Global patterns of submicroscopic Plasmodium falciparum malaria infection: insights from a systematic review and meta-analysis of population surveys
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background: Adoption of molecular techniques to detect Plasmodium falciparum infection has revealed many previously undetected (by microscopy) yet transmissible low-density infections. The proportion of these infections is typically highest in low transmission settings, but drivers of submicroscopic infection remain unclear. Here, we update a previously conducted systematic review of asexual P. falciparum prevalence by microscopy and polymerase chain reaction (PCR) in the same population. We conduct a meta-analysis to explore potential drivers of submicroscopic infection and identify the locations where submicroscopic infections are most common.
Methods: PubMed and Web of Science databases were searched up to 11th October 2020 for cross-sectional studies reporting data on asexual P.falciparum prevalence by both microscopy and PCR. Surveys of pregnant women, where participants had been chosen based on symptoms/treatment or that did not involve a population from a defined location were excluded. Both the number of individuals tested and positive by microscopy and PCR for P. falciparum infection were extracted from each reference. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geography, seasonality, age, methodology and current/historical patterns of transmission.
Findings: A total of 166 references containing 551 cross-sectional survey microscopy/PCR prevalence pairs were included. Our results highlight that submicroscopic infections predominate in low transmission settings across all settings, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of the infected population (with submicroscopic infection more likely in adults than children) and the PCR/microscopy methodology utilised. We also observed a statistically significant influence of seasonality, with fewer submicroscopic infections observed in the wet season. Integrating these results with estimates of infectivity in relation to parasite density suggests the contribution of submicroscopic infections to transmission across different settings is likely to be highly variable.
Interpretation: Significant variation in the prevalence of submicroscopic infection exists even across settings characterised by similar current levels of transmission. These differences in submicroscopic epidemiology potentially warrant different approaches to targeting this infected sub-group in the approach to elimination.
Methods: PubMed and Web of Science databases were searched up to 11th October 2020 for cross-sectional studies reporting data on asexual P.falciparum prevalence by both microscopy and PCR. Surveys of pregnant women, where participants had been chosen based on symptoms/treatment or that did not involve a population from a defined location were excluded. Both the number of individuals tested and positive by microscopy and PCR for P. falciparum infection were extracted from each reference. Bayesian regression modelling was used to explore determinants of the size of the submicroscopic reservoir including geography, seasonality, age, methodology and current/historical patterns of transmission.
Findings: A total of 166 references containing 551 cross-sectional survey microscopy/PCR prevalence pairs were included. Our results highlight that submicroscopic infections predominate in low transmission settings across all settings, but also reveal marked geographical variation, with the proportion of infections that are submicroscopic being highest in South American surveys and lowest in West African studies. Whilst current transmission levels partly explain these results, we find that historical transmission intensity also represents a crucial determinant of the size of the submicroscopic reservoir, as does the demographic structure of the infected population (with submicroscopic infection more likely in adults than children) and the PCR/microscopy methodology utilised. We also observed a statistically significant influence of seasonality, with fewer submicroscopic infections observed in the wet season. Integrating these results with estimates of infectivity in relation to parasite density suggests the contribution of submicroscopic infections to transmission across different settings is likely to be highly variable.
Interpretation: Significant variation in the prevalence of submicroscopic infection exists even across settings characterised by similar current levels of transmission. These differences in submicroscopic epidemiology potentially warrant different approaches to targeting this infected sub-group in the approach to elimination.
Date Issued
2021-08
Date Acceptance
2021-02-22
Citation
The Lancet Microbe, 2021, 2 (8), pp.e366-e374
ISSN
2666-5247
Publisher
Elsevier
Start Page
e366
End Page
e374
Journal / Book Title
The Lancet Microbe
Volume
2
Issue
8
Copyright Statement
© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license
License URL
Sponsor
Medical Research Council (MRC)
The Royal Society
Medical Research Council (MRC)
Identifier
https://www.sciencedirect.com/science/article/pii/S2666524721000550?via%3Dihub
Grant Number
MR/K010174/1B
DH140134
MR/R015600/1
Subjects
Science & Technology
Life Sciences & Biomedicine
Infectious Diseases
Microbiology
TRANSMISSION
EPIDEMIOLOGY
ELIMINATION
MOSQUITOS
Publication Status
Published
Date Publish Online
2021-05-25