National Laboratory System Research Articles

Updating Antimicrobial Susceptibility Testing Present and Future Relevance

1. Cynthia B. Schofield, MPH, MT (CAMT)[⇑][1] 1. VA San Diego Healthcare System (retired), San Diego, CA 1. Address for Correspondence: Cynthia B. Schofield, MPH, MT (CAMT), VA San Diego Healthcare System (retired), 7050 Weller St., San Diego, CA, (858) 450-9651, cschofield{at}san.rr.com 1. Discuss the “state of the art” of antimicrobial susceptibility testing (AST) from the National Laboratory System (NLS) surveys. 2. Summarize the critical factors in disk diffusion and broth dilution testing. 3. Explain the potential sources of error inherent in AST methods. 4. Discuss breakpoints and reasons for microbiologists concern. 5. Discuss the controversy surrounding AST interpretive values. 6. Compare and contrast AST and molecular assays for routine laboratory use. State of the Art Testing methods and reporting of results vary widely among clinical, reference and public health laboratories. Accordingly, institutional size and resources dictate both antimicrobial susceptibility testing (AST) needs and the cost effectiveness of test methods. Results of evaluations from 102 laboratories by the National Laboratory System (NLS) between 2001 and 2005 proved fewer than 50% of these laboratories published antibiograms of local resistance patterns and fewer than 50% adhered to the guidelines and standards established by the Clinical and Laboratory Standards Institute (CLSI). The effort to improve performance and adherence to CLSI standards and to assure rapid detection and reporting of antimicrobial resistance was undertaken by the NLS. NLS consists a group of microbiologists from the University of Washington, the University of California at Los Angeles and the Centers for Disease Control and Prevention (CDC). The NLS investigators surveyed the labs in 2001 and 2005 to determine the effect of 2003 and 2004 interventions. The interventions included AST workshops according to CLSI guidelines. Investigators trained local faculty in the use of a CDC AST self study and distributed free CLSI documents. Web sites and teleconferences were instituted as educational supplements. The 2001 assessment compared case studies of AST performance when testing Enterococcus sp., methicillin-resistant S. aureus (MRSA) and S. pneumoniae among the 102 laboratories. In a 2002 survey, changes in case studies from the previous year were noted and recorded. Changes over a period of 5 years were tabulated by the surveys (2001 to 2005) in the… ABBREVIATIONS: AST-antimicrobial susceptibility testing; NLS-National Laboratory System; CDC-Center for Disease Control and Prevention; CLSI-Clinical and Laboratory Standards Institute; MIC-minimal inhibitory concentration; MH-Mueller-Hinton; CAP-College of American Pathologists; PK/PD-pharmacokinetic/pharmacodynamics; UTI-urinary tract infection; CSF-cerebrospinal fluid; FDA-Food and Drug Administration; EUCAST-European Committee on Antimicrobial Susceptibility Testing; AUC-area under the concentration curve; PCR-polymerase chain reaction; HAI-hospital-associated infection; CAI-community-associated infection; MRSA-methicillin-resistant Staphylococcus aureus ; VRE-vancomycin-resistant Enterococcus sp.; MTB- Mycobacterium tuberculosis ; ESBL-extended-spectrum beta lactamase; KPC- Klebsiella pneumoniae carbapenem-resistant; MDR-multi-drug resistant. 1. Discuss the “state of the art” of antimicrobial susceptibility testing (AST) from the National Laboratory System (NLS) surveys. 2. Summarize the critical factors in disk diffusion and broth dilution testing. 3. Explain the potential sources of error inherent in AST methods. 4. Discuss breakpoints and reasons for microbiologists concern. 5. Discuss the controversy surrounding AST interpretive values. 6. Compare and contrast AST and molecular assays for routine laboratory use. [1]: #corresp-1

Strengthening systems for communicable disease surveillance: creating a laboratory network in Rwanda

BackgroundThe recent emergence of a novel strain of influenza virus with pandemic potential underscores the need for quality surveillance and laboratory services to contribute to the timely detection and confirmation of public health threats. To provide a framework for strengthening disease surveillance and response capacities in African countries, the World Health Organization Regional Headquarters for Africa (AFRO) developed Integrated Disease Surveillance and Response (IDSR) aimed at improving national surveillance and laboratory systems. IDSR emphasizes the linkage of information provided by public health laboratories to the selection of relevant, appropriate and effective public health responses to disease outbreaks.MethodsWe reviewed the development of Rwanda's National Reference Laboratory (NRL) to understand essential structures involved in creating a national public health laboratory network. We reviewed documents describing the NRL's organization and record of test results, conducted site visits, and interviewed health staff in the Ministry of Health and in partner agencies. Findings were developed by organizing thematic categories and grouping examples within them. We purposefully sought to identify success factors as well as challenges inherent in developing a national public health laboratory system.ResultsAmong the identified success factors were: a structured governing framework for public health surveillance; political commitment to promote leadership for stronger laboratory capacities in Rwanda; defined roles and responsibilities for each level; coordinated approaches between technical and funding partners; collaboration with external laboratories; and use of performance results in advocacy with national stakeholders. Major challenges involved general infrastructure, human resources, and budgetary constraints.ConclusionsRwanda's experience with collaborative partnerships contributed to creation of a functional public health laboratory network.

Laboratory Systems and Services Are Critical in Global Health

The $63 billion comprehensive global health initiative (GHI) emphasizes health systems strengthening (HSS) to tackle challenges, including child and maternal health, HIV/AIDS, family planning, and neglected tropical diseases. GHI and other initiatives are critical to fighting emerging and reemerging diseases in resource-poor countries. HSS is also an increasing focus of the $49 billion program of the US President’s Emergency Plan for AIDS Relief and the Global Fund to Fight AIDS, Tuberculosis and Malaria. Laboratory systems and services are often neglected in resource-poor settings, but the funding offers an opportunity to end the neglect. To sustainably strengthen national laboratory systems in resource-poor countries, the following approaches are needed: (1) developing integrative national laboratory strategic plans and policies and building systems to address multiple diseases; (2) establishing public-private partnerships; (3) ensuring effective leadership, commitment, and coordination by host governments of efforts of donors and partners; (4) establishing and/or strengthening centers of excellence and field epidemiology and laboratory training programs to meet short- and medium-term training and retention goals; and (5) establishing affordable, scalable, and effective laboratory accreditation schemes to ensure quality of laboratory tests and bridge the gap between clinicians and laboratory experts on the use of test results.

Origins and Development of the National Laboratory System for Public Health Testing

Although not recognized as such, a National Laboratory System (NLS) has existed since the inception of public health laboratory (PHL) testing more than a century ago. The NLS has always relied upon the participation of clinical laboratories, both to report test results that represent public health threats and to submit specimens and isolates to PHLs for additional or confirmatory testing. Historically, a number of factors have hindered the strengthening of the relationships between clinical laboratories and PHLs, but the reality of bioterrorism and subsequent focus on strengthening public-private relationships has stimulated the development of a more robust NLS. Since 2002, there has been substantial strengthening of the NLS through the sharing of lessons learned from several demonstration projects. There is a growing emphasis on defining critical elements of the NLS, including the State Public Health Laboratory System (SPH Laboratory System) and the functions of the Laboratory Program Advisor, a position that every state should have at the center of its laboratory system's capacity-building. Additional strengthening of the NLS is occurring through (1) national biennial measurement of state PHLs' abilities to meet the Core Functions and Capabilities of State PHLs, (2) the new Laboratory System Improvement Program (L-SIP) for the SPH Laboratory System, and (3) sharing ideas to integrate and improve the SPH Laboratory System (e.g., using the L-SIP Online Resource Center). Public health emergencies, such as the recent H1N1 epidemic, illustrate and reinforce the need for a strong NLS within which federal, public health, and clinical (i.e., hospital and private reference) laboratories function in close collaboration.

Leadership Principles for Developing a Statewide Public Health and Clinical Laboratory System

In 1999, the Centers for Disease Control and Prevention (CDC), the Association of Public Health Laboratories (APHL), and the Federal Bureau of Investigation established the national Laboratory Response Network (LRN) for bioterrorism readiness. A more broad application of the LRN is the National Laboratory System (NLS), an effort to promote the 10 Essential Public Health Services and the Core Functions and Capabilities of State Public Health Laboratories (hereafter, Core Functions). State public health laboratories (PHLs) are responsible for leading the development of both the LRN and the NLS in their jurisdictions. Based on the experience of creating a laboratory network in Wisconsin, leadership principles are provided for developing and strengthening statewide laboratory networks of PHLs and clinical laboratories, which can also include point-of-care testing sites. Each state PHL, in the context of these Core Functions and leadership principles, sets its priorities, budgets, and strategic plans. For a limited investment of personnel and funds that will yield a large benefit to public health, a robust state laboratory system can be established.

The State Public Health Laboratory System

This article describes the development since 2000 of the State Public Health Laboratory System in the United States. These state systems collectively are related to several other recent public health laboratory (PHL) initiatives. The first is the Core Functions and Capabilities of State Public Health Laboratories, a white paper that defined the basic responsibilities of the state PHL. Another is the Centers for Disease Control and Prevention National Laboratory System (NLS) initiative, the goal of which is to promote public-private collaboration to assure quality laboratory services and public health surveillance. To enhance the realization of the NLS, the Association of Public Health Laboratories (APHL) launched in 2004 a State Public Health Laboratory System Improvement Program. In the same year, APHL developed a Comprehensive Laboratory Services Survey, a tool to measure improvement through the decade to assure that essential PHL services are provided.

Systematic review of antibiograms: A National Laboratory System approach for improving antimicrobial susceptibility testing practices in Michigan.

Public health surveillance is often dependent on sentinel testing performed in clinical microbiology laboratories, and recognition of emerging/ unusual antimicrobial resistance is especially challenging. We obtained cumulative antibiograms from hospitals to determine whether clinical laboratories recognized unusual resistance or reported antimicrobials inappropriate for various bacterial species, as measured before and after public health laboratory (PHL) educational and technical-support interventions. We compared cumulative antibiogram data from 81 clinical laboratories servicing 86 hospitals in Michigan from 2000 through 2005 with a standardized checklist derived from Clinical and Laboratory Standards Institute (CLSI) antimicrobial susceptibility testing (AST) documents. We considered the reporting of unlikely percent-susceptible results and/or inappropriate antimicrobials serious errors, and we calculated error rates for each data year. We used CLSI-recommendation compliance as a measure to determine whether laboratories were implementing changes. Ninety-five of 239 (28%) cumulative antibiograms examined had one or more serious errors. The annual number of cumulative antibiograms with serious errors did not change radically (range: 10-13); however, when expressed as a percentage of cumulative antibiograms received, the occurrence of these errors declined from 59% in 2000 to 19% in 2005. The reporting of misleading or dangerous antimicrobial-organism combinations occurred less frequently than the reporting of unlikely percent-susceptible results. Compliance with new CLSI recommendations did not improve significantly. AST is complex and nuanced. PHL programs can provide resources, guidance, and technical support to help clinical microbiologists differentiate questionable AST results from true emerging antimicrobial resistance.

On the Search for Nuclear Resonance Fluorescence Signatures of $^{235}{\rm U}$ and $^{238}{\rm U}$ Above 3 MeV

Nuclear resonance fluorescence is a physical process that provides an isotope-specific signature that could be used for the identification and characterization of materials. The technique involves the detection of prompt discrete-energy photons emitted from a sample that is exposed to photons in the MeV energy range. Potential applications of the technique range from detection of high explosives to characterization of special nuclear materials such as 235U. Pacific Northwest National Laboratory and Passport Systems have collaborated to conduct a a pair of measurements to search for a nuclear resonance fluorescence response of 235U above 3 MeV and of 238U above 5 MeV using an 8 g sample of highly enriched uranium and a 90 g sample of depleted uranium. No new signatures were observed. The minimum detectable integrated cross section for 235U is presented.

An e-health driven laboratory information system to support HIV treatment in Peru: E-quity for laboratory personnel, health providers and people living with HIV

BackgroundPeru has a concentrated HIV epidemic with an estimated 76,000 people living with HIV (PLHIV). Access to highly active antiretroviral therapy (HAART) expanded between 2004-2006 and the Peruvian National Institute of Health was named by the Ministry of Health as the institution responsible for carrying out testing to monitor the effectiveness of HAART. However, a national public health laboratory information system did not exist. We describe the design and implementation of an e-health driven, web-based laboratory information system - NETLAB - to communicate laboratory results for monitoring HAART to laboratory personnel, health providers and PLHIV.MethodsWe carried out a needs assessment of the existing public health laboratory system, which included the generation and subsequent review of flowcharts of laboratory testing processes to generate better, more efficient streamlined processes, improving them and eliminating duplications. Next, we designed NETLAB as a modular system, integrating key security functions. The system was implemented and evaluated.ResultsThe three main components of the NETLAB system, registration, reporting and education, began operating in early 2007. The number of PLHIV with recorded CD4 counts and viral loads increased by 1.5 times, to reach 18,907. Publication of test results with NETLAB took an average of 1 day, compared to a pre-NETLAB average of 60 days. NETLAB reached 2,037 users, including 944 PLHIV and 1,093 health providers, during its first year and a half. The percentage of overall PLHIV and health providers who were aware of NETLAB and had a NETLAB password has also increased substantially.ConclusionNETLAB is an effective laboratory management tool since it is directly integrated into the national laboratory system and streamlined existing processes at the local, regional and national levels. The system also represents the best possible source of timely laboratory information for health providers and PLHIV, allowing patients to access their own results and other helpful information about their health, extending the scope of HIV treatment beyond the health facility and providing a model for other countries to follow. The NETLAB system now includes 100 diseases of public health importance for which the Peruvian National Institute of Health and the network of public health laboratories provide testing and results.

Emerging Infections: Implications for Sentinel and Public Health Laboratories

After reading the popular novel, “The Cobra Event,” then U.S. President Bill Clinton, concerned with the prospect of use of a biologic agent against the United States, issued Presidential Directive 39. This executive act resulted in the formation of the Laboratory Response Network (LRN), a structured consortium of clinical, governmental, and public health laboratories. The LRN became operational in August 1999, and though few in the laboratory field noticed its birth, by the fall of 2001 and the anthrax letter events, the alliance of clinical and public health laboratories was becoming a reality. The LRN provided the framework for much closer cooperation between clinical (sentinel) laboratories and their public health counterparts and set the stage for a cooperative approach to the ever-evolving list of emerging infections. Subsequently, the National Laboratory System program has been added to reinforce this framework.

Laboratory Challenges in the Scaling Up of HIV, TB, and Malaria Programs

Strengthening national health laboratory systems in resource-poor countries is critical to meeting the United Nations Millennium Development Goals. Despite strong commitment from the international community to fight major infectious diseases, weak laboratory infrastructure remains a huge rate-limiting step. Some major challenges facing laboratory systems in resource-poor settings include dilapidated infrastructure; lack of human capacity, laboratory policies, and strategic plans; and limited synergies between clinical and research laboratories. Together, these factors compromise the quality of test results and impact patient management. With increased funding, the target of laboratory strengthening efforts in resource-poor countries should be the integrating of laboratory services across major diseases to leverage resources with respect to physical infrastructure; types of assays; supply chain management of reagents and equipment; and maintenance of equipment.

Establishing a Simple and Sustainable Quality Assurance Program and Clinical Chemistry Services in Eritrea

As chronic diseases become more prevalent in developing nations, establishment of sustainable clinical chemistry services will become increasingly important. The complexity of automated instruments, coupled with a lack of resources and skilled workers, will present a challenge for these countries. A system emphasizing simplified instrumentation, single source reagents, technical education and support, and simple QC algorithms was established in the small African nation of Eritrea. The same reagents were used on different analyzers, as well as the same lot numbers of QC material. To allow traceability of Eritrea results to an accredited US laboratory, the reagents and QC materials were identical to those used in a large university hospital in the US, and patient samples were frequently exchanged between locations. QC values for 23 clinical chemistry tests in the Eritrean National Health Laboratory compared well to values obtained in the US, showing some statistically different values but no clinically significant differences. QC values were also stable over time in Eritrea. Patient sample values from Eritrea correlated well to values from the US, with r values ranging from 0.71 to 0.99. For 9 chemistry tests, small regional laboratories in Eritrea produced QC and patient values that usually compared well to those from the Eritrea National Health Laboratory, but markedly discrepant values were occasionally observed that prompted investigation. A simple but sustainable national laboratory system has been established in the developing nation of Eritrea.

Workforce Challenges in Our Public Health Laboratory System

Public health laboratories lie at the intersection of 2 vital components of the United States health system (ie, the public health system and the national laboratory system). Unfortunately, both of these components of the health system are somewhat hidden from public view and from the eye of policymakers. The public health system with its focus on populations, disease prevention, environmental protection, and emergency response is overshadowed by the more visible and resource-intensive health care system that deals with personal health. Likewise, the clinical and public health laboratory professionals who make up our national laboratory system are frequently overshadowed by the more visible health professions such as medicine and nursing. Much has been written about the critical workforce challenges and shortages facing public health generally 1-6 and clinical laboratories 7-16 but not about public health laboratories. Although public health laboratories in the United States are found in federal, state, and local health agencies, the description of their core functions has only been formally defined for states. Public health laboratories play a vital role in the support of essential public health services such as disease surveillance, environmental protection, food safety, and emergency response including terrorism response. 17 Specific steps must be taken to ensure that vital public health laboratory workforce needs are addressed.

Policies in place throughout the world: action by the European Union

Policies in place throughout the world: action by the European Union

Demonstrating Data and Test Result Validity for Diagnostic Aquatic Animal Health Laboratories

AbstractThe information in this article is aimed towards the managers in laboratories that conduct testing in support of aquatic animal disease diagnosis or the determination of health status. This includes laboratories that do regulatory work—directly or indirectly—those who do testing for trade, and those who will be required to respond swiftly and effectively in the case of a national animal health emergency. The ability to demonstrate validity is essential for national security, protection of public and animal health, minimization of liability, and support of business and trade. Veterinarians, wildlife specialists, and aquatic animal health specialists may also find it valuable, as many points are directly pertinent to the establishment of a quality program in a clinical or individual practice laboratory. Data and test result validity are critical to timely and accurate diagnosis and treatment, effective disease and health management, reliable surveillance, and quick, appropriate responses in the event of an animal health emergency. There are currently four general areas of importance regarding the demonstration of data and test result validity: The conduct of testing; the use of valid, approved test methods; proficiency testing; and the use of reference materials. Demonstration of validity is achieved via the implementation and use of appropriate and documented technical, operational, and managerial policies, systems, procedures, and specifications that are scientifically sound, that meet the requirements of relevant third‐party consensus standards, and that can be verified by recognized, third‐party accreditation. The basis for the requirements of laboratory accreditation and accreditation body recognition programs in the United States and internationally that address these areas of analytical endeavor is discussed. Recent legislation and activities in establishing a unified national system of accreditation that meets applicable international standards may assist in creating national laboratory systems capable of effectively addressing data and test result validity and credibility in critical diagnostic areas.

The art of science at Fermi National Accelerator Laboratory: The rhetoric of aesthetics and humanism in the national laboratory system in the late 1960s

This paper examines how rhetoric shaped the early history of the National Accelerator Laboratory. In a situation defined by a contentious site search and shrinking budgets for research, Robert Wilson crafted an institutional identity for the NAL that emphasized both aesthetic and scientific experience. The paper addresses the circumstances of the laboratory's founding, the "audiences" important to its success, and the ways in which the physical environment and management structure--framed by Wilson's vision of a scientific utopia--reorganized existing perceptions of physics within a humanistic framework intended to distinguish the NAL from its predecessors in the National Laboratory system.

Toward a national laboratory system for public health.

Toward a national laboratory system for public health.

FUNDAMENTAL INVESTIGATIONS OF SEPARATIONS SCIENCE FOR RADIOACTIVE MATERIALS

ABSTRACT Fundamental investigations of solvent extraction and ion exchange separations of radioactive materials have been conducted within the National Laboratory system of the U. S. Department of Energy (and its predecessor agencies) for the past 50 years. Basic research conducted at Oak Ridge and Argonne National Laboratories has produced both high quality new science and important applications in nuclear technology. The present contribution is an attempt to summarize the most important scientific results arising from this research during the past 10 years, a time of great change in the nuclear separations field, and to suggest possible directions for the next stage of research and development in this field.

Secret Science: A Classified Community in the National Laboratories

American scientists acceded to the imposition of secrecy in a pragmatic andpatriotic adjustment to the context of the Cold War. Scientists and managersin the national laboratory system accommodated the demands of nationalsecurity within a classified community, composed of a system of secretconferences, publications, and interlocking committees.

Advances in the automated detection of metaphase chromosomes labeled with fluorescence dyes

Applications of fluorescence in situ hybridization (FISH) for translocation studies and biological dosimetry would benefit substantially from reliable and efficient automatic detection of metaphase chromosomes labeled with fluorescent dyes. We replicated and evaluated a fluorescence metaphase finder previously developed at the Medical Research Council (MRC), Human Genetics Unit (Scotland) and at Lawrence Berkeley Laboratory (LBL; California). The MRC/LBL system seemed to detect nearly all of the metaphases on the test slides, but it presented an unacceptable number of false positives (about five false positives per one true positive). Furthermore, we determined that the system actually overcalled true detections by counting certain metaphase spreads twice (duplicates). Through modifications of the MRC/LBL system, we developed the Lawrence Livermore National Laboratory (LLNL) system, which minimizes the detection of duplicates, incorporates new detection features, uses a binary decision tree (BDT) for classification, and provides functionalities to improve scanning accuracy and improve the post-detection review. To test the new system, DAPI-stained preparations of metaphase chromosomes from blood lymphocytes of four unrelated donors were placed on slides in drops ranging from 7 mm to 20 mm in diameter. Drops contained between 5 and 200 scorable metaphases each. The LLNL system achieved approximately 90% detection of non-duplicated metaphases as verified by an expert cytogeneticist, with typically less than one false positive per every one true positive detected.