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"Lower respiratory infection"
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Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016
by
Garcia-Basteiro, Alberto L
,
Ruhago, George Mugambage
,
Somayaji, Ranjani
in
Adolescent
,
Adult
,
Adults
2018
Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages.
We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000–16 using the risk factors associated with LRI in GBD 2016.
In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475–720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749–1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584–2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445–1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7–69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden.
Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations.
Bill & Melinda Gates Foundation.
Journal Article
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in children younger than 5 years in 2019: a systematic analysis
2022
Respiratory 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.
In 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).
In 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 in-hospital deaths (6800–28 100), and 45 700 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).
RSV 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.
EU Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Journal Article
Epidemiological Trend of RSV Infection Before and During COVID-19 Pandemic: A Three-Year Consecutive Study in China
2022
Objective: This study aimed to explore the epidemiological trend and clinical characteristics of respiratory syncytial virus (RSV) infection among inpatient children with lower respiratory tract infection (LRTI) before and during the coronavirus disease 2019 (COVID-19) pandemic. Methods: A retrospective study of inpatients with LRTI was conducted at the Department of Pulmonology, The Children's Hospital, Zhejiang University School of Medicine (Hangzhou, China) from January 2019 to December 2021. All respiratory specimens were tested for common respiratory pathogens. The clinical data in children with RSV-induced LRTI in the past three years were collected and analyzed. Results: A total of 11,290 patients were enrolled, and RSV positive cases were 402 (7.6%), 288 (9.6%), 415 (13.8%) in 2019, 2020, 2021, respectively, with a significant statistical difference of the RSV positive rate among the three groups (p < 0.001). Most patients were under 2-year old, especially under 1-year old, and the median age of patients was 4 months, 5 months, 6 months in 2019, 2020, 2021, respectively, with a tendency to increase in age. In terms of the seasonal distribution, most patients of LRTI with RSV infection were admitted in winter, while in 2021 compared with in 2019, the cases significantly reduced in winter and increased in autumn. From 2019 to 2021, there was an increase in autumn trend year by year. Conclusion: RSV infection was still an important cause of hospitalization in children with LRTI after the outbreak of COVID-19, and its proportion increased gradually. LRTI caused by RSV is still more common in infants under 1-year old, but there is a trend of increasing in older children. What deserves the attention of pediatricians and Center for Disease Control is that the incidence of RSV infection continues to rise in autumn, and the difference in seasonal distribution is narrowed. Keywords: respiratory syncytial virus, RSV, COVID-19, lower respiratory tract infection, non-pharmaceutical interventions
Journal Article
Sex differences in the impact of lower respiratory tract infections on older adults’ health trajectories: a population-based cohort study
by
Vetrano, Davide L.
,
Brandtmüller, Agnes
,
Calderón-Larrañaga, Amaia
in
Activities of daily living
,
Adults
,
Aged
2024
Background
Lower respiratory tract infections (LRTIs) are a major global health concern, particularly among older adults, who have an increased risk of poorer health outcomes that persist beyond the acute infectious episode. We aimed to investigate the mid-term (up to 7 years) and long-term (up to 12 years) effects of LRTIs on the objective health status trajectories of older adults, while also considering potential sex differences.
Methods
Cohort data of adults aged ≥ 60 years from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) collected between 2001 and 2016 was analyzed. Information on LRTIs was obtained from the Swedish National Patient Register, and objective health status was assessed using the Health Assessment Tool (HAT) which incorporates indicators of mild and severe disability, cognitive and physical functioning, and multimorbidity. The LRTI-exposed and -unexposed participants were matched using propensity score matching based on an expansive list of potential confounders. Mixed linear models were used to analyze the association between LRTIs and changes in HAT scores.
Results
The study included 2796 participants, 567 of whom were diagnosed with a LRTI. LRTIs were independently associated with an excess annual decline of 0.060 (95% CI: -0.107, -0.013) in the HAT score over a 7-year period. The associations were stronger among males, who experienced an excess annual decline of 0.108 (95% CI: -0.177, -0.039) in up to 7-years follow-up, and 0.097 (95% CI: -0.173, -0.021) in up to 12-years follow-up. The associations were not statistically significant among females in either follow-up period.
Conclusion
LRTIs, even years after the acute infectious period, seem to have a prolonged negative effect on the health of older adults, particularly among males. Preventative public health measures aimed at decreasing LRTI cases among older adults could help in preserving good health and functioning in old age.
Journal Article
Correlation Between Inflammatory Markers and Pathogenic Bacteria in Children’s Winter Respiratory Infections in Xinjiang
2025
This study examines the distribution characteristics of pathogenic bacteria in respiratory infections and their relationship with inflammatory markers to guide clinical drug use.
We selected 120 patients with lower respiratory tract infection in the electronic medical record system of Xinjiang Provincial People's Hospital from March 2019 to March 2023 for a case-control study. Using Indirect Immunofluorescence Antibody test(IFA), blood routine, C-reactive Protein (CRP), and High-sensitivity C-reactive Protein(hsCRP), we detected nine respiratory pathogens (Respiratory syncytial virus; Influenza A virus; Influenza B virus; Parainfluenza virus; Adenovirus; Mycoplasma pneumoniae; Chlamydia pneumoniae; Legionella pneumophila type 1; Rickettsia Q) in all patients and analyzed their distribution and correlation. The patients were divided into three groups [Respiratory Syncytial Virus Immunoglobulin M(RSV-IgM) positive group A, Mycoplasma Immunoglobulin M(MP - IgM) positive group B, antibody - negative group with elevated hsCRP, 40 patients each]. We compared differences in hsCRP, platelet count, White Blood Cells(WBC), and Neutrophil(NE) among the groups.
We conducted a systematic sorting and analysis of variables exhibiting significant differences. The results of the multivariate logistic regression analysis indicated that inflammatory markers, including white blood cell count (WBC) (OR 3.85, 95% CI: 1.116-1.623), neutrophils (NE) (OR 2.26, 95% CI: 1.091-1.312), high-sensitivity C-reactive protein (HsCRP) (OR 1.95, 95% CI: 1.068-14.640), lymphocytes (OR 1.30, 95% CI: 1.045-1.134), platelet count (OR 1.34, 95% CI: 1.625-2.760), and C-reactive protein (CRP) (OR 3.80, 95% CI: 1.232-2.379), were significantly associated with the presence of pathogenic bacteria.
There was significant correlation between inflammatory markers and pathogenic bacteria in patients with lower respiratory tract infection in Xinjiang region.
Journal Article
Decreased number of hospitalized children with severe acute lower respiratory infection after introduction of the pneumococcal conjugate vaccine in the Eastern Democratic Republic of the Congo
by
Andersson, Rune
,
Birindwa, Archippe Muhandule
,
Nordén, Rickard
in
13-valent pneumococcal conjugate vaccine
,
Acute Disease
,
acute lower respiratory infections
2020
acute lower respiratory infections (ALRI) are a leading killer of children under five worldwide including the Democratic Republic of the Congo (DR Congo). We aimed to determine the morbidity and case fatality rate due to ALRI before and after introduction of the 13-valent pneumococcal conjugate vaccine (PVC13) in DR Congo 2013.
data were collected from medical records of children with a diagnosis of ALRI, aged from 2 to 59 months, treated at four hospitals in the Eastern DR Congo. Two study periods were defined; from 2010 to 2012 (before introduction of PCV13) and from 2014 to 2015 (after PCV13 introduction).
out of 21,478 children admitted to the hospitals during 2010-2015, 2,007 were treated for ALRI. The case fatality rate among these children was 4.9%. Death was significantly and independently associated with malnutrition, severe ALRI, congenital disease and symptoms of fatigue. Among the ALRI hospitalised children severe ALRI decreased from 31% per year to 18% per year after vaccine introduction (p = 0.0002) while the fatality rate remained unchanged between the two study periods. Following introduction of PCV13, 63% of the children diagnosed with ALRI were treated with ampicillin combined with gentamicin while 33% received ceftriaxone and gentamicin.
three years after PCV13 introduction in the Eastern part of the DR Congo, we found a reduced risk of severe ALRI among children below five years. Broad-spectrum antibiotics were frequently used for the treatment of ALRI in the absence of any microbiological diagnostic support.
Journal Article
Clinical and economic hospital burden of acute respiratory infection (BARI) due to respiratory syncytial virus in Spanish children, 2015–2018
by
Platero, L.
,
Drago, G.
,
Martinón-Torres, F.
in
Acute lower respiratory infection
,
Analysis
,
Birth weight
2023
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in children, causing frequent outpatient visits and hospitalizations. Our study aimed to describe the clinical and direct economic burden of ALRI hospitalizations related to RSV in children in Spain and the characteristics of patients and their episodes. In this retrospective study, ALRI hospitalizations in children aged < 5 years for 2015–2018 were reviewed using anonymized administrative public hospital discharge data from Spain. Three case definitions were considered: (a) RSV-specific; (b) RSV-specific and unspecified acute bronchiolitis (RSV-specific and bronchiolitis); and (c) RSV-specific and unspecified ALRI (RSV-specific and ALRI). The study reported a mean of 36,743 yearly admissions potentially due to RSV, resulting in a mean annual cost of €87.1 million. RSV-specific codes accounted for 39.2% of cases, unspecified acute bronchiolitis for 20.1%, and other unspecified ALRI codes for the remaining 40.6%. The mean hospitalization rate per 1,000 children was 55.5 in the first year of life, 16.0 in the second, and 5.4 between 24 and 59 months. A considerable proportion of cases occurred in children under two years old (> 80.4%) and even during the first year of life (> 61.7%). Otherwise healthy children accounted for 92.9% of hospitalizations and 83.3% of costs during the period. Children born preterm accounted for 1.3% of hospitalizations and 5.7% of costs. The findings revealed that RSV still contributes to a high burden on the Spanish health care system. Children under one year of age and otherwise healthy term infants accounted for most of the substantial clinical and economic burden of RSV. Current evidence potentially underestimates the true epidemiology and burden of severe RSV infection; thus, further studies focusing on the outpatient setting are needed.
Journal Article
Clinical and economic burden of respiratory syncytial virus in Spanish children: the BARI study
by
Platero, L.
,
Drago, G.
,
Martinón-Torres, F.
in
Acute lower respiratory infection
,
Age groups
,
Bronchiolitis
2022
Respiratory syncytial virus (RSV) infection is a major cause of morbidity in children. However, its disease burden remains poorly understood, particularly outside of the hospital setting. Our study aimed to estimate the burden of medically attended acute lower respiratory infection (ALRI) cases potentially related to RSV in Spanish children. Longitudinal data from September 2017 to June 2018 of 51,292 children aged < 5 years old from the National Healthcare System (NHS) of two Spanish regions were used. Three case definitions were considered: (a) RSV-specific; (b) RSV-specific and unspecified acute bronchiolitis (RSV-specific and Bronchiolitis), and; (c) RSV-specific and unspecified ALRI (RSV-specific and ALRI). A total of 3460 medically attended ALRI cases potentially due to RSV were identified, of which 257 (7.4%), 164 (4.7%), and 3039 (87.8%) coded with RSV-specific, unspecific bronchiolitis, and unspecific ALRI codes, respectively. Medically attended RSV-specific and ALRI cases per 1000 children was 134.4 in the first year of life, 119.4 in the second, and 35.3 between 2 and 5 years old. Most cases were observed in otherwise healthy children (93.1%). Mean direct healthcare cost per medically attended RSV-specific and ALRI case was €1753 in the first year of life, €896 in the second, and €683 between 2 and 5 years old. Hospitalization was the main driver of these costs, accounting for 55.6%, 38.0% and 33.4%, in each respective age group. In RSV-specific cases, mean direct healthcare cost per medically attended case was higher, mostly due to hospitalization: €3362 in the first year of life (72.9% from hospitalizations), €3252 in the second (72.1%), and €3514 between 2 and 5 years old (74.2%). These findings suggest that hospitalization data alone will underestimate the RSV infections requiring medical care, as will relying only on RSV-specific codes. RSV testing and codification must be improved and preventive solutions adopted, to protect all infants, particularly during the first year of life.
Journal Article
Burden of non-COVID-19 lower respiratory infections in China (1990–2021): a global burden of disease study analysis
2025
Background
The assessment of lower respiratory infection (LRI) mortality, incidence, and responsible pathogens in China provides a scientific basis for the prevention and management of LRI, especially for evaluating the impact of coronavirus disease 2019 (COVID-19). We provide a national estimate of the non-COVID-19 LRI burden and trends on people from 1990 to 2021 based on Global Burden of Disease (GBD) study 2021.
Methods
We estimated China’s mortality, incidence, disability-adjusted life years (DALYs), risk factors and aetiology attribution for LRI without including COVID-19 by using the estimated data of GBD study 2021. Mortality, incidence, DALYs, risk factors and aetiology were stratified by sex and age. Trends were evaluated using estimated annual percentage change.
Results
In 2021, it is estimated that there were 206930.22 deaths (95% uncertainty interval [UI]: 171260.88–251990.47), with all-age mortality rate of 14.54 deaths (95% UI: 12.04–17.71) per 100,000 population. Compared to 2019, the all-age mortality rate had a 3.60% increase. Analyzing risk factors from 1990 to 2021, we found that the percentage of DALYs attributed to tobacco increased from 7.44% (95% UI: 1.26–15.72%) to 22.14% (95% UI: 3.28–38.41%), and that attributable to ambient particulate matter pollution increased from 19.84% (95% UI: 8.79–30.20%) to 32.72% (95% UI: 22.78–41.77%). The leading cause of mortality from LRIs remains
Streptococcus pneumoniae
from 1990 to 2021. However, the proportions of viral infections decreased. Compared to 2019, the proportion of deaths in 2021 caused by Influenza decreased from 13.03 to 2.70%, and the proportion of deaths due to RSV decreased from 2.21 to 0.41%.
Conclusions
In China, substantial progress has been made in reducing LRI mortality, yet LRIs have remained a threat in China from 1990 to 2021. During the COVID-19 pandemic, the mortality attributable to Influenza and RSV declined. Effective vaccines and treatments targeted at the main pathogens of LRI are important.
Clinical trial number
Not applicable.
Journal Article
Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults
2018
Lower respiratory tract infections (LRTIs) lead to more deaths each year than any other infectious disease category. Despite this, etiologic LRTI pathogens are infrequently identified due to limitations of existing microbiologic tests. In critically ill patients, noninfectious inflammatory syndromes resembling LRTIs further complicate diagnosis. To address the need for improved LRTI diagnostics, we performed metagenomic next-generation sequencing (mNGS) on tracheal aspirates from 92 adults with acute respiratory failure and simultaneously assessed pathogens, the airway microbiome, and the host transcriptome. To differentiate pathogens from respiratory commensals, we developed a rules-based model (RBM) and logistic regression model (LRM) in a derivation cohort of 20 patients with LRTIs or noninfectious acute respiratory illnesses. When tested in an independent validation cohort of 24 patients, both models achieved accuracies of 95.5%. We next developed pathogen, microbiome diversity, and host gene expression metrics to identify LRTI-positive patients and differentiate them from critically ill controls with noninfectious acute respiratory illnesses. When tested in the validation cohort, the pathogen metric performed with an area under the receiver-operating curve (AUC) of 0.96 (95% CI, 0.86–1.00), the diversity metric with an AUC of 0.80 (95% CI, 0.63–0.98), and the host transcriptional classifier with an AUC of 0.88 (95% CI, 0.75–1.00). Combining these achieved a negative predictive value of 100%. This study suggests that a single streamlined protocol offering an integrated genomic portrait of pathogen, microbiome, and host transcriptome may hold promise as a tool for LRTI diagnosis.
Journal Article