title: Probability of Transmission of Malaria from Mosquito to Human Is Regulated by Mosquito Parasite Density in Naïve and Vaccinated Hosts.
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.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Thomas S
authors.identifier: 0000-0002-8442-0525
authors.initials: TS
authors.lastname: Churcher
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.|The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sinden
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Nick J
authors.identifier: 0000-0002-7030-7839
authors.initials: NJ
authors.lastname: Edwards
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Ian D
authors.initials: ID
authors.lastname: Poulton
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Thomas W
authors.identifier: 0000-0001-9111-2486
authors.initials: TW
authors.lastname: Rampling
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.|Institute of Biodiversity Animal Health and Comparative Medicine, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Patrick M
authors.identifier: 0000-0002-1035-1619
authors.initials: PM
authors.lastname: Brock
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
authors.forename: Jamie T
authors.initials: JT
authors.lastname: Griffin
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Leanna M
authors.initials: LM
authors.lastname: Upton
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Sara E
authors.identifier: 0000-0001-7964-9782
authors.initials: SE
authors.lastname: Zakutansky
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Sala
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Fiona
authors.initials: F
authors.lastname: Angrisano
authors.affiliation: The Jenner Institute, University of Oxford, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.affiliation: Department of Life Sciences, Imperial College London, South Kensington, London, United Kingdom.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blagborough
mesh_terms: D000818:Animals; D000852:Anopheles / Q000469:parasitology*; D000913:Antibodies, Protozoan; D004195:Disease Models, Animal; D006801:Humans; D007303:Insect Vectors / Q000469:parasitology*; D008288:Malaria / Q000469:parasitology / Q000517:prevention & control* / Q000635:transmission; D017780:Malaria Vaccines / Q000008:administration & dosage*; D051379:Mice; D010961:Plasmodium / Q000254:growth & development / Q000276:immunology*; D011157:Population Dynamics; D015800:Protozoan Proteins / Q000276:immunology; D012469:Salivary Glands / Q000469:parasitology; D034101:Sporozoites / Q000276:immunology; D014611:Vaccination
chemical_list: D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins