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      Human exposure to Anopheles farauti bites in the Solomon Islands is not associated with IgG antibody response to the gSG6 salivary protein of Anopheles gambiae

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          Abstract

          Background

          Mosquito saliva elicits immune responses in humans following mosquito blood feeding. Detection of human antibodies recognizing the Anopheles gambiae salivary gland protein 6 (gSG6) or the gSG6-P1 peptide in residents of Africa, South America and Southeast Asia suggested the potential for these antibodies to serve as a universal marker to estimate human biting rates. Validating the utility of this approach requires concurrent comparisons of anopheline biting rates with antibodies to the gSG6 protein to determine the sensitivity and specificity of the assay for monitoring changes in vector populations. This study investigated whether seroprevalence of anti-gSG6 antibodies in humans reflected the relative exposure to Anopheles farauti bites in the Solomon Islands as estimated from sympatric human landing catches.

          Methods

          Human biting rates by An. farauti were estimated by landing catches at 10 sampling sites in each of 4 villages during the wet and dry seasons. Human serum samples from these same villages were also collected during the wet and dry seasons and analysed for antibody recognition of the gSG6 antigen by the Luminex xMAP © platform. Antibody titres and prevalence were compared to HLCs at the sampling sites nearest to participants’ residences for utility of anti-gSG6 antibodies to estimate human exposure to anopheline bites.

          Results

          In this study in the Solomon Islands only 11% of people had very high anti-gSG6 antibody titres, while other individuals did not recognize gSG6 despite nightly exposures of up to 190 bites by An. farauti. Despite clear spatial differences in the human biting rates within and among villages, associations between anti-gSG6 antibody titres and biting rates were not found.

          Conclusions

          Few studies to date have concurrently measured anopheline biting rates and the prevalence of human antibodies to gSG6. The lack of association between anti-gSG6 antibody titres and concurrently measured human biting rates suggests that the assay for human anti-gSG6 antibodies lacks sufficient sensitivity to be a biomarker of An. farauti exposure at an epidemiologically relevant scale. These findings imply that an improvement in the sensitivity of serology to monitor changes in anopheline biting exposure may require the use of saliva antigens from local anophelines, and this may be especially true for species more distantly related to the African malaria vector An. gambiae.

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          Most cited references20

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          Discrimination of all members of the Anopheles punctulatus complex by polymerase chain reaction--restriction fragment length polymorphism analysis.

          A method has been developed to identify the members of the Anopheles punctulatus complex using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Members of the An. punctulatus complex are the most important vectors of malaria in the southwest Pacific and consist of 10 cryptic species, An. farauti no. 1-7, An. punctulatus, An. sp. near punctulatus, and An. koliensis. For each species, PCR amplification of the ribosomal DNA internal transcribed spacer produced a 750-basepair product. Digestion with Msp I and electrophoresis on a 3.0% agarose gel results in banding patterns unique to each species. Isolates of the same species from different locations gave an identical pattern. The technique is sensitive enough so that a PCR-RFLP can be generated from as little as a single mosquito leg, allowing the rest of the mosquito to be used for other important epidemiologic analyses such as determining host feeding source, and for parasite detection.
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            Measuring changes in Plasmodium falciparum transmission: precision, accuracy and costs of metrics.

            As malaria declines in parts of Africa and elsewhere, and as more countries move towards elimination, it is necessary to robustly evaluate the effect of interventions and control programmes on malaria transmission. To help guide the appropriate design of trials to evaluate transmission-reducing interventions, we review 11 metrics of malaria transmission, discussing their accuracy, precision, collection methods and costs and presenting an overall critique. We also review the nonlinear scaling relationships between five metrics of malaria transmission: the entomological inoculation rate, force of infection, sporozoite rate, parasite rate and the basic reproductive number, R0. Our chapter highlights that while the entomological inoculation rate is widely considered the gold standard metric of malaria transmission and may be necessary for measuring changes in transmission in highly endemic areas, it has limited precision and accuracy and more standardised methods for its collection are required. In areas of low transmission, parasite rate, seroconversion rates and molecular metrics including MOI and mFOI may be most appropriate. When assessing a specific intervention, the most relevant effects will be detected by examining the metrics most directly affected by that intervention. Future work should aim to better quantify the precision and accuracy of malaria metrics and to improve methods for their collection. © 2014 Elsevier Ltd All rights reserved.
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              Novel Peptide Marker Corresponding to Salivary Protein gSG6 Potentially Identifies Exposure to Anopheles Bites

              Background In order to improve malaria control, and under the aegis of WHO recommendations, many efforts are being devoted to developing new tools for identifying geographic areas with high risk of parasite transmission. Evaluation of the human antibody response to arthropod salivary proteins could be an epidemiological indicator of exposure to vector bites, and therefore to risk of pathogen transmission. In the case of malaria, which is transmitted only by anopheline mosquitoes, maximal specificity could be achieved through identification of immunogenic proteins specific to the Anopheles genus. The objective of the present study was to determine whether the IgG response to the Anopheles gambiae gSG6 protein, from its recombinant form to derived synthetic peptides, could be an immunological marker of exposure specific to Anopheles gambiae bites. Methodology/Principal Findings Specific IgG antibodies to recombinant gSG6 protein were observed in children living in a Senegalese area exposed to malaria. With the objective of optimizing Anopheles specificity and reproducibility, we designed five gSG6-based peptide sequences using a bioinformatic approach, taking into consideration i) their potential antigenic properties and ii) the absence of cross-reactivity with protein sequences of other arthropods/organisms. The specific anti-peptide IgG antibody response was evaluated in exposed children. The five gSG6 peptides showed differing antigenic properties, with gSG6-P1 and gSG6-P2 exhibiting the highest antigenicity. However, a significant increase in the specific IgG response during the rainy season and a positive association between the IgG level and the level of exposure to Anopheles gambiae bites was significant only for gSG6-P1. Conclusions/Significance This step-by-step approach suggests that gSG6-P1 could be an optimal candidate marker for evaluating exposure to Anopheles gambiae bites. This marker could be employed as a geographic indicator, like remote sensing techniques, for mapping the risk of malaria. It could also represent a direct criterion of efficacy in evaluation of vector control strategies.
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                Author and article information

                Contributors
                tom.burkot@jcu.edu.au
                Journal
                Malar J
                Malar. J
                Malaria Journal
                BioMed Central (London )
                1475-2875
                1 October 2019
                1 October 2019
                2019
                : 18
                : 334
                Affiliations
                [1 ]ISNI 0000 0004 0474 1797, GRID grid.1011.1, Australian Institute of Tropical Health & Medicine, James Cook University, ; Cairns, QLD 4870 Australia
                [2 ]ISNI 0000 0004 0425 469X, GRID grid.8991.9, Department of Infection Biology, , London School of Hygiene & Tropical Medicine, ; London, UK
                [3 ]National Vector Borne Disease Control Program, Ministry of Health and Medical Services, Honiara, Solomon Islands
                [4 ]GRID grid.7841.a, Department of Public Health and Infectious Diseases, Division of Parasitology, , Sapienza Università Di Roma, ; Rome, Italy
                Author information
                http://orcid.org/0000-0002-8994-6729
                Article
                2975
                10.1186/s12936-019-2975-8
                6771112
                31570113
                fd331527-5206-4589-9a26-b9ea037b3be5
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 8 August 2019
                : 24 September 2019
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000865, Bill and Melinda Gates Foundation;
                Award ID: 45114
                Award Recipient :
                Funded by: National Institute of Allergy and Infectious Diseases, National Institutes of Health a
                Award ID: U19AI08986
                Award Recipient :
                Funded by: Australian Institute of Tropical Health and Medicine
                Award ID: 15032
                Award Recipient :
                Funded by: Global Good Fund I
                Funded by: Rotarians Against Malaria
                Categories
                Research
                Custom metadata
                © The Author(s) 2019

                Infectious disease & Microbiology
                gsg6,human biting rate,anopheles farauti,saliva antigens
                Infectious disease & Microbiology
                gsg6, human biting rate, anopheles farauti, saliva antigens

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