Publications

BACKGROUND

Throughout the Ebola virus disease (EVD) epidemic in West Africa, field laboratory testing for EVD has relied on complex, multi-step real-time reverse transcription PCR (RT-PCR) assays; an accurate sample-to-answer RT-PCR test would reduce time to results and potentially increase access to testing. We evaluated the performance of the Cepheid GeneXpert Ebola assay on clinical venipuncture whole blood (WB) and buccal swab (BS) specimens submitted to a field biocontainment laboratory in Sierra Leone for routine EVD testing by RT-PCR ("Trombley assay").

METHODS AND FINDINGS

This study was conducted in the Public Health England EVD diagnostic laboratory in Port Loko, Sierra Leone, using residual diagnostic specimens remaining after clinical testing. EDTA-WB specimens (n = 218) were collected from suspected or confirmed EVD patients between April 1 and July 20, 2015. BS specimens (n = 71) were collected as part of a national postmortem screening program between March 7 and July 20, 2015. EDTA-WB and BS specimens were tested with Xpert (targets: glycoprotein [GP] and nucleoprotein [NP] genes) and Trombley (target: NP gene) assays in parallel. All WB specimens were fresh; 84/218 were tested in duplicate on Xpert to compare WB sampling methods (pipette versus swab); 43/71 BS specimens had been previously frozen. In all, 7/218 (3.2%) WB and 7/71 (9.9%) BS samples had Xpert results that were reported as "invalid" or "error" and were excluded, leaving 211 WB and 64 BS samples with valid Trombley and Xpert results. For WB, 22/22 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 84.6%-100%), and 181/189 Trombley-negative samples were Xpert-negative (specificity 95.8%, 95% confidence interval (CI) 91.8%-98.2%). Seven of the eight Trombley-negative, Xpert-positive (Xpert cycle threshold [Ct] range 37.7-43.4) WB samples were confirmed to be follow-up submissions from previously Trombley-positive EVD patients, suggesting a revised Xpert specificity of 99.5% (95% CI 97.0%-100%). For Xpert-positive WB samples (n = 22), Xpert NP Ct values were consistently lower than GP Ct values (mean difference -4.06, 95% limits of agreement -6.09, -2.03); Trombley (NP) Ct values closely matched Xpert NP Ct values (mean difference -0.04, 95% limits of agreement -2.93, 2.84). Xpert results (positive/negative) for WB sampled by pipette versus swab were concordant for 78/79 (98.7%) WB samples, with comparable Ct values for positive results. For BS specimens, 20/20 Trombley-positive samples were Xpert-positive (sensitivity 100%, 95% CI 83.2%-100%), and 44/44 Trombley-negative samples were Xpert-negative (specificity 100%, 95% CI 92.0%-100%). This study was limited to testing residual diagnostic samples, some of which had been frozen before use; it was not possible to test the performance of the Xpert Ebola assay at point of care.

CONCLUSIONS

The Xpert Ebola assay had excellent performance compared to an established RT-PCR benchmark on WB and BS samples in a field laboratory setting. Future studies should evaluate feasibility and performance outside of a biocontainment laboratory setting to facilitate expanded access to testing.

This review of tuberculosis epidemiology is intended to provide a historical perspective on the public health approach to tuberculosis (TB) control in California. This historical context offers a lens through which to view current epidemiologic trends and insight into how new therapeutic tools can be applied. Since 1993, the year detailed case reporting was instituted, California has had a decrease in recent TB transmission as evidenced by a reduction in pediatric cases and an increased percentage of cases attributable to progression of latent infection to TB disease in the foreign-born population. Overall, there has been a dramatic decline in the annual TB case count, but the speed of the decline has slowed over the last several years. At the current pace and case count of 2137 in 2015, California will not achieve TB elimination (<1 TB case per one million population) for at least 100 years. There are an estimated 2.1 million persons in California with latent TB infection. Modeling suggests that LTBI detection and treatment are important in reaching TB elimination. For this reason, a coalition of stakeholders in California is exploring novel approaches to accelerate the case decline in order to prevent unnecessary disease and death.

OBJECTIVES

We examined whether regional improvement in stress myocardial blood flow (sMBF) following angiography-guided coronary revascularization depends on the existence of a perfusion defect on positron emission tomography (PET).

BACKGROUND

Percent stenosis on coronary angiography often is the main factor when deciding whether to perform revascularization, but it does not reliably relate to maximum sMBF. PET is a validated method of assessing sMBF.

METHODS

19 patients (79% M, 65 ± 12 years) underwent PET stress before and after revascularization (17 PCI, 2 CABG). Pre- and post-revascularization sMBF for each left ventricular quadrant (anterior, septal, lateral, and inferior) was stratified by the presence or absence of a baseline perfusion defect on PET and whether that region was revascularized.

RESULTS

Intervention was performed on 40 of 76 quadrants. When a baseline perfusion defect existed in a region that was revascularized (n = 26), post-revascularization flow increased by 0.6 ± 0.7 cc/min/g (1.2 ± 0.4 vs 1.7 ± 0.8, P < 0.001). When no defect existed but revascularization was performed (n = 14), sMBF did not change significantly (1.7 ± 0.3 vs 1.5 ± 0.4 cc/min/g, P = 0.16). In regions without a defect that were not revascularized (n = 29), sMBF did not significantly change (2.0 ± 0.6 vs 1.9 ± 0.7, P = 0.7).

CONCLUSIONS

When a stress-induced perfusion defect exists on PET, revascularization improves sMBF in that region. When there is no such defect, sMBF shows no net change, whether or not intervention is performed in that area. PET stress may be useful for identifying areas of myocardium that could benefit from revascularization, and also areas in which intervention is unlikely to yield improvement in myocardial blood flow.