1. Epidemiology and Global Health
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Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling

  1. Ellen A Kearney
  2. Paul A Agius
  3. Victor Chaumeau
  4. Julia C Cutts
  5. Julie A Simpson
  6. Freya JI Fowkes  Is a corresponding author
  1. Burnet Institute, Australia
  2. Mahidol University, Thailand
  3. The University of Melbourne, Australia
Research Article
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Cite this article as: eLife 2021;10:e73080 doi: 10.7554/eLife.73080

Abstract

Background: Entomological surveillance for malaria is inherently resource-intensive and produces crude population-level measures of vector exposure which are insensitive in low-transmission settings. Antibodies against Anopheles salivary proteins measured at the individual-level may serve as proxy biomarkers for vector exposure and malaria transmission, but their relationship is yet to be quantified.

Methods: A systematic review of studies measuring antibodies against Anopheles salivary antigens (PROSPERO: CRD42020185449). Multilevel modelling (to account for multiple study-specific observations (level-one), nested within study (level-two), and study nested within country (level-three)) estimated associations between seroprevalence with Anopheles human biting rate (HBR) and malaria transmission measures.

Results: From 3981 studies identified in literature searches, 42 studies across 16 countries were included contributing 393 study-specific observations of anti-Anopheles salivary antibodies determined in 42,764 samples. A positive association between HBR (log transformed) and seroprevalence was found; overall a 2-fold (100% relative) increase in HBR was associated with a 23% increase in odds of seropositivity (OR: 1.23, 95%CI: 1.10-1.37, p<0.001). The association between HBR and Anopheles salivary antibodies was strongest with concordant, rather than discordant Anopheles species. Seroprevalence was also significantly positively associated with established epidemiological measures of malaria transmission: entomological inoculation rate, Plasmodium spp. prevalence, and malarial endemicity class.

Conclusions: Anopheles salivary antibody biomarkers can serve as a proxy measure for HBR and malaria transmission, and could monitor malaria receptivity of a population to sustain malaria transmission. Validation of Anopheles species-specific biomarkers are important given the global heterogeneity in the distribution of Anopheles species. Salivary biomarkers have the potential to transform surveillance by replacing impractical, inaccurate entomological investigations, especially in areas progressing towards malaria elimination.

Funding: Australian National Health and Medical Research Council, Wellcome Trust.

Data availability

The current manuscript is a systematic review with multilevel modelling of study level data. The constructed dataset and associated code used for analyses are available at https://github.com/ellenakearney/Anopheles_salivary_biomarker_systematic_review.git

The following data sets were generated
The following previously published data sets were used
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    3. Lucas
    4. T. C.
    5. Nguyen
    6. M.
    7. Nandi
    8. A. K.
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    11. Battle
    12. K. E.
    13. ... & Gething
    14. P. W.
    (2019) Plasmodium falciparum parasite rate in 2-10 year olds globally, 2000-2017
    Malaria Atlas Project Explorer, Plasmodium falciparum parasite rate in 2-10 year olds globally, 2000-2017.

Article and author information

Author details

  1. Ellen A Kearney

    Burnet Institute, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  2. Paul A Agius

    Burnet Institute, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Victor Chaumeau

    Shoklo Malaria Research Unit, Mahidol University, Maesod, Thailand
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0171-2176
  4. Julia C Cutts

    Burnet Institute, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Julie A Simpson

    Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2660-2013
  6. Freya JI Fowkes

    Burnet Institute, Melbourne, Australia
    For correspondence
    fowkes@burnet.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5832-9464

Funding

National Health and Medical Research Council (1134989)

  • Julie A Simpson
  • Freya JI Fowkes

National Health and Medical Research Council (1166753)

  • Freya JI Fowkes

National Health and Medical Research Council (1196068)

  • Julie A Simpson

Australian Government (Australian Government Research Training Program Scholarship)

  • Ellen A Kearney

Wellcome Trust (220211)

  • Victor Chaumeau

Victorian State Government (Operational Infrastructure Support Program received by the Burnet Institute.)

  • Ellen A Kearney
  • Paul A Agius
  • Julia C Cutts
  • Freya JI Fowkes

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Amy Wesolowski, Johns Hopkins Bloomberg School of Public Health, United States

Publication history

  1. Received: August 16, 2021
  2. Accepted: December 21, 2021
  3. Accepted Manuscript published: December 23, 2021 (version 1)

Copyright

© 2021, Kearney et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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Further reading

    1. Epidemiology and Global Health
    Andria Mousa et al.
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    Background:

    Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focused on high-income settings.

    Methods:

    Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys, we explored how contact characteristics (number, location, duration, and whether physical) vary across income settings.

    Results:

    Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income strata on the frequency, duration, and type of contacts individuals made.

    Conclusions:

    These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens and the effectiveness of different non-pharmaceutical interventions.

    Funding:

    This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

    1. Epidemiology and Global Health
    2. Genetics and Genomics
    Daniel W Belsky et al.
    Research Advance

    Background: Measures to quantify changes in the pace of biological aging in response to intervention are needed to evaluate geroprotective interventions for humans. Previously we showed that quantification of the pace of biological aging from a DNA-methylation blood test was possible (Belsky et al. 2020). Here we report a next-generation DNA-methylation biomarker of Pace of Aging, DunedinPACE (for Pace of Aging Calculated from the Epigenome).

    Methods: We used data from the Dunedin Study 1972-3 birth cohort tracking within-individual decline in 19 indicators of organ-system integrity across four time points spanning two decades to model Pace of Aging. We distilled this two-decade Pace of Aging into a single-time-point DNA-methylation blood-test using elastic-net regression and a DNA-methylation dataset restricted to exclude probes with low test-retest reliability. We evaluated the resulting measure, named DunedinPACE, in five additional datasets.

    Results: DunedinPACE showed high test-retest reliability, was associated with morbidity, disability, and mortality, and indicated faster aging in young adults with childhood adversity. DunedinPACE effect-sizes were similar to GrimAge Clock effect-sizes. In analysis of incident morbidity, disability, and mortality, DunedinPACE and added incremental prediction beyond GrimAge.

    Conclusions: DunedinPACE is a novel blood biomarker of the pace of aging for gerontology and geroscience.

    Funding: This research was supported by US-National Institute on Aging grants AG032282, AG061378, AG066887, and UK Medical Research Council grant MR/P005918/1.