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Field Experience in Implementing ISO 15189 in Kisumu, Kenya

Clement E. Zeh, Seth C. Inzaule, Valentine O. Magero, Timothy K. Thomas, Kayla F. Laserson, Clyde E. Hart, John N. Nkengasong on behalf of the KEMRI/CDC HIV Research Laboratory
DOI: http://dx.doi.org/10.1309/AJCPZIRKDUS5LK2D 410-418 First published online: 1 September 2010

Abstract

Quality medical laboratory services are an integral part of routine health care, medical research, and public health systems. Despite this vital role, quality laboratory services in Africa are scarce. The crucial need for expanding quality laboratory services throughout sub-Saharan Africa is especially critical because of the region’s burden of disease. Fortunately, several plans from supporting international partners are underway to help strengthen laboratory infrastructure in this region. A key component of these initiatives is the enforcement of quality assurance services through accreditation by international standards such as the International Organization for Standardization (ISO) 15189. However, acquisition and maintenance of these standards are a significant challenge, especially in resource-limited settings. The most common limiting factors can include funding, government support, equipment, training opportunities, and poor procurement infrastructure. In this article, we discuss the challenges and benefits accrued in pursuing and sustaining ISO 15189 accreditation for the Kenya Medical Research Institute/Centre for Disease Control HIV-Research Laboratory in Kisumu, Kenya.

Key Words:
  • ISO 15189 implementation
  • Laboratory quality assurance
  • Quality management systems

HIV, malaria, and tuberculosis continue as diseases of great public health concern, especially in resource-limited countries.1 A variety of multinational organizations have undertaken immense efforts to develop strategies to combat these diseases. Such efforts have included vaccine research and other prevention research and service delivery in such areas as HIV testing and treatment. Great success has been reported from some of these initiatives, as is the case with the rollout of antiretroviral therapy (ART) in resource-limited settings, where at least 4 million people are currently receiving therapy.2,3 However, much emphasis has been placed on the quantity of services, as seen for example in the World Health Organization (WHO) “3 by 5” initiative, which aimed to have 3 million people receiving ART by 2005 and, more recently, universal access by 2010.

Unfortunately, less concern has been given to quality-assured scale-up and ways of ensuring long-term ART efficacy.4 Development of a quality health care system is essential for successful scale-up of ART and to support clinical research in resource-limited regions. This includes upgrading laboratory services to ensure accurate disease diagnosis, efficient treatment monitoring, good public health disease surveillance, and effective clinical research. Plans are already underway to help strengthen national laboratory systems in Ethiopia, Nigeria, Tanzania, and other countries.5,6 The key areas for development include the national laboratory network, physical infrastructures, supply-chain management, human resource training programs, and quality service delivery. Providing quality services that are accurate, reliable, and reproducible will most effectively come through adopting laboratory standards that guide daily laboratory practices and institute a framework for quality management at the facility and network levels.

The International Organization for Standardization (ISO) 15189 (medical laboratories: particular requirements for quality and competence), a hybrid of ISO/IEC 17025 and ISO 9001 management standard, is the current internationally recognized standard for medical laboratory practice.7 This standard provides a framework for a laboratory to plan and operate a medical testing laboratory with an effective quality management system (QMS) that has strong elements of quality assurance (QA), quality control, and quality improvement. It not only focuses on assay performance, but also has a holistic approach for global medical patient care, targeting all processes from preanalytical to postanalytical procedures. It further encompasses personnel laboratory safety and medical laboratory ethics. An award of ISO 15189 accreditation is a formal international recognition that a laboratory performs medical laboratory tests that are reliable, accurate, and reproducible and that the results are reported within an acceptable time frame.

In this article, we discuss the challenges and benefits accrued in pursuing and sustaining ISO 15189 accreditation for the Kenya Medical Research Institute (KEMRI)/Center for Disease Control (CDC) HIV-Research Laboratory in Kisumu, Kenya.

Background on the KEMRI/CDC HIV-Research Laboratory

The KEMRI/CDC HIV-Research Laboratory was established in March 2003 to provide support to KEMRI/CDC-sponsored HIV epidemiologic and clinical research. This research included a survey to assess HIV prevalence among adolescents and adults and a therapeutic clinical trial aimed at preventing mother-to-child transmission. Since 2003, the laboratory has grown tremendously and supports multiple HIV studies initiated by KEMRI/CDC and other collaborative groups, including the WHO. Currently the laboratory has 2 main sections: the clinical laboratory section based at the KEMRI/CDC clinical research center on the campus of New Nyanza Provincial General Hospital in Kisumu and the molecular diagnosis and research laboratory section located at the KEMRI/CDC Field Station in Kisian, about 12 km from Kisumu. These sections are further subdivided into various units in which a variety of HIV and sexually transmitted infection diagnostics and monitoring tests are done Table 1.

The KEMRI/CDC HIV-Research Laboratory is certified by the Kenya Medical Laboratory Technician and Technology Board and the RUSH virology QA program (Chicago, IL) for molecular assays. In addition to ISO 15189 certification, the laboratory is WHO accredited as the national reference laboratory for HIV drug-resistance testing in Kenya.

Journey Toward Accreditation

Pursuing ISO 15189 accreditation was a major challenge; it required the revision of existing or development of new systems, while at the same time continuing to provide laboratory support for ongoing HIV research activities. The preparation for accreditation was a collective work involving the entire staff under the guidance of the laboratory management. We commenced the process in March 2006, with the aim of improving overall client services and to meet the criteria required to participate in the proposed US National Institutes of Health–funded Partnership for AIDS Vaccine Evaluation 100 HIV vaccine trials (http://www.cdc.gov/hiv/topics/research/vaccine_unit/index.htm). We first began by outsourcing consultation services from the South African Contract Laboratory Services, who helped us in identifying ISO 15189 as the appropriate international accreditation standard for our laboratory. Contract Laboratory Services conducted an initial gap analysis of our laboratory QMS and advised us on ways to implement the standard requirements. We established an independent quality systems unit (QSU) to help evaluate the areas of improvement as guided by the gap analysis report from Contract Laboratory Services. The QSU developed various documents and systems, including the laboratory quality manual, quality policies, various standard operating procedure manuals, staff competency assessment guidelines, complaint/incidence reporting systems, quality indicator systems, internal QA auditing systems, and documents and records control systems.

Following the ISO 15189 requirements, we began enrolling our assays in external QA programs: the College of American Pathologists, the Virology Quality Assurance program, the United Kingdom National Quality External Assurance Services, and the Humane Quality Assurance Services. We instituted an advisory board, staffed by clinical laboratory and QA experts, whose purpose was to review and provide counsel for our laboratory’s QA and QMS activities. Other units that were established or improved as a requirement for the ISO 15189 included the safety unit, procurement unit, data management unit, and the training coordination group. In addition, a laboratory information management system was adopted to streamline sample reception and repository and tracking. We also installed and verified an automated temperature monitoring system to ensure integrity of samples and reagent storage. Following all these preparations, we requested ISO 15189 certification from the South Africa National Accreditation System (SANAS). In July 2007, before the SANAS assessment visit, our laboratory was assessed by Pharmaceutical Product Development (PPD), contracted by the US National Institutes of Health to assess the site’s preparation for Partnership for AIDS Vaccine Evaluation 100 HIV vaccine trials. PPD identified 75 nonconformances (17 major and 58 minor) Figure 1. Addressing these nonconformances helped us in preparing for the SANAS assessment in October 2007, in which only 23 nonconformances (11 major and 12 minor) were identified. These were addressed within the required time of 25 working days. In March 2008, 2 years after commencing the journey, we were awarded full accreditation and became the first ISO 15189–accredited independent laboratory in Kenya.

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Table 1

Challenges on the Road Toward Accreditation

Although the benefits of accreditation are numerous, the journey toward accreditation had a number of challenges. Establishing the various standard quality requirements was expensive and labor-intensive. Lack of trained personnel, especially in quality system essentials and good clinical laboratory practices, coupled with the lack of professional trainers in the country, required contracting trainers from abroad, and this was costly. In addition, all equipment had to be placed on preventive and corrective maintenance service contracts, which were also costly. Owing to lack of laboratory equipment engineers among local vendors, some services had to be provided by out-of-country contractors. Implementing an efficient procurement infrastructure was also challenging, in part owing to stringent government procurement laws and the fact that many reagents are unavailable in Kenya. There were challenges in implementing safety standards such as waste management owing to the absence of or unclear government policies on disposal of certain waste products. A major hurdle was the nurturing of a quality culture, previously lacking among the staff. The adoption of this standard required major alterations in the daily laboratory operations, which were not initially welcomed by staff. However, regular training with emphasis on postaccreditation benefits and persistence by the QSU led to increased understanding and cooperation.

Figure 1

Preaccreditation and postaccreditation external audit findings by South Africa National Accreditation System (SANAS) and Pharmaceutical Product Development (PPD). Accreditation occurred in March 2008. Major nonconformances (NCs) are deviations from the standard indicative of a total breakdown in the system or one that would significantly affect the patients’ results, whereas minor NCs are those that are indicative of partial breakdown in the system.

Essential Elements for Managing an Accredited Laboratory

Obtaining accreditation is not a certificate to practice but an assurance for providing quality services. Consequently, maintaining high-quality standards is equal in importance to achieving them. Some of the key elements adopted in maintaining quality standards included establishing a well-organized laboratory management system, strengthening of the QSU, establishing a laboratory technical advisory committee, establishing and monitoring laboratory quality indicators, and promoting continuous quality improvement.

Establishing a Well-Organized Laboratory Management System

A component of the QA laboratory infrastructure is a well-organized management system. Our laboratory management system is headed by the chief of HIV research at KEMRI/CDC, followed by the laboratory director and laboratory supervisors, and ends with the unit heads. Each job title in the management structure has distinct responsibilities that are well documented in the quality manual. The unit heads primarily oversee the daily operations of the laboratory activities and are involved in the development, implementation, maintenance, and improvement of quality systems in their specific units. There are 2 section supervisors (the research section supervisor and the clinical and monitoring section supervisor) who oversee the activities implemented by the different units’ heads and act to advise and direct the quality plans being implemented in the different units. The laboratory director reviews and approves all technical and management quality plans established by the technical staff, laboratory supervisors, safety staff, data staff, administrative and procurement staff, and the quality systems unit and ensures a good working environment that complies with good clinical laboratory practices. The chief of the HIV research branch functions at an independent level from the laboratory and periodically reviews laboratory activities with a focus on assigned laboratory projects in progress and a biannual review of the laboratory’s QMS.

All levels of laboratory management are charged with ensuring that continuous communication exists among the staff so that complaints can be quickly identified, addressed, and resolved. To this end, the management and all laboratory personnel attend regular biweekly laboratory meetings in which progress in every unit is assessed and any challenges are addressed. In addition, the biweekly meetings provide an open forum for presenting problems and opportunities for improvement.

Strengthening of the QSU

A cornerstone of laboratory QA infrastructure is the QSU. Owing to this unit’s central role in maintaining and improving laboratory QA, our QSU was made independent of routine laboratory management supervision and reports directly to the laboratory director and the chief of the HIV research branch at KEMRI/CDC. This reporting scheme was particularly important to ensure the unit’s autonomy in monitoring the laboratory QA and management systems. Continuous training, provided through local and international mentorship programs, also helped expand personnel competency in the unit. To further aid the implementation and maintenance of QA, many of the quality systems activities were decentralized to the technical units where the unit heads became fully responsible for QA in their specific units. These measures supported the “ownership” of the standard by technical personnel and reduced discord between the technical units and the QSU. The unit holds regular meetings with laboratory management to advise on areas requiring improvement. Apart from regular internal meetings, the QSU also participates in formal in-country QA meetings every 3 months with other local research laboratories, the US Army Medical Research Unit laboratory at Kericho, Kenya, and the Academic Model Providing Access to Healthcare laboratory in Eldoret, Kenya, to assess ways for improving and maintaining quality standards.

Establishing a Laboratory Technical Advisory Committee

Another key activity was establishing a technical advisory committee composed of laboratory experts from the CDC, Atlanta, GA; principal investigators, pathologists, other physicians (medical), and laboratory QA experts from outside the CDC; and our laboratory management team. This committee meets annually to review key quality management indicators set by the laboratory and to assess opportunities for improvement.

Establishing and Monitoring of Laboratory Quality Indicators

Quality indicators form an integral part of the QMS and are vital for objective monitoring of the laboratory quality systems and for identifying improvement opportunities. The quality indicators chosen in our laboratory involve assessing the following 7 parameters:

  1. Quality management assessment: The laboratory’s project targets are periodically assessed to monitor whether the set targets were achieved within their allocated time. Overall QA is also assessed using findings from internal and external audits.

  2. Resource utilization and financial performance: The laboratory’s budget for a fiscal year is assessed against the achieved targets, and resource utilization is reviewed against the set targets. Apart from overall assessment of resource utilization, unit-specific checks are done via the unit’s inventory system. Reagent control is monitored using reagent tracking logs, and stock management is done by assessing our reorder levels in the inventory. Supplier performance is monitored using score sheets that assess parameters such as delays and damaged or incorrect supplies. Procurement performance is assessed by checking on timely ordering, follow-up, and delivery of laboratory supplies and reagents.

  3. Process efficiency and effectiveness: The entire laboratory’s processing systems are monitored from preanalytical to analytical and postanalytical components. Parameters such as turnaround time, rate of sample rejection, control failures, process documentation assessment, instrument performances, external QA performance, personnel competency assessment, corrective and preventive action assessment, daily quality control plots, daily temperature monitoring charts, internal and external audit findings, and internal and external complaints are used in this assessment.

  4. Risk management and safety: Incidence reports are assessed over time and also include periodic safety drills, quizzes, and audits.

  5. Client satisfaction: Service delivery to clients is checked by assessing the number of complaints, turnaround time, and feedback.

  6. Personnel performance and satisfaction: This component involves staff competency assessment, training program attendance and completion assessment, staff turnover rate, supervisor appraisals, and analysis of internal complaints.

  7. Data management: This parameter involves periodic check of data integrity, ease of data retrieval, and the frequency of data backup.

Promoting Continuous Quality Improvement

A key component of good laboratory management is the continuous promotion of quality improvement. Establishing quality standards requires a conscientious assessment and informed implementation via multiple approaches, which usually takes time. Furthermore, relying solely on recommendations from external auditors and consultants can be misleading because they usually have limited time on site and are likely unable to identify all the significant improvement opportunities in the laboratory’s quality systems. Thus, it is paramount to identify and monitor improvement opportunities through a scheduled routine assessment of quality indicators. This continuous quality improvement has borne fruits as seen in the number of nonconformances identified during the postaccreditation assessment by SANAS and PPD (Figure 1). In addition, working closely with management, the QSU routinely assesses areas requiring improvement using internal and external audit findings and information provided by local peers and mentors.

Accreditation Benefits

Establishing standardized operations for technical support and laboratory management has led to a well-organized laboratory with clear staff responsibilities and a good communication framework. It has also led to the creation of a reliable and competent workforce that has high esteem and pride in their daily activities. The adoption of these standards has led to a greater degree of internal control, a good tracking system for all laboratory processes, an efficient and controlled documentation system, and a reliable infrastructure for tracing errors and complaints.

The adoption of key quality indicators has helped in timely identification of system weaknesses and rapid resolution of problems. The adoption of this standard has also assisted us in rapidly detecting redundant and ineffective systems, leading to reduction in operation costs and increased time savings.

A major benefit in the adoption of these standards was the reduction in reagent wastage leading to increased cost savings to the laboratory. The assessment of reagent wastage from the preaccreditation period (July 2006) through the postaccreditation time revealed a remarkable decline in reagent waste Figure 2. These cost savings came about largely because of increased staff competency and an effective inventory system. The enhanced staff competency resulted in a reduction in redundant retesting, thereby saving on reagents and supplies. The effective inventory system enabled accurate forecasting on reorder levels and helped facilitate interlaboratory exchange of reagents before expiration, therefore minimizing reagent waste.

In addition, there has been a profound improvement in our performance on external quality proficiency testing. This improvement was due to our increased staff competency and an assay validation requirement that ensures reproducibility of the given tests.

Having a well-designed and implemented QMS, based on ISO 15189, has helped the laboratory create an infrastructure that provides accurate, reliable, quality, and timely service delivery. This has led to an increase in our clients’ and stakeholders’ confidence, which is reflected in the reduction in number of complaints. In assessing the number of complaints over time from the preaccreditation to the postaccreditation period, we observed a remarkable decline of 82% within the first 12 months of the accreditation preparation period that has since been maintained at levels below 5% Figure 3.

Figure 2

Reduction in the waste of reagents. Accreditation occurred in March 2008.

Figure 3

Trends in the number of complaints from January 2006 (preaccreditation) to January 2009 (postaccreditation). Accreditation occurred in March 2008.

Another benefit observed after adoption of these standards was a reduction in sample rejection. Before standards implementation, there was a high rate of sample rejection owing to lack of clear rules for sample reception and rejection. The implementation of this standard led to a significant percentage decrease in the number of sample rejections from 4.5% in 2006 to less than 1% in 2007 Figure 4. This improvement was due to an improvement of preanalytical QA, largely from defined systems for sample collection and transportation. Our laboratory currently has a policy on retraining clients in the field on QA regarding field preanalytical processes when the rate of sample rejection exceeds 3% at a given site. This low rate of sample rejection further enhanced reduction in complaints from clients.

Our newly recognized standard of excellence has also increased demand for the services offered, as well as QA training and postacademic field training from KEMRI/CDC-affiliated groups, the Ministry of Health, private health institutions, and students in the region.

Adopting the ISO 15189 standard has greatly assisted the KEMRI/CDC HIV-Research Laboratory in pursuing and achieving WHO accreditation for HIV drug-resistance genotyping in less than 6 months during 2008. Our selection as the national WHO reference laboratory for HIV drug resistance has led to increased international acceptance of our services, reduced the need for international reference testing for drug-resistance tests, and, thus, reduced the cost for patients and ongoing clinical trials in the region.

In summary, accreditation benefits are numerous, including reduction in costs, ease in management and process control, increased quality service delivery and client satisfaction, and enhanced staff competency.

Figure 4

Percentage of samples rejected from the preaccreditation period to the postaccreditation period. Accreditation occurred in March 2008.

Postaccreditation Issues

As noted previously, the accreditation certificate acts as an identity for QA services and implies that all processes from this point forward are carried out within certain standards. Consequently, to ensure quality service delivery, the standards must be maintained or, better yet, superseded, which may sometimes offer certain challenges. In our case, the challenges included staff retention and hiring of a motivated and qualified staff. Owing to the increased training and enhanced competency and experience of our staff members, they are now coveted by other laboratories in our region. Subsequently, it is becoming more difficult to find and retain the highly skilled personnel who are needed to maintain the accredited standards now in place in our laboratory. This lack of local trained personnel underlies the need for improving the skills of the country’s entire local health and research scientist workforce.

In addition, there are challenges in maintaining a reliable procurement infrastructure that provides a timely supply of commodities at a manageable cost. This problem is compounded because most laboratory commodities must come from out-of-country vendors. These vendors frequently batch the orders of multiple laboratories to reduce shipping costs. If the goods are damaged or erroneously delivered, additional delays occur, often for frustratingly long periods because supplies must be reordered from overseas. Although interlaboratory borrowing or supply exchanges are viable solutions, the processes and platforms for the same tests vary among laboratories, thus limiting the use of such options. In addition, the stringent government procurement laws sometimes slow the procurement process.

The same procurement challenges affect equipment service maintenance. Apart from the high cost of annual and sometimes biannual preventive service of equipment, it is equally difficult to ensure timely corrective maintenance of equipment. This problem is usually due to limited availability of qualified engineers and replacement parts, which usually come from South Africa. This can lead to delays in service delivery, resulting in increased complaints from clients, which may lower staff morale.

Despite the many advantages achieved by accreditation, accreditation can lead to increased demands by clients in need of quality laboratory support; this can stretch the laboratory capacity to provide quality services and negatively impact the working environment for staff. In these instances, laboratory management carefully assesses how an additional workload would impact the KEMRI/CDC HIV-Research Laboratory mission and goals and then decides whether to accept or reject an outside client’s request.

Continuous improvement calls for continuous training of personnel, especially in good clinical laboratory practices, QA, and safety. Owing to the absence of local or online training for some courses, laboratory management has had to send staff overseas for training or contract tutors from abroad. To keep pace with the ever-changing elements of our scientific research and maintain a knowledge base equal to that of our peer groups, we have sent staff to local and international conferences, an approach that has high cost implications.

A major internal challenge is the continuous nurturing of the “culture of quality” that enables staff buy-in and ownership of our QMS. This has been an uphill task owing to the demands of the standards, such as the stringent requirement for proper documentation of all laboratory processes, which has been difficult owing to our large workload.

Informing and educating prospective clients on the need for quality standards adoption in the field has also not been an easy task. QA requires implementation of systems guiding preanalytical steps to help assess sample integrity and the adoption of a standardized test request and results reporting system. Owing to the high number of poor-quality samples necessitating rejection, it was vital to train our clients on better sample collection, transportation, and storage methods. It was equally important to train them on the laboratory requirements for test requests and result interpretation. Such programs have yielded positive results, but challenges still remain, with some sites requiring periodic refresher training. Communicating with clients on the increase in cost owing to the implementation of the given standards such as the annual or biannual equipment service maintenance and the increase in controls per test has also been challenging.

Implementation of Quality Standards in Resource-Limited Settings

Although it may be feasible, as in our situation, to implement and maintain international standards in laboratories situated in resource-limited settings, this may not be the case for most laboratories in Africa. The entire accreditation process did cost approximately US$126,553 in the initial phase and a further US$71,143 were required to effectively maintain the accreditation Table 2. These costs, however, exclude the required good clinical laboratory practices such as preventive and corrective equipment maintenance, the need for backup equipment, and other infrastructure maintenance, which are equally expensive. As observed, the accreditation process can be expensive and requires commitments, especially from the management team. The KEMRI/CDC laboratory is donor-funded and operates on a platform supported mainly by the CDC laboratory infrastructure. For this reason, we were able to address most of the impediments inherent in most resource-limited settings. Lack of local government support and health policies to ensure provision of quality health care, training programs, reliable equipment, and funding opportunities and the absence of a well-organized national laboratory network are some of the difficulties faced by public laboratories in resource-limited settings.8,9 These challenges make it difficult for laboratories in such regions to acquire internationally recognized accreditation. However, there is an increased need for quality laboratory services to support research programs and public health disease surveillance and to assist in early detection of emerging drug-resistant pathogens and new infectious diseases. As previously noted, various programs have been initiated to help strengthen the laboratory infrastructure systems in resource-limited settings, although such programs have been project-specific. A preferred system for implementation of quality standards in such regions would likely be the newly proposed WHO Regional Office for Africa laboratory accreditation system, which focuses on a stepwise improvement process in the strengthening of a national laboratory health care infrastructure over an unlimited time based on the laboratory’s capability in meeting the targets at different stages.10 If successful, this approach may be a better alternative to the ISO accreditation system, which focuses mainly on the assessment of implemented standards with a “pass or fail” verdict and requires standards be implemented within a short time frame.

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Table 2

Conclusion

The provision of quality medical laboratory services is vital for global patient care, disease surveillance, and clinical research. Laboratory accreditation gives a formal international recognition of quality laboratory services. This allows for improved health care, increased client confidence, and efficient service delivery, as well as well-organized management systems and other benefits. The acquisition and maintenance of these standards may, however, be especially challenging in resource-limited regions owing to impediments of inadequate funds, lack of government support, lack of harmonized and efficient policies to ensure easy procurement of laboratory commodities, and inadequate skilled staff and laboratory-oriented training opportunities. While some of these challenges may be overcome by private or donor-funded laboratories, it may be more difficult for government-funded laboratories. Even so, such laboratories may benefit from the proposed WHO Regional Office for Africa stepwise accreditation system that focuses on incremental quality advancements over time rather than the shorter periods required under ISO and similar accrediting programs.

Acknowledgments

We thank the HIV-R Laboratory staff who worked long hours in implementing and maintaining the ISO 15189 accreditation. We also thank the Kenya Medical Research Institute and Kenya Ministry of Health, whose participation made this possible.

Footnotes

  • Supported by the Division of HIV/AIDS Prevention-Surveillance and Epidemiology; National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta.

  • Disclaimer: The findings and conclusions in this article are those of the authors and do not necessarily represent the views of the US Centers for Disease Control and Prevention (CDC). Use of trade names is for identification purposes only and does not constitute endorsement by the CDC or the US Department of Health and Human Services.

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