Comparison of etiology of sporadic acute and fulminant viral hepatitis in hospitalized patients in Pune, India during 1978-81 and 1994-97

Objective: To determine and compare the etiology of sporadic acute and fulminant viral hepatitis in two groups of patients 16 years apart. Methods: Serologic diagnostic tests for hepatitis A, B, C, D and E, and cytomegalovirus infection were carried out in 276 patients during 1994-1997 (Group A) and 206 patients during 1978-1981 (Group B). Results: Among children, hepatitis A virus was the major etiologic agent (81.6% in Group A and 51.4% in Group B), followed by hepatitis E virus (12.2%, 46.4%) and hepatitis B virus (5.4%, none). Among adults, hepatitis E virus was the main causative agent (42.4% in Group A and 71.2% in Group B) followed by HBV (28%, 25.5%) and hepatitis A virus (10.6%, 3.5%). Delta hepatitis was found only in Group A. No viral cause was found in 25% of patients in Group A and 13.5% patients in Group B. Conclusions: Hepatitis E virus is a major cause of sporadic acute and fulminant hepatitis. There has been an increase in hepatitis A in adults who developed fulminant hepatic failure. Our data points to the emergence of hepatitis A in adults and emergence of delta virus infection. Hepatitis C virus was unimportant in causing sporadic hepatitis

Genetic divergence of Chikungunya viruses in India (1963-2006) with special reference to the 2005-2006 explosive epidemic

Re-emergence of Chikungunya (CHIK), caused by CHIK virus, was recorded in India during 2005-2006 after a gap of 32 years, causing 1.3 million cases in 13 states. Several islands of the Indian Ocean reported similar outbreaks in the same period. These outbreaks were attributed to the African genotype of CHIK virus. To examine relatedness of the Indian isolates (IND-06) with Reunion Island isolates (RU), full-genome sequences of five CHIK virus isolates representative of different Indian states were determined. In addition, an isolate obtained from mosquitoes in the year 2000 (Yawat-2000), identified as being of the African genotype, and two older strains isolated in 1963 and 1973 (of the Asian genotype), were sequenced. The IND-06 isolates shared 99.9 % nucleotide identity with RU isolates, confirming involvement of the same strain in these outbreaks. The IND-06 isolates shared 98.2 % identity with the Yawat-2000 isolate. Of two crucial substitutions reported for RU isolates in the E1 region, M269V was noted in the Yawat-2000 and IND-06 isolates, whereas D284E was seen only in the IND-06 isolates. The A226V shift observed with the progression of the epidemic in Reunion Island, probably associated with adaptation to the mosquito vector, was absent in all of the Indian isolates. Three unique substitutions were noted in the IND-06 isolates: two (T128K and T376M) in the Nsp1 region and one (P23S) in the capsid protein. The two Asian strains showed 99.4 % nucleotide identity to each other, indicating relative stability of the virus. No evidence of recombination of the Asian and African genotypes, or of positive selection was observed. The results may help in understanding the association, if any, of the unique mutations with the explosive nature of the CHIK outbreak

Increased risk of hepatitis E in sewage workers from India

Considering feco-oral transmission of hepatitis E virus (HEV), the risk of the infection was assessed among sewage workers. On the basis of the close contact with sewage, the participants (n=147) were divided into sewage workers (n=92) and others (n=55); none used personal protective equipment (eg, coveralls, boots, gloves) Age-matched individuals from lower socioeconomic status and without any exposure to sewage were used as controls. IgG-anti-HEV positivity in enzyme-linked immunosorbent assay was significantly higher (P < 0.01) among staff members (83/147, 56.5%) than the controls (19%). A significant rise in anti-HEV positivity (P < 0.05) was recorded in sewage workers working for > 5 years. Multivariate regression analysis identified contact with sewage as the independent variable associated with anti-HEV positivity. Strict adherence to good working practices must take top priority for protection of these workers from sewage pathogens

Hepatitis G virus infection in India: prevalence and phylogenetic analysis based on 5' non-coding region

Objectives: To determine the prevalence of hepatitis G virus (HGV) infection in western India and to carry out phylogenetic analysis of HGV isolates. Methods: Reverse transcription-polymerase chain reaction (RT-PCR) assay was used to detect HGV RNA in serum samples obtained from paid plasma donors, patients with hemophilia and voluntary blood donors. Nine Indian and one Kenyan HGV RNA-positive samples were sequenced in the 5' non-coding region (5'-NCR). Phylogenetic analysis based on the comparison of a 101 nucleotide fragment from a large number of HGV isolates from 22 countries (including Indian and Kenyan sequences obtained during the present study) was carried out. Results: HGV RNA positivity rates among paid plasma donors from a commercial plasmapheresis unit (7/43, 16.3%) and patients with hemophilia (5/44, 11.4%) were significantly higher than that in voluntary blood donors (0/51; p=0.003 and 0.019, respectively). Among patients with acute non-A to E hepatitis and fulminant hepatic failure, 1 of 50 and 1 of 28 were HGV RNA-positive, whereas 6 of 49 (12%) patients with chronic liver disease had circulating HGV RNA. All Indian isolates belonged to genotype 2, whereas the Kenyan isolate formed a distinct branch within genotype 1 consisting of African isolates. Conclusion: Our results suggest existence of parenteral transmission of HGV in the Indian population. HGV was not an important cause of acute non-A to E hepatitis or fulminant hepatic failure among the patients investigated. Genotype 2 seems to be the most prevalent genotype in western India

Evolutionary rates and timescale comparison of Chikungunya viruses inferred from the whole genome/E1 gene with special reference to the 2005-07 outbreak in the Indian subcontinent

Chikungunya (CHIK) virus reemerged during 2005-07 as an important pathogen causing massive disease outbreaks affecting India and several countries of the Indian Ocean. Knowledge of the evolutionary rates and divergence times of the CHIK virus may help to better understand the disease epidemiology. Considering the limited availability of such information, we estimated the substitution rates and the ancestral times for all the CHIK genotypes and also the time to the most recent common ancestor (tMRCA) of the 2005-07 isolates. Using whole genomes and partial E1 gene datasets, we applied the Bayesian Markov Chain Monte Carlo (MCMC) framework that explicitly accounts for lineage-specific evolutionary rates through the use of 'relaxed' molecular clock models. Under a constant population relaxed clock model, the evolutionary timescale of CHIK viruses in this study was estimated to be in the last 300 years. The progenitor of the 2005-07 viruses was found to have existed around 9 years ago, and to have originated from Central Africa. The presence of a strain in India in 2000 that bears 99% identity with a Ugandan strain of 1982, which correlates with the tMRCA of the Indian and Indian Ocean isolates, confirms our earlier report that the progenitor of the 2005-07 isolates originates from Uganda's neighbourhood. The 'A226V' mutation that existed in the Indian Ocean isolates since late 2005 was found to occur only in the 2007 isolate from India. The study confirms the epidemiological data, specifically with regard to the re-emergence of CHIKV and throws light on the evolutionary dynamics of CHIK viruses

Neutralizing Antibody Response to Genotypically Diverse Measles Viruses in Clinically Suspected Measles Cases

The neutralizing antibody (Nt-Ab) response to vaccine and wild-type measles viruses (MeV) was studied in suspected measles cases reported during the years 2012–2016. The neutralization activity against MeV A, D4 and D8 genotypes was studied on sera (Panel A; n = 68 (measles-immunized) and Panel B; n = 50 (unvaccinated)) that were either laboratory confirmed or not confirmed by the presence of IgM antibodies. Additionally, the Nt-Ab response in Panel A was measured against the MeV vaccine and four wild-type viruses. Neutralization results were compared using homology modeling and molecular dynamics simulation (MDS) of MeV-hemagglutinin (H) and fusion (F) proteins. Overall, the Nt-Ab titres for MeV-A were found to be significantly lower than MeV-D4 and MeV-D8 viruses for Panel A. No major difference was noted in Nt-Ab titres between MeV-D8 viruses (Jamnagar and New Delhi), whereas MeV-D4 (Sindhudurg and Bagalkot (BGK) viruses) showed significant differences between Nt-Ab titres for Panel B. Interestingly, the substitutions observed in epitopes of H-protein, L249P and G316A are observed to be unique to MeV-BGK. MDS of H-protein revealed significant fluctuations in neutralizing epitopes due to L249P substitution. The majority of the clinically suspected cases showed Nt-Abs to MeV wild-types. Higher IgG antibody avidity and Nt-Ab titres were noted in IgM-negatives than in IgM-positives cases, indicating reinfection or breakthrough. MDS revealed reduced neutralization due to decreased conformational flexibility in the H-epitope