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The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

Background & Objectives: Dengue is a major public health problem in northeast India where the majority of the cases go unreported and undiagnosed. Even though all four dengue serotypes are reported, there is a dearth of information on genetic diversity. The present cross-sectional study was undertaken during 2016-17 to determine the genetic variance of dengue virus serotype 2 (DENV-2) based on the envelope (E) glycoprotein gene., Methods: The serum samples collected from the northeast parts of India, as a part of hospital-based acute febrile illness surveillance, were serotyped. Viral RNA was extracted from DENV-2 serum samples using QIAquick® RNA Extraction Kit. The E gene was amplified by conventional reverse-transcriptase polymerase chain reaction (RT-PCR) and the PCR products were sequenced., Results: The E glycoprotein gene of nine serum samples with high viral RNA concentration (Ct <25) was sequenced. The E gene sequences of eight DENV-2 strains from Assam and Meghalaya aligned with genotype IV (Cosmopolitan) and one strain from Tripura segregated with Asian-I genotype., Interpretation & Conclusion: Ongoing laboratory-based surveillance is mandatory to understand the transmission dynamics of dengue in endemic countries. This study concluded that in northeast India, presently two distinct genotypes of DENV-2, namely genotype IVb (Cosmopolitan) and Asian-I genotype are in circulation., Competing Interests: None

Background & Objectives: Dengue virus infection is endemic in India with all the four serotypes of dengue virus in circulation. This study was aimed to determine the geographic distribution of the primary and secondary dengue cases in India., Methods: A multicentre cross-sectional study was conducted at Department of Health Research / Indian Council of Medical Research (DHR)/(ICMR) viral research and diagnostic laboratories (VRDLs) and selected ICMR institutes located in India. Only laboratory-confirmed dengue cases with date of onset of illness less than or equal to seven days were included between September and October 2017. Dengue NS1 antigen ELISA and anti-dengue IgM capture ELISA were used to diagnose dengue cases while anti-dengue IgG capture ELISA was used for identifying the secondary dengue cases., Results: Of the 1372 dengue cases, 897 (65%) were classified as primary dengue and 475 (35%) as secondary dengue cases. However, the proportion varied widely geographically, with Theni, Tamil Nadu; Tirupati, Andhra Pradesh and Udupi-Manipal, Karnataka reporting more than 65 per cent secondary dengue cases while Srinagar, Jammu and Kashmir reporting as low as 10 per cent of the same. The median age of primary dengue cases was 25 yr [interquartile range (IQR 17-35] while that of secondary dengue cases was 23 yr (IQR 13.5-34). Secondary dengue was around 50 per cent among the children belonging to the age group 6-10 yr while it ranged between 20-43 per cent among other age groups., Interpretation & Conclusions: Our findings showed a wide geographical variation in the distribution of primary and secondary dengue cases in India. It would prove beneficial to include primary and secondary dengue differentiation protocol in the national dengue surveillance programme., Competing Interests: None

Background: The WHO dengue classification 1997 was revised in 2009 and the revised classification system has now been in use for the past decade. This study was carried out to compare the 1997 and revised classifications in assessing the severity of dengue infection among all age groups during a dengue outbreak in southwest India., Methodology: This retrospective cross-sectional study was carried out including serologically confirmed dengue cases. A total of 1033 dengue cases were classified on the basis of the 1997 WHO classification and 2009 revised classification. The statistical analysis was carried out using SPSS 15.0 for Windows (SPSSTM Inc, Chicago, IL, USA)., Results: Both the 1997 and revised WHO classifications were applied to 1033 confirmed dengue cases, including 692 males (67%) and 341 females (33%). The median age of the study participants was 23 years (IQR 10-33), including 112 (10.8%) children at and below the age of 5 years. The level of agreement between the two systems of classification was poor (kappa=0.143, 0.055-0.198, p-value <0.001)., Conclusion: A greater sensitivity and specificity of the revised classification was observed in comparison with the 1997 WHO classification. In the context of changing dengue epidemiology and geographical expansion, the revised classification is helpful in the identification of severe cases, facilitating timely management.

Dengue is the most prevalent arboviral disease affecting humans, with tropical and subtropical regions having the highest risk of dengue virus infections. The clinical symptoms often range from mild fever to fever with hemorrhagic manifestations and shock. Since 2010, India has been witnessing a marked increase in the number of dengue virus serotype 1 (DENV-1) infections, apart from those of serotypes 2 (DENV-2) and 3 (DENV-3). The present study was undertaken to understand the circulating genotypes of DENV-1 in South West India, by sequencing the envelope gene of DENV-1 samples representative of the 2014-2015 time period. The extracted RNAs from dengue NS1 antigen ELISA-positive samples, archived at the APEX Referral Laboratory for Arboviruses (National Vector Borne Disease Control Programme, Manipal Centre for Virus Research), were used for the study. The currently circulating genotypes of DENV-1 identified from the study area belong to genotypes V and I. Multicentric laboratory-based studies analyzing the envelope gene of all dengue serotypes are required from endemic countries like India.