![]() ![]() ![]() gambiae s.l., was present with additional DVS, or where An. gambiae sensu lato ( s.l.) was the only DVS, where An. For the purposes of the modelling analyses we defined DVS as where An. Malarial endemicity classes were derived by applying established endemicity cut-offs to PfPR 2-10 estimates. falciparum rates in 2-10 year olds ( PfPR 2-10) and dominant vector species (DVS) from the Malaria Atlas Project (MAP). Where exposure estimates were not provided, we attempted to source data from other publications by the authors, or using the site geolocation and year to obtain estimates of EIR from the Pangaea dataset, P. infection (confirmed by either microscopy, rapid diagnostic test, or polymerase chain reaction (PCR)) and seroprevalence of antimalarial antibodies against pre-erythrocytic and blood-stage Plasmodium spp. ![]() Secondary exposures included study-reported prevalence of Plasmodium spp. The primary exposures of interest were the entomological metrics HBR (average number of bites received per person per night) and EIR (infectious bites received per person per year). mosquito allergic patients, soldiers, returned travellers) were excluded. Studies that were solely performed in participants not representative of the wider naturally exposed population ( i.e. We considered for inclusion: cross-sectional, cohort, intervention and case-control studies of individuals or populations living in all geographies with natural exposure to Anopheles mosquitoes. The primary criteria for inclusion in this systematic review was the reporting of estimates of seroprevalence or total levels of Immunoglobulin (Ig) in human sera against Anopheles salivary antigens. The protocol (Supplementary File 1) was registered with PROSPERO (CRD42020185449). Five databases were searched for published studies investigating antibodies to Anopheles salivary antigens as a biomarker for mosquito exposure or malaria transmission published before 30 th of June 2020. We performed a systematic review with multilevel modelling according to the MOOSE and PRISMA guidelines (Reporting Standards Document). This knowledge is pertinent to advance the use of salivary antibody biomarkers as a vector and malaria transmission sero-surveillance tool. We undertook a systematic review with multilevel modelling, to quantify the association between HBR, EIR, and other markers of malaria transmission, with anti- Anopheles salivary antibody responses and to understand how these associations vary according to transmission setting and dominant Anopheles vectors. However, a major short-coming of the literature is that studies are largely descriptive and do not quantify the association between entomological and malariometric measures and anti- Anopheles salivary antibody responses. Several Anopheles salivary proteins have been shown to be immunogenic in individuals naturally exposed to the bites of Anopheles vectors and have been investigated as serological biomarkers to measure Anopheles exposure, malaria transmission and as an outcome for vector control intervention studies. salivary proteins has the potential to be a logistically practical approach to estimate levels of exposure to vector bites at an individual-level. The sensitivity of EIR is further compromised in low transmission settings where the number of Plasmodium-infected specimens detected is low and often zero.Įvaluation of the human antibody response to Anopheles spp. For example, indoor human landing catches provide poor estimates of outdoor biting and thus total vector exposure. Furthermore, these approaches provide a crude population-level measure of total vector exposure at a particular time and location, precluding investigation of heterogeneity and natural transmission dynamics of individual-level vector-human interactions. However, estimation of EIR and HBR via entomological investigations are inherently labour and resource intensive, requiring trained collectors, specialised laboratories and skilled entomologists. EIR is calculated as the human biting rate (HBR measured at the population-level by entomological vector-sampling methodologies (gold standard: human landing catch)) multiplied by the sporozoite index (proportion of captured Anopheles with sporozoites present in their salivary glands). Currently, the gold standard measurement of malaria transmission intensity is the entomological inoculation rate (EIR), a population-measure defined as the number of infective Anopheles mosquito bites a person receives per unit of time. Sensitive and accurate tools to measure and monitor changes in malaria transmission are essential to track progress towards malaria control and elimination goals. ![]()
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