Infectious and Inflammatory Pathways to Cough.

Coughing is a dynamic physiological process resulting from input of vagal sensory neurons innervating the airways and perceived airway irritation. Although cough serves to protect and clear the airways, it can also be exploited by respiratory pathogens to facilitate disease transmission. Microbial components or infection-induced inflammatory mediators can directly interact with sensory nerve receptors to induce a cough response. Analysis of cough-generated aerosols and transmission studies have further demonstrated how infectious disease is spread through coughing. This review summarizes the neurophysiology of cough, cough induction by respiratory pathogens and inflammation, and cough-mediated disease transmission.

Episodic Cost of Lower Respiratory Tract Illness due to Respiratory Syncytial Virus Among US Infants During the First Year of Life.

A study of 2 health care claims databases (commercial, Medicaid) was undertaken to estimate the episodic cost of lower respiratory tract illness due to respiratory syncytial virus among infants aged <12 months overall, by age, and by birth gestational age. Among commercial-insured infants, mean costs were $28 812 for hospitalized episodes, $2575 for emergency department episodes, and $336 for outpatient clinic episodes. Costs were highest among infants aged <1 month and infants with a gestational age ≤32 weeks and were comparable among Medicaid-insured infants, albeit somewhat lower. The cost of lower respiratory tract illness due to respiratory syncytial virus during the acute phase of illness is high, especially among the youngest infants and those born premature.

Epidemiological characteristics and outcome of viral respiratory tract infections in the first year after allogeneic hematopoietic cell transplantation.

Adverse outcomes of viral respiratory tract infections (RTI) have been reported in recipients of allogeneic hematopoietic cell transplantation. Using a laboratory-developed multiparameter PCR in a consecutive series of 242 patients, we found the highest incidence of viral RTI in the pre-engraftment phase. The occurrence of multiple episodes of viral RTI or viral pneumonia was significantly associated with a higher hazard of non-relapse mortality in the first year after transplantation. We observed a 90-day mortality of 19.7% after viral RTI, which was significantly different between patient groups stratified according to the ISI score.

Antibiotic prescribing for respiratory tract infections in urgent care: a comparison of in-person and virtual settings.

BACKGROUND: Little is known about antibiotic prescribing for respiratory tract infections (RTIs) in virtual versus in-person urgent care within the same health system. METHODS: This is a retrospective study using electronic health record data from Cleveland Clinic Health System. We identified RTI patients via ICD-10 codes and assessed whether the visit resulted in an antibiotic. We described differences in diagnoses and prescribing by type of urgent care (virtual versus in-person.) We used mixed effects logistic regression to model the odds of a patient receiving an antibiotic by urgent care setting. We applied the model first to all physicians and second only to those who saw patients in both settings. RESULTS: There were 69,189 in-person and 19,003 virtual visits. Fifty-eight percent of virtual visits resulted in an antibiotic compared to 43% of in-person visits. Sinusitis diagnoses were more than twice as common in virtual versus in-person care (36% versus 14%) and were associated with high rates of prescribing in both settings (95% in person, 91% virtual). Compared to in-person care, virtual urgent care was positively associated with a prescription (OR:1.64, 95%CI:1.53-1.75). Among visits conducted by 39 physicians who saw patients in both settings, odds of antibiotic prescription in virtual care were 1.71 times higher than in in-person care (95%CI:1.53-1.90). CONCLUSIONS: Antibiotic prescriptions were more common in virtual versus in-person urgent care settings, including among physicians who provided care in both platforms. This appears to be related to the high rate of sinusitis diagnosis in virtual urgent care.

Antibiotic Prescribing Patterns for Respiratory Tract Illnesses Following the Conclusion of an Education and Feedback Intervention in Primary Care.

BACKGROUND: A study previously conducted in primary care practices found that implementation of an educational session and peer comparison feedback was associated with reduced antibiotic prescribing for respiratory tract diagnoses (RTDs). Here, we assess the long-term effects of this intervention on antibiotic prescribing following cessation of feedback. METHODS: RTD encounters were grouped into tiers based on antibiotic prescribing appropriateness: tier 1, almost always indicated; tier 2, possibly indicated; and tier 3, rarely indicated. A χ2 test was used to compare prescribing between 3 time periods: pre-intervention, intervention, and post-intervention (14 months following cessation of feedback). A mixed-effects multivariable logistic regression analysis was performed to assess the association between period and prescribing. RESULTS: We analyzed 260 900 RTD encounters from 29 practices. Antibiotic prescribing was more frequent in the post-intervention period than in the intervention period (28.9% vs 23.0%, P < .001) but remained lower than the 35.2% pre-intervention rate (P < .001). In multivariable analysis, the odds of prescribing were higher in the post-intervention period than the intervention period for tier 2 (odds ratio [OR], 1.19; 95% confidence interval [CI]: 1.10-1.30; P < .05) and tier 3 (OR, 1.20; 95% CI: 1.12-1.30) indications but was lower compared to the pre-intervention period for each tier (OR, 0.66; 95% CI: 0.59-0.73 tier 2; OR, 0.68; 95% CI: 0.61-0.75 tier 3). CONCLUSIONS: The intervention effects appeared to last beyond the intervention period. However, without ongoing provider feedback, there was a trend toward increased prescribing. Future studies are needed to determine optimal strategies to sustain intervention effects.

Analyzing infections caused by 11 respiratory pathogens in children: Pre- and post-COVID-19 pandemic trends in China.

With the lifting of coronavirus disease 2019 (COVID-19) restrictions in December 2022 in China, the population was widely infected with COVID-19. We aim to analyzed changes in the epidemiological characteristics of other respiratory pathogens in children before and after the COVID-19 pandemic. We conducted a retrospective analysis of 44 704 children with acute respiratory infections who underwent 11 respiratory pathogen tests based on multiplex polymerase chain reaction between February and December in both 2022 and 2023. The total pathogen detection rate (24861, 74.80% vs. 6423, 56.01%; p = 0.000) and detection rates of coinfection (4059, 12.21% vs. 676, 5.89%; p = 0.000) in 2023 was significantly higher than that in 2022. The detection rates of influenza A (2567, 7.72% vs. 222, 1.94%; p = 0.000), influenza B (383, 1.15% vs. 37, 0.32%; p = 0.000), human parainfluenza virus (2175, 6.54% vs. 602, 5.25%; p = 0.000), human metapneumovirus (1354, 4.07% vs. 346, 3.01%; p = 0.000), respiratory syncytial virus (3148, 9.47% vs. 870, 7.59%; p = 0.000), and Mycoplasma pneumonia (MP; 9494, 28.56% vs. 1790, 15.61%; p = 0.000) in 2023 were significantly higher than those in 2022, whereas the detection rates of human adenovirus (1124, 3.38% vs. 489, 4.26%; p = 0.000) and human bocavirus (629, 1.89% vs. 375, 3.27%; p = 0.000) were significantly lower than those in 2022. Chlamydia, human rhinovirus, and human coronavirus showed similar detection rates between 2023 and 2022. In 2023, the influenza virus and human parainfluenza virus regained seasonal characteristic, an outbreak of MP infection occurred, the epidemic season of respiratory syncytial virus changed, and the proportion of children with acute respiratory infection aged 0-28 days and over 3 years old increased. Influenza B, metapneumovirus, and human bocavirus were detected in children aged 0-28 days in 2023, but not in 2022. After the COVID-19 pandemic, we should be alert to the increase of respiratory diseases and the change of epidemic season and susceptible age.

Duration of PCR positivity by type of respiratory virus among children using a multiplex PCR test.

Prolonged positive polymerase chain reaction (PCR) results, irrespective of the transmission risk, can lead to prolonged restrictions on daily activities and infection precaution interventions. Studies evaluating the duration of PCR positivity for multiple pathogens in a single patient cohort are scarce. This study aimed to evaluate and compare the durations of PCR positivity for multiple respiratory viruses among children and adolescents. This retrospective study was conducted between April 2018 and March 2024 using a multiplex PCR respiratory panel for symptomatic children and adolescents who had at least two tests within 90 days of study period, with the first PCR test positive. The rate and likelihood of persistent PCR positivity were evaluated for multiple respiratory viruses. For 1325 positive results, repeat tests were conducted within 90 days. The persistent PCR positivity rate at repeat testing decreased over time (60.6%, Days 1-15 and 21.7%, Days 76-90, after the first test). In multivariate logistic regression analysis, an increased likelihood of persistent PCR positivity was observed for rhinovirus/enterovirus and adenovirus, whereas decreased likelihood of persistent positivity was seen in influenza and seasonal coronaviruses, compared with parainfluenza viruses. Persistent PCR positivity is common for multiple respiratory viruses in symptomatic children.

Respiratory syncytial virus immunoprophylaxis: Novel opportunities and a call for equity.

With the approval of the first vaccines against respiratory syncytial virus (RSV) and a novel RSV-neutralizing antibody, 2023 has been perceived as a game-changing year in preventing severe outcomes of RSV infections in infants and the elderly. However, the costs of these pharmaceuticals are high, while RSV disproportionately impacts populations of low-to-middle-income regions, which may continue to suffer from a lack of pharmaceutical measures for RSV prevention under health and socioeconomic disparities. This paper presents an overview of the characteristics, clinical results, and approval status of various RSV vaccines and anti-RSV antibodies. It posits that wealthy nations cannot monopolize RSV immunoprophylaxis and should work jointly to make it available to lower-income countries. An approach toward RSV immunoprophylaxis equity based on five points is offered: (1) integration of RSV vaccines and antibodies into the existing global humanitarian distribution systems, (2) using affordable RSV vaccine pricing models, (3) enforcing equity as a part of national and global public health strategy, (4) implementing equitable allocation frameworks for RSV immunoprophylaxis, and (5) promoting local manufacturing. Such a plan needs to be put into action as soon as possible to avoid delays in serving the populations with the highest needs related to RSV burden.

High-dose vitamin D3 supplementation shows no beneficial effects on white blood cell counts, acute phase reactants, or frequency of respiratory infections.

BACKGROUND: Vitamin D has been suggested to influence the immune system, and vitamin D metabolites and the vitamin D receptor (VDR) are generated and expressed in white blood cells (WBC). Moreover, vitamin D status has been associated with incidence and prognosis of some respiratory tract infections (RTI). Therefore, we investigated the effect of vitamin D3 supplementation on WBC, acute phase reactants (APR), and the risk of developing RTIs. METHODS: A double-blinded, randomized, placebo-controlled clinical trial of 307 infertile men with multiple secondary immunological endpoints. The vitamin D3 group (n = 151) initially received 300,000 IU (7,500 µg) cholecalciferol once - followed by 1,400 IU (35 µg) daily for 150 days. The placebo group (n = 156) did not receive active ingredients. RESULTS: At baseline, stratification into clinically relevant groups of vitamin D status (< 25; 25-50; 50-75; >75 nmol/L), showed an inverse association with total leucocyte concentrations (7.0 vs. 6.0 vs. 6.0 vs. 5.5 (109/L); p = 0.007), lymphocytes (2.4 vs. 2.1 vs. 2.0 vs. 2.0 (109/L); p = 0.048), CRP (2.0 vs. 1.7 vs. 1.2 vs. 1.2 (mg/L); p = 0.037), and orosomucoid (0.82 vs. 0.77 vs. 0.76 vs. 0.70 (g/L); p = 0.015). After 150 days, no differences were detected in WBC counts or APRs between the vitamin D3 and the placebo group. However, vitamin D3 treated men had a higher prevalence of self-reported RTIs compared with the placebo group (55% vs. 39%; p = 0.005). CONCLUSIONS: High-dose vitamin D3 supplementation did not alter WBCs or APRs, but a higher prevalence of respiratory infections was observed in the vitamin D3 group. Serum 25(OH)D3 was negatively correlated with most WBCs, indicating that vitamin D status may be linked with inflammation and WBC turnover, but not an important determinant of developing RTIs. TRIAL REGISTRATION: NCT01304927 (ClinicalTrials.gov). Registered February 20, 2011.

A single-center, retrospective study of hospitalized patients with lower respiratory tract infections: clinical assessment of metagenomic next-generation sequencing and identification of risk factors in patients.

INTRODUCTION: Lower respiratory tract infections(LRTIs) in adults are complicated by diverse pathogens that challenge traditional detection methods, which are often slow and insensitive. Metagenomic next-generation sequencing (mNGS) offers a comprehensive, high-throughput, and unbiased approach to pathogen identification. This retrospective study evaluates the diagnostic efficacy of mNGS compared to conventional microbiological testing (CMT) in LRTIs, aiming to enhance detection accuracy and enable early clinical prediction. METHODS: In our retrospective single-center analysis, 451 patients with suspected LRTIs underwent mNGS testing from July 2020 to July 2023. We assessed the pathogen spectrum and compared the diagnostic efficacy of mNGS to CMT, with clinical comprehensive diagnosis serving as the reference standard. The study analyzed mNGS performance in lung tissue biopsies and bronchoalveolar lavage fluid (BALF) from cases suspected of lung infection. Patients were stratified into two groups based on clinical outcomes (improvement or mortality), and we compared clinical data and conventional laboratory indices between groups. A predictive model and nomogram for the prognosis of LRTIs were constructed using univariate followed by multivariate logistic regression, with model predictive accuracy evaluated by the area under the ROC curve (AUC). RESULTS: (1) Comparative Analysis of mNGS versus CMT: In a comprehensive analysis of 510 specimens, where 59 cases were concurrently collected from lung tissue biopsies and BALF, the study highlights the diagnostic superiority of mNGS over CMT. Specifically, mNGS demonstrated significantly higher sensitivity and specificity in BALF samples (82.86% vs. 44.42% and 52.00% vs. 21.05%, respectively, p < 0.001) alongside greater positive and negative predictive values (96.71% vs. 79.55% and 15.12% vs. 5.19%, respectively, p < 0.01). Additionally, when comparing simultaneous testing of lung tissue biopsies and BALF, mNGS showed enhanced sensitivity in BALF (84.21% vs. 57.41%), whereas lung tissues offered higher specificity (80.00% vs. 50.00%). (2) Analysis of Infectious Species in Patients from This Study: The study also notes a concerning incidence of lung abscesses and identifies Epstein-Barr virus (EBV), Fusobacterium nucleatum, Mycoplasma pneumoniae, Chlamydia psittaci, and Haemophilus influenzae as the most common pathogens, with Klebsiella pneumoniae emerging as the predominant bacterial culprit. Among herpes viruses, EBV and herpes virus 7 (HHV-7) were most frequently detected, with HHV-7 more prevalent in immunocompromised individuals. (3) Risk Factors for Adverse Prognosis and a Mortality Risk Prediction Model in Patients with LRTIs: We identified key risk factors for poor prognosis in lower respiratory tract infection patients, with significant findings including delayed time to mNGS testing, low lymphocyte percentage, presence of chronic lung disease, multiple comorbidities, false-negative CMT results, and positive herpesvirus affecting patient outcomes. We also developed a nomogram model with good consistency and high accuracy (AUC of 0.825) for predicting mortality risk in these patients, offering a valuable clinical tool for assessing prognosis. CONCLUSION: The study underscores mNGS as a superior tool for lower respiratory tract infection diagnosis, exhibiting higher sensitivity and specificity than traditional methods.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Asthma development is associated with low mucosal IL-10 during viral infections in early life.

BACKGROUND: Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting. OBJECTIVES: To investigate in situ virus-specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma. METHODS: We included 493 episodes of acute respiratory illnesses in 277 children aged 0-3 years from the COPSAC2010 mother-child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high-sensitivity MesoScale Discovery kits and compared between children with and without viral PCR-identification in nasopharyngeal samples. Finally, we investigated whether the virus-specific immune response was associated with asthma by age 6 years. RESULTS: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-É£, TNF-α, CCL4, CXCL10 and IL-10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL-10 (FDR <0.05) during viral episodes compared to children not developing asthma. CONCLUSION: We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL-10) immune mediator level. This provides insight into the interplay between early-life viral infections, airway immunity and asthma development.

Mycoplasma pneumoniae infection outbreak in Guangzhou, China after COVID-19 pandemic.

BACKGROUNDS: Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen causing respiratory diseases in children. This study aimed to characterize epidemiological and disease severity shifts of M. pneumoniae: infections in Guangzhou, China during and after the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Throat swab samples were obtained from 5405 hospitalized patients with symptoms of acute respiratory infections to detect M. pneumoniae. Differences in epidemiological and clinical characteristics of M. pneumoniae: infections were investigated during 2020-2022 and after COVID-19 pandemic (2023). RESULTS: M. pneumoniae were detected in 849 (15.6%, 849/5405) patients. The highest annual positive rate was 29.4% (754/2570) in 2023, followed by 5.3% (72/1367) in 2022, 1.2% (12/1015) in 2021, and 2.0% (11/553) in 2020, with significantly increasing annual prevalence from 2020 to 2023. M. pneumoniae incidence peaked between July and December post-COVID-19 pandemic in 2023, with the highest monthly positive rate (56.4%, 165/293). Clinical characteristics and outcomes of patients with M. pneumoniae did not vary between periods during and after COVID-19 pandemic except that patients with M. pneumoniae post-COVID-19 pandemic were more likely to develop fever. Patients with severe M. pneumoniae pneumonia (SMPP) were more likely to develop respiratory complications, myocardial damage, and gastrointestinal dysfunction than those with non-SMPP. Patients with SMPP had lower lymphocytes, CD3+ T cells, CD4+ T cells, CD8+ T cells, B cells, and higher IL-4, IL-6, IL-10 levels than those with non-SMPP. Bronchoalveolar lavage fluid specimens from infected patients were obtained to identify macrolide resistance mutations. Macrolide-resistant M. pneumoniae (MRMP) proportion in 2023 was 91.1% (215/236). CONCLUSION: Outbreaks of M. pneumoniae: occurred in Guangzhou, China in 2023 upon Non-pharmaceutical interventions easing. Despite the increasing incidence of M. pneumoniae, the disease severity remained similar during and after the COVID-19 pandemic.

Respiratory tract infections: an update on the complexity of bacterial diversity, therapeutic interventions and breakthroughs.

Respiratory tract infections (RTIs) have a significant impact on global health, especially among children and the elderly. The key bacterial pathogens Streptococcus pneumoniae, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus and non-fermenting Gram Negative bacteria such as Acinetobacter baumannii and Pseudomonas aeruginosa are most commonly associated with RTIs. These bacterial pathogens have evolved a diverse array of resistance mechanisms through horizontal gene transfer, often mediated by mobile genetic elements and environmental acquisition. Treatment failures are primarily due to antimicrobial resistance and inadequate bacterial engagement, which necessitates the development of alternative treatment strategies. To overcome this, our review mainly focuses on different virulence mechanisms and their resulting pathogenicity, highlighting different therapeutic interventions to combat resistance. To prevent the antimicrobial resistance crisis, we also focused on leveraging the application of artificial intelligence and machine learning to manage RTIs. Integrative approaches combining mechanistic insights are crucial for addressing the global challenge of antimicrobial resistance in respiratory infections.

A critical analysis of the effect of OM-85 for the prevention of recurrent respiratory tract infections or wheezing/asthma from systematic reviews with meta-analysis.

Acute respiratory tract infections (RTIs) are one of the most common causes of pediatric consultations/hospitalizations and a major trigger for asthma exacerbations. Some consensus statements have recommended the use of immunostimulants to boost natural defenses against severe or repeated infections. One of the most common immunostimulants is OM-85; while several randomized clinical trials (RCTs) have evaluated its efficacy in preventing acute RTIs and wheezing/asthma exacerbations, results have been conflicting. Similarly, various systematic reviews with meta-analyses (SRMs) on OM-85 have used different strategies, populations, and outcomes; moreover, SRM conclusions are limited when the original studies are highly heterogeneous or have a low quality, hindering the generalizability of the findings. Here we summarize the evidence on the effect of OM-85 to prevent acute RTIs, wheezing/asthma episodes, or loss of asthma control in children, by including and critically evaluating all SRMs published to date. We searched for SRMs on OM-85 in three publication databases and found nine SRMs (seven for RTI, and two for wheezing/asthma). Among those, one had a high confidence evaluation of quality (AMSTAR-2 tool) and found a reduction in the total number of acute RTIs among the OM-85 group. Overall, no strong recommendations can be derived from the existing literature, mainly due to the high heterogeneity among included RCTs and SRMs. Further, large, high-quality RCTs are needed to confirm the true efficacy of OM-85 for the prevention of acute RTIs, asthma development, and asthma exacerbations.

Genetic analysis of human parainfluenza type 2 virus in Riyadh, Saudi Arabia.

The extensive mass gathering of pilgrims from all over the world, as well as the constant flow of foreign workers via country entry crossings, raises the likelihood of respiratory virus outbreaks spreading and evolving in Saudi Arabia. Here, we report the sequence and phylogenetic analysis of the human parainfluenza type-2 (HPIV-2) in nasopharyngeal aspirates (NPAs) collected from Riyadh, Saudi Arabia, from 2020/21 to 2021/22 seasons. RNA was extracted from the clinical samples and subjected to RT-PCR analysis for the detection of IAV and IBV. The full-length HN gene of HPIV-2 was amplified and sequenced. Multiple sequence alignments (both nucleotides and deduced amino acids) were aligned using Clustal W, MegAlign program of Lasergene software, and MEGA 7.0. HPIV-2 was found in (4; 2% of 200) NPAs. Sequence and phylogenetic analysis results showed that indicated a genotype shifting from G3 to G4a with 83% sequence homology 62-M786 from Japan, which was prominent throughout the winter seasons of 2008/09. Multiple amino acid sequence alignment revealed 25 sites of possible difference between G3 genotypes and G4a. A total of twenty- two of these locations were shared by the other G4a genotypes, whereas three positions, 67 V, 175 S, and 377Q, were exclusively shared by G3. Only eight conserved N-glycosylation sites were found at amino acids 6(NLS), 286(NTT), 335(NIT), 388(NNS), 498(NES), 504(NPT), 517(NTT), and 539(NGT) in four Riyadh isolates. Our findings also revealed that the G4a genotype of HPIV-2 predominated in our samples population during the winter seasons of 2020/21 and 2021/22. Further research with a larger sample size covering numerous regions of Saudi Arabia throughout different epidemic seasons is needed to achieve an improved knowledge of HPIV-2 circulation.

Molecular characterization of human adenoviruses associated with pediatric respiratory infections in Karachi, Pakistan.

Human adenoviruses (HAdVs) are a diverse group of viruses associated with respiratory infections in humans worldwide. However, there is a lack of research on the genetic diversity and epidemiology of HAdVs in Pakistan. This study characterized HAdVs in pediatric patients with respiratory tract infections in Karachi, Pakistan, between 2022 and 2023. We analyzed 762 nasopharyngeal samples of children ≤ 5 years. DNA extraction, followed by PCR targeting E2B and hexon genes, was carried out. Data analysis was performed on SPSS 25.0, and phylogenetic analysis of hexon gene was performed on MEGA 11. HAdV was detected in 7.34% (56/762) of patients round the year, but at a significantly higher rate during the winter season. Age was insignificantly associated with HAdV incidence (p = 0.662), but more than 62.5% (35/56) of positive cases were younger than 10 months. The circulating HAdVs were identified as six different types from species B (78.57%) and C (21.42%), with the majority of isolates found to be like B3. HAdV was found to be co-infected with bocavirus (5.4%) and measles (7.14%). These findings revealed a high frequency and genetic diversity of respiratory HAdVs in Karachi, Pakistan. We conclude that periodic and continuous surveillance of adenoviruses and other respiratory pathogens is necessary to improve the prognosis and management of respiratory diseases, thereby reducing the child mortality rate in Pakistan.

Mapping the evidence about the natural history of acute infections commonly seen in primary care and managed with antibiotics: a scoping review.

BACKGROUND: Knowing the natural history of acute infections in primary care, defined as the course of a disease over time in the absence of specific therapy or treatment, can inform clinicians' and patients' expectations about illness recovery, but this evidence is fragmented across the literature. This scoping review aimed to map existing research and research gaps relevant to the natural history of acute infections. METHODS: We searched MEDLINE, Embase and CENTRAL using a 2-phase hierarchical search approach. In Phase A, we focused on identifying systematic reviews synthesising natural history data for eligible infections (acute respiratory, urinary, and skin and soft tissue) and systematic reviews of treatment effectiveness (of RCTs with placebo or no treatment arm, or cohort studies). For infections without existing reviews, in Phase B, we searched for primary studies (placebo-controlled RCTs or cohort studies). Two reviewers independently screened and extracted the data (study characteristics, outcome data - e.g., symptom duration, proportion with resolution at various time points). RESULTS: We identified 40 systematic reviews, reporting on 45 infections, most commonly (90%) respiratory tract infections. Six (15%) of these aimed to synthesise natural history information. Most reviews reported the proportion of participants with symptom resolution at various time point/s, with 58% providing data on mean symptom duration. Recovery data show the spontaneous resolution of some infections in some people. We found no eligible studies for cellulitis, ecthyma, carbuncle, and erysipelas. CONCLUSIONS: Our review has shown that natural history evidence exists for many common acute infections. It can be utilised by clinicians in implementing patient-centred antibiotic stewardship strategies in primary care. Future research should focus on generating natural history evidence for skin and soft tissue infections and urinary tract infections.

Modelling the potential clinical and economic impact of universal immunisation with nirsevimab versus standard of practice for protecting all neonates and infants in their first respiratory syncytial virus season in Spain.

BACKGROUND: Respiratory syncytial virus (RSV) is associated with substantial morbidity among infants. This study modelled the potential public health and economic impact of nirsevimab, a long-acting monoclonal antibody, as an immunoprophylactic strategy for all infants in Spain in their first RSV season. METHODS: A static decision-analytic model of the Spanish birth cohort during its first RSV season was developed to estimate the impact of nirsevimab on RSV-related health events and costs versus the standard of practice (SoP). Spain-specific costs and epidemiological data were used as model inputs. Modelled outcomes included RSV-related outpatient visits, emerging room (ER) visits, hospitalisations - including pediatric intensive care unit (PICU) admission, mechanical ventilation, and inpatient mortality. RESULTS: Under the current SoP, RSV caused 151,741 primary care visits, 38,798 ER visits, 12,889 hospitalisations, 1,412 PICU admissions, and 16 deaths over a single season, representing a cost of €71.8 million from a healthcare payer perspective. Universal immunisation of all infants with nirsevimab was expected to prevent 97,157 primary care visits (64.0% reduction), 24,789 ER visits (63.9%), 8,185 hospitalisations (63.5%), 869 PICU admissions (61.5%), and 9 inpatient deaths (52.6%), saving €47.8 million (62.4%) in healthcare costs. CONCLUSIONS: These results suggest that immunisation with nirsevimab of all infants experiencing their first RSV season in Spain is likely to prevent thousands of RSV-related health events and save considerable costs versus the current SoP.

Syndromic case definitions for lower respiratory tract infection (LRTI) are less sensitive in older age: an analysis of symptoms among hospitalised adults.

BACKGROUND: Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥ 65y) as compared to younger adults (< 65y). METHODS: We included adults (≥ 18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022. Logistic regression was used to assess whether age ≥ 65y reduced the probability of meeting syndromic LRTI case definitions, using patients' symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. RESULTS: Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. After controlling for sex, dementia and comorbidities, age ≥ 65y significantly reduced the probability of meeting the case definition (aOR = 0.67, 95% CI:0.63-0.71). Cases aged ≥ 65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥ 85y were characterised by lack of cough but frequent confusion and falls. CONCLUSIONS: LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.