Association of dengue severity with the serotype of infection: a systematic review and meta-analysis
File(s)
Accepted version
Author(s)
Ang, Hadrian Jules
McCormack, Clare
Donnelly, Christl
Dorigatti, Ilaria
Type
Journal Article
Abstract
Background
Dengue is a mosquito-borne infection caused by one of four dengue virus serotypes (DENV1-4) that circulates endemically across the tropics and subtropics. To date, there is contrasting evidence on the relationship between the serotype of infection and disease severity.
Methods
We conducted a systematic review (PROSPERO, CRD42023443101) and meta-analysis to examine the association between the serotype of symptomatic infections with severe disease while accounting for both prior exposure status and geographic region, with 18
severity defined by (i) the 1997 World Health Organization (WHO) guidelines, (ii) the 2009 WHO guidelines or (iii) hospitalisation. We searched the Global Health, Embase Classic + Embase, and Medline databases using Ovid for studies published up to 20 January 2025 and extracted case counts with matched serotype and severity information. We fitted generalised linear mixed models to estimate the proportions of severe cases, running independent analyses per severity definition, and stratifying by prior exposure-serotype combinations (e.g. primary DENV2) and geographic region (Asia versus Americas). Heterogeneity was assessed using the 𝜏 26
and 𝐼 metrics and risk of bias was assessed by adapting an established tool for risk of bias in prevalence studies. 28
Findings
Our search yielded 4621 unique records, with 71 studies included for the meta-analysis. We found that, on average, DENV3 in Asia resulted in the highest proportion of DHF/DSS (21·00% [95% CrI: 13·02 to 30·44%]) and hospitalised (22·00% [95% CrI: 0·88 to 75·31%]) cases among symptomatic primary infections, while also causing the highest proportion
Dengue is a mosquito-borne infection caused by one of four dengue virus serotypes (DENV1-4) that circulates endemically across the tropics and subtropics. To date, there is contrasting evidence on the relationship between the serotype of infection and disease severity.
Methods
We conducted a systematic review (PROSPERO, CRD42023443101) and meta-analysis to examine the association between the serotype of symptomatic infections with severe disease while accounting for both prior exposure status and geographic region, with 18
severity defined by (i) the 1997 World Health Organization (WHO) guidelines, (ii) the 2009 WHO guidelines or (iii) hospitalisation. We searched the Global Health, Embase Classic + Embase, and Medline databases using Ovid for studies published up to 20 January 2025 and extracted case counts with matched serotype and severity information. We fitted generalised linear mixed models to estimate the proportions of severe cases, running independent analyses per severity definition, and stratifying by prior exposure-serotype combinations (e.g. primary DENV2) and geographic region (Asia versus Americas). Heterogeneity was assessed using the 𝜏 26
and 𝐼 metrics and risk of bias was assessed by adapting an established tool for risk of bias in prevalence studies. 28
Findings
Our search yielded 4621 unique records, with 71 studies included for the meta-analysis. We found that, on average, DENV3 in Asia resulted in the highest proportion of DHF/DSS (21·00% [95% CrI: 13·02 to 30·44%]) and hospitalised (22·00% [95% CrI: 0·88 to 75·31%]) cases among symptomatic primary infections, while also causing the highest proportion
Date Acceptance
2026-09-07
Citation
EClinicalMedicine
ISSN
2589-5370
Publisher
Elsevier
Journal / Book Title
EClinicalMedicine
Copyright Statement
Copyright This paper is embargoed until publication. Once published the Version of Record (VoR) will be available on immediate open access.
License URL
Publication Status
Accepted