Changing trends in circulating rotavirus strains in Pune, western India in 2009–2012: Emergence of a rare G9P[4] rotavirus strain

AbstractBackgroundA vast diversity in rotaviruses at inter- and intra-genotypic level underscores the need for monitoring of circulating rotavirus strains. The aim of this study was to update the data on rotavirus disease and strains for the period from January 2009 to December 2012 in Pune, western India which has been one of the sites of the Indian Rotavirus Strain Surveillance Network since November 2005.MethodsChildren aged <5 years admitted for acute gastroenteritis in three different hospitals from Pune city were included in the study. The stool specimens were collected and tested for rotavirus antigen by a commercial enzyme immunoassay. The rotavirus strains were genotyped by multiplex reverse transcription polymerase chain reaction.ResultsDuring the study period, we found 35.1% of 685 stool specimens contained rotavirus antigen. Frequency of rotavirus detection was greatest (58.5%) among children aged 7–12 months. The G1P[8] (31.4%), G2P[4] (20.2%) and G9P[8] (11.8%) strains were the most common types. We noted predominance of G1P[8] strains (39.6%-46.1%) in all the years of study except 2009 wherein G9P[8] strains scored highest level (15.3%). Subsequent to this, we identified G9P[8] strains at the second highest position in 2010, their sudden decline and rise in G9P[4] strains in 2011–2012. We detected G12 strains in combination with P[6] and P[8] at variable rates (0–10.2%) and highest level (27.1%) of mixed rotavirus infections in 2009 as compared to 2010–2012 (0–3.8%).ConclusionThe study highlights the huge burden of rotavirus disease and changing profile of circulating rotavirus strains displaying emergence of G9P[4] reassortant strains in Pune, western India and emphasizes the need to analyze the entire genomic constellation of rotavirus strains for better evaluation of the impact of rotavirus

Insights from global data for use of rotavirus vaccines in India

Rotavirus vaccines are being introduced in several low- and middle-income countries across the world with and without support from the GAVI Alliance. India has the highest disease burden of rotavirus based on morbidity and mortality estimates and several indigenous vaccine manufacturers are developing rotavirus vaccines. One candidate has undergone phase III testing and others have completed evaluation in phase II. Global data on licensed vaccine performance in terms of impact on disease, strain diversity, safety and cost-effectiveness has been reviewed to provide a framework for decision making in India

Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from a meta-analysis of 13,000 Salmonella Typhi genomes

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal ‘sentinel’ surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. Conclusions: The consortium’s aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies

Nations within a nation: variations in epidemiological transition across the states of India, 1990–2016 in the Global Burden of Disease Study

18% of the world's population lives in India, and many states of India have populations similar to those of large countries. Action to effectively improve population health in India requires availability of reliable and comprehensive state-level estimates of disease burden and risk factors over time. Such comprehensive estimates have not been available so far for all major diseases and risk factors. Thus, we aimed to estimate the disease burden and risk factors in every state of India as part of the Global Burden of Disease (GBD) Study 2016

Fulminant hepatic failure: etiology, viral markers and outcome

Objective: To investigate the etiology and outcome of fulminant hepatic failure (FHF) in children. Setting: Hospital based descriptive. Methods: 36 children (22 males and 14 females) presenting with FHF over a period of one year were investigated. The ages ranged from 1.5 to 9 years. FHF was defined as occurrence of encephalopathy within eight weeks of onset of jaundice with no evidence of pre-existing liver disease. Detailed history, clinical examination, routine biochemical parameters and relevant diagnostic tests were carried out. Viral markers studied were anti HAV-IgM, HBsAg, anti HBc-IgM, anti-HCV and anti HEV-IgM. Results: A viral etiology could be established in 22 children (61.1%). Hepatitis A (n=12), Hepatitis B (n=3), Hepatitis A and B (n=2), and Hepatitis A and E (n=4). Two children had enteric fever (1 with associated HEV), 2 children had Wilson's disease, 1 child had Indian Childhood Cirrhosis (ICC) and 2 children had drug induced hepatitis. Etiological diagnosis was not possible in 8 children (22%). Fourteen children (39%) died. Poor outcome was associated with spontaneous bleeding, raised prothrombin time, lower transaminases and higher bilirubin on admission. Conclusion: Viral hepatitis is the commonest cause of FHF in children. HAV alone or in combination is responsible for upto 50% of all FHF in children. Chronic liver disease can also present as FHF. Etiological diagnosis is not possible to upto one-fourth of all cases

TNFA and IL10 Polymorphisms and IL-6 and IL-10 Levels Influence Disease Severity in Influenza A(H1N1)pdm09 Virus Infected Patients

Cytokines are key modulators of immune response, and dysregulated production of proinflammatory and anti-inflammatory cytokines contributes to the pathogenesis of influenza A(H1N1)pdm09 virus infection. Cytokine production is impacted by single nucleotide polymorphisms (SNPs) in the genes coding for them. In the present study, SNPs in the IL6, TNFA, IFNG, IL17A, IL10, and TGFB were investigated for their association with disease severity and fatality in influenza A(H1N1)pdm09-affected patients with mild disease (n = 293) and severe disease (n = 86). Among those with severe disease, 41 patients had fatal outcomes. In a subset of the patients, levels of IL-2, IL-4, IL-6, IL-10, TNF, IFN-&gamma;, and IL-17 were assayed in the plasma for their association with severe disease. The frequency of TNFA rs1800629 G/A allele was significantly higher in severe cases and survived severe cases group compared to that of those with mild infection (OR with 95% for mild vs. severe cases 2.95 (1.52&ndash;5.73); mild vs. survived severe cases 4.02 (1.84&ndash;8.82)). IL10 rs1800896-rs1800872 G-C haplotype was significantly lower (OR with 95% 0.34 (0.12&ndash;0.95)), while IL10 rs1800896-rs1800872 G-A haplotype was significantly higher (OR with 95% 12.11 (2.23&ndash;76.96)) in fatal cases group compared to that of the mild group. IL-6 and IL-10 levels were significantly higher in fatal cases compared to that of survived severe cases. IL-6 levels had greater discriminatory power than IL-10 to predict progression to fatal outcome in influenza A(H1N1)pdm09 virus-infected patients. To conclude, the present study reports the association of TNFA and IL10 SNPs with severe disease in Influenza A(H1N1)pdm09 virus-infected subjects. Furthermore, IL-6 levels can be a potential biomarker for predicting fatal outcomes in Influenza A(H1N1)pdm09 virus infected subjects

Triglyceride associated polymorphisms of the APOA5 gene have very different allele frequencies in Pune, India compared to Europeans

Background: the APOA5 gene variants, -1131T&gt;C and S19W, are associated with altered triglyceride concentrations in studies of subjects of Caucasian and East Asian descent. There are few studies of these variants in South Asians. We investigated whether the two APOA5 variants also show similar association with various lipid parameters in Indian population as in the UK white subjects. Methods: we genotyped 557 Indian adults from Pune, India, and 237 UK white adults for -1131T&gt;C and S19W variants in the APOA5 gene, compared their allelic and genotype frequency and determined their association with fasting serum triglycerides, total cholesterol, HDL and LDL cholesterol levels using univariate general linear analysis. APOC3 SstI polymorphism was also analyzed in 175 Pune Indian subjects for analysis of linkage disequilibrium with the APOA5 variants. Results: the APOA5 -1131C allele was more prevalent in Indians from Pune (Pune Indians) compared to UK white subjects (allele frequency 20% vs. 4%, p = 0.00001), whereas the 19W allele was less prevalent (3% vs. 6% p = 0.0015). Patterns of linkage disequilibrium between the two variants were similar between the two populations and confirmed that they occur on two different haplotypes. In Pune Indians, the presence of -1131C allele and the 19W allele was associated with a 19% and 15% increase respectively in triglyceride concentrations although only -1131C was significant (p = 0.0003). This effect size was similar to that seen in the UK white subjects. Analysis of the APOC3 SstI polymorphism in 175 Pune Indian subjects showed that this variant is not in appreciable linkage disequilibrium with the APOA5 -1131T&gt;C variant (r2 = 0.07). Conclusions: this is the first study to look at the role of APOA5 in Asian Indian subjects that reside in India. The -1131C allele is more prevalent and the 19W allele is less prevalent in Pune Indians compared to UK Caucasians. We confirm that the APOA5 variants are associated with triglyceride levels independent of ethnicity and that this association is similar in magnitude in Asian Indians and Caucasians. The -1131C allele is present in 36% of the Pune Indian population making it a powerful marker for looking at the role of elevated triglycerides in important conditions such as pancreatitis, diabetes and coronary heart disease