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Background Prompt differentiation of viral from bacterial infections in febrile children is pivotal in reducing antibiotic overuse. Myxovirus resistance protein A (MxA) is a promising viral biomarker. Methods We evaluated the accuracy of a point-of-care (POC) measurement for blood MxA level compared to the reference enzyme immunoassay in 228 febrile children aged between 4 weeks and 16 years, enrolled primarily at the emergency department (ED). Furthermore, we analyzed the ability of MxA to differentiate viral from bacterial infections. Results The mean difference between POC and reference MxA level was −76 µg/L (95% limits of agreement from −409 to 257 µg/L). Using a cutoff of 200 µg/L, POC results were uniform with the reference assay in 199 (87.3%) children. In ED-collected samples, the median POC MxA level was 571 (interquartile range [IQR], 240–955) µg/L in children with viral infections, 555 (IQR, 103–889) µg/L in children with viral-bacterial coinfections, and 25 (IQR, 25–54) µg/L in children with bacterial infections (P <.001). MxA cutoff of 101 µg/L differentiated between viral and bacterial infections with 92% sensitivity and 91% specificity. Conclusions POC MxA measurement demonstrated acceptable analytical accuracy compared to the reference method, and good diagnostic accuracy as a biomarker for viral infections. [ABSTRACT FROM AUTHOR]

Background and Objective: Understanding the seasonal behaviours of respiratory viruses is crucial for preventing infections. We evaluated the seasonality of respiratory viruses using time‐series analyses. Methods: This study analysed prospectively collected nationwide surveillance data on eight respiratory viruses, gathered from the Korean Influenza and Respiratory Surveillance System. The data were collected on a weekly basis by 52 nationwide primary healthcare institutions between 2015 and 2019. We performed Spearman correlation analyses, similarity analyses via dynamic time warping (DTW) and seasonality analyses using seasonal autoregressive integrated moving average (SARIMA). Results: The prevalence of rhinovirus (RV, 23.6%–31.4%), adenovirus (AdV, 9.2%–16.6%), human coronavirus (HCoV, 3.0%–6.6%), respiratory syncytial virus (RSV, 11.7%–20.1%), influenza virus (IFV, 11.7%–21.5%), parainfluenza virus (PIV, 9.2%–12.6%), human metapneumovirus (HMPV, 5.6%–6.9%) and human bocavirus (HBoV, 5.0%–6.4%) were derived. Most of them exhibited a high positive correlation in Spearman analyses. In DTW analyses, all virus data from 2015 to 2019, except AdV, exhibited good alignments. In SARIMA, AdV and RV did not show seasonality. Other viruses showed 12‐month seasonality. We describe the viruses as winter viruses (HCoV, RSV and IFV), spring/summer viruses (PIV, HBoV), a spring virus (HMPV) and all‐year viruses with peak incidences during school periods (RV and AdV). Conclusion: This is the first study to comprehensively analyse the seasonal behaviours of the eight most common respiratory viruses using nationwide, prospectively collected, sentinel surveillance data. [ABSTRACT FROM AUTHOR]

Aim: To explore whether children in specialist care with COVID-19 have increased post-discharge health care use when compared with children in specialist care with 1) respiratory syncytial virus (RSV) infection, and 2) other respiratory tract infections (RTIs). Methods: In 34,214 children aged 1 month to 5 years who were registered as having one or more hospital visit (outpatient or inpatient) with a diagnosis of COVID-19 (N = 128), RSV infection (N = 4,009), or other RTIs (N = 34,458) from 2017 to 2021, we used a difference-in-differences study design to investigate individual all-cause primary and specialist health care use from 12 weeks prior to 12 weeks after the hospital visit, stratified by infants (1 to 11 months) and children (1 to 5 years). Results: We found a slight increase in primary health care use in the first 4 weeks after the hospital visit for infants with COVID-19 when compared with infants with RSV infection (6 per 10,000; 95% CI [2, 13], a 0.52% relative increase). For infants diagnosed with COVID-19, we found a similar post-visit increase in inpatients when compared with infants with RSV infection, which lasted for 12 weeks. Conclusions: Our findings imply a slightly increased health care use among infants after a hospital visit for COVID-19 than among infants with other RTIs, the potential etiological mechanisms of which deserve future clinical research. Severe COVID-19 in young children will not represent any markedly increased burden on the health services. [ABSTRACT FROM AUTHOR]

Background: The most prevalent infectious disorders are Urinary Tract Infections (UTI) and Respiratory Tract Infections (RTI), which are frequently related to morbidity and mortality. Due to improper antibiotic administration in these diseases, antibiotic resistance increased. This study aims to identify the patterns of antibiotic resistance in RTI and UTI. Materials and Methods: An investigation of a prospective observational cross-sectional type of study was carried out at the government general hospital's Department of general medicine between November 2021 and April 2022. The study included all patients of either gender over the age of 20 who had received at least one prescription for an antibiotic and had culture sensitivity test results. Information was gathered from the patient's medical case sheet regarding demographics, primary complaints, current medication history, and the results of an antibiotic sensitivity test. Based on the culture sensitivity test, the most prevalent microorganisms isolated from RTI and UTI were identified, and the antibiotic resistance pattern was established. Results: 160 samples from the general medicine department of the government public hospital were processed during the study period (100 sputum samples and 60 urine samples). A total of 293 antibiotics were prescribed among 160 samples, of which 183 (62.5%) were prescribed for RTI and 50 (27.32%) were found to be resistant. 40 (36.3%) of the 110 antibiotics administered for UTIs were found to be resistant. The remaining 203 (69.26%) patients received suitable antibiotic prescriptions for RTI and UTI. Conclusion: The isolates seen in recent years show the value of longitudinal surveillance data to identify shifts in antibiotic resistance trends, and it is not entirely excluded that the movements may pick up again. [ABSTRACT FROM AUTHOR]

Bacterial Lysates are immunostimulants clinically prescribed for the prevention of respiratory tract infections (RTIs). It has been shown that Bacterial Lysates upregulate the immune system, acting both on innate and adaptive reactions. In fact, there are demonstrations of their efficacy in restoring the integrity and immune function of epithelial barriers, activating ILC3 and dendritic cells with an enhanced Th1 response, and producing serum IgG and serum and salivary IgA specific to the administered bacterial antigens. The activated immune system also protects against other bacteria and viruses due to a trained immunity effect. Most studies show that the number of RTIs and their severity decrease in Bacterial Lysates-pretreated patients, without relevant side effects. The Bacterial Lysates treatment, in addition to reducing the number of RTIs, also prevents the deterioration of the underlying disease (i.e., COPD) induced by repeated infections. Despite these positive data, the most recent meta-analyses evidence the weakness of the studies performed, which are of low quality and have an inadequate number of patients, some of which were non-randomized while others were without a control group or were performed contemporarily in different clinical conditions or with different ages. The high heterogeneity of the studies does not allow us to state Bacterial Lysates' effectiveness in preventing RTIs with sufficient certainty. To completely define their indications, double-blind, placebo-controlled, multicenter, randomized clinical trials should be performed for each product and for each indication. The study population should be adequate for each indication. For this purpose, an adequate run-in phase will be necessary. [ABSTRACT FROM AUTHOR]

The absence of sensitive, multiplexed, and point‐of‐care assays poses a critical obstacle in promptly responding to emerging human respiratory virus (HRV) pandemics. Herein, RECOGNIZER (re‐building commercial pregnancy strips via large‐size nanoflowers), an innovative one‐pot CRISPR assay, is presented that employs commercially available strips to identify several types of HRVs. The superiority of the RECOGNIZER assay mainly relies on two aspects: (i) DNA nanoflowers possessing a high surface‐to‐volume ratio and well‐defined surface allow for a considerable probe loading density and minimized non‐specific interaction, achieving an impressive signal‐to‐noise proportion exceeding tenfold at 1 nM target. (ii) The design of the one‐pot reaction, multi‐channel chip, and custom‐made app enables the rapid, sample‐to‐answer, and multiplexed analysis of four HRVs in 25 min. This assay demonstrates a sensitivity of 5.42 pM for synthetic SARS‐CoV‐2 RNA and 10 copies µL−1 for SARS‐CoV‐2 plasmids after pre‐amplification. Finally, the proposed approach indicated 100% accuracy in 50 clinical swab samples, demonstrating the robust performance in distinguishing SARS‐CoV‐2 from other HRVs. The versatility and scalability of RECOGNIZER renders it a user‐friendly platform for virus infection monitoring, offering significant potential for improving pandemic response efforts. [ABSTRACT FROM AUTHOR]

Purpose Procalcitonin (PCT) levels may play a role in decreasing the duration of antimicrobial therapy in institutions that have long durations of therapy for management of community-acquired pneumonia. We assessed the impact of the combination of pharmacist stewardship interventions assisted by a clinical decision support (CDS) tool and PCT assessment on the antimicrobial days of therapy (DOT) prescribed for respiratory tract infections (RTIs). Methods We conducted a quasi-experimental study in which patients in the preintervention group were admitted between April and June 2021 and patients in the intervention group were admitted between April and June 2022. In the intervention phase, a CDS tool was utilized to alert clinical pharmacists when patients met specific criteria. This alert was programmed to activate for individual patients when a reported PCT level was less than 0.25 ng/mL and the patient was on antimicrobials prescribed for an RTI as indicated by providers in the electronic health record. Stewardship interventions were made by pharmacists via prospective audit and feedback. The primary endpoint was inpatient antimicrobial DOT for RTIs. Results There were 90 patients in the preintervention group and 104 patients in the intervention group. Although baseline characteristics were not well matched between the groups, favoring the preintervention group, the median DOT was lower in the intervention group, at 3 days (interquartile range [IQR], 2-4 days), compared to 4 days (IQR, 2.8-5 days) in the preintervention group (P = 0.001). Conclusion The results of our study demonstrate the utility of pharmacist interventions coupled with CDS and PCT in reducing antimicrobial DOT prescribed for RTIs. Antimicrobial stewardship programs may benefit from implementing a PCT bundle. [ABSTRACT FROM AUTHOR]

Background: ALRTI (acute lower respiratory tract infection) is the major cause of mortality in children 0-5 years of age. The burden of ALRTI can be markedly reduced by identifying the modifiable risk factors for severe ALRTI. Aim: The present study aimed to assess the risk factors for acute lower respiratory tract infection in children 0-5 years of age. Methods: The present study utilized the case definition of ALRTI given by WHO (World Health Organization). The study included subjects with ALRTI and subjects visiting the Outpatient Department of Pediatrics for immunization served as controls. A preformed structured proforma was used to record the potential risk factors in cases and controls. Results: The present study assessed 256 children with 101 cases and 155 control subjects. It was seen that family history of ALRTI, inappropriate immunization age, cooking on other mediums than LPG, severe malnutrition, upper respiratory tract infection in siblings, and lack of breastfeeding were significant risk factors for ALRTI with OR of 5.13, 2.83, 2.3, 1.83, 24.93, and 6.51 respectively. Non-significant risk factors for ALRTI are housing type, inadequate caloric intake, anemia, number of children at home, education of the parents, age of the parents, and gender of the child. Conclusions: The present study concludes that family history of ALRTI, inappropriate immunization age, cooking on other mediums than LPG, severe malnutrition, upper respiratory tract infection in siblings, and lack of breastfeeding were significant risk factors for ALRTI and should be monitored. [ABSTRACT FROM AUTHOR]

With approximately half a billion events per year, lower respiratory tract infections (LRTIs) represent a major challenge for the global public health. Among LRTI cases, those caused by Gram-negative bacteria (GNB) are associated with a poorer prognostic. Standard-of-care etiologic diagnostics is lengthy and difficult to establish, with more than half of cases remaining microbiologically undocumented. Recently, syndromic molecular diagnostic panels became available, enabling simultaneous detection of tens of pathogen-related and antimicrobial-resistance genetic markers within a few hours. In this narrative review, we summarize the available data on the performance of molecular diagnostics in GNB pneumonia, highlighting the main strengths and limitations of these assays, as well as the main factors influencing their clinical utility. We searched MEDLINE and Web of Science databases for relevant English-language articles. Molecular assays have higher analytical sensitivity than cultural methods, and show good agreement with standard-of-care diagnostics regarding detection of respiratory pathogens, including GNB, and identification of frequent patterns of resistance to antibiotics. Clinical trials reported encouraging results on the usefulness of molecular assays in antibiotic stewardship. By providing early information on the presence of pathogens and their probable resistance phenotypes, these assays assist in the choice of targeted therapy, in shortening the time from sample collection to appropriate antimicrobial treatment, and in reducing unnecessary antibiotic use. [ABSTRACT FROM AUTHOR]

Rhinovirus (RV) is a common pathogen that causes respiratory tract infection and can cause outbreaks in hospitals and welfare institutions. A cluster of respiratory diseases occurred in a primary school in Shenyang City, Liaoning Province, China, in 2022. In this outbreak, a total of 31 students had symptoms similar to those of upper respiratory tract infection, mainly cough and sore throat. Among them, 27 throat swabs were collected and identified for respiratory pathogens by TaqMan low-density array (TLDA), quantitative real-time polymerase chain reaction (PCR), reverse transcription-nested PCR and whole-genome sequencing. Out of the 27 specimens, 24 tested positive for RV, and 21 RV viral protein 1 sequences were obtained, of which 15 (71.43%) were identified as RV-A49, while 2 RV-A20 and 4 sequences from 2 specimens were RV-A30 coinfected with RV-C15. In addition, one whole-genome sequence (WGS) of RV-A49 was obtained, and three unique amino acid mutations were found compared to 23 WGS of RV-A49 from GenBank. In conclusion, this outbreak of upper respiratory tract infection is caused by RV, mainly RV-A49.

Cornelius J Clancy,1 Oliver A Cornely,2– 4 Stephen W Marcella,5 Sean T Nguyen,6 Laurence Gozalo,7 Bin Cai8 1Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA; 2Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; 3Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany; 4German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; 5Global Epidemiology and Real-World Evidence, Shionogi Inc, Florham Park, NJ, USA; 6Medical Affairs, Shionogi Inc, Florham Park, NJ, USA; 7Advanced Analytics, Genesis Research, Hoboken, NJ, USA; 8Center of Real-World Data and Analytics, Shionogi Inc, Florham Park, NJ, USACorrespondence: Bin Cai, Center of Real-World Data and Analytics, Shionogi Inc, 400 Campus Drive, Florham Park, NJ, 07932, USA, Email bin.cai@shionogi.comPurpose: The international PROVE retrospective chart-review study aims to assess the real-world effectiveness and safety of cefiderocol for treatment of patients with carbapenem-resistant Gram-negative infections.Patients and Methods: US centers selected hospitalized patients receiving their first cefiderocol treatment for ≥ 72 hours for a Gram-negative bacterial infection (November 2020–March 2023). Patient demographics, clinical characteristics, hospitalization, course of infection, antibiotic use, clinical cure (excluding patients with a relapse/reinfection), clinical response at the end of treatment, microbiology, in-hospital all-cause mortality (IH-ACM) at Day 30, and safety were analyzed using descriptive statistics.Results: This interim analysis included 244 patients. The most frequent infection sites were respiratory tract (55.7%), skin and skin structure (16.8%), and blood (9.8%). The median duration of cefiderocol use was 12 days (interquartile range 8– 18.5). Clinical cure was reported for 64.8% (158/244) of patients, clinical response for 74.2% (181/244), and 9.4% (23/244) had relapse/reinfection; 30-day IH-ACM was 18.4% (45/244). Of 82 patients with monomicrobial Pseudomonas aeruginosa infections, 64.6% (n = 53) and 74.4% (n = 61) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 25.6%. Among 43 patients with monomicrobial Acinetobacter baumannii infections, 60.5% (n = 26) and 74.4% (n = 32) had clinical cure and clinical response, respectively, and 30-day IH-ACM was 18.6%. Five patients experienced six adverse drug reactions (one serious event: interstitial nephritis/acute kidney injury), and cefiderocol was discontinued in two cases.Conclusion: Cefiderocol had similar clinical cure and response rates to previous retrospective studies and lower mortality. Cefiderocol was well tolerated in real-world settings in critically ill US patients with problematic Gram-negative pathogens.Keywords: bloodstream infection, carbapenem resistance, cefiderocol, nonfermenters, real-world evidence, respiratory tract infection

Objective: This review evaluates the efficacy and safety of novel respiratory syncytial virus (RSV) vaccines approved for adults aged 60 years and older. Data Sources: A literature search through February 27, 2024 was conducted using search terms, such as RSV, viral respiratory illness, vaccine, RSVpreF, RSVpreF3, Prefusion F, Abrysvo, and Arexvy. Study Selection and Data Extraction: Data from primary literature and vaccine prescribing information were reviewed, encompassing evaluations of clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. Data Synthesis: The literature review process resulted in 10 articles included within this article's scope, including the results of 2 major phase III trials presented in detail. Two RSV vaccines, Respiratory Syncytial Virus Vaccine (recombinant [adjuvanted]; RSVpreF3-ASO1E, Arexvy) and Respiratory Syncytial Virus Vaccine (recombinant; RSVpreF, Abrysvo), approved for preventing RSV-associated lower respiratory tract disease (LRTD) in adults aged 60 years or older in the United States are discussed. Results from Phase III trials have demonstrated the efficacy of 1 dose of these vaccines in preventing RSV-associated LRTD across 2 RSV seasons. Relevance to Patient Care and Clinical Practice: The Advisory Committee on Immunization Practices currently recommends use of these vaccines under shared clinical decision-making for adults aged 60 years or older. Most common adverse effects include injection site reactions (eg, site pain, redness, and swelling). Administration requires a single intramuscular injection of 0.5 mL, reconstituted prior to administration. Conclusions: The RSVpreF3-ASO1E and RSVpreF vaccines effectively prevent RSV-associated LRTD in adults aged 60 years and older. [ABSTRACT FROM AUTHOR]

Abstract Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19–2019/20. The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression. The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged

Abstract Objective To assess the impact of an intervention package on the prescription of antibiotic and subsequently the rate of clinical recovery for non-severe acute febrile illnesses at primary health centers. Methods Patients over 6 months of age presenting to primary health care centres with fever or history of fever within the past 7 days were randomized to receive either the intervention package constituted of point-of-care tests including COVID-19 antigen tests, a diagnostic algorithm and training and communication packages, or the standard practice. The primary outcomes were antibiotic prescriptions at Day 0 (D0) and the clinical recovery at Day 7 (D7). Secondary outcomes were non-adherence of participants and parents/caregivers to prescriptions, health workers’ non-adherence to the algorithm, and the safety of the intervention. Results A total of 1098 patients were enrolled. 551 (50.2%) were randomized to receive the intervention versus 547 (49.8%) received standard care. 1054 (96.0%) completed follow-up and all of them recovered at D7 in both arms. The proportion of patients with antibiotic prescriptions at D0 were 33.2% (183/551) in the intervention arm versus 58.1% (318/547) under standard care, risk difference (RD) -24.9 (95% CI -30.6 to -19.2, p

Abstract Background The burden and characteristics of respiratory viral infections in children hospitalized for acute respiratory tract infections (ARTIs) during the post-COVID-19 pandemic era are unclear. We analyzed the epidemiological and clinical characteristics of pediatric patients hospitalized with common respiratory virus infections before and after relaxation of non-pharmaceutical interventions in Hangzhou, China and evaluated the diagnostic value of the six-panel respiratory pathogen detection system. Methods Six types of respiratory viruses were detected in respiratory samples from children with suspected ARTIs by multiplex real-time quantitative polymerase chain reaction (RT-qPCR). Changes in virus detection rates and epidemiological and clinical characteristics, obtained from electronic health records, were analyzed. Binary logistic regression was used to identify respiratory tract infections risk factors. Multiplex RT-qPCR and targeted next-generation sequencing results were compared in random samples. Results Among the 11,056 pediatric samples, 3228 tested positive for one or more of six common respiratory pathogens. RSV and PIV-3 detection rates differed significantly across age groups (both P

Abstract Background Inappropriate or overuse of antibiotic prescribing in primary care highlights an opportunity for antimicrobial stewardship (AMS) programs aimed at reducing unnecessary use of antimicrobials through education, policies and practice audits that optimize antibiotic prescribing. Evidence from the early part of the pandemic indicates a high rate of prescribing of antibiotics for patients with COVID-19. It is crucial to surveil antibiotic prescribing by primary care providers from the start of the pandemic and into its endemic stage to understand the effects of the pandemic and better target effective AMS programs. Methods This was a matched pair population-based cohort study that used electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Participants included all patients that visited their primary care provider and met the inclusion criteria for COVID-19, respiratory tract infection (RTI), or non-respiratory or influenza-like-illness (negative). Four outcomes were evaluated (a) receipt of an antibiotic prescription; (b) receipt of a non-antibiotic prescription; (c) a subsequent primary care visit (for any reason); and (d) a subsequent primary care visit with a bacterial infection diagnosis. Conditional logistic regression was used to evaluate the association between COVID-19 and each of the four outcomes. Each model was adjusted for location (rural or urban), material and social deprivation, smoking status, alcohol use, obesity, pregnancy, HIV, cancer and number of chronic conditions. Results The odds of a COVID-19 patient receiving an antibiotic within 30 days of their visit is much lower than for patients visiting for RTI or for a non-respiratory or influenza-like-illnesses (AOR = 0.08, 95% CI[0.07, 0.09] compared to RTI, and AOR = 0.43, 95% CI[0.38, 0.48] compared to negatives). It was found that a patient visit for COVID-19 was much less likely to have a subsequent visit for a bacterial infection at all time points. Conclusions Encouragingly, COVID-19 patients were much less likely to receive an antibiotic prescription than patients with an RTI. However, this highlights an opportunity to leverage the education and attitude change brought about by the public health messaging during the COVID-19 pandemic (that antibiotics cannot treat a viral infection), to reduce the prescribing of antibiotics for other viral RTIs and improve antibiotic stewardship.

Influenza-like illness (ILI) patients co-detected with respiratory pathogens exhibit poorer health outcomes than those with single infections. To address the paucity of knowledge concerning the incidence of concurrent respiratory pathogens, their relationships, and the clinical differences between patients detected with single and multiple pathogens, we performed an in-depth characterization of the oropharyngeal samples of primary care patients collected in Genoa (Northwest Italy), during winter seasons 2018/19–2019/20. The apriori algorithm was employed to evaluate the incidence of viral, bacterial, and viral-bacterial pairs during the study period. The grade of correlation between pathogens was investigated using the Phi coefficient. Factors associated with viral, bacterial or viral-bacterial co-detection were assessed using logistic regression. The most frequently identified pathogens included influenza A, rhinovirus, Haemophilus influenzae and Streptococcus pneumoniae. The highest correlations were found between bacterial-bacterial and viral-bacterial pairs, such as Haemophilus influenzae-Streptococcus pneumoniae, adenovirus-Haemophilus influenzae, adenovirus-Streptococcus pneumoniae, RSV-A-Bordetella pertussis, and influenza B Victoria-Bordetella parapertussis. Viruses were detected together at significantly lower rates. Notably, rhinovirus, influenza, and RSV exhibited significant negative correlations with each other. Co-detection was more prevalent in children aged < 4, and cough was shown to be a reliable indicator of viral co-detection. Given the evolving epidemiological landscape following the COVID-19 pandemic, future research utilizing the methodology described here, while considering the circulation of SARS-CoV-2, could further enrich the understanding of concurrent respiratory pathogens. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of an intervention package on the prescription of antibiotic and subsequently the rate of clinical recovery for non-severe acute febrile illnesses at primary health centers. Methods: Patients over 6 months of age presenting to primary health care centres with fever or history of fever within the past 7 days were randomized to receive either the intervention package constituted of point-of-care tests including COVID-19 antigen tests, a diagnostic algorithm and training and communication packages, or the standard practice. The primary outcomes were antibiotic prescriptions at Day 0 (D0) and the clinical recovery at Day 7 (D7). Secondary outcomes were non-adherence of participants and parents/caregivers to prescriptions, health workers' non-adherence to the algorithm, and the safety of the intervention. Results: A total of 1098 patients were enrolled. 551 (50.2%) were randomized to receive the intervention versus 547 (49.8%) received standard care. 1054 (96.0%) completed follow-up and all of them recovered at D7 in both arms. The proportion of patients with antibiotic prescriptions at D0 were 33.2% (183/551) in the intervention arm versus 58.1% (318/547) under standard care, risk difference (RD) -24.9 (95% CI -30.6 to -19.2, p < 0.001), corresponding to one more antibiotic saved every four (95% CI: 3 to 5) consultations. This reduction was also statistically significant in children from 6 to 59 months (RD -34.5; 95% CI -41.7 to -27.3; p < 0.001), patients over 18 years (RD -35.9; 95%CI -58.5 to -13.4; p = 0.002), patients with negative malaria test (RD -46.9; 95% CI -53.9 to -39.8; p < 0.001), those with a respiratory diagnosis (RD -48.9; 95% CI -56.9 to -41.0, p < 0.001) and those not vaccinated against COVID-19 (-24.8% 95%CI -30.7 to -18.9, p-value: <0.001). A significant reduction in non-adherence to prescription by patients was reported (RD -7.1; 95% CI -10.9 to -3.3; p < 0.001). Conclusion: The intervention was associated with significant reductions of antibiotic prescriptions and non-adherence, chiefly among patients with non-malaria fever, those with respiratory symptoms and children below 5 years of age. The addition of COVID-19 testing did not have a major impact on antibiotic use at primary health centers. Trial registration: Clinitrial.gov; NCT04081051 registered on 06/09/2019. [ABSTRACT FROM AUTHOR]

Objective To analyze the epidemiological characteristics of pathogens in patients with fever and respiratory tract infection in Hechuan district, Chongqing. Methods From 2022 to 2023, a total of 246 patients with fever and acute respiratory tract infection in a hospital in Hechuan District were selected to detect 18 pathogens such as influenza A/B virus, novel coronavirus (SARS-CoV-2) and respiratory syncytial virus (RSV) by multiple polymerase chain reaction (PCR). At the same time, real-time fluorescent quantitative PCR was used to detect SARS-CoV-2, influenza virus and their subtypes. The situation of respiratory pathogen infection was analyzed, and the consistency of the two detection methods was compared. Results Among the 246 patients. 159 patients were positive for respiratory pathogens, of which 144(58.54%) were infected with one or more pathogens. There was no statistically significant difference in the total detection rate of respiratory pathogens among the patients of different genders (P>0.05). There was no statistically significant difference in the detection rates of various respiratory pathogens among the patients of different genders (P> 0.05). The total detection rate of respiratory pathogens in the patients of different age groups was compared. and the difference was statistically significant(P<0.05). The detection rates of influenza virus and RSV in the patients of different age groups were statistically significant(P<0.05), while the detection rates of other respiratory pathogens were not statistically significant (P>0.05). The total detection rate of respiratory pathogens in the patients visiting different seasons was compared, and the difference was statistically significant (P<0.05). The detection rates of H3N2+SARS-CoV-2, H1N1, SARS-CoV-2 in the patients visiting different seasons were statistically significant (P<0.05), while the detection rates of other respiratory pathogens were not statistically significant (P>0.05). For SARS-CoV-2 and influenza viruses, the sensitivity of multiplex PCR technology and real-time fluorescence quantitative PCR method was basically the same, and the two had good consistency. Conclusion Influenza virus is the main pathogen causing fever with respiratory infections in Hechuan district from 2022 to 2023, and mixed infection with other pathogens is not uncommon. For SARSCoV-2 and influenza viruses, the sensitivity of multiplex PCR and real-time fluorescence quantitative PCR methods is basically the same. [ABSTRACT FROM AUTHOR]

We sequenced and genotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza, adenovirus, and respiratory syncytial virus, among other pathogens, from residual anterior nasal swabs self-collected for rapid SARS-CoV-2 antigen testing at the US Naval Academy. This is a key proof-of-concept for an acute respiratory infection surveillance approach, which could leverage prevalent SARS-CoV-2 antigen self-testing. [ABSTRACT FROM AUTHOR]

Cryptococcosis is a prevalent fungal infection of the central nervous system (CNS) caused by Cryptococcus neoformans, a yeast with a polysaccharide capsule in the basidiomycete group. Normally, C. neoformans infects the respiratory tract and then breaches the blood–brain barrier (BBB), leading to meningitis or meningoencephalitis, which leads to hundreds of thousands of deaths each year. Although the mechanism by which C. neoformans infiltrates the BBB to invade the brain has yet to be fully understood, research has revealed that C. neoformans can cross the BBB using transcellular penetration, paracellular traversal, and infected phagocytes (the "Trojan horse" mechanism). The secretion of multiple virulence factors by C. neoformans is crucial in facilitating the spread of infection after breaching the BBB and causing brain infections. Extensive research has shown that various virulence factors play a significant role in the dissemination of infection beyond the lungs. This review explores the mechanisms of C. neoformans entering the CNS and explains how it bypasses the BBB. Additionally, it aims to understand the interplay between the regulatory mechanisms and virulence factors of C. neoformans. [ABSTRACT FROM AUTHOR]

Although antibiotics are most frequently prescribed for respiratory tract infections, effective interventions for their proper use by physicians have not been fully established. We assessed the impact of educational films on the rates of antibiotic prescriptions for respiratory tract infections using fictitious scenarios. In this nationwide web-based survey prospective study, a total of 1100 physicians were included. The physicians were required to view educational short films and determine the need for prescribing antibiotics in 10 fictitious scenarios involving adults diagnosed with different acute respiratory tract infectious diseases. The antibiotic prescription rates for each scenario were compared before and after viewing the educational short film. The rates of antibiotic prescription significantly decreased after viewing the educational film, especially in cases with a narrowly defined common cold (from 51% to 15%), mild pharyngolaryngitis (from 71% to 25%), and acute bronchitis without chronic respiratory underlying diseases (from 63% to 23%). Alternatively, a slight decrease in rates was observed in cases with moderate or severe rhinosinusitis (from 94% to 79%), moderate or severe acute pharyngitis (from 88% to 69%), and acute bronchitis with chronic lung disease (from 70% to 58%), for which antibiotics are recommended. Educational short films may encourage the proper use of antibiotics for respiratory tract infections; however, the possibility of undertreatment in patients requiring antibiotics must be considered. [ABSTRACT FROM AUTHOR]

Background: The burden and characteristics of respiratory viral infections in children hospitalized for acute respiratory tract infections (ARTIs) during the post-COVID-19 pandemic era are unclear. We analyzed the epidemiological and clinical characteristics of pediatric patients hospitalized with common respiratory virus infections before and after relaxation of non-pharmaceutical interventions in Hangzhou, China and evaluated the diagnostic value of the six-panel respiratory pathogen detection system. Methods: Six types of respiratory viruses were detected in respiratory samples from children with suspected ARTIs by multiplex real-time quantitative polymerase chain reaction (RT-qPCR). Changes in virus detection rates and epidemiological and clinical characteristics, obtained from electronic health records, were analyzed. Binary logistic regression was used to identify respiratory tract infections risk factors. Multiplex RT-qPCR and targeted next-generation sequencing results were compared in random samples. Results: Among the 11,056 pediatric samples, 3228 tested positive for one or more of six common respiratory pathogens. RSV and PIV-3 detection rates differed significantly across age groups (both P < 0.001), and were more common in younger children. PIV-1 was more common in infants, toddlers, and preschoolers than in school-age children (P < 0.001). FluB was predominantly detected in school-age children (P < 0.001). RSV-, ADV-, and PIV-1-positivity rates were higher in 2022 than in 2023. Seasonal viral patterns differed across years. RSV (OR 9.156. 95% CI 5.905–14.195) and PIV-3 (OR 1.683, 95% CI 1.133–2.501) were risk factors for lower respiratory tract infections. RSV-positivity was associated with severe pneumonia (P = 0.044). PIV-3 (OR 0.391, 95% CI 0.170–0.899), summer season (OR 1.982, 95% CI 1.117–3.519), and younger age (OR 0.938, 95% CI 0.893–0.986) influenced pneumonia severity. Multiplex RT-qPCR showed good diagnostic performance. Conclusion: After changes in COVID-19 prevention and control strategies, six common respiratory viruses in children were prevalent in 2022–2023, with different seasonal epidemic characteristics and age proclivities. RSV and PIV-3 cause lower, and FluA, FluB, and ADV more typically cause upper respiratory tract infections. Infancy and summer season influence severe pneumonia risk. Multiplex RT-qPCR is valuable for accurate and timely detection of respiratory viruses in children, which facilitates management, treatment, and prevention of ARTIs. [ABSTRACT FROM AUTHOR]

Background: Inappropriate or overuse of antibiotic prescribing in primary care highlights an opportunity for antimicrobial stewardship (AMS) programs aimed at reducing unnecessary use of antimicrobials through education, policies and practice audits that optimize antibiotic prescribing. Evidence from the early part of the pandemic indicates a high rate of prescribing of antibiotics for patients with COVID-19. It is crucial to surveil antibiotic prescribing by primary care providers from the start of the pandemic and into its endemic stage to understand the effects of the pandemic and better target effective AMS programs. Methods: This was a matched pair population-based cohort study that used electronic medical record (EMR) data from the Canadian Primary Care Sentinel Surveillance Network (CPCSSN). Participants included all patients that visited their primary care provider and met the inclusion criteria for COVID-19, respiratory tract infection (RTI), or non-respiratory or influenza-like-illness (negative). Four outcomes were evaluated (a) receipt of an antibiotic prescription; (b) receipt of a non-antibiotic prescription; (c) a subsequent primary care visit (for any reason); and (d) a subsequent primary care visit with a bacterial infection diagnosis. Conditional logistic regression was used to evaluate the association between COVID-19 and each of the four outcomes. Each model was adjusted for location (rural or urban), material and social deprivation, smoking status, alcohol use, obesity, pregnancy, HIV, cancer and number of chronic conditions. Results: The odds of a COVID-19 patient receiving an antibiotic within 30 days of their visit is much lower than for patients visiting for RTI or for a non-respiratory or influenza-like-illnesses (AOR = 0.08, 95% CI[0.07, 0.09] compared to RTI, and AOR = 0.43, 95% CI[0.38, 0.48] compared to negatives). It was found that a patient visit for COVID-19 was much less likely to have a subsequent visit for a bacterial infection at all time points. Conclusions: Encouragingly, COVID-19 patients were much less likely to receive an antibiotic prescription than patients with an RTI. However, this highlights an opportunity to leverage the education and attitude change brought about by the public health messaging during the COVID-19 pandemic (that antibiotics cannot treat a viral infection), to reduce the prescribing of antibiotics for other viral RTIs and improve antibiotic stewardship. [ABSTRACT FROM AUTHOR]

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ABSTRACT The number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and to provide evidence for the prevention and control strategies of M. pneumoniae in children in this region. A total of 66,488 pediatric patients with respiratory tract infection were enrolled from January 2015 to November 2023 in this study. The results of this study exhibited that M. pneumoniae infection in the Anhui region was characterized by a high positive rate during 2021–2023, especially this year is considered a year of pandemic for M. pneumoniae infection. Moreover, the positive rate of M. pneumoniae in female children is significantly higher than in male children, and the infection rate of M. pneumoniae in children increases significantly with age, particularly in school-aged children.IMPORTANCEThe number of pediatric respiratory tract infection cases in China has significantly increased this year, and Mycoplasma pneumoniae is one of the main pathogens. This study aimed to investigate the epidemiological characteristics of M. pneumoniae in children in the Anhui region and provide evidence for the prevention and control strategies of M. pneumoniae in children in this region.

Introduction: The Kahramanmaraş earthquake, which has been classified as an earthquake with significant and destructive consequences on a global scale, has been referred to as ''the disaster of the century.'', occurred on February 6, 2023. A considerable number of structures were destroyed and a significant amount of damage was incurred in 11 provinces, including Kahramanmaraş. Respiratory tract infections are a serious public health problem seen in all age groups among earthquake victims living in tent and container cities. Objective: The aim of the study was to determine the causative agents in respiratory tract samples taken for screening purposes from earthquake victims living in tent cities in the earthquake zone and to provide early diagnosis. Method: Gaziantep Provincial Health Directorate Infectious Diseases Unit filiation teams collected nasopharyngeal swabs from earthquake victims living in tent cities around Gaziantep province between March 25 and March 30, 2023. The presence of 18 viruses and 6 bacteria that are causing respiratory tract infections were simultaneously detected by the Real-Time qPCR (RT-qPCR) technique. Results: In the present study, respiratory pathogens were detected in 470 (56.62 %) of a total of 830 patients. The most frequently isolated agents were rhinovirus (20 %, 94/470), S. pneumoniae (12.87 %, 60/470), RSV A/B (12.12 %, 57/470), H. influenza type b (10. 85 %, 51/470) and others. Rhinovirus was the most frequently detected pathogen in the study. The coexistence of more than one pathogen was also detected. The most common association was found between HRV and S. pneumoniae (20.93 %, 9/43). Conclusion: The results of the present study indicate that public health measures should be prioritized in natural disasters, and ıt demonstrates that infectious diseases became a significant problem in the time period after the earthquake. Early results can be obtained by screening viral and bacterial pathogen in respiratory tract samples with RT-qPCR, and an early diagnosis is ensured.

Background: Viral infection is responsible for the majority of respiratory tract infections (RTI). This retrospective study evaluates the advantages of using the multiplex Xpert Xpress CoV-2/Flu/RSV plus kit in laboratory diagnosis of RTI caused by the most related viruses. Materials and Methods: Data were obtained from medical records between November 2021 and May 2023 for any sample tested using either the Xpert Xpress Flu/RSV kit, Xpert Xpress Flu kit, Xpert Xpress SARS-CoV-2 kit, and Xpert Xpress CoV-2/Flu/RSV plus kit. Results: Influenza virus A was detected in 8.5% (55/649) of the samples using the Flu PCR kit and in 4.9% (123/2538) using CoV-2/Flu/RSV plus kit, while influenza virus B detection rates were 3.7% (24/649) using the Flu PCR kit and 1.7% (43/2538) using the CoV-2/Flu/RSV plus kit. However, the detection rates using the two kits were comparable when evaluated for the same time period of the year. SARS-CoV-2 infections were detected in 16.9% (1545/9153) and 10.5% (266/2538) of the cases using the SARS-CoV-2 kit and CoV-2/Flu/RSV plus kits, respectively. Respiratory syncytial virus (RSV) was identified in 17.7% (66/372) of children using Flu/RSV kit; this number dropped significantly when age-targeted testing of RSV was performed due to involvements of adults. With the CoV-2/Flu/RSV plus kit, about 34% (35/103) of RSV infections detected were in patients aged >20 years; these cases would have previously been overlooked because adults are not routinely tested for RSV using the Flu/RSV kit. All coinfection cases (n = 16) were only detected with the CoV-2/Flu/RSV plus kit. Conclusion: The use of Xpert Xpress CoV-2/Flu/RSV plus kit not only results in shorter turnaround times through accurate detection of all four viruses, but also provides information on RSV infection in adults and coinfection rates.

Background Despite considerable research into COVID-19 sequelae, little is known about differences in illness duration and complications in patients presenting in primary care with symptoms of acute respiratory tract infections (RTI) that are and are not attributed to SARS-CoV-2 infection.Objective To explore whether aetiology impacted course of illness and prediction of complications in patients presenting in primary care with symptoms of RTI early in the COVID-19 pandemic.Methods Between April 2020-March 2021 general practitioners from nine European countries recruited consecutively contacting patients with RTI symptoms. At baseline, an oropharyngeal-nasal swab was obtained for aetiology determination using PCR after follow-up of 28 days. Time to self-reported recovery was analysed with Kaplan-Meier curves. Predictors (baseline variables of demographics, patient and disease characteristics) of a complicated course (composite of hospital admission and persisting signs/symptoms at 28 days follow-up) were explored with logistic regression modelling.Results Of 855 patients with RTI symptoms, 237 (27.7%) tested SARS-CoV-2 positive. The proportion not feeling fully recovered (15.6% vs 18.1%, p = 0.39), reporting being extremely tired (9.7% vs 12.8%, p = 0.21), and not having returned to usual daily activities (18.1% vs 14.4%, p = 0.18) at day 28 were comparable between SARS-CoV-2 positive (n = 237) and negative (n = 618) groups. However, among those feeling fully recovered (SARS-CoV-2 positive: 200 patients, SARS-CoV-2 negative: 506 patients), time to full recovery was significantly longer in SARS-CoV-2 patients (10.6 vs 7.7 days, p

ABSTRACTThere is a growing interest in development of novel vaccines against respiratory tract infections, due to COVID-19 pandemic. Here, we examined mucosal adjuvanticity and the mucosal booster effect of membrane vesicles (MVs) of a novel probiotic E. coli derivative lacking both flagella and potentially carcinogenic colibactin (ΔflhDΔclbP). ΔflhDΔclbP-derived MVs showed rather strong mucosal adjuvanticity as compared to those of a single flagellar mutant strain (ΔflhD-MVs). In addition, glycoengineered ΔflhDΔclbP-MVs displaying serotype-14 pneumococcal capsular polysaccharide (CPS14+MVs) were well-characterized based on biological and physicochemical parameters. Subcutaneous (SC) and intranasal (IN) booster effects of CPS14+MVs on systemic and mucosal immunity were evaluated in mice that have already been subcutaneously prime-immunized with the same MVs. With a two-dose regimen, an IN boost (SC-IN) elicited stronger IgA responses than homologous prime-boost immunization (SC-SC). With a three-dose regimen, serum IgG levels were comparable among all tested regimens. Homologous immunization (SC-SC-SC) elicited the highest IgM responses among all regimens tested, whereas SC-SC-SC failed to elicit IgA responses in blood and saliva. Furthermore, serum IgA and salivary SIgA levels were increased with an increased number of IN doses administrated. Notably, SC-IN-IN induced not only robust IgG response, but also the highest IgA response in both serum and saliva among the groups. The present findings suggest the potential of a heterologous three-dose administration for building both systemic and mucosal immunity, e.g. an SC-IN-IN vaccine regimen could be beneficial. Another important observation was abundant packaging of colibactin in MVs, suggesting increased applicability of ΔflhDΔclbP-MVs in the context of vaccine safety.

Early and differential diagnosis of sepsis is essential to avoid unnecessary antibiotic use and further reduce patient morbidity and mortality. Here, we aimed to identify predictors of sepsis and advance a machine-learning strategy to predict sepsis-induced respiratory tract infection (RTI). Patients with sepsis and RTI were selected via retrospective analysis, and essential population characteristics and laboratory parameters were recorded. To improve the performance of the primary model and avoid over-fitting, a recursive feature elimination with cross-validation (RFECV) strategy was used to screen the optimal subset of biomarkers and construct nine machine-learning models based on this subset; the average accuracy, precision, recall, and F1-score were used for evaluation of the models. We identified 430 patients with sepsis and 686 patients with RTI. A total of 39 features were collected, with 23 features identified for initial model construction. Using the RFECV algorithm, we found that the XGBoost classifier, which only needed to include seven biomarkers, demonstrated the best performance among all prediction models, with an average accuracy of 89.24 ± 2.28, while the Ridge classifier, which included 11 biomarkers, had an average accuracy of only 83.87 ± 4.69. The remaining models had prediction accuracies greater than 88%. We developed nine models for predicting sepsis using a strategy that combined RFECV with machine learning. Among these models, the XGBoost classifier, which included seven biomarkers, showed the best performance and highest accuracy for predicting sepsis and may be a promising tool for the timely identification of sepsis. [ABSTRACT FROM AUTHOR]

Obejective: To explore the clinical characteristics of bronchial asthma in children of different ages and its risk factors for concurrent respiratory infections. Methods: A study was conducted on 256 children with bronchial asthma admitted to our hospital from January 2018 to January 2023. They were grouped according to their age. 128 children aged<5 years were divided into a younger group, and 128 children aged ≥ 5 years were divided into an older group. The clinical symptoms, disease severity, and inhalation allergen test results of the two groups of children were compared. Subsequently, 256 children with bronchial asthma were divided into two subgroups based on whether they were complicated with respiratory infections, namely the respiratory infection group (n=100) and the non respiratory infection group (n=156). Their general clinical situation was analyzed, and the independent influencing factors of respiratory infections in children with bronchial asthma were analyzed using a logistic regression model. Results: There was no significant difference in the incidence of wheeze, lung wheezing symptoms, and disease severity between the younger and older groups (P>0.05). The incidence of wheezing, shortness of breath, cough symptoms, and disease severity in the younger group was significantly higher than that in the older group (P<0.05); There was no significant difference in the allergenic rates of soybeans, fish, and shrimp between the younger and older groups (P>0.05). The allergenic rates of milk and mold in the younger group were lower than those in the older group, while the allergenic rates of animal fur, dust mites, or dust mites in the younger group were higher than those in the older group (P<0.05); There was no significant difference in gender and course of disease between the respiratory infection group and the non respiratory infection group (P>0.05). However, there were significant differences in age, frequency of seizures every six months, onset season, intravenous corticosteroids, total serum IgE, and EOS count between the respiratory infection group and the non respiratory infection group (P<0.05); The results of logistic regression analysis showed that the number of episodes per six months was ≥ 3, the onset season was autumn and winter, intravenous corticosteroids were injected, total serum IgE<100 IU/mL, and EOS count ≥ 0.52 ×109 /L is an independent risk factor for respiratory tract infection in children with bronchial asthma (P<0.05). Conclusion: There are certain differences in clinical symptoms, severity, and allergen distribution of bronchial asthma in children of different ages, with ≥ 3 episodes every six months, onset season in autumn and winter, intravenous corticosteroids, serum total IgE<100IU/mL, and EOS count ≥ 0.52 × 109 /L is an independent risk factor for respiratory tract infection in children with bronchial asthma. Relevant measures should be taken to prevent the occurrence of respiratory tract infection in such children during the acute onset of asthma. [ABSTRACT FROM AUTHOR]

Background: Viral infection is responsible for the majority of respiratory tract infections (RTI). This retrospective study evaluates the advantages of using the multiplex Xpert Xpress CoV-2/Flu/RSV plus kit in laboratory diagnosis of RTI caused by the most related viruses. Materials and Methods: Data were obtained from medical records between November 2021 and May 2023 for any sample tested using either the Xpert Xpress Flu/RSV kit, Xpert Xpress Flu kit, Xpert Xpress SARS-CoV-2 kit, and Xpert Xpress CoV-2/Flu/RSV plus kit. Results: Influenza virus A was detected in 8.5% (55/649) of the samples using the Flu PCR kit and in 4.9% (123/2538) using CoV-2/Flu/RSV plus kit, while influenza virus B detection rates were 3.7% (24/649) using the Flu PCR kit and 1.7% (43/2538) using the CoV-2/Flu/RSV plus kit. However, the detection rates using the two kits were comparable when evaluated for the same time period of the year. SARS-CoV-2 infections were detected in 16.9% (1545/9153) and 10.5% (266/2538) of the cases using the SARS-CoV-2 kit and CoV-2/ Flu/RSV plus kits, respectively. Respiratory syncytial virus (RSV) was identified in 17.7% (66/372) of children using Flu/RSV kit; this number dropped significantly when age-targeted testing of RSV was performed due to involvements of adults. With the CoV-2/Flu/RSV plus kit, about 34% (35/103) of RSV infections detected were in patients aged >20 years; these cases would have previously been overlooked because adults are not routinely tested for RSV using the Flu/RSV kit. All coinfection cases (n = 16) were only detected with the CoV-2/Flu/RSV plus kit. Conclusion: The use of Xpert Xpress CoV-2/Flu/RSV plus kit not only results in shorter turnaround times through accurate detec [ABSTRACT FROM AUTHOR]

Introduction: Convulsion is most common neurological disorder finding in children having high grade fever. Factors affecting convulsions and prevention of febrile seizures are therefore of utmost importance. The aim of study was to study the risk factors associated with febrile seizures among under 5 children. Methods: A cross sectional study was conducted in the department of Pediatrics GS Medical College and Hospital Pilakhuwa, a tertiary care teaching hospital in North India. All children under 5years of age who had febrile convulsions from March2022 to March2023 were included in the study. Results: In a total of 100 children in the study, 59 were boys (59%) and 41 were girls (41%). 59% of children were in the age group of 6months to 3 years. Mean age was 2.23 years (+_1.19years). 32% of children had positive family history. 80% children had simple and 20% children had complex seizures. Conclusions: Respiratory tract infection and acute gastroenteritis were two most common comorbidity. It was seen more in boys than in girls. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The outcome data and predictors for mortality among patients with congenital heart disease (CHD) affected by COVID-19 are limited. A more detailed understanding may aid in implementing targeted prevention measures in potential future pandemic events. Methods: Based on nationwide administrative health insurance data, all the recorded in-hospital cases of patients with CHD with COVID-19 in 2020 were analyzed. The demographics, treatment details, as well as 30-day mortality rate were assessed. The associations of the patients' characteristics with death were assessed using multivariable logistic regression analysis. Results: Overall, 403 patients with CHD were treated in- hospital for COVID-19 in 2020. Of these, 338 patients presented with virus detection but no pneumonia whilst, 65 patients suffered from associated pneumonia. The cohort of patients with pneumonia was older (p = 0.04) and presented with more cardiovascular comorbidities such as diabetes mellitus (p = 0.08), although this parameter did not reach a statistically significant difference. The 30-day mortality rate was associated with highly complex CHD (odds ratio (OR) 7.81, p = 0.04) and advanced age (OR 2.99 per 10 years, p = 0.03). No child died of COVID-related pneumonia in our dataset. Conclusions: COVID-19 infection with associated pneumonia chiefly affected the older patients with CHD. Age and the complexity of CHD were identified as additional predictors of mortality. These aspects might be helpful to retrospectively audit the recommendations and guide health politics during future pandemic events. [ABSTRACT FROM AUTHOR]

During the COVID-19 pandemic, nonpharmaceutical interventions (NPIs) were implemented in order to control the transmission of SARS-CoV-2, potentially affecting the prevalence of respiratory syncytial virus (RSV). This review evaluated the impact of NPIs on RSV-related hospitalizations in children during the lockdown (2020–2021) compared to the pre-pandemic (2015–2020) and post-lockdown (2021–2022) periods. In this systematic review and meta-analysis, we searched through PubMed, Scopus, and Web of Science for studies published in English between 1 January 2015 and 31 December 2022. Additionally, we conducted hand searches of other records published between 1 January 2023 and 22 January 2024. Our target population was hospitalized children aged 0–18 years with RSV-related lower respiratory tract infections confirmed through immunofluorescence, antigen testing, or molecular assays. We focused on peer-reviewed observational studies, analyzing the primary outcome of pooled RSV prevalence. A generalized linear mixed model with a random-effects model was utilized to pool each RSV prevalence. Heterogeneity was assessed using Cochran's Q and I2 statistics, while publication bias was evaluated through funnel plots and Egger's tests. We identified and analyzed 5815 publications and included 112 studies with 308,985 participants. Notably, RSV prevalence was significantly lower during the lockdown period (5.03% [95% CI: 2.67; 9.28]) than during the pre-pandemic period (25.60% [95% CI: 22.57; 28.88], p < 0.0001). However, RSV prevalence increased notably in the post-lockdown period after the relaxation of COVID-19 prevention measures (42.02% [95% CI: 31.49; 53.33] vs. 5.03% [95% CI: 2.67; 9.28], p < 0.0001). Most pooled effect estimates exhibited significant heterogeneity (I2: 91.2% to 99.3%). Our findings emphasize the effectiveness of NPIs in reducing RSV transmission. NPIs should be considered significant public health measures to address RSV outbreaks. [ABSTRACT FROM AUTHOR]

Community-acquired pneumonia (CAP) is a common disease in children, and its aetiological and clinical diagnosis are challenging for physicians in both private practice and hospitals. Over the past three decades, conjugate vaccines have successfully reduced the burden of the former main causes of CAP, Streptococcus pneumoniae and Haemophilus influenzae type b. Today, viruses are by far the most commonly detected pathogens in children with CAP. Conclusion: New insights into the aetiology and treatment of CAP in children in recent years have influenced management and are the focus of this review. In addition to reducing diagnostic uncertainty, there is an urgent need to reduce antibiotic overuse and antimicrobial resistance in children with CAP. What is Known: • Conjugate vaccines against Streptococcus pneumoniae and Haemophilus influenzae type b have shifted the epidemiology of childhood CAP to predominantly viral pathogens and Mycoplasma pneumoniae. • Clinical, laboratory, and radiological criteria cannot reliably distinguish between bacterial and viral aetiology in children with CAP. What is New: • Test results and epidemiological data must be carefully interpreted, as no single diagnostic method applied to non-pulmonary specimens has both high sensitivity and high specificity for determining pneumonia aetiology in childhood CAP. • This review provides a simple and pragmatic management algorithm for children with CAP to aid physicians in providing optimal and safe care and reducing antibiotic prescribing. [ABSTRACT FROM AUTHOR]

Aim: Respiratory tract infections (RTIs) are major contributors to childhood antibiotic use. We aimed to investigate geographical and temporal trends in the prescription of antibiotics and consultations for RTIs in children <18 years living in Norway from 2010 to 2017. Methods: In a nationwide observational study, we analysed antibiotic prescriptions from the Norwegian Prescription Database and reimbursed contacts from primary care physicians. We limited the study to airway antibiotics and diagnostic codes indicating RTIs. Results: Antibiotic prescriptions due to an RTI varied from 75 to 134 per 1000 consultation due to RTI across counties in Norway (relative risk 1.79, 95% CI 1.68–1.90 for highest compared to lowest). The use of health care varied from 414 to 585 consultations for RTI per 1000 inhabitant/year (relative risk 1.43, 95% CI 1.41–1.44 for highest compared to lowest). From 2010 to 2017, we observed a 21% reduction in antibiotic prescriptions per RTI consultation and of 6% for the number of consultations for an RTI. At the county level, the use of health care was positively associated with the proportion of RTIs that resulted in antibiotic prescription. Conclusion: We found a reduction in doctors' antibiotic prescription and the use of health care for RTIs, and a variation across counties. [ABSTRACT FROM AUTHOR]

Background: It is speculated that the coronavirus disease 2019 (COVID-19) pandemic–associated reduction in the prevalence of respiratory tract infections has influenced the incidence of asthma in young children. Objectives: We investigated an association between the reduction in viral infections and the reduction in asthma in young children. Methods: The subjects were infants born in the early stages of the COVID-19 pandemic in Japan, which began in February 2020. A questionnaire survey related to asthma and allergy was conducted at 18 months and 3 years of age. These results were compared to those of age-matched infants during the nonpandemic period. Results: There were no epidemics of viral infectious diseases until the target child was 18 months old. At 18 months, the incidence of asthma/asthmatic bronchitis diagnosed by physicians in pandemic children was significantly lower than that in nonpandemic children. In 3-year-olds, no marked difference was observed between nonpandemic infants and pandemic children, except for an increase in respiratory syncytial virus infection in pandemic children. In a comparative study of the same children at ages 18 months and 3 years, an increased prevalence of asthma/asthmatic bronchitis was observed in pandemic children. Furthermore, the incidence of asthma after respiratory syncytial virus infection in pandemic infants was significantly lower than that in nonpandemic children. Conclusion: The COVID-19 pandemic–associated reduction in respiratory tract infections may have reduced the incidence of asthma in early childhood, and respiratory syncytial virus infection after 18 months of age had little effect on the onset of asthma. These results indicate the importance of preventing respiratory tract infections in early infancy.

Abstract Background A number of laboratory data and clinical studies have shown that probiotic bacteria may be beneficial in respiratory viral diseases. We investigated the role of probiotics in coronavirus disease-19 (COVID -19), post-disease symptoms, and humoral immune responses to viral antigens. Methods This was a randomized, double-blind, placebo-controlled, prospective, multicenter study. We included symptomatic patients aged 18–65 years without risk of severe disease, and positive antigen/PCR test for SARS-CoV-2. Patients received (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total) or placebo 1 capsule a day for 28 days and recorded symptoms. Three months later patients completed Post-COVID-19 Questionnaire (PCQ-19). On days 0–5 and 28–35, blood was sampled for IgG to nucleocapsid protein (NCP) and receptor binding domain (RBD)/spike 1 (S1) protein. The primary outcome measure was a patient global symptom score on day 10 of observation. The difference between groups was assessed using the Mann–Whitney U test. Results Seventy-three patients were assessed for clinical endpoints and 44 patients were evaluated for antibody production. At day 10, the median global symptom score (interquartile range) was lower in the probiotic group (0.0 (0.0–2.0) vs. 2.0 (1.0–5.0), P

Abstract Background Type 2 diabetes mellitus (T2DM) is widely prevalent worldwide, and respiratory tract infections (RTIs) have become the primary cause of death for T2DM patients who develop concurrent infections. Among these, Pseudomonas aeruginosa infection has been found to exhibit a high mortality rate and poor prognosis and is frequently observed in bacterial infections that are concurrent with COVID-19. Studies have suggested that acarbose can be used to treat T2DM and reduce inflammation. Our objective was to explore the effect of acarbose on P. aeruginosa RTI in T2DM individuals and elucidate its underlying mechanism. Methods High-fat diet (HFD) induction and P. aeruginosa inhalation were used to establish a RTI model in T2DM mice. The effect and mechanism of acarbose administered by gavage on P. aeruginosa RTI were investigated in T2DM and nondiabetic mice using survival curves, pathological examination, and transcriptomics. Results We found that P. aeruginosa RTI was more severe in T2DM mice than in nondiabetic individuals, which could be attributed to the activation of the NF-κB and TREM-1 signaling pathways. When acarbose alleviated P. aeruginosa RTI in T2DM mice, both HIF-1α and NF-κB signaling pathways were inhibited. Furthermore, inhibition of the calcium ion signaling pathway and NF-κB signaling pathway contributed to the attenuation of P. aeruginosa RTI by acarbose in nondiabetic mice. Conclusions This study confirmed the attenuating effect of acarbose on P. aeruginosa RTIs in T2DM and nondiabetic mice and investigated its mechanism, providing novel support for its clinical application in related diseases.

Bacterial Lysates are immunostimulants clinically prescribed for the prevention of respiratory tract infections (RTIs). It has been shown that Bacterial Lysates upregulate the immune system, acting both on innate and adaptive reactions. In fact, there are demonstrations of their efficacy in restoring the integrity and immune function of epithelial barriers, activating ILC3 and dendritic cells with an enhanced Th1 response, and producing serum IgG and serum and salivary IgA specific to the administered bacterial antigens. The activated immune system also protects against other bacteria and viruses due to a trained immunity effect. Most studies show that the number of RTIs and their severity decrease in Bacterial Lysates-pretreated patients, without relevant side effects. The Bacterial Lysates treatment, in addition to reducing the number of RTIs, also prevents the deterioration of the underlying disease (i.e., COPD) induced by repeated infections. Despite these positive data, the most recent meta-analyses evidence the weakness of the studies performed, which are of low quality and have an inadequate number of patients, some of which were non-randomized while others were without a control group or were performed contemporarily in different clinical conditions or with different ages. The high heterogeneity of the studies does not allow us to state Bacterial Lysates’ effectiveness in preventing RTIs with sufficient certainty. To completely define their indications, double-blind, placebo-controlled, multicenter, randomized clinical trials should be performed for each product and for each indication. The study population should be adequate for each indication. For this purpose, an adequate run-in phase will be necessary.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide, being responsible for about 3.5 million deaths so far. Despite ongoing investigations, there is still more to understand the mechanism of COVID-19 infection completely. However, it has been evidenced that SARS-CoV-2 can cause Coronavirus disease (COVID-19) notably in diabetic people. Approximately 35% of the patients who died of this disease had diabetes. A growing number of studies have evidenced that hyperglycemia is a significant risk factor for severe SARS-CoV-2 infection and plays a key role in COVID-19 mortality and diabetes comorbidity. The uncontrolled hyperglycemia can produce low-grade inflammation and impaired immunity-mediated cytokine storm that fail multiple organs and sudden death in diabetic patients with SARS-CoV-2 infection. More importantly, SARS-CoV-2 infection and interaction with ACE2 receptors also contribute to pancreatic and metabolic impairment. Thus, using of diabetes medications has been suggested to be beneficial in the better management of diabetic COVID-19 patients. Herbal treatments, as safe and affordable therapeutic agents, have recently attracted a lot of attention in this field. Accordingly, in this review, we intend to have a deep look into the molecular mechanisms of diabetic complications in SARS-CoV-2 infection and explore the therapeutic potentials of herbal medications and natural products in the management of diabetic COVID-19 patients based on recent studies and the existing clinical evidence. [ABSTRACT FROM AUTHOR]

Introduction: Following lockdown periods and restricting public health measures in response to the COVID-19 pandemic, respiratory tract infections (RTIs) rose significantly worldwide. This led to an increased burden on children's hospitals compromising medical care of acutely and chronically ill children. We characterized changes in the epidemiological pattern of circulating respiratory viral infections. Methods: We assessed the number of patients with RTIs and the annual distribution of virus detections between 2019 and 2022 based on 4809 clinical samples (4131 patients) from a German pediatric tertiary care-center. We investigated the impact of lockdown periods on spectra of circulating respiratory viruses, pattern of coinfections, age, and seasonality of infections. Results: A fourfold increase in the number of respiratory virus detections was observed in 2022 vs 2019 with numbers doubling in 2022 (vs 2021). In 2022, seasonal patterns of circulating virus, particularly Adeno and seasonal Coronavirus were far less pronounced compared to previous years, in fact almost disappeared for Rhinoviruses.". SARS-CoV-2, Parainfluenza- and human Metapneumovirus detections increased significantly in 2022 (2019 vs 2022, p < 0.01). Coinfections with multiple viruses occurred more frequently since 2021 compared to pre-pandemic years, especially in younger children (2019 vs 2022, p < 0.01). Conclusion: Compared to pre-pandemic years, we observed a dramatic increase in pediatric RTIs with an incrementing spectrum of viruses and a predominance in Rhino/Enterovirus infections – leading to a high rate of hospital admissions, particularly in conjunction with other viruses. This caused an acute shortage in medical care and may also be followed by an increase of virus-triggered secondary chronic respiratory diseases like asthma—rendering a burden on the health system. [ABSTRACT FROM AUTHOR]

Background: A number of laboratory data and clinical studies have shown that probiotic bacteria may be beneficial in respiratory viral diseases. We investigated the role of probiotics in coronavirus disease-19 (COVID -19), post-disease symptoms, and humoral immune responses to viral antigens. Methods: This was a randomized, double-blind, placebo-controlled, prospective, multicenter study. We included symptomatic patients aged 18–65 years without risk of severe disease, and positive antigen/PCR test for SARS-CoV-2. Patients received (Bifidobacterium (B.) lactis BI040, B. longum BL020, Lactobacillus (L) rhamnosus LR110, L. casei LC130, L. acidophilus LA120, 5 billion CFU total) or placebo 1 capsule a day for 28 days and recorded symptoms. Three months later patients completed Post-COVID-19 Questionnaire (PCQ-19). On days 0–5 and 28–35, blood was sampled for IgG to nucleocapsid protein (NCP) and receptor binding domain (RBD)/spike 1 (S1) protein. The primary outcome measure was a patient global symptom score on day 10 of observation. The difference between groups was assessed using the Mann–Whitney U test. Results: Seventy-three patients were assessed for clinical endpoints and 44 patients were evaluated for antibody production. At day 10, the median global symptom score (interquartile range) was lower in the probiotic group (0.0 (0.0–2.0) vs. 2.0 (1.0–5.0), P < 0.05). The probiotic group had a shorter duration of fatigue and anxiety after COVID -19 (P < 0.05) and a greater change in IgG concentration on RBD/S1 (225.9 vs. 105.6 binding antibody units/mL, P < 0.05). Conclusions: Use of probiotics alleviates acute and post-disease symptoms, and improves humoral immune response to viral antigens. Trial registration: Registered at clinicaltrials.gov as NCT04907877, June 1, 2021. [ABSTRACT FROM AUTHOR]

Purpose: Antibiotic-resistant bacterial pneumonia poses a significant therapeutic challenge. In China, Chinese herbal compound (CHC) is commonly used to treat bacterial pneumonia. We aimed to evaluate the efficacy and safety of CHC and identify core herb combinations for the treatment of multidrug-resistant or extensively drug-resistant bacterial pneumonia. Methods: Stata 16 and TSA 0.9.5.10 beta software were used for meta-analysis and trial sequential analysis (TSA), respectively. Exploring the sources of heterogeneity through meta-regression and subgroup analysis. Results: Thirty-eight studies involving 2890 patients were included in the analyses. Meta-analysis indicated that CHC combined with antibiotics improved the response rate (RR = 1.24; 95% CI: 1.19-1.28; p < 0.0001) and microbiological eradication (RR = 1.41; 95% CI: 1.27-1.57; p < 0.0001), lowered the white blood cell count (MD = -2.09; 95% CI: -2.65 to -1.53; p < 0.0001), procalcitonin levels (MD = -0.49; 95% CI: -0.59 to -0.40; p < 0.0001), C-reactive protein levels (MD = -11.80; 95% CI: -15.22 to -8.39; p < 0.0001), Clinical Pulmonary Infection Scores (CPIS) (MD = -1.97; 95% CI: -2.68 to -1.26; p < 0.0001), and Acute Physiology and Chronic Health Evaluation (APACHE)-II score (MD = -4.08; 95% CI: -5.16 to -3.00; p < 0.0001), shortened the length of hospitalization (MD = -4.79; 95% CI: -6.18 to -3.40; p < 0.0001), and reduced the number of adverse events. TSA indicated that the response rate and microbiological eradication results were robust. Moreover, Scutellaria baicalensis Georgi, Fritillaria thunbergii Miq, Lonicera japonica Thunb, and Glycyrrhiza uralensis Fisch were identified as core CHC prescription herbs. Conclusion: Compared with antibiotic treatment, CHC + antibiotic treatment was superior in improving response rate, microbiological eradication, inflammatory response, CPIS, and APACHE-II score and shortening the length of hospitalization. Association rule analysis identified four core herbs as promising candidates for treating antibiotic-resistant bacterial pneumonia. However, large-scale clinical studies are still required. [ABSTRACT FROM AUTHOR]

Background In autumn 2022, the epidemics due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory syncytial virus (RSV), and influenza overlapped, and these diseases can present with the same symptomatology. The use of a triple antigen test (SARS-CoV-2 + influenza A/B + RSV) seems crucial for accurate viral diagnosis in the context of implementing long-acting monoclonal antibody vaccination against RSV in the upcoming RSV season. Methods We assessed the usefulness of the triple test in real life in this prospective study performed from October 2022 to May 2023 and involving 116 pediatricians (2 emergency department pediatricians and 114 ambulatory pediatricians). Children <15 years old with flu-like illness (with fever), bronchiolitis (dyspnea ± wheezing), otitis, and croup were enrolled and sampled with a nasal triple test. Results For 8329 children with flu-like illness (65.3%), bronchiolitis (17.9%), otitis (8.8%), and croup (6.3%), the use of the triple test led to a viral diagnosis in 47.9% of cases. The highest RSV positivity occurred in children with bronchiolitis (32.9%). The highest influenza A and B positivity (24.6% and 19.6%) occurred in children with flu-like illness. A succession of 3 epidemics (RSV and influenza A and B) occurred over time with several overlap periods. Conclusions The triple test allowed for a viral diagnosis in half of our cases. The upcoming introduction of RSV prevention will emphasize the need for active surveillance with viral results both in ambulatory settings and hospitals. Clinical Trials Registration. NCT0441231. [ABSTRACT FROM AUTHOR]

Introduction: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, particularly in young children. In Bhutan, respiratory disease continues to be among the top 10 diseases of morbidity for several years. This study aimed to estimate the prevalence of RSV among hospitalized patients with severe acute respiratory infection (SARI) in Bhutan. Method: Respiratory specimens were collected from SARI patients of all ages in 2016 and 2018 following influenza surveillance guidelines. Specimens were tested for influenza and RSV, human metapneumovirus, adenovirus, and human parainfluenza virus types 1, 2, and 3 using real‐time reverse‐transcription polymerase chain reaction assay. Descriptive statistics were used to analyze the result in STATA 16.1. Result: Of the 1339 SARI specimens tested, 34.8% were positive for at least one viral pathogen. RSV was detected in 18.5% of SARI cases, followed by influenza in 13.4% and other respiratory viruses in 3%. The median age of SARI cases was 3 (IQR: 0.8–21 years) years. RSV detection was higher among children aged 0–6 (Adj OR: 3.03; 95% CI: 1.7–5.39) and 7–23 months (Adj OR: 3.01; 95% CI: 1.77–5.12) compared with the children aged 5–15 years. RSV was also associated with breathing difficulty (Adj OR: 1.73; 95% CI: 1.17–2.56) and pre‐existing lung disease, including asthma (Adj OR: 2.78; 95% CI: 0.99–7.8). Conclusion: Respiratory viruses were detected in a substantial proportion of SARI hospitalizations in Bhutan. [ABSTRACT FROM AUTHOR]