title: Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies.
abstract: Mass-screen-and-treat and targeted mass-drug-administration strategies are being considered as a means to interrupt transmission of Plasmodium falciparum malaria. However, the effectiveness of such strategies will depend on the extent to which current and future diagnostics are able to detect those individuals who are infectious to mosquitoes. We estimate the relationship between parasite density and onward infectivity using sensitive quantitative parasite diagnostics and mosquito feeding assays from Burkina Faso. We find that a diagnostic with a lower detection limit of 200 parasites per microlitre would detect 55% of the infectious reservoir (the combined infectivity to mosquitoes of the whole population weighted by how often each individual is bitten) whereas a test with a limit of 20 parasites per microlitre would detect 83% and 2 parasites per microlitre would detect 95% of the infectious reservoir. Using mathematical models, we show that increasing the diagnostic sensitivity from 200 parasites per microlitre (equivalent to microscopy or current rapid diagnostic tests) to 2 parasites per microlitre would increase the number of regions where transmission could be interrupted with a mass-screen-and-treat programme from an entomological inoculation rate below 1 to one of up to 4. The higher sensitivity diagnostic could reduce the number of treatment rounds required to interrupt transmission in areas of lower prevalence. We predict that mass-screen-and-treat with a highly sensitive diagnostic is less effective than mass drug administration owing to the prophylactic protection provided to uninfected individuals by the latter approach. In low-transmission settings such as those in Southeast Asia, we find that a diagnostic tool with a sensitivity of 20 parasites per microlitre may be sufficient for targeted mass drug administration because this diagnostic is predicted to identify a similar village population prevalence compared with that currently detected using polymerase chain reaction if treatment levels are high and screening is conducted during the dry season. Along with other factors, such as coverage, choice of drug, timing of the intervention, importation of infections, and seasonality, the sensitivity of the diagnostic can play a part in increasing the chance of interrupting transmission.
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Slater
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.|University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ross
authors.affiliation: Institute for Disease Modelling, Bellevue, Washington 98005, USA.|Department of Biomedical Sciences, Centre National de Recherche et de Formation sur le Paludisme, 01 B.P. 2208, Ouagadougou, Burkina Faso.
authors.forename: André Lin
authors.initials: AL
authors.lastname: Ouédraogo
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.|Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, UK.
authors.forename: Lisa J
authors.initials: LJ
authors.lastname: White
authors.affiliation: National Malaria Center, Ministry of Health, Phnom Penh 12302, Cambodia.
authors.forename: Chea
authors.initials: C
authors.lastname: Nguon
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Patrick G T
authors.initials: PG
authors.lastname: Walker
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.|National Malaria Center, Ministry of Health, Phnom Penh 12302, Cambodia.
authors.forename: Pengby
authors.initials: P
authors.lastname: Ngor
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Aguas
authors.affiliation: Department of Statistical Sciences, University of Cape Town, Rondebosch 7701, Cape Town, South Africa.
authors.forename: Sheetal P
authors.initials: SP
authors.lastname: Silal
authors.affiliation: Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand.|Centre for Tropical Medicine, Nuffield Department of Medicine, University of Oxford, Oxford OX3 7LJ, UK.
authors.forename: Arjen M
authors.initials: AM
authors.lastname: Dondorp
authors.affiliation: PATH, 2201 Westlake Avenue, Seattle, Washington 98121, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: La Barre
authors.affiliation: PATH, 2201 Westlake Avenue, Seattle, Washington 98121, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Burton
authors.affiliation: Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.affiliation: London School of Hygiene &Tropical Medicine, Keppel St, London WC1E 7HT, UK.
authors.forename: Chris
authors.initials: C
authors.lastname: Drakeley
authors.affiliation: Swiss Tropical and Public Health Institute, Socinstrasse 57, 4002 Basel, Switzerland.|University of Basel, Petersplatz 1, 4001 Basel, Switzerland.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Smith
authors.affiliation: Radboud University Medical Center, 6525 HP Nijmegen, the Netherlands.|London School of Hygiene &Tropical Medicine, Keppel St, London WC1E 7HT, UK.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.affiliation: MRC Centre for Outbreak Analysis and Modelling, Department of Infectious Disease Epidemiology, Faculty of Medicine, Imperial College London, Norfolk Place, London W2 1PG, UK.
authors.forename: Azra C
authors.initials: AC
authors.lastname: Ghani
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002648:Child; D002675:Child, Preschool; D003955:Diagnostic Tests, Routine; D005260:Female; D006801:Humans; D016778:Malaria, Falciparum / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology / Q000469:parasitology; D008297:Male; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D015995:Prevalence; D015203:Reproducibility of Results; D055815:Young Adult