Incidence, risk factors and viral aetiology of lower respiratory infections among older adults: a 5-year multicentric cohort study in India.

Effect of an improved biomass stove on acute lower respiratory infections in young children in rural Nepal: a cluster-randomised, step-wedge trial

Acute lower respiratory tract infections (ALRIs) especially severe ALRIs, constitute a global high burden of morbidity and mortality in children <5 y of age and respiratory syncytial virus (RSV) has been documented to a play a major aetiological role. However, Nigerian reports on severe childhood RSV ALRIs are rare and most reports are old. With recent advances in RSV preventive strategy, arises the need for a recent appraisal of RSV infection in children with severe ALRI. The current study thus set out to determine the prevalence of RSV infection among hospitalized children <5 y of age and describe the related social determinants. We performed a descriptive cross-sectional study conducted over 1 y of 120 children, ages 2-59 months, diagnosed with ALRI. Relevant data were obtained and an antigen detection assay was used for viral studies. The prevalence of RSV infection was 34.2% and its peak was in the rainy months. The proportion of infants in the RSV-positive group was significantly higher than that in the RSV-negative group (82.9% vs 54.4%; p=0.002). These findings were largely consistent with those of earlier reports. RSV has remained a common cause of severe ALRI in infants, especially during the rainy months in Nigeria. It is thus suggested that more effort be focused towards implementing the current global recommendations for the prevention of RSV-associated LRI, particularly in infants.

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

Global burden of respiratory infections due to seasonal influenza in young children: a systematic review and meta-analysis

Influenza virus (IFV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and parainfluenza virus (hPIV) cause substantial disease burden in children under 5 years, but the infection spectrum remains unclear. We systematically reviewed studies published between 1995 and 2023 to estimate probabilities between viral test positivity, symptomatic infections, acute lower respiratory infections (ALRI), ALRI with chest-wall indrawing (CWI), ALRI hospitalization, and very severe ALRI - p(symptomatic | test positive), p(ALRI | symptomatic), p(CWI | ALRI), p(hosp | ALRI) and p(very severe | hosp). (PROSPERO CRD42024584039; CRD42023439269). Based on 129 studies, we estimated that 67.7% of IFV test-positives were symptomatic and 16.2% of symptomatic IFV infections developed ALRI. In children under 2 years, 71.8% of RSV test-positives were symptomatic. Across the viruses, the estimated p(CWI | ALRI) and p(hosp | ALRI) were higher in infants than older children; between 2.6% and 41.2% of hospitalized children with ALRI were very severe, with higher estimates in low and lower-middle income countries. Infants and children under 5 years in low and lower-middle income countries are important risk groups for immunization due to their high vulnerability to severe outcomes. These findings provide critical data to support immunization assessment and development of immunization strategies.

AimTo estimate the proportional contribution of influenza viruses (IV), parainfluenza viruses (PIV), adenoviruses (AV), and coronaviruses (CV) to the burden of severe acute lower respiratory infections (ALRI).MethodsThe review of the literature followed PRISMA guidelines. We included studies of hospitalized children aged 0-4 years with confirmed ALRI published between 1995 and 2011. A total of 51 studies were included in the final review, comprising 56 091 hospitalized ALRI episodes.ResultsIV was detected in 3.0% (2.2%-4.0%) of all hospitalized ALRI cases, PIV in 2.7% (1.9%-3.7%), and AV in 5.8% (3.4%-9.1%). CV are technically difficult to culture, and they were detected in 4.8% of all hospitalized ALRI patients in one study. When respiratory syncytial virus (RSV) and less common viruses were included, at least one virus was detected in 50.4% (40.0%-60.7%) of all hospitalized severe ALRI episodes. Moreover, 21.9% (17.7%-26.4%) of these viral ALRI were mixed, including more than one viral pathogen. Among all severe ALRI with confirmed viral etiology, IV accounted for 7.0% (5.5%-8.7%), PIV for 5.8% (4.1%-7.7%), and AV for 8.8% (5.3%-13.0%). CV was found in 10.6% of virus-positive pneumonia patients in one study.ConclusionsThis article provides the most comprehensive analysis of the contribution of four viral causes to severe ALRI to date. Our results can be used in further cost-effectiveness analyses of vaccine development and implementation for a number of respiratory viruses.

To investigate the clinical characteristics and analyze risk factors for severe respiratory syncytial virus (RSV) infection in hospitalized infants with acute lower respiratory tract infections (ALRIs). A retrospective review of the medical records of infants with RSV-associated ALRIs between March 1st, 2011 and February 29th, 2012 was conducted. Subjects were followed up over the phone or by outpatient visit six and twelve months after discharge. Among 913 RSV-associated ALRIs infants, 288 (31.5%) had severe infections, which accounted for 4.2% of hospitalized children. The hospital RSV mortality rate was 1.0%. The proportions of cases with tachypnea, apnea, cyanosis, and fine rales were significantly higher in the severe ALRIs group (all P<0.001). Multivariate logistic regression showed that low-birth-weight [1.698 (1.028-2.805)], age less than 3 months old [3.385 (2.174-5.271)], congenital heart disease [1.667 (1.149-2.418)], bronchopulmonary dysplasia [8.505 (1.731-41.780)], and airway abnormalities [2.246 (1.008-5.005)] were independent risk factors for severe ALRIs. The incidence of bronchitis, pneumonia and readmission in the severe group was significantly higher than that of the non-severe group during the one-year follow-up (all P<0.001). Younger age, low birth weight and underlying disease are associated with severe RSVassociated ALRIs. Furthermore, severe RSV infections may be associated with a higher frequency of subsequent bronchitis, pneumonia and re-hospitalization in the following year.

BackgroundAcute respiratory infection (ARI) is a major killer of children in developing countries. Although the frequency of ARI is similar in both developed and developing countries, mortality due to ARI is 10–50 times higher in developing countries. Viruses are common causes of ARI among such children, yet the disease burden of these infections in rural communities is unknown.Methodology/Principal FindingsA prospective longitudinal study was carried out in children enrolled from two rural Indian villages at birth and followed weekly for the development of ARI, classified as upper respiratory infection, acute lower respiratory infection (ALRI), or severe ALRI. Respiratory syncytial virus (RSV), influenza, parainfluenza viruses and adenoviruses in nasopharyngeal aspirates were detected by direct fluorescent antibody testing (DFA) and, in addition, centrifugation enhanced culture for RSV was done. 281 infants enrolled in 39 months and followed until 42 months. During 440 child years of follow-up there were 1307 ARIs, including 236 ALRIs and 19 severe ALRIs. Virus specific incidence rates per 1000 child years for RSV were total ARI 234, ALRI 39, and severe ALRI 9; for influenza A total ARI 141, ALRI 39; for INF B total ARI 37; for PIV1 total ARI 23, for PIV2 total ARI 28, ALRI 5; for parainfluenza virus 3 total ARI 229, ALRI 48, and severe ALRI 5 and for adenovirus total ARI 18, ALRI 5. Repeat infections with RSV were seen in 18 children.Conclusions/SignificanceRSV, influenza A and parainfluenza virus 3 were important causes of ARI among children in rural communities in India. These data will be useful for vaccine design, development and implementation purposes.

Although predictors of severe viral acute lower respiratory infections (ALRIs) in children have been reported, there have been few research studies performed in low- and middle-income countries (LMIC). The aim of the present study was to determine predictors of disease severity in a population of Colombian children <5 years of age with ALRI. In a prospective cohort study, we determined independent predictors of severe ALRI in a hospitalized population of children under 5 years old with ALRI during a 1-year period. We included both underlying disease conditions and the infecting respiratory viruses as predictor variables of severe disease. We defined severe disease as the necessity of pediatric intensive care unit admission. Of a total of 1,180 patients admitted with a diagnosis of ALRI, 416 (35.3%) were included because they were positive for any kind of respiratory virus. After controlling for potential confounders, it was found that a history of pulmonary hypertension (RR 3.62; CI 95% 2.38-5.52; P < 0.001) and a history of recurrent wheezing (RR 1.77; CI 95% 1.12-2.79; P = 0.015) were independent predictors of severe disease. The present study shows that respiratory viruses are significant causes of ALRI in infants and young children in Colombia, a typical tropical LMIC, especially during the rainy season. Additionally, the results of the present study show that clinical variables such as a history of pulmonary hypertension and a history of recurrent wheezing are more relevant for predicting ALRI severity than the infecting respiratory viruses.

BackgroundNo comprehensive analysis is available on the viral etiology and clinical characterization among children with severe acute lower respiratory tract infection (SALRTI) in Southern China.MethodsCohort of 659 hospitalized children (2 months to 14 years) with SALRTI admitted to the Pediatric Intensive Care Unit (PICU) in the Guangzhou from May 2015 to April 2018 was enrolled in this study. Nasopharyngeal aspirate specimens or induced sputum were tested for eight categories respiratory viral targets. The viral distribution and its clinical characters were statistically analyzed.ResultsViral pathogen was detected in 326 (49.5%) of children with SALRTI and there were 36 (5.5%) viral coinfections. Overall, the groups of viruses identified were, in descending order of prevalence: Influenza virus (IFV) (n = 94, 14.3%), respiratory syncytial virus (RSV) (n = 75, 11.4%), human rhinovirus (HRV) (n = 56, 8.5%), adenovirus (ADV) (n = 55, 8.3%), parainfluenza (PIV) (n = 47, 7.1%), human coronavirus (HCoV) (n = 15, 2.3%), human metapneumovirus (HMPV) (n = 14, 2.1%) and human bocavirus (HBoV) (n = 11, 1.7%). The positive rate in younger children (< 5 years) was significantly higher than the positive rate detected in elder children (> 5 years) (52.5% vs 35.1%, P = 0.001). There were clear seasonal peaks for IFV, RSV, HRV, ADV, PIV, and HMPV. And the individuals with different viral infection varied significantly in terms of clinical profiles.ConclusionsViral infections are present in a consistent proportion of patients admitted to the PICU. IFV, RSV, HRV, and ADV accounted for more than two‐thirds of all viral SALRTI. Our findings could help the prediction, prevention and potential therapeutic approaches of SALRTI in children.

SummaryBackgroundHuman parainfluenza virus (hPIV) is a common virus in childhood acute lower respiratory infections (ALRI). However, no estimates have been made to quantify the global burden of hPIV in childhood ALRI. We aimed to estimate the global and regional hPIV-associated and hPIV-attributable ALRI incidence, hospital admissions, and mortality for children younger than 5 years and stratified by 0–5 months, 6–11 months, and 12–59 months of age.MethodsWe did a systematic review of hPIV-associated ALRI burden studies published between Jan 1, 1995, and Dec 31, 2020, found in MEDLINE, Embase, Global Health, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Global Health Library, three Chinese databases, and Google search, and also identified a further 41 high-quality unpublished studies through an international research network. We included studies reporting community incidence of ALRI with laboratory-confirmed hPIV; hospital admission rates of ALRI or ALRI with hypoxaemia in children with laboratory-confirmed hPIV; proportions of patients with ALRI admitted to hospital with laboratory-confirmed hPIV; or in-hospital case–fatality ratios (hCFRs) of ALRI with laboratory-confirmed hPIV. We used a modified Newcastle-Ottawa Scale to assess risk of bias. We analysed incidence, hospital admission rates, and hCFRs of hPIV-associated ALRI using a generalised linear mixed model. Adjustment was made to account for the non-detection of hPIV-4. We estimated hPIV-associated ALRI cases, hospital admissions, and in-hospital deaths using adjusted incidence, hospital admission rates, and hCFRs. We estimated the overall hPIV-associated ALRI mortality (both in-hospital and out-hospital mortality) on the basis of the number of in-hospital deaths and care-seeking for child pneumonia. We estimated hPIV-attributable ALRI burden by accounting for attributable fractions for hPIV in laboratory-confirmed hPIV cases and deaths. Sensitivity analyses were done to validate the estimates of overall hPIV-associated ALRI mortality and hPIV-attributable ALRI mortality. The systematic review protocol was registered on PROSPERO (CRD42019148570).Findings203 studies were identified, including 162 hPIV-associated ALRI burden studies and a further 41 high-quality unpublished studies. Globally in 2018, an estimated 18·8 million (uncertainty range 12·8–28·9) ALRI cases, 725 000 (433 000–1 260 000) ALRI hospital admissions, and 34 400 (16 400–73 800) ALRI deaths were attributable to hPIVs among children younger than 5 years. The age-stratified and region-stratified analyses suggested that about 61% (35% for infants aged 0–5 months and 26% for 6–11 months) of the hospital admissions and 66% (42% for infants aged 0–5 months and 24% for 6–11 months) of the in-hospital deaths were in infants, and 70% of the in-hospital deaths were in low-income and lower-middle-income countries. Between 73% and 100% (varying by outcome) of the data had a low risk in study design; the proportion was 46–65% for the adjustment for health-care use, 59–77% for patient groups excluded, 54–93% for case definition, 42–93% for sampling strategy, and 67–77% for test methods. Heterogeneity in estimates was found between studies for each outcome.InterpretationWe report the first global burden estimates of hPIV-associated and hPIV-attributable ALRI in young children. Globally, approximately 13% of ALRI cases, 4–14% of ALRI hospital admissions, and 4% of childhood ALRI mortality were attributable to hPIV. These numbers indicate a potentially notable burden of hPIV in ALRI morbidity and mortality in young children. These estimates should encourage and inform investment to accelerate the development of targeted interventions.FundingBill & Melinda Gates Foundation.

SummaryBackgroundRespiratory syncytial virus (RSV) is the most common cause of acute lower respiratory infection in young children. We previously estimated that in 2015, 33·1 million episodes of RSV-associated acute lower respiratory infection occurred in children aged 0–60 months, resulting in a total of 118 200 deaths worldwide. Since then, several community surveillance studies have been done to obtain a more precise estimation of RSV associated community deaths. We aimed to update RSV-associated acute lower respiratory infection morbidity and mortality at global, regional, and national levels in children aged 0–60 months for 2019, with focus on overall mortality and narrower infant age groups that are targeted by RSV prophylactics in development.MethodsIn this systematic analysis, we expanded our global RSV disease burden dataset by obtaining new data from an updated search for papers published between Jan 1, 2017, and Dec 31, 2020, from MEDLINE, Embase, Global Health, CINAHL, Web of Science, LILACS, OpenGrey, CNKI, Wanfang, and ChongqingVIP. We also included unpublished data from RSV GEN collaborators. Eligible studies reported data for children aged 0–60 months with RSV as primary infection with acute lower respiratory infection in community settings, or acute lower respiratory infection necessitating hospital admission; reported data for at least 12 consecutive months, except for in-hospital case fatality ratio (CFR) or for where RSV seasonality is well-defined; and reported incidence rate, hospital admission rate, RSV positive proportion in acute lower respiratory infection hospital admission, or in-hospital CFR. Studies were excluded if case definition was not clearly defined or not consistently applied, RSV infection was not laboratory confirmed or based on serology alone, or if the report included fewer than 50 cases of acute lower respiratory infection. We applied a generalised linear mixed-effects model (GLMM) to estimate RSV-associated acute lower respiratory infection incidence, hospital admission, and in-hospital mortality both globally and regionally (by country development status and by World Bank Income Classification) in 2019. We estimated country-level RSV-associated acute lower respiratory infection incidence through a risk-factor based model. We developed new models (through GLMM) that incorporated the latest RSV community mortality data for estimating overall RSV mortality. This review was registered in PROSPERO (CRD42021252400).FindingsIn addition to 317 studies included in our previous review, we identified and included 113 new eligible studies and unpublished data from 51 studies, for a total of 481 studies. We estimated that globally in 2019, there were 33·0 million RSV-associated acute lower respiratory infection episodes (uncertainty range [UR] 25·4–44·6 million), 3·6 million RSV-associated acute lower respiratory infection hospital admissions (2·9–4·6 million), 26 300 RSV-associated acute lower respiratory infection in-hospital deaths (15 100–49 100), and 101 400 RSV-attributable overall deaths (84 500–125 200) in children aged 0–60 months. In infants aged 0–6 months, we estimated that there were 6·6 million RSV-associated acute lower respiratory infection episodes (4·6–9·7 million), 1·4 million RSV-associated acute lower respiratory infection hospital admissions (1·0–2·0 million), 13 300 RSV-associated acute lower respiratory infection inhospital deaths (6800–28 100), and 45700 RSV-attributable overall deaths (38 400–55 900). 2·0% of deaths in children aged 0–60 months (UR 1·6–2·4) and 3·6% of deaths in children aged 28 days to 6 months (3·0–4·4) were attributable to RSV. More than 95% of RSV-associated acute lower respiratory infection episodes and more than 97% of RSV-attributable deaths across all age bands were in low-income and middle-income countries (LMICs).InterpretationRSV contributes substantially to morbidity and mortality burden globally in children aged 0–60 months, especially during the first 6 months of life and in LMICs. We highlight the striking overall mortality burden of RSV disease worldwide, with one in every 50 deaths in children aged 0–60 months and one in every 28 deaths in children aged 28 days to 6 months attributable to RSV. For every RSV-associated acute lower respiratory infection in-hospital death, we estimate approximately three more deaths attributable to RSV in the community. RSV passive immunisation programmes targeting protection during the first 6 months of life could have a substantial effect on reducing RSV disease burden, although more data are needed to understand the implications of the potential age-shifts in peak RSV burden to older age when these are implemented.FundingEU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).

Respiratory viruses in infants in a pediatric sentinel surveillance unit, Brazil

Background and Objectives: Acute respiratory tract infections are a prominent cause of mortality and morbidity in children residing in poor countries. This inquiry focuses on the serum levels of zinc in patients with acute lower respiratory tract infections. This is linked to the severity of acute lower respiratory tract infection, the need for intravenous antibiotics, and the pattern of recovery. Material and Methods: This study is a case-control inquiry conducted at the Department of Paediatrics, RVS Institute of Medical Science, Chittore, Andhra Pradesh, India. The study was conducted from October 2018 to September 2019. The study's sample included 70 cases of Acute lower respiratory tract infection, as well as 70 children who were selected as controls based on their matching sex, age, and nutritional condition.Results: An extended duration of hospitalization was linked to a decrease in the average concentration of zinc in the blood. The mean zinc concentration declined within the range of typical zinc levels in children who were hospitalized for a duration of less than 7 days. Furthermore, there was a greater occurrence of zinc insufficiency detected when comparing patients to controls. A higher percentage of children with bronchiolitis showed a normal zinc level. A greater percentage of children with pneumonia, namely lobar pneumonia, displayed a zinc deficit. Furthermore, a higher percentage of children with severe acute lower respiratory tract infections demonstrated zinc insufficiency in comparison to those with mild and moderate acute lower respiratory tract infections.Conclusion: Severe acute lower respiratory tract infections exhibited a significant reduction in serum zinc levels when compared to mild and moderate acute lower respiratory tract infections. In addition, it was noted that children who needed to stay in the hospital for a longer period of time had lower amounts of zinc in their blood.

A descriptive study was undertaken to document clinical and socio-demographic features and also to identify risk factors for mortality in children hospitalized with acute lower respiratory tract infection (ALRI). A total of 704 children aged from 1 month to 5 years admitted to Harare Central Hospital were studied. The peak age group was between 1 and 6 months. Seventy per cent of the children were found to have normal nutrition and 12% severe malnutrition. Seventy-eight per cent had severe and the remainder moderate ALRI (WHO classification). Clinical HIV infection was diagnosed in 219 (31%) children. One hundred and four children died, an overall case fatality rate (CFR) of 15%. In the clinically HIV-infected children, a CFR of 28% occurred, which constituted 60% of the overall ALRI mortality. A much lower CFR of 9% was found in the clinically non-HIV-infected children. Malnutrition, severe ALRI, age of 1 to 6 months, concurrent diarrhoea, duration of cough > or = 14 days and previous history of admission for ALRI were significant risk factors for mortality in ALRI. Low birthweight was not found to be a risk factor in this study. The impact of HIV infection on mortality in children with ALRI is of major concern in Zimbabwe and should be an important component of the national ALRI programme.