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Laboratory Surveillance for Wild and Vaccine-Derived Polioviruses, January 2002--June 2003
After the 1988 World Health Assembly resolution to eradicate poliomyelitis, the Global Laboratory Network for Poliomyelitis Eradication (the laboratory network) was established by the World Health Organization (WHO) (1). The laboratory network is one component of an international surveillance system for detecting polioviruses through laboratory investigation of stool samples from persons with acute flaccid paralysis (AFP). This infrastructure is critical for guiding strategies to eradicate polio globally (2--4). This report summarizes the laboratory network's performance and describes the location and characterization of wild poliovirus (WPV) and vaccine-derived poliovirus (VDPV) during January 2002--June 2003. The achievement and maintenance of polio eradication globally requires the continued support of national governments and partner agencies.
Laboratory Network Performance
The laboratory network covers all six WHO regions and comprises 145 laboratories whose responsibilities include poliovirus isolation, intratypic differentiation (ITD) to distinguish WPV and VDPV, and genomic sequencing. The network encompasses 123 national (83 national and 40 subnational), 15 regional, and seven international specialized laboratories. Laboratories report results weekly to national, regional, and international health authorities.
Laboratory performance quality is evaluated through a WHO accreditation program that includes proficiency testing, annual performance review, and use of standard indicators to evaluate the timeliness and accuracy of laboratory results. In 2002, of the 145 laboratories, 133 (92%) were fully accredited, 10 (7%) were provisionally accredited (reflecting satisfactory performance in proficiency tests but deficiency in another aspect of the work), and two (1%) were not accredited. While implementing measures to improve performance, nonaccredited laboratories split samples for parallel testing in accredited laboratories. During 2002--2003, all samples from persons with AFP were tested in WHO-accredited laboratories.
In 2002, network laboratories processed 71,478 specimens (Table 1), an increase of 10% compared with 2001 and 17% compared with 2000 (2). Despite this increased workload, targets for indicators measuring laboratory efficiency continued to be met, including percentage of cases with poliovirus isolation results available within 28 days of receipt of specimen (target: >80%) and percentage of differentiation results available within 60 days of onset of paralysis (target: >80%). In 2002, all regions met the 28-day target, and four regions (all except the African and Western Pacific regions) met the 60-day target. The proportion of specimens with nonpolio enterovirus (NPEV) isolated is used as a combined indicator of quality of specimen transport and sensitivity of laboratory processing; a rate of >10% usually is considered acceptable. The global NPEV isolation rates were 15% for 2002 and 12% for January--June 2003. The NPEV isolation rate was >10% for all regions except the European and Western Pacific regions. During January 2002--June 2003, genomic sequencing was performed for 90% of all WPVs. Genomic sequencing results usually were available within 2--4 weeks of virus detection, with the exception of viruses from India, where a large outbreak occurred and sequencing of all outbreak isolates was not necessary.
WPV was detected in nine countries during 2002 and in eight countries during January--June 2003 (Table 2). In 2001, WPV was detected in 15 countries. During January 2002--June 2003, both WPV type 1 (P1) and type 3 (P3) were detected in five countries (Afghanistan, India, Niger, Nigeria, and Pakistan), P1 was detected in five countries (Burkina Faso, Egypt, Ghana, Lebanon, and Zambia), and P3 was detected in Somalia (Table 2). The last WPV type 2 (P2) was detected in October 1999 from a patient in Uttar Pradesh, India (5). However, in India during late 2002--early 2003, P2 reference strains (MEF-1) were isolated from seven persons with AFP, one healthy child, and an environmental sample (6,7). MEF-1 is used commonly as a reference or control strain in various laboratory procedures or as the P2 component in production of inactivated polio vaccine. The isolation of MEF-1 from AFP cases in India is unusual; investigations are ongoing.
Among the 11 countries in which WPV was detected during January 2002--June 2003, genomic sequencing results indicated that seven countries (Afghanistan, Egypt, India, Niger, Nigeria, Pakistan, and Somalia) experienced indigenous transmission. Four countries experienced importations from countries in which polio is endemic; the Burkina Faso (2002) and Ghana (2003) viruses were imported from the Nigeria/Niger reservoir, the Lebanon (2003) virus from India, and the Zambia (2002) virus from Angola. Genomic sequencing results from the laboratory network have documented a steady reduction in the number of WPV genotypes. During 2001--2002, the number of surviving type-1 genotypes decreased from eight to four, and the number of surviving type-3 genotypes decreased from six to three.
The first known VDPV outbreak occurred in Hispaniola in 2000 (2); in January 2001, network laboratories began screening for VDPV. In March 2001, three cases of AFP associated with VDPV isolates were detected in the Philippines (8). All poliovirus isolates identified through AFP surveillance undergo two methods of ITD testing. Isolates with dissimilar results in the ITD tests are sequenced, and viruses with 1%--15% sequence divergence from the Sabin virus are considered to be VDPV (2). During January 2002--June 2003, a total of 3,933 Sabin-related isolates were sequenced; 17 (<1%) were identified as VDPVs (Table 3). These 17 VDPV isolates came from nine persons with AFP; eight had two positive isolates, and one had one positive isolate. Four cases were associated with an outbreak in Madagascar in 2002 (9,10), and five cases (China [two], Kazakstan [one], Nigeria [one], and Romania [one]) were not associated with an outbreak. During this period, three other VDPVs were reported to the laboratory network from sources other than the network's screening of AFP cases: one (type 1) from a healthy, nonparalyzed child in Mongolia, one (type 2) from a sewage sample collected in Slovakia, and one (type 3) from a sewage sample collected in Estonia.
Reported by: Vaccines and Biologicals Dept, World Health Organization, Geneva, Switzerland. Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases; Global Immunization Div, National Immunization Program, CDC.
During January 2002--June 2003, the laboratory network provided data to monitor progress toward the goal of polio eradication. The laboratory network documented the polio-free status of the three WHO regions (the Americas, European, and Western Pacific regions) that have achieved certification. In the countries where polio remains endemic, the laboratory network generated data on the location of virus circulation and the geographic origin of the virus, which are essential for guiding polio vaccination and surveillance activities. Providing virology results within 60 days of paralysis onset for >80% of cases of persons with AFP investigated has facilitated timely response in the four regions that have achieved this standard. The laboratory network's high performance level and virus detection sensitivity as measured through NPEV isolation rates ensure that poliovirus probably would be detected if present in specimens collected through the AFP surveillance system.
The laboratory network has provided timely and complete genomic sequencing data that have been used to trace the origin of viruses imported into polio-free areas, interpret virus transmission patterns during outbreaks, and document the progress of eradication by measuring the extinction of genotypes. Screening for VDPV led to the detection of a VDPV outbreak in Madagascar in 2002 and provided data for identifying potential risk factors for VDPV outbreaks in the polio-free era. As polio eradication nears, integrating all possible sources of detection of poliovirus with the AFP surveillance system is critical. The laboratory network has expanded its mandate further by integrating results from other non-AFP sources, including environmental surveillance, into routine reporting.
Challenges facing the laboratory network include a growing workload and the need to provide virology results more quickly. Turnaround times have been shortened through the increased frequency of shipping samples from the field and among laboratories. However, this has increased costs at a time of a funding shortage for the polio-eradication program. In addition, the reassignment of trained staff to other public health activities, especially in polio-free areas, poses a risk to sustaining high-quality laboratory performance. WHO and its partners are developing a 5-year strategic plan to define requirements for sustaining the polio laboratory network's performance at least until global certification of polio eradication. The plan will address technical and resource needs of the laboratory network and will be used for resource mobilization. The continued support of national governments and partner agencies* is essential to ensure the achievement and maintenance of polio eradication globally.
*WHO; Rotary International; United Nations Children's Fund (UNICEF); U.S. Agency for International Development (USAID); United Nations Foundation; Lederle-Wyeth American Association for World Health; Canadian International Development Agency; Japan International Cooperation Agency; Australian Agency for International Development; national governments, especially the governments of Bhutan, Finland, Italy, Sri Lanka, Thailand, and the Netherlands; and CDC.
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