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BackgroundInfluenza surveillance is an important tool to identify emerging/reemerging strains, and defining seasonality. We describe the distinct patterns of circulating strains of the virus in different areas in India from 2009 to 2013.MethodsPatients in ten cities presenting with influenza like illness in out-patient departments of dispensaries/hospitals and hospitalized patients with severe acute respiratory infections were enrolled. Nasopharangeal swabs were tested for influenza viruses by real-time RT-PCR, and subtyping; antigenic and genetic analysis were carried out using standard assays.ResultsOf the 44,127 ILI/SARI cases, 6,193 (14.0%) were positive for influenza virus. Peaks of influenza were observed during July-September coinciding with monsoon in cities Delhi and Lucknow (north), Pune (west), Allaphuza (southwest), Nagpur (central), Kolkata (east) and Dibrugarh (northeast), whereas Chennai and Vellore (southeast) revealed peaks in October-November, coinciding with the monsoon months in these cities. In Srinagar (Northern most city at 34°N latitude) influenza circulation peaked in January-March in winter months. The patterns of circulating strains varied over the years: whereas A/H1N1pdm09 and type B co-circulated in 2009 and 2010, H3N2 was the predominant circulating strain in 2011, followed by circulation of A/H1N1pdm09 and influenza B in 2012 and return of A/H3N2 in 2013. Antigenic analysis revealed that most circulating viruses were close to vaccine selected viral strains.ConclusionsOur data shows that India, though physically located in northern hemisphere, has distinct seasonality that might be related to latitude and environmental factors. While cities with temperate seasonality will benefit from vaccination in September-October, cities with peaks in the monsoon season in July-September will benefit from vaccination in April-May. Continued surveillance is critical to understand regional differences in influenza seasonality at regional and sub-regional level, especially in countries with large latitude span.

BackgroundThe burden estimation studies for respiratory syncytial virus (RSV) have been based on varied case definitions, including case–definitions designed for influenza surveillance systems. We used all medical admissions among children aged 0–59 months to study the effect of case definitions on estimation of RSV–associated hospitalizations rates.MethodsThe hospital–based daily surveillance enrolled children aged 0–59 months admitted with acute medical conditions from July 2009–December 2012, from a well–defined rural population in Ballabgarh in northern India. All study participants were examined and nasal and throat swabs taken for testing by real–time polymerase chain reaction (RT–PCR) for RSV and influenza virus. Clinical data were used to retrospectively evaluate World Health Organization (WHO) case definitions (2011) commonly used for surveillance of respiratory pathogens, ie, acute respiratory illness (WHO–ARI), severe ARI (SARI) and influenza–like illness (ILI), for determination of RSV–associated hospitalization. RSV–associated hospitalization rates adjusted for admissions at non–study hospitals were calculated.FindingsOut of 505 children enrolled, 82 (16.2%) tested positive for RSV. Annual incidence rates of RSV–associated hospitalization per 1000 children were highest among infants aged 0–5 months (15.2; 95% confidence interval (CI) 8.3–26.8), followed by ages 6–23 months (5.3, 95% CI 3.2–8.7) and lowest among children 24–59 months (0.5, 95% CI 0.1–1.5). The RSV positive children were more likely to have signs of respiratory distress like wheeze, chest in–drawing, tachypnea, and crepitation compared to RSV–negative based on bivariate comparisons. Other less commonly seen signs of respiratory distress, ie, nasal flaring, grunting, accessory muscle usage were also significantly associated with being RSV positive. Compared to the estimated RSV hospitalization rate based on all medical hospitalizations, the WHO–ARI case definition captured 86% of the total incidence, while case definitions requiring fever like ILI and SARI underestimated the incidence by 50–80%.ConclusionsOur study suggests that RSV is a substantial cause of hospitalization among children aged <24months especially those aged <6 months. The WHO–ARI case definition appeared to be the most suitable screening definition for RSV surveillance because of its high sensitivity.

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Background Influenza illness burden is substantial, particularly among young children, older adults, and those with underlying conditions. Initiatives are underway to develop better global estimates for influenza-associated hospitalizations and deaths. Knowledge gaps remain regarding the role of influenza viruses in severe respiratory disease and hospitalizations among adults, particularly in lower-income settings. Methods and findings We aggregated published data from a systematic review and unpublished data from surveillance platforms to generate global meta-analytic estimates for the proportion of acute respiratory hospitalizations associated with influenza viruses among adults. We searched 9 online databases (Medline, Embase, CINAHL, Cochrane Library, Scopus, Global Health, LILACS, WHOLIS, and CNKI; 1 January 1996–31 December 2016) to identify observational studies of influenza-associated hospitalizations in adults, and assessed eligible papers for bias using a simplified Newcastle–Ottawa scale for observational data. We applied meta-analytic proportions to global estimates of lower respiratory infections (LRIs) and hospitalizations from the Global Burden of Disease study in adults ≥20 years and by age groups (20–64 years and ≥65 years) to obtain the number of influenza-associated LRI episodes and hospitalizations for 2016. Data from 63 sources showed that influenza was associated with 14.1% (95% CI 12.1%–16.5%) of acute respiratory hospitalizations among all adults, with no significant differences by age group. The 63 data sources represent published observational studies (n = 28) and unpublished surveillance data (n = 35), from all World Health Organization regions (Africa, n = 8; Americas, n = 11; Eastern Mediterranean, n = 7; Europe, n = 8; Southeast Asia, n = 11; Western Pacific, n = 18). Data quality for published data sources was predominantly moderate or high (75%, n = 56/75). We estimate 32,126,000 (95% CI 20,484,000–46,129,000) influenza-associated LRI episodes and 5,678,000 (95% CI 3,205,000–9,432,000) LRI hospitalizations occur each year among adults. While adults <65 years contribute most influenza-associated LRI hospitalizations and episodes (3,464,000 [95% CI 1,885,000–5,978,000] LRI hospitalizations and 31,087,000 [95% CI 19,987,000–44,444,000] LRI episodes), hospitalization rates were highest in those ≥65 years (437/100,000 person-years [95% CI 265–612/100,000 person-years]). For this analysis, published articles were limited in their inclusion of stratified testing data by year and age group. Lack of information regarding influenza vaccination of the study population was also a limitation across both types of data sources. Conclusions In this meta-analysis, we estimated that influenza viruses are associated with over 5 million hospitalizations worldwide per year. Inclusion of both published and unpublished findings allowed for increased power to generate stratified estimates, and improved representation from lower-income countries. Together, the available data demonstrate the importance of influenza viruses as a cause of severe disease and hospitalizations in younger and older adults worldwide.

Signal transduction by the IL-36 receptor (IL-36R) is linked to several human diseases. However, the structure and function of the IL-36R is not well understood. A molecular model of the IL-36R complex was generated and a cell-based reporter assay was established to assess the signal transduction of recombinant subunits of the IL-36R. Mutational analyses and functional assays have identified residues of the receptor subunit IL-1Rrp2 needed for cytokine recognition, stable protein expression, disulfide bond formation and glycosylation that are critical for signal transduction. We also observed that, overexpression of ectodomain (ECD) of Il-1Rrp2 or IL-1RAcP exhibited dominant-negative effect on IL-36R signaling. The presence of IL-36 cytokine significantly increased the interaction of IL-1Rrp2 ECD with the co-receptor IL-1RAcP. Finally, we found that single nucleotide polymorphism A471T in the Toll-interleukin 1 receptor domain (TIR) of the IL-1Rrp2 that is present in ϳ2% of the human population, down-regulated IL-36R signaling by a decrease of interaction with IL-1RAcP.

BackgroundDespite acute respiratory infections being a major cause of death among children in developing countries including India, there is a lack of community-based studies that document its burden and aetiology.MethodsA dynamic cohort of children aged 0–10 years was established in four villages in a north Indian state of Haryana from August 2012 onwards. Trained health workers conducted weekly home visits to screen children for acute respiratory infection (ARI) defined as one of the following: cough, sore throat, nasal congestion, earache/discharge, or breathing difficulty. Nurses clinically assessed these children to grade disease severity based on standard age-specific guidelines into acute upper or lower respiratory infection (AURI or ALRI) and collected nasal/throat swabs for pathogen testing.ResultsOur first year results show that ARI incidence in 0–10 years of age was 5.9 (5.8–6.0) per child-year with minimal gender difference, the ALRI incidence in the under-five age group was higher among boys (0.43; 0.39–0.49) as compared to girls (0.31; 0.26–0.35) per child year. Boys had 2.4 times higher ARI-related hospitalization rate as compared to girls.ConclusionARI impose a significant burden on the children of this cohort. This study platform aims to provide better evidence for prevention and control of pneumonia in developing countries.

The seasonality of influenza in the tropics complicates vaccination timing. We investigated influenza seasonality in northern India and found influenza positivity peaked in Srinagar (34.09°N) in January–March but peaked in New Delhi (28.66°N) in July–September. Srinagar should consider influenza vaccination in October–November, but New Delhi should vaccinate in May–June.