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PLoS Neglected Tropical Diseases 2012Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised... (Comparative Study)
Comparative Study Meta-Analysis Review
BACKGROUND
Human visceral leishmaniasis (VL), a potentially fatal disease, has emerged as an important opportunistic condition in HIV infected patients. In immunocompromised patients, serological investigation is considered not an accurate diagnostic method for VL diagnosis and molecular techniques seem especially promising.
OBJECTIVE
This work is a comprehensive systematic review and meta-analysis to evaluate the accuracy of serologic and molecular tests for VL diagnosis specifically in HIV-infected patients.
METHODS
Two independent reviewers searched PubMed and LILACS databases. The quality of studies was assessed by QUADAS score. Sensitivity and specificity were pooled separately and compared with overall accuracy measures: diagnostic odds ratio (DOR) and symmetric summary receiver operating characteristic (sROC).
RESULTS
Thirty three studies recruiting 1,489 patients were included. The following tests were evaluated: Immunofluorescence Antibody Test (IFAT), Enzyme linked immunosorbent assay (ELISA), immunoblotting (Blot), direct agglutination test (DAT) and polimerase chain reaction (PCR) in whole blood and bone marrow. Most studies were carried out in Europe. Serological tests varied widely in performance, but with overall limited sensitivity. IFAT had poor sensitivity ranging from 11% to 82%. DOR (95% confidence interval) was higher for DAT 36.01 (9.95-130.29) and Blot 27.51 (9.27-81.66) than for IFAT 7.43 (3.08-1791) and ELISA 3.06 (0.71-13.10). PCR in whole blood had the highest DOR: 400.35 (58.47-2741.42). The accuracy of PCR based on Q-point was 0.95; 95%CI 0.92-0.97, which means good overall performance.
CONCLUSION
Based mainly on evidence gained by infection with Leishmania infantum chagasi, serological tests should not be used to rule out a diagnosis of VL among the HIV-infected, but a positive test at even low titers has diagnostic value when combined with the clinical case definition. Considering the available evidence, tests based on DNA detection are highly sensitive and may contribute to a diagnostic workup.
Topics: Clinical Laboratory Techniques; HIV Infections; Humans; Leishmaniasis, Visceral; Molecular Diagnostic Techniques; Parasitology; Sensitivity and Specificity; Serologic Tests
PubMed: 22666514
DOI: 10.1371/journal.pntd.0001665 -
PloS One 2021Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant...
BACKGROUND
Increasingly, vaccine efficacy studies are being recommended in low-and-middle-income countries (LMIC), yet often facilities are unavailable to take and store infant blood samples correctly. Dried blood spots (DBS), are useful for collecting blood from infants for diagnostic purposes, especially in low-income settings, as the amount of blood required is miniscule and no refrigeration is required. Little is known about their utility for antibody studies in children. This systematic review aims to investigate the correlation of antibody concentrations against infectious diseases in DBS in comparison to serum or plasma samples that might inform their use in vaccine clinical trials.
METHODS AND FINDINGS
We searched MEDLINE, Embase and the Cochrane library for relevant studies between January 1990 to October 2020 with no language restriction, using PRISMA guidelines, investigating the correlation between antibody concentrations in DBS and serum or plasma samples, and the effect of storage temperature on DBS diagnostic performance. We included 40 studies in this systematic review. The antibody concentration in DBS and serum/plasma samples reported a good pooled correlation, (r2 = 0.86 (ranged 0.43 to 1.00)). Ten studies described a decline of antibody after 28 days at room temperature compared to optimal storage at -20°C, where antibodies were stable for up to 200 days. There were only five studies of anti-bacterial antibodies.
CONCLUSIONS
There is a good correlation between antibody concentrations in DBS and serum/plasma samples, supporting the wider use of DBS in vaccine and sero-epidemiological studies, but there is limited data on anti-bacterial antibodies. The correct storage of DBS is critical and may be a consideration for longer term storage.
Topics: Antibodies; Antibodies, Bacterial; Communicable Diseases; Dried Blood Spot Testing; Humans; Protein Stability; Sensitivity and Specificity; Temperature
PubMed: 33720928
DOI: 10.1371/journal.pone.0248218 -
Annals of Internal Medicine Sep 2016Diagnosis of chronic hepatitis C virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). Testing for hepatitis C... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Diagnosis of chronic hepatitis C virus (HCV) infection requires both a positive HCV antibody screen and confirmatory nucleic acid testing (NAT). Testing for hepatitis C virus core antigen (HCVcAg) is a potential alternative to NAT.
PURPOSE
To evaluate the accuracy of diagnosis of active HCV infection among adults and children for 5 HCVcAg tests compared with NAT.
DATA SOURCES
EMBASE, PubMed, Web of Science, Scopus, and Cochrane Database of Systematic Reviews from 1990 through 31 March 2016.
STUDY SELECTION
Case-control, cross-sectional, cohort, or randomized trials that compared any of 5 HCVcAg tests with an NAT reference standard.
DATA EXTRACTION
2 independent reviewers extracted data and assessed quality using an adapted QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool.
DATA SYNTHESIS
44 studies evaluated 5 index tests. Studies for the Abbott ARCHITECT HCV Ag assay had the highest quality, whereas those for the Ortho HCV Ag enzyme-linked immunosorbent assay (ELISA) had the lowest quality. From bivariate analyses, the sensitivity and specificity of the assays were as follows: Abbott ARCHITECT, 93.4% (95% CI, 90.1% to 96.4%) and 98.8% (CI, 97.4% to 99.5%); Ortho ELISA, 93.2% (CI, 81.6% to 97.7%) and 99.2% (CI, 87.9% to 100%); and Hunan Jynda Bioengineering Group HCV Ag ELISA, 59.5% (CI, 46.0% to 71.7%) and 82.9% (CI, 58.6% to 94.3%). Insufficient data were available for a meta-analysis about the Fujirebio Lumipulse Ortho HCV Ag and Eiken Lumispot HCV Ag assays. In 3 quantitative studies using Abbott ARCHITECT, HCVcAg correlated closely with HCV RNA levels greater than 3000 IU/mL.
LIMITATIONS
Insufficient data were available on covariates, such as HIV or hepatitis B virus status, for subgroup analyses. Few studies reported genotypes of isolates, and data for genotypes 4, 5, and 6 were scant. Most studies were conducted in high-resource settings and reference laboratories.
CONCLUSION
The HCVcAg assays with signal amplification have high sensitivity, high specificity, and good correlation with HCV RNA levels greater than 3000 IU/mL and have the potential to replace NAT in settings with high HCV prevalence.
PRIMARY FUNDING SOURCE
National Institutes of Health.
Topics: Cross-Sectional Studies; Genotype; Hepacivirus; Hepatitis C; Hepatitis C Antigens; Humans; Nucleic Acid Amplification Techniques; RNA, Viral; Sensitivity and Specificity
PubMed: 27322622
DOI: 10.7326/M16-0065 -
Genetics in Medicine : Official Journal... Jan 2012Women with recurrent pregnancy loss are offered Factor V Leiden (F5) and/or prothrombin G20210A (F2) testing to identify candidates for anticoagulation to improve... (Review)
Review
Can Factor V Leiden and prothrombin G20210A testing in women with recurrent pregnancy loss result in improved pregnancy outcomes?: Results from a targeted evidence-based review.
Women with recurrent pregnancy loss are offered Factor V Leiden (F5) and/or prothrombin G20210A (F2) testing to identify candidates for anticoagulation to improve outcomes. A systematic literature review was performed to estimate test performance, effect sizes, and treatment effectiveness. Electronic searches were performed through April 2011, with review of references from included articles. English-language studies addressed analytic validity, clinical validity, and/or clinical utility and satisfied predefined inclusion criteria. Adequate evidence showed high analytic sensitivity and specificity for F5 and F2 testing. Evidence for clinical validity was adequate. The summary odds ratio for association of recurrent pregnancy loss with F5 in case-controlled studies was 2.02 (95% confidence interval, 1.60-2.55), with moderate heterogeneity and suggestion of publication bias. Longitudinal studies in women with recurrent pregnancy loss or unselected cohorts showed F5 carriers were more likely to have a subsequent loss than noncarriers (odds ratios: 1.93 and 2.03, respectively). Results for F2 testing were similar. For clinical utility, evidence was adequate that anticoagulation treatments were ineffective (except in antiphospholipid antibody syndrome) and had treatment-associated harms. The certainty of evidence is moderate (high, moderate, and low) that anticoagulation of women with recurrent pregnancy loss and F5/F2 variants would currently lead to net harms.
Topics: Abortion, Habitual; Evidence-Based Medicine; Factor V; Female; Genetic Testing; Humans; Mutation, Missense; Pregnancy; Pregnancy Outcome; Prothrombin
PubMed: 22237430
DOI: 10.1038/gim.0b013e31822e575b -
The Canadian Journal of Infectious... 2018IgM against may be detected by enzyme-linked immunosorbent assays (ELISAs) based on phenolic glycolipid I (PGL-I) or natural disaccharide octyl bovine serum albumin... (Review)
Review
IgM against may be detected by enzyme-linked immunosorbent assays (ELISAs) based on phenolic glycolipid I (PGL-I) or natural disaccharide octyl bovine serum albumin (ND-O-BSA) as antigens, and the IgG response can be detected by an ELISA based on lipid droplet protein 1 (LID-1). The titers of antibodies against these antigens vary with operational classification. The aim of this study was to compare the accuracy of ELISAs involving PGL-I and ND-O-BSA with that involving LID-1. We included studies that analyze multibacillary and paucibacillary leprosy cases and evaluate the diagnostic accuracy of ELISAs based on LID-1 and/or PGL-I or ND-O-BSA as antigens to measure antibody titers against . Studies were found via PubMed, the Virtual Health Library Regional Portal, Literatura Latino-Americana e do Caribe em Ciências da Saúde, Índice Bibliográfico Espanhol de Ciências de Saúde, the Brazilian Society of Dermatology, National Institute for Health and Clinical Excellence, Cochrane Library, Embase (the Elsevier database), and Cumulative Index to Nursing and Allied Health Literature. The Quality Assessment of Diagnostic Accuracy Studies served as a methodological validity tool. Quantitative data were extracted using the Standards for Reporting of Diagnostic Accuracy. Sensitivity, specificity, and a diagnostic odds ratio were calculated, and a hierarchical summary receiver-operating characteristic curve and forest plots were constructed. The protocol register code for this meta-analysis is PROSPERO 2017: CRD42017055983. Nineteen studies were included. ND-O-BSA showed better overall performance in terms of sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio when compared with PGL-I and LID-1. The multibacillary group showed better performance on these parameters (than the paucibacillary group did), at 94%, 99%, 129, 0.05, and 2293, respectively. LID-1 did not provide any advantage regarding the overall estimate of sensitivity in comparison with PGL-I or ND-O-BSA.
PubMed: 30622658
DOI: 10.1155/2018/9828023 -
European Journal of Nuclear Medicine... Aug 2017Post-traumatic osteomyelitis (PTO) is difficult to diagnose and there is no consensus on the best imaging strategy. The aim of this study is to present a systematic... (Review)
Review
AIMS
Post-traumatic osteomyelitis (PTO) is difficult to diagnose and there is no consensus on the best imaging strategy. The aim of this study is to present a systematic review of the recent literature on diagnostic imaging of PTO.
METHODS
A literature search of the EMBASE and PubMed databases of the last 16 years (2000-2016) was performed. Studies that evaluated the accuracy of magnetic resonance imaging (MRI), three-phase bone scintigraphy (TPBS), white blood cell (WBC) or antigranulocyte antibody (AGA) scintigraphy, fluorodeoxyglucose positron emission tomography (FDG-PET) and plain computed tomography (CT) in diagnosing PTO were considered for inclusion. The review was conducted using the PRISMA statement and QUADAS-2 criteria.
RESULTS
The literature search identified 3358 original records, of which 10 articles could be included in this review. Four of these studies had a comparative design which made it possible to report the results of, in total, 17 patient series. WBC (or AGA) scintigraphy and FDG-PET exhibit good accuracy for diagnosing PTO (sensitivity ranged from 50-100%, specificity ranged from 40-97% versus 83-100% and 51%-100%, respectively). The accuracy of both modalities improved when a hybrid imaging technique (SPECT/CT & FDG-PET/CT) was performed. For FDG-PET/CT, sensitivity ranged between 86 and 94% and specificity between 76 and 100%. For WBC scintigraphy + SPECT/CT, this is 100% and 89-97%, respectively.
CONCLUSIONS
Based on the best available evidence of the last 16 years, both WBC (or AGA) scintigraphy combined with SPECT/CT or FDG-PET combined with CT have the best diagnostic accuracy for diagnosing peripheral PTO.
Topics: Diagnostic Imaging; Humans; Osteomyelitis; Sensitivity and Specificity; Wounds and Injuries
PubMed: 28451827
DOI: 10.1007/s00259-017-3683-7 -
Alimentary Pharmacology & Therapeutics Jul 2006With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive... (Review)
Review
BACKGROUND
With the appreciation of the high prevalence of coeliac disease there is increasing use of serology in screening asymptomatic people and testing those with suggestive features.
AIM
To compare the sensitivities and specificities of the endomysial antibody and the tissue transglutaminase antibody tests.
METHODS
Using electronic databases a search was made for relevant papers using the terms tissue transglutaminase and endomysial antibody.
RESULTS
Both the endomysial antibody and tissue transglutaminase antibody have very high sensitivities (93% for both) and specificities (>99% and >98% respectively) for the diagnosis of typical coeliac disease with villous atrophy. Human recombinant tissue transglutaminase performs much better than guinea pig tissue transglutaminase. Review of studies comparing endomysial antibody with human recombinant tissue transglutaminase antibody shows that endomysial antibody more often has a higher specificity and human recombinant tissue transglutaminase antibody more often has a higher sensitivity.
CONCLUSION
The human recombinant tissue transglutaminase antibody is the preferred test for screening asymptomatic people and for excluding coeliac disease in symptomatic individuals with a low pretest probability (i.e. <25%) for coeliac disease. Furthermore, it has a number of practical and financial advantages. If the pretest probability is >25%, biopsy is preferred as the post-test probability of coeliac disease with a negative test is still >2%.
Topics: Antibodies; Celiac Disease; Humans; Immunologic Tests; Sensitivity and Specificity; Transglutaminases
PubMed: 16803602
DOI: 10.1111/j.1365-2036.2006.02967.x -
PloS One 2014The survival rate of colorectal cancer (CRC) patients carrying wild-type KRAS is significantly increased by combining anti-EGFR monoclonal antibody (mAb) with standard... (Meta-Analysis)
Meta-Analysis Review
PCR-based assays versus direct sequencing for evaluating the effect of KRAS status on anti-EGFR treatment response in colorectal cancer patients: a systematic review and meta-analysis.
BACKGROUND
The survival rate of colorectal cancer (CRC) patients carrying wild-type KRAS is significantly increased by combining anti-EGFR monoclonal antibody (mAb) with standard chemotherapy. However, conflicting data exist in both the wild-type KRAS and mutant KRAS groups, which strongly challenge CRC anti-EGFR treatment. Here we conducted a meta-analysis in an effort to provide more reliable information regarding anti-EGFR treatment in CRC patients.
METHODS
We searched full reports of randomized clinical trials using Medline, the American Society of Clinical Oncology (ASCO), and the European Society for Medical Oncology (ESMO). Two investigators independently screened the published literature according to our inclusive and exclusive criteria and the relative data were extracted. We used Review Manager 5.2 software to analyze the data.
RESULTS
The addition of anti-EGFR mAb to standard chemotherapy significantly improved both progression-free survival (PFS) and median overall survival (mOS) in the wild-type KRAS group; hazard ratios (HRs) for PFS and mOS were 0.70 [95% confidence interval (CI), 0.58-0.84] and 0.83 [95% CI, 0.75-0.91], respectively. In sub-analyses of the wild-type KRAS group, when PCR-based assays are employed, PFS and mOS notably increase: the HRs were 0.74 [95% CI, 0.62-0.88] and 0.87 [95% CI, 0.78-0.96], respectively. In sub-analyses of the mutant KRAS group, neither PCR-based assays nor direct sequencing enhance PFS or mOS.
CONCLUSION
Our data suggest that PCR-based assays with high sensitivity and specificity allow accurate identification of patients with wild-type KRAS and thus increase PFS and mOS. Furthermore, such assays liberate patients with mutant KRAS from unnecessary drug side effects, and provide them an opportunity to receive appropriate treatment. Thus, establishing a precise standard reference test will substantially optimize CRC-targeted therapies.
Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; ErbB Receptors; Humans; Mutation; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); Randomized Controlled Trials as Topic; ras Proteins
PubMed: 25260023
DOI: 10.1371/journal.pone.0107926 -
Euro Surveillance : Bulletin Europeen... May 2023BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological... (Meta-Analysis)
Meta-Analysis
BackgroundSerological surveys have been the gold standard to estimate numbers of SARS-CoV-2 infections, the dynamics of the epidemic, and disease severity. Serological assays have decaying sensitivity with time that can bias their results, but there is a lack of guidelines to account for this phenomenon for SARS-CoV-2.AimOur goal was to assess the sensitivity decay of seroassays for detecting SARS-CoV-2 infections, the dependence of this decay on assay characteristics, and to provide a simple method to correct for this phenomenon.MethodsWe performed a systematic review and meta-analysis of SARS-CoV-2 serology studies. We included studies testing previously diagnosed, unvaccinated individuals, and excluded studies of cohorts highly unrepresentative of the general population (e.g. hospitalised patients).ResultsOf the 488 screened studies, 76 studies reporting on 50 different seroassays were included in the analysis. Sensitivity decay depended strongly on the antigen and the analytic technique used by the assay, with average sensitivities ranging between 26% and 98% at 6 months after infection, depending on assay characteristics. We found that a third of the included assays departed considerably from manufacturer specifications after 6 months.ConclusionsSeroassay sensitivity decay depends on assay characteristics, and for some types of assays, it can make manufacturer specifications highly unreliable. We provide a tool to correct for this phenomenon and to assess the risk of decay for a given assay. Our analysis can guide the design and interpretation of serosurveys for SARS-CoV-2 and other pathogens and quantify systematic biases in the existing serology literature.
Topics: Humans; SARS-CoV-2; COVID-19; Sensitivity and Specificity; COVID-19 Testing; Serologic Tests; Antibodies, Viral
PubMed: 37227301
DOI: 10.2807/1560-7917.ES.2023.28.21.2200809 -
The Lancet. Infectious Diseases May 2021Cryptosporidiosis is a common cause of diarrhoea in young children (aged younger than 24 months) in low-resource settings but is currently challenging to diagnose....
BACKGROUND
Cryptosporidiosis is a common cause of diarrhoea in young children (aged younger than 24 months) in low-resource settings but is currently challenging to diagnose. Light-emitting diode fluorescence microscopy with auramine-phenol staining (LED-AP), recommended for tuberculosis testing, can also detect Cryptosporidium species. A lateral-flow test not requiring refrigerator storage (by contrast with most immunochromatographic lateral-flow assays) has also recently been developed for Cryptosporidium spp detection. We aimed to evaluate the diagnostic accuracy and operational feasibility of LED-AP and the lateral-flow test strip for cryptosporidiosis in children.
METHODS
We did a prospective diagnostic accuracy study in two health-care facilities in Ethiopia, in a consecutive series of children younger than 5 years of age with diarrhoea (three or more loose stools within the previous 24 h) or dysentery (at least one loose stool with stains of blood within the previous 24 h). Stool samples were tested for Cryptosporidium spp by LED-AP and the lateral-flow test strip; accuracy of each test was estimated by independent and blind comparison with a composite reference standard comprising quantitative immunofluorescent antibody test (qIFAT), ELISA, and quantitative PCR (qPCR). Quantitative cutoff values for diarrhoea-associated infection were established in an embedded case-control substudy, with cases of cryptosporidiosis coming from the 15 districts in and around Jimma and the eight districts surrounding Serbo, and community controls without diarrhoea in the previous 48 h recruited by weekly frequency matching by geographical district of the household, age group, and enrolment week.
FINDINGS
Stool samples from 912 children with diarrhoea or dysentery and 706 controls from the case-control substudy were tested between Dec 22, 2016, and July 6, 2018. Estimated reference-standard cutoff values for cryptosporidiosis positivity were 2·3 × 10 DNA copies per g of wet stool for qPCR, and 725 oocysts per g for qIFAT. LED-AP had a sensitivity for cryptosporidiosis of 88% (95% CI 79-94; 66 of 75 samples) and a specificity of 99% (98-99; 717 of 726 samples); the lateral-flow test strip had a sensitivity of 89% (79-94; 63 of 71 samples) and a specificity of 99% (97-99; 626 of 635 samples).
INTERPRETATION
LED-AP has high sensitivity and specificity for cryptosporidiosis and should be considered as a dual-use technology that can be easily integrated with existing laboratory infrastructures in low-resource settings. The lateral-flow test strip has similar sensitivity and specificity and provides an alternative that does not require microscopy, although purchase cost of the test strip is unknown as it is not yet available on the market.
FUNDING
Norwegian Research Council GLOBVAC fund, The Bill & Melinda Gates Foundation, Norwegian Society for Medical Microbiology, University of Bergen, and Vestfold Hospital Trust.
Topics: Child; Cryptosporidiosis; Cryptosporidium; Databases, Factual; Diagnostic Tests, Routine; Diarrhea; Ethiopia; Feasibility Studies; Feces; Humans; Immunoassay; Prospective Studies; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity
PubMed: 33278916
DOI: 10.1016/S1473-3099(20)30556-9