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PCR diagnosis of invasive candidiasis: systematic review and meta-analysis.

ABSTRACT: Invasive candidiasis (IC) is a significant cause of morbidity and mortality. Diagnosis relies on culture-based methods, which lack sensitivity and delay diagnosis. We conducted a systematic review assessing the diagnostic accuracy of PCR-based methods to detect Candida spp. directly in blood samples. We searched electronic databases for prospective or retrospective cohort and case-control studies. Two reviewers abstracted data independently. Meta-analysis was performed using a hierarchical logistic regression model. Random-effects metaregression was performed to assess the effects of study methods and infection characteristics on sensitivity or specificity values. We included 54 studies with 4,694 patients, 963 of whom had proven/probable or possible IC. Perfect (100%) sensitivity and specificity for PCR in whole-blood samples was observed when patients with cases had candidemia and controls were healthy people. When PCR was performed to evaluate patients with suspected invasive candidiasis, the pooled sensitivity for the diagnosis of candidemia was 0.95 (confidence interval, 0.88 to 0.98) and the pooled specificity was 0.92 (0.88 to 0.95). A specificity of >90% was maintained in several analyses considering different control groups. The use of whole-blood samples, rRNA, or P450 gene targets and a PCR detection limit of ? 10 CFU/ml were associated with improved test performance. PCR positivity rates among patients with proven or probable IC were 85% (78 to 91%), while blood cultures were positive for 38% (29 to 46%). We conclude that direct PCR using blood samples had good sensitivity and specificity for the diagnosis of IC and offers an attractive method for early diagnosis of specific Candida spp. Its effects on clinical outcomes should be investigated.

SUBMITTER: Avni T

PROVIDER: S-EPMC3043518 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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PCR diagnosis of invasive candidiasis: systematic review and meta-analysis.

Avni Tomer T Leibovici Leonard L Paul Mical M

Journal of clinical microbiology 20101124 2

Invasive candidiasis (IC) is a significant cause of morbidity and mortality. Diagnosis relies on culture-based methods, which lack sensitivity and delay diagnosis. We conducted a systematic review assessing the diagnostic accuracy of PCR-based methods to detect Candida spp. directly in blood samples. We searched electronic databases for prospective or retrospective cohort and case-control studies. Two reviewers abstracted data independently. Meta-analysis was performed using a hierarchical logis ...[more]

PMID: 21106797

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Project description:The use of molecular-based methods for the diagnosis of bacterial infections in blood is appealing, but they have not yet passed the threshold for clinical practice. A systematic review of prospective and case-control studies assessing the diagnostic utility of PCR directly with blood samples for the diagnosis of invasive pneumococcal disease (IPD) was performed. A broad search was conducted to identify published and unpublished studies. Two reviewers independently extracted the data. Summary estimates for sensitivity and specificity with 95% confidence intervals (CIs) were calculated by using the hierarchical summary receiver operating characteristic method. The effects of sample processing, PCR type, the gene-specific primer, study design, the participants' age, and the source of infection on the diagnostic odds ratios were assessed through meta-regression. Twenty-nine studies published between 1993 and 2009 were included. By using pneumococcal bacteremia for case definition and healthy people or patients with bacteremia caused by other bacteria as controls (22 studies), the summary estimates for sensitivity and specificity were 57.1% (95% CI, 45.7 to 67.8%) and 98.6% (95% CI, 96.4 to 99.5%), respectively. When the controls were patients suspected of having IPD without pneumococcal bacteremia (26 studies), the respective values were 66.4% (95% CI, 55.9 to 75.6%) and 87.8% (95% CI, 79.5 to 93.1%). With lower degrees of proof for IPD (any culture or serology result and the clinical impression), the sensitivity of PCR decreased and the specificity increased. All analyses were highly heterogeneous. The use of nested PCR and being a child were associated with low specificity, while the use of a cohort study design was associated with a low sensitivity. The lack of an appropriate reference standard might have caused underestimation of the performance of the PCR. Currently available methods for PCR with blood samples for the diagnosis of IPD lack the sensitivity and specificity necessary for clinical practice.

Project description:BACKGROUND: Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance. METHODS: A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease. RESULTS: Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied. CONCLUSIONS: Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.

Project description:Tuberculosis is a rising global public health emergency. Then, it is a priority to undertake innovations in preventive, diagnostic, and therapeutic methods. Improved diagnostic methods for tuberculosis are urgently needed to address this global epidemic. These methods should be rapid, accurate, affordable, and able to detect drug-resistant tuberculosis. The benefits of these new diagnostic technics include earlier diagnosis and treatment, improved patient outcomes, and reduced economic burden. Therefore, we aimed to systematically review the diagnostic performance of droplet digital PCR (ddPCR)-a third-generation PCR-compared with quantitative Real Time-PCR (qPCR) for diagnosing pulmonary and extrapulmonary tuberculosis. We included 14 diagnostic accuracy test studies performed in Asia, Europe, and Latin America, 1,672 participants or biological samples, and 975 events (pulmonary or extrapulmonary tuberculosis). Most of the included studies had a low risk of bias (QUADAS-C tool). Sensitivity and specificity were lower for ddPCR [0.56 (95% CI 0.53-0.58) and 0.97 (95% CI 0.96-0.98), respectively] than for qPCR [0.66 (95% CI 0.60-0.71) and 0.98 (95% CI 0.97-0.99), respectively]. However, the area under the ROC curve (AUC) was higher for ddPCR than for qPCR (0.97 and 0.94, respectively). Comparing both AUCs using the Hanley & McNeil method, we found statistically significant differences (AUC difference of 4.40%, p = 0.0020). In the heterogeneity analysis, we found significant differences between both techniques according to the continent of origin of the study and the location of tuberculosis (pulmonary or extrapulmonary disease). The AUCs of both methods were similar in pulmonary tuberculosis. However, for extrapulmonary tuberculosis, the AUC was higher for ddPCR. We found some limitations: (1) significant heterogeneity of the studies, and (2) we could not perform subgroup analyses according to other relevant variables, such as the age and sex of the participants. Nonetheless, this study is the first meta-analysis that shows that ddPCR has a comparable diagnostic performance than qPCR for pulmonary tuberculosis. However, for extrapulmonary tuberculosis, ddPCR has a better discriminant capacity to differentiate between patients with and without extrapulmonary tuberculosis. We conclude that ddPCR is likely the best diagnostic technic for tuberculosis diagnosis, especially for extrapulmonary tuberculosis. More studies are still needed yet.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022382768, CRD42022382768.

Dataset Information

PCR diagnosis of invasive candidiasis: systematic review and meta-analysis.

Publications

PCR diagnosis of invasive candidiasis: systematic review and meta-analysis.

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