Sex differences in dengue-related neurological complications: insights from the 2023 Taiwan outbreak

Dengue is a prevalent vector-borne disease that threatens nearly half of the world's population. Although not traditionally classified as neurotropic, dengue can lead to a wide range of neurological manifestations beyond the conventional spectrum of disease severity. This study investigated neurological manifestations during the 2023 dengue outbreak in Tainan, Taiwan, with a focus on the observed male predominance in symptomatic and severe cases. In 2023, the national infectious disease reporting system recorded 21 513 dengue cases in Tainan, of whom 53% were male. Among these, 768 patients (56.4% male; 10.2% paediatric) required hospitalization in tertiary medical centres. Neurological manifestations were observed in 12.0% of hospitalized patients, corresponding to 0.43% of all reported dengue cases in the Tainan area. Among hospitalized patients, neurological manifestations included encephalitis (0.4%), myelitis (0.1%), myositis (7.8%), encephalopathy (2.0%), intracranial haemorrhage (1.0%), ischaemic stroke (0.9%), myasthenia gravis (0.4%), seizures (1.0%), Guillain-Barré syndrome (0.8%), and opsoclonus-myoclonus syndrome (0.1%). Myositis was the most common neurological manifestation, occurring in 26.9% of paediatric and 5.7% of adult patients. Risk factors for neurological complications included male sex, coexisting chronic kidney disease, and neurodegenerative disorders. Male patients showed a higher likelihood of symptomatic dengue infection in the overall population (odds ratio 1.15, 95% confidence interval 1.12-1.18), as well as increased risks of severe disease, hospitalization in tertiary medical centres (crude odds ratio 1.25, 95% confidence interval 1.06-1.46), and neurological complications (adjusted odds ratio 2.37, 95% confidence interval 1.32-4.26) among those older than 40 years. Although the overall case fatality rate in 2023 was 0.9 per 1000 cases, neurological complications were relatively frequent among hospitalized patients. These findings highlight the need for heightened clinical awareness of dengue-associated neurological complications, particularly among neurologists. The consistent male predominance across symptomatic infection, hospitalization, and neurological involvement suggests that sex may be an independent determinant of dengue severity and neurological risk, especially in older adults. Incorporating sex-specific risk stratification and comprehensive neurological assessment into dengue care may improve early detection and clinical management during future outbreaks.