EBOLA Ag K-SeT rapid test: field evaluation in Sierra Leone

ObjectivesEfficient interruption of Ebola virus disease (EVD) transmission chains critically depends on reliable and fast laboratory diagnosis. We evaluated the performance of the EBOLA Virus Antigen Detection K-SeT (EBOLA Ag K-SeT), a new rapid diagnostic antigen test in field settings.MethodsThe study was conducted in a field laboratory located in Freetown (Sierra Leone) by the Italian National Institute for Infectious Diseases ‘L. Spallanzani’ and the EMERGENCY Onlus NGO. The EBOLA Ag K-SeT was tested on 210 residual plasma samples (EVD prevalence 50%) from patients hospitalized at the EMERGENCY Ebola treatment center in Goderich (Freetown), comparing the results with quantitative real-time PCR.ResultsOverall, the sensitivity of EBOLA Ag K-SeT was 88.6% (95% confidence interval (CI), 82.5–94.7), and the corresponding specificity was 98.1% (95% CI, 95.5–100.7). The positive and negative predictive values were 97.9% (95% CI, 95.0–100.8) and 89.6% (95% CI, 84–95.2), respectively. The sensitivity strongly increased up to 98.7% (95% CI, 96.1–101.2) for those samples with high virus load (≥6.2 log RNA copies/mL).ConclusionsOur results suggest that EBOLA Ag K-SeT could represent a new effective diagnostic tool for EVD, meeting a need for resource-poor settings and rapid diagnosis for individuals with suspected EVD.     

Accuracy of cholera rapid diagnostic tests: a systematic review and meta-analysis

BackgroundCholera is an acute diarrheal disease caused by Vibrio cholerae O1 or O139. Cholera rapid diagnostic tests (RDTs) are widely used to screen for cholera cases. However, their accuracy has not been systematically reviewed.ObjectivesTo evaluate the diagnostic accuracy of cholera RDTs.MethodsSystematic review and meta-analysis.Data sourcesMedline, EMBASE and Web of science through to November 2020; references of included studies and a technical guidance on cholera RDTs. This review is registered with PROSPERO (CRD42021233124).Study eligibility criteriaCross-sectional studies comparing the performance of cholera RDTs either to stool culture or PCR.ParticipantsIndividuals with clinically suspected cholera.Data extractionTwo authors independently extracted data and assessed the quality using Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria.ResultsEighteen studies were included in the systematic review of which 17 were used for meta-analysis. Crystal VC was the most frequently used RDT (13 studies), followed by Cholkit and Institut Pasteur cholera dipstick (three studies each), SD Bioline (two studies), Artron (one study) and Smart (one study). Using direct testing (n = 12 627 specimens), the bivariate random-effects model yielded a pooled sensitivity and specificity of 91% (95% CI 87%–94%) and 80% (95% CI 74%–84%), respectively. However, through alkaline peptone water (APW) enrichment (n = 3403 specimens), the pooled sensitivity and specificity were 89% (95% CI 79%–95%) and 98% (95% CI 95%–99%), respectively.ConclusionCholera RDTs, especially when enriched with APW, have moderate sensitivity and specificity. Although less useful for clinical management, the current generation of RDTs have clear utility for surveillance efforts if used in a principled manner. Enrichment of stool specimens in APW before using cholera RDTs reduces the possibility of obtaining false-positive results, despite the few cholera cases that go undetected. It is noteworthy that APW-enriched cholera RDTs are not necessarily rapid tests, and are not listed in the Global Task Force on Cholera Control/WHO target product profile.     

Diagnostic accuracy of antibody-based rapid diagnostic tests in detecting coronavirus disease 2019: systematic review

IntroductionThe rapid transmission of coronavirus disease 2019 (COVID-19) requires a fast, accurate, and affordable detection method. Despite doubts of their diagnostic accuracy, rapid diagnostic tests (RDTs) are used worldwide due to their practicality. This systematic review aims to determine the diagnostic accuracy of antibody-based RDTs in detecting COVID-19.Material and methodsA literature search was carried out on five journal databases using the PRISMA-P 2015 method. We included all studies published up to February 2021. The risk of bias was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Diagnostic Test Accuracy Studies. Data regarding peer-review status, study design, test kit information, immunoglobulin class, target antigen, and the number of samples were extracted and tabulated. We estimated the pooled sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) with a 95% confidence interval.ResultsThirty-three studies met the eligibility criteria. The pooled data results showed that the combined detection method of IgM or IgG had the highest sensitivity and NPV, which were 73.41% (95% CI: 72.22–74.57) and 75.34% (95% CI: 74.51–76.16), respectively. The single IgG detection method had the highest specificity and PPV of 96.68% (95% CI: 96.25–97.07) and 95.97% (95% CI: 95.47–96.42%), respectively.ConclusionsAntibody-based RDTs are not satisfactory as primary diagnostic tests but have utility as a screening tool.     

Diagnostic accuracy of tests for leprosy: a systematic review and meta-analysis

ObjectivesOwing to difficulties in the clinical diagnosis of leprosy, several complementary tests have been developed and used. The aim was to systematically summarize the accuracy of diagnostic tests for leprosy.MethodsWe searched for relevant articles in Embase, Medline, and Global Health databases, until June 2017. Studies evaluating the accuracy of any diagnostic techniques for differentiating between people with and without leprosy were included. Studies solely focusing on differentiating between the separate forms of leprosy were excluded. Our protocol was registered on PROSPERO (CRD42017071803). We assessed study quality using the QUADAS-2 checklist. A bivariate random effects regression model was used for the meta-analyses.ResultsWe included 78 studies, most of those evaluating the detection of IgM antibodies against phenolic glycolipid I using ELISA. Sensitivity of the 39 studies evaluating ELISA was 63.8% (95% CI 55.0–71.8); specificity 91.0% (95% CI 86.9–93.9). The lateral flow test (nine studies) and the agglutination test (five studies) had a slightly higher sensitivity and a slightly lower specificity. Sensitivity of qPCR was (five studies) 78.5% (95% CI 61.9–89.2) and specificity 89.3% (95% CI 61.4–97.8). Sensitivity of conventional PCR was (17 studies) 75.3% (95% CI 67.9–81.5) and specificity 94.5% (95% CI 91.4–96.5).ConclusionsAlthough the test accuracy looks reasonable, the studies suffered from heterogeneity and low methodological quality.     

Direct Blood PCR in Combination with Nucleic Acid Lateral Flow Immunoassay for Detection of Plasmodium Species in Settings Where Malaria Is Endemic

Declining malaria transmission and known difficulties with current diagnostic tools for malaria, such as microscopy and rapid diagnostic tests (RDTs) in particular at low parasite densities, still warrant the search for sensitive diagnostic tests. Molecular tests need substantial simplification before implementation in clinical settings in countries where malaria is endemic. Direct blood PCR (db-PCR), circumventing DNA extraction, to detect Plasmodium was developed and adapted to be visualized by nucleic acid lateral flow immunoassay (NALFIA). The assay was evaluated in the laboratory against samples from confirmed Sudanese patients (n = 51), returning travelers (n = 214), samples from the Dutch Blood Bank (n = 100), and in the field in Burkina Faso (n = 283) and Thailand (n = 381) on suspected malaria cases and compared to RDT and microscopy. The sensitivity and specificity of db-PCR-NALFIA compared to the initial diagnosis in the laboratory were 94.4% (95% confidence interval [CI] = 0.909 to 0.969) and 97.4% (95% CI = 0.909 to 0.969), respectively. In Burkina Faso, the sensitivity was 94.8% (95% CI = 0.88.7 to 97.9%), and the specificity was 82.4% (95% CI = 75.4 to 87.7%) compared to microscopy and 93.3% (95% CI = 87.4 to 96.7%) and 91.4% (95% CI = 85.2 to 95.3%) compared to RDT. In Thailand, the sensitivity and specificity were 93.4% (CI = 86.4 to 97.1%) and 90.9 (95% CI = 86.7 to 93.9%), respectively, compared to microscopy and 95.6% (95% CI = 88.5 to 98.6%) and 87.1% (95% CI = 82.5 to 90.6) compared to RDT. db-PCR-NALFIA is highly sensitive and specific for easy and rapid detection of Plasmodium parasites and can be easily used in countries where malaria is endemic. The inability of the device to discriminate Plasmodium species requires further investigation.     

Clinical evaluation of the BioFire FilmArray® BioThreat-E test for the diagnosis of Ebola Virus Disease in Guinea

BackgroundThe recent West Africa Ebola outbreak highlighted the need to provide access to rapid, safe and reliable Ebola Virus Disease diagnostics.ObjectivesThe objective of this field study was to assess the clinical performance of the FilmArray^® BioThreat-E test for the detection of Ebola Zaïre virus in whole blood in symptomatic patients suspected of Ebola Virus Disease in Conakry (Guinea) from March to July 2015.Study designThe BioThreat-E test was compared to the two RT-PCRs, using serum, implemented at Donka Hospital in the emergency context: an in-house developed quantitative one-step RT-PCR adapted from the Weidmann technique, and the RealStar^® Filovirus RT-PCR Kit 1.0 (Altona-Diagnostics). We also assessed the performance of this assay in noninvasive specimens (urine and saliva) to detect infected patients.ResultsOf 135 patients enrolled and eligible for performance assessment on whole blood, the sensitivity was 95.7% [95% CI: 85.5–99.5] and specificity 100% [95% CI: 95.9–100]. Of the 37 symptomatic infected patients able to provide saliva and/or urine samples, 34 of the 35 saliva samples and all 3 of the urine samples were positive with the BioThreat-E test.ConclusionsThis study showed that the FilmArray BioThreat-E test performs comparably to conventional molecular tests under field conditions, providing results and interpretation in approximately 1 h. Due to its operational characteristics, it can be easily deployed in the field during an epidemic and could also be a useful tool for post-outbreak surveillance.     

Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis: a diagnostic evaluation study

ObjectivesThe diagnosis of extrapulmonary tuberculosis (EPTB) is often made on clinical suspicion alone, resulting in both under- and overdiagnosis and relatively poor outcomes. In this study, we evaluated the clinical utility of the Xpert MTB/RIF on routinely collected extrapulmonary specimens in Ethiopia.MethodsThis study was carried out at Jimma University Specialized Hospital, Southwest Ethiopia. Extrapulmonary specimens were collected from 572 patients clinically suspected of suffering from EPTB. All specimens were tested for TB by smear microscopy, culture, and Xpert MTB/RIF. The diagnostic accuracy of Xpert MTB/RIF was calculated and compared to a composite reference standard (CRS), comprising clinical and laboratory results.ResultsIn total, 572 extrapulmonary specimens (279 lymph node, 159 pleural, 80 peritoneal, 45 cerebrospinal, and nine pericardial fluids) were tested. The pooled sensitivity and specificity of Xpert MTB/RIF were calculated to be 75% (95% CI 70–80) and 98% (95% CI 97–100) respectively when compared to the CRS. The highest sensitivity was documented for lymph node specimens (90%; 95% CI 86–94), moderate sensitivity for cerebrospinal fluid (53%; 95% CI 28–79), while the sensitivity was lowest for pleural (30%; 95% CI 17–44) and peritoneal (32%; 95% CI 12–51) fluids. Xpert MTB/RIF in addition detected rifampicin resistance in 13 patients, in perfect agreement with results from the line probe assay.ConclusionsXpert MTB/RIF may be used as initial diagnostic tool for testing of lymph node specimens from patients suspected of having TB lymphadenitis. The added value of Xpert MTB/RIF to diagnose pleural or peritoneal TB is limited by its poor sensitivity.     

Novel point-of-care biomarker combination tests to differentiate acute bacterial from viral respiratory tract infections to guide antibiotic prescribing: a systematic review

BackgroundAcute respiratory tract infections (RTIs) are the most common reason to seek medical care, with many patients receiving inappropriate antibiotics. Novel testing approaches to identify aetiology at the point-of-care are required to accurately guide antibiotic treatment.ObjectiveTo assess the diagnostic accuracy of biomarker combinations to rapidly differentiate between acute bacterial or viral RTI aetiology.Data sourcesMEDLINE, Embase and Web of Science databases were searched to February 2021.Study eligibility criteriaDiagnostic accuracy studies comparing accuracy of point-of-care and rapid diagnostic tests in primary or secondary care, consisting of biomarker combinations, to identify bacterial or viral aetiology of RTI.MethodsRisk of bias was assessed using the QUADAS-2 tool. Sensitivity and specificity of tests reported by more than one study were meta-analysed using a random effects model.ResultsTwenty observational studies (3514 patients) were identified. Eighteen were judged at high risk of bias. For bacterial aetiologies, sensitivity ranged from 61% to 100% and specificity from 18% to 96%. For viral aetiologies, sensitivity ranged from 59% to 97% and specificity from 74% to 100%. Studies evaluating two commercial tests were meta-analysed. For ImmunoXpert, the summary sensitivity and specificity were 85% (95% CI 75%–91%, k = 4) and 86% (95% CI 73%–93%, k = 4) for bacterial infections, and 90% (95% CI 79%–96%, k = 3) and 92% (95% CI 83%–96%, k = 3) for viral infections, respectively. FebriDx had pooled sensitivity and specificity of 84% (95% CI 75%–90%, k = 4) and 93% (95% CI 90%–95%, k = 4) for bacterial infections, and 87% (95% CI 72%–95%; k = 4) and 82% (95% CI 66%–86%, k = 4) for viral infections, respectively.ConclusionCombinations of biomarkers show potential clinical utility in discriminating the aetiology of RTIs. However, the limitations in the evidence base, due to a high proportion of studies with high risk of bias, preclude firm conclusions. Future research should be in primary care and evaluate patient outcomes and cost-effectiveness with experimental study designs.Clinical trialPROSPERO registration number: CRD42020178973.     

Diagnostic value of cerebrospinal fluid CXCL13 for acute Lyme neuroborreliosis. A systematic review and meta-analysis

ObjectivesThe utility of cerebrospinal fluid (CSF) CXCL13 for diagnosis of acute Lyme neuroborreliosis (LNB) has been debated and the test is not yet routinely performed. This study's aim was to evaluate its overall diagnostic accuracy through meta-analysis.MethodsElectronic searches in PubMed MEDLINE and Web of Science were performed to identify relevant articles published before January 2018. A summary receiver operating characteristic curve and an optimal cut-off were estimated modelling multiple cut-offs. Publication bias was evaluated using a funnel plot and the associated regression test.ResultsA total of 18 studies involving 618 individuals with acute LNB and 2326 individuals with other neurological disorders meeting the eligibility criteria were identified. The pooled sensitivity for CSF CXCL13 was 89% (95% CI 85%–93%) and the pooled specificity was 96% (95% CI 92%–98%), using the identified optimal cut-off value of 162 pg/mL. There was marked heterogeneity between studies, caused by differences in the designs of the study populations and age distribution. The optimal cut-off in the seven studies with a cross-sectional design was 91 pg/mL (sensitivity 96%, 95% CI 92%–98%; specificity 94%, 95% CI 86%–97%) and in the 11 case–control studies it was 164 pg/mL (sensitivity 85%, 95% CI 78%–91%; specificity 95%, 95% CI 90%–98%). CSF CXCL13 values above the optimal cut-off level (determined in this meta-analysis) were also detectable in some other central nervous system disorders, namely neurosyphilis and central nervous system lymphoma.ConclusionsOur meta-analysis shows that CSF CXCL13 has the potential to become a useful adjunct in the diagnosis of acute LNB.     

Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected coronavirus disease 2019 presenting to the hospital

ObjectivesTo assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared with an ELISA and nucleic acid amplification tests (NATs) in individuals with suspected coronavirus disease 2019 (COVID-19).MethodsPatients presenting to a Dutch teaching hospital were eligible between 17 March and 10 April 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group.ResultsIn the pilot analysis, sensitivity characteristics of LFA were heterogeneous, ranging from 2/20 (10%; 95% CI 0%–23%) to 11/20 (55%; 95% CI 33%–77%). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34%–53%) and specificity of 126/129 (98%; 95% CI 95%–100%). Sensitivity increased to 31/52 (60%; 95% CI 46%–73%) in patients with at least 7 days of symptoms, and to 21/33 (64%; 95% CI 47%–80%) in patients with C-reactive protein (CRP) ≥100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52%–72%) and 125/128 (98%; 95% CI 95%–100%) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68%–91%) in patients with at least 7 days of symptoms.ConclusionsThere is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.     

Diagnostic accuracy of rapid antigen tests in cerebrospinal fluid for pneumococcal meningitis: a systematic review and meta-analysis

BackgroundStreptococcus pneumoniae is a leading cause of bacterial meningitis worldwide. Conventional microbiological assays take several days and require the use of various drugs for empirical treatment. Rapid antigen tests in cerebrospinal fluid (CSF) may be useful to triage pneumococcal meningitis immediately.ObjectivesTo elucidate whether rapid antigen tests in CSF are useful in the triage of pneumococcal meningitis.MethodsData sourcesCochrane CENTRAL, MEDLINE, EMBASE, World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov databases were searched.Study eligibility criteriaAll types of cohort studies except multiple-group studies, where the sensitivity and specificity of rapid antigen tests in CSF compared with CSF culture can be extracted.ParticipantsPatients with suspected meningitis.TestsRapid antigen tests in CSF.Reference standardsOne or more of the following: blood culture, CSF culture, and polymerase chain reaction in CSF.Assessment of risk of biasThe methodological quality of the included studies was assessed using QUADAS-2.Methods of data synthesisWe used a random-effects bivariate model for the meta-analysis. We conducted a subgroup analysis by dividing studies into types of antigen tests, adults and children, low-income and high-income countries, and with or without exposure to antibiotics before lumbar puncture.ResultsForty-four studies involving 14 791 participants were included. Most studies had a moderate-to-low methodological quality. Summary sensitivity and specificity were 99.5% (95% confidence interval (CI), 92.4–100%) and 98.2% (95% CI, 96.9–98.9%), respectively. Positive predictive values and negative predictive values at the median prevalence (4.2%) in the included studies were 70.8% (95% CI, 56.6–79.9%) and 100% (95% CI, 99.7–100%), respectively. The diagnostic accuracy was consistent across the various subgroups, except for slightly reduced sensitivity in high-income countries.ConclusionsRapid antigen tests in CSF would be useful in triaging pneumococcal meningitis. Further studies are warranted to investigate the clinical benefit of ruling out pneumococcal meningitis based on the results of rapid antigen tests.     

Diagnostic performance of neck circumference to identify overweight and obesity as defined by body mass index in children and adolescents: systematic review and meta-analysis

Background: The neck circumference (NC) has been shown to be an accurate index for screening overweight and obesity in children and adolescents.

Aim: To perform a meta-analysis to assess the performance of NC for the assessment of overweight and obesity.

Subjects and methods: Data sources were PubMed and EMBASE up to March 2016. Studies providing measures of diagnostic performance of NC and using body mass index as reference standard were included.

Results: Six eligible studies that evaluated 11 214 children and adolescents aged 6–18 years were included in the meta-analysis. NC showed pooled sensitivity to detect high body mass index of 0.780 (95% confidence interval [CI]?=?0.765–0.794), specificity of 0.746 (95% CI?= 0.736–0.756) and a diagnostic odds ratio of 17.343 (95% CI?= 8.743–34.405).

Conclusions: The NC had moderate diagnostic accuracy for identifying overweight and obesity in children and adolescents.     

Accuracy of interferon-γ-induced protein 10 for diagnosing latent tuberculosis infection: a systematic review and meta-analysis

BackgroundEffective diagnostic methods for detecting latent tuberculosis infection (LTBI) are important for its eradication. A number of studies have evaluated the use of interferon-γ-induced protein 10 (IP-10), which is elevated after tuberculosis infection, as a biomarker for LTBI, but conclusive results regarding its effectiveness have not been reported.ObjectivesOur objective was to assess the diagnostic value of IP-10 for LTBI.Data sourcesWe searched the PubMed, Embase, the Cochrane Library and Web of Science databases to find eligible studies.Study eligibility criteriaWe included cohort, case–control and cross-sectional studies that evaluated IP-10 in LTBI participants in comparison with tuberculin skin tests (TST) and interferon-γ release assays (IGRA).ParticipantsIndividuals with LTBI and uninfected participants.InterventionsIP-10 (index test) compared with TST and IGRA (reference standard) for diagnosing LTBI.MethodsPubMed, Embase, the Cochrane Library, and Web of Science databases were searched up to June 2018. A hierarchical summary receiver operating characteristic (HSROC) model was used to evaluate the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and HSROC curve for the diagnostic efficiency of IP-10.ResultsTwelve studies including 1023 participants and 1122 samples were included. The overall pooled sensitivity was 0.85 (95% CI 0.80–0.88), specificity was 0.89 (95% CI 0.84–0.92), PLR was 7.55 (95% CI 5.20–10.97), NLR was 0.17 (95% CI 0.13–0.22) and DOR was 44.23 (95% CI 28.86–67.79), indicating a high accuracy for diagnosing LTBI. Based on a meta-regression analysis, high-burden countries, study design, IP-10 method, reference standard and the IP-10 cut-off could not explain the heterogeneity (p >0.05).ConclusionsOur results suggested that IP-10 is a promising biomarker for the diagnosis of LTBI.     

Utility of bronchoalveolar lavage fluid galactomannan alone or in combination with PCR for the diagnosis of invasive aspergillosis in adult hematology patients: A systematic review and meta-analysis

Abstract

Background: The clinical utility of bronchoalveolar lavage (BAL) fluid galactomannan (GM) for the early diagnosis of invasive aspergillosis (IA) varies widely across studies mainly due to heterogeneity of the studied populations. Methods: We conducted a systematic review and meta-analysis of 16 studies involving 783 adults with hematological malignancies to derive summary estimates of the overall accuracy of BAL-GM for diagnosing IA. Findings: Summary estimates of BAL-GM using an optical density (OD) index cutoff value of 1.5 for proven and probable IA were: sensitivity 0.92 (95% CI?=?0.48–0.99), specificity 0.98 (95% CI?=?0.78–1.00), positive likelihood ratio 53.7 (95% CI?=?3.7–771.8), and negative likelihood ratio 0.08 (95% CI?=?0.01–0.83). Comparing serum GM and Aspergillus PCR testing on BAL fluid, BAL-GM conferred greater sensitivity, but lower specificity than the serum GM test, and similar specificity as the PCR assay. The use of BAL-GM with serum GM or BAL-PCR tests increased the sensitivity moderately when a positive result was defined by either assay. Interpretation: GM quantification in BAL fluid at an OD index cutoff value of 1.5 has excellent sensitivity and specificity to assist clinical decision-making in confirming or excluding a diagnosis of IA when results are interpreted with clinical findings. Additional research investigating the effects of antifungal agents, optimal timing and processing of BAL sampling are needed to improve the diagnostic accuracy of BAL-GM testing.     

Diagnostic accuracy of rapid nucleic acid tests for group A streptococcal pharyngitis: systematic review and meta-analysis

BackgroundAcute pharyngitis is one of the most common conditions in outpatient settings and an important source of inappropriate antibiotic prescribing. Rapid antigen detection tests (RADTs) offer diagnosis of group A streptococcus at the point of care but have limited sensitivity. Rapid nucleic acid tests (RNATs) are now available; a systematic review of their accuracy is lacking.ObjectivesTo evaluate the accuracy of RNATs in patients with pharyngitis; to explore test-level and study-level factors that could explain variability in accuracy; and to compare the accuracy of RNATs with that of RADTs.Data sourcesMEDLINE, Embase, Web of Science (1990–2020).Study eligibility criteriaCross-sectional studies and randomized trials.ParticipantsPatients with pharyngitis.Index test/s and reference standardsRNAT commercial kits compared with throat culture.MethodsWe assessed risk of bias and applicability using QUADAS-2. We performed meta-analysis of sensitivity and specificity using the bivariate random-effects model. Variability was explored by subgroup analyses and meta-regression.ResultsWe included 38 studies (46 test evaluations; 17 411 test results). RNATs were most often performed in a laboratory. The overall methodological quality of primary studies was uncertain because of incomplete reporting. RNATs had a summary sensitivity of 97.5% (95% CI 96.2%–98.3%) and a summary specificity of 95.1% (95% CI 93.6%–96.3%). There was low variability in estimates across studies. Variability in sensitivity and specificity was partially explained by test type (p < 0.05 for both). Sensitivity analyses limited to studies with low risk of bias showed robust accuracy estimates. RNATs were more sensitive than RADTs (13 studies; 96.8% versus 82.3%, p 0.004); there was no difference in specificity (p 0.92).ConclusionsThe high diagnostic accuracy of RNATs may allow their use as stand-alone tests to diagnose group A streptococcus pharyngitis. Based on direct comparisons, RNATs have greater sensitivity than RADTs and equal specificity. Further studies should evaluate RNATs in point-of-care settings.     

Non-invasive diagnosis of Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis

BackgroundPneumocystis jirovecii pneumonia (PCP) is an opportunistic infection commonly affecting immunocompromised people. Diagnosis usually requires invasive techniques to obtain respiratory specimens. Minimally invasive detection tests have been proposed, but their operating characteristics are poorly described.ObjectivesTo systematically review and meta-analyse the performance of minimally invasive PCP detection tests to inform diagnostic algorithms.Data sourcesMedline, Embase, Cochrane Library (inception to 15 October 2020).Study eligibility criteriaStudies of minimally invasive PCP detection tests were included if they contained a minimum of ten PCP cases.ParticipantsAdults at risk of PCP.TestsNon-invasive PCP detection tests.Reference standardDiagnosis using the combination of clinical and radiographical features with invasive sampling.Assessment of risk biasUsing the QUADAS-2 tool.MethodsWe used bivariate and, when necessary, univariate analysis models to estimate diagnostic test sensitivity and specificity.ResultsFifty-two studies were included; most studies (40) comprised exclusively human immunodeficiency virus (HIV) -infected individuals; nine were mixed (HIV and non-HIV), two were non-HIV and one study did not report HIV status. Sampling sites included induced sputum, nasopharyngeal aspirate, oral wash and blood. The four testing modalities evaluated were cytological staining, fluorescent antibody, PCR and lactate dehydrogenase. Induced sputum had the most data available; this modality was both highly sensitive at 99% (95% CI 51%–100%) and specific at 96% (95% CI 88%–99%). Induced sputum cytological staining had moderate sensitivity at 50% (95% CI 39%–61%) and high specificity at 100% (95% CI 100%–100%), as did fluorescent antibody testing with sensitivity 74% (95% CI 62%–87%) and specificity 100% (95% CI 91%–100%).ConclusionThere are several promising minimally invasive PCP diagnostic tests available, some of which may reduce the need for invasive respiratory sampling. Understanding the operating characteristics of these tests can augment current diagnostic strategies and help establish a more confident clinical diagnosis of PCP. Further studies in non-HIV infected populations are needed.     

The value of microRNAs as the novel biomarkers for colorectal cancer diagnosis: A meta-analysis

BackgroundNumerous studies have reported that microRNAs (miRNAs) hold great potential as the biomarkers for colorectal cancer (CRC). However, inconsistent results have made it challenging to evaluate their diagnostic performance. Thus, the aim of this meta-analysis was to systematically assess the pooled efficacy of miRNAs for CRC diagnosis.MethodsA search for eligible studies up to October 30, 2019 was conducted using PubMed, Web of Science and EMBASE databases. A random-effects model was used to evaluate the pooled sensitivity and specificity. The summary receiver operator characteristic (SROC) curve and area under the curve (AUC) were calculated to assess the overall diagnostic efficacy.ResultsA total of 3258 CRC patients and 2683 healthy controls were identified in 35 included studies. The overall diagnostic accuracy was as follows: sensitivity, 0.80 [95 % confidence interval (CI) 0.75−0.83]; specificity, 0.80 (95 % CI, 0.75−0.84); positive likelihood ratio (PLR), 4.0 (95 % CI, 3.2−5.0); negative likelihood ratio (NLR), 0.26 (95 % CI, 0.21−0.31); diagnostic odds ratio (DOR), 16 (95 % CI, 11−23); and AUC, 0.87 (95 % CI, 0.83−0.89).ConclusionThe results indicated that miRNAs, particularly serum-derived miRNAs, can serve as the powerful and promising biomarkers for early CRC screening.