Jessica Minion

Accuracy of rapid influenza diagnostic tests: a meta-analysis.

BACKGROUND Timely diagnosis of influenza can help clinical management. PURPOSE To examine the accuracy of rapid influenza diagnostic tests (RIDTs) in adults and children with influenza-like illness and evaluate factors associated with higher accuracy. DATA SOURCES PubMed and EMBASE through December 2011; BIOSIS and Web of Science through March 2010; and citations of articles, guidelines, reviews, and manufacturers. STUDY SELECTION Studies that compared RIDTs with a reference standard of either reverse transcriptase polymerase chain reaction (first choice) or viral culture. DATA EXTRACTION Reviewers abstracted study data by using a standardized form and assessed quality by using Quality Assessment of Diagnostic Accuracy Studies criteria. DATA SYNTHESIS 159 studies evaluated 26 RIDTs, and 35% were conducted during the H1N1 pandemic. Failure to report whether results were assessed in a blinded manner and the basis for patient recruitment were important quality concerns. The pooled sensitivity and specificity were 62.3% (95% CI, 57.9% to 66.6%) and 98.2% (CI, 97.5% to 98.7%), respectively. The positive and negative likelihood ratios were 34.5 (CI, 23.8 to 45.2) and 0.38 (CI, 0.34 to 0.43), respectively. Sensitivity estimates were highly heterogeneous, which was partially explained by lower sensitivity in adults (53.9% [CI, 47.9% to 59.8%]) than in children (66.6% [CI, 61.6% to 71.7%]) and a higher sensitivity for influenza A (64.6% [CI, 59.0% to 70.1%) than for influenza B (52.2% [CI, 45.0% to 59.3%). LIMITATION Incomplete reporting limited the ability to assess the effect of important factors, such as specimen type and duration of influenza symptoms, on diagnostic accuracy. CONCLUSION Influenza can be ruled in but not ruled out through the use of RIDTs. Sensitivity varies across populations, but it is higher in children than in adults and for influenza A than for influenza B. PRIMARY FUNDING SOURCE Canadian Institutes of Health Research.

Novel and improved technologies for tuberculosis diagnosis: progress and challenges.

Despite a decade of success in improving cure rates for tuberculosis (TB), diagnosis and case detection remain a major obstacle to TB control. This article reviews the existing evidence base on TB diagnostics, describes the progress of new technologies, and ends with a review of cost-effectiveness and modeling studies on the potential effect of new diagnostics in TB control.

Microscopic-observation drug susceptibility and thin layer agar assays for the detection of drug resistant tuberculosis: a systematic review and meta-analysis

BACKGROUND Simple, rapid, and affordable tests are needed to detect drug resistance in Mycobacterium tuberculosis. We did a systematic review and meta-analysis to investigate the accuracy of microscopic-observation drug susceptibility (MODS) and thin layer agar (TLA) assays for rapid screening of patients at risk of drug-resistant tuberculosis. METHODS In accordance with protocols and methods recommended by the Cochrane Diagnostic Test Accuracy Working Group, we systematically searched PubMed, Embase, and Biosis for reports published between January, 1990, and February, 2009. We included studies investigating detection of drug resistance in M tuberculosis with the MODS or TLA assay, and in which an accepted reference standard was used. Data extracted from the studies were combined by use of bivariate random-effects regression models and hierarchical summary receiver operating characteristic curves to estimate sensitivity and specificity for detection of resistance to specific drugs. FINDINGS We identified 12 studies, of which nine investigated the MODS assay and three investigated the TLA assay. For the MODS assay of rifampicin resistance, pooled estimates were 98·0% (95% CI 94·5-99·3) for sensitivity and 99·4% (95·7-99·9) for specificity. For the MODS assay of isoniazid resistance with a 0·1 μg/mL cutoff, pooled sensitivity was 97·7% (94·4-99·1) and pooled specificity was 95·8% (88·1-98·6), but with a 0·4 μg/mL cutoff, sensitivity decreased to 90·0% (84·5-93·7) and specificity increased to 98·6% (96·9-99·4). All assessments of rifampicin and isoniazid resistance with the TLA assay yielded 100% accuracy. Mean turnaround time was 9·9 days (95% CI 4·1-15·8) for the MODS assay and 11·1 days (10·1-12·0) for the TLA assay. INTERPRETATION MODS and TLA assays are inexpensive, rapid alternatives to conventional methods for drug susceptibility testing of M tuberculosis. Our data and expert opinion informed WHOs recommendation for use of selected non-commercial drug susceptibility tests, including MODS, as an interim solution until capacity for genotypic or automated liquid culture drug susceptibility testing is developed. FUNDING Stop TB Department of WHO.

New and improved tuberculosis diagnostics: evidence, policy, practice, and impact

Purpose of review The aim is to summarize the evidence base for tuberculosis (TB) diagnostics, review recent policies on TB diagnostics, and discuss issues such as how evidence is translated into policy, limitations of the existing evidence base, and challenges involved in translating policies into impact. Recent findings Case detection continues to be a major obstacle to global TB control. Fortunately, due to an unprecedented level of interest, funding, and activity, the new diagnostics pipeline for TB has rapidly expanded. There have been several new policies and guidelines on TB diagnostics. However, there are major gaps in the existing pipeline (e.g. lack of a point-of-care test) and the evidence base is predominantly made up of research studies of test accuracy. Summary With the availability of new diagnostics and supporting policies, the next major step is translation of policy into practice. The impact of new tests will depend largely on the extent of their introduction and acceptance into the global public sector. This will itself depend in part on policy decisions by international technical agencies and national TB programs. With the engagement of all key stakeholders, we will need to translate evidence-based policies into epidemiological and public health impact.

Serotypes and antimicrobial susceptibilities of invasive Streptococcus pneumoniae pre- and post-seven valent pneumococcal conjugate vaccine introduction in Alberta, Canada, 2000-2006.

Alberta, Canada introduced the Streptococcus pneumoniae seven valent conjugate vaccine (PCV7) program for children less than 2 years of age in September 2002. We determined the rates of invasive pneumococcal disease in Alberta, Canada 2 years pre- and 4 years post-PCV7 introduction (2000-2006) as well as the rates of antibiotic resistance and serotype distribution in this same time period. Overall, PCV7 serotypes decreased 61% from 2000 to 2006. The greatest decrease in incidence of invasive pneumococcal disease occurred in children less than 2 years of age declining from a high of 96.7/100,000 (2000) to 25.8/100,000 (2006) (P<0.0001). Non-susceptibility of S. pneumoniae isolates to penicillin dropped significantly from 14% in 2000 to 4.6% in 2006 (P<0.0001). Non-susceptible erythromycin isolates also decreased from 8.8% (2000) to 5.8% (2006) (P=0.13). The introduction of PCV7 in Alberta, Canada has decreased the incidence of invasive pneumococcal disease in Alberta as well as resulting in a decrease in antibiotic resistance over this same time frame, principally for penicillin resistance.

Systematic Review and Meta-Analysis of Antigen Detection Tests for the Diagnosis of Tuberculosis

ABSTRACT Tests that detect Mycobacterium tuberculosis antigens in clinical specimens could provide rapid direct evidence of active disease. We performed a systematic review to assess the diagnostic accuracy of antigen detection tests for active tuberculosis (TB) according to standard methods and summarized test performance using bivariate random effects meta-analysis. Overall, study quality was a concern. For pulmonary TB (47 studies, 5,036 participants), sensitivity estimates ranged from 2% to 100% and specificity from 33% to 100%. Lipoarabinomannan (LAM) was the antigen most frequently targeted (23 studies, 49%). The pooled sensitivity of urine LAM was higher in HIV-infected than HIV-uninfected individuals (47%; 95% confidence interval [CI], 26 to 68% versus 14%; 95% CI, 4 to 38%); pooled specificity estimates were similar: 96%; 95% CI, 81 to 100% and 97%; 95% CI, 86 to 100%, respectively. For extrapulmonary TB (21 studies, 1,616 participants), sensitivity estimates ranged from 0% to 100% and specificity estimates from 62% to 100%. Five studies targeting LAM, ESAT-6, Ag85 complex, and the 65-kDa antigen in cerebrospinal fluid, when pooled, yielded the highest sensitivity (87%; 95% CI, 61 to 98%), but low specificity (84%; 95% CI, 60 to 95%). Because of the limited number of studies targeting any specific antigen other than LAM, we could not draw firm conclusions about the overall clinical usefulness of these tests. Further studies are warranted to determine the value of LAM detection for TB meningitis in high-HIV-prevalence settings. Considering that antigen detection tests could be translated into rapid point-of-care tests, research to improve their performance is urgently needed.

Microcolony culture techniques for tuberculosis diagnosis: a systematic review

BACKGROUND There is considerable demand for quicker and more affordable yet accurate diagnostic tools for tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay and the thin-layer agar (TLA) assay are inexpensive, rapid microcolony-based culture methods. METHODS A systematic review and meta-analysis was performed to assess the accuracy and other test characteristics of MODS and TLA compared to a reference standard of traditional solid or liquid culture. Pooled estimates of sensitivity and specificity and their 95% confidence intervals were estimated with an exact binomial likelihood random effects meta-analysis. RESULTS A total of 21 eligible studies were identified, 12 that evaluated MODS, seven that evaluated TLA and two that evaluated both. The overall pooled sensitivity and specificity of MODS were respectively 92% (95%CI 87-97) and 96% (90-100), and for TLA they were respectively 87% (95%CI 79-94) and 98% (95%CI 94-100), although there was considerable heterogeneity of results. When the studies were restricted to those assessing accuracy of MODS in sputum samples only, the sensitivity was 96% (95%CI 94-98) and the specificity 96% (95%CI 89-100). The mean intervals from reception of specimens to results were 9.2 days with MODS and 11.5 days with TLA; contamination rates averaged 6.6% with MODS and 12.3% with TLA; materials and supplies costs averaged US

Diagnostic Accuracy and Reproducibility of WHO-Endorsed Phenotypic Drug Susceptibility Testing Methods for First-Line and Second-Line Antituberculosis Drugs

1.48 for MODS and US

Comparison of LED and Conventional Fluorescence Microscopy for Detection of Acid Fast Bacilli in a Low-Incidence Setting

2.42 for TLA. CONCLUSIONS MODS and TLA appear to be accurate and rapid yet inexpensive diagnostic tools for active TB. However, this review did not find sufficient evidence on the feasibility and costs of implementation of these tests, nor on the impact of these tests on patient outcomes.BACKGROUND There is considerable demand for quicker and more affordable yet accurate diagnostic tools for tuberculosis (TB). The microscopic observation drug susceptibility (MODS) assay and the thin-layer agar (TLA) assay are inexpensive, rapid microcolony-based culture methods. METHODS A systematic review and meta-analysis was performed to assess the accuracy and other test characteristics of MODS and TLA compared to a reference standard of traditional solid or liquid culture. Pooled estimates of sensitivity and specificity and their 95% confidence intervals were estimated with an exact binomial likelihood random effects meta-analysis. RESULTS A total of 21 eligible studies were identified, 12 that evaluated MODS, seven that evaluated TLA and two that evaluated both. The overall pooled sensitivity and specificity of MODS were respectively 92% (95%CI 87-97) and 96% (90-100), and for TLA they were respectively 87% (95%CI 79-94) and 98% (95%CI 94-100), although there was considerable heterogeneity of results. When the studies were restricted to those assessing accuracy of MODS in sputum samples only, the sensitivity was 96% (95%CI 94-98) and the specificity 96% (95%CI 89-100). The mean intervals from reception of specimens to results were 9.2 days with MODS and 11.5 days with TLA; contamination rates averaged 6.6% with MODS and 12.3% with TLA; materials and supplies costs averaged US

Multidrug and Extensively Drug-resistant Tuberculosis in Canada 1997–2008: Demographic and Disease Characteristics

1.48 for MODS and US