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Introduction Tuberculosis (TB) continues to be one of the deadliest infectious diseases over the centuries, killing more people worldwide than any other single infectious disease. There is an urgent need for additional strategies which can expedite efforts to combat TB including a preventive vaccine. In this endeavour, we have developed a protocol for a multisite, double-blind, placebo-controlled clinical trial in India that aims to evaluate the efficacy and safety of two TB vaccines; namely, VPM1002 and Immuvac (M.w) (Mycobacterium Indicus Pranii) (MIP) among healthy household contacts (HHCs) of sputum smear-positive pulmonary TB (PTB) patients.Methods and analysis In the three-arm randomised double-blind placebo-controlled trial study protocol, a total of 12 000 HHCs (aged 6−99 years) of sputum smear-positive PTB patients will be randomised to receive either of the two vaccine candidates VPM1002 and MIP or placebo. The primary efficacy endpoint is the prevention of microbiologically confirmed TB. Secondary endpoints will include (1) prevention against Latent TB infection, (2) incidence of adverse events and serious adverse events in study participants, (3) efficacy of vaccine in prevention of PTB/extra PTB in different age groups (6–18 years, 19–35 years, 36–60 years and above 60 years) and (4) immunogenicity of VPM1002 and MIP at month 2 and month 6 after first vaccination in terms of flow cytometric analysis of M.Tb specific CD4+ and CD8+ T cells secreting cytokines and Luminex assays for the presence of different cytokines in the sera and supernatants of peripheral blood mononuclear cells cultures stimulated with whole cell lysates of M.Tb and subsequently similar analysis for the cases who develop TB postvaccination during the follow-up period.Ethics and dissemination Ethics committees’ approvals have been granted by the Institutional Human Ethics Committees of all participating centres in this study and the names of the ethics committees and approvals are as follows: (1) National Institute for Research in Tuberculosis (NIRT)-Chennai (including subsites): ECR/135/Inst/TN/2013/RR-19, Approval No. 390/NIRT-Institutional Ethics Committee (IEC)/2018 dated 5 December 2018 (NIRT-Madurai-ECR/1365/Inst/TN/2020; approval dated 8 June 2020; NIRT, Vellore: ECR/1215/Inst/TN/2019; approval dated 26 September 2020); (2) All India Institute of Medical Sciences (AIIMS), Delhi (including subsites)-Institute Ethics Committee, ECR/547/Inst/DL/2014/RR-17 ECR/538/Inst/DL/2014/RR-20; approval No.IEC-385/06-07-2018, approval OP-28/05.04.2019 and SFH- ECR/593/Inst/DL/2014/RR-20 IEC/VMMC/SJH/project/2019-05/25 ; 23 May 2019; (3) National Institute of Tuberculosis and Respiratory Diseases (NITRD), Delhi: ECR/315/Inst/DL/2013/RR-19; approval IEC-No-NITRD/EC/2019/9004; 8 January 2019; (4) Pune-National AIDS Research Institute (NARI) and subsite-ECR/23/Inst/MH/2013/RR-19; IEC-NARI/EC/approval/2018/196; 29 May 2018; (5) Regional Medical Research Centre-Bhubaneshwar-ECR/911/Inst/OR-2017/RR-21; approval, dated 25 April 2018; Subsites- AIIMS, Bhubaneshwar ECR/534/Inst/OD/2014/RR-17 and 20 approval No. T/EMF/Pulm. Med/19/01 dated 13 May 2019; SCB, Cuttack No. No.ECR/84/Inst/OR/2013/RR-20; approval no.186 dated 7 February 2020; (6) NTI-Bengaluru: Ethics Committee-No-ECR/1819/Inst/KA/2019; approval No NTI-IEC/1.2019/principal investigator, dated 31 January 2019; (7) BMMRC, Hyderabad- ECR/450/Inst/AP/2013/RR-16 approval No. 779/BMMRC/2018/IEC, dated 11 June 2018 (Subsite Share India- Mediciti Ethics Committee-ECR/283/Inst/AP/2013/RR-20; Approval no. EC/11/VII/2K20(1) dated 11 July 2020) and (8) SJMC-Bengaluru: ECR/238/Inst/KA/2013/RR-19; approval IEC/1/491/2020; 7 August 2020.The trial findings will be published in accordance with the Consolidated Standards of Reporting Trials guidance. The results of this clinical trial will be presented at scientific conferences and disseminated through publications in peer-reviewed journals, conference presentations and shared with Ministry of Health and Family Welfare, policy-makers and other stakeholders.Trial registration number CTRI/2019/01/017026.

Background: The risk of tuberculosis (TB) disease is higher in individuals with TB infection. In a TB endemic country like India, it is essential to understand the current burden of TB infection at the population level. The objective of the present analysis is to estimate the prevalence of TB infection in India and to explore the factors associated with TB infection. Methods: Individuals aged > 15 years in the recently completed National TB prevalence survey in India who were tested for TB infection by QuantiFERON-TB Gold Plus (QFT-Plus) assay were considered for this sub-analysis. TB infection was defined as positive by QFT-Plus (value >0.35 IU/ml). The estimates for prevalence, prevalence ratio (PR) and adjusted risk ratio (aRR) estimates with 95% confidence intervals (CIs) were calculated. Results: Of the 16864 individuals analysed, the prevalence of TB infection was 22.6% (95% CI:19.4 −25.8). Factors more likely to be associated with TB infection include age > 30 years (aRR:1.49;95% CI:1.29–1.73), being male (aRR:1.26; 95%CI: 1.18–1.34), residing in urban location (aRR:1.58; 95%CI: 1.03–2.43) and past history of TB (aRR:1.49; 95%CI: 1.26–1.76). Conclusion: About one fourth (22.6%) of the individuals were infected with TB in India. Individuals aged > 30 years, males, residing in urban location, and those with past history of TB were more likely to have TB infection. Targeted interventions for prevention of TB and close monitoring are essential to reduce the burden of TB in India.

Introduction The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities.Methods Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020–October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting.Results Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30–60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6–7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03).Conclusion Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Background: Improved longevity of people living with HIV on highly active antiretroviral therapy and accelerated aging processes are considered contributory to Metabolic Syndrome. Objectives: The current study investigated metabolic syndrome (MetS) in people living with HIV (PLH) who were receiving antiretroviral therapy (ART) under the ongoing National AIDS Control Program. Methods: Clinic attendees (n = 3088) who were on ART for more than 6 months constituted the sampling frame, from which 378 study participants were randomly drawn and included in the analysis following the eligibility check. One hundred and fifty-nine clinic attendees, initiated on ART in ≤6 months, provided an opportunity to estimate the prevalence of MetS in them. Sixty-two PLH from this smaller group were enrolled. Results: MetS was found among 19% (73/378; 95% confidence interval [CI] 15.5%–23.7%) PLH who were on ART >6 months compared with 24% (15/62; 95% CI 14.2%–36.7%) in those who were on ART for ≤6 months based on harmonization criteria for the Asian population; the confidence intervals overlapped and apparently observed difference was not statistically significant. Adjusted for age, body mass index (BMI), protease inhibitor (PI)-based ART regimen, duration of ART, insulin resistance (IR), reported family history of hypertension and residential setting, factors independently associated with MetS were PI containing ART regimen, IR, duration of ART intake and BMI. In the adjusted model, the odds of MetS were three times higher among PLH on PI containing ART regimen (95% CI of adjusted odds ratio; aOR 1.27–8.51) and those having IR (95% CI of aOR 1.48–5.07). The odds of MetS among PLH with BMI ≥23 kg/m2 was 4 (95% CI of aOR 2.08–6.81) times higher than those with lower BMI. Conclusions: MetS in PLH requires the attention of health-care workers in India. Appropriate screening would help initiate early management.

Background: During October 2020, Delta variant was detected for the first time in India and rampantly spread across the globe. It also led to second wave of pandemic in India which affected millions of people. However, there is limited information pertaining to the SARS-CoV-2 strain infecting the children in India. Methods: Here, we assessed the SARS-CoV-2 lineages circulating in the pediatric population of India during the second wave of the pandemic. Clinical and demographic details linked with the nasopharyngeal/oropharyngeal swabs (NPS/OPS) collected from SARS-CoV-2 cases (n = 583) aged 0–18 year and tested positive by real-time RT-PCR were retrieved from March to June 2021. Results: Symptoms were reported among 37.2% of patients and 14.8% reported to be hospitalized. The E gene CT value had significant statistical difference at the point of sample collection when compared to that observed in the sequencing laboratory. Out of these 512 sequences 372 were VOCs, 51 were VOIs. Most common lineages observed were Delta, followed by Kappa, Alpha and B.1.36, seen in 65.82%, 9.96%, 6.83% and 4.68%, respectively in the study population. Conclusion: Overall, it was observed that Delta strain was the leading cause of SARS-CoV-2 infection in Indian children during the second wave of the pandemic. We emphasize on the need of continuous genomic surveillance in SARS-CoV-2 infection even amongst children.

Abstract Background Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case–control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. Methods Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. Results CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. Conclusions Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Background: India had the second-highest number of COVID-19 cases globally. We evaluated the progression of the pandemic across the lockdowns and phased reopenings at the district level during the first wave (in India). Methods: For the analysis in this study, we used more than 100 million COVID-19 test results along with other parameters available in the Indian Council of Medical Research database from March 2020 to October 2020. The districts were stratified as high, moderate, and low caseload districts and data analysis was done for each phase of lockdown. Findings: Of the 110.5 million tests included in the analysis, 54.79 million tests were performed using molecular methods, 53.58 million by rapid antigen tests, and 2.13 million using the indigenous TruNat platform. The proportion of positive cases among symptomatic individuals (22.6%) was significantly higher than asymptomatic individuals (8.6%). The tests conducted and proportions of positivity were significantly higher in high caseload districts; 58% of these tests were conducted using molecular methods as opposed to only one-third in low caseload districts. Interpretation: Laboratory parameters, along with other demographic information, can help us better understand the spread of the pandemic in a country. This information can be crucial to formulating and implementing public health policies in future waves of the pandemic.

IntroductionMizoram, the northeastern State of India bordering Myanmar, is presently witnessing a burgeoning generalized HIV epidemic along with the highest State-level HIV prevalence among female sex workers (FSWs, 24.7%) and people who inject drugs (PWID,19.8%) in the country. The present study was conducted against such background to understand the current situation of HIV prevention and care services in Mizoram, and capture community voices as well as concerns so that the way forward could be informed appropriately.MethodsThe study period was October through December 2020 (in the midst of COVID-restrictions) in the districts of Aizawl, Mamit, Kolasib, Lunglei, and Champhai where HIV prevalence crossed 1% among ante-natal clinic (ANC) attending women. Contrastingly, the national average HIV prevalence among ANC attendees is 0.24%, which formed the basis for selecting the aforementioned five high burden districts for this current inquiry. In-depth-interviews were conducted with community members and youth leaders, vulnerable and general population groups as well as HIV-program officials. Interviews were recorded, transcribed, translated and later coded for analysis following thematic approach.ResultsThe emerging issues were grouped in three thematic layers; (1) HIV vulnerability, (2) challenges pertaining to prevention and care services, and (3) program elements and future roadmap. Discrimination at the community level, unfriendly behavior of some of the HIV-service staff, occasional interruption in supplies of anti-retroviral treatment and sterile syringes and needles were voiced as deterrents to accessing HIV prevention and care services by the participants. Community engagement, based on restorative approach rather than retribution and ensuring enhanced performance of the district AIDS program control units emerged as necessary programmatic elements.ConclusionThis inquiry highlighted macro-social and structural forces contributing to stigma and discrimination toward people at risk of HIV. It is urgent that HIV-services are re-aligned through de-centralized district level innovations and creation of safer spaces at the physical, societal and familial level. These, even during the time of stress such as a pandemic, would help health services to remain resilient. HIV outreach, sensitization of the community leaders and health-care professionals through strategic communication and ownership of the communities in these endeavors appeared paramount.

Timely delivery of medical supplies is essential in the healthcare sector, which is hampered by factors such as poor transportation network, traffic and adverse environmental conditions. Alternatively, drone operations can leapfrog the last mile logistic solutions in hard-to-reach terrains. The present paper elucidates the implementation process of drone-based delivery of medical supplies, operational challenges and innovations adopted by scientists in Manipur and Nagaland. Three districts, Bishnupur, Imphal West and Churachandpur from Manipur and two districts, Mokokchung and Tuensang from Nagaland, were selected for the study. Regulatory and ethical approvals and coordination with state health and administrative authorities were accorded. Implementation and operational challenges faced by the research team were recorded elaborately in the field diaries and assessed qualitatively. The experiences encountered by the team for case-to-case based permission and coordination with the central and state aviation authorities, district administration and health authorities were observed. The drone-related technical and logistic challenges were identified as the deployment of suitable drones, payload capacity, time management for operations, and transportation of drones. The officials adopted mitigation strategies to overcome field-based challenges. Drone-based deliveries of medical supplies are proving to be time efficient, however, overcoming operational challenges could provide an effective long-term deployment strategy.

The disease anthrax occurs generally in herbivores and the causative organism (Bacillus anthracis) infects humans who come in contact with infected animals or their products. The persistence of anthrax spores for decades and its lethality contribute to its biowarfare potential. We conducted this systematic review along with risk mapping to investigate the spatio-temporal distribution, clinico-epidemiological, socio-behavioural and programmatic issues pertaining to anthrax in India over the last two decades.Peer reviewed quantitative and qualitative studies and grey literature comprising weekly reports of the ‘Integrated Disease Surveillance Program’ (IDSP), were accessed for extracting data. IDSP data were used for geo-referencing of the villages of anthrax cases; Pseudo-absence was generated to fit a Bayesian Additive Regression Trees (BART) model to develop anthrax risk map.The case fatality rate of cutaneous anthrax ranged from 2% to 38%, while the gastrointestinal and inhalational types were 100% fatal. Our synthesis revealed that human anthrax outbreaks in India were clustered around the eastern coastal regions. The states of Odisha, West Bengal, Andhra Pradesh and Jharkhand reported maximum number of outbreaks. Odisha reported a maximum number of 439 human anthrax cases since 2009, of which Koraput district contributed to 200 cases (46%). While handling or consumption of infected animal product were proximal drivers of these events, poverty, lack of awareness, traditional beliefs and local practices served as facilitatory factors. Other structural determinants were wild life-livestock interface, historical forest loss, soil pH, soil-water balance, organic carbon content, temperature, rainfall and humidity.The programmatic issues identified through this review were lack of active surveillance, non-availability of diagnostic facility at the periphery, delayed reporting, absence of routine livestock vaccination and lack of adequate veterinary services. Interventions based on One-health approach in the country merit immediate policy and program attention; high risk zones for anthrax identified during present investigation, should be prioritized.

Summary: Background: NVX-CoV2373, a Covid-19 vaccine was developed in the USA with ∼90% efficacy. The same vaccine is manufactured in India after technology transfer (called as SII-NVX-CoV2373), was evaluated in this phase 2/3 immuno-bridging study. Methods: This was an observer-blind, randomised, phase 2/3 study in 1600 adults. In phase 2, 200 participants were randomized 3:1 to SII-NVX-CoV2373 or placebo. In phase 3, 1400 participants were randomized 3:1 to SII-NVX-CoV2373 or NVX-CoV2373 (940 safety cohort and 460 immunogenicity cohort). Two doses of study products (SII-NVX-CoV2373, NVX-CoV2373 or placebo) were given 3 weeks apart. Primary objectives were to demonstrate non-inferiority of SII-NVX-CoV2373 to NVX-CoV2373 in terms of geometric mean ELISA units (GMEU) ratio of anti-S IgG antibodies 14 days after the second dose (day 36) and to determine the incidence of causally related serious adverse events (SAEs) through 180 days after the first dose. Anti-S IgG response was assessed using an Enzyme-Linked Immunosorbent Assay (ELISA) and neutralizing antibodies (nAb) were assessed by a microneutralization assay using wild type SARS CoV-2 in participants from the immunogenicity cohort at baseline, day 22, day 36 and day 180. Cell mediated immune (CMI) response was assessed in a subset of 28 participants from immunogenicity cohort by ELISpot assay at baseline, day 36 and day 180. The total follow-up was for 6 months. Trial registration: CTRI/2021/02/031554. Findings: Total 1596 participants (200 in Phase 2 and 1396 in Phase 3) received the first dose. SII-NVX-CoV2373 was found non-inferior to NVX-CoV2373 (anti-S IgG antibodies GMEU ratio 0.91; 95% CI: 0.79, 1.06). At day 36, there was more than 58-fold rise in anti-S IgG and nAb titers compared to baseline in both the groups. On day 180 visit, these antibody titers declined to levels slightly lower than those after the first dose (13–22 fold-rise above baseline). Incidence of unsolicited and solicited AEs was similar between the SII-NVX-CoV2373 and NVX-CoV2373 groups. No adverse event of special interest (AESI) was reported. No causally related SAE was reported. Interpretation: SII-NVX-CoV2373 induced a non-inferior immune response compared to NVX-CoV2373 and has acceptable safety profile. Funding: SIIPL, Indian Council of Medical Research, Novavax.

Abstract We evaluated the performance of oral swab specimen both health-care worker (HCW) collected and self-collected for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) detection with rapid antigen test (RAT) as compared to reverse transcriptase polymerase chain reaction (RT-PCR). Of the 529 participants enrolled, 121 (22.8%) were RT-PCR positive. Among the RT-PCR positives, 62 (51.2%) were RAT positive using oral swab. When compared with RT-PCR, RAT with oral swab had sensitivity and specificity of 63.3 and 96.8% respectively among symptomatic individuals. No statistically significant difference was observed in RAT positivity with HCW collection and self-collection, p = 0.606. Ct values were significantly lower in RT-PCR and RAT positive samples (ORF gene: 18.85 ± 4.36; E gene: 18.72 ± 4.84) as compared to RT-PCR positive and RAT negative samples (ORF gene: 26.98 ± 7.09; E gene: 26.97 ± 7.07), p

An HIV outbreak investigation during 2017–2018 in Unnao District, Uttar Pradesh, India, unearthed high prevalence of hepatitis C virus (HCV) antibodies among the study participants. We investigated these HCV infections by analyzing NS5B and core regions. We observed no correlation between HIV–HCV viral loads and clustering of HCV sequences, regardless of HIV serostatus. All HCV isolates belonged to genotype 3a. Monophyletic clustering of isolates in NS5B phylogeny indicates emergence of the outbreak from a single isolate or its closely related descendants. The nucleotide substitution rate for NS5B was 6 × 10−3 and for core was 2 × 10−3 substitutions/site/year. Estimated time to most recent common ancestor of these isolates was 2012, aligning with the timeline of this outbreak, which might be attributable to unsafe injection practices while seeking healthcare. HIV–HCV co-infection underlines the need for integrated testing, surveillance, strengthening of healthcare systems, community empowerment, and molecular analyses as pragmatic public health tools.

Background: Considering the potential threat from emerging Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) variants and the rising COVID-19 cases, SARS-CoV-2 genomic surveillance is ongoing in India. We report herewith the isolation of the P.2 variant (B.1.1.28.2) from international travelers and further its pathogenicity evaluation and comparison with D614G variant (B.1) in hamster model. Methods: Virus isolation was performed in Vero CCL81 cells and genomic characterization by next generation sequencing. The pathogenicity and host immune response of the isolate was assessed in Syrian hamster model and compared with B.1 variant. Results: B.1.1.28.2 variant was isolated from nasal/throat swabs of international travelers returned to India from United Kingdom and Brazil. The B.1.1.28.2 variant induced body weight loss, viral replication in the respiratory tract and caused severe lung pathology in infected Syrian hamster model in comparison, with B.1 variant infected hamsters. The sera from B.1.1.28.2 infected hamsters efficiently neutralized the D614G variant virus whereas 6-fold reduction in the neutralization was seen in case of D614G variant infected hamsters’ sera with the B.1.1.28.2 variant. Conclusions: B.1.1.28.2 lineage variant could be successfully isolated and characterization could be performed. Pathogenicity of the isolate was demonstrated in Syrian hamster model and the findings of neutralization reduction is of great concern and point towards the need for screening the vaccines for efficacy.

Learning from the past – is easier said than done. In this narrative, “travel” refers to the forward movement of the society at large on the path of health and development. It is suggested that looking back and learning from the lived experiences of the past outbreaks could help generating public health insights and incorporating them in planning for a better future. In the process, a country may choose to revisit what took place in the recent past during the COVID-19 pandemic within its boundary and beyond. However, unfolding of events in the past, which is not as immediate as COVID neither too far as the flu pandemic of 1918, also has lessons to offer. Recognizably, a few alarms, that rang in the recent past and cried for mass attention towards beefed up public health preparedness, were missed. It is therefore necessary now to critically examine the past-efforts to eradicate, eliminate or control diseases such as small pox, polio, HIV, tuberculosis, leprosy, measles or malaria. Results of such evaluation could inform the future courses of actions around disease elimination science and health (DESH) and help develop better nations.

The COVID-19 associated opportunistic fungal infections have posed major challenges in recent times. Global scientific efforts have identified several SARS-CoV2 host-pathogen interactions in a very short time span. However, information about the molecular basis of COVID-19 associated opportunistic fungal infections is not readily available. Previous studies have identified a number of host targets involved in these opportunistic fungal infections showing association with COVID-19 patients. We screened host targets involved in COVID-19-associated opportunistic fungal infections, in addition to host-pathogen interaction data of SARS-CoV2 from well-known and widely used biological databases. Venn diagram was prepared to screen common host targets involved in studied COVID-19-associated fungal infections. Moreover, an interaction network of studied disease targets was prepared with STRING to identify important targets on the basis of network biological parameters. The host-pathogen interaction (HPI) map of SARS-CoV2 was also prepared and screened to identify interactions of the virus with targets involved in studied fungal infections. Pathway enrichment analysis of host targets involved in studied opportunistic fungal infections and the subset of those involved in SARS-CoV2 HPI were performed separately. This data-based analysis screened six common targets involved in all studied fungal infections, among which CARD9 and CYP51A1 were involved in host-pathogen interactions with SARS-CoV2. Moreover, several signaling pathways such as integrin signaling were screened, which were associated with disease targets involved in SARS-CoV2 HPI. The results of this study indicate several host targets deserving detailed investigation to develop strategies for the management of SARS-CoV2-associated fungal infections.

Healthcare personnel who deal with COVID-19 experience stigma. There is a lack of national-level representative qualitative data to study COVID-19-related stigma among healthcare workers in India. The present study explores factors associated with stigma and manifestations experienced by Indian healthcare workers involved in COVID-19 management. We conducted in-depth interviews across 10 centres in India, which were analysed using NVivo software version 12. Thematic and sentiment analysis was performed to gain deep insights into the complex phenomenon by categorising the qualitative data into meaningful and related categories. Healthcare workers (HCW) usually addressed the stigma they encountered when doing their COVID duties under the superordinate theme of stigma. Among them, 77.42% said they had been stigmatised in some way. Analyses revealed seven interrelated themes surrounding stigma among healthcare workers. It can be seen that the majority of the stigma and coping sentiments fall into the mixed category, followed by the negative sentiment category. This study contributes to our understanding of stigma and discrimination in low- and middle-income settings. Our data show that the emergence of fear of the virus has quickly turned into a stigma against healthcare workers.

Abstract Background The Coronavirus disease 2019 (COVID-19) pandemic poses a serious public health concern worldwide. Certain regions of the globe were severely affected in terms of prevalence and mortality than other. Although the cause for this pattern is not clearly understood, lessons learned from previous epidemics and emerging evidences suggest the major role of ecological factors like ambient air pollutants (AAP) and meteorological parameters in increased COVID-19 incidence. The present study aimed to understand the impact of these factors on SARS-CoV-2 transmission and their associated mortality in major cities of India. Methods This study used secondary AAP, meteorological and COVID-19 data from official websites for the period January-November 2020, which were divided into Pre-lockdown (January-March 2020), Phase I (April to June 2020) and Phase II (July to November 2020) in India. After comprehensive screening, five major cities that includes 48 CPCB monitoring stations collecting daily data of ambient temperature, particulate matter PM2.5 and 10 were analysed. Spearman and Kendall’s rank correlation test was performed to understand the association between SARS-CoV-2 transmission and AAP and, meteorological variables. Similarly, case fatality rate (CFR) was determined to compute the correlation between AAP and COVID-19 related morality. Results The level of air pollutants in major cities were significantly reduced during Phase I compared to Pre-lock down and increased upon Phase II in all the cities. During the Phase II in Delhi, the strong significant positive correlation was observed between the AAP and SARS-CoV-2 transmission. However, in Bengaluru, Hyderabad, Kolkata and Mumbai AAP levels were moderate and no correlation was noticed. The relation between AT and SARS-CoV-2 transmission was inconclusive as both positive and negative correlation observed. In addition, Delhi and Kolkata showed a positive association between long-term exposure to the AAP and COVID-19 CFR. Conclusion Our findings support the hypothesis that the particulate matter upon exceeding the satisfactory level serves as an important cofactor in increasing the risk of SARS-CoV-2 transmission and related mortality. These findings would help public health experts to understand the SARS-CoV-2 transmission against ecological variables in India and provides supporting evidence to healthcare policymakers and government agencies for formulating strategies to combat the COVID-19.

Abstract Background Ending AIDS by 2030 is a global target, to which India is a signatory. HIV-self-test (HIVST) coupled with counselling and AIDS-care, including antiretroviral therapy, has the potential to achieve this. However, national programs are at varying stages of acceptance of HIVST, as discussions around its introduction spark controversy and debates. HIV-self-test, as yet, is not part of the AIDS control program in India. Against this backdrop, we explored acceptability of an HIV oral self-test (HIVOST) among truckers and young men and women. Methods A qualitative investigation with 41 in-depth-interviews and 15 group discussions were conducted in the district of Pune, in the western state of Maharashtra, India. These interactions were built around a prototype HIVOST kit, helped in taking the discussions forward. The software N-vivo (version 11.0) was used to manage the volumes of data generated through the aforementioned process. The study was conducted during June through December, 2019. Results While the truckers belonged to the age bracket 21–67 year, the youths were in the age group 18–24 year. ‘Ease of doing HIVOST’ and ‘fear of needle pricks’ were the reasons behind acceptance around HIVOST by both the study groups. Truckers felt that HIVOST would encourage one to know one’s HIV status and seek help as appropriate. Accuracy of HIVOST result and disposal of the kits following use were concerns of a few. Most of the participants preferred saliva over blood as the specimen of choice. Instructions in local language reportedly would enable test-use by self. The truck drivers preferred undertaking HIVOST at the truckers-friendly ‘Khushi clinics’ or in the vehicle, while youths preferred the privacy of home. Some of the young men mis-perceived the utility of HIVOST by referring to doing a test on a partner immediately prior to sexual encounter. On the other hand, a few truckers had wrong information on HIV cure. Conclusions Overall, the study communities expressed their acceptance towards HIV-self-test. The National AIDS Control Program, India would benefit by drawing upon the findings of the current investigation. Existing myths and misconceptions around HIV test and treatment require program attention.

Objective: This review was performed to compare the efficacy and safety among hospitalized patients with COVID-19 who received baricitinib and those who received tocilizumab independently with placebo or the standard of care (SOC).Methods: Relevant databases were searched for randomized controlled trials which evaluated the effect of baricitinib or tocilizumab as compared to placebo or the SOC in hospitalized patients with COVID-19. The primary endpoint was the comparison of the 28-day mortality. Risk ratios (RR) and mean differences were compared and pooled for dichotomous and continuous variables, respectively. A two-staged exploratory network meta-analysis using a multivariate meta-analysis was also performed. All analyses were performed in Stata version 16.0. The GRADE approach was used to assess the quality of the generated evidence (PROSPERO ID: CRD42022323363).Results: Treatment with baricitinib [RR, 0.69 (95% CI, 0.50–0.94), p = 0.02, i2 = 64.86%] but not with tocilizumab [RR, 0.87 (95% CI, 0.71–1.07), p = 0.19, i2 = 24.41%] led to a significant improvement in the 28-day mortality as compared to that with the SOC. Treatment with baricitinib or tocilizumab, both independently led to a significant reduction in the duration of hospitalization [baricitinib: mean difference, −1.13 days (95% CI, −1.51 to −0.76), p < 0.001, i2 = 0.00%; tocilizumab: mean difference, −2.80 days (95% CI, −4.17 to −1.43), p < 0.001, i2 = 55.47%] and a significant improvement in the proportion of patients recovering clinically by day 28 [baricitinib: RR, 1.24 (95% CI, 1.03–1.48), p = 0.02, i2 = 27.20%; tocilizumab: RR, 1.41 (95% CI, 1.12–1.78), p < 0.001, i2 = 34.59%] as compared to those with the SOC. From the safety point of view, both these drugs showed similar results. There were fewer patients who experienced any serious adverse event following treatment with barictinib and tocilizumab as compared to those following treatment with the SOC [baricitinib: RR, 0.76 (95% CI, 0.62–0.92), p = 0.01, i2 = 12.63%; tocilizumab: RR, 0.85 (95% CI, 0.72–1.01), p = 0.07, i2 = 0.00%].Conclusion: As baricitinib and tocilizumab are recommended interchangeably by various guidelines for the management of COVID-19, considering the better 28-day mortality data and other comparable efficacy and safety outcomes, baricitinib may be favored over tocilizumab considering its ease of administration, shorter half-life, and lower cost of treatment.

Background: Earlier serosurveys in India revealed seroprevalence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) of 0.73% in May–June 2020 and 7.1% in August–September 2020. A third serosurvey was conducted between December 2020 and January 2021 to estimate the seroprevalence of SARS-CoV-2 infection among the general population and healthcare workers (HCWs) in India. Methods: The third serosurvey was conducted in the same 70 districts as the first and second serosurveys. For each district, at least 400 individuals aged ≥10 years from the general population and 100 HCWs from subdistrict-level health facilities were enrolled. Serum samples from the general population were tested for the presence of immunoglobulin G (IgG) antibodies against the nucleocapsid (N) and spike (S1-RBD) proteins of SARS-CoV-2, whereas serum samples from HCWs were tested for anti-S1-RBD. Weighted seroprevalence adjusted for assay characteristics was estimated. Results: Of the 28,598 serum samples from the general population, 4585 (16%) had IgG antibodies against the N protein, 6647 (23.2%) had IgG antibodies against the S1-RBD protein, and 7436 (26%) had IgG antibodies against either the N protein or the S1-RBD protein. Weighted and assay-characteristic-adjusted seroprevalence against either of the antibodies was 24.1% [95% confidence interval (CI) 23.0–25.3%]. Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI 23.5–27.8%). Conclusions: Nearly one in four individuals aged ≥10 years from the general population as well as HCWs in India had been exposed to SARS-CoV-2 by December 2020.

SARS-CoV-2 vaccines are needed to fight the pandemic. Here, authors show protective efficacy and immunogenicity of the inactivated SARS-CoV-2 vaccine BBV152 in rhesus macaques. This vaccine is currently in clinical development.

Certain rural and semiurban settings in the Unnao district, Uttar Pradesh, India observed an unprecedented increase in the detection of HIV cases during July 2017. Subsequent investigations through health camps and a follow-up case-control study attributed the outbreak to the unsafe injection exposures during treatment. In this study, we have undertaken a secondary analysis to understand the phylogenetic aspects of the outbreak-associated HIV-1 sequences along with the origin and phylodynamics of these sequences. The initial phylogenetic analysis indicated separate monophyletic grouping and there was no mixing of outbreak-associated sequences with sequences from other parts of India. Transmission network analysis using distance-based and non-distance-based methods revealed the existence of transmission clusters within the monophyletic Unnao clade. The median time to the most recent common ancestor (tMRCA) for sequences from Unnao using the pol gene region was observed to be 2011.87 [95% highest posterior density (HPD): 2010.09–2013.53], while the estimates using envelope (env) gene region sequences traced the tMRCA to 2010.33 (95% HPD: 2007.76–2012.99). Phylodynamics estimates demonstrated that the pace of this local epidemic has slowed down in recent times before the time of sampling, but was certainly on an upward track since its inception till 2014.

India experienced a second wave of COVID-19 infection with an unprecedented upsurge in the number of cases. We have analyzed the effect of different restrictive measures implemented in six Indian states. Further, based on available national and international data on disease transmission and clinical presentation, we have proposed a decision-making matrix for planning adequate resources to combat the future waves of COVID-19. We conclude that pragmatic and well calibrated localized restrictions, tailored as per specific needs may achieve a decline in disease transmission comparable to drastic steps like national lockdowns. Additionally, we have underscored the critical need for countries to generate local epidemiological, clinical and laboratory data alongwith community perception and uptake of various non-pharmaceutical interventions, for effective planning and policy making.

Background COVID-19 has inundated the entire world disrupting the lives of millions of people. The pandemic has stressed the healthcare system of India impacting the psychological status and functioning of health care workers. The aim of this study is to determine the burnout levels and factors associated with the risk of psychological distress among healthcare workers (HCW) engaged in the management of COVID 19 in India. Methods A cross-sectional study was conducted from 1 September 2020 to 30 November 2020 by telephonic interviews using a web-based Google form. Health facilities and community centres from 12 cities located in 10 states were selected for data collection. Data on socio-demographic and occupation-related variables like age, sex, type of family, income, type of occupation, hours of work and income were obtained was obtained from 967 participants, including doctors, nurses, ambulance drivers, emergency response teams, lab personnel, and others directly involved in COVID 19 patient care. Levels of psychological distress was assessed by the General health Questionnaire -GHQ-5 and levels of burnout was assessed using the ICMR-NIOH Burnout questionnaire. Multivariable logistic regression analysis was performed to identify factors associated with the risk of psychological distress. The third quartile values of the three subscales of burnout viz EE, DP and PA were used to identify burnout profiles of the healthcare workers. Results Overall, 52.9% of the participants had the risk of psychological distress that needed further evaluation. Risk of psychological distress was significantly associated with longer hours of work (≥ 8 hours a day) (AOR = 2.38, 95% CI(1.66–3.41), income≥20000(AOR = 1.74, 95% CI, (1.16–2.6); screening of COVID-19 patients (AOR = 1.63 95% CI (1.09–2.46), contact tracing (AOR = 2.05, 95% CI (1.1–3.81), High Emotional exhaustion score (EE ≥16) (AOR = 4.41 95% CI (3.14–6.28) and High Depersonalisation score (DP≥7) (AOR = 1.79, 95% CI (1.28–2.51)). About 4.7% of the HCWs were overextended (EE>18); 6.5% were disengaged (DP>8) and 9.7% HCWs were showing signs of burnout (high on all three dimensions). Conclusion The study has identified key factors that could have been likely triggers for psychological distress among healthcare workers who were engaged in management of COVID cases in India. The study also demonstrates the use of GHQ-5 and ICMR-NIOH Burnout questionnaire as important tools to identify persons at risk of psychological distress and occurrence of burnout symptoms respectively. The findings provide useful guide to planning interventions to mitigate mental health problems among HCW in future epidemic/pandemic scenarios in the country.

Objective We aimed to determine the ocular manifestation and refractive error prevalences among people living with HIV (PLHIV) in Pune, India. Methods This cross-sectional study included HIV-infected adults attending a National AIDS Research Institute clinic. Ophthalmologic examination included visual acuity estimation, refraction, orthoptic evaluation, slit lamp and fundus examination, and photography. Results In total, 441 HIV-infected individuals were enrolled. The participants' median age was 44 (interquartile range 38–49) years and 227 (51.5%) were men. Refractive errors occurred in 132 (29.9%) individuals. Ocular manifestations were present in 93 (21.1%) participants and the most frequent was cataract in 59 (13.4%) participants. Multivariate logistic regression analysis showed that participants who were illiterate (adjusted odds ratio [AOR] 2.80, 95% confidence interval [CI] 1.47–5.33) and those aged greater than 40 years (AOR 5.59, 95% CI 2.69–11.61) were more likely to have ocular manifestations. The odds of having ocular manifestations were greater in participants with treatment substitution or changes (AOR 2.11, 95% CI 1.16–3.82). Conclusions Cataract and refractive errors were prevalent among PLHIV. PLHIV should be encouraged to have regular ophthalmic checkups. Individuals with lower education levels and older age should be counseled regarding eye care and timely reporting of ocular symptoms.

Objectives To investigate the impact of targeted vaccination strategies on morbidity and mortality due to COVID-19, as well as on the incidence of SARS-CoV-2, in India.Design Mathematical modelling.Settings Indian epidemic of COVID-19 and vulnerable population.Data sources Country-specific and age-segregated pattern of social contact, case fatality rate and demographic data obtained from peer-reviewed literature and public domain.Model An age-structured dynamical model describing SARS-CoV-2 transmission in India incorporating uncertainty in natural history parameters was constructed.Interventions Comparison of different vaccine strategies by targeting priority groups such as keyworkers including healthcare professionals, individuals with comorbidities (24–60 years old) and all above 60.Main outcome measures Incidence reduction and averted deaths in different scenarios, assuming that the current restrictions are fully lifted as vaccination is implemented.Results The priority groups together account for about 18% of India’s population. An infection-preventing vaccine with 60% efficacy covering all these groups would reduce peak symptomatic incidence by 20.6% (95% uncertainty intervals (UI) 16.7–25.4) and cumulative mortality by 29.7% (95% CrI 25.8–33.8). A similar vaccine with ability to prevent symptoms (but not infection) will reduce peak incidence of symptomatic cases by 10.4% (95% CrI 8.4–13.0) and cumulative mortality by 32.9% (95% CrI 28.6–37.3). In the event of insufficient vaccine supply to cover all priority groups, model projections suggest that after keyworkers, vaccine strategy should prioritise all who are >60 and subsequently individuals with comorbidities. In settings with weakest transmission, such as sparsely populated rural areas, those with comorbidities should be prioritised after keyworkers.Conclusions An appropriately targeted vaccination strategy would witness substantial mitigation of impact of COVID-19 in a country like India with wide heterogeneity. ‘Smart vaccination’, based on public health considerations, rather than mass vaccination, appears prudent.

Summary: The availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) threat. Here, we have assessed the immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidates BBV152A, BBV152B, and BBV152C in Syrian hamsters. Three dose vaccination regimes with vaccine candidates induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamster was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology, and robust humoral immune response. These findings confirm the immunogenic potential of the vaccine candidates and further protection of hamsters challenged with SARS-CoV-2. Of the three candidates, BBV152A showed the better response.

The integrated counseling and testing center (ICTC) located in the district hospital, Unnao in the northern state of Uttar Pradesh (UP), India witnessed an increased detection of HIV among its attendees in July 2017. Subsequently, health camps were organized by the UP State AIDS Control Society in the villages and townships contributing to such detection. We conducted a case-control study to identify factors associated with this increased detection; 33 cases and 125 controls were enrolled. Cases were individuals, detected HIV sero-reactive during November 2017-April 2018 from three locations namely Premganj, Karimuddinpur and Chakmeerapur in the Bangarmau block of the district of Unnao. Controls hailed from the same geographical setting and tested HIV sero-nonreactive either in health camps or at ICTC centers from where the cases were detected. Misclassification bias was avoided by confirming HIV sero-status of both cases as well as controls prior to final analysis. Study participants were interviewed on various risk practices and invasive treatment procedures. They were also tested for HIV and other bio-markers reflecting unsafe injecting and sexual exposures such as hepatitis B surface antigen (HBsAg), anti-HCV antibody (HCV Ab), anti-herpes simplex-2 Immunoglobulin G (HSV-2 IgG) and rapid plasma regain (RPR) test for syphilis. Secondary data analysis on three time points during 2015 through 2018 revealed a rising trend of HIV among attendees of the ICTCs (ICTC-Hasanganj, ICTC-Unnao district hospital and ICTC- Nawabganj) catering to the entire district of Unnao. While there was a seven fold rise of HIV among ICTC attendees of Hasanganj (χ2 value for trend 23.83; p < 0.001), the rise in Unnao district hospital was twofold (χ2 value for trend 4.37; p < 0.05) and was tenfold at ICTC-Nawabganj (χ2 value for trend 5.23; p < 0.05) indicating risk of infection prevailing throughout the district. Primary data was generated through interviews and laboratory investigations as mentioned above. The median age of cases and controls was 50 year (minimum 18 -maximum 68; IQR 31-57) and 38 year (minimum 18 -maximum 78; IQR 29-50) respectively. Thirty six percent of the cases and 47% of controls were male. A significantly higher proportion of cases (85%) had HCV Ab compared to controls (56%; OR 4.4, 95% CI 1.5-12.1); none reported injection drug use. However, cases and controls did not differ significantly regarding presence of HSV-2 IgG (6% versus 8% respectively). Neither any significant difference existed between cases and controls in terms of receiving blood transfusion, undergoing invasive surgical procedures, tattooing, tonsuring of head or skin piercing. In multivariate logistic regression model, 'unsafe injection exposure during treatment-seeking'(AOR 6.61, 95% CI 1.80-24.18) and 'receipt of intramuscular injection in last five years' (AOR 7.20, 95% CI 1.48-34.88) were independently associated with HIV sero-reactive status. The monophyletic clustering of HIV sequences from 14 cases (HIV-1 pol gene amplified) indicated a common ancestry. Availability of auto-disabled syringes and needles, empowerment of the local communities and effective regulatory practices across care settings would serve as important intervention measures in this context.

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission and evolution. Against the backdrop of the global emergence of “variants of concern” (VOCs) during December 2020 and an upsurge in a state in the western part of India since January 2021, whole genome sequencing and analysis of spike protein mutations using sequence and structural approaches were undertaken to identify possible new variants and gauge the fitness of the current circulating strains. Phylogenetic analysis revealed that newly identified lineages B.1.617.1 and B.1.617.2 were predominantly circulating. The signature mutations possessed by these strains were L452R, T478K, E484Q, D614G and P681R in the spike protein, including within the receptor-binding domain (RBD). Of these, the mutations at residue positions 452, 484 and 681 have been reported in other globally circulating lineages. The structural analysis of RBD mutations L452R, T478K and E484Q revealed that these may possibly result in increased ACE2 binding while P681R in the furin cleavage site could increase the rate of S1-S2 cleavage, resulting in better transmissibility. The two RBD mutations, L452R and E484Q, indicated decreased binding to select monoclonal antibodies (mAbs) and may affect their neutralization potential. Further in vitro/in vivo studies would help confirm the phenotypic changes of the mutant strains. Overall, the study revealed that the newly emerged variants were responsible for the second wave of COVID-19 in Maharashtra. Lineage B.1.617.2 has been designated as a VOC delta and B.1.617.1 as a variant of interest kappa, and they are being widely reported in the rest of the country as well as globally. Continuous monitoring of these and emerging variants in India is essential.

The number of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) cases is increasing in India. This study looks upon the geographic distribution of the virus clades and variants circulating in different parts of India between January and August 2020. The NPS/OPS from representative positive cases from different states and union territories in India were collected every month through the VRDLs in the country and analyzed using next-generation sequencing. Epidemiological analysis of the 689 SARS-CoV-2 clinical samples revealed GH and GR to be the predominant clades circulating in different states in India. The northern part of India largely reported the ‘GH’ clade, whereas the southern part reported the ‘GR’, with a few exceptions. These sequences also revealed the presence of single independent mutations—E484Q and N440K—from Maharashtra (first observed in March 2020) and Southern Indian States (first observed in May 2020), respectively. Furthermore, this study indicates that the SARS-CoV-2 variant (VOC, VUI, variant of high consequence and double mutant) was not observed during the early phase of virus transmission (January–August). This increased number of variations observed within a short timeframe across the globe suggests virus evolution, which can be a step towards enhanced host adaptation.

In 2015, the swine derived A(H1N1)pdm09 pandemic strain outbreak became widespread throughout the different states of India. The reported cases and deaths in 2015 surpassed the previous years with more than 39000 laboratory confirmed cases and a death toll of more than 2500 people. There are relatively limited complete genetic sequences available for this virus from Asian countries. In this study, we describe the full genome analysis of influenza 2015 A(H1N1)pdm09 viruses isolated from West Bengal between January through December 2015. The phylogenetic analysis of the haemagglutinin sequence revealed clustering with globally circulating strains of genogroup 6B. This was further confirmed by the constructed concatenated tree using all eight complete gene segments of Kolkata A(H1N1)pdm09 isolates with the other strains from different timeline and lineages. A study from Massachusetts Institute of Technology (MIT) in 2015 reported novel mutations T200A and D225N in haemagglutinin gene of a 2014 Indian strain (A/India/6427/2014). However, in all the pandemic strains of 2014-2015 reported from India, so far including A(H1N1)pdm09 strains from Kolkata, D225N mutation was not observed, though the T200A mutation was found to be conserved. Neuraminidase gene of the analyzed strains did not show any oseltamivir resistant mutation H275Y suggesting continuation of Tamiflu® as drug of choice. The amino acid sequences of the all gene segments from 2015 A(H1N1)pdm09 isolates identified several new mutations compared to the 2009 A(H1N1)pdm09 strains, which may have contributed towards enhanced virulence, compared to 2009 A(H1N1)pdm09 strains.