Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua

SummaryDengue, a major public health threat, is a viral infection spread by mosquitoes that can cause a range of symptoms from mild to life-threatening. Our study analyzed 19 years of data from two pediatric studies in children 2 to 17 years of age in Managua, Nicaragua. We aimed to understand how dengue severity varies with different serotypes of dengue virus (DENV1-4) and whether the child had a previous dengue infection. We found that DENV2 and DENV3 caused the most sever disease in children. DENV3 lead to sever outcomes in both primary (first-time) and secondary (repeat) infections, while DENV2 is particularly severe in secondary infections. These findings highlight the importance of a balanced dengue vaccine that can protect against all four virus strains, as current vaccines show varying effectiveness. Our research emphasizes the need for effective prevention and treatment strategies to manage dengue, particularly in regions where the virus is widespread. BackgroundDengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease. MethodsThis study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients. ResultsWe enrolled a total of 15,266 participants, of whom 3,227 (21%) were positive for DENV infection. Of 2,630 cases with serotype result by RT-PCR, 557 corresponded to DENV1, 992 to DENV2, 759 to DENV3 and 322 to DENV4. Severe disease was more prevalent among secondary DENV2 and DENV4 cases, while similar disease severity was observed in both primary and secondary DENV1 and DENV3 cases. According to the 1997 World Health Organization (WHO) severity classification, both DENV2 and DENV3 caused a higher proportion of severe disease compared to other serotypes, whereas DENV3 caused the greatest percentage of severity according to the WHO-2009 classification. DENV2 was associated with increased odds of pleural effusion and low platelet count, while DENV3 was associated with both hypotensive and compensated shock. ConclusionsThese findings demonstrate differences in dengue severity by serotype and immune status and emphasize the critical need for a dengue vaccine with balanced effectiveness against all four serotypes, particularly as existing vaccines show variable efficacy by serotype and serostatus.