Homotypic Dengue Virus Reinfections in Nicaraguan Children

Background. Infection with any of the 4 related dengue virus serotypes (DENV-1-4) is thought to result in lifelong immunity to homotypic reinfection (ie, reinfection with the same serotype). Methods. Archived serum samples collected as part of an ongoing pediatric dengue cohort study in Nicaragua were tested for DENV by real-time reverse transcription polymerase chain reaction. Samples were collected from 2892 children who presented with an acute febrile illness clinically attributed to a non-DENV cause (hereafter, "C cases"). Test results were added to a database of previously identified symptomatic dengue cases in the cohort to identify repeat infections. Results. Four patients with homotypic DENV reinfections were identified and confirmed among 29 repeat DENV infections (13.8%) with serotype confirmation. Homotypic reinfections with DENV-1, DENV-2, and DENV-3 occurred 325-621 days after the initial infection. Each patient experienced 1 symptomatic dengue case and 1 DENV-positive C case, and 2 patients presented with symptomatic dengue during their second infection. These DENV-positive C cases did not elicit long-lived humoral immune responses, despite viremia levels of up to 6.44 log(10) copies per mL of serum. Conclusions. We describe the first set of virologically confirmed homotypic DENV reinfections. Such cases challenge the current understanding of DENV immunity and have important implications for modeling DENV transmission.