Adverse outcomes in patients hospitalized with pneumonia at age 60 or more: A prospective multi-centric hospital-based study in India.

BACKGROUND: Limited data exists regarding risk factors for adverse outcomes in older adults hospitalized with Community-Acquired Pneumonia (CAP) in low- and middle-income countries such as India. This multisite study aimed to assess outcomes and associated risk factors among adults aged ≥60 years hospitalized with pneumonia. METHODS: Between December 2018 and March 2020, we enrolled ≥60-year-old adults admitted within 48 hours for CAP treatment across 16 public and private facilities in four sites. Clinical data and nasal/oropharyngeal specimens were collected by trained nurses and tested for influenza, respiratory syncytial virus (RSV), and other respiratory viruses (ORV) using the qPCR. Participants were evaluated regularly until discharge, as well as on the 7th and 30th days post-discharge. Outcomes included ICU admission and in-hospital or 30-day post-discharge mortality. A hierarchical framework for multivariable logistic regression and Cox proportional hazard models identified risk factors (e.g., demographics, clinical features, etiologic agents) associated with critical care or death. FINDINGS: Of 1,090 CAP patients, the median age was 69 years; 38.4% were female. Influenza viruses were detected in 12.3%, RSV in 2.2%, and ORV in 6.3% of participants. Critical care was required for 39.4%, with 9.9% in-hospital mortality and 5% 30-day post-discharge mortality. Only 41% of influenza CAP patients received antiviral treatment. Admission factors independently associated with ICU admission included respiratory rate >30/min, blood urea nitrogen>19mg/dl, altered sensorium, anemia, oxygen saturation <90%, prior cardiovascular diseases, chronic respiratory diseases, and private hospital admission. Diabetes, anemia, low oxygen saturation at admission, ICU admission, and mechanical ventilation were associated with 30-day mortality. CONCLUSION: High ICU admission and 30-day mortality rates were observed among older adults with pneumonia, with a significant proportion linked to influenza and RSV infections. Comprehensive guidelines for CAP prevention and management in older adults are needed, especially with the co-circulation of SARS-CoV-2.

Genomic Expedition: Deciphering Human Adenovirus Strains from the 2023 Outbreak in West Bengal, India: Insights into Viral Evolution and Molecular Epidemiology.

Understanding the genetic dynamics of circulating Human Adenovirus (HAdV) types is pivotal for effectively managing outbreaks and devising targeted interventions. During the West Bengal outbreak of 2022-2023, an investigation into the genetic characteristics and outbreak potential of circulating HAdV types was conducted. Twenty-four randomly selected samples underwent whole-genome sequencing. Analysis revealed a prevalent recombinant strain, merging type 3 and type 7 of human mastadenovirus B1 (HAd-B1) species, indicating the emergence of recent strains of species B in India. Furthermore, distinctions in VA-RNAs and the E3 region suggested that current circulating strains of human mastadenovirus B1 (HAd-B1) possess the capacity to evade host immunity, endure longer within hosts, and cause severe respiratory infections. This study underscores the significance of evaluating the complete genome sequence of HAdV isolates to glean insights into their outbreak potential and the severity of associated illnesses.

Cost of acute respiratory illness episode and its determinants among community-dwelling older adults: a four-site cohort study from India.

Introduction: Advocacy for the provision of public health resources, including vaccine for the prevention of acute respiratory illnesses (ARIs) among older adults in India, needs evidence on costs and benefits. Using a cohort of community-dwelling adults aged 60 years and older in India, we estimated the cost of ARI episode and its determinants. Methods: We enrolled 6016 participants in Ballabgarh, Chennai, Kolkata and Pune from July 2018 to March 2020. They were followed up weekly to identify ARI and classified them as acute upper respiratory illness (AURI) or pneumonia based on clinical features based on British Thoracic Society guidelines. All pneumonia and 20% of AURI cases were asked about the cost incurred on medical consultation, investigation, medications, transportation, food and lodging. The cost of services at public facilities was supplemented by WHO-Choosing Interventions that are Cost-Effective(CHOICE) estimates for 2019. Indirect costs incurred by the affected participant and their caregivers were estimated using human capital approach. We used generalised linear model with log link and gamma family to identify the average marginal effect of key determinants of the total cost of ARI. Results: We included 2648 AURI and 1081 pneumonia episodes. Only 47% (range 36%-60%) of the participants with pneumonia sought care. The mean cost of AURI episode was US$13.9, while that of pneumonia episode was US$25.6, with indirect costs comprising three-fourths of the total. The cost was higher among older men by US$3.4 (95% CI: 1.4 to 5.3), those with comorbidities by US$4.3 (95% CI: 2.8 to 5.7) and those who sought care by US$17.2 (95% CI: 15.1 to 19.2) but not by influenza status. The mean per capita annual cost of respiratory illness was US$29.5. Conclusion: Given the high community disease and cost burden of ARI, intensifying public health interventions to prevent and mitigate ARI among this fast-growing older adult population in India is warranted.

Evolutionary dynamics of influenza A/H1N1 virus circulating in India from 2011 to 2021.

Influenza A viruses (IAV) are fast-evolving pathogens with a very high mutation rate (2.0 × 10-6 to 2.0 × 10-4) compared to the influenza B (IBV) and influenza C (ICV) viruses. Generally, the tropical regions are considered as the reservoir for the IAV's genetic and antigenic evolutionary modification to be reintroduced into the temperate region. Therefore, in connection to the above facts, the present study emphasized on the evolutionary dynamic of the pandemic-2009 H1N1 (pdmH1N1) influenza virus in India. A total of Ninety-two whole genome sequences of pdmH1N1 viruses circulating in India during the 2009 post-pandemic era were analysed. The temporal signal of the study, indicating strict molecular clock evolutionary process and the overall substitution rate is 2.21 × 10-3/site/year. We are using the nonparametric Bayesian Skygrid coalescent model to estimates the effective past population dynamic or size over time. The study exhibits a strong relation between the genetic distances and collection dates of the Indian pdmH1N1 strain. The skygrid plot represents the highest exponential growth of IAV in rainy and winter seasons. All the genes of Indian pdmH1N1 were under purifying selective pressure. The Bayesian time-imprinted phylogenetic tree represents the following clade distributions in the country within the last 10 years; I) clade 6, 6C, and 7 were co-circulating between the 2011 to 2012 flu season; II) the clade 6B was introduced into circulation in the late seasons of 2012; III) lastly, the clade 6B remain existing in the circulation and segregated into subclade 6B.1 with five different subgroup (6B.1A, 6B.1A.1, 6B.1A.5a, 6B.1A.5a.2, 6B.1A.7). The recent circulating strain of Indian H1N1 strain represent the insertion of basic-amino acid arginine (R) in the cleavage site (325/K-R) of HA protein and amino acid mutation (314/I-M) on the lateral head surface domain of NA protein. Moreover, the study indicates the sporadic presence of the oseltamivir-resistant (275/H-Y) H1N1 variant in circulation. The present study suggests the purifying selective pressure and stochastic ecological factors for the existence and adaptation of a certain clade 6B in the host populations and additional information on the emergence of mutated strains in the circulation.

Development of lab score system for predicting COVID-19 patient severity: A retrospective analysis.

AIM: To develop an accurate lab score based on in-hospital patients' potent clinical and biological parameters for predicting COVID-19 patient severity during hospital admission. METHODS: To conduct this retrospective analysis, a derivation cohort was constructed by including all the available biological and clinical parameters of 355 COVID positive patients (recovered = 285, deceased = 70), collected in November 2020-September 2021. For identifying potent biomarkers and clinical parameters to determine hospital admitted patient severity or mortality, the receiver operating characteristics (ROC) curve and Fischer's test analysis was performed. Relative risk regression was estimated to develop laboratory scores for each clinical and routine biological parameter. Lab score was further validated by ROC curve analysis of the validation cohort which was built with 50 COVID positive hospital patients, admitted during October 2021-January 2022. RESULTS: Sensitivity vs. 1-specificity ROC curve (>0.7 Area Under the Curve, 95% CI) and univariate analysis (p<0.0001) of the derivation cohort identified five routine biomarkers (neutrophil, lymphocytes, neutrophil: lymphocytes, WBC count, ferritin) and three clinical parameters (patient age, pre-existing comorbidities, admitted with pneumonia) for the novel lab score development. Depending on the relative risk (p values and 95% CI) these clinical parameters were scored and attributed to both the derivation cohort (n = 355) and the validation cohort (n = 50). ROC curve analysis estimated the Area Under the Curve (AUC) of the derivation and validation cohort which was 0.914 (0.883-0.945, 95% CI) and 0.873 (0.778-0.969, 95% CI) respectively. CONCLUSION: The development of proper lab scores, based on patients' clinical parameters and routine biomarkers, would help physicians to predict patient risk at the time of their hospital admission and may improve hospital-admitted COVID-19 patients' survivability.

A retrospective study reveals the Porcine circovirus-2f genotype predominant in the indigenous pig population of North-eastern India.

Porcine circovirus-2 (PCV2) is a widespread virus and presents sub-clinically in most of the swineherd. Globally, eight genotypes of PCV2 have been identified that is PCV2a to 2h. To determine the region-wide genotype distribution of PCV2 infection, with additional reference to indigenous breeds, a total of 1314 pig's clinical samples from the eight states of North-eastern India between 2011 and 2014; were analyzed. The overall prevalence rate of PCV2 in this region was 28.2% (370/1314) by PCR. The state-wise PCR based PCV2 prevalence rate was: Tripura (20.8%), Nagaland (25.0%), Meghalaya (25.8%), Assam (32.1%), Sikkim (32.6%), Manipur (33.3%), Mizoram (36.7%) and Arunachal Pradesh (42.3%). Subsequently, a total of 29 complete genomes of PCV2 were amplified and sequenced from these PCV2 positive samples. The phylogenetic tree represents that the 29 PCV2 isolates of this study were divided into four distinct genetic groups; PCV2a, PCV2b, PCV2d, and PCV2f. Among these, 14 PCV2 strains were classified as PCV2f, 13 classified as PCV2d, and one isolate of each classified as PCV2a and PCV2b. All the 14 PCV2f strains appeared from indigenous pigs of this region. Based on the date of collection, the present study further describes that the PCV2f genotypes circulate in the indigenous pigs' population back in 2011. The amino acid residues and the atomic coordinate structure (3D model) of PCV2f capsid protein represents similarity to PCV2d capsid protein support the efficacy of the existing PCV2 vaccine against the PCV2f. The observation of this study helps to understand the genotype distribution of PCV2 and stands as a reference for future molecular epidemiological studies in North-eastern India.

Development of cost-effective quantitative PCR method for parallel detection of porcine circovirus2 and porcine parvovirus in perspective of North-eastern India.

Pig farming performs as an intricate part in the socio-economic situation in the north-eastern region of India. This region contributes 38% (3.95 million) of total pigs in India. In spite of this, the region unables to flourish as an enterprise as per the expectation due to a low productivity rate. Porcine infectious pathogens like porcine cirovirus2 (PCV2) and porcine parvovirus (PPV) have a direct economic impact on pig farming through slow growth rate, abortion, and mortality and ultimately maximize the production cost by increasing the usage of antibiotic or antiviral drugs. The veterinary diagnostic infrastructure is a fundamental aspect of the development of livestock status by rapid and effective detection of pathogens. Quantitative PCR (qPCR) is a precise and fast-track technique used for the routine diagnostic method. Hence, we developed a highly precise and comparatively cost-effective SYBR Green reporter dye-based qPCR assay for parallel identification of PCV2 and PPV. In the present assay, the correlation coefficient (R2) value was 0.99, and 10 copies of the gene/µl were the least limit of detection (LOD) concerning both viruses. Melt curve analysis of this study represented PCV2-specific melt curve (Tm) at 81.2 °C and PPV-specific melt curve (Tm) at 73.5 °C. Therefore, the assay easily differentiates the true positive amplicons of PCV2 and PPV through specific Tm values. Among the 50 field samples, 26 (52%) samples were PCV2 positive, 18 (36%) samples PPV positive, and 11 (22%) samples were co-infected of both the viruses. This method is cost-effective, precise, and sensitive to diagnose the concurrent or individual infection of the PCV2 and PPV in the pig. Hence, considering the impact of pig farming in the north-eastern part of the country, the present assay gives an unprecedented achievement in disease diagnosis.

Emergence of Novel Coronavirus and COVID-19: whether to stay or die out?

The last century has witnessed several assaults from RNA viruses, resulting in millions of death throughout the world. The 21st century appears no longer an exception, with the trend continued with escalated fear of SARS coronavirus in 2002 and further concern of influenza H5N1 in 2003. A novel influenza virus created the first pandemic of the 21st century, the pandemic flu in 2009 preceded with the emergence of another deadly virus, MERS-CoV in 2012. A novel coronavirus "SARS-CoV-2" (and the disease COVID-19) emerged suddenly, causing a rapid outbreak with a moderate case fatality rate. This virus is continuing to cause health care providers grave concern due to the lack of any existing immunity in the human population, indicating their novelty and lack of previous exposure. The big question is whether this novel virus will be establishing itself in an endemic form or will it eventually die out? Endemic viruses during circulation may acquire mutations to infect naïve, as well as individual with pre-existing immunity. Continuous monitoring is strongly advisable, not only to the newly infected individuals, but also to those recovered individuals who were infected by SARS-CoV-2 as re-infection may lead to the selection of escape mutants and subsequent dissemination to the population.

Characterization of Marek's disease virus and phylogenetic analyses of meq gene from an outbreak in poultry in Meghalaya of Northeast India.

The aim of the present study was to characterize the virus from the lesions and histopathology of organs associated with mortality in Kuroiler (dual purpose variety of poultry developed and marketed by Keggfarms Pvt. Ltd, India) birds suspected of Marek's disease. Among 1047 birds from two farms of different location with 5.5 and 34% mortality, two types of lesion were observed in post mortem examination; tumors in vital organs-liver, spleen, kidney, lung and ovaries and generalized small nodular tumour in the abdominal cavity. Molecular characterization based on detection of ICP4 gene showed the presence of Marek's disease virus (MDV) from tissues and cell culture adapted isolates in Madin Darby Canine Kidney cell lines. Histopathological examination revealed multinucleated immature lymphoid cells infiltration in the organs. Phylogenetic analysis of the isolates based on meq gene showed the isolates belongs to cluster I genotype of MDV. This is for the first time the MDV virus is characterized from an outbreak in the poultry flock in farmer's field affecting production in Meghalaya state of North east India.

Complete genome sequence of emerging porcine circovirus types 2a and 2b from India.

We report here the first characterized complete genome sequence of porcine circovirus types 2a and 2b from northeastern states of India. These isolates may serve as a potential reference for the Indian strains of porcine circovirus types 2a and 2b.

Complete genome sequence of classical Swine Fever virus subgenogroup 2.1 from assam, India.

We report the complete genome sequence of a classical swine fever virus (genogroup 2.1), isolated from an outbreak in Assam, India. This particular isolate showed a high degree of genetic variation within the subgenogroup 2.1 and may serve as a potential reference strain of the 2.1 genogroup of classical swine fever virus (CSFV) in the Indian subcontinent.