Hadley and Stephen C Peiper. "From malaria to chemokine receptor: the emerging physiologic role of the Duffy blood group antigen". In: Blood, The Journal of the American Society of Hematology 89.9 (1997), pp. 3077–3091.
  • Gabriela Höher, Marilu Fiegenbaum, and Silvana Almeida. "Molecular basis of the Duffy blood group system". In: Blood Transfusion 16.1 (2018), p. 93.
  • Rosalind E Howes et al. "Global epidemiology of Plasmodium vivax". In: The American Journal of Tropical Medicine and Hygiene 95.6 Suppl (2016), p. 15.
  • Rosalind E Howes et al. "The Global Distribution of the Duffy Blood Group". In: Nature Communications 2.1 (2011), p. 266.
  • Sarafa Adewale Iyaniwura et al. "Regional variation and epidemiological insights in malaria underestimation in Cameroon". In: medRxiv (2023), pp. 1–11.
  • Flora Satiko Kano et al. "Susceptibility to Plasmodium vivax malaria associated with DARC (Duffy antigen) polymorphisms is influenced by the time of exposure to malaria". In: Scientific reports 8.1 (2018), p. 13851.
  • Simeone Marino et al. "A methodology for performing global uncertainty and sensitivity analysis in systems biology". In: Journal of theoretical biology 254.1 (2008), pp. 178–196.
  • GM1 Meny. "The Duffy blood group system: a review". In: Immunohematology 26.2 (2010), pp. 51–56.
  • Joseli Oliveira-Ferreira et al. "Malaria in Brazil: an overview". In: Malaria journal 9 (2010), pp. 1–15.
  • Jean Popovici, Camille Roesch, and Virginie Rougeron. "The enigmatic mechanisms by which Plasmodium vivax infects Duffy-negative individuals". In: PLoS Pathogens 16.2 (2020), e1008258.
  • Marissa Renardy et al. "Global sensitivity analysis of biological multiscale models". In: Current opinion in biomedical engineering 11 (2019), pp. 109–116
  • David J Sullivan, Peter Agre, et al. "Human Plasmodium vivax mosquito experimental transmission". In: The Journal of Clinical Investigation 130.6 (2020), pp. 2800–2802
  • Priya Venkatesan. "The 2023 WHO World malaria report". In: The Lancet Microbe 5.3 (2024), e214.
  • Amy Yomiko Vittor et al. "The effect of deforestation on the human-biting rate of Anopheles darlingi, the primary vector of falciparum malaria in the Peruvian Amazon". In: American Journal of Tropical Medicine and Hygiene 74.1 (2006), pp. 3–11.
  • Liping Wang et al. "Modeling the transmission and control of Zika in Brazil". In: Scientific reports 7.1 (2017), p. 7721.
  • Michael T White et al. "Immunogenicity of the RTS, S/AS01 malaria vaccine and implications for duration of vaccine efficacy: secondary analysis of data from a phase 3 randomised controlled trial". In: The Lancet infectious diseases 15.12 (2015), pp. 1450– 1458.
  • Michael T White et al. "Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses". In: Malaria journal 17 (2018), pp. 1–15.