Laboratory support for poliomyelitis eradication: memorandum from a WHO meeting.

Memoranda Memorandums Laboratory support for poliomyelitis eradication: Memorandum from a WHO Meeting* This Memorandum summarizes the conclusions and recommendations of the participants at the Consulta- tion on Strategy for Isolation and Characterization of Poliovirus Strains and Surveillance of Wild Polio- viruses held in Geneva, 28-30 November 1988. Introduction The following general considerations are important. (1) For the success of the poliomyelitis eradi- cation programme it is essential that clinicians, epi- demiologists and virologists in each country should work together as a team. The establishment and smooth functioning of these teams will form an important part of the work of the national pro- gramme manager. (2) The nature and extent of the activities in national programmes will depend on the incidence of poliomyelitis in individual countries and on the epi- demiological and virological facilities available. Each country will require a programme which is to a greater or lesser extent individually tailored. (3) In countries with a high incidence of polio- myelitis, it is desirable that, as early as possible in national campaigns, a few strains of virus isolated from cases should be preserved as samples of the indigenous strains in the country (or the region). (4) Polioviruses represent only a small propor- tion of the enteroviruses. In the early stages of the eradication programme, efforts should be focused * This Memorandum is based on a report which was drafted by the following signatories on the occasion of a meeting held in Geneva on 28-30 November 1988: W. Al-Nakib (Kuwait); I. Arita and M. Arita (Japan); W.C. Cockburn (United Kingdom); K. Dave (India); T. Domok (Hungary); F. Horaud (France); T. Hovi (Finland); I. Kapsenberg (Netherlands, as observer); M. Korolev (USSR); 0. Kew (USA); B. Le Guenno (Senegal); J. Melnick (USA); P. Minor (United Kingdom); C. Mordhorst (Denmark); A. Osterhaus (Netherlands); H. Schatzmayr (Brazil); and M. Yin- Murphy (Singapore). WHO Secretariat: T. Bektimirov, G. Torri- giani, R. Henderson, P. Lambert, D. Magrath, Y. Ghendon (Secretary), J. Keja; J. Milstien, and Y. Pervikov (WHO, Geneva); 0. Tomori (African Regional Office), B. Bytchenko (European Regional Office), and H. Endo (Western Pacific Regional Office). A French translation of this article will appear in a later issue of the Bulletin. Requests for reprints should be sent to Microbiology and Immunology Support Services, Division of Communicable Diseases, World Health Organization, 1211 Geneva 27, Switzer- land. Reprint No. 4987 on the polioviruses; then, as the incidence of polio- myelitis decreases, the role of other enteroviruses as causes of paralysis will require investigation. Role of laboratories Laboratories provide essential support and should concentrate on the simplest methods that will facili- tate the eradication of the disease. Most of the coun- tries with laboratories capable of isolating and identifying polioviruses are in WHO's American and European regions, and to a lesser extent in the Western Pacific. In the other regions adequate labor- atory coverage is at present available only in some of the countries. This unequal distribution is not such a hindrance because the eradication strategy dis- tinguishes between two groups of countries. Those with comprehensive laboratory services are also the countries with a low incidence of poliomyelitis, where laboratory confirmation of every case of poliomyelitis is necessary so as to determine com- pletely the characteristics of the virus and thus arrive at a conclusion about its origin. In most countries with a low incidence and adequate laboratory ser- vices, only a minimum of financial and technical support is required, mainly for developing a system of information exchange and arranging the dispatch to a reference laboratory of those virus strains that cannot be fully characterized locally. In countries with a high incidence of poliomyel- itis, on the other hand, the objective in the first few years is to organize and execute vaccination pro- grammes which effectively cover the highest possible proportion of the susceptible population. Not until the incidence of the disease has reached a low level will it be necessary to make thorough epidemiologi- cal and virological investigations in every case. In these countries a high priority should be given to the development of laboratory services which should be developed concurrently with the extension of the Bulletin of the World Health Organization, 67 (4): 365-367 (1989) © World Health Organization 1989 365 Memorandum immunization programme. Existing national labor- atories should assist neighbouring countries, which are not able to develop their own national labor- atories because of inadequate human and material resources. The designation of laboratories of two types (national laboratories and reference laboratories) was recommended, and a plan of objectives for the years 1990, 1995 and 2000 was identified. National laboratories The main tasks of national laboratories are confir- mation of clinical cases of poliomyelitis through the isolation and identification of virus from patients and/or the investigation of antibody responses in samples of serum. These laboratories will also be responsible for the isolation and identification of polioviruses and for antibody surveys arising from epidemiological investigations. In those national laboratories that are able to do so, poliovirus iso- lates may be characterized as wild or vaccine- associated poliovirus by using a panel of monoclonal antibodies. For the isolation and identification of viruses, and for antibody determinations, only standard methods should be used in accordance with the WHO manual for poliovirus isolation, identification, intratypic differentiation and serological techniques (see below). To promote the standardization of results, national laboratories should use standard supplies and equipment in addition to standard methods. Tests of the potency of vaccine at different points in the distribution chain may be required. With training and certification, some national labor- atories may be selected to perform potency testing of OPV (oral polio vaccine) lots, including those recovered from the field. Reference laboratories Not all countries will have competent national viro- logical laboratories, at least at the beginning of their programme. Suitable laboratories in other countries will be invited to provide the necessary support and these are described as "reference laboratories". They may be responsible for all the necessary work from a given country, and for certain other duties such as: - supporting the development of national labor- atories by helping with the distribution of reference materials (including the distribution of agreed cell lines and wild and vaccine strains of polioviruses for control purposes), and by assisting with training and with proficiency testing; - performing intratypic characterization of polio- virus isolates obtained from national laboratories; - serving as a collaborating laboratory for check- testing of poliovaccine potency, including performing this service for countries in the region with no national laboratories. Reference laboratories may also take part in training programmes. Though most of the reference laboratories are expected to be in the same part of the world as the countries they serve, there may be instances in which, for example, laboratories in Europe may function as reference laboratories for countries in Africa or Asia. A small number of reference laboratories will be identified to perform one or more specialized func- tions in lieu of or in addition to those described above. These will include responsibility for obtaining and distributing relevant standards and reference material (including type-specific antisera and the panel of monoclonal antibodies), for acting as resources for the development and use of training materials and for obtaining and distributing panels of unknown sera and viruses to other designated laboratories. They will also include provision of definitive identification of viral isolates, using cDNA probes to differentiate wild and vaccine strains and to determine the origins of wild strains. These specialized laboratories may serve as participants in collaborative studies to assess proposed standards and reference materials and to answer specific research questions related to the programme. The guide to poliovirus isolation and sero- logical techniques for poliomyelitis surveillance (WHO Offset Publication No. 46, 1979) is now being rewritten for publication as a manual. Since new techniques useful in diagnostic virology and/or in laboratory surveillance of poliovirus circulation can be expected, the manual will be published in loose- leaf form so that pages can be replaced easily with updates. Resarch priorities Priorities for laboratory research include: (1) The analysis of serum antibodies with a view to establishing whether the immune response observed is a result of exposure to a wild type or vaccine strain of poliovirus. (2) The establishment of panels of monoclonal antibodies for intratypic differentiation and assess- ment of their usefulness and validity in the field, including their use in different assay systems, such as neutralization tests of ELISA. (3) Detection and identification of virus in clini- cal specimens by ELISA, cDNA probes, gene ampli- fication, and other methods. Direct examination of faecal and other specimens by ELISA may be pos- sible using an antibody to capture the virus and a WHO Bulletin OMS Vol. 67 1989w Laboratory support for poliomyelitis eradication second antibody to detect it. Early results are encouraging and further developments are awaited. The amplification of nucleic acid sequences by poly- merase chain reaction (PCR) has been shown to be extremely sensitive and, potentially, can be adapted to detect sequences characteristic of local wild-type virus or vaccine virus. It might therefore be used to detect a low level of wild-type virus in the presence of an excess of vaccine strain, as might occur when examining sewage specimens of a country with an established OPV programme. Developments in this technology are likely to have a profound effect in the future. (4) Development of sensitive non-isotopic detec- tion systems for cDNA probes for virus isolates or for virus in clinical specimens. Recommendations The Consultation recommended that laboratory activities, by levels of poliomyelitis incidence, should be as follows: Group A. Countries with reliable reporting systems, which have reported no indigenous cases for the pre- vious three years, and with 80% vaccine coverage: * for every case, isolation of virus and/or diagnostic serology; * examination of specimens obtained from epidemi- ological investigations (e.g., healthy persons or sewage); WHO Bulletin OMS Vol. 67 1989 * type identification and intratypic characterization of strains, including relation to vaccine strains and evidence of origin of wild strains (local or imported); * seroepidemiological studies may be required in certain specific circumstances. Group B. Countries with < 10 cases per annum and vaccine coverage rates of > 50%: * recommendations as for Group A. Group C. Countries with >10 cases and coverage rates of > 50%: * isolation and type identification of viruses from representative endemic cases and from representative cases in outbreaks; * when <50 cases per annum are reported, the countries should consider establishing an expert review committee which will be responsible for the final diagnosis of cases reported as poliomyelitis, based on examinations as for group A. Group D. Countries with > 10 cases of poliomyelitis or unknown incidence and/or coverage rates of < 50% or unknown: * isolation and type identification of viruses from representative endemic cases and from representative cases in outbreaks. Estimation of vaccine potency may be necessary under certain circumstances at all stages of eradi- cation, which service may be provided by national or reference laboratories. 3w