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Developing and Expanding Contributions of the Global Laboratory Network for Poliomyelitis Eradication, 1997-1999

In 1988, the World Health Assembly resolved to eradicate poliomyelitis globally by 2000 (1). Substantial progress toward achieving this goal has been reported from all countries where polio is endemic (2,3), and three regions of the World Health Organization (WHO) (American Region, European Region, and Western Pacific Region) appear to be free of indigenous wild poliovirus transmission (4-6). One key strategy for polio eradication is establishing sensitive surveillance systems for polio (through notification of acute flaccid paralysis [AFP] cases) and poliovirus (7). To ensure that specimens from AFP cases undergo appropriate processing for viral isolation, WHO has established a global laboratory network. This report describes the proficiency of the network and provides updates on structure, accreditation, performance, expanding activities, and future plans.

In December 1999, the network was operational in all six WHO regions encompassing 148 laboratories, including 126 national (or subnational) laboratories, 16 regional reference laboratories, and six global specialized laboratories (Figure 1). Standard guidelines, procedures, cell lines, and reagents have been established and implemented in laboratories at each level of the network. National and subnational laboratories perform primary poliovirus isolation and typing for poliovirus types 1, 2, or 3. Regional laboratories conduct intratypic differentiation of poliovirus isolates as wild or vaccine-derived, and specialized laboratories conduct genomic sequencing to determine the molecular relation of poliovirus genotypes and to determine whether the viruses are indigenous or imported. A global laboratory network coordinator and regional coordinators in each region ensure technical and financial support* and the provision of standard reagents and equipment, if necessary.

During 1998-1999, the network's major focus was implementing an annual accreditation process formulated in 1997 to ensure high-quality laboratory support to the polio eradication initiative. Six accreditation criteria were used initially: 1) timeliness (proportion of test results reported within 28 days after receipt of specimens); 2) workload (process >150 stool specimens per year); 3) nonpolio enterovirus (NPEV) isolation rate; 4) serotyping of poliovirus isolates confirmed by regional reference laboratories; 5) proficiency testing; and 6) on-site review of operating procedures and work practices. Recognizing that the NPEV isolation rate is affected by latitude, altitude, hygiene, and climate, this accreditation criterion was removed, but documenting appropriate internal control activities for cell culture sensitivity was added to the list. As of December 1999, 108 laboratories (73%) were fully accredited, 16 (11%) were provisionally accredited, 14 (9%) have been reviewed and could not be accredited, and 10 (7%) were pending review. To ensure that all specimens from AFP cases are processed in accredited laboratories, including those  from countries without a laboratory, specimens should be shipped and processed in parallel in accredited laboratories. Only the Democratic People's Republic of Korea has no accredited laboratory nor access to such a laboratory outside the country.

To improve coordination among the laboratories in the network and timeliness of reporting results, another major focus was to ensure that each laboratory has adequate communication, including local communication to the respective ministries of health, and international communication by telephone, fax, or e-mail to other network laboratories and to the regional offices and headquarters of WHO. In December 1999, 123 (83%) laboratories had international telephone or fax lines and/or access to e-mail, but 25 (17%) laboratories had inadequate communication facilities.

During 1997-1999, the workload of the network more than doubled. The network processed approximately 50,000 specimens for viral isolation during 1999 (including 48,370 stool specimens from AFP cases only [Table 1]), isolated approximately 5000 polioviruses and approximately 10,000 NPEVs, carried out serotyping and intratypic differentiation on all poliovirus isolates, and provided genomic sequencing information on most wild poliovirus isolates. India and Nigeria illustrate the dramatic increase in laboratory workload (in India, from 5864 specimens in 1997 to 15,800 specimens in 1999, and in Nigeria, from 71 specimens in 1997 to 2534 specimens in 1999).

Reported by: Vaccines and Biologicals Dept, World Health Organization, Geneva, Switzerland. Respiratory and Enteric Viruses Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; Vaccine Preventable Disease Eradication Div, National Immunization Program, CDC.

Editorial Note:

During 1997-1999, the global laboratory network for polio eradication improved substantially. During 1999, almost all stool specimens from AFP cases were processed in WHO-accredited laboratories. The network exchanges information, standardizes techniques, and develops strategies to improve the information provided to eradication efforts. The accreditation process particularly has been useful in ensuring the quality of the procedures performed by network laboratories. Through these reviews, laboratories improve their adoption of standard procedures, improve data management, and identify methods to improve performance.

The polio laboratory network continues to evolve as the demands of the program change. To enhance further the timeliness of laboratory results, and recognizing the increased level of proficiency of many national laboratories, intratypic differentiation as wild or vaccine-derived poliovirus also has been carried out in selected national laboratories. These national laboratories have been provided with appropriate training and laboratory equipment and additional accreditation requirements. Whether a poliovirus isolate is wild has considerable implications in polio-free countries, and early institution of control measures is critical to prevent or minimize subsequent poliovirus transmission. Similarly, in countries where polio is endemic and poliovirus transmission is reduced increasingly to focal areas, early notification of wild virus can target resources to the most appropriate areas.

At the final stages of polio eradication, in addition to the timeliness of intratypic differentiation, the rapid availability of genomic sequencing data is another priority. Arrangements are being made by WHO to ensure that wild poliovirus isolates are shipped in a timely manner to specialized laboratories that have the capacity to sequence the isolates. Viral isolation, serotyping, intratypic differentiation, and genomic sequencing data have become increasingly relevant and important to guide programmatic action.

Despite the progress achieved in the network, additional efforts will be necessary to absorb the increasing workload anticipated once countries reached the minimum level of AFP performance (>1 case of nonpolio AFP per 100,000 population aged <15 years). Nigeria has demonstrated that laboratories need to be prepared to process huge numbers of additional specimens when surveillance activities improve substantially. Laboratories in Bangladesh and Ethiopia, where polio is endemic, have not yet been accredited. Although specimens from these countries can be processed in accredited laboratories elsewhere, these large countries should obtain the virologic capacity to process stool specimens.

The priorities in the network for 2000 are to establish intratypic differentiation in selected national laboratories, to sequence all wild-type poliovirus isolates, to complete the accreditation process, to improve the timeliness of all virologic procedures, and to contain wild poliovirus, a process that requires substantial, ongoing attention (8). The polio network has become a model for planning laboratory networks for other infectious disease-control initiatives. A measles laboratory network, functioning in the Region of the Americas, has an elimination target date of December 2000. Efforts are being made to develop such a network in the other regions of WHO, especially in the European and Eastern Mediterranean regions, both of which have adopted regional measles elimination target dates. Many of the laboratories selected for the polio eradication network will participate in the measles efforts. Similar efforts will be extended to rubella and other priority diseases.

Progress achieved by the network has demonstrated that high-quality virology in support of public health activities can be made accessible to all areas of the world, including war-torn countries and countries without organized government or health infrastructure. Although further development of the network is needed, the global capacity to process stool specimens can compensate for any national or regional bottlenecks. The improving capacity and performance quality of the network and accelerated vaccination efforts will provide critical data when wild poliovirus transmission has been interrupted globally.

References

  1. World Health Assembly. Global eradication of poliomyelitis by the year 2000. Geneva, Switzerland: World Health Organization, 1988 (WHA resolution no. 41.28).
  2. World Health Organization. Progress toward global poliomyelitis eradication, 1988-1997. Wkly Epidemiol Rec 1998;73:161-8.
  3. World Health Organization. Progress toward global poliomyelitis eradication, as of May 1999. Wkly Epidemiol Rec 1999;74:165-70.
  4. CDC. Certification of poliomyelitis eradication--the Americas, 1994. MMWR 1994;43:720-2.
  5. World Health Organization. Final stages of poliomyelitis eradication, WHO Western Pacific Region, 1997-1998. Wkly Epidemiol Rec 1999;74:20-4.
  6. World Health Organization Regional Office for Europe. One year since the last case of polio in the European Region. EURO Polio Page, November 1999 (special edition).
  7. Hull HF, Ward NA, Hull BP, Milstien J, de Quadros C. Paralytic poliomyelitis: seasoned strategies, disappearing disease. Lancet 1994;343:1331-7.
  8. Department of Vaccines and Biologicals. WHO global action plan for laboratory containment of wild polioviruses. Geneva, Switzerland: World Health Organization, 1999 (Reference WHO/V&B/99.32).

* Financial support for the network is provided by WHO; United Nations Children's Fund (UNICEF); Rotary International; UN Foundation; Department for International Development (DFID), United Kingdom; Japan International Cooperation Agency (JICA); the governments of Canada, Finland, Netherlands, Italy, the Republic of Korea, and the United States (through CDC and the U.S. Agency for International Development [USAID]); and American Association for World Health.


Table 1

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Figure 1

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