Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.

Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vector...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Geoffrey L Johnston, Peter W Gething, Simon I Hay, David L Smith, David A Fidock
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/7167b31602f640889399b84c73b754c1
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:7167b31602f640889399b84c73b754c1
record_format	dspace
spelling	oai:doaj.org-article:7167b31602f640889399b84c73b754c12021-11-18T05:53:12ZModeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.1553-734X1553-735810.1371/journal.pcbi.1003434https://doaj.org/article/7167b31602f640889399b84c73b754c12014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465196/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria R C (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R 0<10 based on 2010 data. Our modeling predicts that treating 93-98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81-85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment.Geoffrey L JohnstonPeter W GethingSimon I HayDavid L SmithDavid A FidockPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 10, Iss 1, p e1003434 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Geoffrey L Johnston Peter W Gething Simon I Hay David L Smith David A Fidock Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
description	Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria R C (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R 0<10 based on 2010 data. Our modeling predicts that treating 93-98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81-85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment.
format	article
author	Geoffrey L Johnston Peter W Gething Simon I Hay David L Smith David A Fidock
author_facet	Geoffrey L Johnston Peter W Gething Simon I Hay David L Smith David A Fidock
author_sort	Geoffrey L Johnston
title	Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
title_short	Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
title_full	Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
title_fullStr	Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
title_full_unstemmed	Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.
title_sort	modeling within-host effects of drugs on plasmodium falciparum transmission and prospects for malaria elimination.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7167b31602f640889399b84c73b754c1
work_keys_str_mv	AT geoffreyljohnston modelingwithinhosteffectsofdrugsonplasmodiumfalciparumtransmissionandprospectsformalariaelimination AT peterwgething modelingwithinhosteffectsofdrugsonplasmodiumfalciparumtransmissionandprospectsformalariaelimination AT simonihay modelingwithinhosteffectsofdrugsonplasmodiumfalciparumtransmissionandprospectsformalariaelimination AT davidlsmith modelingwithinhosteffectsofdrugsonplasmodiumfalciparumtransmissionandprospectsformalariaelimination AT davidafidock modelingwithinhosteffectsofdrugsonplasmodiumfalciparumtransmissionandprospectsformalariaelimination
_version_	1718424672349978624

Modeling within-host effects of drugs on Plasmodium falciparum transmission and prospects for malaria elimination.

Ejemplares similares