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Introduction: We evaluated knowledge, attitudes, and practices (KAP) related to influenza and influenza vaccination among pregnant women in three selected countries. Methods: During 2017, pregnant women seeking antenatal care at hospitals at participating sites were enrolled. We described characteristics and responses to KAP questions. We also evaluated predictors associated with influenza vaccination during pregnancy at sites with substantial influenza vaccine uptake by multivariable logistic regression. Results: Overall, 4,648 pregnant women completed the survey. There were substantial differences among the three survey populations; only 8% of the women in Nagpur had heard of influenza, compared to 90% in Lima and 96% in Bangkok (p-value

Summary: Background: Paediatric vaccination against influenza can result in indirect protection, by reducing transmission to their unvaccinated contacts. We investigated whether influenza vaccination of children would protect them and their household members in a resource-limited setting. Methods: We did a cluster-randomised, blinded, controlled study in three villages in India. Clusters were defined as households (ie, dwellings that shared a courtyard), and children aged 6 months to 10 years were eligible for vaccination as and when they became age-eligible throughout the study. Households were randomly assigned (1:1) by a computer-based system to intramuscular trivalent inactivated influenza vaccine (IIV3) or a control of inactivated poliovirus vaccine (IPV) in the beginning of the study; vaccination occurred once a year for 3 years. The primary efficacy outcome was laboratory-confirmed influenza in a vaccinated child with febrile acute respiratory illness, analysed in the modified intention-to-treat population (ie, children who received at least one dose of vaccine, were under surveillance, and had not an influenza infection within 15 days of last vaccine dose). The secondary outcome for indirect effectiveness (surveillance study) was febrile acute respiratory illness in an unvaccinated household member of a vaccine study participant. Data from each year (year 1: November, 2009, to October, 2010; year 2: October, 2010, to October, 2011; and year 3: October, 2011, to May, 2012) were analysed separately. Safety was analysed among all participants who were vaccinated with at least one dose of the vaccine. This trial is registered with ClinicalTrials.gov, number NCT00934245. Findings: Between Nov 1, 2009, to May 1, 2012, we enrolled 3208 households, of which 1959 had vaccine-eligible children. 1010 households were assigned to IIV3 and 949 households were assigned to IPV. In 3 years, we vaccinated 4345 children (2132 with IIV3 and 2213 with IPV) from 1868 households (968 with IIV3 and 900 with IPV) with 10 813 unvaccinated household contacts. In year 1, influenza virus was detected in 151 (10%) of 1572 IIV3 recipients and 206 (13%) of 1633 of IPV recipients (total IIV3 vaccine efficacy 25·6% [95% CI 6·8–40·6]; p=0·010). In year 2, 105 (6%) of 1705 IIV3 recipients and 182 (10%) of 1814 IPV recipients had influenza (vaccine efficacy 41·0% [24·1–54·1]; p

Historical specimens collected from hospitalized children were tested for the following 13 viruses: influenza A and B; respiratory syncytial virus (RSV); parainfluenza viruses 1–3; human metapneumovirus; rhinovirus; coronaviruses 229E, OC43, NL63 and HKU1 and Adenovirus using monoplex real-time reverse transcriptase polymerase chain reaction (rRT-PCR). They were retested using TaqMan Array Card (TAC), a micro-fluidic system, capable of simultaneous multi-pathogen testing, to evaluate its sensitivity and specificity against monoplex rRT-PCR. TAC showed high sensitivity (71%–100%) and specificity (98%–100%) for these viruses in comparison to monoplex rRT-PCR. Multi-specimen detection with high sensitivity and specificity makes TAC a potentially useful tool for both surveillance and outbreak investigations.

Background There are limited data on incidence, risk factors and etiology of acute lower respiratory tract infection (LRTI) among older adults in low- and middle-income countries. Methods We established a cohort of community dwelling older adults ≥60 years and conducted weekly follow-up for acute respiratory infections (ARI) during 2015-2017. Nurses assessed ARI cases for LRTI, collecting combined nasal/throat swabs from all LRTI cases and an equal number of age- and sex-matched asymptomatic neighbourhood controls. Swabs were tested for influenza viruses, respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and parainfluenza viruses (PIV) using polymerase chain reaction. LRTI and virus-specific LRTI incidence was calculated per 1000 person-years. We estimated adjusted incidence rate ratios (IRR) for risk factors using Poisson regression and calculated etiologic fractions (EF) using adjusted odds ratios for detection of viral pathogens in LRTI cases vs controls. Results We followed 1403 older adults for 2441 person-years. LRTI and LRTI-associated hospitalization incidences were 248.3 (95% confidence interval (CI) = 229.3-268.8) and 12.7 (95% CI = 8.9-18.1) per 1000 person-years. Persons with pre-existing chronic bronchitis as compared to those without (incidence rate ratio (IRR) = 4.7, 95% CI = 3.9-5.6); aged 65-74 years (IRR = 1.6, 95% CI = 1.3-2.0) and ≥75 years (IRR = 1.8, 95% CI = 1.4-2.4) as compared to 60-64 years; and persons in poorest wealth quintile (IRR = 1.4, 95% CI = 1.1-1.8); as compared to those in wealthiest quintile were at higher risk for LRTI. Virus was detected in 10.1% of LRTI cases, most commonly influenza (3.8%) and RSV (3.0%). EF for RSV and influenza virus was 83.9% and 83.6%, respectively. Conclusion In this rural cohort of older adults, the incidence of LRTI was substantial. Chronic bronchitis was an important risk factor; influenza virus and RSV were major viral pathogens.

Background Influenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years. Methods and findings In June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years. Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year. In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted. Conclusions In this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children. Trial registration Clinical Trials Registry of India CTRI/2015/06/005902., Anand Krishnan and co-workers study the efficacy and safety of influenza vaccines for children in India., Author summary Why was this study done? In recent years, 2 community-based trials of the single-dose Russian-backbone live attenuated influenza vaccine (LAIV) in low- and middle-income countries (LMIC) have been published, with contrasting results. In Senegal, LAIV vaccine efficacy (VE) was demonstrated to be 0.0% (95% confidence interval (CI) −26.4 to 20.9), and in Bangladesh, LAIV VE was demonstrated to be 41.0% (95% CI 28.0 to 51.6) against all influenza virus strains. In addition, observational studies for VE of LAIV such as in the United States and Europe have also shown mixed results. While the World Health Organization (WHO) continues to recommend LAIV use in children, conflicting data on LAIV have led countries to review and reconsider national preferential recommendations for LAIV use in children. Given these gaps in evidence and the potential for indigenously produced LAIV to be used for prevention of influenza virus infection in Indian children, we evaluated the absolute efficacy of LAIV and inactivated influenza vaccine (IIV) and relative efficacy of LAIV versus IIV among children aged 2 to 10 years in rural India. What did the researchers do and find? We conducted a 2-year, triple (participant–observer–analyst) blind, community-based vaccine trial. We randomly assigned 3,041 children aged 2 to 10 years to receive age appropriate doses of LAIV, IIV, or a control vaccine. In Year 1, VE was 40.0% (95% CI 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). We found that LAIV and IIV were safe and moderately efficacious against laboratory-confirmed influenza virus infection. In Year 1, LAIV, as a single dose in a vaccine-naïve population, was significantly less efficacious than IIV, whereas in Year 2, VE for LAIV and IIV was similar. This was the first randomized controlled trial to our knowledge in a developing country setting that compared LAIV efficacy with IIV and provided VE by age group and influenza type/subtype across seasons spanning 2 consecutive years. Importantly, during both years, LAIV and IIV were protective against influenza A(H3N2) viruses. However, LAIV had limited efficacy against influenza A(H1N1)pdm09 for both years. What do these findings mean? Influenza vaccination is an important tool for preparedness and response against seasonal epidemics and pandemics. However, decisions on specific vaccine introductions into national immunization platforms depend on multiple factors including effectiveness, presence of existing immunization platforms and cold chain infrastructure, cost, and local production of the vaccines. Availability of indigenous, safe, and moderately efficacious influenza vaccines, including LAIV, should initiate discussion on the optimal use of vaccines for the national strategy for influenza prevention and control in India.

Background Influenza causes substantial morbidity and mortality worldwide, however, reliable burden estimates from developing countries are limited, including India. We aimed to quantify influenza-associated mortality for India utilizing 2010-2013 nationally representative data sources for influenza virus circulation and deaths. Methods Virological data were obtained from the influenza surveillance network of 10 laboratories led by National Institute of Virology, Pune covering eight states from 2010-2013. Death data were obtained from the nationally representative Sample Registration System for the same time period. Generalized linear regression with negative binomial distribution was used to model weekly respiratory and circulatory deaths by age group and proportion of specimens positive for influenza by subtype; excess deaths above the seasonal baseline were taken as an estimate of influenza-associated mortality counts and rates. Annual excess death rates and the 2011 India Census data were used to estimate national influenza-associated deaths. Results Estimated annual influenza-associated respiratory mortality rates were highest for those ≥65 years (51.1, 95% confidence interval (CI) = 9.2-93.0 deaths/100 000 population) followed by those

Evidence on influenza vaccine effectiveness from low and middle countries (LMICs) is limited due to limited institutional capacities; lack of adequate resources; and lack of interest by ministries of health for influenza vaccine introduction. There are concerns that the highest ethical standards will be compromised during trials in LMICs leading to mistrust of clinical trials. These factors pose regulatory and operational challenges to researchers in these countries. We conducted a community-based vaccine trial to assess the efficacy of live attenuated influenza vaccine and inactivated influenza vaccine in rural north India. Key regulatory challenges included obtaining regulatory approvals, reporting of adverse events, and compensating subjects for trial-related injuries; all of which were required to be completed in a timely fashion. Key operational challenges included obtaining audio-visual consent; maintaining a low attrition rate; and administering vaccines during a narrow time period before the influenza season, and under extreme heat. We overcame these challenges through advanced planning, and sustaining community engagement. We adapted the trial procedures to cope with field conditions by conducting mock vaccine camps; and planned for early morning vaccination to mitigate threats to the cold chain. These lessons may help investigators to confront similar challenges in other LMICs.

Background No estimates of influenza-associated mortality exist for India. Objective To evaluate national mortality and viral surveillance data from India for assessing their appropriateness in estimating influenza-associated mortality using varied analytic approaches. Methods We reviewed influenza virus surveillance data from a national influenza surveillance network. We also reviewed national mortality data from Civil Registration System (CRS), Medical Certification of Cause of Death (MCCD) and the Sample Registration System (SRS). We compared and scored the different sources of mortality data using specific criteria, including the process of cause of death assignment, sample size, proportion of ill-defined deaths, representativeness and availability of time series data. Each of these 5 parameters was scored on a scale from 1 to 5. To evaluate how to generate an influenza-associated mortality estimate for India, we also reviewed 4 methodologic approaches to assess the appropriateness of their assumptions and requirements for these data sets. Results The influenza virus surveillance data included year-round sample testing for influenza virus and was found to be suitable for influenza mortality estimation modelling. Based on scoring for the 5 mortality data criteria, the SRS data had the highest score with 20 of 25 possible score, whereas MCCD and CRS scored 16 and 12, respectively. The SRS which used verbal autopsy survey methods was determined to be nationally representative and thus adequate for estimating influenza-associated mortality. Evaluation of the modelling methods demonstrated that Poisson regression, risk difference and mortality multiplier methods could be applied to the Indian setting. Conclusion Despite significant challenges, it is possible to estimate influenza-associated mortality in India.

Background In India, community-based acute lower respiratory infections (ALRI) burden studies are limited, hampering development of prevention and control strategies. Methods We surveyed children

Background & objectives: Respiratory tract infections are common among Hajj and Umrah pilgrims which pose a public health risk of spread of respiratory infections. Influenza has been reported from Indian Hajj and Umrah returning pilgrims, but data on other respiratory pathogens are sparse in India. Here we report the presence of common respiratory viral pathogens in returning Hajj and Umrah pilgrims suffering from acute respiratory illness (ARI) in 2014-2015. Methods: Respiratory specimens (nasopharyngeal and throat swabs) were collected from 300 consenting pilgrims with ARI in the past one week and tested for influenza and Middle East Respiratory Syndrome coronavirus (MERS-CoV) and other respiratory viruses using in-house standardized quantitative real-time reverse-transcription polymerase chain reaction. Clinical features among the pathogen positive and negative patients were compared. The patients received symptomatic treatment and antivirals where appropriate and were followed telephonically to collect data on illness outcome. Results: Ninety seven (32.3%) of the 300 participants were tested positive for any virus, most common being influenza viruses (n=33, 11%). Other respiratory viruses that were detected included human coronaviruses [n=26, 8.7%; OC43 (n=19, 6.3%) and C229E (n=7, 2.3%)], rhinovirus (n=20, 6%), adenoviruses (n=8, 2.6%), parainfluenza viruses (n=7, 2.3%), respiratory syncytial virus (n=3, 1%) and bocaviruses (n=2, 0.6%). Clinical features observed in pathogen positive and pathogen negative patients did not differ significantly. Eighteen influenza positive patients were treated with oseltamivir. Interpretation & conclusions: Pilgrims returning from mass gatherings are often afflicted with respiratory pathogens with a potential to facilitate transmission of respiratory pathogens across international borders. The study reinforces the need for better infection prevention and control measures such as vaccination, health education on cough etiquette and hand hygiene.

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.

Background The increasing reports of Middle East Respiratory Syndrome (MERS) caused by MERS coronavirus (MERS-CoV) from many countries emphasize its importance for international travel. Muslim pilgrimages of Hajj and Umrah involve mass gatherings of international travellers. We set out to assess the presence of influenza and MERS-CoV in Hajj/Umrah returnees with acute respiratory infection. . Methods Disembarking passengers (n = 8753) from Saudi Arabia (October 2014 to April 2015) were interviewed for the presence of respiratory symptoms; 977 (11%) reported symptoms and 300 (age 26–90, median 60 years; 140 male) consented to participate in the study. After recording clinical and demographic data, twin swabs (nasopharyngeal and throat) were collected from each participant, pooled in viral transport media and tested by real-time RT PCR for MERS-CoV and influenza A and B viruses and their subtypes. Results The participants had symptoms of 1–15 days (median 5d); cough (90%) and nasal discharge (86%) being the commonest. None of the 300 participants tested positive for MERS-CoV; however, 33 (11%) tested positive for influenza viruses (A/H3N2 = 13, A/H1N1pdm09 = 9 and B/Yamagata = 11). Eighteen patients received oseltamivir. No hospitalizations were needed and all had uneventful recovery. Conclusion Despite a high prevalence of acute respiratory symptoms, MERS coV was not seen in returning pilgrims from Hajj and Umrah. However detection of flu emphasises preventive strategies like vaccination.

Objective To estimate rates of community-level influenza-like-illness (ILI) and influenza-associated ILI in rural north India. Methods During 2011, we conducted household-based healthcare utilization surveys (HUS) for any acute medical illness (AMI) in preceding 14days among residents of 28villages of Ballabgarh, in north India. Concurrently, we conducted clinic-based surveillance (CBS) in the area for AMI episodes with illness onset ≤3days and collected nasal and throat swabs for influenza virus testing using real-time polymerase chain reaction. Retrospectively, we applied ILI case definition (measured/reported fever and cough) to HUS and CBS data. We attributed 14days of risk-time per person surveyed in HUS and estimated community ILI rate by dividing the number of ILI cases in HUS by total risk-time. We used CBS data on influenza positivity and applied it to HUS-based community ILI rates by age, month, and clinic type, to estimate the community influenza-associated ILI rates. Findings The HUS of 69,369 residents during the year generated risk-time of 3945 person-years (p-y) and identified 150 (5%, 95%CI: 4–6) ILI episodes (38 ILI episodes/1,000 p-y; 95% CI 32–44). Among 1,372 ILI cases enrolled from clinics, 126 (9%; 95% CI 8–11) had laboratory-confirmed influenza (A (H3N2) = 72; B = 54). After adjusting for age, month, and clinic type, overall influenza-associated ILI rate was 4.8/1,000 p-y; rates were highest among children

Background The 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. Methods The 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. Findings Out 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%. Conclusions Our study suggests that RSV is a substantial cause of hospitalization among children aged

Background Despite 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. Methods A 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. Results Our 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. Conclusion ARI 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.