Special Programme for Research and Training in Tropical Diseases (WHO), Wellcome Trust, Canadian Institutes of Health Research, UK Medical Research Council, and the European and Developing Countries Clinical Trials Partnership.

The global extensively drug-resistant tuberculosis (TB) response plan calls for implementation of rapid tests to screen patients at risk of drug-resistant TB. Currently, two line probe assays exist, the INNO-LiPA1Rif.TB assay (Innogenetics, Ghent, Belgium) and the GenoType1 MTBDR assay (Hain LifeScience GmbH, Nehren, Germany). While LiPA studies have been reviewed, the accuracy of GenoType assays has not been systematically reviewed.The present authors carried out a systematic review and used meta-analysis methods appropriate for diagnostic accuracy. After the literature searches, 14 comparisons for rifampicin and 15 comparisons for isoniazid were identified in 10 articles that used GenoType MTBDR assays. Accuracy results were summarised in forest plots and pooled using bivariate randomeffects regression.The pooled sensitivity (98.1%, 95% confidence interval (CI) 95.9-99.1) and specificity (98.7%, 95% CI 97.3-99.4) estimates for rifampicin resistance were very high and consistent across all subgroups, assay versions and specimen types. The accuracy for isoniazid was variable, with lower sensitivity (84.3%, 95% CI 76.6-89.8) and more inconsistent than specificity (99.5%, .GenoType MDTBR assays demonstrate excellent accuracy for rifampicin resistance, even when used on clinical specimens. While specificity is excellent for isoniazid, sensitivity estimates were modest and variable. Together with data from demonstration projects, the meta-analysis provides evidence for policy making and clinical practice.

BackgroundThe accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB®-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.MethodsLAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis.ResultsOf 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus >200 cells/mm3 (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%–100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm3 were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species.ConclusionsThese preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm3, who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection.

BackgroundHundreds of studies have evaluated the diagnostic accuracy of nucleic-acid amplification tests (NAATs) for tuberculosis (TB). Commercial tests have been shown to give more consistent results than in-house assays. Previous meta-analyses have found high specificity but low and highly variable estimates of sensitivity. However, reasons for variability in study results have not been adequately explored. We performed a meta-analysis on the accuracy of commercial NAATs to diagnose pulmonary TB and meta-regression to identify factors that are associated with higher accuracy.Methodology/Principal FindingsWe identified 2948 citations from searching the literature. We found 402 articles that met our eligibility criteria. In the final analysis, 125 separate studies from 105 articles that reported NAAT results from respiratory specimens were included. The pooled sensitivity was 0.85 (range 0.36–1.00) and the pooled specificity was 0.97 (range 0.54–1.00). However, both measures were significantly heterogeneous (p<.001). We performed subgroup and meta-regression analyses to identify sources of heterogeneity. Even after stratifying by type of commercial test, we could not account for the variability. In the meta-regression, the threshold effect was significant (p = .01) and the use of other respiratory specimens besides sputum was associated with higher accuracy.Conclusions/SignificanceThe sensitivity and specificity estimates for commercial NAATs in respiratory specimens were highly variable, with sensitivity lower and more inconsistent than specificity. Thus, summary measures of diagnostic accuracy are not clinically meaningful. The use of different cut-off values and the use of specimens other than sputum could explain some of the observed heterogeneity. Based on these observations, commercial NAATs alone cannot be recommended to replace conventional tests for diagnosing pulmonary TB. Improvements in diagnostic accuracy, particularly sensitivity, need to be made in order for this expensive technology to be worthwhile and beneficial in low-resource countries.

Trewin, J, Meylan, C, Varley, MC, Cronin, J, and Ling, D. Effect of match factors on the running performance of elite female soccer players. J Strength Cond Res 32(7): 2002-2009, 2018-The purpose of this study was to examine the effects of match factors on the match running of elite female soccer players. Players from the same women's national team (n = 45) were monitored during 47 international fixtures (files = 606) across 4 years (2012-2015) using 10-Hz global positioning system devices. A mixed model was used to analyze the effects of altitude, temperature, match outcome, opposition ranking, and congested schedules. At altitude (>500 m), a small increase in the number of accelerations (effect size [ES] = 0.40) and a small decrease in total distance (ES = -0.54) were observed, whereas at higher temperatures, there were decreases in all metrics (ES = -0.83 to -0.16). Playing a lower ranked team in a draw resulted in a moderate increase in high-speed running (ES = 0.89), with small to moderate decreases in total distance and low-speed running noted in a loss or a win. Winning against higher ranked opponents indicated moderately higher total distance and low-speed running (ES = 0.75), compared with a draw. Although the number of accelerations were higher in a draw against lower ranked opponents, compared with a win and a loss (ES = 0.95 and 0.89, respectively). Practitioners should consider the effect of match factors on match running in elite female soccer.