Clinico Virological Characterization of Hand, Foot and Mouth Disease in a Tertiary Care Hospital, South India.

Introduction: Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease, caused by enteroviruses (EVs) which can present with typical or atypical lesions. Although the disease is self-limiting, it can also lead to serious complications. In the era of polio eradication, it is important to understand the population dynamics of enteroviruses causing HFMD as one of the circulating strains may become dominant. Methods: It was a collaborative study carried out in the Department of Dermatology and Microbiology of a tertiary care teaching hospital. The throat swabs were collected from 132 suspected HFMD cases. Real-time polymerase chain reaction (PCR) was performed to detect the presence of pan enteroviruses, followed by genotype-specific PCR targeting Human Enterovirus 71 (HEV-71) and Coxsackie virus A16 (CVA-16) and CVA-6 for pan Enterovirus-positive samples. Follow-up samples were collected from 14 children in the 2nd week and subjected to molecular testing to detect enteroviruses. Results: Among 132 children suspected to have HFMD, 44 were girls and 88 were boys, and the majority of them 76.5% (101/132) were under 2 years of age. A history of exposure to a similar clinical presentation was present in 15 children. Of 132 suspected cases, 60 samples (45.5%) were positive for pan Enterovirus. The predominantly circulating genotype was found to be CVA-6 (31.6% [19/60]). There were about 10 cases (16.6%) which had co-infection with both HEV71 and CVA-6. Rash with fever was the most common presentation (57%). In most of the cases with HEV 71, 92.3% (12/13) presented within 3 days of illness to the health-care facility. Of 60 positive cases, 25% (15/60) of children had the atypical distribution of rashes in the face, trunk, genitalia, thigh, neck, and axilla and 16.7% of children (10/60) had the atypical type of lesion either only papular lesions or erythema multiforme. Out of 14 follow-up samples, 13 were negative for EVs; one was positive for pan EV in the 2nd week, however, the patient lost to follow-up after that. Conclusion: HFMD outbreaks in our region were caused by various genotypes of enteroviruses. No severe complications were seen in the affected children. Nearly 30% had atypical presentation either in the form of lesion or site. Robust molecular epidemiological surveillance of HFMD is required to know the strain variations and other emerging genotypes in our setup.

Emergence of dengue virus 4 as the predominant serotype during the outbreak of 2017 in South India.

Context: Dengue virus (DENV) causes acute febrile illness in tropical and subtropical countries. In India there is a steady increase in incidence since 1950s which could be attributed to emergence of new serotype or lineage\clade shifts in circulating DENV. Aims: We aimed to perform molecular characterisation and phylogenetic analysis on samples from the recent outbreak (August-October 2017). Settings and Design: Retrospective epidemiological analysis of dengue outbreak. Subjects and Methods: Samples positive for non-steroidal 1 antigen by enzyme-linked immunosorbent assay (n = 147) were included. The study was approved by our institute ethics committee (JIP/IEC/2018/496). Five hundred and eleven base pair of capsid and pre-membrane encoding genes (CprM) region was amplified using Lanciotti primers, followed by second round of polymerase chain reaction using serotype specific primers. Samples which were positive by second round (n = 68) were sequenced and genotyped using Basic Local Alignment Search Tool analysis and phylogenetic tree was constructed by MEGA7 software. Results: Phylogenetic analysis of CprM sequences identified all 4 serotypes in circulation during this outbreak. We observed both single (n = 50) and concurrent infections (n = 18), with DENV4 as the major contributor (64%). Within Genotype I of DENV4 we observed a distinct new clade (Clade E) which was 2.6% ± 0.9%-5.5% ± 1.1% divergent from the other clades. Among the concurrent infection, DENV 4 and DENV 2 combination was observed to form the majority (77.8%). Conclusions: Overall this study documents the emergence of DENV4 as the major serotype in circulation, replacing DENV1, 2 and 3 which had been previously reported from Tamil Nadu and Puducherry. This substantiates the need for continuous monitoring in endemic countries like India, where such data may impact the formulation of vaccine policy for dengue.

Family-Based Genome-Wide Association Study of South Indian Pedigrees Supports WNT7B as a Central Corneal Thickness Locus.

Purpose: To identify genetic risk factors contributing to central corneal thickness (CCT) in individuals from South India, a population with a high prevalence of ocular disorders. Methods: One hundred ninety-five individuals from 15 large South Indian pedigrees were genotyped using the Omni2.5 bead array. Family-based association for CCT was conducted using the score test in MERLIN. Results: Genome-wide association study (GWAS) identified strongest association for single nucleotide polymorphisms (SNPs) in the first intron of WNT7B and CCT (top SNP rs9330813; ß = -0.57, 95% confidence interval [CI]: -0.78 to -0.36; P = 1.7 × 10-7). We further investigated rs9330813 in a Latino cohort and four independent European cohorts. A meta-analysis of these data sets demonstrated statistically significant association between rs9330813 and CCT (ß = -3.94, 95% CI: -5.23 to -2.66; P = 1.7 × 10-9). WNT7B SNPs located in the same genomic region that includes rs9330813 have previously been associated with CCT in Latinos but with other ocular quantitative traits related to myopia (corneal curvature and axial length) in a Japanese population (rs10453441 and rs200329677). To evaluate the specificity of the observed WNT7B association with CCT in the South Indian families, we completed an ocular phenome-wide association study (PheWAS) for the top WNT7B SNPs using 45 ocular traits measured in these same families including corneal curvature and axial length. The ocular PheWAS results indicate that in the South Indian families WNT7B SNPs are primarily associated with CCT. Conclusions: The results indicate robust evidence for association between WNT7B SNPs and CCT in South Indian pedigrees, and suggest that WNT7B SNPs can have population-specific effects on ocular quantitative traits.