Neurological Events Associated With Acute Dengue Infection

With increasing global incidence of acute dengue virus (DENV) infection, more accurate estimates of the burden of neurological events following infection are required; however, population-based estimates are lacking.

To evaluate the risk and excess burden of neurological events in a cohort of DENV-infected adults in the acute postinfectious period vs population-based comparators without DENV infection.

This was a retrospective, population-based cohort study in Singapore. National registries were used to construct a cohort of all adults (aged ≥18 years) infected with DENV from January 1, 2017, through December 31, 2023, for whom the index date (time 0 [T0]) was taken as the date of notification, and a cohort of uninfected population-based comparators, for whom T0 was randomly assigned to match T0 distribution in DENV-infected cases. As the period overlapped with the COVID-19 pandemic, individuals infected with SARS-CoV-2 within 30 days of T0 were additionally excluded, as were individuals who died before T0 and uninfected comparators with no prior health care contact. Data analysis was performed from January 1, 2017, through March 30, 2024.

DENV infection recorded in the national registry.

New-incident neurological events, including any neurological event, memory loss, movement disorders, and other neurological disorders (eg, fatigue or malaise, encephalitis or encephalopathy), following DENV infection were identified using national health care claims records, and risk was assessed over the acute follow-up period. Odds of new-incident neurological events in DENV-infected cases vs uninfected comparators were estimated using overlap-weighted logistic regression at 30 to 90 days after T0.

A total of 65 207 confirmed DENV-infected cases (mean [SD] age, 48.4 [17.8] years; 34 876 [53.5%] male) were compared against 1 616 865 uninfected comparators (mean [SD] age, 54.8 [18.3] years; 730 702 [45.2%] male). At 30 days following DENV infection, individuals with DENV infection, compared with uninfected individuals, had elevated odds of any new-incident neurological event (adjusted odds ratio [aOR], 9.69; 95% CI, 6.59-14.90), memory loss (aOR, 3.19; 95% CI, 1.36-8.69), movement disorders (aOR, 7.10; 95% CI, 2.49-29.18), and other neurological events (aOR, 14.32; 95% CI, 8.61-26.04); risk trajectories diverged up to 90 days after infection. However, the overall excess burden was modest, with less than 1 excess event per 100 cases. The DENV-infected cases, compared with uninfected individuals, had increased odds of memory loss (aOR, 2.99; 95% CI, 1.30-7.87) and movement disorders (aOR, 6.38; 95% CI, 2.23-25.96) only among those aged 60 years or older and in cases infected during DENV serotype 3 transmission.

DENV infection was associated with significantly higher odds of acute new-incident neurological events following infection, although the excess burden was modest. Older adults should be monitored for a wider spectrum of potential neurological complications following DENV infection.