Clinical and Virological Factors Influencing the Performance of a NS1 Antigen-Capture Assay and Potential Use as a Marker of Dengue Disease Severity

Dengue is the most prevalent arthropod-borne disease in tropical regions. The clinical manifestation may vary from asymptomatic to potentially fatal dengue shock syndrome. Early laboratory confirmation of dengue diagnosis is essential since many symptoms are not specific. Dengue non-structural protein 1 (NS1) may be used in simple antigen-capture ELISA for early detection of dengue virus infection. Our result demonstrated that the Platelia NS1 antigen detection kit had a quite low overall sensitivity. However, sensitivity rises significantly when used in combination with MAC-ELISA. When taking into account the various forms of dengue infection, the NS1 antigen detection was found relatively high in patients sampled during the first 3 days of fever onset, in patients with primary infection, DENV-1 infection, with high level of viremia and in mild form of dengue fever. In asymptomatically infected individuals, RT-PCR assay has proved to be more sensitive than NS1 antigen detection. Moreover, the NS1 antigen level correlated significantly with high viremia and low level of NS1 antigen was associated with more severe disease

Genome-Wide Expression Profiling Deciphers Host Responses Altered during Dengue Shock Syndrome and Reveals the Role of Innate Immunity in Severe Dengue

International audienceBackgroundDeciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians.Methodology/Principal FindingsBased on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammatory and repair/remodeling transcripts. We also show that unexpected pro-inflammatory gene patterns at the interface between innate immunity, inflammation and host lipid metabolism, known to play pathogenic roles in acute and chronic inflammatory diseases associated with systemic vascular dysfunction, are transcriptionnally active in the blood cells of DSS children.Conclusions/SignificanceWe provide a global while non exhaustive overview of the molecular mechanisms altered in of DSS children and suggest how they may interact to lead to final vascular homeostasis breakdown. We suggest that some mechanisms identified should be considered putative therapeutic targets or biomarkers of progression to DSS

National dengue surveillance in Cambodia 1980–2008: epidemiological and virological trends and the impact of vector control

International audienceOBJECTIVE: Dengue has been reportable in Cambodia since 1980. Virological surveillance began in 2000 and sentinel surveillance was established at six hospitals in 2001. Currently, national surveillance comprises passive and active data collection and reporting on hospitalized children aged 0-15 years. This report summarizes surveillance data collected since 1980. METHODS: Crude data for 1980-2001 are presented, while data from 2002-2008 are used to describe disease trends and the effect of vector control interventions. Trends in dengue incidence were analysed using the Prais-Winsten generalized linear regression model for time series. FINDINGS: During 1980-2001, epidemics occurred in cycles of 3-4 years, with the cycles subsequently becoming less prominent. For 2002-2008 data, linear regression analysis detected no significant trend in the annual reported age-adjusted incidence of dengue (incidence range: 0.7-3.0 per 1000 population). The incidence declined in 2.7% of the 185 districts studied, was unchanged in 86.2% and increased in 9.6%. The age-specific incidence was highest in infants aged < 1 year and children aged 4-6 years. The incidence was higher during rainy seasons. All four dengue virus (DENV) serotypes were permanently in circulation, though the predominant serotype has alternated between DENV-3 and DENV-2 since 2000. Although larvicide has been distributed in 94 districts since 2002, logistic regression analysis showed no association between the intervention and dengue incidence. CONCLUSION: The dengue burden remained high among young children in Cambodia, which reflects intense transmission. The national vector control programme appeared to have little impact on disease incidence