3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

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

      Preprint
      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Intervention against falciparum malaria in high transmission regions remains challenging, with relaxation of control efforts typically followed by rapid resurgence. Resilience to intervention co-occurs with incomplete immunity, whereby children eventually become protected from severe disease but not infection and a large transmission reservoir results from high asymptomatic prevalence across all ages. Incomplete immunity relates to the vast antigenic variation of the parasite, with the major surface antigen of the blood stage of infection encoded by the multigene family known as var. Recent deep sampling of var sequences from individual isolates in northern Ghana showed that parasite population structure exhibited persistent features of high-transmission regions despite the considerable decrease in prevalence during transient intervention with indoor residual spraying (IRS). We ask whether despite such apparent limited impact, the transmission system had been brought close to a transition in both prevalence and resurgence ability. With a stochastic agent-based model, we investigate the existence of such a transition to pre-elimination with intervention intensity, and of molecular indicators informative of its approach. We show that resurgence ability decreases sharply and nonlinearly across a narrow region of intervention intensities in model simulations, and identify informative molecular indicators based on var gene sequences. Their application to the survey data indicates that the transmission system in northern Ghana was brought close to transition by IRS. These results suggest that sustaining and intensifying intervention would have pushed malaria dynamics to a slow-rebound regime with an increased probability of local parasite extinction.

          One Sentence Summary:

          Population genomics of hyper-diverse var genes inform resurgence dynamics in falciparum malaria.

          Related collections

          Most cited references89

          • Record: found
          • Abstract: not found
          • Article: not found

          Measurement of Diversity

          E. SIMPSON (1949)
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Measures of the Amount of Ecologic Association Between Species

            Lee Dice (1945)
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              A general method for numerically simulating the stochastic time evolution of coupled chemical reactions

                Bookmark

                Author and article information

                Contributors
                Role: ConceptualizationRole: MethodologyRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Journal
                medRxiv
                MEDRXIV
                medRxiv
                Cold Spring Harbor Laboratory
                05 February 2024
                : 2024.02.01.24301818
                Affiliations
                [1 ]Committee on Genetics, Genomics and Systems Biology, The University of Chicago; Chicago, IL, 60637, USA.
                [2 ]Department of Biological Sciences, Purdue University; West Lafayette, IN, 47907, USA.
                [3 ]Department of Microbiology and Immunology, Bio21 Institute and Peter Doherty Institute, The University of Melbourne; Melbourne, Australia.
                [4 ]Department of Biology, New York University; New York, NY, 10012, USA.
                [5 ]Department of Environmental Studies, New York University; New York, NY, 10012, USA.
                [6 ]Santa Fe Institute; Santa Fe, NM, 87501, USA.
                Author information
                http://orcid.org/0000-0001-7959-817X
                http://orcid.org/0000-0002-6115-6135
                Article
                10.1101/2024.02.01.24301818
                10871444
                38370729
                6473e353-bbf1-487d-88ae-6c163081f7a4

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

                History
                Funding
                Funded by: NIH-NSF-NIFA Ecology and Evolution of Infectious Disease
                Award ID: R01-TW009670
                Award ID: R01-AI149779
                Categories
                Article

                Comments

                Comment on this article