John C. Ridderhof

roles of laboratories and laboratory systems in effective tuberculosis control

Laboratories and laboratory networks are a fundamental component of tuberculosis (TB) control, providing testing for diagnosis, surveillance and treatment monitoring at every level of the health-care system. New initiatives and resources to strengthen laboratory capacity and implement rapid and new diagnostic tests for TB will require recognition that laboratories are systems that require quality standards, appropriate human resources, and attention to safety in addition to supplies and equipment. To prepare the laboratory networks for new diagnostics and expanded capacity, we need to focus efforts on strengthening quality management systems (QMS) through additional resources for external quality assessment programmes for microscopy, culture, drug susceptibility testing (DST) and molecular diagnostics. QMS should also promote development of accreditation programmes to ensure adherence to standards to improve both the quality and credibility of the laboratory system within TB programmes. Corresponding attention must be given to addressing human resources at every level of the laboratory, with special consideration being given to new programmes for laboratory management and leadership skills. Strengthening laboratory networks will also involve setting up partnerships between TB programmes and those seeking to control other diseases in order to pool resources and to promote advocacy for quality standards, to develop strategies to integrate laboratories’ functions and to extend control programme activities to the private sector. Improving the laboratory system will assure that increased resources, in the form of supplies, equipment and facilities, will be invested in networks that are capable of providing effective testing to meet the goals of the Global Plan to Stop TB.

Performance of Tuberculosis Drug Susceptibility Testing in U.S. Laboratories from 1994 to 2008

ABSTRACT We present a statistical summary of results from the Model Performance Evaluation Program (MPEP) for Mycobacterium tuberculosis Drug Susceptibility Testing, 1994 to 2008, implemented by the U.S. Centers for Disease Control and Prevention (CDC). During that period, a total of 57,733 test results for culture isolates were reported by 216 participating laboratories for the first-line antituberculosis drugs used in the United States—isoniazid (INH), rifampin (RMP), ethambutol (EMB), and pyrazinamide (PZA). Using Clinical Laboratory and Standards Institute (CLSI)-recommended concentrations for one or more of three methods, agar proportion (AP), BACTEC460 (Bactec), and MGIT-960 (MGIT), yielded overall agreement of 97.0% for first-line drugs. For susceptible strains, agreement was 98.4%; for resistant strains, agreement was 91.0%, with significantly lower accuracy (chi-square test, P < 0.0001). For resistant strains, overall agreement by methods was 91.3% for AP, 93.0% for Bactec, and 82.6% for MGIT and by drugs was 92.2% for INH, 91.5% for RMP, 79.0% for EMB, and 97.5% for PZA. For some strains, performance by method varied significantly. Use of duplicate strains in the same shipment and repeat strains over time revealed consistent performance even for strains with higher levels of interlaboratory discordance. No overall differences in performance between laboratories were observed based on volume of testing or type of facility (e.g., health department, hospital, independent). By all methods, decreased performance was observed for strains with low-level INH resistance, RMP resistance, and EMB-resistant strains. These results demonstrate a high level of performance in detection of drug-resistant M. tuberculosis in U.S. laboratories.

Laboratory Reporting of Tuberculosis Test Results and Patient Treatment Initiation in California

ABSTRACT Prompt laboratory reporting of tuberculosis (TB) test results is necessary for TB control. To understand the extent of and factors contributing to laboratory reporting delays and the impact of reporting delays on initiation of treatment of TB patients, we analyzed data from 300 consecutive culture-positive TB cases reported in four California counties in 1998. Laboratory reporting to the specimen submitter was delayed for 26.9% of smear-positive patients and 46.8% of smear-negative patients. Delays were associated with the type of laboratory that performed the testing and with delayed transport of specimens. Referral laboratories (public health and commercial) had longer median reporting time frames than hospital and health maintenance organization laboratories. Among patients whose treatment was not started until specimens were collected, those with delayed laboratory reporting were more likely to have delayed treatment than patients with no laboratory reporting delays (odds ratio [OR] of 3.9 and 95% confidence interval [CI] of 1.6 to 9.7 for smear-positive patients and OR of 13.1 and CI of 5.3 to 32.2 for smear-negative patients). This relation remained after adjustment in a multivariate model for other factors associated with treatment delays (adjusted OR of 25.64 and CI of 7.81 to 83.33 for smear-negative patients). These findings emphasize the need to reduce times of specimen transfer between institutions and to ensure rapid communication among laboratories, health care providers, and health departments serving TB patients.

Identification of a Mycobacterium tuberculosis strain with stable, low-level resistance to isoniazid

ABSTRACT We have identified a potential quality control strain of Mycobacterium tuberculosis to monitor isoniazid susceptibility testing. This strain (strain A) has a stable phenotypic low-level resistance to isoniazid, has a mutation of C (−15) → T in the inhA promoter region, and gave consistent susceptibility test results in 141 laboratories.

Global laboratory initiative tool for a stepwise process towards tuberculosis laboratory accreditation.

made with this new test in detecting tuberculosis among patients excreting few bacilli and in identifying rifampicin resistance. For the reasons outlined above and in our article, sputum smear microscopy must be retained as a routine test at peripheral level in low-income countries, at least for the time being. We wish to emphasise the need for good operational research before recommending any replacement of smear microscopy. The old cloth must not be discarded without due assurance that the new cloth is affordable, durable and resistant to stormy weather!

Comparison of Two Different Strengths of Carbol Fuchsin in Ziehl-Neelsen Staining for Detecting Acid-Fast Bacilli

Selvakumar et al. ([5][1]) compared smear staining of acid-fast bacilli (AFB) by two different strengths of carbol fuchsin in Ziehl-Neelsen staining. First we would like to applaud the authors for providing a study on an important test method, the Ziehl-Neelsen AFB staining procedure, which receives

Assessment of Laboratory Performance of Nucleic Acid Amplification Tests for Detection of Mycobacterium tuberculosis

ABSTRACT During implementation of the Centers for Disease Control and Preventions Mycobacterium tuberculosis nucleic acid amplification (NAA) evaluation program, 27.1% of participants used the same biological safety cabinet for NAA and specimen processing; 28.8% reported not using unidirectional workflow. An association between false positives and adverse responses to quality assurance questions (P = 0.04) illustrated the need for following NCCLS recommendations.

The evolving Public Health Laboratory System.

Charles Darwins On the Origin of Species celebrated its 150th anniversary in 2009.1 In this publication that has shaped our understanding of biology, the author proposes that organisms evolve increasingly complex independent and interdependent systems to survive and flourish in an ever-changing environment. The evolution of public health laboratories (PHLs) can be compared with that of multi-celled organisms. PHL history tracks the progress from simply having laboratory testing available for public health programs to the development and fine-tuning of laboratory networks requiring special linkages and shared efforts to provide populations with comprehensive laboratory testing for rapid diagnosis, surveillance, and disease-control efforts. The evolution, from a PHL to the new definition of a PHL system that includes public and private laboratories, is reflected by a new focus on the relationships between laboratories, which complement the technical capabilities—similar to the increasingly complex interactions of multi-celled organisms responding to a changing environment.

Public health laboratory systems: at the crossroads.

Twenty years ago, Walter Dowdle1 observed that the word “laboratory” did not even appear in the index of the now classic 1988 Institute of Medicine (IOM) report, “The Future of Public Health.”2 It was Dr. Dowdle’s contention that despite the significant role of laboratories dating back more than 100 years to the earliest days of public health, a point had been reached where laboratories and their many contributions to public health were being taken for granted. During the last 20 years, much has changed to elevate the visibility of public health laboratories (PHLs). Their expanded roles, their engagement with partners, and their core functions have all been described and reaffirmed.3,4 This special supplement of Public Health Reports (PHR) is devoted to PHL systems, with an emphasis on activities and approaches that represent managing and improving the system across many different dimensions. It has become clear that, to meet the broad array of laboratory services required to support both public health and health care in the United States, PHLs have been and will continue operating within systems, especially state public health laboratory (SPHL) systems.5 How those systems are set up and funded and which entities are included vary by state or locality. Irrespective of how laboratory systems are put together, the evidence confirms that the laboratory services provided by these systems go well beyond the mere performance of laboratory tests and analyses. These systems are critical in their support of the 10 Essential Public Health Services (hereafter, Essential Services).6 PHLs at all levels, along with their respective leaders and partners, have in the past maintained and will continue to maintain the important linkages required to strengthen and sustain their respective systems. In 2010, PHR published a supplement on PHLs that focused on their many evolving roles and how they provide unique and ever-changing functions in support of public health and health care. The evolution of PHL systems, which was primarily influenced by emerging diseases, threats, programs, technologies, and innovation, is now being driven by a convergence of health reform, state and federal funding cuts, and the evolving role of public health.7,8