scholarly journals Introducing a New Algorithm for Classification of Etiology in Studies on Pediatric Pneumonia: Protocol for the Trial of Respiratory Infections in Children for Enhanced Diagnostics Study (Preprint)

2018 ◽  
Author(s):  
Samuel Arthur Rhedin ◽  
Annika Eklundh ◽  
Malin Ryd-Rinder ◽  
Pontus Naucler ◽  
Andreas Mårtensson ◽  
...  

BACKGROUND There is a need to better distinguish viral infections from antibiotic-requiring bacterial infections in children presenting with clinical community-acquired pneumonia (CAP) to assist health care workers in decision making and to improve the rational use of antibiotics. OBJECTIVE The overall aim of the Trial of Respiratory infections in children for ENhanced Diagnostics (TREND) study is to improve the differential diagnosis of bacterial and viral etiologies in children aged below 5 years with clinical CAP, by evaluating myxovirus resistance protein A (MxA) as a biomarker for viral CAP and by evaluating an existing (multianalyte point-of-care antigen detection test system [mariPOC respi] ArcDia International Oy Ltd.) and a potential future point-of-care test for respiratory pathogens. METHODS Children aged 1 to 59 months with clinical CAP as well as healthy, hospital-based, asymptomatic controls will be included at a pediatric emergency hospital in Stockholm, Sweden. Blood (analyzed for MxA and C-reactive protein) and nasopharyngeal samples (analyzed with real-time polymerase chain reaction as the gold standard and antigen-based mariPOC respi test as well as saved for future analyses of a novel recombinase polymerase amplification–based point-of-care test for respiratory pathogens) will be collected. A newly developed algorithm for the classification of CAP etiology will be used as the reference standard. RESULTS A pilot study was performed from June to August 2017. The enrollment of study subjects started in November 2017. Results are expected by the end of 2019. CONCLUSIONS The findings from the TREND study can be an important step to improve the management of children with clinical CAP. INTERNATIONAL REGISTERED REPOR DERR1-10.2196/12705

2020 ◽  
Author(s):  
Faezeh Sabet ◽  
Ali Mirhosseini ◽  
Samira Basharkhah ◽  
Mehran Mohereri ◽  
Fatemeh Sadat Mohammadi ◽  
...  

Abstract BackgroundMicrobes can influence on the development and somehow on triggering of asthma attacks. Therefore, in this study the more significant microbial infections which trigger the attacks in children were evaluated.MethodsA total of 41 nasopharyngeal and oro-pharyengeal swabs were obtained from the Pediatric Allergy Clinic of two educational hospitals, and sent to a Molecular Laboratory for evaluation of 21 bacterial and viral respiratory pathogens using qPCR-TaqMan method.ResultsThe main bacterial infections were S.aur 18/41 (43.9%), S.pneu 16/41 (39%), C.pneu 12 /41 (29.3%), and HIB 17/41 (41.5%) while the most viral infections were and HRSV 3/41 (7.3%) and FluB, HRV, HMPVA.B, HPIV-2,3,4, HcoV-63 and HcoV-229 in 2 cases (4,9%), in asthmatic children. Although, bacterial infections were more common in both gender, the frequency of those agents were statistically difference between girls and boys population (P=0.02). There were positive correlations between S. pneu infection with asthma attack and bronchitis (P= 0.02 and P= 0.001, respectively). Furthermore, a positive correlation was found between AV and RSVA.B infections with allergic rhinitis (P= 0.02 and P= 0.001, respectively).ConclusionIn conclusion, it is more likely that in this region with a population of 6.2 million and more than 25 million tourists, the bacterial respiratory infections, particularly, HIB, S.aur and S. pneu were more common, however, and consistence with other studies HRSV and Flu.B have been dominant viral infections in asthmatic attacks.


Author(s):  
Timo Huber ◽  
Philipp Steininger ◽  
Pascal Irrgang ◽  
Klaus Korn ◽  
Matthias Tenbusch ◽  
...  

AbstractSARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.


Author(s):  
Paul C. Adamson ◽  
Jeffrey D. Klausner

Chlamydia trachomatis and Neisseria gonorrhoeae are two of the most often reported bacterial infections in the United States. The rectum and oropharynx are important anatomic sites of infection and can contribute to ongoing transmission. Nucleic acid amplification tests (NAATs) are the mainstays for the detection of C. trachomatis and N. gonorrhoeae infections owing to their high sensitivity and specificity. Several NAATs have been evaluated for testing in rectal and pharyngeal infections. A few assays recently received clearance by the Food and Drug Administration, including one point-of-care test. Those assays can be used for testing in symptomatic individuals, as well as for asymptomatic screening in certain patient populations. Routine screening for C. trachomatis in pharyngeal specimens is not recommended by the Centers for Disease Control and Prevention, though is often performed due to the use of multiplex assays. While expanding the types of settings for screening and using self-collected rectal and pharyngeal specimens can help to increase access and uptake of testing, additional research is needed to determine the potential benefits and costs associated with increased screening for rectal and pharyngeal C. trachomatis and N. gonorrhoeae infections on a population level.


2015 ◽  
Vol 22 (9) ◽  
pp. 1025-1032 ◽  
Author(s):  
Per Venge ◽  
Lena Douhan-Håkansson ◽  
Daniel Garwicz ◽  
Christer Peterson ◽  
Shengyuan Xu ◽  
...  

ABSTRACTThe distinction between causes of acute infections is a major clinical challenge. Current biomarkers, however, are not sufficiently accurate. Human neutrophil lipocalin (HNL) concentrations in serum or whole blood activated by formyl-methionine-leucine-phenylalanine (fMLP) were shown to distinguish acute infections of bacterial or viral cause with high accuracy. The aim was therefore to compare the clinical performance of HNL with currently used biomarkers. Seven hundred twenty-five subjects (144 healthy controls and 581 patients with signs and symptoms of acute infections) were included in the study. C-reactive protein (CRP), the expression of CD64 on neutrophils, procalcitonin (PCT), and blood neutrophil counts were measured by established techniques, and HNL concentrations were measured in whole-blood samples after activation with fMLP. All tested biomarkers were elevated in bacterial as opposed to viral infections (P< 0.001). CRP, PCT, and CD64 expression in neutrophils was elevated in viral infections compared to healthy controls (P< 0.001). In the distinction between healthy controls and patients with bacterial infections, the areas under the receiver operating characteristic (ROC) curves were >0.85 for all biomarkers, whereas for the distinction between bacterial and viral infections, only HNL concentration in fMLP-activated whole blood showed an area under the ROC curve (AUROC) of >0.90 and superior clinical performance. The clinical performance of HNL in fMLP-activated whole blood was superior to current biomarkers and similar to previous results of HNL in serum. The procedure can be adopted for point-of-care testing with response times of <15 min.


1993 ◽  
Vol 39 (2) ◽  
pp. 293-297 ◽  
Author(s):  
T Nakayama ◽  
S Sonoda ◽  
T Urano ◽  
T Yamada ◽  
M Okada

Abstract We examined serum amyloid protein A (SAA) and C-reactive protein (CRP) as inflammatory markers of viral and bacterial infections. Both acute-phase reactants increased in the acute stage and thereafter decreased in the convalescent stage. In viral infections, the mean serum concentrations of SAA during the acute stage were 141 mg/L in infections with adenovirus, 77 mg/L with measles virus, 63 mg/L with influenza virus, 55 mg/L with parainfluenza virus, 31 mg/L with respiratory syncytial virus, and 31 mg/L in aseptic meningitis. The mean serum concentration of CRP was 19 mg/L for adenovirus infection and &lt; 7 mg/L in all other viral infections. The SAA concentrations were 5- to 11-fold greater than the CRP concentrations. Both the SAA and the CRP concentrations were higher in bacterial infections than in viral infections. Changes in the concentrations of serum SAA paralleled those in serum CRP in bacterial infection; during the course of viral infection, however, serum SAA tended to disappear more quickly than CRP did. SAA appears to be a clinically useful marker of inflammation in acute viral infections, with or without significant changes in the CRP concentration.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S260-S260
Author(s):  
Allison Bloom ◽  
Sunil Suchindran ◽  
Micah T Mcclain

Abstract Background Elderly individuals experience increased morbidity and mortality from acute respiratory infections (ARI), which are complicated by difficulties defining etiologies of ARI and risk-stratifying patients in order to guide care. A number of scoring tools have been developed to predict illness severity and patient outcome for proven pneumonia, however less is known about the use of such metrics for all causes of ARIs. Methods We analyzed risk factors, clinical course and major outcomes of individuals ≥60 years of age presenting to the emergency department with a clinical diagnosis of ARI over a 5-year period. Results Of the enrolled individuals 40 had proven viral infection and 52 proven bacterial infections, but 184 patients with clinically adjudicated ARI (67%) remained without a proven microbial etiology despite extensive workup. Age (71.5 vs. 65.9 years, P &lt; 0.001) and presence of cancer and heart failure were strongly predictive of illness severe enough to require hospital admission as compared with treatment in the outpatient setting. Of those with proven etiology, individuals with bacterial infection were more likely to require hospital and ICU admission (P &lt; 0.001). When applied to this study, a modified PORT score was found to correlate more closely with clinical outcome measures than a modified CURB-65 (r, 0.54 vs. 0.39). Jackson symptom scores, historically used for viral illness, were found to inversely correlate with outcomes (r, −0.34) and show potential for differentiating viral and bacterial etiologies (P = 0.02). Interestingly, a multivariate analysis showed that a novel scoring tool utilizing sex, heart rate, respiratory rate, blood pressure, BUN, glucose and presence of chronic lung disease and cancer was highly predictive of poor outcome in elderly subjects with all-cause ARI. Conclusion Elderly subjects are at increased risk for poor clinical outcomes from ARI and their clinical management remains challenging. However, modified PORT, CURB-65, Jackson symptom score, and a novel scoring tool presented herein all offer some predictive ability for all-cause ARI in elderly subjects. Such broadly applicable scoring metrics have the potential to assist in treatment and triage decisions at the point of care. Disclosures All authors: No reported disclosures.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Marta Molero-Luis ◽  
Didac Casas-Alba ◽  
Gabriela Orellana ◽  
Aida Ormazabal ◽  
Cristina Sierra ◽  
...  

Abstract The elevation of neopterin in cerebrospinal fluid (CSF) has been reported in several neuroinflammatory disorders. However, it is not expected that neopterin alone can discriminate among different neuroinflammatory etiologies. We conducted an observational retrospective and case–control study to analyze the CSF biomarkers neopterin, total proteins, and leukocytes in a large cohort of pediatric patients with neuroinflammatory disorders. CSF samples from 277 subjects were included and classified into four groups: Viral meningoencephalitis, bacterial meningitis, acquired immune-mediated disorders, and patients with no-immune diseases (control group). CSF neopterin was analyzed with high-performance liquid chromatography. Microbiological diagnosis included bacterial CSF cultures and several specific real-time polymerase chain reactions. Molecular testing for multiple respiratory pathogens was also included. Antibodies against neuronal and glial proteins were tested. Canonical discriminant analysis of the three biomarkers was conducted to establish the best discriminant functions for the classification of the different clinical groups. Model validation was done by biomarker analyses in a new cohort of 95 pediatric patients. CSF neopterin displayed the highest values in the viral and bacterial infection groups. By applying canonical discriminant analysis, it was possible to classify the patients into the different groups. Validation analyses displayed good results for neuropediatric patients with no-immune diseases and for viral meningitis patients, followed by the other groups. This study provides initial evidence of a more efficient approach to promote the timely classification of patients with viral and bacterial infections and acquired autoimmune disorders. Through canonical equations, we have validated a new tool that aids in the early and differential diagnosis of these neuroinflammatory conditions.


2015 ◽  
Vol 53 (7) ◽  
pp. 2079-2083 ◽  
Author(s):  
Jukka Vakkila ◽  
Janne O. Koskinen ◽  
Annika Brandt ◽  
Anna Muotiala ◽  
Viivi Liukko ◽  
...  

mariPOC is a novel point-of-care test system for rapid detection of respiratory tract infections. We compared the performance of the mariPOC test to that of bacterial culture for detecting group A streptococcus (GAS) in 219 pharyngitis patients (ages 1–64 years) and 109 healthy asymptomatic controls (ages 19–69 years). In addition, 42 patient samples were analyzed by quantitative PCR (qPCR). Of the 219 pharyngeal patient samples, 32 were positive in a GAS bacterial culture (prevalence 15%) and 65 (30%) in the mariPOC test. The amount of GAS in samples reported positive by the mariPOC test and negative by culture was, on average, 10-fold less than that of those positive in both methods. This indicated that the negative results in bacterial cultures were due to lower sensitivity. The qPCR results were positive and in line with the mariPOC results in 43% of the discordant samples studied. Two GAS culture-positive samples were negative by the mariPOC test. The prevalences of GAS in the control subjects were 2% and 6% by culture and mariPOC results, respectively. We conclude that the mariPOC antigen detection test is more sensitive than the conventional bacterial culture for the detection of GAS among symptomatic pharyngitis patients. The higher prevalence of GAS by the mariPOC test among symptomatic patients was probably not due to carriership, since among the control patients, the difference in the prevalence of GAS by the mariPOC test and culture was not nearly as high, 15% versus 4%, respectively. Clinical trials are needed to show the clinical importance of our findings.


2019 ◽  
Vol 13 (16) ◽  
pp. 1373-1386 ◽  
Author(s):  
Pénélope Bourgoin ◽  
Thomas Soliveres ◽  
Dalia Ahriz ◽  
Isabelle Arnoux ◽  
Christian Meisel ◽  
...  

Aim: Management of patients with infections within the Emergency Department (ED) is challenging for practitioners, as the identification of infectious causes remains difficult with current techniques. A new combination of two biomarkers was tested with a new rapid flow cytometry technique. Materials & methods: Subjects from the ED were tested for their CD64 on neutrophils (nCD64) and CD169 on monocytes (mCD169) levels and results were compared to their clinical records. Results: Among 139 patients, 29% had confirmed bacterial infections and 5% viral infections. nCD64 and mCD169 respectively showed 88 and 86% sensitivity and 90 and 100% specificity for identifying subjects in bacterial or viral conditions. Conclusion: This point-of-care technique could allow better management of patients in the ED.


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