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Clinical Microbiology and Infection :... Dec 2022Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rapid and accurate diagnosis of herpes simplex virus (HSV)-1 and -2 (HSV1/2) in cerebrospinal fluid (CSF) is important for patient management.
OBJECTIVES
Summarize the diagnostic accuracy of commercial rapid sample-to-answer PCR assays (results in <90 minutes, without a separate nucleic acid extraction step) for HSV1/2 detection in CSF.
DATA SOURCES
Four databases (MEDLINE, EMBASE, Scopus, and CENTRAL) and five conference abstract datasets from January 2012 to March 2022.
STUDY ELIGIBILITY CRITERIA
Eligible diagnostic accuracy studies provided sufficient data for the construction of a standard diagnostic accuracy two-by-two table.
PARTICIPANTS
Patients with suspected meningitis and/or encephalitis.
TESTS
FilmArray Meningitis-Encephalitis Panel and Simplexa HSV 1&2 Direct Kit PCR.
REFERENCE STANDARD
Real-time PCR assay.
ASSESSMENT OF RISK OF BIAS
Two investigators independently extracted data, rated risk of bias, and assessed quality using QUADAS-2. METHODS OF DATA SYNTHESIS: Accuracy estimates were pooled using Bayesian random effects models.
RESULTS
Thirty-one studies were included (27 FilmArray; 4 Simplexa), comprising 9924 samples, with 95 HSV-1 and 247 HSV-2 infections. Pooled FilmArray sensitivities were 84.3% (95% credible interval, 72.3-93.0) and 92.9% (95% credible interval (CrI), 82.0-98.5) for HSV-1 and HSV-2, respectively; specificities were 99.8% (95% CrI, 99.6-99.9) and 99.9% (95% CrI, 99.9-100). Pooled Simplexa sensitivities were 97.1% (95% CrI, 88.1-99.6) and 97.9% (95% CrI, 89.6-99.9), respectively; specificities were 98.9% (95% CrI, 96.8-99.7) and 98.9% (95% CrI, 97.1-99.7). Pooled FilmArray sensitivities favoured industry-sponsored studies by 10.0 and 13.0 percentage points for HSV-1 and HSV-2, respectively. Incomplete reporting frequently led to unclear risk of bias. Several FilmArray studies did not fully report true negative data leading to their exclusion.
CONCLUSIONS
Our results suggest Simplexa is accurate for HSV1/2 detection in CSF. Moderate FilmArray sensitivity for HSV-1 suggests additional testing and/or repeat CSF sampling is required for suspected HSV encephalitis when the HSV-1 result is negative. Low prevalence of HSV-1 infections limited summary estimates' precision. Underreporting of covariates limited exploration of heterogeneity.
Topics: Humans; Herpesvirus 1, Human; Bayes Theorem; Sensitivity and Specificity; Encephalitis, Herpes Simplex; Real-Time Polymerase Chain Reaction; Meningitis; Cerebrospinal Fluid
PubMed: 35718347
DOI: 10.1016/j.cmi.2022.06.004 -
Journal of Medical Virology Jan 2021Although not common, gastrointestinal and liver symptoms have reportedly been the initial presentation of coronavirus disease-2019 (COVID-19) in a large group of... (Meta-Analysis)
Meta-Analysis
Although not common, gastrointestinal and liver symptoms have reportedly been the initial presentation of coronavirus disease-2019 (COVID-19) in a large group of patients. Therefore, knowing the frequency and characteristics of these manifestations of COVID-19 is important for both clinicians and health policy makers. A systematic review and meta-analysis of the available data on the gastrointestinal and liver manifestations of patients with COVID-19 was performed. PubMed and Scopus databases and Google Scholar search engine were searched for published and unpublished preprint articles up to 10 April 2020. Original studies providing information on clinical digestive symptoms or biomarkers of liver function in patients with polymerase chain reaction confirmed diagnosis of COVID-19 were included. After quality appraisal, data were extracted. Prevalence data from individual studies were pooled using a random-effects model. Overall, 67 studies were included in this systematic review and meta-analysis, comprising a pooled population of 13 251 patients with confirmed COVID-19. The most common gastrointestinal symptoms were anorexia (10.2%, 95% confidence interval [CI] = 6.2%-16.4%), diarrhea (8.4%, 95% CI = 6.2%-11.2%), and nausea (5.7%, 95% CI = 3.7%-8.6%), respectively. Decreased albumin levels (39.8%, 95% CI = 15.3%-70.8%), increased aspartate aminotransferase (22.8%, 95% CI = 18.1%-28.4%), and alanine aminotransferase (20.6%, 95% CI = 16.7%-25.1%) were common hepatic findings. After adjusting for preexisting gastrointestinal (5.9%) and liver diseases (4.2%), the most common gastrointestinal findings were diarrhea (8.7%, 95% CI = 5.4%-13.9%), anorexia (8.0%, 95% CI = 3.0%-19.8%), and nausea (5.1%, 95% CI = 2.2%-14.3%). Gastrointestinal and liver manifestations are not rare in patients with COVID-19, but their prevalence might be affected by preexisting diseases. Diarrhea and mild liver abnormalities seem to be relatively common in COVID-19, regardless of comorbidities.
Topics: COVID-19; Gastrointestinal Diseases; Humans; Liver Diseases; SARS-CoV-2
PubMed: 32681674
DOI: 10.1002/jmv.26314 -
PLoS Neglected Tropical Diseases Jan 2015Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology... (Review)
Review
BACKGROUND
Sub-microscopic (SM) Plasmodium infections represent transmission reservoirs that could jeopardise malaria elimination goals. A better understanding of the epidemiology of these infections and factors contributing to their occurrence will inform effective elimination strategies. While the epidemiology of SM P. falciparum infections has been documented, that of SM P. vivax infections has not been summarised. The objective of this study is to address this deficiency.
METHODOLOGY/PRINCIPAL FINDINGS
A systematic search of PubMed was conducted, and results of both light microscopy (LM) and polymerase chain reaction (PCR)-based diagnostic tests for P. vivax from 44 cross-sectional surveys or screening studies of clinical malaria suspects were analysed. Analysis revealed that SM P. vivax is prevalent across different geographic areas with varying transmission intensities. On average, the prevalence of SM P. vivax in cross-sectional surveys was 10.9%, constituting 67.0% of all P. vivax infections detected by PCR. The relative proportion of SM P. vivax is significantly higher than that of the sympatric P. falciparum in these settings. A positive relationship exists between PCR and LM P. vivax prevalence, while there is a negative relationship between the proportion of SM P. vivax and the LM prevalence for P. vivax. Amongst clinical malaria suspects, however, SM P. vivax was not identified.
CONCLUSIONS/SIGNIFICANCE
SM P. vivax is prevalent across different geographic areas, particularly areas with relatively low transmission intensity. Diagnostic tools with sensitivity greater than that of LM are required for detecting these infection reservoirs. In contrast, SM P. vivax is not prevalent in clinical malaria suspects, supporting the recommended use of quality LM and rapid diagnostic tests in clinical case management. These findings enable malaria control and elimination programs to estimate the prevalence and proportion of SM P. vivax infections in their settings, and develop appropriate elimination strategies to tackle SM P. vivax to interrupt transmission.
Topics: Global Health; Humans; Malaria, Vivax; Plasmodium vivax; Polymerase Chain Reaction
PubMed: 25569135
DOI: 10.1371/journal.pntd.0003413 -
Neuroendocrinology 2022The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain...
The NETest is a standardized and reproducible liquid biopsy for neuroendocrine tumors (NETs). It evaluates the expression of 51 NET genes by real-time polymerase chain reaction, providing an accurate molecular profile of the neoplasm. Diagnostic utility of NETest has been widely demonstrated, while its role in predicting prognosis and treatment response is less studied. This systematic review aims to collect and discuss the available evidence on the prognostic and predictive role of NETest, trying to answer 3 questions, frequently raised in clinical practice. Is NETest able to differentiate stable from progressive disease? Increased NETest levels (at least >40%) correlate with disease progression. Is NETest able to predict tumor progression and tumor response to treatment? Some studies demonstrated that the baseline NETest score >33-40% could predict tumor progression. Moreover, NETest performed after treatment (as peptide receptor radionuclide therapy) could predict treatment response also before radiological findings, since the decrease or stability of NETest score predicts tumor response to treatment. Is NETest able to evaluate tumor recurrence risk after surgery? NETest can predict surgical treatment outcome detecting minimal residual disease after radical surgery, which is characterized by a lower but positive NETest score (20-40%), while a higher score (>33-40%) is associated with nonradical surgery. In conclusion, in addition to its demonstrated diagnostic role, this systematic review highlights the efficacy of NETest to assess disease status at the moment of the NETest execution and to predict tumor recurrence after surgery. The efficacy for other applications should be proven by additional studies.
Topics: Biomarkers, Tumor; Humans; Liquid Biopsy; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Prognosis
PubMed: 34515175
DOI: 10.1159/000518873 -
Medical Journal of the Islamic Republic... 2022Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In... (Review)
Review
An Evaluation of The Diagnostic Value of Sputum Smears Microscopy and Pcr Relative to Sputum Culture in The Diagnosis of Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis in Iran.
Tuberculosis is one of the oldest known diseases in humans, and early detection of tuberculosis is one of the main measures to decrease the spread of tuberculosis. In many parts of the world, including Iran, the diagnosis of tuberculosis is based on the detection of acid-fast bacillus in sputum smear microscopy and PCR. this study aimed to synthesize evidence on the diagnostic accuracy of sputum smear and PCR compared to sputum culture for the diagnosis of PT in Iranian patients. This systematic review and meta-analysis was conducted based on PRISMA guideline for systematic review and meta-analysis. Eligible studies were cross-sectional original diagnostic studies published in English and Persian in Iran which examined the sensitivity or specificity(study outcome) of sputum smear microscopy or PCR( as the test) relative to sputum culture (as the gold standard/comparator) among Iranian patients suspected of having tuberculosis( study population). Studies whose data were not complete or extractable were excluded. A total of 3518 subjects were evaluated from 15 eligible studies. The pooled sensitivity of sputum smear and PCR was 75.12 (95% CI: 66.68-83.56) and 88.02 (95% CI: 82.87-93.27), respectively. The specificity for sputum smear and PCR was 93.94 (95% CI: 91.26-96.63) and 91.82 (95% CI: 87.29-96.35) respectively. The sensitivity of both sputum smears was higher in studies published after 2010, and had higher quality. The specificity of sputum smear was a bit lower in studies published after2010 but higher in studies with higher quality. The specificity of PCR was higher in studies published after 2010 but higher in studies with higher quality. The increased sensitivity of sputum smear and PCR during recent years suggests the improvement of preparation and laboratory methods in recent years. However, the imperfect sensitivity of these tests highlights the need for a more accurate diagnostic method for the detection of pulmonary tuberculosis in Iran.
PubMed: 36447544
DOI: 10.47176/mjiri.36.112 -
Journal of Medical Virology Dec 2022Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports... (Meta-Analysis)
Meta-Analysis
Accuracy of reverse-transcription polymerase chain reaction and loop-mediated isothermal amplification in diagnosing severe fever with thrombocytopenia syndrome: A systematic review and meta-analysis.
Nucleic acid molecular diagnostic technology plays an important role in the detection of severe fever with thrombocytopenia syndrome (SFTS). However, no relevant reports have been published on the accuracy of reverse-transcription polymerase chain reaction (RT-PCR) and reverse-transcription loop-mediated isothermal amplification (RT-LAMP) in the diagnosis of SFTS. Thus, we conducted a meta-analysis and systematic review to evaluate the accuracy of the two methods. On June 19, 2022, we comprehensively searched the PubMed, Embase, Cochrane Library, Web of Science, Scoups, Ovid, Proquest, China National Knowledge Infrastructure Database, Wan Fang Data, Traditional Chinese Medicine Database (Sinomed), VIP Database, and Reading Showing Database for articles on nucleic acid diagnostic techniques, such as RT-PCR and RT-LAMP, used to diagnose SFTS. Statistical analysis was performed using STATA 14.0 and Meta-Disc 1.4. Sixteen articles involving 2942 clinical blood samples were included in the analysis. RT-PCR and RT-LAMP were used as index tests, whereas RT-PCR or other detection methods were used as reference standards. The pooled values for the sensitivity, specificity, positive and negative likelihood ratios of the RT-PCR test were 0.97 (95% confidence interval [CI]: 0.92-0.99), 1.00 (95% CI: 0.98-1.00), 483.87 (95% CI: 58.04-4033.76), and 0.03 (95% CI:0.01-0.08), respectively. Those for the RT-LAMP test were 0.95 (95% CI: 0.91-0.97), 0.99 (95% CI: 0.93-1.00), 111.18 (95% CI: 13.96-885.27), and 0.05 (95% CI: 0.03-0.09), respectively. Both RT-PCR and RT-LAMP have high diagnostic value in SFTS and can be applied in different scenarios for laboratory confirmation or on-site screening.
Topics: Humans; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Nucleic Acids; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Severe Fever with Thrombocytopenia Syndrome
PubMed: 35968756
DOI: 10.1002/jmv.28068 -
Diagnostics (Basel, Switzerland) Jan 2022The identification of viral RNA using reverse transcription quantitative polymerase chain reaction (RT-qPCR) is the gold standard for identifying an infection caused by... (Review)
Review
The identification of viral RNA using reverse transcription quantitative polymerase chain reaction (RT-qPCR) is the gold standard for identifying an infection caused by SARS-CoV-2. The limitations of RT-qPCR such as requirement of expensive instruments, trained staff and laboratory facilities led to development of rapid antigen tests (RATs). The performance of RATs has been widely evaluated and found to be varied in different settings. The present systematic review aims to evaluate the pooled sensitivity and specificity of the commercially available RATs. This review was registered on PROSPERO (registration number: CRD42021278105). Literature search was performed through PubMed, Embase and Cochrane COVID-19 Study Register to search studies published up to 26 August 2021. The overall pooled sensitivity and specificity of RATs and subgroup analyses were calculated. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to assess the risk of bias in each study. The overall pooled sensitivity and specificity of RATs were 70% (95% CI: 69-71) and 98% (95% CI: 98-98), respectively. In subgroup analyses, nasal swabs showed the highest sensitivity of 83% (95% CI: 80-86) followed by nasopharyngeal swabs 71% (95% CI: 70-72), throat swabs 69% (95% CI: 63-75) and saliva 68% (95% CI: 59-77). Samples from symptomatic patients showed a higher sensitivity of 82% (95% CI: 82-82) as compared to asymptomatic patients at 68% (95% CI: 65-71), while a cycle threshold (Ct) value ≤25 showed a higher sensitivity of 96% (95% CI: 95-97) as compared to higher Ct value. Although the sensitivity of RATs needs to be enhanced, it may still be a viable option in places where laboratory facilities are lacking for diagnostic purposes in the early phase of disease.
PubMed: 35054277
DOI: 10.3390/diagnostics12010110 -
European Urology Open Science Oct 2022Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are... (Review)
Review
CONTEXT
Urine culture has low sensitivity in the diagnosis of urinary tract infection (UTI). Next-generation sequencing (NGS) and polymerase chain reaction (PCR) are culture-independent molecular methods available for commercial use to diagnose UTI.
OBJECTIVE
To systematically evaluate the evidence comparing the diagnostic and therapeutic values of molecular diagnostic methods to urine culture in the management of UTI in adults.
EVIDENCE ACQUISITION
We performed a critical review of Embase, Ovid, and PubMed in February 2022 according to the Preferred Reporting Items for Systematic Review and Meta-analyses statement. Studies involving pregnant women, ureteral stones, ureteral stents, and percutaneous nephrostomy tubes were excluded. Risk of bias and methodological quality were assessed using the Cochrane risk of bias tool and Newcastle Ottawa Scale. Fifteen publications were selected for inclusion.
EVIDENCE SYNTHESIS
Included reports compared NGS (nine studies) and PCR (six studies) to urine culture. A meta-analysis of seven similar studies utilizing NGS demonstrates that NGS is more sensitive in the identification of urinary bacteria and detects greater species diversity per urine sample than culture. PCR protocols designed to detect a diverse range of microbes had increased sensitivity and species diversity compared with culture. Phenotypic and genotypic resistomes are concordant in approximately 85% of cases. There is insufficient evidence to compare patient symptomatic responses to antibiotic therapy guided by molecular testing versus standard susceptibility testing.
CONCLUSIONS
Moderately strong evidence exists that molecular diagnostics demonstrate increased sensitivity in detecting urinary bacteria at the expense of poor specificity in controls. Additional data comparing patient symptoms and cure rates following antibiotic selection directed by molecular methods compared with culture are needed to elucidate their place in UTI care.
PATIENT SUMMARY
We compare culture-independent molecular methods with urine culture in the management of urinary tract infection. We found good evidence that molecular methods detect more bacteria than culture; however, the clinical implications to support their routine use are unclear.
PubMed: 36093322
DOI: 10.1016/j.euros.2022.08.009 -
Health Technology Assessment... May 2015There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen... (Review)
Review
Rapid detection of health-care-associated bloodstream infection in critical care using multipathogen real-time polymerase chain reaction technology: a diagnostic accuracy study and systematic review.
BACKGROUND
There is growing interest in the potential utility of real-time polymerase chain reaction (PCR) in diagnosing bloodstream infection by detecting pathogen deoxyribonucleic acid (DNA) in blood samples within a few hours. SeptiFast (Roche Diagnostics GmBH, Mannheim, Germany) is a multipathogen probe-based system targeting ribosomal DNA sequences of bacteria and fungi. It detects and identifies the commonest pathogens causing bloodstream infection. As background to this study, we report a systematic review of Phase III diagnostic accuracy studies of SeptiFast, which reveals uncertainty about its likely clinical utility based on widespread evidence of deficiencies in study design and reporting with a high risk of bias.
OBJECTIVE
Determine the accuracy of SeptiFast real-time PCR for the detection of health-care-associated bloodstream infection, against standard microbiological culture.
DESIGN
Prospective multicentre Phase III clinical diagnostic accuracy study using the standards for the reporting of diagnostic accuracy studies criteria.
SETTING
Critical care departments within NHS hospitals in the north-west of England.
PARTICIPANTS
Adult patients requiring blood culture (BC) when developing new signs of systemic inflammation.
MAIN OUTCOME MEASURES
SeptiFast real-time PCR results at species/genus level compared with microbiological culture in association with independent adjudication of infection. Metrics of diagnostic accuracy were derived including sensitivity, specificity, likelihood ratios and predictive values, with their 95% confidence intervals (CIs). Latent class analysis was used to explore the diagnostic performance of culture as a reference standard.
RESULTS
Of 1006 new patient episodes of systemic inflammation in 853 patients, 922 (92%) met the inclusion criteria and provided sufficient information for analysis. Index test assay failure occurred on 69 (7%) occasions. Adult patients had been exposed to a median of 8 days (interquartile range 4-16 days) of hospital care, had high levels of organ support activities and recent antibiotic exposure. SeptiFast real-time PCR, when compared with culture-proven bloodstream infection at species/genus level, had better specificity (85.8%, 95% CI 83.3% to 88.1%) than sensitivity (50%, 95% CI 39.1% to 60.8%). When compared with pooled diagnostic metrics derived from our systematic review, our clinical study revealed lower test accuracy of SeptiFast real-time PCR, mainly as a result of low diagnostic sensitivity. There was a low prevalence of BC-proven pathogens in these patients (9.2%, 95% CI 7.4% to 11.2%) such that the post-test probabilities of both a positive (26.3%, 95% CI 19.8% to 33.7%) and a negative SeptiFast test (5.6%, 95% CI 4.1% to 7.4%) indicate the potential limitations of this technology in the diagnosis of bloodstream infection. However, latent class analysis indicates that BC has a low sensitivity, questioning its relevance as a reference test in this setting. Using this analysis approach, the sensitivity of the SeptiFast test was low but also appeared significantly better than BC. Blood samples identified as positive by either culture or SeptiFast real-time PCR were associated with a high probability (> 95%) of infection, indicating higher diagnostic rule-in utility than was apparent using conventional analyses of diagnostic accuracy.
CONCLUSION
SeptiFast real-time PCR on blood samples may have rapid rule-in utility for the diagnosis of health-care-associated bloodstream infection but the lack of sensitivity is a significant limiting factor. Innovations aimed at improved diagnostic sensitivity of real-time PCR in this setting are urgently required. Future work recommendations include technology developments to improve the efficiency of pathogen DNA extraction and the capacity to detect a much broader range of pathogens and drug resistance genes and the application of new statistical approaches able to more reliably assess test performance in situation where the reference standard (e.g. blood culture in the setting of high antimicrobial use) is prone to error.
STUDY REGISTRATION
The systematic review is registered as PROSPERO CRD42011001289.
FUNDING
The National Institute for Health Research Health Technology Assessment programme. Professor Daniel McAuley and Professor Gavin D Perkins contributed to the systematic review through their funded roles as codirectors of the Intensive Care Foundation (UK).
Topics: Bacteremia; Critical Care; Cross Infection; England; False Negative Reactions; False Positive Reactions; Humans; Prospective Studies; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; State Medicine; Technology Assessment, Biomedical; Time Factors
PubMed: 25961752
DOI: 10.3310/hta19350 -
European Journal of Dentistry Jul 2023The efficacy of mouthwash for reducing the viral load in patients with the novel coronavirus disease 2019 (COVID-19) remains unclear. This systematic review and...
The efficacy of mouthwash for reducing the viral load in patients with the novel coronavirus disease 2019 (COVID-19) remains unclear. This systematic review and meta-analysis comprehensively examined the effects of chlorhexidine (CHX) and povidone-iodine (PVP-I) on the viral load in patients with COVID-19. We performed methodological analysis, systematic review, and meta-analysis of included studies using the Comprehensive Meta-analysis Software. PubMed, EMBASE, Cochrane Library, and ProQuest were searched from December 1, 2019, to December 2, 2021. In total, we included 10 studies of 1,339 patients with COVID-19. Compared with the control group, both CHX and PVP-I significantly reduced the number of negative reverse-transcription polymerase chain reaction (RT-PCR) results (<0.001) among COVID-19 patients. The CHX and PVP-I were effective on reducing the number of negative RT-PCR results in COVID-19 patients. Additional studies using adequate randomization methods and larger samples are warned.
PubMed: 36075270
DOI: 10.1055/s-0042-1753470