---
title: "Post-acute and long-term cardiovascular effects after dengue infection: systematic review protocol"
id: "plos-one-0-post-acute-and-long-term-cardiovascular-effects-following-dengue-infection-a"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-0-post-acute-and-long-term-cardiovascular-effects-following-dengue-infection-a"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838"
published_at: "2026-08-21T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Post-acute and long-term cardiovascular effects after dengue infection: systematic review protocol
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-0-post-acute-and-long-term-cardiovascular-effects-following-dengue-infection-a
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838)
- **Published At:** 2026-08-21T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This protocol describes a planned systematic review to appraise evidence on **post-acute and long-term cardiovascular** outcomes following dengue infection, including clinical events, subclinical cardiac or vascular changes, and related biomarkers. - The review will include human studies of any age reporting cardiovascular outcomes assessed at least 4 weeks after acute dengue illness; outcomes from 4 weeks to under 3 months will be considered post-acute and outcomes at 3 months or later considered long-term. - Study designs eligible are cohort, case-control, cross-sectional, and case-series; comparative studies with dengue-negative or defined reference controls will be used to estimate comparative risk where available, while non-comparative studies will inform descriptive synthesis. - Primary synthesis will prioritise laboratory-confirmed dengue; clinically diagnosed dengue studies will contribute descriptively and in subgroup or sensitivity analyses when appropriate. - Outcomes to be extracted include major clinical cardiovascular and cerebrovascular events (e.g., myocardial infarction, stroke/TIA, heart failure), arrhythmias, thromboembolic events, subclinical myocardial dysfunction, endothelial dysfunction, vascular changes, and cardiovascular-related biomarkers. - Searches will be conducted in PubMed/MEDLINE, Scopus, Cochrane Library, CINAHL, ScienceDirect, ProQuest, and Google Scholar. Two independent reviewers will screen, extract data, and assess risk of bias and methodological quality. - Evidence will be synthesised narratively; where studies are sufficiently comparable, random-effects meta-analysis and GRADE assessment will be performed. - The protocol is registered on PROSPERO (CRD420261354181) and follows PRISMA-P reporting. Planned review phases span literature search and screening (June 2026), full-text review and extraction (from July 2026), synthesis (from August 2026), and manuscript drafting/submission (October–November 2026). - The authors report no specific funding and no competing interests. The protocol emphasises assessment of heterogeneity, bias, and the identification of evidence gaps to guide future research and clinical follow-up in dengue-endemic settings.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosone%2Farticle%3Fid%3D10.1371%2Fjournal.pone.0356838) * * About * Browse * Publish * [](https://journals.plos.org/plosone/ "PLOS One") * Search [advanced search](https://journals.plos.org/plosone/search) * [Browse Topics](https://journals.plos.org/plosone/subjectAreaBrowse) Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click [here](https://github.com/PLOS/plos-thesaurus/blob/master/README.md "Link opens in new window"). [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838) [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838) * 0 [Save](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#savedHeader) * 0 [Citation](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#citedHeader) * 31 [View](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#viewedHeader) * 0 [Share](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838#discussedHeader) Open Access Study Protocol # Post-acute and long-term cardiovascular effects following dengue infection: A systematic review protocol * Niroshan Chandrajith Lokunarangoda , Roles Conceptualization, Methodology, Project administration, Writing – original draft * E-mail: niroshanl@uom.lk Affiliation Department of Medicine and Mental Health, Faculty of Medicine, University of Moratuwa, Moratuwa, Sri Lanka [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0001-8216-8381 ](https://orcid.org/0000-0001-8216-8381 "ORCID Registry") ⨯ * Akhila Rakshitha Wimalasundera, Roles Methodology, Writing – review & editing Affiliation Department of Anatomy, Faculty of Medicine, University of Moratuwa, Moratuwa, Sri Lanka ⨯ * Manikka H. M. Thisara S. Perera, Roles Methodology, Project administration, Writing – review & editing Affiliation Center for Research and Training, National Institute of Infectious Diseases, Gothatuwa, Sri Lanka ⨯ * Damayanthi Idampitiya, Roles Methodology, Project administration, Writing – review & editing Affiliation Center for Research and Training, National Institute of Infectious Diseases, Gothatuwa, Sri Lanka ⨯ * H. Naveen Tharaka Perera, Roles Methodology, Writing – review & editing Affiliation Center for Research and Training, National Institute of Infectious Diseases, Gothatuwa, Sri Lanka ⨯ * K. Gayana Dilki Kothalawala, Roles Methodology, Writing – review & editing Affiliation Center for Research and Training, National Institute of Infectious Diseases, Gothatuwa, Sri Lanka ⨯ * Arunasalam Pathmeswaran, Roles Methodology, Supervision, Writing – review & editing Affiliation Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0000-0003-4065-2639 ](https://orcid.org/0000-0003-4065-2639 "ORCID Registry") ⨯ * Namal P. M. Liyanage, Roles Methodology, Supervision, Writing – review & editing Affiliation Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, Ohio, United States of America ⨯ * Ananda Wijewickrama, Roles Methodology, Supervision, Writing – review & editing Affiliation Department of Medicine and Mental Health, Faculty of Medicine, University of Moratuwa, Moratuwa, Sri Lanka ⨯ * U. Arjuna Bandara Medagama Roles Methodology, Supervision, Writing – review & editing Affiliation Department of Medicine, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka ⨯ # Post-acute and long-term cardiovascular effects following dengue infection: A systematic review protocol * Niroshan Chandrajith Lokunarangoda, * Akhila Rakshitha Wimalasundera, * Manikka H. M. Thisara S. Perera, * Damayanthi Idampitiya, … * H. Naveen Tharaka Perera, * K. Gayana Dilki Kothalawala, * Arunasalam Pathmeswaran, * Namal P. M. Liyanage, * Ananda Wijewickrama, * U. Arjuna Bandara Medagama ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: August 21, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0356838) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0356838) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0356838) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0356838) * [Peer Review](https://journals.plos.org/plosone/article/peerReview?id=10.1371/journal.pone.0356838) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#sec004) * [Data synthesis and analysis](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#sec025) * [Supporting information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#sec030) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0356838) ## Abstract ### Background and Aim Dengue is a major arboviral disease in tropical and subtropical regions, traditionally regarded as an acute, self-limiting illness. However, emerging evidence suggests that its consequences may extend beyond the acute phase, especially involving the cardiovascular system. Reported manifestations include major adverse cardiovascular events, arrhythmias, thromboembolic complications, subclinical myocardial dysfunction, endothelial dysfunction, and vascular changes. Evidence remains fragmented due to variation in study designs, population characteristics, outcome definitions, and follow-up durations. This systematic review aims to appraise and synthesise evidence on post-acute and long-term cardiovascular outcomes following dengue infection, including their spectrum, comparative risk, and determinants. ### Methods and analysis This protocol outlines a systematic review of cardiovascular outcomes in the post-acute and long-term phases of dengue infection. Human studies of any age group will be included if they report cardiovascular outcomes at least 4 weeks after acute dengue illness. Laboratory-confirmed dengue will be prioritised for primary comparative synthesis; clinically diagnosed dengue will contribute to descriptive synthesis and, where appropriate, subgroup or sensitivity analyses. Studies using cohort, case-control, cross-sectional, or case-series designs will be eligible. Comparative studies with dengue-negative or clearly defined reference controls will estimate effects where available, while non-comparative follow-up studies will contribute to descriptive synthesis. Outcomes will include major clinical cardiovascular events, including stroke or transient ischaemic attacks, subclinical cardiac or vascular abnormalities, and cardiovascular-related biomarkers. Searches will be conducted in PubMed/MEDLINE, Scopus, Cochrane Library, CINAHL, ScienceDirect, ProQuest, and Google Scholar. Two reviewers will independently perform screening, data extraction, and risk-of-bias and critical appraisal assessments. Evidence will be synthesized narratively; where comparable, random-effects meta-analysis and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment will be conducted. PROSPERO registration: CRD420261354181. ### Discussion This review will summarize post-dengue cardiovascular sequelae and identify evidence gaps. Findings may clarify post-dengue cardiovascular risk and inform future research, clinical follow-up, and public health planning in dengue-endemic settings. **Citation:** Lokunarangoda NC, Wimalasundera AR, Perera MHMTS, Idampitiya D, Perera HNT, Kothalawala KGD, et al. (2026) Post-acute and long-term cardiovascular effects following dengue infection: A systematic review protocol. PLoS One 21(8): e0356838. https://doi.org/10.1371/journal.pone.0356838 **Editor:** Benjamin M. Liu, Children's National Hospital, George Washington University, UNITED STATES OF AMERICA **Received:** May 28, 2026; **Accepted:** August 9, 2026; **Published:** August 21, 2026 This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the [Creative Commons CC0](https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. **Data Availability:** No datasets were generated or analysed during the current protocol study. Upon completion of the systematic review, all relevant data underlying the findings, including the study-selection file, extracted data, risk-of-bias assessments, and any analysis files, will be made publicly available in Zenodo and/or as [Supporting Information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#sec030), in accordance with PLOS ONE data availability requirements. **Funding:** The author(s) received no specific funding for this work. **Competing interests:** The authors have declared that no competing interests exist. ## Introduction Dengue is an arboviral disease caused by four dengue virus serotypes (DENV-1 to DENV-4) and transmitted primarily by _Aedes_ mosquitoes. It is endemic in more than 100 countries and represents a major public health threat in tropical and subtropical regions, particularly in South and Southeast Asia, Africa, and Latin America [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref001),[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref002)]. Approximately half of the world’s population is now at risk of dengue, with an estimated 100–400 million infections occurring each year [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref002)]. The reported dengue burden has increased substantially over recent decades, with reported cases rising from 505,430 in 2000 to 14.6 million in 2024 [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref002)]. In 2024, the World Health Organization (WHO) received reports of 14,434,584 dengue cases, including 52,738 severe cases and 11,201 deaths across all six WHO regions, marking the highest global reported dengue burden to date [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref003)]. Traditionally, dengue has been considered an acute illness with minimal long-term sequelae. However, emerging epidemiological evidence suggests that dengue infection may be associated with post-acute and longer-term complications affecting multiple organ systems, particularly the cardiovascular system. A population-based cohort study in Taiwan reported a significantly increased risk of major adverse cardiovascular events, including myocardial infarction, stroke, and heart failure, beyond the early period following dengue infection [[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref004)]. Another large retrospective cohort study from Singapore reported an increased risk of new-onset cardiovascular disorders within 31–300 days after dengue infection, including dysrhythmias, ischaemic heart disease, and thrombotic events [[5](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref005)]. In addition, observational studies have identified evidence of residual subclinical left ventricular impairment among individuals with previous dengue infection [[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref006)]. Although recent observations suggest a potential association, the long-term cardiovascular consequences of dengue infection have not been systematically synthesized. Existing studies vary considerably in terms of design, population characteristics, dengue diagnostic criteria, comparator definitions, outcome definitions, and follow-up duration, resulting in fragmented and inconsistent evidence [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref001),[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref004)–[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref006)]. Given the considerable global burden of dengue, a systematic review is necessary to delineate the magnitude and spectrum of post-acute and chronic cardiovascular complications among dengue-exposed populations. Such a review may clarify the diversity of reported cardiovascular outcomes, identify higher-risk subgroups, and guide future epidemiological research and long-term management strategies in dengue-endemic settings. ### Objectives #### Primary objective. To systematically review and synthesize available evidence on post-acute and long-term cardiovascular consequences of dengue virus infection, including clinical cardiovascular and cerebrovascular events, subclinical cardiac or vascular changes, and related biomarkers, and to estimate comparative cardiovascular risk where suitable data are available. #### Specific objectives. 1. To describe the range of post-acute and long-term cardiovascular outcomes reported among individuals with prior dengue infection, including major clinical cardiovascular and cerebrovascular events and subclinical cardiac or vascular abnormalities. 2. To estimate post-acute and long-term cardiovascular risk in dengue-exposed populations compared with non-dengue or general population comparison groups, where comparative data are available. 3. To summarise the evidence on cardiovascular-related biomarkers, including inflammatory, endothelial, and other relevant biomarkers associated with post-acute and long-term cardiovascular risk after dengue infection. 4. To identify reported factors associated with increased post-acute and long-term cardiovascular risk following dengue infection, including patient characteristics, dengue severity, and other reported determinants. Methodological quality, risk of bias, and heterogeneity across included studies will be assessed and explicitly considered when interpreting findings for all objectives. #### PROSPERO registration and reporting information. This protocol is prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD420261354181. This protocol was prepared and is reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement [[7](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref007),[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref008)], and the PRISMA-P checklist is provided in [**S1 Checklist**](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.s001). #### Protocol amendments. If important protocol amendments are made after registration, the date, description, and rationale for each amendment will be documented in an amendment log, updated in the PROSPERO record where applicable, and reported in the final systematic review manuscript. ### Planned timeline The review is planned across four phases. Literature searching and title/abstract screening are planned for June 2026. Full-text review, study selection, data extraction, and risk-of-bias/critical appraisal assessment will take place starting in July 2026. Data synthesis, including narrative synthesis and any meta-analyses, subgroup analyses, or sensitivity analyses, will be conducted from August 2026. Manuscript drafting and submission are planned for October -November 2026. The timeline may be adjusted depending on article retrieval, study volume, and reviewer consensus processes, with regular team meetings used to monitor progress. ### Review question and scope This review will address two linked questions: #### Primary comparative question. Among human participants of any age, is documented dengue infection associated with post-acute and long-term cardiovascular outcomes, compared with individuals without documented recent or index dengue infection or with general-population comparison groups? #### Secondary descriptive question. What post-acute and long-term cardiovascular manifestations, including clinical cardiovascular events, subclinical cardiac or vascular abnormalities, and cardiovascular-related biomarkers, have been reported among individuals with prior dengue infection? For this review, eligible outcomes will be those assessed at least 4 weeks after acute dengue illness or recovery. For synthesis, outcomes will be grouped by timing, where data permit: post-acute outcomes will be considered those assessed from 4 weeks to less than 3 months, and long-term outcomes those assessed at 3 months or later. The 4-week threshold was selected pragmatically to separate post-acute outcomes from acute-phase dengue manifestations and early convalescence. The 3-month threshold was selected to distinguish longer-term follow-up from early post-acute findings. These thresholds are not intended to represent strict biological boundaries. Where studies use different timing definitions or broad follow-up windows, the original definitions will be retained, and timing heterogeneity will be considered in synthesis and interpretation. The review will focus on cardiovascular sequelae after dengue, including clinical events, subclinical abnormalities, and relevant biomarkers. Stroke and transient ischaemic attack (TIA) will be considered within the broader cardiovascular/cerebrovascular outcome domain. Both comparative studies with a non-dengue control or reference group and non-comparative descriptive studies will be included to capture the full range of available evidence. ### Eligibility criteria Eligibility criteria were defined using a PECOS-informed framework (Population, Exposure, Comparator, Outcomes, and Study design), adapted from the PECO approach recommended for systematic reviews of exposure–health outcome associations, while also allowing the inclusion of non-comparative descriptive studies where relevant [[9](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref009),[10](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0356838#pone.0356838.ref010)]. #### Population (P). Human participants of any age, including children, adolescents, adults, and mixed-age populations. Studies restricted to specific age
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