Respiratory viral infections in bone marrow transplant patients: insights from a tertiary care hospital in Rawalpindi, Pakistan.

OBJECTIVE: To determine the incidence of respiratory viral infections in bone marrow transplant patients. METHODS: The prospective, descriptive, cross-sectional study was conducted at a tertiary care hospital in Rawalpindi, Pakistan, from September 2019 to August 2020, and comprised respiratory specimens from recipients of haematopoietic stem cell transplant. The specimens were collected in viral transport medium, and were then taken to the Department of Virology. Multiplex polymerase chain reaction was performed on the specimens to ascertain the incidence and prevalence of respiratory viruses. Data was analysed using SPSS 24. RESULTS: Of the 85 subjects, 53(62.35%) were males and 32(37.65%) were females. The overall median age was 20.0 years (interquartile range: 11.0-32.0 years). Respiratory viral infections were detected in 31(36.4%) specimens. Among them, human rhinovirus was detected in 12(38.7%) cases, respiratory syncytial virus in 5(16.1%), influenza A/H3 in 4(13%), human parainfluenza virus-1 in 3(9.7%), adenovirus in 2(6.4%), human parainfluenza virus-3 in 1(3.2%), human parainfluenza virus-4 in 1(3.2%) and human metapneumovirus in 1(3.2%) case. There were 2(6.4%) cases of co-infection. CONCLUSIONS: More than one-third recipients of haematopoietic stem cell transplant were found to have respiratory viral infections, highlighting the importance of employing multiplex respiratory polymerase chain reaction in early diagnosis and treatment of such infections.

Advances in nucleic acid aptamer-based detection of respiratory virus and bacteria: a mini review.

Respiratory pathogens infecting the human respiratory system are characterized by their diversity, high infectivity, rapid transmission, and acute onset. Traditional detection methods are time-consuming, have low sensitivity, and lack specificity, failing to meet the needs of rapid clinical diagnosis. Nucleic acid aptamers, as an emerging and innovative detection technology, offer novel solutions with high specificity, affinity, and broad target applicability, making them particularly promising for respiratory pathogen detection. This review highlights the progress in the research and application of nucleic acid aptamers for detecting respiratory pathogens, discussing their selection, application, potential in clinical diagnosis, and future development. Notably, these aptamers can significantly enhance the sensitivity and specificity of detection when combined with detection techniques such as fluorescence, colorimetry and electrochemistry. This review offers new insights into how aptamers can address the limitations of traditional diagnostic methods and advance clinical diagnostics. It also highlights key challenges and future research directions for the clinical application of nucleic acid aptamers.

Identifying viral infections through analysis of head space volatile organic compounds.

Volatile organic compounds (VOCs) produced by human respiratory cells reflect metabolic and pathophysiological processes which can be detected with the use of modern technology. Analysis of exhaled breath or indoor air may potentially play an important role in screening of upper respiratory tract infections such as COVID-19 or influenza in the future. In this experimental study, air samples were collected and analyzed from the headspace of anin vitrocell culture infected by selected pathogens (influenza A H1N1 and seasonal coronaviruses OC43 and NL63). VOCs were measured with a real-time proton-transfer-reaction time-of-flight mass spectrometer and a differential mobility spectrometer. Measurements were performed every 12 h for 7 d. Non-infected cells and cell culture media served as references. In H1N1 and OC43 we observed four different VOCs which peaked during the infection. Different, individual VOCs were also observed in both infections. Activity began to clearly increase after 2 d in all analyses. We did not see increased VOC production in cells infected with NL63. VOC analysis seems to be suitable to differentiate the infected cells from those which are not infected as well as different viruses, from another. In the future, this could have practical value in both individual diagnostics and indoor environment screening.

Diagnostics of viral infections using high-throughput genome sequencing data.

Plant viral infections cause significant economic losses, totalling $350 billion USD in 2021. With no treatment for virus-infected plants, accurate and efficient diagnosis is crucial to preventing and controlling these diseases. High-throughput sequencing (HTS) enables cost-efficient identification of known and unknown viruses. However, existing diagnostic pipelines face challenges. First, many methods depend on subjectively chosen parameter values, undermining their robustness across various data sources. Second, artifacts (e.g. false peaks) in the mapped sequence data can lead to incorrect diagnostic results. While some methods require manual or subjective verification to address these artifacts, others overlook them entirely, affecting the overall method performance and leading to imprecise or labour-intensive outcomes. To address these challenges, we introduce IIMI, a new automated analysis pipeline using machine learning to diagnose infections from 1583 plant viruses with HTS data. It adopts a data-driven approach for parameter selection, reducing subjectivity, and automatically filters out regions affected by artifacts, thus improving accuracy. Testing with in-house and published data shows IIMI's superiority over existing methods. Besides a prediction model, IIMI also provides resources on plant virus genomes, including annotations of regions prone to artifacts. The method is available as an R package (iimi) on CRAN and will integrate with the web application www.virtool.ca, enhancing accessibility and user convenience.

The Role of MicroRNA in the Pathophysiology and Diagnosis of Viral Myocarditis.

Myocarditis is a non-ischemic condition with a heterogeneous etiology, clinical course and prognosis. The most common etiology of myocarditis are viral infections, whereas the most severe complications are acute and chronic heart failure and sudden cardiac death. The heterogeneous clinical course of the disease, as well as the availability and costs of diagnostic tools such as cardiac magnetic resonance and endomyocardial biopsy, hinder the diagnosis of myocarditis and its underlying cause. Non-coding RNAs such as micro-RNAs (miRNAs; miR) have been shown to be involved in the disease's pathophysiology; however, their potential in disease diagnosis and treatment should also be considered. Non-coding RNAs are RNAs that are not translated into proteins, and they have the ability to regulate several intracellular pathways. MiRNAs regulate gene expression by binding with their targets and inhibiting protein synthesis by interfering with the translation of coding genes or causing the degradation of messenger RNA. Several miRNAs, such as miR-1, -133, -21, -15, -98, -126, -155, -148, -203, -208, -221, -222, -203 and -590, have been shown to be involved in the pathophysiology of viral myocarditis (VMC), and some of them have been shown to have diagnostic abilities. This article summarizes the available data on miRNAs and their associations with VMC.

Metagenomic next generation sequencing of plasma RNA for diagnosis of unexplained, acute febrile illness in Uganda.

Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.

Viral diarrheas - newer advances in diagnosis and management.

PURPOSE OF REVIEW: Viruses are the most common etiological agents of diarrhea in children. Despite rotavirus vaccine introduction, rotavirus remains as the leading cause of death globally, followed by norovirus, which represents a diagnostic challenge. Here, we describe new advances in the diagnosis and management of viral diarrheas. RECENT FINDINGS: Although immunoassays are widely used for their fast turnaround time and low cost, molecular techniques have become the most reliable diagnostic method due to their high sensitivity and capacity to analyze multiple pathogens in gastrointestinal panels. Isothermal nucleic acid amplification assays (LAMP and RPA) are promising techniques since they do not require sophisticated equipment and can be used as point-of-care testing. CRISPR/Cas nucleic acid detection systems are new diagnostic methods with great potential. Several recent published articles describe the role of human intestinal enteroids to characterize norovirus infection, to test new drugs, and for vaccine development. The interaction between the human gut microbiota and gastrointestinal viral infections has been extensively reviewed and offers some innovative mechanisms for therapeutic and preventive measures. SUMMARY: Although important advances have been made, more research is needed to address remaining challenges and further improve diagnostic capabilities and better management strategies for this critical infectious disease.

Serologic screening for viral infections among blood donors: a study in a blood bank in southern Brazil.

BACKGROUND: Routine screening for viral infections at blood donation is important to avoid transfusion-transmitted infections. It also offers an opportunity to detect an asymptomatic infection. OBJECTIVE: To study changes in serology positivity for viral infections (B and C hepatitis, HTLV-1/2, and HIV) at blood donation in a blood bank from Southern Brazil, comparing two periods of 5 years: the period from 2013 to 2017 with the period from 2018 to 2022. In addition, data on the donor fidelity rate during the studied period were sought. METHODS: Retrospective study using data from 2013 to 2022 from a single blood center electronic database from Curitiba, Southern Brazil. RESULTS: A significant drop in positive serology for all studied viruses was observed: highest in HIV (OR=0.39; 95% CI=0.27-0.57) and lowest in total anti HBc (0.56; 95 CI=0.50-0.63). Anti HBc serology became more commonly seen in women in the period of 2018-2022 when compared to men. No changes in the distribution of positive serology according to donors' ages were observed. Loyalty rates had a median of 70%, with the lowest being 60% in 2013, while the highest was 73% in 2018 and 2022. CONCLUSION: A significant reduction in discarded blood bags due to viral serology was observed when the period of 2013-2017 was compared to 2018-2022 on this blood bank; the highest reduction was observed in HIV serology and the lowest in HBc serology, which became more common in women in the second period. High rates of donor fidelity were observed during the period studied.

Plasma cell-free RNA signatures of inflammatory syndromes in children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections. We developed machine learning models based on these cfRNA profiles, which effectively differentiated KD from MIS-C-two conditions presenting with overlapping symptoms-with high performance [test area under the curve = 0.98]. We further extended this methodology into a multiclass machine learning framework that achieved 80% accuracy in distinguishing among KD, MIS-C, viral, and bacterial infections. We further demonstrated that cfRNA profiles can be used to quantify injury to specific tissues and organs, including the liver, heart, endothelium, nervous system, and the upper respiratory tract. Overall, this study identified cfRNA as a versatile analyte for the differential diagnosis and characterization of a wide range of pediatric inflammatory syndromes.

Laboratory testing for respiratory viruses for the clinician.

Testing for respiratory viruses has changed greatly over the past decade, owing to advances in technology, drug development, vaccine research, and a growing recognition of the importance of improving patient access. Here, we focus on the most common respiratory viruses and review preanalytic variables (eg, collection and storage) that affect test results, testing methods including nucleic acid amplification testing (NAAT), and controversies, challenges, and trends in diagnostic testing relevant to clinicians.

Evaluating metagenomics and targeted approaches for diagnosis and surveillance of viruses.

BACKGROUND: Metagenomics is a powerful approach for the detection of unknown and novel pathogens. Workflows based on Illumina short-read sequencing are becoming established in diagnostic laboratories. However, high sequencing depth requirements, long turnaround times, and limited sensitivity hinder broader adoption. We investigated whether we could overcome these limitations using protocols based on untargeted sequencing with Oxford Nanopore Technologies (ONT), which offers real-time data acquisition and analysis, or a targeted panel approach, which allows the selective sequencing of known pathogens and could improve sensitivity. METHODS: We evaluated detection of viruses with readily available untargeted metagenomic workflows using Illumina and ONT, and an Illumina-based enrichment approach using the Twist Bioscience Comprehensive Viral Research Panel (CVRP), which targets 3153 viruses. We tested samples consisting of a dilution series of a six-virus mock community in a human DNA/RNA background, designed to resemble clinical specimens with low microbial abundance and high host content. Protocols were designed to retain the host transcriptome, since this could help confirm the absence of infectious agents. We further compared the performance of commonly used taxonomic classifiers. RESULTS: Capture with the Twist CVRP increased sensitivity by at least 10-100-fold over untargeted sequencing, making it suitable for the detection of low viral loads (60 genome copies per ml (gc/ml)), but additional methods may be needed in a diagnostic setting to detect untargeted organisms. While untargeted ONT had good sensitivity at high viral loads (60,000 gc/ml), at lower viral loads (600-6000 gc/ml), longer and more costly sequencing runs would be required to achieve sensitivities comparable to the untargeted Illumina protocol. Untargeted ONT provided better specificity than untargeted Illumina sequencing. However, the application of robust thresholds standardized results between taxonomic classifiers. Host gene expression analysis is optimal with untargeted Illumina sequencing but possible with both the CVRP and ONT. CONCLUSIONS: Metagenomics has the potential to become standard-of-care in diagnostics and is a powerful tool for the discovery of emerging pathogens. Untargeted Illumina and ONT metagenomics and capture with the Twist CVRP have different advantages with respect to sensitivity, specificity, turnaround time and cost, and the optimal method will depend on the clinical context.

Mapping disparities in viral infection rates using highly multiplexed serology.

Despite advancements in medical interventions, the disease burden caused by viral pathogens remains large and highly diverse. This burden includes the wide range of signs and symptoms associated with active viral replication as well as a variety of clinical sequelae of infection. Moreover, there is growing evidence supporting the existence of sex- and ethnicity-based health disparities linked to viral infections and their associated diseases. Despite several well-documented disparities in viral infection rates, our current understanding of virus-associated health disparities remains incomplete. This knowledge gap can be attributed, in part, to limitations of the most commonly used viral detection methodologies, which lack the breadth needed to characterize exposures across the entire virome. Additionally, virus-related health disparities are dynamic and often differ considerably through space and time. In this study, we utilize PepSeq, an approach for highly multiplexed serology, to broadly assess an individual's history of viral exposures, and we demonstrate the effectiveness of this approach for detecting infection disparities through a pilot study of 400 adults aged 30-60 in Phoenix, AZ. Using a human virome PepSeq library, we observed expected seroprevalence rates for several common viruses and detected both expected and previously undocumented differences in inferred rates of infection between our male/female and Hispanic/non-Hispanic White individuals. IMPORTANCE: Our understanding of population-level virus infection rates and associated health disparities is incomplete. In part, this is because of the high diversity of human-infecting viruses and the limited breadth and sensitivity of traditional approaches for detecting infection events. Here, we demonstrate the potential for modern, highly multiplexed antibody detection methods to greatly increase our understanding of disparities in rates of infection across subpopulations (e.g., different sexes or ethnic groups). The use of antibodies as biomarkers allows us to detect evidence of past infections over an extended period, and our approach for highly multiplexed serology (PepSeq) allows us to measure antibody responses against hundreds of viruses in an efficient and cost-effective manner.

DVsc: An Automated Framework for Efficiently Detecting Viral Infection from Single-cell Transcriptomics Data.

Single-cell RNA sequencing (scRNA-seq) has emerged as a valuable tool for studying cellular heterogeneity in various fields, particularly in virological research. By studying the viral and cellular transcriptomes, the dynamics of viral infection can be investigated at a single-cell resolution. However, limited studies have been conducted to investigate whether RNA transcripts from clinical samples contain substantial amounts of viral RNAs, and a specific computational framework for efficiently detecting viral reads based on scRNA-seq data has not been developed. Hence, we introduce DVsc, an open-source framework for precise quantitative analysis of viral infection from single-cell transcriptomics data. When applied to approximately 200 diverse clinical samples that were infected by more than 10 different viruses, DVsc demonstrated high accuracy in systematically detecting viral infection across a wide array of cell types. This innovative bioinformatics pipeline could be crucial for addressing the potential effects of surreptitiously invading viruses on certain illnesses, as well as for designing novel medicines to target viruses in specific host cell subsets and evaluating the efficacy of treatment. DVsc supports the FASTQ format as an input and is compatible with multiple single-cell sequencing platforms. Moreover, it could also be applied to sequences from bulk RNA sequencing data. DVsc is available at http://62.234.32.33:5000/DVsc.

[Infections and liver cirrhosis]. / Infektionen und Leberzirrhose.

End-stage liver disease is a life-threatening clinical syndrome combined with a state of immune dysfunction. In this constellation patients are prone to bacterial, fungal and viral infections associated with markedly increased morbidity and mortality rates. Bacterial infections are the most prevalent kind of infection in patients with end-stage liver disease accounting for nearly 30%. The evolving rates of multidrug resistant organisms present enormous challenges in treatment strategies. Therefore, the urgent needs for prevention, early detection strategies and widespread treatment options are a necessity to handle the rising incidence of infection complications in end-stage liver disease.

New methods to detect bacterial or viral infections in patients with chronic obstructive pulmonary disease.

INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) are frequently colonized and infected by respiratory pathogens. Identifying these infectious etiologies is critical for understanding the microbial dynamics of COPD and for the appropriate use of antimicrobials during exacerbations. AREAS COVERED: Traditional methods, such as bacterial and viral cultures, have been standard in diagnosing respiratory infections. However, these methods have significant limitations, including lack of sensitivity and prolonged turnaround time. Modern molecular approaches offer rapid, sensitive, and specific detection, though they also come with their own challenges. This review explores and evaluates the clinical utility of the latest advancements in detecting bacterial and viral respiratory infections in COPD, encompassing molecular techniques, biomarkers, and emerging technologies. EXPERT OPINION: In the evolving landscape of COPD management, integrating molecular diagnostics and emerging technologies holds great promise. The enhanced sensitivity of molecular techniques has significantly advanced our understanding of the role of microbes in COPD. However, many of these technologies have primarily been developed for pneumonia diagnosis or research applications, and their clinical utility in managing COPD requires further evaluation.

School knowledge of infectious diseases in schools: conducting surveillance and on-demand, symptomatic respiratory viral testing in a large pre-kindergarten-12th grade school district.

Background: Limited data about acute respiratory illness (ARI) and respiratory virus circulation are available in congregate community settings, specifically schools. To better characterize the epidemiology of ARI and respiratory viruses in schools, we developed School Knowledge of Infectious Diseases in Schools (School KIDS). Methods: School KIDS is a prospective, respiratory viral testing program in a large metropolitan school district (pre-kindergarten-12th grade) in Kansas City, Missouri. During the 2022-2023 school year, all students and staff were eligible to participate in surveillance respiratory viral testing at school by submitting observed self-administered nasal swabs monthly. Participants could also submit a nasal swab for on-demand symptomatic testing when experiencing ≥1 ARI symptom, including cough, fever, nasal congestion, runny nose, shortness of breath, sore throat, and/or wheezing. Swabs were tested in a research laboratory using multipathogen respiratory polymerase chain reaction assays. Participants were evaluated for ongoing viral shedding by collecting two weekly nasal swabs (i.e., convalescent), following initial on-demand symptomatic testing. Participants were asked to complete an electronic survey to capture the presence and type of ARI symptom(s) before the collection of respiratory swabs. Results: From 31 October 2022 to 29 June 2023, School KIDS enrolled 978 participants, including 700 students, representing 3.4% of the district student population, and 278 staff members. Participants submitted a median of six surveillance, one symptomatic, and two convalescent specimens during the study period. A total of 6,315 respiratory specimens, including 4,700 surveillance, 721 on-demand symptomatic, and 894 convalescent specimens, were tested. Overall, a virus was detected in 1,168 (24.9%) surveillance and 363 (50.3%) symptomatic specimens. Of the 5,538 symptom surveys sent to participants before scheduled surveillance testing, 4,069 (73.5%) were completed; ARI symptoms were reported on 1,348 (33.1%) surveys. Conclusion: Respiratory surveillance testing in schools is feasible and provides novel information about respiratory virus detections in students and staff attending school. Schools are an important community setting, and better knowledge of respiratory virus circulation in schools may be useful to identify respiratory virus transmission in the community and assess the impact of effective infection prevention measures.

Utilization of multiplex polymerase chain reaction for simultaneous and rapid detection of viral infections from different ocular structures.

The impact of viral keratitis (VK) on individuals and society is notable. Early diagnosis and treatment are crucial in managing viral keratitis effectively. Timely intervention with antiviral medications and supportive care can help mitigate the severity of the infection and improve visual outcomes. We examined the prevalence of varicella-zoster virus (VZV), herpes simplex virus type 1 (HSV-1), adenovirus (AdV) and herpes simplex virus type 2 (HSV-2) in patients suspected for ocular infections. Patients included in the study exhibited various clinical manifestations indicative of ocular pathology, such as infectious keratitis, corneal scar, endogenous endophthalmitis, panuveitis, endothelitis, stromal edema, and other relevant conditions. Four different types of tear fluid, corneal samples epithelium, aqueous humor and vitreous humor were taken. After genome extraction, multiplex real-time PCR was used for diagnosis of viruses. 48 (29.6%) out of the total of 162 (100%) eye specimen were positive. The dominant prevalence was VZV (12.3%) and HSV-1 (11.7%) followed by AdV (4.9%) and HSV-2 (0.6%). There were 4 (8.3%) coinfections within the samples (HSV-1 and VZV). Aqueous humor samples demonstrated superior virus detection ability and our only HSV-2 positive sample was from aqueous humor. The utilization of multiplex real-time PCR assays in differential diagnosis of VK holds promise for expeditious diagnoses while also preventing unwarranted antibiotic prescriptions. Moreover, the aqueous humor appears to be a more sensitive site for detecting viral keratitis.

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

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

What diagnostic tests are available for respiratory infections or pulmonary exacerbations in cystic fibrosis: A scoping literature review.

A scoping review methodological framework formed the basis of this review. A search of two electronic databases captured relevant literature published from 2013. 1184 articles were screened, 200 of which met inclusion criteria. Included studies were categorised as tests for either respiratory infections OR pulmonary exacerbations. Data were extracted to ascertain test type, sample type, and indication of use for each test type. For infection, culture is the most common testing method, particularly for bacterial infections, whereas PCR is utilised more for the diagnosis of viral infections. Spirometry tests, indicating lung function, facilitate respiratory infection diagnoses. There is no clear definition of what an exacerbation is in persons with CF. A clinical checklist with risk criteria can determine if a patient is experiencing an exacerbation event, however the diagnosis is clinician-led and will vary between individuals. Fuchs criteria are one of the most frequently used tests to assess signs and symptoms of exacerbation in persons with CF. This scoping review highlights the development of home monitoring tests to facilitate earlier and easier diagnoses, and the identification of novel biomarkers for indication of infections/exacerbations as areas of current research and development. Research is particularly prevalent regarding exhaled breath condensate and volatile organic compounds as an alternative sampling/biomarker respectively for infection diagnosis. Whilst there are a wide range of tests available for diagnosing respiratory infections and/or exacerbations, these are typically used clinically in combination to ensure a rapid, accurate diagnosis which will ultimately benefit both the patient and clinician.

Using blood TNF-related apoptosis-inducing ligand levels to discriminate between viral and bacterial infections: A prospective observational study.

OBJECTIVE: The aim of the investigation was to evaluate variations in blood TNF-related apoptosis-inducing ligand (TRAIL) levels between patients with viral and bacterial infections and the diagnostic performance of TRAIL for identifying viral and bacterial infections. METHODS: The investigation included 169 adult (>18 years) patients presenting with medical signs of acute infections (inclusion criteria included a body temperature over 37.5 °C, an onset of symptoms no more than 12 days). Reference standard was based on a rigorous expert panel and the majority of the panel determined the infectious etiology. Finally, 104 patients with 78 bacterial and 26 viral reference standard outcomes were enrolled in this investigation (24 were eliminated depending on the exclusion criteria; 41 had indeterminate reference standard diagnosis). ELISA was employed to measure TRAIL levels in the group of 78 subjects with bacterial infections and 26 individuals with viral infections, and the diagnostic performance of TRAIL was identified by receiver operating characteristic (ROC) analysis. RESULTS: The TRAIL level in individuals with bacterial infections was significantly lower than that in subjects with viral infections (16.59 (2.61-32.6) pg/mL vs. 97.39 (36.18-127.74) pg/mL, P < 0.05). The area under the ROC curve (AUC) of TRAIL was 0.86 (95 %CI:0.79 to 0.94) for identifying bacterial and viral infections. Combining TRAIL with C-reactive protein (CRP), the AUC was 0.94 (95 %CI:0.89 to 1.00). CONCLUSIONS: TRAIL is diagnostic for discriminating between viral and bacterial infections. Combining TRAIL with CRP increases the AUC.