TY - JOUR
T1 - Incomplete Protection against Dengue Virus Type 2 Re-infection in Peru
AU - Forshey, Brett M.
AU - Reiner, Robert C.
AU - Olkowski, Sandra
AU - Morrison, Amy C.
AU - Espinoza, Angelica
AU - Long, Kanya C.
AU - Vilcarromero, Stalin
AU - Casanova, Wilma
AU - Wearing, Helen J.
AU - Halsey, Eric S.
AU - Kochel, Tadeusz J.
AU - Scott, Thomas W.
AU - Stoddard, Steven T.
N1 - Publisher Copyright:
© 2016 Public Library of Science. All Rights Reserved.
PY - 2016/2/5
Y1 - 2016/2/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84959565208&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0004398
DO - 10.1371/journal.pntd.0004398
M3 - Article
C2 - 26848841
AN - SCOPUS:84959565208
SN - 1935-2727
VL - 10
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 2
M1 - e0004398
ER -
