Determinants of Mortality in Severe Dengue: A Retrospective Cohort Analysis

Overview

This population-based retrospective cohort study examines factors associated with death among 251 patients with laboratory-confirmed severe dengue in Espírito Santo, Brazil, from 2020 through 2024. Mortality is predominantly associated with advanced hemodynamic instability, while exploratory analyses suggest age-related differences in mortality-associated manifestations.

Background

Severe dengue can involve severe plasma leakage causing shock or respiratory distress, severe bleeding, or organ dysfunction. Brazil reported more than 6000 dengue-related deaths in 2024. Factors associated with progression to severe dengue may differ from those associated with death once severe disease is established, particularly in older adults with less typical presentations.

Data Highlights

• Among 251 patients, 117 (46.6%) died.

• Weak or undetectable pulse was associated with higher mortality: risk ratio (RR), 1.74; 95% CI, 1.34–2.26.

• Late-stage arterial hypotension was associated with higher mortality: RR, 1.80; 95% CI, 1.34–2.42.

• Progressive hematocrit increase was associated with higher mortality: RR, 1.43; 95% CI, 1.10–1.85.

• Altered consciousness was associated with higher mortality: RR, 1.31; 95% CI, 1.02–1.67.

Key Findings

• Fatal cases were significantly older than survivors.

• Weak or undetectable pulse and late-stage hypotension remained associated with higher mortality in both exploratory age groups: <60 years and ≥60 years.

• Progressive hematocrit increase was associated with higher mortality only among patients aged <60 years.

• Sudden platelet decline was associated with lower mortality only among patients aged <60 years.

• Fever was associated with lower mortality only among patients aged ≥60 years.

• Diabetes and hypertension were not significantly associated with death in this severe-dengue cohort.

Interpretation

The findings identify associations with established hemodynamic collapse rather than validated early predictors of death. Associations of fever and sudden platelet decline with lower mortality do not establish protective effects. Their absence should not be interpreted as reassuring.

Limitations

Surveillance data may be affected by underreporting or misclassification. Restriction to laboratory-confirmed cases excluded a substantial number of severe cases and deaths. The timing of individual manifestations relative to outcomes was unavailable, as were data on time to care, fluid management, medications, and socioeconomic factors. Residual confounding cannot be excluded. Age-stratified analyses were exploratory, without formal interaction testing, and used a cutoff selected from the study population.

Clinical Implications

The authors emphasize advanced hemodynamic instability and altered consciousness as important manifestations associated with poor outcomes. Classical warning signs may have less pronounced associations with mortality in older adults. These findings require prospective evaluation before being used as early prediction tools.

Conclusion

Mortality among patients with severe dengue is predominantly associated with advanced hemodynamic instability. Potential age-related differences warrant prospective studies with precisely timed clinical data and longitudinal follow-up.

Related Resources & Content

1. Dengue: diagnóstico e manejo clínico: adulto e criança, sixth edition — Ministério da Saúde do Brasil — Ministério da Saúde, 2024.

2. Risk predictors of progression to severe disease during the febrile phase of dengue: a systematic review and meta-analysis — Sangkaew S, Ming D, Boonyasiri A, et al. — The Lancet Infectious Diseases, 2021;21:1014–1026.

3. Challenges in dengue fever in the elderly: atypical presentation and risk of severe dengue and hospital-acquired infection — Rowe EK, Leo YS, Wong JG, et al. — PLOS Neglected Tropical Diseases, 2014;8:e2777.

4. Clinical manifestations, laboratory profile and outcomes of dengue virus infection in hospitalised older patients — Ng WY, Ngim CF, Chow KY, Goh SXM, Zaid M, Dhanoa A — Transactions of the Royal Society of Tropical Medicine and Hygiene, 2022;116:545–554.

5. Prognosis and mortality risk in elderly patients with dengue virus infection: excess fatality and the urgent need for revising current WHO criteria for elderly patients — Jeng MJ, Lee NY, Lee IK, et al. — Travel Medicine and Infectious Disease, 2025;65:102855.

6. Relevance of non-communicable comorbidities for the development of the severe forms of dengue: a systematic literature review — Toledo J, George L, Martinez E, et al. — PLOS Neglected Tropical Diseases, 2016;10:e0004284.