The gene for the circumsporozoite (CS) protein of Plasmodium falciparum has been cloned and its nucleotide sequence determined. The gene encodes a protein of 412 amino acids as deduced from the nucleotide sequence. The protein contains 41 tandem repeats of a tetrapeptide, 37 of which are Asn-Ala-Asn-Pro and four of which are Asn-Val-Asp-Pro. Monoclonal antibodies against the CS protein of Plasmodium falciparum were inhibited from binding to the protein by synthetic peptides of the repeat sequence. The CS protein of Plasmodium falciparum and the CS protein of a simian malaria parasite, Plasmodium knowlesi, have two regions of homology, one of which is present on either side of the repeat. One region contains 12 of 13 identical amino acids. Within the nucleotide sequence of this region, 25 of 27 nucleotides are conserved. The conservation of these regions in parasites widely separated in evolution suggests that they may have a function such as binding to liver cells and may represent an invariant target for immunity.

Knowledge of how mosquitoes respond to insecticides is of paramount importance in understanding how an insecticide functions to prevent disease transmission. A suite of laboratory assays was used to quantitatively characterize mosquito responses to toxic, contact irritant, and non-contact spatial repellent actions of standard insecticides. Highly replicated tests of these compounds over a range of concentrations proved that all were toxic, some were contact irritants, and even fewer were non-contact repellents. Of many chemicals tested, three were selected for testing in experimental huts to confirm that chemical actions documented in laboratory tests are also expressed in the field. The laboratory tests showed the primary action of DDT is repellent, alphacypermethrin is irritant, and dieldrin is only toxic. These tests were followed with hut studies in Thailand against marked-released populations. DDT exhibited a highly protective level of repellency that kept mosquitoes outside of huts. Alphacypermethrin did not keep mosquitoes out, but its strong irritant action caused them to prematurely exit the treated house. Dieldrin was highly toxic but showed no irritant or repellent action. Based on the combination of laboratory and confirmatory field data, we propose a new paradigm for classifying chemicals used for vector control according to how the chemicals actually function to prevent disease transmission inside houses. The new classification scheme will characterize chemicals on the basis of spatial repellent, contact irritant and toxic actions.

A modular and novel assay system for rapid mass screening of chemical compounds for contact irritant and spatial repellent actions against adult mosquitoes is described. The responses of Aedes aegypti to various concentrations of 3 topical repellents, deet, Bayrepel, and SS220, were evaluated. At treatment concentrations > or = 25 nmol/cm2 of SS220, mosquitoes exhibited significant contact irritant (escape) and spatial repellent (movement away from the chemical source) responses, whereas, a 10-fold increase in the treatment concentration of deet and Bayrepel was required to produce similar responses. The novel bioassay system detected contact irritancy and spatial repellency activity with reproducible results and provided baseline data for determining minimum effective concentrations for other chemicals. The system is compact in size, easy to decontaminate, and requires only a minute quantity of chemical compound.

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