Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission

Plasmodium vivax relapse infections occur following activation of latent liver-stages parasites (hypnozoites) causing new blood-stage infections weeks to months after the initial infection. We develop a within-host mathematical model of liver-stage hypnozoites, and validate it against data from trop...

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Main Authors: Michael T White, Stephan Karl, Katherine E Battle, Simon I Hay, Ivo Mueller, Azra C Ghani
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2014-11-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/04692
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spelling doaj-28daf24a8514431f9be6b353e65bb53b2021-05-04T23:31:46ZengeLife Sciences Publications LtdeLife2050-084X2014-11-01310.7554/eLife.04692Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmissionMichael T White0Stephan Karl1Katherine E Battle2Simon I Hay3https://orcid.org/0000-0002-0611-7272Ivo Mueller4Azra C Ghani5MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United KingdomDepartment of Infection and Immunity, Walter and Eliza Hall Institute, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, AustraliaSpatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United KingdomSpatial Ecology and Epidemiology Group, Department of Zoology, University of Oxford, Oxford, United Kingdom; Fogarty International Center, National Institutes of Health, Bethesda, United StatesDepartment of Infection and Immunity, Walter and Eliza Hall Institute, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia; Centre de Recerca en Salut Internacional de Barcelona, Barcelona, SpainMRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Imperial College London, London, United KingdomPlasmodium vivax relapse infections occur following activation of latent liver-stages parasites (hypnozoites) causing new blood-stage infections weeks to months after the initial infection. We develop a within-host mathematical model of liver-stage hypnozoites, and validate it against data from tropical strains of P. vivax. The within-host model is embedded in a P. vivax transmission model to demonstrate the build-up of the hypnozoite reservoir following new infections and its depletion through hypnozoite activation and death. The hypnozoite reservoir is predicted to be over-dispersed with many individuals having few or no hypnozoites, and some having intensely infected livers. Individuals with more hypnozoites are predicted to experience more relapses and contribute more to onwards P. vivax transmission. Incorporating hypnozoite killing drugs such as primaquine into first-line treatment regimens is predicted to cause substantial reductions in P. vivax transmission as individuals with the most hypnozoites are more likely to relapse and be targeted for treatment.https://elifesciences.org/articles/04692malariavivaxrelapsemathematicalmodel
collection DOAJ
language English
format Article
sources DOAJ
author Michael T White
Stephan Karl
Katherine E Battle
Simon I Hay
Ivo Mueller
Azra C Ghani
spellingShingle Michael T White
Stephan Karl
Katherine E Battle
Simon I Hay
Ivo Mueller
Azra C Ghani
Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
eLife
malaria
vivax
relapse
mathematical
model
author_facet Michael T White
Stephan Karl
Katherine E Battle
Simon I Hay
Ivo Mueller
Azra C Ghani
author_sort Michael T White
title Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
title_short Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
title_full Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
title_fullStr Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
title_full_unstemmed Modelling the contribution of the hypnozoite reservoir to Plasmodium vivax transmission
title_sort modelling the contribution of the hypnozoite reservoir to plasmodium vivax transmission
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2014-11-01
description Plasmodium vivax relapse infections occur following activation of latent liver-stages parasites (hypnozoites) causing new blood-stage infections weeks to months after the initial infection. We develop a within-host mathematical model of liver-stage hypnozoites, and validate it against data from tropical strains of P. vivax. The within-host model is embedded in a P. vivax transmission model to demonstrate the build-up of the hypnozoite reservoir following new infections and its depletion through hypnozoite activation and death. The hypnozoite reservoir is predicted to be over-dispersed with many individuals having few or no hypnozoites, and some having intensely infected livers. Individuals with more hypnozoites are predicted to experience more relapses and contribute more to onwards P. vivax transmission. Incorporating hypnozoite killing drugs such as primaquine into first-line treatment regimens is predicted to cause substantial reductions in P. vivax transmission as individuals with the most hypnozoites are more likely to relapse and be targeted for treatment.
topic malaria
vivax
relapse
mathematical
model
url https://elifesciences.org/articles/04692
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