Coinfection with Respiratory Pathogens and Dengue Disease Severity in Puerto Rico, 2012-2024

Differentiating between acute febrile illnesses (AFIs) caused by arboviruses like dengue virus (DENV) and other pathogens is challenging, particularly in the case of coinfections, which often require comprehensive diagnostic testing for accurate identification. Recognizing DENV coinfections is important because they may contribute to increased disease severity, and their identification can aid in patient management decisions. Using data from the Sentinel Enhanced Dengue Surveillance System in Puerto Rico (2012-2024), we compared patients with DENV monoinfection to those coinfected with DENV and another pathogen. All pathogens were identified via nucleic acid detection by using real-time, reverse transcriptase-polymerase chain reaction or serology. We examined demographic and clinical features linked to coinfection using Mann-Whitney-Wilcoxon, χ2, or Fisher's exact tests. Among 50,189 participants tested for DENV, 1,218 (2.4%) had DENV infections, with 1,172 (96.2%) monoinfections and 46 (3.8%) coinfections. The most frequent coinfecting pathogens were adenovirus (17.4%), influenza A (15.2%), human metapneumovirus (15.2%), and respiratory syncytial virus (10.9%). Dengue virus coinfections were associated with younger age (median: 13 versus 16 years; P = 0.011) and symptoms of rhinorrhea (52.2% versus 27.3%; P <0.001) and cough (60.9% versus 36.4%; P = 0.001). Among 549 hospitalized dengue patients, 20 (3.6%) had coinfections. Five of seven participants with DENV/influenza A coinfection were hospitalized. Hospitalization, intensive care unit admission, the administration of blood products, and severe dengue indicators (plasma leakage, severe bleeding, and organ involvement) were not significantly associated with DENV coinfection. Overall, DENV coinfections were uncommon in AFI cases in Puerto Rico, and they primarily involved respiratory viruses. Overlapping symptoms may complicate clinical management, emphasizing the importance of comprehensive pathogen testing in settings where arboviruses and respiratory viruses cocirculate.