Submicroscopic Infection in Plasmodium falciparum –Endemic Populations: A Systematic Review and Meta‐Analysis

Okell, Lucy C.; Ghani, Azra C.; Lyons, Emily; Drakeley, Chris J.

doi:10.1086/644781

Cited by 532Malaria Research and ControlBird parasitology and diseasesHemoglobinopathies and Related Disorders

Submicroscopic Infection in Plasmodium falciparum –Endemic Populations: A Systematic Review and Meta‐Analysis

Okell, Lucy C., Ghani, Azra C., Lyons, Emily, Drakeley, Chris J.·2009·The Journal of Infectious Diseases

DOI 10.1086/644781

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Abstract

INTRODUCTION: Light microscopy examination of blood slides is the main method of detecting malaria infection; however, it has limited sensitivity. Low-density infections are most likely to be missed, but they contribute to the infectious reservoir. Quantifying these submicroscopic infections is therefore key to understanding transmission dynamics and successfully reducing parasite transmission. METHODS: We conducted a systematic review of endemic population surveys in which P. falciparum prevalence had been measured by both microscopy and a more-sensitive polymerase chain reaction (PCR)-based technique. The combined microscopy:PCR prevalence ratio was estimated by random-effects meta-analysis, and the effect of covariates was determined by meta-regression. RESULTS: Seventy-two pairs of prevalence measurements were included in the study. The prevalence of infection measured by microscopy was, on average, 50.8% (95% confidence interval [CI], 45.2%-57.1%) of that measured by PCR. For gametocyte-specific detection, the microscopy prevalence was, on average, 8.7% (95% CI, 2.8%-26.6%) of the prevalence measured by PCR. A significantly higher percentage of total infections was detected by microscopy in areas of high, compared with low, transmission (74.5% when the prevalence determined by PCR was >75% versus 12.0% when the prevalence determined by PCR was <10%). DISCUSSION: Microscopy can miss a substantial proportion of P. falciparum infections in surveys of endemic populations, especially in areas with low transmission of infection. The extent of the submicroscopic reservoir needs to be taken into account for effective surveillance and control.

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Several studies have demonstrated submicroscopic P. falciparum infection detectable only by sensitive molecular (PCR) methods in Sub-Saharan Africa and documented high prevalence rates of low-density parasitaemia, especially in pregnant women.
“Over the past decades, several studies have demonstrated submicroscopic P. falciparum infection, detectable only by sensitive molecular (PCR) methods in Sub-Saharan Africa (SSA) and documented high prevalence rates of low-density parasitaemia, shedding new light on the real prevalence of malaria infections [11], especially in pregnant women [2].”
From Intermittent preventive treatment with Sulphadoxine-Pyrimethamine (IPTp-SP) is associated with protection against sub-microscopic P. falciparum infection in pregnant women during the low transmission dry season in southwestern Cameroon: A Semi - longitudinal study (2022) · cites this paper as [11]
Between low and high transmission extremes, there is an inverse relationship between the proportion of submicroscopic infections and transmission intensity (by PCR prevalence).
“Between these two extremes, there was an inverse relationship between the proportion of submicroscopic infections and the transmission intensity (by PCR prevalence).”
From What is the burden of submicroscopic malaria in pregnancy in central India? (2015) · cites this paper as [5]
The proportion of malarial infections that are submicroscopic is higher in areas of low transmission; a meta-analysis reported 88% undetected by microscopy in low-transmission areas compared to 25.5% in high-transmission areas.
“A meta-analysis of surveys conducted in endemic areas reported that 88% of all infections went undetected by microscopy in areas of low transmission compared to only 25.5% in areas of high transmission. 5”
From What is the burden of submicroscopic malaria in pregnancy in central India? (2015) · cites this paper as [5]

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Authors: Okell, L. C., Ghani, A. C., Lyons, E., & Drakeley, C. J.
Affiliations: London School of Hygiene & Tropical Medicine (GB)
Imperial College London (GB)
Corresponding author: Okell, Lucy C.
ORCID: Okell, Lucy C.
Ghani, Azra C.
Lyons, Emily
Drakeley, Chris J.
Venue: The Journal of Infectious Diseases
Publisher: Oxford University Press (OUP)
Published: 2009-11-15
Volume: 200
Issue: 10
Pages: 1509-1517
ISSN: 0022-1899 (ISSN-L)
1537-6613
DOI: 10.1086/644781
OpenAlex: W2125263196
Cited by: 532
References: 158
Citations by year: 2026: 13 · 2025: 26 · 2024: 21 · 2023: 24 · 2022: 30 · 2021: 38 · 2020: 39 · 2019: 36 · 2018: 34 · 2017: 39 · 2016: 43 · 2015: 46 · 2014: 34 · 2013: 40 · 2012: 30
FWCI: 3.03
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Infectious Diseases (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Medical Research Council
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
Keywords: Plasmodium falciparum, submicroscopic malaria infection, malaria prevalence, PCR detection, gametocytes, infectious reservoir, transmission intensity, malaria surveillance, endemic populations
MeSH terms: Disease Reservoirs, Humans, Prevalence, Polymerase Chain Reaction, Malaria, Falciparum, Endemic Diseases

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Submicroscopic Infection in Plasmodium falciparum –Endemic Populations: A Systematic Review and Meta‐Analysis

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