PLoS Neglected Tropical Diseases (Feb 2016)

Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru.

  • Brett M Forshey,
  • Robert C Reiner,
  • Sandra Olkowski,
  • Amy C Morrison,
  • Angelica Espinoza,
  • Kanya C Long,
  • Stalin Vilcarromero,
  • Wilma Casanova,
  • Helen J Wearing,
  • Eric S Halsey,
  • Tadeusz J Kochel,
  • Thomas W Scott,
  • Steven T Stoddard

DOI
https://doi.org/10.1371/journal.pntd.0004398
Journal volume & issue
Vol. 10, no. 2
p. e0004398

Abstract

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BACKGROUND:Nearly half of the world's population is at risk for dengue, yet no licensed vaccine or anti-viral drug is currently available. Dengue is caused by any of four dengue virus serotypes (DENV-1 through DENV-4), and infection by a DENV serotype is assumed to provide life-long protection against re-infection by that serotype. We investigated the validity of this fundamental assumption during a large dengue epidemic caused by DENV-2 in Iquitos, Peru, in 2010-2011, 15 years after the first outbreak of DENV-2 in the region. METHODOLOGY/PRINCIPAL FINDINGS:We estimated the age-dependent prevalence of serotype-specific DENV antibodies from longitudinal cohort studies conducted between 1993 and 2010. During the 2010-2011 epidemic, active dengue cases were identified through active community- and clinic-based febrile surveillance studies, and acute inapparent DENV infections were identified through contact tracing studies. Based on the age-specific prevalence of DENV-2 neutralizing antibodies, the age distribution of DENV-2 cases was markedly older than expected. Homologous protection was estimated at 35.1% (95% confidence interval: 0%-65.2%). At the individual level, pre-existing DENV-2 antibodies were associated with an incomplete reduction in the frequency of symptoms. Among dengue cases, 43% (26/66) exhibited elevated DENV-2 neutralizing antibody titers for years prior to infection, compared with 76% (13/17) of inapparent infections (age-adjusted odds ratio: 4.2; 95% confidence interval: 1.1-17.7). CONCLUSIONS/SIGNIFICANCE:Our data indicate that protection from homologous DENV re-infection may be incomplete in some circumstances, which provides context for the limited vaccine efficacy against DENV-2 in recent trials. Further studies are warranted to confirm this phenomenon and to evaluate the potential role of incomplete homologous protection in DENV transmission dynamics.