Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling

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Data availability
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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

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5. Simpson JA
6. Fowkes FJI
(2021) Anopheles salivary biomarkers review.dta
GitHub.

https://github.com/ellenakearney/Anopheles_salivary_biomarker_systematic_review.git

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17. Patil
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19. Temperley
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21. Gething
22. P.W.
23. Kabaria
24. C.W.
25. Burkot
26. T.R.
27. Harbach
28. R.E. and Hay
29. S.I.
(2012) Dominant malaria vector species globally, 2010
Malaria Atlas Project Explorer, Dominant malaria vector species globally, 2010.

https://malariaatlas.org/explorer/#/
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5. Nguyen
6. M.
7. Nandi
8. A. K.
9. Bisanzio
10. D.
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.

https://malariaatlas.org/explorer/#/

Article and author information

Author details

Ellen A Kearney

Burnet Institute, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Paul A Agius

Burnet Institute, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
Victor Chaumeau

Shoklo Malaria Research Unit, Mahidol University, Maesod, Thailand

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0171-2176
Julia C Cutts

Burnet Institute, Melbourne, Australia

Competing interests
The authors declare that no competing interests exist.
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.

"This ORCID iD identifies the author of this article:" 0000-0002-2660-2013
Freya JI Fowkes

Burnet Institute, Melbourne, Australia

For correspondence
fowkes@burnet.edu.au

Competing interests
The authors declare that no competing interests exist.

"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.

Copyright

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.