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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.
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Hospitalización , Neumonía , Humanos , Femenino , Masculino , Anciano , India/epidemiología , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Neumonía/epidemiología , Neumonía/mortalidad , Neumonía/virología , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/mortalidad , Infecciones Comunitarias Adquiridas/virología , Anciano de 80 o más Años , Mortalidad Hospitalaria , Unidades de Cuidados IntensivosRESUMEN
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.
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BACKGROUND: We present post-vaccination nasal shedding findings from the phase IV, community-based, triple-blinded RCT conducted to assess efficacy of trivalent LAIV and inactivated influenza vaccines in rural north India. METHODS: Children aged 2-10 years received LAIV or intranasal placebo across 2015 and 2016, as per initial allocation. On days 2 and 4 post-vaccination, trained study nurses collected nasal swabs from randomly selected subset of trial participants based on operational feasibility, accounting for 10.0% and 11.4% of enrolled participants in 2015 and 2016, respectively. Swabs were collected in viral transport medium and transported under cold chain to laboratory for testing by reverse transcriptase real-time polymerase chain reaction. RESULTS: In year 1, on day 2 post-vaccination, 71.2% (74/104) of LAIV recipients shed at least one of vaccine virus strains compared to 42.3% (44/104) on day 4. During year 1, on day 2 post-vaccination, LAIV-A(H1N1)pdm09 was detected in nasal swabs of 12% LAIV recipients, LAIV-A(H3N2) in 41%, and LAIV-B in 59%. In year 2, virus shedding was substantially lower; 29.6% (32/108) of LAIV recipients shed one of the vaccine virus strains on day 2 compared to 21.3% on day 4 (23/108). CONCLUSION: At day 2 post-vaccination in year 1, two-thirds of LAIV recipients were shedding vaccine viruses. Shedding of vaccine viruses varied between strains and was lower in year 2. More research is needed to determine the reason for lower virus shedding and vaccine efficacy for LAIV-A(H1N1)pdm09.
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Subtipo H1N1 del Virus de la Influenza A , Vacunas contra la Influenza , Niño , Humanos , Subtipo H3N2 del Virus de la Influenza A , Vacunación , Inmunización , Vacunas Atenuadas , IndiaRESUMEN
PURPOSE: We describe here a multicentric community-dwelling cohort of older adults (>60 years of age) established to estimate incidence, study risk factors, healthcare utilisation and economic burden associated with influenza and respiratory syncytial virus (RSV) in India. PARTICIPANTS: The four sites of this cohort are in northern (Ballabgarh), southern (Chennai), eastern (Kolkata) and western (Pune) parts of India. We enrolled 5336 participants across 4220 households and began surveillance in July 2018 for viral respiratory infections with additional participants enrolled annually. Trained field workers collected data about individual-level and household-level risk factors at enrolment and quarterly assessed frailty and grip strength. Trained nurses surveilled weekly to identify acute respiratory infections (ARI) and clinically assessed individuals to diagnose acute lower respiratory infection (ALRI) as per protocol. Nasal and oropharyngeal swabs are collected from all ALRI cases and one-fifth of the other ARI cases for laboratory testing. Cost data of the episode are collected using the WHO approach for estimating the economic burden of seasonal influenza. Handheld tablets with Open Data Kit platform were used for data collection. FINDINGS TO DATE: The attrition of 352 participants due to migration and deaths was offset by enrolling 680 new entrants in the second year. All four sites reported negligible influenza vaccination uptake (0.1%-0.4%), low health insurance coverage (0.4%-22%) and high tobacco use (19%-52%). Ballabgarh had the highest proportion (54.4%) of households in the richest wealth quintile, but reported high solid fuel use (92%). Frailty levels were highest in Kolkata (11.3%) and lowest in Pune (6.8%). The Chennai cohort had highest self-reported morbidity (90.1%). FUTURE PLANS: The findings of this cohort will be used to inform prioritisation of strategies for influenza and RSV control for older adults in India. We also plan to conduct epidemiological studies of SARS-CoV-2 using this platform.
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COVID-19 , Gripe Humana , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Virus , Anciano , Humanos , India/epidemiología , Lactante , Gripe Humana/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , SARS-CoV-2RESUMEN
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.
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Vacunas contra la Influenza/farmacología , Gripe Humana/prevención & control , Vacunas Atenuadas/farmacología , Vacunas de Productos Inactivados/farmacología , Administración Intranasal , Niño , Preescolar , Femenino , Humanos , India , Vacunas contra la Influenza/administración & dosificación , Masculino , Población Rural , Vacunación/estadística & datos numéricos , Vacunas Atenuadas/administración & dosificación , Vacunas de Productos Inactivados/administración & dosificación , Vacunas de Productos Inactivados/inmunologíaRESUMEN
Background & objectives: Chloroquine (CQN) administered as nasal drops has the potential to achieve much greater local tissue levels than with oral/systemic administration. This trial was undertaken to study the efficacy and safety profile of topical nasal administration of CQN drops in reducing viral load and preventing clinical progression in early COVID-19 infection. Methods: This randomized clinical trial was done with a sample size of 60. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed asymptomatic patients or those with mild COVID-19 illness [National Early Warning Score (NEWS) ≤4] were included. Patients were randomized in a 1:1 manner. Control arm (standard supportive treatment, n=30) was compared with intervention arm (n=30) of standard treatment plus CQN eye drops (0.03%) repurposed as nasal drops administered six times daily (0.5 ml/dose) for 10 days. Outcome measures were adverse events and adherence; clinical progression and outcomes were measured by NEWS; sequential RT-PCR cycle threshold (Ct) values were also noted on days 0, 3, 7 and 10. Results: Nasal CQN was associated with local irritation in seven and non-compliance in one of 30 patients. Eleven patients were excluded due to enrolment error (2 - recovered; 9 - false-positive referral), and 49 patients were analyzed as per modified intention-to-treat analysis. Clinical recovery was noted as similar with 100 per cent asymptomatic by day seven in both arms. Virological outcomes also indicated similarly improving Ct values in both arms, and similar proportion of patients transitioning to non-infectivity by day 10 (controls - 19/25; nasal CQN - 15/24). Nine false-positive patients with enrolment error and day 0 RT-PCR negative were initially uninfected but had continuing COVID-19 exposure and treatment as per randomization. Patients receiving nasal CQN (n=5) demonstrated stable Ct values from day 0 to 10, while patients with no nasal CQN (n=4) demonstrated significant dip in Ct value indicating to infection (Ct<35) and infectivity (Ct<33). Interpretation & conclusions: The present study suggests to the potential of topical nasal CQN in the prevention of COVID-19 infection if administered before the infection is established. No significant differences in clinical or virological outcome were however, demonstrated in patients with mild but established illness.
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Administración Intranasal , Tratamiento Farmacológico de COVID-19 , Cloroquina/uso terapéutico , Humanos , Resultado del TratamientoRESUMEN
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.
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Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Infecciones del Sistema Respiratorio , Anciano , Humanos , Incidencia , India/epidemiología , Lactante , Infecciones del Sistema Respiratorio/epidemiología , Factores de RiesgoRESUMEN
BACKGROUND/OBJECTIVE: There is a paucity of data on the management of gastrointestinal (GI) bleeding in patients with Coronavirus disease -2019 (COVID-19) amid concerns about the risk of transmission during endoscopic procedures. We aimed to study the outcomes of conservative treatment for GI bleeding in patients with COVID-19. METHODS: In this retrospective analysis, 24 of 1342 (1.8%) patients with COVID-19, presenting with GI bleeding from 22nd April to 22nd July 2020, were included. RESULTS: The mean age of patients was 45.8 ± 12.7 years; 17 (70.8%) were males; upper GI (UGI) bleeding: lower GI (LGI) 23:1. Twenty-two (91.6%) patients had evidence of cirrhosis- 21 presented with UGI bleeding while one had bleeding from hemorrhoids. Two patients without cirrhosis were presumed to have non-variceal bleeding. The medical therapy for UGI bleeding included vasoconstrictors-somatostatin in 17 (73.9%) and terlipressin in 4 (17.4%) patients. All patients with UGI bleeding received proton pump inhibitors and antibiotics. Packed red blood cells (PRBCs), fresh frozen plasma (FFPs) and platelets were transfused in 14 (60.9%), 3 (13.0%) and 3 (13.0%), respectively. The median PRBCs transfused was 1 (0-3) unit(s). The initial control of UGI bleeding was achieved in all 23 patients and none required an emergency endoscopy. At 5-day follow-up, none rebled or died. Two patients later rebled, one had intermittent bleed due to gastric antral vascular ectasia, while another had rebleed 19 days after discharge. Three (12.5%) cirrhosis patients succumbed to acute hypoxemic respiratory failure during hospital stay. CONCLUSION: Conservative management strategies including pharmacotherapy, restrictive transfusion strategy, and close hemodynamic monitoring can successfully manage GI bleeding in COVID-19 patients and reduce need for urgent endoscopy. The decision for proceeding with endoscopy should be taken by a multidisciplinary team after consideration of the patient's condition, response to treatment, resources and the risks involved, on a case to case basis.
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OBJECTIVES: To ascertain if topical lignocaine application in oropharynx prior to swab sampling to test for COVID-19 improves a patient's comfort and to assess its effect on the swab sample taken to conduct the RT-PCR. METHODS: Adult patients testing positive on the RT-PCR COVID-19 test were sampled again within 48 h after administering topical oropharyngeal anaesthesia. Patients were asked to rate their discomfort on a visual analog scale (VAS) for both sample A and B. A qualitative real-time RT-PCR for detection of SARS-CoV-2 RNA, was performed, and the cycle threshold value (Ct), used as a surrogate marker for the viral load, was measured for the sample taken without lignocaine (sample A) and the sample taken post-lignocaine application (sample B). The difference in Ct values of both the groups was checked for any statistical significance using paired t-test. Wilcoxon signed rank test was used on VAS scores to determine any significant decrease in discomfort. RESULTS: Forty patients were included in the study. Twenty-nine patients (72.5%) reported the procedure to be more comfortable post-lignocaine application. Median (IQR) discomfort on VAS decreased from 7 (1) to 5 (2) after lignocaine use, which was statistically significant (p < 0.05). Mean Ct value for sample A was 17.21 ± 5.25 and for sample B was 18.44 ± 4.8 (p > 0.05), indicating a non-significant effect of lignocaine on SARS-CoV-2 concentration in the sample. CONCLUSION: Topical lignocaine, while improving the comfort of the procedure of oropharyngeal sampling for patient did not alter the SARS-CoV-2 viral load that was detected in nasal and oropharyngeal samples taken together.
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Anestesia , COVID-19 , Adulto , Humanos , Lidocaína , Orofaringe , ARN Viral , SARS-CoV-2RESUMEN
BACKGROUND: Sore throat is one of the commonest symptoms that patients present to a primary care physician. We describe the epidemiology of sore throat and performance of an algorithm to predict viral sore throat in a part of India. METHODS: Children below 10 years of age were followed in 4 villages of Haryana, India from Aug 2012 to Aug 2014 through weekly domiciliary visits by trained field workers who screened for symptoms of acute respiratory infection (ARI) including sore throat. Nasal and throat swabs were obtained from a random sample of sore throat cases by nurses and sent in appropriate transport media for real-time polymerase chain reaction for detection of viral nucleic acid. Incidence of sore throat and viral sore throat are reported as number of sore throat episodes per 1000 child-years (EPTCY) with 95% confidence-interval (CI). Symptoms, associated with viral sore throat were identified by logistic regression, combined into a clinical score and Receiver Operating Characteristic curve was plotted. RESULTS: Over a two-year period, 3765 children were followed up for 5578 child years. 1069 episodes of sore throat were reported, and swabs were collected from 8% of the cases randomly. The incidence of sore throat and viral sore throat was 191.7 (95%CI: 180.5-203.6) and 60.1 (95%CI: 55.1-68.2) EPTCY, respectively. Fever (aOR 5.40,95%CI: 1.16-25.18) and running nose (aOR 10.16,95%CI: 1.01-102.42) was significantly associated with viral sore throat. The clinical score (fever, running nose, and headache) had an overall sensitivity of 86.2% (68.3-96.1%), specificity of 62% (47.2-75.3%) and AUC of 0.78 (0.67-0.87) in predicting viral sore throat. CONCLUSION: Viruses contributed to one-third of burden of sore throat and clinical score can be used in primary care settings to aid antibiotic prescription by physicians.
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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 <10 years old at home weekly from August 2012-August 2014, for cough, sore throat, rhinorrhoea, ear discharge, and shortness of breath. Symptomatic children were assessed for ALRI using World Health Organization definitions. Nasal and throat swabs were obtained from all ALRI cases and asymptomatic controls and tested using polymerase chain reaction for respiratory syncytial virus (RSV), human metapneumovirus (hMPV), parainfluenza viruses (PIV), and influenza viruses (IV). We estimated adjusted odds ratios (aOR) using logistic regression to calculate etiologic fractions (EF). We multiplied agent-specific ALRI incidence rates by EF to calculate the adjusted incidence as episodes per child-year. RESULTS: ALRI incidence was 0.19 (95% confidence interval (CI) = 0.18-0.20) episode per child-year. Association between virus and ALRI was strongest for RSV (aOR = 15.9; 95% CI = 7.3-34.7; EF = 94%) and least for IV (aOR = 4.6; 95% CI = 2.0-10.6; EF = 78%). Adjusted agent-specific ALRI incidences were RSV (0.03, 95% CI = 0.02-0.03), hMPV (0.02, 95% CI = 0.01-0.02), PIV (0.02, 95% CI = 0.01-0.02), and IV (0.01, 95% CI = 0.01-0.01) episode per child-year. CONCLUSIONS: ALRI among children in rural India was high; RSV was a significant contributor.
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Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Población Rural , Enfermedad Aguda , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , India/epidemiología , Lactante , Masculino , Población Rural/estadística & datos numéricosRESUMEN
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 <24months especially those aged <6 months. The WHO-ARI case definition appeared to be the most suitable screening definition for RSV surveillance because of its high sensitivity.
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Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitiales Respiratorios/aislamiento & purificación , Distribución por Edad , Preescolar , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , India/epidemiología , Lactante , Recién Nacido , Masculino , Vigilancia de la Población/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa , Infecciones por Virus Sincitial Respiratorio/diagnóstico , Población RuralRESUMEN
Human metapneumovirus (hMPV) causes acute respiratory infections in children and adults. It is classified into two major genetic lineages and each lineage into two sublineages. The purpose of the study was to identify and characterize hMPV in children who presented to the All India Institute of Medical Sciences, New Delhi, India with acute respiratory infection from April 2005 to March 2007. By reverse-transcription polymerase chain reaction, hMPV was detected in 21 (3%) of the 662 nasopharyngeal samples from children with acute respiratory infection and in none of the 120 control children. Seven of the 21 (33%) children infected with hMPV required hospital admission for pneumonia or bronchiolitis. Most hMPV detections were during the winter and spring seasons. The majority (67%, 11/21) of children positive for hMPV were within 24 months of age. Phylogenetic analysis of partial F and N gene and the full G gene sequences showed three sub-lineages of hMPV circulated during the study period, B1, B2, and the novel sub-lineage A2b. The circulation pattern of hMPV genotypes varied by season. Comparison of the F and G genes of eight strains revealed incongruencies in lineage assignments, raising the possibility that recombination had occurred. Sequence analysis also revealed the F gene was relatively conserved whereas the G gene was more variable between the A and B lineages. This study demonstrates that hMPV is an important contributor to acute respiratory infection in children in India, resulting in both outpatient visits and hospitalizations.
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Variación Genética , Metapneumovirus/genética , Metapneumovirus/aislamiento & purificación , Infecciones por Paramyxoviridae/virología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/virología , Secuencia de Aminoácidos , Secuencia de Bases , Niño , Preescolar , Femenino , Genotipo , Humanos , India , Lactante , Masculino , Metapneumovirus/clasificación , Nasofaringe/virología , Infecciones por Paramyxoviridae/diagnóstico , Infecciones por Paramyxoviridae/epidemiología , Filogenia , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Alineación de Secuencia , Análisis de Secuencia de ARNRESUMEN
BACKGROUND: Noroviruses (NoVs) are the most common cause of viral gastroenteritis. Their high incidence and importance in health care facilities result in a great impact on public health. Studies from around the world describing increasing prevalence have been difficult to compare because of differing nomenclatures for variants of the dominant genotype, GII.4. We studied the global patterns of GII.4 epidemiology in relation to its genetic diversity. METHODS: Data from NoV outbreaks with dates of onset from January 2001 through March 2007 were collected from 15 institutions on 5 continents. Partial genome sequences (n=775) were collected, allowing phylogenetic comparison of data from different countries. RESULTS: The 15 institutions reported 3098 GII.4 outbreaks, 62% of all reported NoV outbreaks. Eight GII.4 variants were identified. Four had a global distribution--the 1996, 2002, 2004, and 2006b variants. The 2003Asia and 2006a variants caused epidemics, but they were geographically limited. Finally, the 2001 Japan and 2001 Henry variants were found across the world but at low frequencies. CONCLUSIONS: NoV epidemics resulted from the global spread of GII.4 strains that evolved under the influence of population immunity. Lineages show notable (and currently unexplained) differences in geographic prevalence. Establishing a global NoV network by which data on strains with the potential to cause pandemics can be rapidly exchanged may lead to improved prevention and intervention strategies.
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Infecciones por Caliciviridae/epidemiología , Infecciones por Caliciviridae/virología , Brotes de Enfermedades , Gastroenteritis/epidemiología , Gastroenteritis/virología , Norovirus/clasificación , Norovirus/aislamiento & purificación , Análisis por Conglomerados , Evolución Molecular , Variación Genética , Genotipo , Geografía , Humanos , Epidemiología Molecular , Norovirus/genética , Filogenia , Prevalencia , ARN Viral/genética , Homología de SecuenciaRESUMEN
BACKGROUND: Human caliciviruses (HuCVs) cause gastroenteritis throughout the world. Limited information is available on molecular epidemiology of caliciviruses from developing countries including India. OBJECTIVES: Standardization and evaluation of a two-step multiplex RT-PCR assay for HuCVs and characterization of strains. STUDY DESIGN: Two hundred and twenty-six stool samples were collected from children with acute gastroenteritis (AGE) over a one and half year to study the prevalence and diversity of HuCVs in children with AGE in New Delhi, India. A multiplex two-step RT-PCR using 3 sets of external and 4 sets of internal primers from the RdRp gene was standardized for detection of NoVs and SaVs. Molecular characterization of some HuCV strains was done by sequencing followed by phylogenetic analysis. RESULTS: Fifty-nine HuCVs strains were detected in 54 (24%) of the samples; 5 samples had mixed infections. Of these 59 HuCVs, 36 (61%) were norovirus (34 were GGII; 2 were GGI) and 23 (39%) were sapovirus (22 were GGI; 1 was GGII). Phylogenetic analysis of partial RdRp gene of 12 HuCV strains identified three genotypes (GGI/4, GGII/3 and a newly identified GIIb/Hilversum cluster) in NoVs and one genotype (GGI/1) in SaVs. CONCLUSION: This is one of the few reports from India on detection and characterization of HuCVs by multiplex RT-PCR assay. This assay can be a useful tool for epidemiological studies of HuCV infections.