Homotypic Dengue Virus Reinfections in Nicaraguan Children

Abstract

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 log10 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.

Keywords: dengue immunity; dengue virus; homotypic reinfection; repeat infection.

Figure 1.

Phylogeny of dengue virus (DENV) strains from patients with homotypic reinfections. A, DENV-1 from patient 1. B, DENV-3 from patients 3 and 4. Phylograms were generated by neighbor joining analysis of all unique envelope (E) gene sequences in the National Center for Biotechnology Information nucleotide database from contemporaneous Nicaraguan isolates of DENV-1 and DENV-3. Patient DENV sequences are labeled with a dot. Reference DENV-1 and DENV-3 E gene sequences representing established genotypes were also included (open diamonds). Sequences are named using the following convention: GenBank accession number/place of origin/year of collection. The scale bars represent the number of nucleotide substitutions per site. Abbreviations: FI, Fiji; MY, Malaysia; NI, Nicaragua; PH, Philippines; SL, Sri Lanka; TH, Thailand; US-FL, Florida; US-HI, Hawaii; US-PR, Puerto Rico.