Innovative applications and future prospects of myxovirus resistance protein A in the precision diagnosis and treatment of pediatric respiratory infections

Objective: To investigate the application of WBC, CRP and SAA combined detection in the early diagnosis of respiratory tract infection in children. Methods: Collect the literature reports on the early diagnosis of respiratory tract infection in children by the combined detection of WBC, CRP and SAA in recent years, and follow up the relevant literature reports from the selection of “new three routine” laboratory items for rapid diagnosis in pediatric outpatient department and the application of the combined detection of WBC, CRP and SAA in the early diagnosis of respiratory tract infection in children. Results: Many literature studies found that the combined detection of WBC, CRP and SAA has important clinical significance in the early diagnosis of respiratory tract infection in children. Conclusion: Through reviewing the relevant literature, we can understand the application of WBC, CRP and SAA combined detection in the early diagnosis of respiratory tract infection in children. To provide more accurate and reliable laboratory data for the early diagnosis and treatment of respiratory tract infection in children in the future.

Acute infections of the respiratory tract are very common in pediatric patients, with an estimated global incidence of 17.2 billion cases in 2019. Accurate and timely diagnosis and treatment of acute respiratory infections can prevent progression to more serious pathologies, especially in the young, elderly, immunocompromised, and other high-risk groups. Due to the significant increase in the number of multiplex molecular tests available, there are now many diagnostic options which generate results within minutes or hours, many of which can be performed at point-of-care or near-patient rather than being sent out to a centralized laboratory. Rapid molecular single- or multiplex testing conducted at point-of-care or near-patient offers the potential to improve timely and accurate diagnosis, decrease inappropriate antibiotic use, decrease reliance on chest radiographs, improve timely antiviral administration, reduce the length of hospital stay, reduce the number of clinical visits, and, ultimately, improve patient outcomes. Optimal use of user-friendly multiplex molecular panels also has the potential to improve regional and global disease surveillance and to fill gaps that exist in our understanding of the epidemiology of respiratory infections. These potential benefits, however, come with limitations. For example, use of multiplex PCR assays is not always a cost effective approach. Despite their potential, there are clinical and/or laboratory circumstances where their use becomes cost prohibitive. Another recognized limitation of multiplex PCR assays is that the pathogen detected may not be the cause of a patient’s current symptom complex. Such false positive results may occur because the assays are designed to detect pathogen-specific nucleic acid (which may be residual from a prior illness), rather than replication competent pathogens, or because some pathogens can be present without causing symptomatic infection. Further study is needed to determine optimal use of these tests across different patient groups and settings. Incorporating recommendations for best practice use of multiplex molecular assays into clinical guidelines helps offer a framework for their most appropriate use in the diagnosis of pediatric acute respiratory infections.

Respiratory infections have heterogeneous causes and variable manifestations.How to make an individual and correct judge for each pediatric respiratory infection and make the patients receive an individualized and rational therapy, according to the principles and methods of clinical thinking, is a great challenge for every pediatrician, each day.Based on a briefly introduction of features of clinical thinking, this article focus on key principles in the diagnosis and treatment of pediatric respiratory infections. Key words: Child; Respiratory infection; Clinical thinking

Background and AimsPrevious studies have indicated a coherency between coronavirus disease 2019 (COVID-19) and acute kidney injury (AKI), indicating poor outcomes. However, most studies only included patients with COVID-19 and lacked a control group. Therefore, the aim of this study was to investigate the prevalence and prognostic impact of AKI in patients with COVID-19 in comparison with other respiratory tract infections.MethodThe prospective single-center observational case-control COronaVIrus surviVAl (COVIVA, clinicaltrials.gov NCT04366765) study performed at the University Hospital Basel Switzerland consecutively enrolled patients presenting to the emergency department with symptoms suggestive of COVID-19 between March 23 and May 31, 2020. The final diagnosis that led to the inclusion in the study was adjudicated by physicians after reviewing all available medical data including laboratory test results 30 days after discharge. For this analysis, we compared patients tested positive for SARS-CoV-2 with patients tested negative but with an adjudicated diagnosis of upper or lower respiratory tract infection including pneumonia. Primary outcome measure was death at 30 days, secondary outcomes were AKI incidence, renal recovery and need for renal replacement therapy. AKI was defined according to the serum creatinine criteria of the 2012 KDIGO clinical practice guideline.ResultsOf the 1086 patients included, 507 had a final adjudicated diagnosis of respiratory tract infection and were eligible for this analysis. Of those, 183 (36%) had a positive PCR swab test for SARS-CoV-2. Baseline characteristics were comparable between patients with and without COVID-19.AKI occurred in 95 patients (19%) with a higher incidence (30%, 95%CI 24-37 versus 12%, 95%CI 9-17, p<0.001) and a higher severity (KDIGO stage 3, 22% versus 10%, p=0.003) in patients with COVID-19 as compared to controls, respectively. Need for intensive care (22% versus 6%, p<0.001) and requirement for RRT were higher in patients with COVID-19 (8 patients (4.4%) versus 2 patients (0.62%); p=0.01). Renal recovery at discharge in survivors was similar in patients with (64%) and without COVID-19 (48%, p=0.175). Survival analysis identified AKI as a predictor of 30-day mortality independent of COVID-19 status (adjusted hazard ratio (aHR) 3.44, 95% confidence interval (CI) 1.55-7.63, p=0.002), but COVID-19 patients with AKI carried the highest risk (aHR 4.24, 95%CI 1,82-9.88, p<0.001). (Figure 1)ConclusionAKI occurs more frequently and more severely in patients with COVID-19 compared to other respiratory tract infections. It is associated with an increased risk for death, with the highest risk observed in COVID-19 patients. This underlines the augmented burden of AKI during the COVID-19 pandemic.

Acute respiratory tract infections frequently occur in children and represent one of the leading causes of morbidity and mortality worldwide. Quick and accurate pathogen detection can lead to a more appropriate use of antimicrobial treatment as well as timely implementation of isolation precautions. In the last decade, several commercial assays have been developed for the simultaneous diagnosis of respiratory pathogens, which substantially vary in formulation and performance characteristics. The aim of this study was to compare the performance of the “AllplexTM Respiratory Panel Assays” (Seegene) with that of the automated “Fast Track Diagnostics Respiratory pathogens 21” assay (Siemens) for the diagnosis of pediatric respiratory viral infections. One hundred forty-five nasopharyngeal wash samples, collected at the Bambino Gesù Pediatric Hospital in Rome during the fall-winter 2017-2018 season, were processed and analyzed with both workflows. Our results suggest a high concordance between the two methods for positive and negative samples. Sensitivity and specificity were calculated with both tests as a reference method. For the AllplexTM Respiratory Panel Assays, they were 98% and 100%, respectively, and for the Fast Track Diagnostics Respiratory pathogens 21 assay, they were both 100%. This comparative study allowed us to highlight the characteristics of the two assays to evaluate the best solution, on the basis of diagnostic routine and laboratory workflows, keeping in mind local epidemiology.

Evaluation of the Uro4 HB&L™ system for the rapid diagnosis of lower respiratory tract infections in intensive care units

For many years, the cornerstone of the diagnostic armamentarium for respiratory infections has been culture, whether for bacteria, mycobacteria, fungi, or viruses. Relatively more recently, adjunctive tests, such as antibody-based detection of microbial antigens in sptum, bronchoalveolar lavage fluid, and other biological specimens, have also been applied [1]. The limitations of these techniques for sensitive and specific diagnosis of upper and lower respiratory tract infections are well known. For example, many series have demonstrated that, despite extensive laboratory investigation, only about 50% of cases of community-acquired pneumonia can be ascribed to a specific pathogen [2, 3]. For this reason, the evolution of the polymerase chain reaction (PCR) as a potential diagnostic tool in clinical medicine has been followed with great interest by those in pulmonary medicine [4]. Potentially, PCR offers unmatched diagnostic sensitivity and specificity: this technique can create millions of identical copies of unique DNA sequences from a single template (a single bacteria or virus, for example) in only a few hours.

(1) To describe interpractice variation in diagnosis of respiratory infections at consultation. (2) To test the hypotheses that: (a) The decision to prescribe an antibiotic in respiratory infection is influenced by the diagnosis, the perceived certainty of diagnosis, and whether or not a consultation takes place. (b) The choice of antibiotic is influenced by the diagnosis. A regional survey of prescribing and associated morbidity in general practice, over a 2-week period in April 1994. Stratified quota sample of 22 Northern Ireland practices. There was wide interpractice variation in diagnosis of common respiratory infections at consultation, especially tonsillitis (5.0-157.5/1000 consultations). Overall, different diagnoses predicted the decision to prescribe an antibiotic at different levels (coryza 42.3%, tonsillitis 84.8%), but there was wide interpractice variation in the decision to prescribe for most diagnoses. With the exception of coryza and sinusitis, the perceived certainty of diagnosis did not significantly influence the decision to prescribe. The decision to prescribe was not significantly influenced by whether or not a consultation took place. Overall, broad spectrum penicillins were the therapeutic group most frequently prescribed for a given diagnosis with the exception of tonsillitis (phenoxymethylpenicillin) and sinusitis (tetracyclines), but there was wide interpractice variation in choice of antibiotic. Little consensus exists among practices regarding rational prescribing decisions in respiratory illness. The absence of a consultation was no deterrent to antibiotic prescribing. At one extreme, it is suggested that some practices are avoiding consultations for respiratory infections. There is wide variation in choice of antibiotic, despite existing guidelines.

BackgroundThis paper tries to describe prevalence and patterns of antibiotics prescription and bacteria detection and sensitivity to antibiotics in rural China and implications for future antibiotic stewardship.MethodsThe study was implemented in one village clinic and one township health center in each of four rural residential areas in Anhui Province, China. It used mixed-methods comprising non-participative observations, exit-survey and microbiological study. Observations were conducted to record clinical diagnosis and antibiotic prescription. Semi-structured questionnaire survey was used to collect patient’s sociodemographic information and symptoms. Sputum and throat swabs were collected for bacterial culture and susceptibility testing.ResultsA total of 1068 (51.0% male vs 49.0% female) patients completed the study with diagnosis of respiratory tract infection (326,30.5%), bronchitis/tracheitis (249,23.3%), pharyngitis (119,11.1%) and others (374, 35.0%). They provided 683 sputum and 385 throat swab specimens. Antibiotics were prescribed for 88% of the RTI patients. Of all the specimens tested, 329 (31%) were isolated with bacteria. The most frequently detected bacteria were K. pneumonia (24% in all specimens), H. influenza (16%), H. parainfluenzae (15%), P. aeruginosa (6%), S.aureus (5%), M. catarrhalis (3%) and S. pneumoniae (2%).ConclusionsThe study establishes the feasibility of conducting microbiological testing outside Tier 2 and 3 hospitals in rural China. It reveals that prescription of antibiotics, especially broad-spectrum and combined antibiotics, is still very common and there is a clear need for stewardship programs aimed at both reducing the number of prescriptions and promoting single and narrow-spectrum antibiotics.

Clinical considerations in the diagnosis of viral respiratory infections

Early and accurate diagnosis of acute respiratory infections is important because these diseases negatively affect public health and can lead to loss of workforce and an increase in health expenditures. In this study, we aimed to determine the respiration panel multiplex polymerase chain reaction (PCR) test results and seasonal distribution in our region. Three thousand and seventy-four patients samples multiplex PCR (Anatolia, Bosphore® Respiratory Pathogens Panel Kit v1) test results, which were sent to our laboratory, from 13 hospitals in our region between January 2018 and December 2018, were evaluated retrospectively. A total of 3074 patients samples, 1465 (48%) were positive and 1609 (52%) were negative test results. The most common factors were rhinovirus 30.2%, influenza A 23.1%, and respiratory syncytial virus (RSV) A/B 19.1%, respectively. When the distribution of these three most common viruses by months is examined, the most frequent months were determined as June for rhinovirus, November for influenza A, and February for RSV A/B. In the period between October and February, there was a significant increase in the positivity level of viral factors. The use of molecular methods in the diagnosis of respiratory infections will prevent unnecessary use of antibiotics and ensure correct and rapid treatment.

This study aimed to present and evaluate a novel co-detection method that enables the simultaneous identification of 11 bacterial and 7 viral pathogens in about 7 hours using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Our approach utilizes a combination of multiplex reverse transcription-PCR and matrix-assisted laser desorption/ionization time of flight mass spectrometry, which overcomes the limitations of conventional assays, which include a long assessment time, technical difficulty, and high costs. As a screening method for common respiratory pathogens in children, common respiratory pathogen mass spectrometry assay has the potential to revolutionize the diagnosis of respiratory tract infections by providing an accurate etiological diagnosis. The common respiratory pathogen mass spectrometry assay is expected to be a critical tool for the diagnosis of respiratory infections in children, offering a more efficient, cost-effective, and accurate approach for the detection of common respiratory pathogens.

(1) Background: Respiratory viral infections, including those caused by SARS-CoV-2, respiratory syncytial virus (RSV), influenza viruses, rhinovirus, and adenovirus, are major causes of acute respiratory infections (ARIs) in children. Symptom-based predictive models are valuable tools for expediting diagnoses, particularly in primary care settings. This study assessed the effectiveness of machine learning-based models in estimating infection probabilities for these common pediatric respiratory viruses, using symptom data. (2) Methods: Data were collected from 868 children with ARI symptoms evaluated across 14 primary care centers, members of COPEDICAT (Coronavirus Pediatria Catalunya), from October 2021 to October 2023. Random forest and boosting models with 10-fold cross-validation were used, applying SMOTE-NC to address class imbalance. Model performance was evaluated via area under the curve (AUC), sensitivity, specificity, and Shapley additive explanations (SHAP) values for feature importance. (3) Results: The model performed better for RSV (AUC: 0.81, sensitivity: 0.64, specificity: 0.77) and influenza viruses (AUC: 0.71, sensitivity: 0.70, specificity: 0.59) and effectively ruled out SARS-CoV-2 based on symptom absence, such as crackles and wheezing. Predictive performance was lower for non-enveloped viruses like rhinovirus and adenovirus, due to their nonspecific symptom profiles. SHAP analysis identified key symptoms patterns for each virus. (4) Conclusions: The study demonstrated that symptom-based predictive models effectively identify pediatric respiratory infections, with notable accuracy for those caused by RSV, SARS-CoV-2, and influenza viruses.

Background and objective Human rhinovirus (HRV) is one of the leading causes of pediatric respiratory tract infection with a prevalence rate of 30-50%, mostly affecting children below five years of age and causing a substantial amount of economic loss. In children, it can alone or as a co-infection, cause a wide range of symptoms from mild to life-threatening ones. With the above background, the current study was carried out to emphasize the role of HRV mono-infection in pediatric acute respiratory tract infections by correlating clinical and molecular laboratory findings. Methods This study was carried out in a tertiary care teaching hospital over a duration of four years (March 2019-October 2023). Children up to 14 years of age visiting the outpatient department or admitted to the ward with diagnoses of acute respiratory tract infections (ARTIs) were included. The clinical and laboratory data were retrieved and analyzed. A nasopharyngeal swab (NPS) or throat swab (TS) was collected and sent to the Microbiology laboratory maintaining the cold chain. Nucleic acid was extracted and subjected to multiplex real-time polymerase chain reaction (RT-PCR). Result Of the 245 samples tested for the respiratory viral pathogen, 52 samples tested positive for HRV, of which 27 had HRV mono-infection. The clinico-demographic details of these 27 patients were studied in detail. The majority of the cases (24/27; 88.8%) were less than five years of age. Fever and shortness of breath were the most consistent symptoms in all. Nineteen (19/27; 62.9%) HRV mono-infection cases had underlying co-morbidities, all requiring respiratory support. The HRV mono-infection cases either developed bronchiolitis, lower respiratory tract infection, or pneumonia. All mono-infection cases had cycle threshold value (Ct) < 25, while the Ct value of HRV was > 30 in co-infection with other viruses. Conclusion Mono-infection of HRV in under-five children with underlying comorbidities and a lesser Ct value indicates severe disease manifestation and should be dealt with more cautiously.

Improving Development of the Molecular Signature for Diagnosis of Acute Respiratory Viral Infections