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The design and interpretation of laboratory assays measuring mosquito transmission of Plasmodium

2012; Elsevier BV; Volume: 28; Issue: 11 Linguagem: Inglês

10.1016/j.pt.2012.07.005

1471-5007

Robert E. Sinden, Andrew M. Blagborough, Thomas S. Churcher, Chandra Ramakrishnan, Sumi Biswas, Michael J. Delves,

Mosquito-borne diseases and control

Since 2010 two global reviews of malaria research have recognized that local elimination and eradication of Plasmodium parasites are key drivers for further experimentation. To achieve these ambitious objectives it is universally recognized we must reduce malaria transmission through the mosquito vectors. A plethora of new laboratory assays are being developed to interrogate malaria transmission from the gametocyte to the sporozoite stage: assays that augment well-established field protocols to determine the entomological inoculation rate. However, the diverse readouts of these assays are not directly comparable. Here we attempt to identify the utility of each assay and provide rational frameworks by which to compare the impacts recorded by the diverse methodologies. Since 2010 two global reviews of malaria research have recognized that local elimination and eradication of Plasmodium parasites are key drivers for further experimentation. To achieve these ambitious objectives it is universally recognized we must reduce malaria transmission through the mosquito vectors. A plethora of new laboratory assays are being developed to interrogate malaria transmission from the gametocyte to the sporozoite stage: assays that augment well-established field protocols to determine the entomological inoculation rate. However, the diverse readouts of these assays are not directly comparable. Here we attempt to identify the utility of each assay and provide rational frameworks by which to compare the impacts recorded by the diverse methodologies. the numbers of oocysts are counted on the midguts of mosquitoes fed on the skin of a treated host are compared with those of a replicate group fed on the same host before treatment. as for the DFA except that blood is withdrawn before treatment, divided into replicate aliquots and experimental reagents, and relevant control reagents are added to separate aliquots. These are then fed to replicate groups of mosquitoes through artificial membranes. the gene encoding EIF1α is expressed at all stages of the parasite life-cycle and is highly upregulated in the female but not the male gametocytes. the number of malaria infectious bites received by an individual in a defined period (usually expressed per year). the gamete-forming cells in the malarial parasite life-cycle, formed in the peripheral bloodstream of the vertebrate host. They exist in two forms: females which form a single large gamete when the gametocyte enters the mosquito bloodmeal, and males that form eight flagellate 'sperm' – termed microgametes. the gene encoding GFP is inserted behind the promoter of a gene of interest to identify the time and, if inserted into the protein-coding sequence, the place of expression of putative stage-/sex-specific proteins. a vegetative stage of development formed from the ookinete after it comes to rest beneath the basal lamina of the mosquito midgut epithelium. a motile stage formed from the fertilized zygote that penetrates the mosquito gut wall. the daughter cells formed by the oocyst. Each oocyst produces between 500 and 9555 sporozoites, which are carried through the hemocoel of the mosquito from where they invade the salivary glands. The female mosquito injects the sporozoites into the vertebrate host when taking a bloodmeal. as for the DMFA with the exception that the infectious blood is derived from cultured gametocytes. this can be in the form of a drug, vaccine, or other measure that reduces the probability that the malaria parasite is successfully transmitted through the mosquito vectors.