Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling
- Burnet Institute, Australia
- Mahidol University, Thailand
- The University of Melbourne, Australia
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
-
Dominant malaria vector species globally, 2010Malaria Atlas Project Explorer, Dominant malaria vector species globally, 2010.
-
Plasmodium falciparum parasite rate in 2-10 year olds globally, 2000-2017Malaria Atlas Project Explorer, Plasmodium falciparum parasite rate in 2-10 year olds globally, 2000-2017.
Article and author information
Author details
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
- Amy Wesolowski, Johns Hopkins Bloomberg School of Public Health, United States
Publication history
- Received: August 16, 2021
- Preprint posted: September 17, 2021 (view preprint)
- Accepted: December 21, 2021
- Accepted Manuscript published: December 23, 2021 (version 1)
- Version of Record published: February 21, 2022 (version 2)
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.
Metrics
-
- 824
- Page views
-
- 153
- Downloads
-
- 3
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Anopheles salivary antigens as serological biomarkers of vector exposure and malaria transmission: A systematic review with multilevel modelling
eLife 10:e73080.
https://doi.org/10.7554/eLife.73080
Further reading
-
- Epidemiology and Global Health
Background:
Affectionate touch, which is vital for mental and physical health, was restricted during the Covid-19 pandemic. This study investigated the association between momentary affectionate touch and subjective well-being, as well as salivary oxytocin and cortisol in everyday life during the pandemic.
Methods:
In the first step, we measured anxiety and depression symptoms, loneliness and attitudes toward social touch in a large cross-sectional online survey (N = 1050). From this sample, N = 247 participants completed ecological momentary assessments over 2 days with six daily assessments by answering smartphone-based questions on affectionate touch and momentary mental state, and providing concomitant saliva samples for cortisol and oxytocin assessment.
Results:
Multilevel models showed that on a within-person level, affectionate touch was associated with decreased self-reported anxiety, general burden, stress, and increased oxytocin levels. On a between-person level, affectionate touch was associated with decreased cortisol levels and higher happiness. Moreover, individuals with a positive attitude toward social touch experiencing loneliness reported more mental health problems.
Conclusions:
Our results suggest that affectionate touch is linked to higher endogenous oxytocin in times of pandemic and lockdown and might buffer stress on a subjective and hormonal level. These findings might have implications for preventing mental burden during social contact restrictions.
Funding:
The study was funded by the German Research Foundation, the German Psychological Society, and German Academic Exchange Service.
-
- Epidemiology and Global Health
Background: Home-based self-sampling for human papillomavirus (HPV) testing may be an alternative for women not attending clinic-based cervical cancer screening.
Methods: We assessed barriers to care and motivators to use at-home HPV self-sampling kits during the COVID-19 pandemic as part of a randomized controlled trial evaluating kit effectiveness. Participants were women aged 30-65 and under-screened for cervical cancer in a safety-net healthcare system. We conducted telephone surveys in English/Spanish among a subgroup of trial participants, assessed differences between groups, and determined statistical significance at p<0.05.
Results: Over half of 233 survey participants reported that clinic-based screening (Pap) is uncomfortable (67.8%), embarrassing (52.4%), and discomfort seeing male providers (63.1%). The last two factors were significantly more prevalent among Spanish versus English speakers (66.4% vs. 30% (p=0.000) and 69.9 vs. 52.2% (p=0.006), respectively). Most women who completed the kit found Pap more embarrassing (69.3%), stressful (55.6%), and less convenient (55.6%) than the kit. The first factor was more prevalent among Spanish versus English speakers (79.6% vs. 53.38%, p=0.001) and among patients with elementary education or below.
Conclusions: The COVID-19 pandemic influenced most (59.5%) to participate in the trial due to fear of COVID, difficulty making appointments, and ease of using kits. HPV self-sampling kits may reduce barriers among under-screened women in a safety-net system.
Funding: This study is supported by a grant from the National Institute for Minority Health and Health Disparities (NIMHD, R01MD013715, PI: JR Montealegre).
Clinical trial number: NCT03898167.
