Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.

Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irresp...

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Main Authors: Thomas S Churcher, Robert E Sinden, Nick J Edwards, Ian D Poulton, Thomas W Rampling, Patrick M Brock, Jamie T Griffin, Leanna M Upton, Sara E Zakutansky, Katarzyna A Sala, Fiona Angrisano, Adrian V S Hill, Andrew M Blagborough
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS Pathogens
Online Access:http://europepmc.org/articles/PMC5230737?pdf=render
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spelling doaj-06b851e695e24547811f54f4638795712020-11-25T01:34:03ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742017-01-01131e100610810.1371/journal.ppat.1006108Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.Thomas S ChurcherRobert E SindenNick J EdwardsIan D PoultonThomas W RamplingPatrick M BrockJamie T GriffinLeanna M UptonSara E ZakutanskyKatarzyna A SalaFiona AngrisanoAdrian V S HillAndrew M BlagboroughOver a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period. Mosquitoes with a higher numbers of sporozoites in their salivary glands following blood-feeding are more likely to have caused infection (and have done so quicker) than mosquitoes with fewer parasites. A similar dose response for the probability of infection was seen for humans given a pre-erythrocytic vaccine candidate targeting circumsporozoite protein (CSP), and in mice with and without transfusion of anti-CSP antibodies. These interventions prevented infection more efficiently from bites made by mosquitoes with fewer parasites. The importance of parasite number has widespread implications across malariology, ranging from our basic understanding of the parasite, how vaccines are evaluated and the way in which transmission should be measured in the field. It also provides direct evidence for why the only registered malaria vaccine RTS,S was partially effective in recent clinical trials.http://europepmc.org/articles/PMC5230737?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Thomas S Churcher
Robert E Sinden
Nick J Edwards
Ian D Poulton
Thomas W Rampling
Patrick M Brock
Jamie T Griffin
Leanna M Upton
Sara E Zakutansky
Katarzyna A Sala
Fiona Angrisano
Adrian V S Hill
Andrew M Blagborough
spellingShingle Thomas S Churcher
Robert E Sinden
Nick J Edwards
Ian D Poulton
Thomas W Rampling
Patrick M Brock
Jamie T Griffin
Leanna M Upton
Sara E Zakutansky
Katarzyna A Sala
Fiona Angrisano
Adrian V S Hill
Andrew M Blagborough
Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
PLoS Pathogens
author_facet Thomas S Churcher
Robert E Sinden
Nick J Edwards
Ian D Poulton
Thomas W Rampling
Patrick M Brock
Jamie T Griffin
Leanna M Upton
Sara E Zakutansky
Katarzyna A Sala
Fiona Angrisano
Adrian V S Hill
Andrew M Blagborough
author_sort Thomas S Churcher
title Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
title_short Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
title_full Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
title_fullStr Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
title_full_unstemmed Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
title_sort probability of transmission of malaria from mosquito to human is regulated by mosquito parasite density in naïve and vaccinated hosts.
publisher Public Library of Science (PLoS)
series PLoS Pathogens
issn 1553-7366
1553-7374
publishDate 2017-01-01
description Over a century since Ronald Ross discovered that malaria is caused by the bite of an infectious mosquito it is still unclear how the number of parasites injected influences disease transmission. Currently it is assumed that all mosquitoes with salivary gland sporozoites are equally infectious irrespective of the number of parasites they harbour, though this has never been rigorously tested. Here we analyse >1000 experimental infections of humans and mice and demonstrate a dose-dependency for probability of infection and the length of the host pre-patent period. Mosquitoes with a higher numbers of sporozoites in their salivary glands following blood-feeding are more likely to have caused infection (and have done so quicker) than mosquitoes with fewer parasites. A similar dose response for the probability of infection was seen for humans given a pre-erythrocytic vaccine candidate targeting circumsporozoite protein (CSP), and in mice with and without transfusion of anti-CSP antibodies. These interventions prevented infection more efficiently from bites made by mosquitoes with fewer parasites. The importance of parasite number has widespread implications across malariology, ranging from our basic understanding of the parasite, how vaccines are evaluated and the way in which transmission should be measured in the field. It also provides direct evidence for why the only registered malaria vaccine RTS,S was partially effective in recent clinical trials.
url http://europepmc.org/articles/PMC5230737?pdf=render
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