Strengthening the Tuberculosis Specimen Referral Network in Uganda: The Role of Public-Private Partnerships.

BACKGROUND: Diagnosis of multidrug-resistant tuberculosis and prompt initiation of effective treatment rely on access to rapid and reliable drug-susceptibility testing. Efficient specimen transport systems and appropriate training on specimen referral contribute to optimal and timely access to tuberculosis diagnostic services. METHODS: With support and technical assistance from a public-private partnership (PPP) between Becton Dickinson and the US President's Emergency Plan for AIDS Relief, the Uganda National TB Reference Laboratory (NTRL) and National TB and Leprosy Program redesigned the tuberculosis specimen transport network and trained healthcare workers with the goal of improving multidrug-resistant tuberculosis detection. RESULTS: Between 2008 and 2011, the PPP mapped 93% of health facilities and trained 724 healthcare and postal staff members covering 72% of districts. Strengthening the tuberculosis specimen referral system increased referrals from presumptive multidrug-resistant tuberculosis cases by >10-fold, with 94% of specimens reaching the NTRL within the established target transport time. CONCLUSIONS: This study demonstrates the potential of PPP collaborations with ministries of health to positively influence patient care by strengthening laboratory systems through increased access to drug-susceptibility testing in Uganda. Ongoing efforts to integrate specimen transport networks will maximize resources and improve patient management.

Learning-oriented assessment increases performance and written skills in a second year metabolic biochemistry course.

Assessment plays a critical role in learning and teaching and its power to enhance engagement and student outcomes is still underestimated in tertiary education. The current project considers the impact of a staged redesign of an assessment strategy that emphasized relevance of learning, formative assessment, student engagement, and feedback on student performance, failure rates and overall engagement in the course. Significant improvements in final grades (p < 0.0001) and written performance (p < 0.0001) in the final examination were noted that coincided with increased lecture attendance and overall engagement in the course. This study reinforces the importance of an integrated approach to assessment that includes well developed formative tasks and a continuous summative assessment strategy. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):412-420, 2016.

Access and Quality of HIV-Related Point-of-Care Diagnostic Testing in Global Health Programs.

Access to point-of-care testing (POCT) improves patient care, especially in resource-limited settings where laboratory infrastructure is poor and the bulk of the population lives in rural settings. However, because of challenges in rolling out the technology and weak quality assurance measures, the promise of human immunodeficiency virus (HIV)-related POCT in resource-limited settings has not been fully exploited to improve patient care and impact public health. Because of these challenges, the Joint United Nations Programme on HIV/AIDS (UNAIDS), in partnership with other organizations, recently launched the Diagnostics Access Initiative. Expanding HIV programs, including the "test and treat" strategies and the newly established UNAIDS 90-90-90 targets, will require increased access to reliable and accurate POCT results. In this review, we examine various components that could improve access and uptake of quality-assured POC tests to ensure coverage and public health impact. These components include evaluation, policy, regulation, and innovative approaches to strengthen the quality of POCT.

Multicenter feasibility study to assess external quality assessment panels for Xpert MTB/RIF assay in South Africa.

External quality assessment (EQA) for the Xpert MTB/RIF assay is part of the quality system required for clinical and laboratory practice. Five newly developed EQA panels that use different matrices, including a lyophilized sample (Vircell, Granada, Spain), a dried tube specimen (CDC), liquid (Maine Molecular Quality Control, Inc. [MMQCI], Scarborough, ME), artificial sputum (Global Laboratory Initiative [GLI]), and a dried culture spot (National Health Laboratory Services [NHLS]), were evaluated at 11 GeneXpert testing sites in South Africa. The panels comprised Mycobacterium tuberculosis complex (MTBC)-negative, MTBC-positive (including rifampin [RIF] susceptible and RIF resistant), and nontuberculosis mycobacterial material that was inactivated and safe for transportation. Twelve qualitative and quantitative variables were scored as acceptable (1) or unacceptable (0); the overall panel performance score for the Vircell, CDC, GLI, and NHLS panels was 9 of 12, while the MMQCI panel scored 6 of 12 (owing to the need for cold chain maintenance). All panels showed good compatibility with Xpert MTB/RIF testing, and none showed PCR inhibition. The use of a liquid or dry matrix did not appear to be a distinguishing criterion, as both matrices had reduced scores on insufficient volumes, a need for extra consumables, and the ability to transfer to the Xpert MTB/RIF cartridge. EQA is an important component of the quality system required for diagnostic testing programs, but it must be complemented by routine monitoring of performance indicators and instrument verification. This study aims to introduce EQA concepts for Xpert MTB/RIF testing and evaluates five potential EQA panels.

Advances in tuberculosis diagnostics: the Xpert MTB/RIF assay and future prospects for a point-of-care test.

Rapid progress has been made in the development of new diagnostic assays for tuberculosis in recent years. New technologies have been developed and assessed, and are now being implemented. The Xpert MTB/RIF assay, which enables simultaneous detection of Mycobacterium tuberculosis (MTB) and rifampicin (RIF) resistance, was endorsed by WHO in December, 2010. This assay was specifically recommended for use as the initial diagnostic test for suspected drug-resistant or HIV-associated pulmonary tuberculosis. By June, 2012, two-thirds of countries with a high tuberculosis burden and half of countries with a high multidrug-resistant tuberculosis burden had incorporated the assay into their national tuberculosis programme guidelines. Although the development of the Xpert MTB/RIF assay is undoubtedly a landmark event, clinical and programmatic effects and cost-effectiveness remain to be defined. We review the rapidly growing body of scientific literature and discuss the advantages and challenges of using the Xpert MTB/RIF assay in areas where tuberculosis is endemic. We also review other prospects within the developmental pipeline. A rapid, accurate point-of-care diagnostic test that is affordable and can be readily implemented is urgently needed. Investment in the tuberculosis diagnostics pipeline should remain a major priority for funders and researchers.

Opportunities and challenges for cost-efficient implementation of new point-of-care diagnostics for HIV and tuberculosis.

Stakeholders agree that supporting high-quality diagnostics is essential if we are to continue to make strides in the fight against human immunodeficiency virus (HIV) and tuberculosis. Despite the need to strengthen existing laboratory infrastructure, which includes expanding and developing new laboratories, there are clear diagnostic needs where conventional laboratory support is insufficient. Regarding HIV, rapid point-of-care (POC) testing for initial HIV diagnosis has been successful, but several needs remain. For tuberculosis, several new diagnostic tests have recently been endorsed by the World Health Organization, but a POC test remains elusive. Human immunodeficiency virus and tuberculosis are coendemic in many high prevalence locations, making parallel diagnosis of these conditions an important consideration. Despite its clear advantages, POC testing has important limitations, and laboratory-based testing will continue to be an important component of future diagnostic networks. Ideally, a strategic deployment plan should be used to define where and how POC technologies can be most efficiently and cost effectively integrated into diagnostic algorithms and existing test networks prior to widespread scale-up. In this fashion, the global community can best harness the tremendous capacity of novel diagnostics in fighting these 2 scourges.

An integrated approach to rapid diagnosis of tuberculosis and multidrug resistance using liquid culture and molecular methods in Russia.

OBJECTIVE: To analyse the feasibility, cost and performance of rapid tuberculosis (TB) molecular and culture systems, in a high multidrug-resistant TB (MDR TB) middle-income region (Samara, Russia) and provide evidence for WHO policy change. METHODS: Performance and cost evaluation was conducted to compare the BACTEC MGIT 960 system for culture and drug susceptibility testing (DST) and molecular systems for TB diagnosis, resistance to isoniazid and rifampin, and MDR TB identification compared to conventional Lowenstein-Jensen culture assays. FINDINGS: 698 consecutive patients (2487 sputum samples) with risk factors for drug-resistant tuberculosis were recruited. Overall M. tuberculosis complex culture positivity rates were 31.6% (787/2487) in MGIT and 27.1% (675/2487) in LJ (90.5% and 83.2% for smear-positive specimens). In total, 809 cultures of M. tuberculosis complex were isolated by any method. Median time to detection was 14 days for MGIT and 36 days for LJ (10 and 33 days for smear positive specimens) and indirect DST in MGIT took 9 days compared to 21 days on LJ. There was good concordance between DST on LJ and MGIT (96.8% for rifampin and 95.6% for isoniazid). Both molecular hybridization assay results correlated well with MGIT DST results, although molecular assays generally yielded higher rates of resistance (by approximately 3% for both isoniazid and rifampin). CONCLUSION: With effective planning and logistics, the MGIT 960 and molecular based methodologies can be successfully introduced into a reference laboratory setting in a middle incidence country. High rates of MDR TB in the Russian Federation make the introduction of such assays particularly useful.

Clinical reasoning: the relative contribution of identification, interpretation and hypothesis errors to misdiagnosis.

The aim of this study was to identify and describe the types of errors in clinical reasoning that contribute to poor diagnostic performance at different levels of medical training and experience. Three cohorts of subjects, second- and fourth- (final) year medical students and a group of general practitioners, completed a set of clinical reasoning problems. The responses of those whose scores fell below the 25th centile were analysed to establish the stage of the clinical reasoning process--identification of relevant information, interpretation or hypothesis generation--at which most errors occurred and whether this was dependent on problem difficulty and level of medical experience. Results indicate that hypothesis errors decrease as expertise increases but that identification and interpretation errors increase. This may be due to inappropriate use of pattern recognition or to failure of the knowledge base. Furthermore, although hypothesis errors increased in line with problem difficulty, identification and interpretation errors decreased. A possible explanation is that as problem difficulty increases, subjects at all levels of expertise are less able to differentiate between relevant and irrelevant clinical features and so give equal consideration to all information contained within a case. It is concluded that the development of clinical reasoning in medical students throughout the course of their pre-clinical and clinical education may be enhanced by both an analysis of the clinical reasoning process and a specific focus on each of the stages at which errors commonly occur.