Lower Respiratory Tract Infections In Children Research Articles

Complications and long-term impact of early life pneumonia.

Pneumonia is an infection affecting the lower airway, where the air sacs are filled with mucus and pus; and typically presents with cough, fever, and fast breathing. Pneumonia is estimated to be the leading cause of mortality in children under five worldwide with 120 million episodes result in 1 million deaths globally. The Low-Income and Middle-Income Countries (LMICs) are more affected. In a study in southeast Nigeria, bronchopneumonia accounted for 41.9%, of the cases admitted in the tertiary hospitals and in another hospital based study among children, pneumonia had the highest respiratory admission rates at 34.0%. Pneumonia can be caused by various organisms: Bacterial (Streptococcus, staphylococcus etc), Viral (RSV) and recently COVID 19 pneumonia. RSV has been noted globally to be a major cause of childhood lower respiratory tract infection, with morbidity/mortality occurring in 99% of (LMICs). Some of the long term sequalae are discussed.

Infectious acute respiratory failure in patients under 5 years of age: a retrospective cohort study

BackgroundAcute lower respiratory infections in children under 5 years present a real challenge for diagnosis and treatment and are the first cause of mortality for this group of age. The...

Pediatric COVID-19 in Lesotho and Post-pandemic Implications on Lower Respiratory Infections in Children.

Background The United States Agency for International Development (USAID) Reaching Impact, Saturation, and Epidemic Control (RISE) program funded Jhpiego to support the Government of Lesotho's COVID-19 response, including two national COVID-19 treatment centers. To evaluate the status of post-pandemic pediatric respiratory care in Lesotho, we analyzed pediatric treatment center data and healthcare worker (HCW) performance on pediatric COVID-19 training offered to HCWs at COVID-19 treatment centers. Methods We conducted a retrospective cohort study of patients 15 years of age or less hospitalized at two COVID-19 treatment centers in Lesotho from May 1, 2020, to April 30, 2022. Patient data were extracted from hospital files. We used the independent sample t-test, Mann-Whitney U test, or Fisher's exact test to evaluate associations between exposure variables and death. We also assessed differences between pre- and post-training examination scores of three one-day HCW training on pediatric COVID-19 using paired t-tests. Results Overall, <15-year-olds comprised 18/1,448 (1.2%) hospitalizations. Twenty-two percent (4/18) of children were hypoxemic (oxyhemoglobin saturation <94%) within the first 24 hours and 44% (8/18) at any point in the hospitalization. Oxygen utilization increased over the two-year period (p=0.004) and all eight children with hypoxemia received oxygen (p<0.001). Four of 18 (22%) patients died. For HCW training, pre- and post-training examinations were completed by 76/82 (92.7%) participants. The overall mean pretraining score was 44.6% (standard deviation (SD) 15.7%). Mean scores improved by an average of 32.2% (95% confidence interval (CI) 27.7%, 36.6%, p<0.001) on the same day post-training examination. Conclusions National COVID-19 treatment center data indicate a low burden of severe pediatric COVID-19 disease in Lesotho. However, recognized HCW knowledge gaps suggest deficiencies in identifying and referring severely ill children, which may detrimentally impact the ongoing post-pandemic care of children with severe lower respiratory infections.

Choices of morbidity outcomes and concentration-response functions for health risk assessment of long-term exposure to air pollution.

Air pollution health risk assessment (HRA) has been typically conducted for all causes and cause-specific mortality based on concentration-response functions (CRFs) from meta-analyses that synthesize the evidence on air pollution health effects. There is a need for a similar systematic approach for HRA for morbidity outcomes, which have often been omitted from HRA of air pollution, thus underestimating the full air pollution burden. We aimed to compile from the existing systematic reviews and meta-analyses CRFs for the incidence of several diseases that could be applied in HRA. To achieve this goal, we have developed a comprehensive strategy for the appraisal of the systematic reviews and meta-analyses that examine the relationship between long-term exposure to particulate matter with an aerodynamic diameter smaller than 2.5 µm (PM2.5), nitrogen dioxide (NO2), or ozone (O3) and incidence of various diseases. To establish the basis for our evaluation, we considered the causality determinations provided by the US Environmental Protection Agency Integrated Science Assessment for PM2.5, NO2, and O3. We developed a list of pollutant/outcome pairs based on these assessments and the evidence of a causal relationship between air pollutants and specific health outcomes. We conducted a comprehensive literature search using two databases and identified 75 relevant systematic reviews and meta-analyses for PM2.5 and NO2. We found no relevant reviews for long-term exposure to ozone. We evaluated the reliability of these studies using an adaptation of the AMSTAR 2 tool, which assesses various characteristics of the reviews, such as literature search, data extraction, statistical analysis, and bias evaluation. The tool's adaptation focused on issues relevant to studies on the health effects of air pollution. Based on our assessment, we selected reviews that could be credible sources of CRF for HRA. We also assessed the confidence in the findings of the selected systematic reviews and meta-analyses as the sources of CRF for HRA. We developed specific criteria for the evaluation, considering factors such as the number of included studies, their geographical distribution, heterogeneity of study results, the statistical significance and precision of the pooled risk estimate in the meta-analysis, and consistency with more recent studies. Based on our assessment, we classified the outcomes into three lists: list A (a reliable quantification of health effects is possible in an HRA), list B+ (HRA is possible, but there is greater uncertainty around the reliability of the CRF compared to those included on list A), and list B- (HRA is not recommended because of the substantial uncertainty of the CRF). In our final evaluation, list A includes six CRFs for PM2.5 (asthma in children, chronic obstructive pulmonary disease, ischemic heart disease events, stroke, hypertension, and lung cancer) and three outcomes for NO2 (asthma in children and in adults, and acute lower respiratory infections in children). Three additional outcomes (diabetes, dementia, and autism spectrum disorders) for PM2.5 were included in list B+. Recommended CRFs are related to the incidence (onset) of the diseases. The International Classification of Diseases, 10th revision codes, age ranges, and suggested concentration ranges are also specified to ensure consistency and applicability in an HRA. No specific suggestions were given for ozone because of the lack of relevant systematic reviews. The suggestions formulated in this study, including CRFs selected from the available systematic reviews, can assist in conducting reliable HRAs and contribute to evidence-based decision-making in public health and environmental policy. Future research should continue to update and refine these suggestions as new evidence becomes available and methodologies evolve.

Confronting the challenge: a regional perspective by the Latin American pediatric infectious diseases society (SLIPE) expert group on respiratory syncytial virus-tackling the burden of disease and implementing preventive solutions.

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infections in children around the world. The post-pandemic era has resulted in a notable increase in reported cases of RSV infections, co-circulation of other respiratory viruses, shifts in epidemiology, altered respiratory season timing, and increased healthcare demand. Low- and middle-income countries are responsible for the highest burden of RSV disease, contributing significantly to health expenses during respiratory seasons and RSV-associated mortality in children. Until recently, supportive measures were the only intervention to treat or prevent RSV-infection, since preventive strategies like palivizumab are limited for high-risk populations. Advances in new available strategies, such as long-acting monoclonal antibodies during the neonatal period and vaccination of pregnant women, are now a reality. As the Regional Expert Group of the Latin American Pediatric Infectious Diseases Society (SLIPE), we sought to evaluate the burden of RSV infection in Latin America and the Caribbean (LAC) region, analyze current strategies to prevent RSV infection in children, and provide recommendations for implementing new strategies for preventing RSV infection in children in LAC region.

A Scoring System to Predict Severe Acute Lower Respiratory Infection in Children Caused by Respiratory Syncytial Virus.

There were several factors associated with respiratory syncytial virus (RSV) severe acute lower respiratory infection (RSV-sALRI) in infants and young children. It is vital to develop a convenient scoring system to predict RSV-sALRI in children. Pediatric patients with RSV-ALRI from January 2009 to December 2021 were recruited retrospectively. Two-third of them were randomly grouped into the development set and one-third to the validation set. In the development set, risk factors for RSV-sALRI were transferred into the logistic regression analysis, then their receiver operating characteristic (ROC) curves were built to obtain the area under the ROC curve (AUC), and regression coefficients for each predictor were converted to points. Finally, the value of the scoring system was evaluated in the validation set. A total of 1 066 children with RSV-ALRI were recruited, including 710 in the development set and 356 in the validation set. By logistic regression analysis, six factors (younger than 2 years, gestational age <37 weeks, have siblings, birth weight ≤2500 g, artificial/mix feeding, CHD) showed statistical difference and then were scored with points according to the coefficient value (OR) in the development set. In the validation set, the sensitivity of the scoring system was 70.25%, the specificity 85.53%, the positive predictive value 71.43%, the negative predictive value 84.81%, and coincidence rate 0.80. The Kolmogorov-Smirnov test showed the distribution of AUC 0.765 (SE = 0.027; 95% CI = 0.713-0.818; p < 0.001). A simplified scoring system was developed in the study with high prediction value for RSV-sALRI in children.

Introduction to the database “efficacy of different treatment modalities for lower respiratory tract infections in children”

AbstractThis study aimed to establish a registry database of different treatment modalities for lower respiratory tract infections (LRTIs) in Chinese children, thereby filling gaps in knowledge on clinical characteristics, treatment modalities, and rational drug use in relation to LRTIs in Chinese children, and providing large amounts of continuous, complete, scientific, and objective clinical data, and an information exchange platform. Multicenter data from these children's clinical visits were collected, pooled, and analyzed using medical informatics and statistical techniques to explore their potential value. The database was preliminarily established and a real‐world study cohort was constructed based on a total of 4805 patients registered in this database. Pneumonia was identified as the most common type of LRTIs (72.44%), followed by acute bronchitis (20.71%). The mean age of the enrolled children with LRTIs was 3.26 ± 2.84 years, and boys accounted for 59.21% of the samples. Among the enrolled children, pneumonia and acute bronchitis had the highest incidence in children aged 1–3 years (27.44%) and those aged 3–6 years (34.16%), respectively. In this national, multicenter, observational database of LRTIs in children, the real‐world characteristics and treatment modalities for LRTIs in Chinese children are elucidated. This database will help improve the research efficiency of clinicians and facilitate the exploration of underlying clinical patterns in real‐world medical big data.

Risk factors for respiratory syncytial virus-associated acute lower respiratory infection in children under 5 years: An updated systematic review and meta-analysis

ObjectivesRespiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection (ALRI) in young children. With substantial advances in RSV research, we aimed to conduct an updated systematic review of risk factors for RSV-ALRI in children under 5 years. MethodsWe updated our previously published literature search to November 2022 among three English databases and additionally searched three Chinese databases (from January 1995) to identify all relevant publications. We performed random-effects meta-analyses to estimate the pooled odds ratio (OR) and 95% confidence interval (CI) for each risk factor and each outcome (RSV-ALRI in the community and RSV-ALRI hospitalization). ResultsA total of 47 studies were included (26 from the updated search). Indoor air pollution was identified as a possible risk factor for RSV-ALRI in the community (OR 1.45, 95% CI: 1.10-1.90). The identified risk factors for RSV-ALRI hospitalization fall into four categories: demographic (male sex, Māori and Pacific ethnicities vs European or other ethnicities), pre- and post-neonatal (prematurity, low birth weight, small for gestational age, maternal smoking during pregnancy or lactation, maternal age <30 years vs 30-34 years, multiparity, caesarean section vs vaginal), household and environmental (having siblings, passive smoking, maternal asthma, daycare centre attendance) and health and medical conditions (any chronic diseases, bronchopulmonary dysplasia, HIV infections, congenital heart disease, Down syndrome, cystic fibrosis, previous asthma). The pooled ORs ranged from 1.14 to 4.55. ConclusionOur findings on the risk factors for RSV-ALRI help identify RSV high-risk groups, which has important implications for RSV prevention at both individual and population levels.

Occurrence and management of lower respiratory tract infections in children at a Nigerian tertiary hospital

Objectives Infectious diseases such as pneumonia, diarrhea, and malaria are the major causes of child mortality, with pneumonia, a lower respiratory tract infection (LRTI), being the foremost of the three. Antimicrobial agents are required to treat LRTIs, such as pneumonia caused by bacteria, while those commonly caused by viruses, such as bronchiolitis, do not benefit from antimicrobial therapy unless laboratory tests indicate otherwise. When not shown, empirical management of patients using antimicrobials remains a risk factor for antimicrobial resistance in the management of LRTIs. This study aimed to determine the occurrence of LRTIs in children who presented with acute respiratory tract infections (RTIs) and evaluate their management in comparison with the guidelines. Material and Methods The study was a descriptive retrospective review of prescribing records for respiratory tract infections (RTIs) presented at the Alex Ekwueme Federal University Teaching Hospital, Abakaliki (AE-FUTHA), Ebonyi State, Nigeria. Data were collected through systematic sampling of the case folders of children aged five years and below who presented with RTIs from January to December 2021, using a data collection proforma. Collected data were cleaned and coded, and Statistical Package for Social Sciences (SPSS) Version 28 was used for analysis. Results There were 422 case folders containing diagnoses of RTIs. Of these, 36 (8.5%) were diagnosed with LRTIs and 28 (6.6%) had no comorbidity. Of the 28 cases without comorbidities, pneumonia (20;71.4%) and bronchiolitis (8;28.6%) were the only two LRTIs. Antibiotics were the most prescribed medications, followed by vitamins (8;28.6%) and antihistamines (7;25.0%). There were seven types and three combinations of antibiotic medications, the most being cefuroxime (10;35.7%) followed by amoxicillin/clavulanic acid (7; 25.0%). One case of pneumonia did not receive an antibiotic. Laboratory investigations were not conducted for the majority (25;89.3%) of the cases presented. Conclusion This study showed that the LRTIs presented were mostly managed using the recommended antibiotics for pneumonia. Antibiotics for bronchiolitis without confirmation by laboratory tests may not have been justified as most of them are of viral origin. Deviations from guidelines may be reduced if national protocols are developed in managing LRTIs.

Respiratory Syncytial Virus and Influenza Infections in Children in Ulaanbaatar, Mongolia, 2015-2021.

Data available for RSV and influenza infections among children < 2 years in Mongolia are limited. We present data from four districts of Ulaanbaatar from April 2015 to June 2021. This study was nested in an enhanced surveillance project evaluating pneumococcal conjugate vaccine (PCV13) impact on the incidence of hospitalized lower respiratory tract infections (LRTIs). Our study was restricted to children aged < 2 years with arterial O2 saturation < 93% and children with radiological pneumonia. Nasopharyngeal (NP) swabs collected at admission were tested for RSV and influenza using qRT-PCR. NP swabs of all patients with radiological pneumonia and of a subset of randomly selected NP swabs were tested for S. pneumoniae (S.p.) by qPCR and for serotypes by culture and DNA microarray. Among 5705 patients, 2113 (37.0%) and 386 (6.8%) had RSV and influenza infections, respectively. Children aged 2-6 months had a higher percentage of very severe RSV infection compared to those older than 6 months (42.2% versus 31.4%, p-value Fisher's exact = 0.001). S.p. carriage was detected in 1073/2281 (47.0%) patients. Among S.p. carriage cases, 363/1073 (33.8%) had S.p. and RSV codetection, and 82/1073 (7.6%) had S.p. and influenza codetection. S.p. codetection with RSV/influenza was not associated with more severe LRTIs, compared to only RSV/influenza cases. In Mongolia, RSV is an important pathogen causing more severe LRTI in children under 6 months of age. Codetection of RSV or influenza virus and S.p. was not associated with increased severity.

Exploring Clinical Predictors of Severe Human Metapneumovirus Respiratory Tract Infections in Children: Insights from a Recent Outbreak.

Human metapneumovirus (hMPV) is an important pathogen that causes both upper (URTIs) and lower respiratory tract infections (LRTIs) in children. The virus can be implicated in severe bronchiolitis and pneumonia, necessitating hospitalization, with certain cases requiring intensive care unit intervention. As part of a retrospective observational study, we aimed to identify indicators of severe hMPV respiratory tract infections in children referred to the University Children's Hospital Ljubljana and the Department of Infectious Diseases Ljubljana, Slovenia, during a recent outbreak. We analyzed clinical data from November 2022 to January 2023 and compared the characteristics of children presenting with URTIs and LRTIs. We also examined the characteristics of children with hMPV LRTIs, distinguishing between children with and without LRTI-associated hypoxemia. Of 78 hMPV-PCR-positive pediatric patients (mean age 3.1 years; 60.3% boys), 36% had a URTI, and 64% had an LRTI. Hospitalization was required in 64% (50/78), with 42% (21/50) requiring oxygen therapy. LRTI-associated hypoxemia was more common in patients with atopy who showed dyspnea, tachypnea, crackles, and wheezing on lung auscultation. In a multivariable logistic regression analysis, wheezing detected on lung auscultation was a significant predictive factor for hypoxemic hMPV-LRTI. Specifically, children presenting with wheezing were found to be ten times more likely to experience hypoxemia. Prematurity and chronic conditions did not influence the presentation or severity of hMPV infection. This study highlights wheezing and atopy as crucial indicators of severe hMPV LRTI in children, emphasizing the importance of early recognition and intervention.

Investigating Nonspecific Effects of the Live-Attenuated Japanese Encephalitis Vaccine on Lower Respiratory Tract Infections in Children Aged 25-35 Months: Retrospective Cohort Study.

Live attenuated vaccines may be used to prevent nontargeted diseases such as lower respiratory tract infections (LRTIs) due to their nonspecific effects (NSEs). We aimed to analyze the NSEs of the Japanese encephalitis vaccine on pediatric LRTIs in children aged 25 months to 35 months. A retrospective cohort study was conducted by using a population-based electronic health record database in Zhejiang, China. Enrolled participants were children born from January 1, 2017, to December 31, 2017, and who were inoculated with the live-attenuated Japanese encephalitis vaccine (JE-L) or inactivated Japanese encephalitis vaccine (JE-I) as the most recent vaccine at 24 months of age. The study was carried out between January 1, 2019, and December 31, 2019. All inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months were recorded. The Andersen-Gill model was used to assess the NSEs of JE-L against LRTIs in children and compared with those of JE-I as the most recent vaccine. A total of 810 children born in 2017 were enrolled, of whom 585 received JE-L (JE-L cohort) and 225 received JE-I (JE-I cohort) as their last vaccine. The JE-L cohort showed a reduced risk of LRTIs (adjusted hazard ratio [aHR] 0.537, 95% CI 0.416-0.693), including pneumonia (aHR 0.501, 95% CI 0.393-0.638) and acute bronchitis (aHR 0.525, 95% CI 0.396-0.698) at 25 months to 35 months of age. The NSEs provided by JE-L were especially pronounced in female children (aHR 0.305, 95% CI 0.198-0.469) and children without chronic diseases (aHR 0.553, 95% CI 0.420-0.729), without siblings (aHR 0.361, 95% CI 0.255-0.511), with more than 30 inpatient and outpatient hospital visits prior to 24 months of age (aHR 0.163, 95% CI 0.091-0.290), or with 5 to 10 inpatient and outpatient hospital visits due to infectious diseases prior to 24 months old (aHR 0.058, 95% CI 0.017-0.202). Compared with JE-I, receiving JE-L as the most recent vaccine was associated with lower risk of inpatient and outpatient hospital visits for LRTIs among children aged 25 months to 35 months. The nature of NSEs induced by JE-L should be considered for policymakers and physicians when recommending JE vaccines to those at high risk of infection from the Japanese encephalitis virus.

Respiratory adenovirus infections in children: a focus on Africa.

Lower respiratory tract infections (LRTIs) are an important cause of child morbidity and mortality globally, especially in children under the age of 5 years in Africa. Respiratory viruses, including human adenoviruses (HAdVs), are common causes of LRTIs in children. This review aims to shed light on the epidemiology, clinical manifestations, sequelae, and treatment options specific to adenovirus respiratory infections in African children. Recent evidence has challenged the perception that adenovirus is a negligible cause of LRTIs. Studies show HAdV emerging as the third most common viral pathogen in fatal pneumonias among under-5 children in low-income and middle-income African countries, contributing to 5.5% of all pneumonia deaths and ranking second in hospital-associated viral pneumonia deaths. Predominant HAdV serotypes associated with disease differ by country and region, and have changed over time. Risk factors for increased disease severity and long-term respiratory sequelae in previously healthy African children with HAdV LRTIs are not well established. Although respiratory viruses, including HAdV, are recognized contributors to LRTIs, the prevalence and impact of adenovirus infections have been under-recognized and understated. Available data suggests that African children, particularly those under 5 years old, are at risk of severe sequelae from respiratory HAdV infections. Long-term sequelae, including bronchiectasis and postinfectious bronchiolitis obliterans, further underscore the significant impact of HAdV infections. However, the scarcity of comprehensive data hampers our understanding of the extent of the impact of HAdV infections on child lung health in Africa. We recommend scaled-up HAdV surveillance, ensuring its consistent inclusion in population-level LRTI assessments, and expanded and equitable access to diagnostics for early recognition of African children at risk of developing chronic sequelae and death. Enhanced understanding of adenovirus epidemiology and clinical outcomes and the availability of therapeutic options are essential for informed public health strategies and clinical care.

Impact of normalized COVID-19 prevention and control measures on lower respiratory tract infection pathogenesis in hospitalized children.

This study aimed to investigate the epidemiological characteristics of common pathogens contributing to childhood lower respiratory tract infections (LRTIs) in Xiangtan City, Hunan Province before and during the coronavirus disease 2019 (COVID-19) pandemic. A total of 11,891 enrolled patients, aged 1 month to 14 years, diagnosed with LRTIs and admitted to Xiangtan Central Hospital from January 2018 to December 2021 were retrospectively reviewed in this study. Specifically, the epidemiological characteristics of these pathogens before and during the COVID-19 pandemic were analyzed. There was a significant decrease in the number of children hospitalized with LRTIs during the COVID-19 pandemic (2020-2021) compared to data from 2018 to 2019 (before the COVID-19 pandemic). Of these cases, 60.01% (7,136/11,891) were male and 39.99% (4,755/11,891) were female. 78.9% (9,381/11,891) cases occurred in children under 4 years of age. The average pathogen detection rate among 11,891 hospitalized LRTIs children was 62.19% (7,395/11,891), with the average pathogen detection rate of 60.33% (4,635/7,682) and 65.57% (2,670/4,209) before and during COVID-19 pandemic, respectively. The detection rates of adenovirus (ADV), bordetella pertussis (BP) and moraxella catarrhalis (M. catarrhalis) decreased dramatically, while the detection rates of influenza viruses (IFV), parainfluenza viruses (PIV), respiratory syncytial virus (RSV), haemophilus influenzae (H. influenzae), streptococcus pneumoniae (S. pneumoniae), and staphylococcus aureus (S. aureus) increased significantly during the COVID-19 pandemic. Overall, RSV, mycoplasma pneumoniae (MP), H. influenzae, and IFV were the major pathogens causing LRTIs in hospitalized children before and during the COVID-19 pandemic. Public health interventions for COVID-19 prevention are beneficial to reduce the incidence of LRTIs in children by limiting the prevalence of ADV, MP, BP, and M. catarrhalis, but which have limited restrictive effects on other common LRTIs-associated pathogens. Collectively, the data in this study comprehensively investigated the effects of COVID-19 pandemic on the epidemiological characteristics of respiratory pathogens, which will be beneficial for improving early preventive measures.

Distinct roles for type I and type III interferons in virulent human metapneumovirus pathogenesis.

Human metapneumovirus (HMPV) is an important cause of acute lower respiratory infection in children and adults worldwide. There are four genetic subgroups of HMPV and both neutralizing antibodies and T cells contribute to protection. However, little is known about mechanisms of pathogenesis and most published work is based on a few extensively passaged, laboratory-adapted strains of HMPV. In this study, we isolated and characterized a panel of low passage HMPV clinical isolates representing all four genetic subgroups. The clinical isolates exhibited lower levels of in vitro replication compared to a lab-adapted strain. We compared disease phenotypes using a well-established mouse model. Several virulent isolates caused severe weight loss, lung pathology, airway dysfunction, and fatal disease in mice, which was confirmed in three inbred mouse strains. Disease severity did not correlate with lung viral titer, as virulent strains exhibited restricted replication in the lower airway. Virulent HMPV isolates were associated with markedly increased proinflammatory cytokine production and neutrophil influx; however, depletion of neutrophils or genetic ablation of inflammasome components did not reverse disease. Virulent clinical isolates induced markedly increased type I and type III interferon (IFN) secretion in vitro and in vivo. STAT1/2-deficient mice lacking both type I and type III IFN signaling showed reduced disease severity and increased lung viral replication. Inhibition of type I IFN signaling using a blocking antibody or genetic ablation of the type I IFN receptor reduced pathology with minimal effect on viral replication. Conversely, blockade of type III IFN signaling with a neutralizing antibody or genetic ablation of the IFN-lambda receptor had no effect on pathogenesis but restored viral replication. Collectively, these results demonstrate distinct roles for type I and type III IFN in HMPV pathogenesis and immunity.

Clinical predictors of hypoxemia in patients of acute lower respiratory tract infections: A hospital-based study

Aim: The aim of this study was to study clinical predictors of hypoxemia in patients of acute lower respiratory infections in children. Materials and Methods: An observational prospective study was conducted for 8 months in the General Pediatric Ward and Pediatric Intensive Care Unit of Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, a tertiary care hospital in Rohilkhand region. This is a hospital-based study. All children admitted with acute lower respiratory tract infections between the age group of 1 month to 59 months of age and diagnosed with pneumonia and bronchiolitis were enrolled and oxygen saturation of patients was recorded and compared with arterial blood gas. Results: A total of 40 patients were enrolled in the study. More than 90% cases of pneumonia and bronchiolitis presented with difficulty in breathing followed by rapid breathing as the next most common symptom. The least common symptom was noisy breathing and pain in abdomen. The most common signs observed were tachypnea which was present in 100% cases of mild, moderate, and severe hypoxemia. Tachypnea (91%), pallor (89%) and nasal flaring (84%), crepitations (added sounds), and subcostal retractions had better sensitivity for detecting hypoxemia. Conclusion: It was observed that a combination of clinical signs and symptoms can be used to predict hypoxemia when facilities of pulse oximetry and arterial blood gas analysis are not available, especially in low-resource settings.

Integration of lipidomics and metabolomics reveals plasma and urinary profiles associated with pediatric Mycoplasma pneumoniae infections and its severity.

Mycoplasma pneumoniae is a significant contributor to lower respiratory infections in children. However, the lipidomics and metabolics bases of childhood M. pneumoniae infections remain unclear. In this study, lipidomics and metabolomics analyses were conducted using UHPLC-LTQ-Orbitrap XL mass spectrometry and gas chromatography-triple quadrupole mass spectrometry on plasma (n = 65) and urine (n = 65) samples. MS-DIAL software, in combination with LipidBlast and Fiehn BinBase DB, identified 163 lipids and 104 metabolites in plasma samples, as well as 208 metabolites in urine samples. Perturbed lipid species (adjusted p < 0.05) were observed, including lysophosphatidylethanolamines, phosphatidylinositols, phosphatidylcholines, phosphatidylethanol amines, and triglycerides. Additionally, differential metabolites (adjusted p < 0.05) exhibited associations with amino acid metabolism, nucleotide metabolism, and energy metabolism. Thirteen plasma metabolites, namely l-hydroxyproline, 3-phosphoglycerate, citric acid, creatine, inosine, ribitol, α tocopherol, cholesterol, cystine, serine, uric acid, tagatose, and glycine, showed significant associations with disease severity (p < 0.05) and exhibited distinct separation patterns in M. pneumoniae-infected bronchitis and pneumonia, with an area under the curve of 0.927. Nine of them exhibited either positive or negative correlations with neutrophil or lymphocyte percentages. These findings indicated significant systemic metabolic shifts in childhood M. pneumoniae infections, offering valuable insights into the associated metabolic alterations and their relationship with disease severity.

Changes in clinical, demographic, and outcome patterns of children hospitalized with non-SARS-CoV-2 viral low respiratory tract infections before and during the COVID pandemic in Rome, Italy.

We performed this study aiming to evaluate changes in epidemiology, clinical presentation and outcomes of children hospitalized for viral lower respiratory tract infections (LRTI). We performed a retrospective study of children younger than 18 years of age hospitalized for LRTIs with a positive respiratory viral testing from 2018 to 2022. We compared need of pediatric intensive care unit (PICU), invasive ventilation, and other respiratory support, viral etiologies, clinical presentations, imaging, and laboratory results in the precovid (2018-2019) and covid (2020-2022) period. A total of 523 were included in the analysis. In the pandemic period, the detection of influenza was 95% less likely to occur (odds ratio [OR]: 0.05; 95% confidence interval [95% CI]: 0.02-0.12; p < .001), likewise the detection of adenovirus was 77% less likely to occur (OR: 0.23; 95% CI: 0.10-0.51; p < .001). In the pandemic period, the number of codetections increased from 15.52% in 2018 to 57.25% in 2022, resulting in a significantly increasing trend (p < .001). The odds of transfer to PICU was more than five times greater during the pandemic period (OR: 5.31; 95% CI: 1.78-15.86; p = .003). We found that the pattern of LRTI in children during COVID-19 pandemic significantly changed in terms of etiologies and increased severity.

Surge of lower respiratory tract group A streptococcal infections in England in winter 2022: epidemiology and clinical profile

BackgroundFollowing low incidence of invasive group A streptococcal (iGAS) infections during the COVID-19 pandemic, marked increases were noted in many countries during 2022, particularly in children. In November 2022, severe presentations of lower respiratory tract infections (LRTIs), including empyema, were notified by clinicians across the UK. UKHSA investigated this rise with the aim of informing clinical management and public health response. MethodsWe undertook a case-series analysis using multiple routine data sources, exempted from ethics approval or patient consent. We identified iGAS cases in England in children younger than 15 years with an LRTI reported between Oct 1 and Dec 21, 2022, using UKHSA laboratory surveillance data (GAS detected in LRT specimens) and notifications by clinicians and Health Protection Teams (HPTs). Symptoms, diagnoses, health-care interactions, and outcome (death or recovery) data were obtained from HPT case management notes, the National Child Mortality Database, and the NHS Digital Emergency Care Dataset. FindingsWe identified 147 cases of LRTI iGAS in children across England (77 [52%] male, 70 [48%] female; median age 4 years [IQR 2–6]). Predominant ethnicities were White (74 [65%] of 113 with known ethnicity) and Asian (18 [16%] of 113). Most reported symptoms were fever (90 [75%] of 120 children with ≥1 symptom) and cough (60 [50%] of 120), and 71 (48%) of all 147 children had a diagnosed respiratory viral coinfection (most commonly hMPV and RSV). 127 (86%) of children attended an emergency department, 31% (n=36/114 with onset date) at least twice within 21 days after symptom onset. 37 (25%) of 147 children died, with a median time from symptom onset to death of 4 days (IQR 3–7). Of 32 children with sample dates, 16 (84%) were tested for GAS on or after the day they died. Over half of deaths (21 [57%] of 37 deaths) occurred in the community after rapid deterioration, of whom 18 had previous contact with health-care services documented. InterpretationThe UK saw an unusual rise in iGAS LRTIs in children in late 2022. One in four cases died, over half in the community. Non-specific symptoms, viral symptoms, or positive virology might have lowered suspicion of bacterial infection. Although the use of multiple available data sources expedited the analysis, varying data completeness limited interpretation. Our study highlights the need for earlier detection and identification of effective measures to prevent death. FundingNone.

Metagenomic next-generation sequencing of bronchoalveolar lavage fluid assists in the diagnosis of pathogens associated with lower respiratory tract infections in children.

Worldwide, lower respiratory tract infections (LRTI) are an important cause of hospitalization in children. Due to the relative limitations of traditional pathogen detection methods, new detection methods are needed. The purpose of this study was to evaluate the value of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) samples for diagnosing children with LRTI based on the interpretation of sequencing results. A total of 211 children with LRTI admitted to the First Affiliated Hospital of Guangzhou Medical University from May 2019 to December 2020 were enrolled. The diagnostic performance of mNGS versus traditional methods for detecting pathogens was compared. The positive rate for the BALF mNGS analysis reached 95.48% (95% confidence interval [CI] 92.39% to 98.57%), which was superior to the culture method (44.07%, 95% CI 36.68% to 51.45%). For the detection of specific pathogens, mNGS showed similar diagnostic performance to PCR and antigen detection, except for Streptococcus pneumoniae, for which mNGS performed better than antigen detection. S. pneumoniae, cytomegalovirus and Candida albicans were the most common bacterial, viral and fungal pathogens. Common infections in children with LRTI were bacterial, viral and mixed bacterial-viral infections. Immunocompromised children with LRTI were highly susceptible to mixed and fungal infections. The initial diagnosis was modified based on mNGS in 29.6% (37/125) of patients. Receiver operating characteristic (ROC) curve analysis was performed to predict the relationship between inflammation indicators and the type of pathogen infection. BALF mNGS improves the sensitivity of pathogen detection and provides guidance in clinical practice for diagnosing LRTI in children.