Acute Lower Respiratory Infections Research Articles

Different Clinical Manifestations of Adenoviral Infection Confirmed Using Point-of-Care Testing in a Group of Hospitalized Children.

Objective: A restrospective analysis of the clinical picture (inflammatory markers, characteristics of fever, comorbidities) in different clinical manifestations of human adenovirus (HAdV) infections confirmed using point-of-care testing in a group of hospitalized children. Material and Methods: A total of 135 children with confirmed HAdV infections were divided into three groups according to their clinical symptoms: Group A—respiratory (n = 57), Group B—gastrointestinal (n = 40), and Griup C—mixed (n = 38). Results: Respiratory and mixed HAdV-infected patients, as compared with gastrointestinal HAdV-infected patients, were younger (median value (Me) and interquartile range (IQR) (months): 17 (12−30) and 17 (12−27) vs. 30 (16−50), p = 0.04), had a longer duration of fever (days): 3 (1−5) and 3 (1−4) vs. 1 (1−2), p = 0.01), and had higher C-reactive protein values (mg/L): 29.2 (10.4−69.1) and 28.7 (10.8−49.1) vs. <5 (<5−20.6), p < 0.001). There were no correlations between CRP levels and patient’s age, fever duration, the occurrence of acute otitis media and lower respiratory tract infection, and antibiotic treatment before admission. Conclusions: Patients with respiratory HAdV infections have fevers more often, the duration of the fever prior to admission is longer, and CRP levels are higher.

Burden of Respiratory Syncytial Virus Related Acute Lower Respiratory Tract Infection in Hospitalized Thai Children: A 6-Year National Data Analysis.

This study sought to determine the epidemiology, seasonal variations, morbidity, and mortality of respiratory syncytial virus (RSV) infection among hospitalized children with lower respiratory tract infection in Thailand. In addition, we assessed the risk factors associated with severe RSV lower respiratory tract infection (LRTI)-related morbidity and mortality. The data were reviewed retrospectively from the National Health Security Office for hospitalized children younger than 18 years old diagnosed with RSV-related LRTI in Thailand, between the fiscal years of 2015 to 2020. The RSV-related LRTIs were identified using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Thai Modification. ICD-10-TM codes J12.1, J20.5, and J21.0, which represent respiratory syncytial virus pneumonia, acute bronchitis due to respiratory syncytial virus, and acute bronchiolitis due to respiratory syncytial virus, respectively, were studied. During the study period, RSV-related LRTI accounted for 19,340 of the 1,610,160 hospital admissions due to LRTI. RSV pneumonia was the leading cause of hospitalization (13,684/19,340; 70.76%), followed by bronchiolitis (2849/19,340; 14.73%) and bronchitis (2807/19,340; 14.51%), respectively. The highest peak incidence of 73.55 percent occurred during Thailand's rainy season, from August to October. The mortality rate of RSV-related LRTI in infants younger than 1 year of age was 1.75 per 100,000 person years, which was significantly higher than that of children 1 to younger than 5 years old and children 5 to younger than 18 years old (0.21 per 100,000 person years and 0.01 per 100,000 person years, respectively, p-value &lt; 0.001). Factors associated with mortality were congenital heart disease, hematologic malignancy, malnutrition, and neurological disease. In children with RSV LRTI, pneumonia was the leading cause of hospitalization. The admission rate was highest during the rainy season. Mortality from RSV-related LRTI was higher in children under 1 year old and in children with underlying illnesses; future preventive interventions should target these groups of patients.

Pneumonia in Children During the 2019 Outbreak in Xiamen, China.

To understand the regional epidemiology and clinical characteristics of adenovirus pneumonia in hospitalized children during the 2019 outbreak of respiratory adenoviruses in China. We analyzed the epidemiologic trend of adenovirus in children hospitalized for acute lower respiratory tract infections in Xiamen in 2019. Adenovirus was identified using direct fluorescent antibody detection. During the peak seasons of adenovirus epidemic, 170 adenovirus-positive specimens were obtained for molecular typing, and the clinical data were collected. Among the 9890 children hospitalized for acute lower respiratory tract infection, 609 (6.2%) were tested positive for adenovirus. The detection rate of adenovirus was significantly higher in boys than in grils (9.5% vs. 4.6%, P < 0.05). Adenovirus activity increased markedly between April and August with the prevalence of 7.3%-12.4%. During the outbreak season, type 7 accounted for 70.6%, followed by type 3 (28.8%) and type 4 (0.6%). Of the 155 cases of adenovirus pneumonia, the median age was 3.0 years (range: 4 month to 9 years), 153 (98.7%) had fever with a mean fever duration of 9.04 ± 5.52 days, 28 (16.5%) had wheezing, 93 (60%) showed segmental or lobar consolidation with atelectasis and 13 (8.4%) showed pleural effusion. Forty-six (29.6%) cases developed severe pneumonia, 7 (4.1%) required mechanical ventilation and 2 (1.2%) died. Younger age, longer duration of fever and higher fever spike were more frequently seen in severe cases (P < 0.05). Twenty-five (16.2%) had C-reactive protein ≥ 40 mg/L, and 91 (58.7%) had procalcitonin ≥ 0.25 mg/L. Adenovirus types 7 and 3 caused the outbreak of adenovirus pneumonia in community children during late spring to summer in 2019 in Xiamen. The majority of adenovirus pneumonia resembles bacterial pneumonia. The incidence of severe pneumonia was high when type 7 predominantly prevailed. Adenovirus type 7 was more common in severe cases than in nonsevere cases.

506. Neonatal CD8+ T Cells Demonstrate PD-1 Dependent Impairment Following Human Metapneumovirus Infection

Abstract Background Human metapneumovirus (HMPV) is a leading cause of pediatric acute respiratory illness, accounting for 14.2 million acute lower respiratory tract infections and 500,000 hospitalizations per year in children less than 5 years of age globally. Infants and neonates are particularly susceptible to severe HMPV disease. Our prior studies in adult mice demonstrated CD8+ T cells were critical for clearance of HMPV infection, although these cells show impaired function due to PD-1:PD-L1 signaling. However, the immune system in the neonatal lung skews towards an anti-inflammatory and tolerogenic response when compared to adults. We therefore sought to explore the roles CD8+ T cell and PD-1 signaling in neonatal mice to recapitulate the population at highest risk. Methods C57BL/6 or Pdcd1-/- pups were infected intranasally with 1.0x106 PFU/g of a clinical isolate of HMPV (TN94-49) on day of life 4-6. Viral burden was assessed via plaque assay and cellular responses were characterized by multispectral flow cytometry. Results HMPV infection led to stunted weight gain in pups compared to mock-infected controls. HMPV-infected neonatal mice had a robust innate immune response comprised of neutrophils, CD103+ dendritic cells, and interstitial macrophages, all of which demonstrated upregulation of PD-L1. From an adaptive perspective, neonatal mice mounted an antigen-specific CD8+ T cell response and resolved HMPV infection by day 8 post-infection. Similar to our prior studies in adult mice, neonatal CD8+ T cells upregulated expression of several inhibitory receptors, such as PD-1, LAG-3, and TIM-3. Neonatal CD8+T cells demonstrated limited effector cytokine production, such as IFN-γ and granzyme B, following ex vivo stimulation with a class I HMPV-specific peptide. Pdcd1-/- mice (lacking PD-1) also mounted an antigen-specific CD8+ T cell response, but had markedly increased production of IFN-γ and granzyme B. Conclusion These data demonstrate that PD-1 signaling on CD8+ T cells constrains the antiviral response in a novel model of neonatal respiratory viral infection. Understanding the mechanisms that inhibit neonatal anti-viral responses could present opportunities for novel therapeutic strategies for common infections with high morbidity and mortality in neonates and infants. Disclosures John Williams, MD, GlaxoSmithKline: Advisor/Consultant|Quidel: Advisor/Consultant.

Development of Inhalable Chitosan-Coated Oxymatrine Liposomes to Alleviate RSV-Infected Mice.

Human respiratory syncytial virus (RSV) infection is the most important cause of acute lower respiratory tract infection in infants, neonates, and young children, even leading to hyperinflation and atelectasis. Oxymatrine (OMT), originating from natural herbs, possessed potential antivirus activity against influenza A virus, Coxsackie B3 virus, and RSV, whereas the absence of an in vivo study indicated the difficulties in overcoming the physiological obstacles. Since RSV basically replicated in lung tissue, in this study, we fabricated and characterized a chitosan (CS)-coated liposome with OMT loaded for the treatment of lethal RSV infection via inhalation. The results uncovered that OMT, as a hydrophilic drug, was liable to diffuse in the mucus layer and penetrate through the gas-blood barrier to enter systemic circulation quickly, which might restrict its inhibitory effect on RSV replication. The CS-coated liposome enhanced the distribution and retention of OMT in lung tissue without restriction from mucus, which contributed to the improved alleviative effect of OMT on lethal RSV-infected mice. Overall, this study provides a novel inhalation therapy for RSV infection, and the CS-coated liposome might be a potential inhalable nanocarrier for hydrophilic drugs to prevent pulmonary infections.

Changes following the Onset of the COVID-19 Pandemic in the Burden of Hospitalization for Respiratory Syncytial Virus Acute Lower Respiratory Infection in Children under Two Years: A Retrospective Study from Croatia.

To understand the changes in RSV hospitalization burden in children younger than two years following the onset of the COVID-19 pandemic, we reviewed hospital records of children with acute lower respiratory infection (ALRI) between January 2018 and June 2022 in Split-Dalmatia County, Croatia. We compared RSV activity, age-specific annualized hospitalization rate, and disease severity between pre-COVID-19 and COVID-19 periods. A total of 942 ALRI hospital admissions were included. RSV activity remained low for the typical RSV epidemic during 2020-2021 winter. An out-of-season RSV resurgence was observed in late spring and summer of 2021. Before the COVID-19 pandemic, the annualized hospitalization rate for RSV-associated ALRI was 13.84/1000 (95% CI: 12.11-15.76) and highest among infants under six months. After the resurgence of RSV in the second half of 2021, the annualized hospitalization rate for RSV-associated ALRI in children younger than two years returned to the pre-pandemic levels with similar age distribution but a statistically higher proportion of severe cases. RSV immunization programs targeting protection of infants under six months of age are expected to remain impactful, although the optimal timing of administration would depend on RSV seasonality that has not yet been established in the study setting since the onset of the COVID-19 pandemic.

Clinical characteristics and molecular epidemiology of human metapneumovirus in children with acute lower respiratory tract infections in China, 2017 to 2019: A multicentre prospective observational study.

Human metapneumovirus (HMPV) infection is one of the leading causes of hospitalization in young children with acute respiratory illness. In this study, we prospectively collected respiratory tract samples from children who were hospitalized with acute lower respiratory tract infection in six hospitals in China from 2017 to 2019. HMPV was detected in 145 out of 2733 samples (5.3%) from the hospitalized children. The majority of HMPV-positive children were under the age of two (67.6%), with a median age of one year. HMPV can independently cause acute lower respiratory tract infection in young children, while all patients showed mild clinical symptoms. Of all the co-infected patients, HMPV was most commonly detected with enterovirus (EV) or rhinovirus (RhV) (38.0%, followed by respiratory syncytial virus (RSV) (32.0%). The highest detection rate occurred from March to May in both northern and southern China. Out of 145 HMPV positive samples, 48 were successfully typed, of which 36 strains were subgrouped into subtypes A2c (75%), eight strains were included in subtype B1 (16.7%), and four strains were included in subtype B2 (8.3%). Moreover, 16 A2c strains contained 111-nucleotide duplications in the G gene. Twenty-seven complete HMPV genomes were successfully obtained, and 25 (92.6%) strains belonged to subtype A2c, whereas one strain was included in subgroup B1 and another was included in subgroup B2. A total of 277 mutations were observed in the complete genomes of 25 A2c strains. All results presented here improve our understanding of clinical characteristics and molecular epidemiology of HMPV infection in children.

Vitamin D status of children with lower respiratory tract infections and its correlation with severity of pneumonia: A comparative study

Background: Acute lower respiratory tract infections (LRTI) is responsible for considerable morbidity and mortality among pediatric age group and remains one of the common causes for pediatric intensive care unit admissions. Vitamin D deficiency is one of the important risk factors not only for the occurrence but also for the increased severity of LRTI. We undertook this study to analyze vitamin D status of children admitted for LRTI and to find out its correlation with severity of LRTI. Aims and Objectives: The aims of this study were as follows: (1) To find out vitamin D status of children presenting with LRTI and (2) to find out correlation of vitamin D levels with severity of LRTI. Materials and Methods: This was a hospital-based comparative study, in which 60 children below age of 5 years and admitted for acute LRTI were included on the basis of a predefined inclusion and exclusion criteria (Group A). Sixty other children admitted for non-respiratory causes were included as control group (Group B). Vitamin D status of children in both the groups was determined. The severity of LRTI and its correlation with vitamin D status was determined. P&lt;0.05 was taken as statistically significant. Results: There was a male predominance in both the groups. The mean age of patients in Group A and Group B was found to be 17.70±7.80 months and 18.41±7.11 months, respectively (P&gt;0.005). In Group A, 42 (70%) patients were having bronchiolitis, whereas bronchopneumonia was seen in 16 (26.67%) patients and two patients (3.33%) were found to have lobar pneumonia. Forty-eight (80%) children were having pneumonia and remaining 12 (20%) children were found to have severe pneumonia. Higher number of children were either vitamin D inefficient or deficient in Group A as compared to Group B and the difference was found to be statistically highly significant (P&lt;0.0001). The mean 25 (OH) D levels were found to be low in patients with severe pneumonia as compared to pneumonia and the difference was found to be statistically highly significant (P&lt;0.0001). Conclusion: Lower levels of vitamin D were found to be a risk factor not only for the development but also for severity of LRTI. Determination and management of vitamin D deficiency status is one of the important parts of management of children with LRTI.

Association between Antihypertensive Therapy and Risk of Acute Lower Respiratory Infections (ALRI): A Retrospective Cohort Study.

Purpose: The aim of this study was to analyze the association between antihypertensive drugs and the incidence of acute lower respiratory infections in patients treated in general practices in Germany. Methods: After propensity score matching of five antihypertensive drug classes, a total of 377,470 patients aged ≥18 years were available for analysis. The association between each antihypertensive drug class and ALRI incidence as compared to all other antihypertensive drug classes (as a group) was studied using conditional Cox regression analyses. Because of multiple comparisons and large patient samples, findings were clinically considered relevant when the hazard ratio was <0.85 or >1.15. Results: The regression analyses applied found no clinically relevant associations between antihypertensive drugs and the incidence of acute lower respiratory infections, as all hazard ratios were between 0.85 and 1.15. Conclusion: In the present study, only slight and not clinically relevant increases or decreases in the ALRI incidence were observed. Additional studies are necessary to further explore the risks associated with antihypertensive agents that are widely embedded in today’s clinical practice.

Burden and severity of children's hospitalizations by respiratory syncytial virus in Portugal, 2015-2018.

Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children and is of considerable burden on healthcare systems. Our study aimed to evaluate ALRI hospitalizations related to RSV in children in Portugal. We reviewed hospitalizations potentially related to RSV in children aged <5years from 2015 to 2018, using anonymized administrative data covering all public hospital discharges in mainland Portugal. Three case definitions were considered: (a) RSV-specific, (b) (a) plus unspecified acute bronchiolitis (RSV-specific & Bronchiolitis), and (c) (b) plus unspecified ALRI (RSV-specific & ALRI). A total of 9697 RSV-specific hospitalizations were identified from 2015 to 2018-increasing to 26 062 for RSV-specific & ALRI hospitalizations-of which 74.7% were during seasons 2015/2016-2017/2018 (November-March). Mean hospitalization rates per season were, for RSV-specific, RSV-specific & Bronchiolitis, and RSV-specific & ALRI, respectively, 5.6, 9.4, and 11.8 per 1000 children aged <5years and 13.4, 22.5, and 25.9 in children aged <2years. Most RSV-specific hospitalizations occurred in healthy children (94.9%) and in children aged <2years (96.3%). Annual direct costs of €2.4 million were estimated for RSV-specific hospitalizations-rising to €5.1 million for RSV-specific & ALRI-mostly driven by healthy children (87.6%). RSV is accountable for a substantial number of hospitalizations in children, especially during their first year of life. Hospitalizations are mainly driven by healthy children. The variability of the potential RSV burden across case definitions highlights the need for a universal RSV surveillance system to guide prevention strategies.

Effect of ambient PM2.5 on healthcare utilisation for acute respiratory illness, Melbourne, Victoria, 2014-2019

ABSTRACT Ambient particulate matter (PM2.5) is an important component of natural and human-generated air pollution and a major contributor to the global burden of disease. Short-term effects of PM2.5 exposure on respiratory illness have been described but most evidence arises from high pollution settings. We used case-crossover methods to estimate effects of outdoor PM2.5 levels on emergency department (ED) presentations and hospital admissions for a range of acute respiratory illnesses and age groups in Melbourne, Australia from 2014-2019, with and without adjustment for other pollutants and weather conditions, using daily and one-week averaged lags. We estimated incidence rate ratios for a 10 μg/m3 increase in 7-day average ambient PM2.5 of 1.043 (95% confidence interval (CI): 1.000 – 1.089) on ED presentation and 1.013 (95% CI: 0.971 – 1.056) on hospital admissions for acute respiratory illnesses for patients of any age. We observed distinct temporal patterns in daily lag effect by disease. The largest effects on acute lower respiratory tract infection and asthma were observed in children. Ambient PM2.5 levels rarely exceeded standards in place at the time. Although uncertainty around most point estimates was relatively wide, these findings are most compatible with adverse health effects of ambient PM2.5 at levels below currently established Australian national standards.

Persistence of RNA Viruses in the Respiratory Tract: An Overview.

Respiratory RNA viruses are a major cause of acute lower respiratory tract infections and contribute substantially to hospitalization among infants, elderly, and immunocompromised. Complete viral clearance from acute infections is not always achieved, leading to persistence. Certain chronic respiratory diseases like asthma and chronic obstructive pulmonary disease have been associated with persistent infection by human respiratory syncytial virus and human rhinovirus, but it is still not clear whether RNA viruses really establish long-term infections as it has been recognized for DNA viruses as human bocavirus and adenoviruses. Herein, we summarize evidence of RNA virus persistence in the human respiratory tract, as well as in some animal models, to highlight how long-term infections might be related to development and/or maintenance of chronic respiratory symptoms.

Impact of Respiratory Syncytial Virus and Influenza Virus Infection in the Adult Population in Spain between 2012 and 2020.

Respiratory syncytial virus (RSV) infection is increasingly recognized as a cause of significant morbidity and mortality in adults. We aimed to estimate the rates of age-specific hospitalization and in-hospital mortality caused by acute lower respiratory tract infections (ALRTIs) in Spain between 2012 and 2020 and to compare the relative impact of RSV and influenza virus infection in adults. We used the discharge reports from the Minimum Basic Data Set to retrospectively analyze hospital discharge data on the basis of the ICD-9-CM and ICD-10-CM diagnosis codes. A total of 1,518,244 patients were hospitalized for ALRTIs, of whom 137,794 (9.1%) were admitted for RSV-related infections and 46,288 (3.0%) for influenza-related infections. In patients aged 60 years or older, the hospitalization rates (per 100,000 population) were estimated at 1.69 (95% CI 1.68-1.70) and 2.72 (95% CI 2.71-2.73) for RSV and influenza patients, respectively. However, in-hospital mortality rates were significantly higher among RSV patients than among influenza patients, 7.91% (95% CI 7.89-7.93) (83.0% of all RSV-related deaths) versus 6.91% (95% CI 6.89-6.93) (85.6% of all influenza-related deaths), respectively (p = 0.007). RSV-associated in-hospital mortality increases exponentially with age, posing a greater risk for older adults, particularly frail and high-risk patients.

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling.

Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infections in infants. Currently, ribavirin, a nucleoside analog containing a 1,2,4-triazole-3-carboxamide moiety, is a first-line drug for its treatment, however, its clinical use has been limited due to its side effects. Here, we designed two new nitroaryl-1,2,3-triazole triterpene derivatives as novel anti-RSV drugs. Their anti-RSV and cytotoxic activity were evaluated in vitro, RSV protein F gene effects by RT-PCR and molecular modeling with inosine monophosphate dehydrogenase (IMPDH) were performed. Compound 8 was the best performing compound, with an EC50 value of 0.053 μM, a TI of 11160.37 and it inhibited hRSV protein F gene expression by approximately 65%. Molecular docking showed a top-ranked solution located in the same region occupied by crystallographic ligands in their complex with IMPDH. The results obtained in this study suggest that compound 8 might be a new anti-RSV candidate.

Respiratory Syncytial Virus Incidence and Severity in a Community-Based Prospective Cohort of Children Aged 0–14 Years

Respiratory syncytial virus (RSV) is a substantial source of severe illnesses including acute lower respiratory infections (ALRIs) like pneumonia. However, its burden in older children remains less well understood. Using a community-based prospective cohort, we assessed the burden of symptomatic reverse-transcription polymerase chain reaction-confirmed RSV among Nicaraguan children aged 0-14 years from 2011 to 2016. ALRI was defined as physician diagnosis of pneumonia, bronchiolitis, bronchitis, or bronchial hyperreactivity. Between 2011 and 2016, 2575 children participated in the cohort. Of these, 630 (24.5%) had at least 1 episode of symptomatic RSV and 194 (7.5%) had multiple episodes. Subtype was identified in 571 (69.3%) episodes with 408 (71.5%) RSV-A, 157 (27.5%) RSV-B, and 6 (1%) positive for both. Children aged <2 years displayed the highest incidence of symptomatic RSV, with 269.3 cases per 1000 person-years (95% confidence interval [CI], 242.1-299.5). Beyond 2 years, incidence (95% CI) of symptomatic RSV decreased rapidly: 145.6 (129.9-163.1), 37.9 (31.9-45.0), and 19.3 (14.9-25.0) cases per 1000 person-years among children aged 2-4, 5-9, and 10-14 years, respectively. Incidence of RSV-associated ALRI was highest in children aged <2 years (85.95 per 1000 person-years [95% CI, 71.30-103.61]): 2.1, 9.5, and 17.3 times that of participants aged 2-4, 5-9, and 10-14 years, respectively. Children <2 years old were significantly more likely to have an RSV-associated hospitalization (P < .001). There is a substantial burden of symptomatic and severe RSV in children. While older children did present with RSV, the rates of symptomatic and severe RSV decreased by as much as 95% beyond age 5.

Assessment of attributable proportion of particulate matter (PM 2.5 and PM10) to different mortalities in Lahore city, Pakistan

&lt;p&gt;This study was conducted to evaluate the attributable proportion and relative risks caused by inevitable exposure of humans to particulate matter (PM2.5 and PM10). The health impacts of particulates in terms of attributable proportion were modulated using AirQ+ software. Input data related to particulates’ concentration, health and population were collected from the Environment Protection Department (EPD), Punjab Bureau of Statistics and Health Department of Punjab. Results showed that PM2.5 with the year average concentration of 55.9 ug/m3 contributes 24.17% attributable-proportion (AP) to all-cause mortality in adults age 30+, and 31.41% AP to Chronic Obstructive Pulmonary Disease (COPD) in adults age 30+. Attributable proportion to stroke mortality in adults age 25+ was 33.4% (BI-150) and 34.09% (BI-630) was in children aged 0-5 years, contributing to acute lower respiratory infection (ALRI) mortality. Modulated results indicated that the attributable proportion to ischemic heart diseases (IHD) was 40.8% (BI-95.2) in adults age 25+ and PM10 with an average concentration of 105 ug/m3 contributes 31.11% AP to infant post-neonatal. There is need of proper mitigation measures for reduction of pollutants’ concentration to decrease potential health impacts of air particulates.&lt;/p&gt;&#x0D;

The Incidence of Acute Respiratory Infection Was Higher in the Older Adults with Lower Limb Fracture Who Receive Spinal Anesthesia Than Those Who Receive General Anesthesia.

Acute respiratory infection (ARI) can significantly reduce postoperative quality of life and impair the recovery of older adult patients with lower-limb fractures, and its relationship with methods of anesthesia remains inconclusive. Using data from the National Health Insurance Research Database (NHIRD) of Taiwan, this study examined the data of patients who received surgical management for lower-limb fractures and compared those who underwent general anesthesia (GA) with those who underwent regional anesthesia (RA) in terms of their incidence of acute upper and lower respiratory infection during the one-month postoperative period. The study also identified related risk factors. Approximately two million patients were randomly sampled from the NHIRD registry. We identified and enrolled patients with lower-limb fractures who were over 60 years old and underwent GA or RA during surgeries conducted between 2010 and 2017. We divided these patients into two groups for further analysis. The outcome of this study was the development of ARI during the one-month postoperative period. In total, 45,032 patients (GA group, 19,580 patients; RA group, 25,452 patients) with a mean age of 75.0 ± 8.9 years were included in our study. The incidence of postoperative ARI within one month of surgery was 8.0% (1562 patients) in the GA group and 9.5% (2412 patients) in the RA group, revealing a significant difference. The significant risk factors for the incidence of ARI were the application of RA for surgery, older age, hypertension, liver disease, and chronic obstructive pulmonary disease (COPD). A subgroup analysis revealed that the RA method was associated with a significantly higher ARI incidence relative to the GA method among patients aged between 60 and 80 years, among male patients, among the patients with or without any comorbidity and among the patients without COPD. The incidence of postoperative ARI within one month of surgery was higher among older patients with lower-limb fractures who received RA for surgery than among those who received GA for surgery. The other major risk factors for ARI were older age, hypertension, liver disease, and COPD. Therefore, we should focus on patients with a high risk of developing ARI, especially during the COVID-19 pandemic.

Optimal Respiratory Syncytial Virus intervention programmes using Nirsevimab in England and Wales

IntroductionRespiratory Syncytial Virus (RSV) is a major cause of acute lower respiratory tract infections (ALRI) in infants. There are no licensed vaccines and only one monoclonal antibody available to protect infants from disease. A new and potentially longer-lasting monoclonal antibody, Nirsevimab, showed promising results in phase IIb/III trials. We evaluate the cost-effectiveness of Nirsevimab intervention programmes in England and Wales. MethodsWe used a dynamic model for RSV transmission, calibrated to data from England and Wales. We considered a suite of potential Nirsevimab programmes, including administration to all neonates (year-round); only neonates born during the RSV season (seasonal); or neonates born during the RSV season plus infants less than six months old before the start of the RSV season (seasonal + catch-up). ResultsIf administered seasonally to all infants at birth, we found that Nirsevimab would have to be priced at £63 or less per dose for at least 50% certainty that it could cost-effectively replace the current Palivizumab programme, using an ICER threshold of £20,000/QALY. An extended seasonal programme which includes a pre-season catch-up becomes the optimal strategy at a purchasing price of £32/dose or less for at least 50% certainty. At a purchasing price per dose of £5-32, the annual implementation costs of a seasonal programme could be as high as £2 million before a switch to a year-round strategy would be optimal. DiscussionNirsevimab has the potential to be cost-effective in England and Wales not only for use in high-risk infants.

Burden of disease attributed to acute respiratory infections in South America.

Respiratory diseases (RD) are an important public health problem. Their burden has not been comprehensively evaluated in South America (SA). This study describes the burden of acute respiratory infections (ARIs) in SA in 2019. This is an exploratory, population-based study with a quantitative approach to incidence, mortality, and Disability-adjusted life years (DALYs) by standardized age group among the 12 countries. Measurements were captured through the Institute for Health Metrics and Evaluation (IHME) website. It used the Burden Study Global Disease, Injury and Risk Factors (GBD) 2019 assessment. Correlation analyses were performed. The age-standardized incidence rate per 1,00,000 people for lower respiratory infections (LRIs) is lowest in Chile (3,902) and highest in Peru (9,997). For upper respiratory infections (URIs), Bolivia (2,25,826) had the lowest rates, while Brazil (3,16,667) and Colombia (3,06,302) had the highest. Standardized mortality rates for LRI were lowest in Colombia (15.10) and highest in Bolivia (80.53). Bolivia had the highest standardized DALY rate (2,083), while Uruguay had the lowest (468). Upper ARI had lower incidence rates than lower ARI. The lowest DALY rates were in Suriname (82) and the highest were in Brazil (111). There is a correlation between sociodemographic and economic health indicators and the standardized rates of incidence and DALY in the upper ARIs. The present paper provides comprehensive ARI burden estimates for the region. The substantial incidence and considerable mortality and DALYs are noteworthy and lead to reflections on preventive measures such as rational use of antibiotics and deeper epidemiological investigations.

Diagnosis and clinical significance of Human bocavirus 1 in children hospitalized for lower acute respiratory infection: molecular detection in respiratory secretions and serum.

Introduction. Human bocavirus 1 (HBoV1) infection occurs with viral genome presence in respiratory secretions (RS) and serum, and therefore both samples can be used for diagnosis.Gap statement. The diagnostic sensitivity of HBoV1 DNA detection in serum and the duration of DNAaemia in severe clinical cases have not been elucidated.Aim. To determine HBoV1 DNA in serum and RS of paediatric patients hospitalized for lower acute respiratory infection (LARI) and to analyse the clinical-epidemiological features of positive cases.Methodology. This was a prospective, transverse study. Physicians selected the clinical situations and obtained paired clinical samples (RS and serum) that were tested by PCR/qPCR for HBoV1. Positive cases were analysed considering time of specimen collection, co-detection, clinical manifestations and viral load; statistical significant level was set at α=0.05.Results. HBoV1 was detected in 98 of 402 cases included (24 %); 18/98 (18 %) patients had the virus detectable in serum and 91/98 (93 %) in RS (P<0.001). Positivity rates were not significantly different in patients with RS and serum collected within or beyond 24 h of admission. Single HBoV1 infection was identified in 39/98 patients (40 %), three patients had HBoV1 in both clinical samples (3/39, 8 %) and 32 (32/39, 82 %) only in RS, 22 of them (69 %) with both clinical samples within 24 h of admission. Cough (P=0.001) and rhinitis (P=0.003) were significantly frequent among them and most patients were diagnosed with bronchiolitis (22/39, 56 %) and pneumonia (9/39, 23 %), which was more frequent compared to cases with co-infection (P=0.04). No significant differences were identified among patients with high, medium or low viral load of HBoV1 regarding rate of positivity in both clinical samples, the time of collection of RS and serum, co-detection, first episode of LARI, clinical manifestations, comorbidity or requirement for assisted ventilation. Intensive care unit (ICU) patients had a significantly higher frequency of detection (P<0.001) and co-detection (P=0.001) compared to patients on standard care.Conclusions. HBoV1 is prevalent among infant patients hospitalized for LARI and including it in the standard testing can add to the aetiological diagnosis in these cases, especially for patients admitted to the ICU. HBoV1 detection in serum did not contribute significantly to the diagnosis as compared to detection in respiratory secretions.