Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso

Ouédraogo, André Lin; Gonçalves, Bronner P.; Gnémé, Awa; Guelbeogo, Wamdaogo M.; Ouedraogo, Amathe; Gerardin, Jaline; Bever, Caitlin A.; Lyons, Hil; Pitroipa, Xavier; Verhave, J.P.; Eckhoff, Philip A.; Drakeley, Chris; Sauerwein, Robert W.; Luty, Adrian J. F.; Kouyaté, Bocar; Bousema, Teun

doi:10.1093/infdis/jiv370

Cited by 147 publications

(170 citation statements)

References 45 publications

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“…If a population is collapsed, then its local vectorial capacity goes to zero. If a population is suppressed and reduced in size, then its vectorial capacity will be reduced by approximately that same factor (43), with the resulting EIR possibly being even further reduced (43), depending on the effect of the resulting lowered transmission on the local human infectious reservoir (44,45). If population replacement is successful with a gene construct that reduces the ability of mosquitos to become infected with malaria parasites, the local vectorial capacity for that species will be reduced by that same factor-all of the way to zero if the construct renders the mosquito completely refractory to the parasite, although a reduction such that R 0 < 1 may suffice to locally eliminate malaria.…”

Section: Discussionmentioning

confidence: 99%

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

Eckhoff

Wenger

Godfray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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175

232

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The renewed effort to eliminate malaria and permanently remove its tremendous burden highlights questions of what combination of tools would be sufficient in various settings and what new tools need to be developed. Gene drive mosquitoes constitute a promising set of tools, with multiple different possible approaches including population replacement with introduced genes limiting malaria transmission, driving-Y chromosomes to collapse a mosquito population, and gene drive disrupting a fertility gene and thereby achieving population suppression or collapse. Each of these approaches has had recent success and advances under laboratory conditions, raising the urgency for understanding how each could be deployed in the real world and the potential impacts of each. New analyses are needed as existing models of gene drive primarily focus on nonseasonal or nonspatial dynamics. We use a mechanistic, spatially explicit, stochastic, individual-based mathematical model to simulate each gene drive approach in a variety of sub-Saharan African settings. Each approach exhibits a broad region of gene construct parameter space with successful elimination of malaria transmission due to the targeted vector species. The introduction of realistic seasonality in vector population dynamics facilitates gene drive success compared with nonseasonal analyses. Spatial simulations illustrate constraints on release timing, frequency, and spatial density in the most challenging settings for construct success. Within its parameter space for success, each gene drive approach provides a tool for malaria elimination unlike anything presently available. Provided potential barriers to success are surmounted, each achieves high efficacy at reducing transmission potential and lower delivery requirements in logistically challenged settings.

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Section: Discussionmentioning

confidence: 99%

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

Eckhoff

Wenger

Godfray

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

175

232

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“…The data set used consists of information on 130 participants from four age groups (<5 years, 5-14 years, 15-30 years and >30 years) in the villages of Laye and Dapélogo in Burkina Faso 21 . Study participants provided 307 venous blood samples at the start of the wet season (n = 104), the peak of the wet season (n = 100) and in the subsequent dry season (n = 103).…”

Section: Datamentioning

confidence: 99%

Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies

Slater

Ross

Ouédraogo

et al. 2015

Nature

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P lasmodium falciparum malaria was responsible for an estimated 584,000 (range 367,000-755,000) deaths in 2013, most of which occurred in young children in sub-Saharan Africa 1 . Although the burden has reduced in response to global efforts to increase the provision of proven malaria interventions such as insecticide-treated bed nets and access to health care and treatment 1 , it remains high. One of the challenges in reducing malaria transmission is the long duration of infection in the human host, which in semi-immune individuals may persist for a year or more 2 . In particular, although infection often leads to disease in naive individuals, those with sufficient acquired immunity can harbour parasites -and hence be onwardly infectious to mosquitoes -without exhibiting symptoms 3 . One option for speeding the decline in transmission could be to target the asymptomatic reservoir of infection 4 by providing either periodic mass-screen-and-treat (MSAT) programmes, focal MSAT or a reactive strategy in which individuals living in the vicinity of an identified clinical case are screened and treated. However, the extent to which such strategies are able to reduce the infectious reservoir will depend on the extent to which the diagnostic used to identify infected individuals also detects those who are onwardly infectious. Another form of targeting could take place at the population level (for example a village) where mass interventions are deployed if the population prevalence *These authors contributed equally.

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“…6 Though infections detected by microscopy and RDT are likely responsible for the majority of transmission, further studies are needed to assess the impact of subpatent infections on the transmission reservoir. 7,8 In the context of vaccine trials, these low-level, subpatent parasitemias may confound estimates of transmission intensity used to study vaccine efficacy.To evaluate the impact of subpatent parasitemias on parasite prevalence estimates, we collected dried blood spots from all participants during the final year of the 3-year MTI study in Lilongwe, Malawi, to allow for nucleic acid detection of parasitemia. Using clinical data and a spatial database to evaluate ecological factors that may influence transmission, we attempted to identify risk factors for subpatent parasitemia.…”

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confidence: 99%

mentioning

confidence: 99%

Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection

Parr

Belson

Patel

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Estimates of malaria transmission intensity (MTI) typically rely upon microscopy or rapid diagnostic testing (RDT). However, these methods are less sensitive than nucleic acid amplification techniques and may underestimate parasite prevalence. We compared microscopy, RDT, and polymerase chain reaction (PCR) for the diagnosis of Plasmodium falciparum parasitemia as part of an MTI study of 800 children and adults conducted in Lilongwe, Malawi. PCR detected more cases of parasitemia than microscopy or RDT. Age less than 5 years predicted parasitemia detected by PCR alone (adjusted odds ratio = 1.61, 95% confidence interval = 1.09-2.38, Wald P = 0.02). In addition, we identified one P. falciparum parasite with a false-negative RDT result due to a suspected deletion of the histidinerich protein 2 (hrp2) gene and used a novel, ultrasensitive PCR assay to detect low-level parasitemia missed by traditional PCR. Molecular methods should be considered for use in future transmission studies as a supplement to RDT or microscopy.Plasmodium falciparum infects hundreds of millions of individuals and kills 600,000 persons every year.1 A recently completed phase three trial of the RTS,S/ASO1 malaria vaccine demonstrated moderate and varying efficacy in different transmission settings.2 Study sites conducted annual malaria transmission intensity (MTI) studies during the trial using microscopy and rapid diagnostic test (RDT) parasite prevalence as a surrogate for transmission intensity.Both microscopy and RDT are known to produce negative results in Africa when parasitemia levels are beneath their limits of detection, 50 and 200 parasites/μL blood, respectively. [3][4][5] Infections not detected by microscopy or RDT, often referred to as subpatent infections, can often be detected by nucleic acid detection methods. 6 Though infections detected by microscopy and RDT are likely responsible for the majority of transmission, further studies are needed to assess the impact of subpatent infections on the transmission reservoir. 7,8 In the context of vaccine trials, these low-level, subpatent parasitemias may confound estimates of transmission intensity used to study vaccine efficacy.To evaluate the impact of subpatent parasitemias on parasite prevalence estimates, we collected dried blood spots from all participants during the final year of the 3-year MTI study in Lilongwe, Malawi, to allow for nucleic acid detection of parasitemia. Using clinical data and a spatial database to evaluate ecological factors that may influence transmission, we attempted to identify risk factors for subpatent parasitemia. We also investigated the impact of other factors on discordances between polymerase chain reaction (PCR) and other assays (RDT and microscopy) including 1) nonfalciparum parasitemia, 2) the occurrence of histidine-rich protein 2 (hrp2) gene deletions on false-negative RDTs, and 3) low-level parasitemia detectable by ultrasensitive PCR targeting high copy number genes. 9 This work adds to the growing literature concerning the rela...

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Dynamics of the Human Infectious Reservoir for Malaria Determined by Mosquito Feeding Assays and Ultrasensitive Malaria Diagnosis in Burkina Faso

Cited by 147 publications

References 45 publications

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

Impact of mosquito gene drive on malaria elimination in a computational model with explicit spatial and temporal dynamics

Assessing the impact of next-generation rapid diagnostic tests on Plasmodium falciparum malaria elimination strategies

Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection

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