Serotype‐specific differences in the laboratory parameters among hospitalized children with dengue and genetic diversity of dengue viruses circulating in Tamil Nadu, India during 2017

Abstract

In 2017, Tamil Nadu, a southern state, had the second highest number of dengue cases from India. In the present study, the serotype‐specific differences in the clinical manifestations and laboratory parameters among hospitalized children with dengue were investigated and molecular characterization of the circulating dengue virus (DENV) serotypes during 2017 in Tamil Nadu was performed. Eighty children with dengue‐like symptoms consecutively admitted to a tertiary care hospital and positive for DENV NS1 antigen were investigated for DENV serotype utilizing a real‐time reverse transcriptase based polymerase chain reaction assay. Complete envelope (E) gene sequencing of the DENV strains was performed. Seventy samples were positive for serotyping (25 DENV‐1, 17 DENV‐2, six DENV‐3, and 22 DENV‐4). DENV‐4 infections were associated with elevated levels of liver enzymes; Alanine aminotransferase (P = .021) and aspartate aminotransferase (P = .001). However, none of the serotype was associated with any specific clinical features and severe dengue. Asian and American/African genotypes of DENV‐1 were cocirculating. The circulating genotype was cosmopolitan for DENV‐2 with multiple lineages, genotype III for DENV‐3 and genotype I for DENV‐4. Unique mutations were present in the 2017 DENV‐4 isolates. The present study suggests the association of DENV‐4 with elevated liver enzymes in children hospitalized for dengue. Further, the study reports the genetic diversity of DENV circulating in Tamil Nadu during 2017. The study calls for continuous monitoring of the circulating serotypes and genotypes at regional level in India which might result in a region wise database useful in predicting future outbreaks.

Emergence of Dengue 4 as Dominant Serotype During 2017 Outbreak in South India and Associated Cytokine Expression Profile

“… Rajesh and colleagues (2019) have reported high cases of hepatomegaly in DENV-4 during the 2017 dengue epidemic in Tamil Nadu, which is similar to our observation ( Tables 1 , S7 ). The γδ T cells of the liver are the major contributor of IL-17 during DENV infection ( Guabiraba and Ryffel, 2014 ).…”

“…In this study, we have documented the co-circulation of all four serotypes in Madurai, Tamil Nadu during the 2017 outbreak. Though DENV-4, a rare serotype, has been isolated from various parts of India ( Cecilia et al., 2011 ; Dash et al., 2011 ; Kumar et al., 2013 ; Shrivastava et al., 2018 ; Rajesh et al., 2019 ), ours is the first report on DENV-4 as a dominant serotype during an outbreak after 1968 (49 years) in Tamil Nadu.…”

“… Clapham and colleagues (2015) have shown serotype-specific primary infection in infants (<1 year old) and children aged ≥1 year old causing dengue severity DHF/DSS, where DENV-2 ( Kliks et al., 1988 ) and DENV-4 cause disease severity in the presence of dengue antibody from maternal transfer. Another interesting factor is that DENV-3 ( Kalayanarooj and Nimmannitya, 2000 ; Souza et al., 2007 ) and DENV-4 ( Kalayanarooj and Nimmannitya, 2000 ; Rajesh et al., 2019 ) have been shown to be associated with serotype-specific DHF/DSS in primary infection by correlating the elevation level of liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Japanese encephalitis virus (JEV) vaccine or prior infection has also been shown to increases DENV severity in children ( Anderson et al., 2011 ; Jeewandara et al., 2015 ).…”

“…Though DENV-3 was circulating in India, this serotype dominated only in few outbreaks, during 2003–04 in Northern India ( Dash et al., 2006 ) and in Pondicherry ( Hoti et al., 2006 ). Most of the DENV-3 isolates from India during 1966–2017 ( Dash et al., 2006 ; Hoti et al., 2006 ; Patil et al., 2012 ; Manakkadan et al., 2013 ; Cecilia et al., 2017 ; Rajesh et al., 2019 ; Parveen et al., 2019 ) fall under GIII. According to Lanciotti and colleagues (1994) , the GIII subtype originated from India (Vellore 1966) and spread to other parts of the world, which is further confirmed from our phylogenetic analysis.…”

Diagnosis and serotyping of dengue using cost-effective high-resolution melting curve based real time PCR

“…One study has reported the absence of link between dengue severity and serotypes (Rao et al, 2020). Few other studies argue that dengue severity is associated with DENV serotype (Vaughn et al, 2000;Kalayanarooj and Nimmannitya, 2000;Endy et al, 2002;Nisalak et al, 2003;Kumaria, 2010;Vicente et al, 2016;Rajesh et al, 2020;Gupta et al, 2021). In particular DENV-3 serotype has been found to be associated with severe dengue in many studies (Kalayanarooj and Nimmannitya, 2000;Endy et al, 2002;Nisalak et al, 2003;Kumaria, 2010).…”