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1.
Allergol Immunopathol (Madr) ; 52(3): 22-30, 2024.
Article in English | MEDLINE | ID: mdl-38721952

ABSTRACT

BACKGROUND: Preschoolers frequently have respiratory infections (RIs), which may cause wheezing in some subjects. Type 2 polarization may favor increased susceptibility to RIs and associated wheezing. Non-pharmacological remedies are garnering increasing interest as possible add-on therapies. The present preliminary study investigated the efficacy and safety of a new multi-component nasal spray in preschoolers with frequent RIs and associated wheezing. METHODS: Some preschoolers with these characteristics randomly took this product, containing lactoferrin, dipotassium glycyrrhizinate, carboxymethyl-beta-glucan, and vitamins C and D3 (Saflovir), two sprays per nostril twice daily for 3 months. Other children were randomly treated only with standard therapy. Outcomes included the number of RIs and wheezing episodes, use of medications, and severity of clinical manifestations. RESULTS: Preschoolers treated add-on with this multicomponent product experienced fewer RIs and used fewer beta-2 agonists than untreated children (P = 0.01 and 0.029, respectively). CONCLUSIONS: This preliminary study demonstrated that a multicomponent product, administered add-on as a nasal spray, could reduce the incidence of RIs and use of symptomatic drugs for relieving wheezing in children.


Subject(s)
Nasal Sprays , Respiratory Sounds , Respiratory Tract Infections , Humans , Child, Preschool , Respiratory Sounds/drug effects , Female , Male , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/diagnosis , Ascorbic Acid/administration & dosage , Lactoferrin/administration & dosage , Glycyrrhizic Acid/administration & dosage , Treatment Outcome , beta-Glucans/administration & dosage , Cholecalciferol/administration & dosage , Infant
2.
Clin Lab ; 70(5)2024 May 01.
Article in English | MEDLINE | ID: mdl-38747932

ABSTRACT

BACKGROUND: Parainfluenza virus (PIV) is a significant etiological agent of acute lower respiratory tract infections (ALRIs) in infants and young children. The present study has been conducted to investigate the prevalence of recently identified respiratory viruses. METHODS: In total, 543 oropharyngeal or nasopharyngeal swab samples collected from hospitalized patients with acute respiratory symptoms (ARS) between January and December 2021 (5,653 females and 4,950 males) were tested for respiratory viruses using RT-PCR. RESULTS: At least one respiratory virus was detected by RT-PCR in 119 out of 175 samples (68%). The most frequently detected virus was human rhinovirus (HRV) (34, 6.5%), followed by human parainfluenza viruses (HPIVs) (19, 3.6%), human bocavirus (HBoV) (8, 1.5%), human adenovirus (HAdV) (7, 1.3%), and human respiratory syncytial virus (HRSV) (4, 0.8%). HPIV-3 accounted for 3.6% (19/175) of all viral pathogens and was the second most frequently detected viral pathogen in our study. HPIV-3 infections peaked in the fall (November) of 2021. Phylogenetic analysis of the coding region of the viral protein HA revealed that all 35 (100%) of 35 HPIV-infected patients were infected with HPIV-3. CONCLUSIONS: HPIV was an important causative pathogen associated with ALRI in children hospitalized in Korea in the late fall of 2021, as the social distancing rules for COVID-19 were relaxed. These findings highlight the im-portance of HPIV as a cause of ALRI.


Subject(s)
Respiratory Tract Infections , Humans , Female , Male , Infant , Child, Preschool , Prevalence , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/diagnosis , Child , Republic of Korea/epidemiology , Paramyxoviridae Infections/epidemiology , Paramyxoviridae Infections/virology , Paramyxoviridae Infections/diagnosis , Adolescent
3.
Front Cell Infect Microbiol ; 14: 1395239, 2024.
Article in English | MEDLINE | ID: mdl-38774626

ABSTRACT

Background: Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV. Methods: We retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens. Results: This study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P<0.001). In addition, 11 patients showed consistent results between the two methods. Futhermore, mNGS showed excellent performance in identifying multi-infections in PLHIV, and 27 pathogens were detected in the BALF of 30 PLHIV by mNGS, among which 15 PLHIV were found to have multiple microbial infections (at least 3 pathogens). Pneumocystis jirovecii, human herpesvirus type 5, and human herpesvirus type 4 were the most common pathogen types. Conclusions: For PLHIV with suspected pulmonary infections, mNGS is capable of rapidly and accurately identifying the pathogen causing the pulmonary infection, which contributes to implement timely and accurate anti-infective treatment.


Subject(s)
Bronchoalveolar Lavage Fluid , HIV Infections , High-Throughput Nucleotide Sequencing , Metagenomics , Humans , High-Throughput Nucleotide Sequencing/methods , Metagenomics/methods , Male , Female , HIV Infections/complications , HIV Infections/virology , Retrospective Studies , Bronchoalveolar Lavage Fluid/microbiology , Bronchoalveolar Lavage Fluid/virology , Adult , Middle Aged , China , Coinfection/diagnosis , Coinfection/microbiology , Coinfection/virology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Respiratory Tract Infections/microbiology
4.
PLoS One ; 19(5): e0302302, 2024.
Article in English | MEDLINE | ID: mdl-38768129

ABSTRACT

BACKGROUND: Antibiotics are prescribed for over 50% of respiratory tract infections in primary care, despite good evidence of there being no benefit to the patient, and evidence of over prescribing driving microbial resistance. The high treatment rates are attributed to uncertainty regarding microbiological cause and clinical prognosis. Point-of-care-tests have been proposed as potential antibiotic stewardship tools, with some providing microbiological results in 15 minutes. However, there is little research on their impact on antibiotic use and clinical outcomes in primary care. METHODS: This is a multi-centre, individually randomised controlled trial with mixed-methods investigation of microbial, behavioural and antibiotic mechanisms on outcomes in patients aged 12 months and over presenting to primary care in the UK with a suspected respiratory tract infection, where the clinician and/or patient thinks antibiotic treatment may be, or is, necessary. Once consented, all participants are asked to provide a combined nose and throat swab sample and randomised to have a rapid microbiological point-of-care-test or no point-of-care-test. For intervention patients, clinicians review the result of the test, before contacting the patient to finalise treatment. Treatment decisions are made as per usual care in control group patients. The primary outcome is whether an antibiotic is prescribed at this point. All swab samples are sent to the central laboratory for further testing. Patients are asked to complete a diary to record the severity and duration of symptoms until resolution or day 28, and questionnaires at 2 months about their beliefs and intention to consult for similar future illnesses. Primary care medical records are also reviewed at 6-months to collect further infection consultations, antibiotic prescribing and hospital admissions. The trial aims to recruit 514 patients to achieve 90% power with 5% significance to detect a 15% absolute reduction in antibiotic prescribing. Qualitative interviews are being conducted with approximately 20 clinicians and 30 participants to understand any changes in beliefs and behaviour resulting from the point-of-care-test and generate attributes for clinician and patient discrete choice experiments. DISCUSSION: This trial will provide evidence of efficacy, acceptability and mechanisms of action of a rapid microbiological point-of-care test on antibiotic prescribing and patient symptoms in primary care. TRIAL REGISTRATION: ISRCTN16039192, prospectively registered on 08/11/2022.


Subject(s)
Anti-Bacterial Agents , Point-of-Care Testing , Primary Health Care , Respiratory Tract Infections , Humans , Anti-Bacterial Agents/therapeutic use , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/diagnosis , Randomized Controlled Trials as Topic , Female , Antimicrobial Stewardship/methods , Male , Point-of-Care Systems
5.
Vaccine ; 42(16): 3547-3554, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38704257

ABSTRACT

BACKGROUND: Within influenza vaccine effectiveness (VE) studies at primary care level with a laboratory-confirmed outcome, clinical case definitions for recruitment of patients can vary. We used the 2022-23 VEBIS primary care European multicentre study end-of-season data to evaluate whether the clinical case definition affected IVE estimates. METHODS: We estimated VE using a multicentre test-negative case-control design. We measured VE against any influenza and influenza (sub)types, by age group (0-14, 15-64, ≥65 years) and by influenza vaccine target group, using logistic regression. We estimated IVE among patients meeting the European Union (EU) acute respiratory infection (ARI) case definition and among those meeting the EU influenza-like illness (ILI) case definition, including only sites providing information on specific symptoms and recruiting patients using an ARI case definition (as the EU ILI case definition is a subset of the EU ARI one). RESULTS: We included 24 319 patients meeting the EU ARI case definition, of whom 21 804 patients (90 %) meet the EU ILI case definition, for the overall pooled VE analysis against any influenza. The overall and influenza (sub)type-specific VE varied by ≤2 % between EU ILI and EU ARI populations. DISCUSSION: Among all analyses, we found similar VE estimates between the EU ILI and EU ARI populations, with few (10%) additional non-ILI ARI patients recruited. These results indicate that VE in the 2022-23 influenza season was not affected by use of a different clinical case definition for recruitment, although we recommend investigating whether this holds true for next seasons.


Subject(s)
Influenza Vaccines , Influenza, Human , Primary Health Care , Vaccine Efficacy , Humans , Influenza Vaccines/immunology , Influenza Vaccines/administration & dosage , Influenza, Human/prevention & control , Influenza, Human/epidemiology , Influenza, Human/diagnosis , Primary Health Care/statistics & numerical data , Adolescent , Europe/epidemiology , Adult , Middle Aged , Female , Aged , Male , Child, Preschool , Child , Young Adult , Case-Control Studies , Infant , Seasons , Infant, Newborn , Vaccination/statistics & numerical data , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/prevention & control
6.
J Med Virol ; 96(6): e29715, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38808542

ABSTRACT

Numerous factors can increase the risk of severe influenza; however, a majority of severe cases occur in previously healthy children. Identification of high-risk children is important for targeted preventive interventions and prompt treatment. The aim of this study was to evaluate MUC5AC as a biomarker for influenza disease severity in children. For this, a prospective cohort study was conducted in 2019. Children hospitalized with acute respiratory infection (ARI) with confirmed positive influenza infection were enrolled. Influenza cases were identified by reverse transcriptase-polymerase chain reaction. Life-threatening disease (LTD) was defined by the need for intensive care and ventilatory support. MUC5AC, epidemiologic, and clinical risk factors were assessed. Three hundred and forty-two patients were hospitalized with ARI, of which 49 (14%) had confirmed influenza infection and 6 (12%) of them developed LTD. MUC5AC levels were higher in those patients with mild disease compared to cases with poorer outcomes. Our results show that the severity of influenza infection in children is significantly associated with low levels of MUC5AC. These findings suggest its potential as a suitable biomarker for predicting disease severity.


Subject(s)
Biomarkers , Influenza, Human , Mucin 5AC , Severity of Illness Index , Humans , Influenza, Human/diagnosis , Influenza, Human/virology , Male , Female , Biomarkers/blood , Mucin 5AC/metabolism , Prospective Studies , Child, Preschool , Infant , Child , Risk Factors , Hospitalization , Adolescent , Respiratory Tract Infections/virology , Respiratory Tract Infections/diagnosis
7.
Emerg Infect Dis ; 30(6): 1096-1103, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38781684

ABSTRACT

Viral respiratory illness surveillance has traditionally focused on single pathogens (e.g., influenza) and required fever to identify influenza-like illness (ILI). We developed an automated system applying both laboratory test and syndrome criteria to electronic health records from 3 practice groups in Massachusetts, USA, to monitor trends in respiratory viral-like illness (RAVIOLI) across multiple pathogens. We identified RAVIOLI syndrome using diagnosis codes associated with respiratory viral testing or positive respiratory viral assays or fever. After retrospectively applying RAVIOLI criteria to electronic health records, we observed annual winter peaks during 2015-2019, predominantly caused by influenza, followed by cyclic peaks corresponding to SARS-CoV-2 surges during 2020-2024, spikes in RSV in mid-2021 and late 2022, and recrudescent influenza in late 2022 and 2023. RAVIOLI rates were higher and fluctuations more pronounced compared with traditional ILI surveillance. RAVIOLI broadens the scope, granularity, sensitivity, and specificity of respiratory viral illness surveillance compared with traditional ILI surveillance.


Subject(s)
Algorithms , Electronic Health Records , Respiratory Tract Infections , Humans , Respiratory Tract Infections/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/diagnosis , Retrospective Studies , Influenza, Human/epidemiology , Influenza, Human/diagnosis , Influenza, Human/virology , COVID-19/epidemiology , COVID-19/diagnosis , Population Surveillance/methods , Massachusetts/epidemiology , Adult , Middle Aged , SARS-CoV-2 , Male , Adolescent , Child , Aged , Female , Seasons , Virus Diseases/epidemiology , Virus Diseases/diagnosis , Virus Diseases/virology , Child, Preschool , Young Adult
8.
Medicine (Baltimore) ; 103(18): e37757, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38701307

ABSTRACT

To explore the effect of targeted second-generation sequencing technique to guide clinical diagnosis and medication on the therapeutic effect and prognosis of respiratory tract infection (RTI) in children. During January 2021 to June 2022, 320 children with RTI cured were selected in our hospital as the object of this retrospective study. The control group accepted empirical broad-spectrum antibacterial therapy and the observation group accepted targeted second-generation sequencing technique to guide diagnosis and medication. The therapeutic effect, improvement time of clinical symptom index, laboratory-related index, level of inflammatory factors, incidence of complications, and parents' treatment satisfaction were compared. The observation group was considerably more efficacious (91.25%) versus the controlled group (72.50%). The duration of enhancement of fever, nasal congestion, tonsillar congestion, and cough symptoms was shorter in the observation group (P < .05). Serum levels of iron, IgA, IgG as well as IgM were substantially elevated in the observation group. The levels of IL-4 and IL-10 were markedly reduced in the observation group after treatment. The prevalence of complications was considerably below that of the comparison group (21.25%) in the observation group (8.75%). Parental satisfaction with therapy was markedly higher in the observation group (92.50%) than in the control group (66.25%). The application of targeted second-generation sequencing technology to guide clinical diagnosis and drug use can elevate the RTIs efficacy and prognosis in childhood. Targeted second-generation sequencing can achieve precise treatment, reduce drug resistance of drug-resistant strains, and improve the efficacy. It has high promotion and application value.


Subject(s)
Anti-Bacterial Agents , Respiratory Tract Infections , Humans , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/diagnosis , Male , Female , Retrospective Studies , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Child , Prognosis , Infant , Treatment Outcome
9.
Ther Adv Respir Dis ; 18: 17534666241254090, 2024.
Article in English | MEDLINE | ID: mdl-38780228

ABSTRACT

BACKGROUND: A significant decline in pulmonary exacerbation rates has been reported in CF patients homozygous for F508del treated with lumacaftor/ivacaftor. However, it is still unclear whether this reduction reflects a diminished microbiological burden. OBJECTIVES: The aim of this study was to determine the impact of lumacaftor/ivacaftor on the bacterial and fungal burden. DESIGN: The study is a prospective multicenter cohort study including 132 CF patients homozygous for F508del treated with lumacaftor/ivacaftor. METHODS: Clinical parameters as well as bacterial and fungal outcomes 1 year after initiation of lumacaftor/ivacaftor were compared to data from 2 years prior to initiation of the treatment. Changes in the slope of the outcomes before and after the onset of treatment were assessed. RESULTS: Lung function measured as ppFEV1 (p < 0.001), body mass index (BMI) in adults (p < 0.001), and BMI z-score in children (p = 0.007) were improved after initiation of lumacaftor/ivacaftor. In addition, the slope of the prevalence of Streptococcus pneumoniae (p = 0.007) and Stenotrophomonas maltophilia (p < 0.001) shifted from positive to negative, that is, became less prevalent, 1 year after treatment, while the slope for Candida albicans (p = 0.009), Penicillium spp (p = 0.026), and Scedosporium apiospermum (p < 0.001) shifted from negative to positive. CONCLUSION: The current study showed a significant improvement in clinical parameters and a reduction of some of CF respiratory microorganisms 1 year after starting with lumacaftor/ivacaftor. However, no significant changes were observed for Pseudomonas aeruginosa, Staphylococcus aureus, or Aspergillus fumigatus, key pathogens in the CF context.


Subject(s)
Aminophenols , Aminopyridines , Benzodioxoles , Cystic Fibrosis , Drug Combinations , Quinolones , Humans , Cystic Fibrosis/drug therapy , Cystic Fibrosis/microbiology , Cystic Fibrosis/physiopathology , Male , Prospective Studies , Female , Aminophenols/therapeutic use , Benzodioxoles/therapeutic use , Child , Adult , Young Adult , Adolescent , Aminopyridines/pharmacology , Aminopyridines/administration & dosage , Aminopyridines/therapeutic use , Aminopyridines/adverse effects , Quinolones/pharmacology , Sweden , Treatment Outcome , Mycoses/microbiology , Mycoses/drug therapy , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/diagnosis , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Lung/microbiology , Lung/physiopathology , Lung/drug effects , Chloride Channel Agonists/therapeutic use , Time Factors , Fungi/isolation & purification , Bacterial Infections/microbiology , Bacterial Infections/drug therapy
10.
Rev Med Suisse ; 20(869): 734-738, 2024 Apr 10.
Article in French | MEDLINE | ID: mdl-38616683

ABSTRACT

While most episodes of community-acquired pneumonia are caused by Streptococcus pneumoniae and respiratory viruses, other atypical pathogens can also be responsible for lung infections. The Infectious Diseases Service of the Lausanne University Hospital (CHUV) organizes an annual meeting aimed at general practitioners, during which interesting clinical cases are presented. In this article, we summarize five cases of community-aquired respiratory infection due to atypical pathogens that were presented during the 2023 meeting, each with a particular teaching point. Although these infections are rare, expanding the differential diagnosis in cases of suboptimal response to therapy or particular exposures is warranted.


La plupart des épisodes de pneumonie acquise en communauté sont causés par Streptococcus pneumoniae et des virus respiratoires, mais d'autres agents pathogènes atypiques peuvent également être responsables d'infections pulmonaires. Le Service des maladies infectieuses du Centre hospitalier universitaire vaudois (CHUV) organise une réunion annuelle destinée aux médecins généralistes, au cours de laquelle des cas cliniques intéressants sont présentés. Dans cet article, nous résumons cinq cas d'infections respiratoires communautaires dus à des agents pathogènes atypiques présentés lors de la réunion de 2023, chacun avec un enseignement particulier. Bien que ces infections soient rares, élargir le diagnostic différentiel en cas de réponse thérapeutique suboptimale ou d'expositions particulières est justifié.


Subject(s)
Respiratory Tract Infections , Humans , Diagnosis, Differential , General Practitioners , Hospitals, University , Respiratory Tract Infections/diagnosis
11.
Health Informatics J ; 30(2): 14604582241233996, 2024.
Article in English | MEDLINE | ID: mdl-38587170

ABSTRACT

Background: Remote mobile examination devices in telemedicine are a new technology in healthcare. Objective: To assess the utilization of visits using remote medical devices. Methods: A retrospective analysis of follow-up visits, referrals, laboratory testing and antibiotic prescriptions of 470,845 children's video visits with and without remote medical examination device and in-clinic visits. Results: Rates of follow-up visits, referrals and laboratory tests were higher in video visits compared to visit with medical device (OR of 1.27, 1.08, 1.93 respectfully). For in-clinic visits, rates of follow-up were lower but higher for referrals to subspecialists and laboratory test referrals when compared to telemedicine. Antibiotic prescriptions were provided at a lower rate in video visits compared to visits with a medical device (OR = 0.48) and in-clinic visits. Conclusions: Incorporating a remote medical device may reduce follow up visits, referrals and laboratory tests compared to a video visit without a device. The prevalence of antibiotic prescriptions did not escalate in telemedicine consultations.


Subject(s)
Respiratory Tract Infections , Telemedicine , Humans , Child , Retrospective Studies , Delivery of Health Care , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/therapy , Anti-Bacterial Agents/therapeutic use
12.
Front Cell Infect Microbiol ; 14: 1230650, 2024.
Article in English | MEDLINE | ID: mdl-38638824

ABSTRACT

Objective: To evaluate the diagnostic value of metagenomic sequencing technology based on Illumina and Nanopore sequencing platforms for patients with suspected lower respiratory tract infection whose pathogen could not be identified by conventional microbiological tests. Methods: Patients admitted to the Respiratory and Critical Care Medicine in Shanghai Ruijin Hospital were retrospectively studied from August 2021 to March 2022. Alveolar lavage or sputum was retained in patients with clinically suspected lower respiratory tract infection who were negative in conventional tests. Bronchoalveolar lavage fluid (BALF) samples were obtained using bronchoscopy. Sputum samples were collected, while BALF samples were not available due to bronchoscopy contraindications. Samples collected from enrolled patients were simultaneously sent for metagenomic sequencing on both platforms. Results: Thirty-eight patients with suspected LRTI were enrolled in this study, consisting of 36 parts of alveolar lavage and 2 parts of sputum. According to the infection diagnosis, 31 patients were confirmed to be infected with pathogens, while 7 patients were diagnosed with non-infectious disease. With regard to the diagnosis of infectious diseases, the sensitivity and specificity of Illumina and Nanopore to diagnose infection in patients were 80.6% vs. 93.5% and 42.9 vs. 28.6%, respectively. In patients diagnosed with bacterial, Mycobacterium, and fungal infections, the positive rates of Illumina and Nanopore sequencer were 71.4% vs. 78.6%, 36.4% vs. 90.9%, and 50% vs. 62.5%, respectively. In terms of pathogen diagnosis, the sensitivity and specificity of pathogens detected by Illumina and Nanopore were 55.6% vs. 77.8% and 42.9% vs. 28.6%, respectively. Among the patients treated with antibiotics in the last 2 weeks, 61.1% (11/18) and 77.8% (14/18) cases of pathogens were accurately detected by Illumina and Nanopore, respectively, among which 8 cases were detected jointly. The consistency between Illumina and diagnosis was 63.9% (23/36), while the consistency between Nanopore and diagnosis was 83.3% (30/36). Between Illumina and Nanopore sequencing methods, the consistency ratio was 55% (22/42) based on pathogen diagnosis. Conclusion: Both platforms play a certain value in infection diagnosis and pathogen diagnosis of CMT-negative suspected LRTI patients, providing a theoretical basis for clinical accurate diagnosis and symptomatic treatment. The Nanopore platform demonstrated potential advantages in the identification of Mycobacterium and could further provide another powerful approach for patients with suspected Mycobacterium infection.


Subject(s)
Nanopore Sequencing , Respiratory Tract Infections , Humans , Retrospective Studies , China , Respiratory Tract Infections/diagnosis , Anti-Bacterial Agents , Bronchoalveolar Lavage Fluid , Metagenomics , High-Throughput Nucleotide Sequencing , Sensitivity and Specificity
13.
Anal Chem ; 96(16): 6282-6291, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38595038

ABSTRACT

Respiratory tract infections (RTIs) pose a grave threat to human health, with bacterial pathogens being the primary culprits behind severe illness and mortality. In response to the pressing issue, we developed a centrifugal microfluidic chip integrated with a recombinase-aided amplification (RAA)-clustered regularly interspaced short palindromic repeats (CRISPR) system to achieve rapid detection of respiratory pathogens. The limitations of conventional two-step CRISPR-mediated systems were effectively addressed by employing the all-in-one RAA-CRISPR detection method, thereby enhancing the accuracy and sensitivity of bacterial detection. Moreover, the integration of a centrifugal microfluidic chip led to reduced sample consumption and significantly improved the detection throughput, enabling the simultaneous detection of multiple respiratory pathogens. Furthermore, the incorporation of Chelex-100 in the sample pretreatment enabled a sample-to-answer capability. This pivotal addition facilitated the deployment of the system in real clinical sample testing, enabling the accurate detection of 12 common respiratory bacteria within a set of 60 clinical samples. The system offers rapid and reliable results that are crucial for clinical diagnosis, enabling healthcare professionals to administer timely and accurate treatment interventions to patients.


Subject(s)
Respiratory Tract Infections , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/microbiology , Humans , Microfluidic Analytical Techniques/instrumentation , Lab-On-A-Chip Devices , Nucleic Acid Amplification Techniques , Clustered Regularly Interspaced Short Palindromic Repeats/genetics , Bacteria/isolation & purification , Bacteria/genetics , Recombinases/metabolism , Automation , Bacterial Infections/diagnosis
14.
BMJ Open ; 14(4): e076338, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38670622

ABSTRACT

INTRODUCTION: Syndromic panel assays, that is, using one test to simultaneously target multiple pathogens with overlapping signs and symptoms, have been integrated into routine paediatric care over the past decade, mainly for more severely ill and hospitalised patients. Their wider availability and short turnaround times open the possibility to apply them to non-hospitalised patients as well. In this context, it is important to trial how clinicians make use of pathogen detection data and if their early availability influences management decisions, particularly antibiotic use and hospitalisation. METHODS AND ANALYSIS: Advanced Diagnostics for Enhanced QUality of Antibiotic prescription in respiratory Tract infections in Emergency rooms is an individually randomised, controlled, open-label effectiveness trial comparing the impact of a respiratory pathogen panel assay (BIOFIRE Respiratory Panel 2.1plus) used as a rapid syndromic test on nasopharyngeal swabs in addition to the standard of care versus standard of care alone. The trial will 1:1 randomise 520 participants under the age of 18 at 7 paediatric emergency departments in 5 European countries. Inclusion criteria for the trial consist of two sets, with the first describing respiratory tract infections in paediatric patients and the second describing the situation of potential management uncertainty in which test results may immediately affect management decisions. Enrolment started in July 2021 and is expected to be completed in early 2024. We will perform a two-sample t-test assuming a pooled variance estimate to compare the log-transformed mean time on antibiotic treatment (in hours) and number of days alive out of the hospital within 14 days after study enrolment between the control and intervention arms. ETHICS AND DISSEMINATION: The trial protocol and materials were approved by research ethics committees in all participating countries. The respiratory pathogen panel assay is CE marked (assessed to meet European regulations) and FDA (United States Food and Drug Administration) cleared for diagnostic use. Participants and caregivers provide informed consent prior to study procedures commencing. The trial results will be published in peer-reviewed journals and at national and international conferences. Key messages will also be disseminated via press and social media where appropriate. TRIAL REGISTRATION NUMBER: NCT04781530.


Subject(s)
Emergency Service, Hospital , Respiratory Tract Infections , Humans , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/diagnosis , Child , Europe , Randomized Controlled Trials as Topic , Anti-Bacterial Agents/therapeutic use , Child, Preschool , Multicenter Studies as Topic , Infant , Adolescent , Female , Male , Acute Disease
15.
J Vis Exp ; (205)2024 Mar 29.
Article in English | MEDLINE | ID: mdl-38619279

ABSTRACT

Respiratory tract infections (RTIs) are among the most common problems in clinical settings. Rapid and accurate identification of bacterial pathogens will provide practical guidelines for managing and treating RTIs. This study describes a method for rapidly detecting bacterial pathogens that cause respiratory tract infections via multi-channel loop-mediated isothermal amplification (LAMP). LAMP is a sensitive and specific diagnostic tool that rapidly detects bacterial nucleic acids with high accuracy and reliability. The proposed method offers a significant advantage over traditional bacterial culturing methods, which are time-consuming and often require greater sensitivity for detecting low levels of bacterial nucleic acids. This article presents representative results of K. pneumoniae infection and its multiple co-infections using LAMP to detect samples (sputum, bronchial lavage fluid, and alveolar lavage fluid) from the lower respiratory tract. In summary, the multi-channel LAMP method provides a rapid and efficient means of identifying single and multiple bacterial pathogens in clinical samples, which can help prevent the spread of bacterial pathogens and aid in the appropriate treatment of RTIs.


Subject(s)
Molecular Diagnostic Techniques , Nucleic Acid Amplification Techniques , Nucleic Acids , Respiratory Tract Infections , Humans , Microfluidics , Reproducibility of Results , Respiratory Tract Infections/diagnosis , Klebsiella pneumoniae
16.
J Med Virol ; 96(4): e29624, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38647075

ABSTRACT

Respiratory infections pose a serious threat to global public health, underscoring the urgent need for rapid, accurate, and large-scale diagnostic tools. In recent years, the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated) system, combined with isothermal amplification methods, has seen widespread application in nucleic acid testing (NAT). However, achieving a single-tube reaction system containing all necessary components is challenging due to the competitive effects between recombinase polymerase amplification (RPA) and CRISPR/Cas reagents. Furthermore, to enable precision medicine, distinguishing between bacterial and viral infections is essential. Here, we have developed a novel NAT method, termed one-pot-RPA-CRISPR/Cas12a, which combines RPA with CRISPR molecular diagnostic technology, enabling simultaneous detection of 12 common respiratory pathogens, including six bacteria and six viruses. RPA and CRISPR/Cas12a reactions are separated by paraffin, providing an independent platform for RPA reactions to generate sufficient target products before being mixed with the CRISPR/Cas12a system. Results can be visually observed under LED blue light. The sensitivity of the one-pot-RPA-CRISPR/Cas12a method is 2.5 × 100 copies/µL plasmids, with no cross-reaction with other bacteria or viruses. Additionally, the clinical utility was evaluated by testing clinical isolates of bacteria and virus throat swab samples, demonstrating favorable performance. Thus, our one-pot-RPA-CRISPR/Cas12a method shows immense potential for accurate and large-scale detection of 12 common respiratory pathogens in point-of-care testing.


Subject(s)
Bacteria , CRISPR-Cas Systems , Molecular Diagnostic Techniques , Respiratory Tract Infections , Viruses , Bacteria/genetics , Bacteria/isolation & purification , Bacterial Infections/diagnosis , Bacterial Infections/microbiology , Molecular Diagnostic Techniques/methods , Nucleic Acid Amplification Techniques/methods , Recombinases/genetics , Recombinases/metabolism , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Respiratory Tract Infections/microbiology , Sensitivity and Specificity , Virus Diseases/diagnosis , Viruses/genetics , Viruses/isolation & purification
17.
Korean J Intern Med ; 39(3): 513-523, 2024 May.
Article in English | MEDLINE | ID: mdl-38649159

ABSTRACT

BACKGROUND/AIMS: Since the coronavirus disease 2019 (COVID-19) outbreak, hospitals have implemented infection control measures to minimize the spread of the virus within facilities. This study aimed to investigate the impact of COVID-19 on the incidence of healthcare-associated infections (HCAIs) and common respiratory virus (cRV) infections in hematology units. METHODS: This retrospective study included all patients hospitalized in Catholic Hematology Hospital between 2019 and 2020. Patients infected with vancomycin-resistant Enterococci (VRE), carbapenemase-producing Enterobacterales (CPE), Clostridium difficile infection (CDI), and cRV were analyzed. The incidence rate ratio (IRR) methods and interrupted time series analyses were performed to compare the incidence rates before and after the pandemic. RESULTS: The incidence rates of CPE and VRE did not differ between the two periods. However, the incidence of CDI increased significantly (IRR: 1.41 [p = 0.002]) after the COVID-19 pandemic. The incidence of cRV infection decreased by 76% after the COVID-19 outbreak (IRR: 0.240 [p < 0.001]). The incidence of adenovirus, parainfluenza virus, and rhinovirus infection significantly decreased in the COVID-19 period (IRRs: 0.087 [p = 0.003], 0.031 [p < 0.001], and 0.149 [p < 0.001], respectively). CONCLUSION: The implementation of COVID-19 infection control measures reduced the incidence of cRV infection. However, CDI increased significantly and incidence rates of CPE and VRE remained unchanged in hematological patients after the pandemic. Infection control measures suitable for each type of HCAI, such as stringent hand washing for CDI and enough isolation capacities, should be implemented and maintained in future pandemics, especially in immunocompromised patients.


Subject(s)
COVID-19 , Cross Infection , Humans , COVID-19/epidemiology , COVID-19/prevention & control , Incidence , Retrospective Studies , Cross Infection/epidemiology , Cross Infection/prevention & control , Cross Infection/diagnosis , Cross Infection/microbiology , Republic of Korea/epidemiology , Male , Female , Middle Aged , Infection Control , Aged , Adult , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Respiratory Tract Infections/microbiology , Respiratory Tract Infections/diagnosis , Hematology , SARS-CoV-2
18.
Tuberk Toraks ; 72(1): 82-90, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38676597

ABSTRACT

Introduction: Flexible bronchoscopy is a valuable method in the diagnosis and treatment of respiratory tract diseases in children. This study aimed to examine the indications for and results of flexible bronchoscopy in children. Materials and Methods: The study included patients aged 0-18 years who underwent flexible bronchoscopy between 1 January 2017 and 31 December 2022. The patients were evaluated for demographic characteristics, indications for bronchoscopy, comorbidities, bronchoscopy findings, and the results of bronchoalveolar lavage. Result: During the defined study period, a total of 410 flexible bronchoscopy procedures were performed. 51.9% of the patient population were male, and 48.1% were female, with a mean age of 96.93 ± 63.45 months. The most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection (26.8%), followed by chronic cough (19.1%). The bronchoalveolar lavage culture results showed that the most commonly isolated microorganisms were H. influenzae non-type b (7.8%) followed by M. catarrhalis (7.3%). Mucus obstruction and secretion (33.0%) constituted the most common bronchoscopic findings, while the flexible bronchoscopy examination was normal in 27% of patients. No serious complications occurred in any patient during or after the procedure. Conclusions: The results of this study demonstrated that the most common indication for flexible bronchoscopy was recurrent lower respiratory tract infection and the most common bronchoscopy finding was purulent secretion with mucus obstruction. Flexible bronchoscopy is an important diagnostic and treatment tool for patients with recurrent respiratory symptoms. It is a highly valuable method as it enables direct visualization of the airways and facilitates the collection of bronchoalveolar lavage samples.


Subject(s)
Bronchoscopy , Humans , Bronchoscopy/methods , Female , Male , Child , Child, Preschool , Adolescent , Infant , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/epidemiology , Bronchoalveolar Lavage/methods , Lung Diseases/diagnosis , Cough , Infant, Newborn , Retrospective Studies
19.
Lab Chip ; 24(9): 2485-2496, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38587207

ABSTRACT

The COVID-19 pandemic greatly impacted the in vitro diagnostic market, leading to the development of new technologies such as point-of-care testing (POCT), multiplex testing, and digital health platforms. In this study, we present a self-contained microfluidic chip integrated with an internet-of-things (IoT)-based point-of-care (POC) device for rapid and sensitive diagnosis of respiratory viruses. Our platform enables sample-to-answer diagnostics within 70 min by automating RNA extraction, reverse transcription-loop-mediated isothermal amplification (RT-LAMP), and fluorescence detection. The microfluidic chip is designed to store all the necessary reagents for the entire diagnostic assay, including a lysis buffer, a washing buffer, an elution buffer, and a lyophilized RT-LAMP cocktail. It can perform nucleic acid extraction, aliquoting, and gene amplification in multiple reaction chambers without cross-contamination. The IoT-based POC device consists of a Raspberry Pi 4 for device control and data processing, a CMOS sensor for measuring fluorescence signals, a resistive heater panel for temperature control, and solenoid valves for controlling the movement of on-chip reagent solutions. The proposed device is portable and features a touchscreen for user control and result display. We evaluated the performance of the platform using 11 clinical respiratory virus samples, including 5 SARS-CoV-2 samples, 2 influenza A samples, and 4 influenza B samples. All tested clinical samples were accurately identified with high specificity and fidelity, demonstrating the ability to simultaneously detect multiple respiratory viruses. The combination of the integrated microfluidic chip with the POC device offers a simple, cost-effective, and scalable solution for rapid molecular diagnosis of respiratory viruses in resource-limited settings.


Subject(s)
COVID-19 , Internet of Things , Lab-On-A-Chip Devices , Nucleic Acid Amplification Techniques , SARS-CoV-2 , Humans , COVID-19/diagnosis , COVID-19/virology , SARS-CoV-2/isolation & purification , SARS-CoV-2/genetics , Nucleic Acid Amplification Techniques/instrumentation , Point-of-Care Systems , Molecular Diagnostic Techniques/instrumentation , Equipment Design , Point-of-Care Testing , RNA, Viral/analysis , RNA, Viral/isolation & purification , RNA, Viral/genetics , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology
20.
Diagn Microbiol Infect Dis ; 109(3): 116308, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38688147

ABSTRACT

Syndromic testing, the simultaneous testing for multiple pathogens causing similar symptoms, has recently gained ground in clinical diagnostics. This approach can significantly shorten time to diagnosis and speed up decision-making, leading to an improved outcome for the patient. Here, we compared three automated multiplex PCR platforms for syndromic testing of respiratory samples in a retrospective study, and assessed their relative sensitivities. The PPA between BioFire and QIAstat compared to ePlex was 98.4 % and 93.8 %, respectively, and 6 discrepant results were observed. The BioFire was identified as the platform with the highest relative sensitivity. Overall, the platforms performed similarly and are all suitable for syndromic testing of respiratory samples.


Subject(s)
Molecular Diagnostic Techniques , Multiplex Polymerase Chain Reaction , Respiratory Tract Infections , Sensitivity and Specificity , Humans , Respiratory Tract Infections/diagnosis , Respiratory Tract Infections/virology , Retrospective Studies , Multiplex Polymerase Chain Reaction/methods , Molecular Diagnostic Techniques/methods , Viruses/isolation & purification , Viruses/genetics , Viruses/classification , Adult , Middle Aged , Virus Diseases/diagnosis , Virus Diseases/virology , Child , Male , Child, Preschool , Female , Adolescent , Aged , Infant , Young Adult
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