Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.

Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of math...

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Autores principales:	Geoffrey L Johnston, David L Smith, David A Fidock
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/41e5255cf1f44d3c82b3f4e2ed53ee50
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spelling	oai:doaj.org-article:41e5255cf1f44d3c82b3f4e2ed53ee502021-11-18T05:52:13ZMalaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.1553-734X1553-735810.1371/journal.pcbi.1003025https://doaj.org/article/41e5255cf1f44d3c82b3f4e2ed53ee502013-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23637586/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic within-host model of Plasmodium falciparum infection in humans and pathogen transmission to the mosquito vector. Our model incorporates the entire parasite lifecycle, including the intra-erythrocytic asexual forms responsible for disease, the onset of symptoms, the development and maturation of intra-erythrocytic gametocytes that are transmissible to Anopheles mosquitoes, and human-to-mosquito infectivity. These model components were parameterized from malaria therapy data and other studies to simulate individual infections, and the ensemble of outputs was found to reproduce the full range of patient responses to infection. Using this model, we assessed human infectivity over the course of untreated infections and examined the effects in relation to transmission intensity, expressed by the basic reproduction number R0 (defined as the number of secondary cases produced by a single typical infection in a completely susceptible population). Our studies predict that net human-to-mosquito infectivity from a single non-immune individual is on average equal to 32 fully infectious days. This estimate of mean infectivity is equivalent to calculating the human component of malarial R0 . We also predict that mean daily infectivity exceeds five percent for approximately 138 days. The mechanistic framework described herein, made available as stand-alone software, will enable investigators to conduct detailed studies into theories of malaria control, including the effects of drug treatment and drug resistance on transmission.Geoffrey L JohnstonDavid L SmithDavid A FidockPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 4, p e1003025 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Geoffrey L Johnston David L Smith David A Fidock Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
description	Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic within-host model of Plasmodium falciparum infection in humans and pathogen transmission to the mosquito vector. Our model incorporates the entire parasite lifecycle, including the intra-erythrocytic asexual forms responsible for disease, the onset of symptoms, the development and maturation of intra-erythrocytic gametocytes that are transmissible to Anopheles mosquitoes, and human-to-mosquito infectivity. These model components were parameterized from malaria therapy data and other studies to simulate individual infections, and the ensemble of outputs was found to reproduce the full range of patient responses to infection. Using this model, we assessed human infectivity over the course of untreated infections and examined the effects in relation to transmission intensity, expressed by the basic reproduction number R0 (defined as the number of secondary cases produced by a single typical infection in a completely susceptible population). Our studies predict that net human-to-mosquito infectivity from a single non-immune individual is on average equal to 32 fully infectious days. This estimate of mean infectivity is equivalent to calculating the human component of malarial R0 . We also predict that mean daily infectivity exceeds five percent for approximately 138 days. The mechanistic framework described herein, made available as stand-alone software, will enable investigators to conduct detailed studies into theories of malaria control, including the effects of drug treatment and drug resistance on transmission.
format	article
author	Geoffrey L Johnston David L Smith David A Fidock
author_facet	Geoffrey L Johnston David L Smith David A Fidock
author_sort	Geoffrey L Johnston
title	Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
title_short	Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
title_full	Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
title_fullStr	Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
title_full_unstemmed	Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.
title_sort	malaria's missing number: calculating the human component of r0 by a within-host mechanistic model of plasmodium falciparum infection and transmission.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/41e5255cf1f44d3c82b3f4e2ed53ee50
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Malaria's missing number: calculating the human component of R0 by a within-host mechanistic model of Plasmodium falciparum infection and transmission.

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