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Clinical Infectious Diseases : An... Apr 2021Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in... (Meta-Analysis)
Meta-Analysis
Cryptococcal Antigen in Serum and Cerebrospinal Fluid for Detecting Cryptococcal Meningitis in Adults Living With Human Immunodeficiency Virus: Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.
Cryptococcal antigen (CrAg) detection could direct the timely initiation of antifungal therapy. We searched MEDLINE and Embase for studies where CrAg detection in serum/cerebrospinal fluid (CSF) and CSF fungal culture were done on adults living with human immunodeficiency virus (HIV) who had suspected cryptococcal meningitis (CM). With Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2), we evaluated the risk of bias in 11 included studies with 3600 participants, and used a random-effects meta-analysis to obtain summary sensitivity and specificity of serum and CSF CrAg, as well as agreement between CSF CrAg and CSF culture. Summary sensitivity and specificity of serum CrAg were 99.7% (97.4-100) and 94.1% (88.3-98.1), respectively, and summary sensitivity and specificity of CSF CrAg were 98.8% (96.2-99.6) and 99.3% (96.7-99.9), respectively. Agreement between CSF CrAg and CSF culture was 98% (97-99). In adults living with HIV who have CM symptoms, serum CrAg negativity may rule out CM, while positivity should prompt induction antifungal therapy if lumbar puncture is not feasible. In a first episode of CM, CSF CrAg positivity is diagnostic.
Topics: AIDS-Related Opportunistic Infections; Adult; Antigens, Fungal; Cryptococcus; Diagnostic Tests, Routine; HIV; HIV Infections; Humans; Meningitis, Cryptococcal
PubMed: 32829406
DOI: 10.1093/cid/ciaa1243 -
BMC Infectious Diseases Nov 2023Parasitological investigation of bone marrow, splenic or lymph node aspirations is the gold standard for the diagnosis of visceral leishmaniasis (VL). However, this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Parasitological investigation of bone marrow, splenic or lymph node aspirations is the gold standard for the diagnosis of visceral leishmaniasis (VL). However, this invasive test requires skilled clinical and laboratory staff and adequate facilities, and sensitivity varies depending on the tissue used. The direct agglutination test (DAT) is a serological test that does not need specialised staff, with just minimal training required. While previous meta-analysis has shown DAT to have high sensitivity and specificity when using parasitology as the reference test for diagnosis, meta-analysis of DAT compared to other diagnostic techniques, such as PCR and ELISA, that are increasingly used in clinical and research settings, has not been done.
METHODS
We conducted a systematic review to determine the diagnostic performance of DAT compared to all available tests for the laboratory diagnosis of human VL. We searched electronic databases including Medline, Embase, Global Health, Scopus, WoS Science Citation Index, Wiley Cochrane Central Register of Controlled Trials, Africa-Wide Information, LILACS and WHO Global Index. Three independent reviewers screened reports and extracted data from eligible studies. A meta-analysis estimated the diagnostic sensitivity and specificity of DAT.
RESULTS
Of 987 titles screened, 358 were selected for full data extraction and 78 were included in the analysis, reporting on 32,822 participants from 19 countries. Studies included were conducted between 1987-2020. Meta-analysis of studies using serum and DAT compared to any other test showed pooled sensitivity of 95% (95%CrI 90-98%) and pooled specificity of 95% (95%CrI 88-98%). Results were similar for freeze-dried DAT and liquid DAT when analysed separately. Sensitivity was lower for HIV-positive patients (90%, CrI 59-98%) and specificity was lower for symptomatic patients (70%, CrI 43-89%). When comparing different geographical regions, the lowest median sensitivity (89%, CrI 67-97%) was in Western Asia (five studies).
CONCLUSIONS
This systematic review and meta-analysis demonstrates high estimated pooled sensitivity and specificity of DAT for diagnosis of VL, although sensitivity and specificity were lower for different patient groups and geographical locations. This review highlights the lack of standardisation of DAT methods and preparations, and the lack of data from some important geographical locations. Future well-reported studies could provide better evidence to inform test implementation for different patient populations and use cases.
PROSPERO REGISTRATION
CRD42021240830.
Topics: Humans; Leishmaniasis, Visceral; Agglutination Tests; Serologic Tests; Sensitivity and Specificity; HIV Seropositivity
PubMed: 37946107
DOI: 10.1186/s12879-023-08772-1 -
Clinical Infectious Diseases : An... Jun 2020We conducted a systematic review of relevant syphilis diagnostic literature to address the question, "What is the sensitivity and specificity of the treponemal tests...
We conducted a systematic review of relevant syphilis diagnostic literature to address the question, "What is the sensitivity and specificity of the treponemal tests currently approved by the Food and Drug Administration (FDA) for the diagnosis of syphilis (by stage)?" There were 16 treponemal assays evaluated: 13 immunoassays and 3 manual assays (fluorescent treponemal antibody absorbed test [FTA-ABS], microhemagglutination assay for Treponema pallidum antibodies [MHA-TP], Treponema pallidum particle agglutination assay [TP-PA]). MHA-TP and FTA-ABS were less sensitive in primary and secondary syphilis than TP-PA; TP-PA is the most specific manual treponemal assay. There is insufficient evidence to recommend one particular treponemal immunoassay (eg, enzyme immunoassays, chemiluminescence immunoassays, microbead immunoassays) over another based on published performance data. For diagnosis of neurosyphilis, cerebrospinal fluid (CSF) TP-PA has similar performance to CSF FTA-ABS in studies with patients with definitive or presumptive neurosyphilis. However, CSF treponemal testing has limitations in its sensitivity and specificity and should be interpreted within the context of the clinical scenario, additional CSF test results and syphilis prevalence.
Topics: Antibodies, Bacterial; Humans; Neurosyphilis; Sensitivity and Specificity; Syphilis; Syphilis Serodiagnosis; Treponema pallidum
PubMed: 32578866
DOI: 10.1093/cid/ciaa349 -
American Journal of Obstetrics and... Feb 2015Nonimmune hydrops is the presence of ≥2 abnormal fetal fluid collections in the absence of red cell alloimmunization. The most common etiologies include... (Review)
Review
OBJECTIVE
Nonimmune hydrops is the presence of ≥2 abnormal fetal fluid collections in the absence of red cell alloimmunization. The most common etiologies include cardiovascular, chromosomal, and hematologic abnormalities, followed by structural fetal anomalies, complications of monochorionic twinning, infection, and placental abnormalities. We sought to provide evidence-based guidelines for the evaluation and management of nonimmune hydrops fetalis.
METHODS
A systematic literature review was performed using MEDLINE, PubMed, EMBASE, and Cochrane Library. The search was restricted to English-language articles published from 1966 through June 2014. Priority was given to articles reporting original research, although review articles and commentaries also were consulted. Abstracts of research presented at symposia and scientific conferences were not considered adequate for inclusion in this document. Evidence reports and guidelines published by organizations or institutions such as the National Institutes of Health, Agency for Health Research and Quality, American Congress of Obstetricians and Gynecologists, and Society for Maternal-Fetal Medicine were also reviewed, and additional studies were located by reviewing bibliographies of identified articles. Grading of Recommendations Assessment, Development, and Evaluation methodology was employed for defining strength of recommendations and rating quality of evidence. Consistent with US Preventive Task Force guidelines, references were evaluated for quality based on the highest level of evidence.
RESULTS AND RECOMMENDATIONS
Evaluation of hydrops begins with an antibody screen (indirect Coombs test) to determine if it is nonimmune, detailed sonography of the fetus(es) and placenta, including echocardiography and assessment for fetal arrhythmia, and middle cerebral artery Doppler evaluation for anemia, as well as fetal karyotype and/or chromosomal microarray analysis, regardless of whether a structural fetal anomaly is identified. Recommended treatment depends on the underlying etiology and gestational age; preterm delivery is recommended only for obstetric indications including development of mirror syndrome. Candidates for corticosteroids and antepartum surveillance include those with an idiopathic etiology, an etiology amenable to prenatal or postnatal treatment, and those in whom intervention is planned if fetal deterioration occurs. Such pregnancies should be delivered at a facility with the capability to stabilize and treat critically ill newborns. The prognosis depends on etiology, response to therapy if treatable, and the gestational age at detection and delivery. Aneuploidy confers a poor prognosis, and even in the absence of aneuploidy, neonatal survival is often <50%. Mirror syndrome is a form of severe preeclampsia that may develop in association with fetal hydrops and in most cases necessitates delivery.
Topics: Anemia; Arrhythmias, Cardiac; Blood Transfusion, Intrauterine; Coombs Test; Delivery, Obstetric; Drainage; Echocardiography; Female; Fetal Diseases; Humans; Hydrops Fetalis; Hydrothorax; Pregnancy; Ultrasonography, Doppler; Ultrasonography, Prenatal
PubMed: 25557883
DOI: 10.1016/j.ajog.2014.12.018 -
Blood Advances Jun 2019The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment.... (Comparative Study)
Comparative Study
The terminology applied to autoimmune hemolytic anemia (AIHA) seems inconsistent. We aimed to evaluate the consistency of definitions used for diagnosis and treatment. In this systematic review of literature from January 2006 to December 2015, we assessed heterogeneity in the definition of AIHA and its subtypes, refractory disease, disease phase, severity, criteria for treatment response, and response durability. A Medline search for anemia, hemolytic, autoimmune was supplemented with keyword searches. Main exclusions were conference abstracts, animal and non-English studies, and studies with <10 cases. Of 1371 articles retrieved, 1209 were excluded based on titles and abstracts. Two authors independently reviewed 10% and 16% of abstracts and full papers, respectively. After full-paper review, 84 studies were included. AIHA was most frequently (32 [52%] of 61) defined as hemolytic anemia with positive direct antiglobulin test (DAT) and exclusion of alternatives, but 10 of 32 also recognized DAT-negative AIHA. A lower threshold for diagnosis of DAT-negative AIHA was observed in literature on chronic lymphocytic leukemia. Definitions of anemia, hemolysis, and exclusion criteria showed substantial variation. Definitions of primary/secondary cold agglutinin disease/syndrome were not consistent. Forty-three studies provided criteria for treatment response, and other than studies from 1 center, these were almost entirely unique. Other criteria were rarely defined. Only 7, 0, 3, 2, 2, and 3 studies offered definitions of warm AIHA, paroxysmal cold hemoglobinuria, mixed AIHA, AIHA severity, disease phase, and refractory AIHA, respectively. Marked heterogeneity in the time period sampled indicates the need to standardize AIHA terminology.
Topics: Anemia, Hemolytic, Autoimmune; Coombs Test; Erythrocytes; Hemoglobinuria, Paroxysmal; Hemolysis; Humans; Immunoglobulin G; Publications; Severity of Illness Index; Terminology as Topic
PubMed: 31235526
DOI: 10.1182/bloodadvances.2019000036 -
BMC Infectious Diseases Feb 2024Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic... (Meta-Analysis)
Meta-Analysis
Diagnosis of human leptospirosis: systematic review and meta-analysis of the diagnostic accuracy of the Leptospira microscopic agglutination test, PCR targeting Lfb1, and IgM ELISA to Leptospira fainei serovar Hurstbridge.
BACKGROUND
Leptospirosis is an underdiagnosed infectious disease with non-specific clinical presentation that requires laboratory confirmation for diagnosis. The serologic reference standard remains the microscopic agglutination test (MAT) on paired serum samples. However, reported estimates of MAT's sensitivity vary. We evaluated the accuracy of four index tests, MAT on paired samples as well as alternative standards for leptospirosis diagnosis: MAT on single acute-phase samples, polymerase chain reaction (PCR) with the target gene Lfb1, and ELISA IgM with Leptospira fainei serovar Hurstbridge as an antigen.
METHODS
We performed a systematic review of studies reporting results of leptospirosis diagnostic tests. We searched eight electronic databases and selected studies that tested human blood samples and compared index tests with blood culture and/or PCR and/or MAT (comparator tests). For MAT selection criteria we defined a threshold for single acute-phase samples according to a national classification of leptospirosis endemicity. We used a Bayesian random-effect meta-analysis to estimate the sensitivity and specificity of MAT in single acute-phase and paired samples separately, and assessed risk of bias using the Quality Assessment of Studies of Diagnostic Accuracy Approach- 2 (QUADAS-2) tool.
RESULTS
For the MAT accuracy evaluation, 15 studies were included, 11 with single acute-phase serum, and 12 with paired sera. Two included studies used PCR targeting the Lfb1 gene, and one included study used IgM ELISA with Leptospira fainei serovar Hurstbridge as antigen. For MAT in single acute-phase samples, the pooled sensitivity and specificity were 14% (95% credible interval [CrI] 3-38%) and 86% (95% CrI 59-96%), respectively, and the predicted sensitivity and specificity were 14% (95% CrI 0-90%) and 86% (95% CrI 9-100%). Among paired MAT samples, the pooled sensitivity and specificity were 68% (95% CrI 32-92%) and 75% (95% CrI 45-93%) respectively, and the predicted sensitivity and specificity were 69% (95% CrI 2-100%) and 75% (2-100%).
CONCLUSIONS
Based on our analysis, the accuracy of MAT in paired samples was not high, but it remains the reference standard until a more accurate diagnostic test is developed. Future studies that include larger numbers of participants with paired samples will improve the certainty of accuracy estimates.
Topics: Humans; Serogroup; Bayes Theorem; Antibodies, Bacterial; Leptospira; Leptospirosis; Agglutination Tests; Sensitivity and Specificity; Enzyme-Linked Immunosorbent Assay; Immunoglobulin M; Polymerase Chain Reaction
PubMed: 38326762
DOI: 10.1186/s12879-023-08935-0 -
Tropical Animal Health and Production Feb 2016The diagnosis of leptospirosis commonly relies on serology, which has three issues that are referred: the sampling, the antigen panel, and the cutoff point. We propose a... (Review)
Review
The diagnosis of leptospirosis commonly relies on serology, which has three issues that are referred: the sampling, the antigen panel, and the cutoff point. We propose a systematic review of the bovine leptospirosis in Latin America, in order to provide a better understanding of the evolution of the research and of the seroepidemiology of bovine leptospirosis in that region. Internet databases were consulted over the year of 2014. Inclusion criteria for analysis included serosurvey using microscopic agglutination test (MAT), a relevant number of animals, the presence in the antigen panel of at least one representant of serogroup Sejroe, and a cutoff point of ≥100. A total of 242 articles that referred to cattle, leptospir*, and one region of Latin America was found. Only 105 articles regarding to serosurveys using MAT were found in several countries, and 61 (58.1 %) met all the inclusion criteria. In conclusion, this systematic review demonstrated a high prevalence of the infection (75.0 % at herd level and 44.2 % at animal level), with predominance of strains of serogroup Sejroe (80.3 %). It was evident that there is the necessity of more studies in several countries, as well as the need for greater standardization in studies, especially with regard to the adopted cutoff point at serological tests.
Topics: Agglutination Tests; Animals; Antigens, Bacterial; Cattle; Cattle Diseases; Leptospira; Leptospirosis; Prevalence; Seroepidemiologic Studies; Serologic Tests; South America
PubMed: 26581437
DOI: 10.1007/s11250-015-0954-9 -
Pathogens (Basel, Switzerland) Nov 2022Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, results in congenital disorders and miscarriages among livestock and humans worldwide. This systematic... (Review)
Review
Toxoplasmosis, a parasitic disease caused by Toxoplasma gondii, results in congenital disorders and miscarriages among livestock and humans worldwide. This systematic review and meta-analysis were conducted to determine the prevalence of T. gondii infection in sheep and goats in Pakistan from 2000 to 2020. We searched the PubMed, Scopus, EMBASE, and Google Scholar databases and selected 17 publications that fulfilled our inclusion criteria. Eight studies were conducted in Southern Punjab, six in Khyber Pakhtunkhwa, two in Northern Punjab, and one in Central Punjab. The diagnostic tests used in the included articles to confirm toxoplasmosis were the latex agglutination test in 56% of the studies, the enzyme-linked immunosorbent assay in 38%, and the indirect hemagglutination assay in 6%. The infection rates were substantially higher among sheep > 1 year of age (37%) than among sheep ≤ 1 year old (19%). Statistically significant differences in infection rates were found between male and female sheep and goats. The overall infection rate by age was also significant among sheep and goats. Sex and age variability between sheep investigations were significant, and sex heterogeneity and age homogeneity were significant among goats. Hence, robust infection control protocols should be implemented to prevent infection in animals and humans.
PubMed: 36422583
DOI: 10.3390/pathogens11111331 -
Animal Health Research Reviews Jun 2022The aim of this systematic review was to investigate the prevalence of leptospirosis among stray and sheltered dogs worldwide. Six databases were searched, which... (Review)
Review
The aim of this systematic review was to investigate the prevalence of leptospirosis among stray and sheltered dogs worldwide. Six databases were searched, which resulted in the retrieval of 476 articles. Sixty articles were selected for analysis according to 10 quality criteria. Among the selected papers, 26 papers [43.4% (26/60)] met five of the 10 quality criteria established, 10 papers [16.7% (10/60)] met three criteria, nine papers [15.0% (9/60)] met four criteria, six papers [10.0% (6/60)] met six criteria, four papers [6.7% (4/60)] met eight criteria, and three papers [5.0% (3/60)] met nine of the 10 criteria, whereas two papers [1.7% (1/60)] met two and seven [1.7% (1/60)] criteria. Publications originated mainly from the Americas [45.0% (27/60)] and in the last 16 years (2003-2019) [81.7% (49/60)], and most of the sampled dogs were stray dogs [65.0% (39/60)]. The most commonly used diagnostic test for leptospirosis was the microscopic agglutination test [78.4% (47/60)] followed by polymerase chain reaction [21.7% (13/60)], and the most common serovars were Canicola [71.4% (35/49)], Icterohaemorrhagiae [65.3% (32/49)], Grippotyphosa [40.8% (20/49)], and Pomona [40.8% (20/49)]. In conclusion, our results showed that spp. are present in unowned dogs worldwide; however, the low-methodological quality of the recovered cross-sectional studies precluded a meta-analysis.
Topics: Animals; Cross-Sectional Studies; Dog Diseases; Dogs; Leptospira; Leptospirosis; Seroepidemiologic Studies
PubMed: 35726571
DOI: 10.1017/S1466252321000190 -
BMC Infectious Diseases Dec 2020Direct agglutination test (DAT) as a simple, accurate and reliable method, has been widely used for serodiagnosis of visceral leishmaniasis (VL) during the last three... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Direct agglutination test (DAT) as a simple, accurate and reliable method, has been widely used for serodiagnosis of visceral leishmaniasis (VL) during the last three decades. The present study is a systematic review and meta-analysis to evaluate the diagnostic accuracy of DAT for serodiagnosis of human VL.
METHODS
Electronic databases, including MEDLINE (via PubMed), SCOPUS, Web of Science, SID and Mag Iran (two Persian scientific search engines) were searched from December 2004 to April 2019. We determined the pooled sensitivity and specificity rates of DAT for the diagnosis of human VL, calculated positive and negative likelihood ratios (LR+ and LR-), and constructed summary receiver operating characteristic (ROC) curves parameters across the eligible studies.
RESULTS
Of the 2928 records identified in the mentioned electronic databases and after examining reference lists of articles, 24 articles met inclusion criteria and were enrolled in the systematic review and out of them 20 records qualified for meta-analysis. The pooled sensitivity and specificity rates of DAT was 96% [95% CI, 92-98] and 95% [CI95% 86-99], respectively. The likelihood ratio of a positive test (LR+) was found to be 21 [CI95%, 6.6-66.5] and the likelihood ratio of a negative test (LR-) was found to be 0.04 [(CI95%, 0.02-0.08]. The combined estimate of the diagnostic odds ratio for DAT was high [467 (CI95%, 114-1912]). We found that the summary receiver operating characteristic curve (SROC) is positioned near the upper left corner of the curve and the area under curve (AUC) was 0.98 (95% CI, 0.97 to 0.99).
CONCLUSION
Referring to our analysis, we determined that DAT can be considered as a valuable tool for the serodiagnosis of human VL with high sensitivity and specificity. As DAT is a simple, accurate and efficient serological test, it can be recommended for serodiagnosis of human VL particularly in endemic areas.
Topics: Agglutination Tests; Data Accuracy; Humans; Leishmania donovani; Leishmaniasis, Visceral; Odds Ratio; ROC Curve; Sensitivity and Specificity
PubMed: 33308170
DOI: 10.1186/s12879-020-05558-7