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Reduced risk of disease during postsecondary dengue virus infections.

ABSTRACT: BACKGROUND: Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1-4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission. METHODS: DENV infections before and during the study period were determined by analysis of serial serum samples with virus neutralization tests. Third and fourth infections were classified as postsecondary infections. Dengue fever cases were detected by door-to-door surveillance for acute febrile illness. RESULTS: Among susceptible participants, 39% (420/1077) and 53% (1595/2997) seroconverted to DENV-3 and DENV-4, respectively. Disease was detected in 7% of DENV-3 infections and 10% of DENV-4 infections. Disease during postsecondary infections was reduced by 93% for DENV-3 and 64% for DENV-4, compared with primary and secondary infections. Despite lower disease rates, postsecondary infections constituted a significant proportion of apparent infections (14% [for DENV-3 infections], 45% [for DENV-4 infections]). CONCLUSIONS: Preexisting heterotypic antibodies markedly reduced but did not eliminate the risk of disease in this study population. These results improve understanding of how preinfection history can be associated with dengue outcomes and DENV transmission dynamics.

SUBMITTER: Olkowski S

PROVIDER: S-EPMC3749012 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Reduced risk of disease during postsecondary dengue virus infections.

Olkowski Sandra S Forshey Brett M BM Morrison Amy C AC Rocha Claudio C Vilcarromero Stalin S Halsey Eric S ES Kochel Tadeusz J TJ Scott Thomas W TW Stoddard Steven T ST

The Journal of infectious diseases 20130617 6

<h4>Background</h4>Antibodies induced by infection with any 1 of 4 dengue virus (DENV) serotypes (DENV-1-4) may influence the clinical outcome of subsequent heterologous infections. To quantify potential cross-protective effects, we estimated disease risk as a function of DENV infection, using data from longitudinal studies performed from September 2006 through February 2011 in Iquitos, Peru, during periods of DENV-3 and DENV-4 transmission.<h4>Methods</h4>DENV infections before and during the s ...[more]

PMID: 23776195

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Project description:IntroductionDengue virus (DENV) infection is currently a major cause of morbidity and mortality in the world; it has become more common and virulent over the past half-century and has gained much attention. Thus, this review compared the percentage of severe cases of both primary and secondary infections with different serotypes of dengue virus.MethodsData related to the number of cases involving dengue fever (DF), dengue hemorrhagic fever (DHF), dengue shock syndrome (DSS) or severe dengue infections caused by different serotypes of dengue virus were obtained by using the SCOPUS, the PUBMED and the OVID search engines with the keywords "(dengue* OR dengue virus*) AND (severe dengue* OR severity of illness index* OR severity* OR DF* OR DHF* OR DSS*) AND (serotypes* OR serogroup*)", according to the MESH terms suggested by PUBMED and OVID.ResultsApproximately 31 studies encompassing 15,741 cases reporting on the dengue serotypes together with their severity were obtained, and meta-analysis was carried out to analyze the data. This study found that DENV-3 from the Southeast Asia (SEA) region displayed the greatest percentage of severe cases in primary infection (95% confidence interval (CI), 31.22-53.67, 9 studies, n = 598, I2 = 71.53%), whereas DENV-2, DENV-3, and DENV-4 from the SEA region, as well as DENV-2 and DENV-3 from non-SEA regions, exhibited the greatest percentage of severe cases in secondary infection (95% CI, 11.64-80.89, 4-14 studies, n = 668-3,149, I2 = 14.77-96.20%). Moreover, DENV-2 and DENV-4 from the SEA region had been found to be more highly associated with dengue shock syndrome (DSS) (95% CI, 10.47-40.24, 5-8 studies, n = 642-2,530, I2 = 76.93-97.70%), while DENV-3 and DENV-4 from the SEA region were found to be more highly associated with dengue hemorrhagic fever (DHF) (95% CI, 31.86-54.58, 9 studies, n = 674-2,278, I2 = 55.74-88.47%), according to the 1997 WHO dengue classification. Finally, DENV-2 and DENV-4 from the SEA region were discovered to be more highly associated with secondary infection compared to other serotypes (95% CI, 72.01-96.32, 9-12 studies, n = 671-2,863, I2 = 25.01-96.75%).ConclusionThis study provides evidence that the presence of certain serotypes, including primary infection with DENV-3 from the SEA region and secondary infection with DENV-2, DENV-3, and DENV-4 also from the SEA region, as well as DENV-2 and DENV-3 from non SEA regions, increased the risk of severe dengue infections. Thus, these serotypes are worthy of special consideration when making clinical predictions upon the severity of the infection.Systematic review registrationPROSPERO CRD42015026093 (http://www.crd.york.ac.uk/PROSPERO).

Project description:Dengue is a major international public health concern, and the number of outbreaks has escalated greatly. Human migration and international trade and travel are constantly introducing new vectors and pathogens into novel geographic areas. Of particular interest is the extent to which dengue virus (DENV) infections are subclinical or inapparent. Not only may such infections contribute to the global spread of DENV by human migration, but also seroprevalence rates in naïve populations may be initially high despite minimal numbers of detectable clinical cases. As the probability of severe disease is increased in secondary infections, populations may thus be primed, with serious public health consequences following introduction of a new serotype. In addition, pre-existing immunity from inapparent infections may affect vaccine uptake, and the ratio of clinically apparent to inapparent infection could affect the interpretation of vaccine trials. We performed a literature search for inapparent DENV infections and provide an analytical review of their frequency and associated risk factors. Inapparent rates were highly variable, but "inapparent" was the major outcome of infection in all prospective studies. Differences in the epidemiological context and type of surveillance account for much of the variability in inapparent infection rates. However, one particular epidemiological pattern was shared by four longitudinal cohort studies: the rate of inapparent DENV infections was positively correlated with the incidence of disease the previous year, strongly supporting an important role for short-term heterotypic immunity in determining the outcome of infection. Primary and secondary infections were equally likely to be inapparent. Knowledge of the extent to which viruses from inapparent infections are transmissible to mosquitoes is urgently needed. Inapparent infections need to be considered for their impact on disease severity, transmission dynamics, and vaccine efficacy and uptake.

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Reduced risk of disease during postsecondary dengue virus infections.

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Reduced risk of disease during postsecondary dengue virus infections.

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