Probability of transmission of malaria from mosquito to human Is regulated by mosquito parasite density in naïve and vaccinated hosts
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2017-02-12
Date Acceptance
2016-12-02
Citation
PLOS Pathogens, 2017, 13 (1)
ISSN
1553-7366
Publisher
Public Library of Science
Journal / Book Title
PLOS Pathogens
Volume
13
Issue
1
Copyright Statement
© 2017 The Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor
Medical Research Council (MRC)
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/28081253
PII: PPATHOGENS-D-16-01786
Grant Number
MR/N00227X/1
Subjects
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Coverage Spatial
United States
Article Number
e1006108