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Bulletin of the World Health Organization

Print version ISSN 0042-9686

Bull World Health Organ vol.78 n.3 Genebra Mar. 2000

http://dx.doi.org/10.1590/S0042-96862000000300004 

THEME PAPERS

 

Surveillance of patients with acute flaccid paralysis in Finland: report of a pilot study

 

Surveillance des malades atteints de paralysie flasque aiguë en Finlande : rapport d’une étude pilote

 

Vigilancia de los casos de parálisis fláccida aguda en Finlandia: informe de un estudio piloto

 

 

T. HoviI; M. StenvikII

IHead, Department of Virology, National Public Health Institute, Mannerheimintie 166, 00300 Helsinki, Finland
IISenior Virologist, Enterovirus Laboratory, National Public Health Institute (KTL), Helsinki, Finland

Correspondence

 

 


ABSTRACT

WHO recommends that surveillance of patients with acute flaccid paralysis (AFP) be used to demonstrate the eradication of wild poliovirus. In this article we report the results of a study to assess the frequency of AFP patients referred to Finnish hospitals and whether virological diagnostic coverage could be improved by repeated reminders and active feedback. For this purpose, we sent monthly questionnaires to all neurological and paediatric neurological units in Finland, requesting retrospective reporting on investigated paralytic patients with defined clinically relevant diagnoses, rather than AFP. Reminder letters included a pre-paid return envelope. Virological investigations were offered cost free. Of the 492 reporting forms sent, 415 (84%) were returned, evenly covering both the population and the study period (July 1997 to June 1998). Of the 90 patients reported, 83 were evaluable. The apparent incidences of the diagnoses covered were 1.6 per 100 000 at any age, and 1.0 per 100 000 for under-15-year-olds. Guillain–Barré syndrome was the most common diagnosis (0.80 per 100 000). The two faecal specimens required were virologically investigated in nine out of the 10 patients under 15 years of age, but in only 46% of all patients. Four adenovirus strains, but no polioviruses or other enteroviruses, were isolated. We conclude that a satisfactory monthly reporting system was readily established and that a sufficient number of patients with diagnoses resembling AFP are being referred to Finnish hospitals. Active feedback did not increase the proportion of virologically investigated patients to an acceptable level in all age groups. It is clear that other approaches must be used to quantify the circulation of poliovirus in Finland.

Keywords: disease notification, methods; epidemiological surveillance; Finland; muscle hypotonia, virology; paralysis, diagnosis; poliomyelitis, epidemiology; pilot projects.


RÉSUMÉ

L’OMS recommande un examen virologique systématique pour les malades atteints de paralysie flasque aiguë (PFA) afin de mettre en évidence l’interruption de la circulation du poliovirus sauvage. Une bonne surveillance de la PFA n’est pas facile à mettre en œuvre si l’on ne recherche pas activement les cas de PFA de manière centralisée. Certains pays, comme la Finlande, qui, historiquement, se trouvent dans une période de postendémie depuis des décennies n’ont pas encore mis en place une surveillance de la PFA. Il faut donc procéder à une analyse rigoureuse des données pour démontrer que le poliovirus ne circule plus en Finlande.

La présente étude a été menée pour obtenir un tableau rapide de la fréquence des transferts de patients atteints de PFA dans les hôpitaux finlandais et pour savoir si la couverture du diagnostic virologique connue pour être faible pouvait être améliorée grâce à des demandes répétées et un bon retour de l’information depuis les laboratoires jusqu’aux services cliniques. C’est dans cette intention que nous avons adressé une fois par mois des questionnaires à tous les services de neurologie et de neurologie pédiatrique de Finlande, leur demandant que soient notifiés de façon rétrospective tous les cas de paralysie étudiés. Plutôt que d’employer le terme PFA, ce questionnaire demande des renseignements sur les malades pour lesquels des diagnostics cliniques précis ont été posés, notamment un syndrome de Guillain-Barré, une plexite, une neuroborréliose et une myélite, ainsi que sur les malades présentant tout autre caractéristique ou symptôme pouvant faire penser à la poliomyélite. Cette enquête a porté sur toutes les classes d’âge, puisque l’expérience que l’on a des flambées de poliomyélite dans la Région européenne indique que la réémergence de la circulation du poliovirus dans une population vaccinée ne se limite pas aux enfants, mais peut également toucher les adultes. Ces lettres de rappel mensuelles comportaient des instructions sur la façon de noter les données et le diagnostic virologique pour chaque patient, un questionnaire partiellement rempli et une enveloppe affranchie pour la réponse. Les études virologiques ont été réalisées gratuitement.

Dans les 42 services cliniques concernés sauf un, on a identifié des correspondants et l’étude a été effectuée entre juillet 1997 et juin 1998. Sur les 492 formulaires de notification envoyés, 415 (84 %) ont été retournés, assurant une couverture uniforme de la population et de la période d’étude. Sur les 90 malades notifiés, 83 ont pu être évalués. Les incidences répertoriées ont été les suivantes: 1,6 cas de PFA pour 100 000 tous âges confondus et 1,0 cas de PFA pour 100 000 chez les moins de 15 ans. Le syndrome de Guillain-Barré a été le diagnostic le plus fréquemment posé (0,80 pour 100 000). Les comparaisons effectuées avec les données enregistrées à la sortie de l’hôpital indiquent que la couverture de la notification des cas de syndrome de Guillain-Barré et de myélite a été excellente dans cet essai. On a procédé à l’examen virologique des deux échantillons de selles demandés pour 9 des 10 cas de PFA identifiés chez des malades de moins de 15 ans, mais seulement pour 46% de l’ensemble des cas. On y a isolé 4 souches d’adénovirus, mais aucun poliovirus ni aucun autre entérovirus. Seul un cas a été notifié par le système de notification passive en raison d’une forte suspicion de poliomyélite de la part du clinicien. Aucun signe d’infection par le poliovirus n’a été décelé lors de l’examen d’échantillons correctement recueillis chez ce malade. Le diagnostic de poliomyélite a été écarté dans les 83 cas évalués, soit par l’étude virologique, soit du fait d’un autre diagnostic.

Un système de notification mensuelle satisfaisant a été rapidement mis en place. Il a permis de constater qu’un nombre satisfaisant de malades avec des diagnostics proches de la PFA sont transférés dans les hôpitaux finlandais. Cependant, l’effort de retour d’information consenti n’a pas permis d’accroître jusqu’à un niveau acceptable pour toutes les classes d’âge la proportion de malades pour lesquels une étude virologique a été effectuée. Il est manifeste qu’il faut employer d’autres approches pour évaluer la circulation présumée du poliovirus en Finlande, par exemple en épluchant soigneusement et en permanence les résultats des recherches d’entérovirus pratiquées pour un motif ou pour un autre et en procédant à une surveillance environnementale couvrant une part importante de la population.


RESUMEN

La OMS recomienda el examen virológico sistemático de los pacientes con parálisis fláccida aguda (PFA) para comprobar la erradicación de la circulación del poliovirus salvaje. No es fácil organizar una vigilancia eficaz de la PFA si se carece de un sistema centralizado de búsqueda activa de pacientes con PFA. Algunos países que salieron de la fase endémica hace decenios, Finlandia incluida, no han establecido aún un sistema de vigilancia de la PFA. Por consiguiente, para demostrar que en Finlandia se ha erradicado la circulación del poliovirus se requieren pruebas suplementarias rigurosamente analizadas.

El presente estudio se realizó para obtener una panorámica rápida de la frecuencia de envío de pacientes con PFA a los hospitales finlandeses, y para investigar la posibilidad de que la cobertura del diagnóstico virológico, reconocidamente baja, pudiera mejorarse mediante el envío repetido de recordatorios y una retroinformación activa de los laboratorios a los dispensarios. Con ese propósito enviamos mensualmente cuestionarios a todas las unidades de neurología y neurología pediátrica de Finlandia solicitando información retrospectiva sobre los pacientes paralíticos investigados. En vez de utilizar la expresión PFA, en los cuestionarios se pedían datos sobre los pacientes con diagnóstico de determinadas afecciones de interés clínico (en particular, el síndrome de Guillain-Barré, neuritis del plexo braquial, neuroborreliosis y mielitis) o con cualquier otra sintomatología parecida a la de la poliomielitis. Se incluyeron en la encuesta todos los grupos de edad, dado que, por lo que se sabía de los brotes de poliomielitis registrados en la Región de Europa, la reaparición del poliovirus en las poblaciones vacunadas no se limita a los niños, sino que puede afectar también a los adultos. En las cartas recordatorias mensuales se incluían instrucciones para anotar detalles sobre el paciente y el diagnóstico virológico, un cuestionario parcialmente cumplimentado y un sobre de respuesta ya franqueado. Las investigaciones virológicas se ofrecían gratuitamente.

En 41 de las 42 unidades clínicas de interés se identificaron personas de contacto, y el estudio se realizó entre julio de 1997 y junio de 1998. De los 492 formularios enviados se devolvieron 415 (84%), que cubrían uniformemente la población y el periodo de estudio. De los 90 casos notificados, 83 eran evaluables. Las incidencias aparentes fueron de 1,6 por 100 000 para la PFA a cualquier edad, y 1,0 por 100 000 para la PFA entre los menores de 15 años. El síndrome de Guillain-Barré fue el diagnóstico más común (0,80 por 100 000). La comparación con los datos de las altas hospitalarias corroboró la impresión de que en este estudio la cobertura de notificación del síndrome de Guillain-Barré y de los casos de mielitis fue muy buena. El preceptivo análisis virológico de dos muestras fecales se realizó en nueve de los 10 pacientes de PFA menores de 15 años, pero sólo en el 46% del total de los pacientes. Se aislaron cuatro cepas de adenovirus, pero no se hallaron poliovirus ni otros enterovirus. Sólo un paciente habría sido objeto de notificación por conducto del sistema pasivo de notificación por tener el médico clínico fuertes sospechas de que pudiera tratarse de un caso de poliomielitis. No se hallaron indicios de infección por poliovirus en muestras correctamente obtenidas de ese paciente. En los 83 casos evaluados se excluyó la poliomielitis, ya fuera como resultado de investigaciones virológicas o porque se formuló un diagnóstico distinto.

Se estableció con facilidad un sistema mensual de notificación de funcionamiento satisfactorio, que puso de manifiesto que se enviaba a los hospitales finlandeses a un número adecuado de pacientes con diagnósticos parecidos a la PFA. Sin embargo, la retroalimentación activa no aumentó hasta un nivel aceptable para todos los grupos de edad la proporción de pacientes sometidos a investigación virológica. Está claro que hay que aplicar otros métodos para evaluar la presunta circulación de poliovirus en Finlandia, en particular el análisis minucioso y continuo de los resultados de los diagnósticos de enterovirus realizados con cualquier motivo, y una vigilancia ambiental que abarque a una parte importante de la población.


 

 

Introduction

Poliomyelitis and its causative agents, pathogenic or wild polioviruses, are the targets of the programme for global eradication being coordinated by WHO. The programme is progressing well, and as the final goal approaches it will be more and more important to know that wild polioviruses are not circulating in populations believed to be virus-free. The WHO recommended approach for assessing the circulation of poliovirus in a population is based on virological examination of two faecal specimens from patients with acute-onset paralytic disease of unknown etiology. These patients are designated with a descriptive working diagnosis, acute flaccid paralysis (AFP). For AFP surveillance to be reliable in a population, it should cover all children under 15 years of age in all geographical regions and demographic groups, more than 80% of all reported AFP cases should be properly examined, and in the absence of poliomyelitis cases the incidence of AFP should be >1 per 100 000 (1). The diagnosis underlying a case of non-poliomyelitis AFP is mostly Guillain–Barré polyradiculitis or transverse myelitis.

Some countries that have been poliomyelitis-free for decades have not been willing to establish AFP surveillance because of the lack of a suitable reporting and active surveillance system, and because there are concerns about the sensitivity of AFP surveillance to detect a possible re-emergence of wild poliovirus in vaccinated populations. Since subclinical and non-paralytic poliovirus infections occur several hundred times more frequently than paralytic infections, sampling only the paralytic patients might — according to this view — delay the detection of an emerging outbreak. Mathematical modelling of the population sensitivity of AFP surveillance (2) can be interpreted as supporting this view. If AFP surveillance cannot be properly performed, other approaches must be used to study wild poliovirus circulation, such as analysis of the results of enterovirus diagnosis (“enterovirus surveillance”) or environmental surveillance. However, even with these approaches, it is still not easy to achieve the required geographical and demographic coverage or adequate sensitivity of poliomyelitis surveillance.

Finland belongs to the set of countries without a working AFP surveillance system. We therefore designed a strategy to launch a temporary, low-cost, laboratory-operated AFP notification system, and carried out a 12-month pilot study to see how well patients in the AFP category would be presented to the Finnish health care system, and whether the identification of a specific contact person at each potential referral unit plus monthly reminder letters would improve the provision of viral diagnosis with regard to these patients.

 

Study design

Background information

Finland is an industrialized country with a population of about 5.15 million and a well-organized public health care system that covers even the most remote regions of the country and all demographic groups of the population. The circulation of indigenous poliovirus was eradicated in Finland in the early 1960s by the extensive use of inactivated poliovirus vaccine (IPV) (3). An outbreak involving the widespread circulation of type-3 poliovirus, which resulted in 9 paralytic cases of poliomyelitis in 1984–85, was stopped by a vigorous immunization campaign (4). Under the Law on communicable diseases, confirmed and strongly suspected cases of poliomyelitis in Finland must be notified immediately to KTL (National Public Health Institute). Similarly, since only IPV is used in regular immunizations, isolation of a poliovirus from any clinical specimen must be notified. No cases of poliomyelitis have been reported in Finland since January 1985, and no wild-type polioviruses have been isolated from clinical specimens derived from Finnish citizens or the environment. The latter is monitored by regular sewage screening (5). All Finnish virological diagnostic laboratories report their findings weekly to each other and to KTL by e-mail, but there is no active surveillance of AFP cases. Analysis of faecal specimens sent for enterovirus isolation during the last few years suggests that the frequency of properly examined AFP cases is well below 1 per 100 000 (unpublished data). Patients with designated AFP, detected mainly at health centres or by private practitioners, are likely to be referred to specialists in neurology or paediatric neurology. Finland is divided into 21 hospital regions, each of which has a central hospital. The larger regions also have one or more district hospitals. All central hospitals have a neurological ward and a paediatric neurological ward, or at least a specialist who works regularly at the central hospital.

Objectives of the study

We designed a nationwide study in order to obtain information on the occurrence of patients treated in Finnish hospitals who are classifiable as AFP cases. A further objective was to determine whether regular reminders sent directly to the relevant clinics would ensure regular reporting, including null-reporting of AFP cases. Furthermore, we wanted to evaluate the efficacy of reminders to increase the coverage of virological diagnosis of AFP patients. The study was designed to cover all age groups in all regions of the country, because in a population with a long poliomyelitis-free history and high immunization coverage there are susceptible adult individuals, as has been demonstrated in all the recent outbreaks of poliomyelitis in the European Region (4, 68).

Problem identification and designed solutions

Since AFP is rare, there is a danger that any specific recommendations for reporting or specimen collection that do not also facilitate the immediate diagnosis or patient care, will in practice be neglected. We therefore sent a regular reminder letter, together with a pre-paid return envelope, requesting that any recently admitted cases of AFP be reported. Each unit was to nominate a contact person responsible for this correspondence.

AFP is not normally used as a diagnosis in hospitals. Therefore, rather than asking for numbers of AFP cases, we requested reports of patients with Guillain–Barré syndrome, plexus neuritis, neuroborreliosis, myelitis or any other diseases resembling poliomyelitis.

In order to encourage units to comply with the study requirements, the laboratory fee was waived for virus isolation from two faecal specimens from AFP patients. The isolation could be carried out at any virus laboratory in Finland.

Preparatory activities

During the spring of 1997, before the study period began, the relevant specialists and especially the heads of the clinical units involved were fully informed about the planned study. It was agreed that each clinical unit would nominate a contact person to do the reporting. The network of 41 contact persons obtained covered the whole country. Only one hospital district of a moderate size remained without a contact person on the (adult) neurological wards.

Reference data

Data from the national hospital discharge register were provided by the National Research and Development Centre for Welfare and Health, Helsinki, Finland.

 

Results

Reporting activity

The first scheduled reporting month was July 1997. Forms were sent in mid-July with a request to fill them in and return them in an enclosed pre-paid envelope in early August. A total of 71% of the first set of forms were returned (Fig. 1). Subsequently, we sent the forms for the next month as a reminder to return the completed form for the previous calendar month. In order to encourage reporting, after 2 months we published an interim report of the study in the widely distributed Public Health Newsletter. This indicated active and less active regions and resulted in a rapid increase in coverage; all the forms (100%) for September 1997 were returned, though some after considerable delay. The reporting level subsequently stabilized at about 85%. The return for the final month was again lower, possibly because there was no reminder letter in July 1998. Altogether, 415 out of 492 forms (84%) were returned. The adherence of individual centres to the study is shown in Fig. 2.

 

 

 

 

Reported patients

Data on the patients are based on information given on the reporting forms. In all, 90 patients were reported over the 12-month period, 40 (44%) of whom were female. The reported diagnosis of two patients did not permit classification as AFP (facial paresis, myositis), and five were referred to the hospital too late for the quality analysis of AFP surveillance. Ten evaluable patients were under 15 years of age. This gives an apparent AFP incidence of 1.62 per 100 000 for the entire population, and 1.00 per 100 000 for those aged under 15 years. The monthly rates of cases varied as expected (Fig. 1), but the use of even a two-month smoothing window stabilized the rate substantially (not shown). The reported cases covered the entire country, although four of the 21 hospital regions did not report a single case. Three of these regions serve a relatively small population and the null result may reflect the true situation, while the fourth has an average population size. However, in this region there was no contact person on the adult neurology wards.

The distribution of patients in the five diagnosis categories is shown in Table 1. As expected, Guillain–Barré polyradiculitis was the most common diagnosis. Among adults, the number of cases initially listed as “other disease resembling poliomyelitis” was also noteworthy. In 10 out of 17 cases in this category, poliovirus infection was excluded by examination of correctly collected faecal specimens. The exact diagnosis was not usually stated in the monthly reports, but retrospective analysis of hospital record summaries revealed that poliomyelitis could also be excluded in the remaining seven cases, based on another diagnosis. In one case, the neurologist contacted KTL because of strong suspicion of poliomyelitis on clinical grounds; however, no evidence for poliovirus infection was obtained, despite intensive virological examination of several faecal, nasopharyngeal, cerebrospinal fluid and serum specimens from the patient.

 

 

To assess the completeness of reporting, we compared the data obtained in this study with those in the national discharge register for Guillain–Barré syndrome and (transverse) myelitis. Data for the corresponding study period were not available and so those for three successive years (including the study period) were used in the comparison (Table 2). The completeness appeared very good for children. However, for adults, especially for Guillain–Barré syndrome, many more cases had been registered in the hospitals. This is most probably due to repeated periods of treatment because of persistent symptoms of a single disease episode, as suggested by the fact that the number of treatment periods was almost double the number of patients, even within a given year (Table 2).

 

 

Virology

At least one faecal specimen was investigated from 53 patients (63%), and two or more specimens from 38 patients (46%). There appeared to be no major difference between the five diagnostic categories in terms of the proportion of patients investigated virologically. Significantly, two faecal specimens were investigated for all but one of the children under 15 years of age. No definite improvement in the proportion of properly virologically investigated patients was observed over the study period. The rate of specimen taking for virological diagnosis did not correlate with the reporting rate, and the proportion of virologically examined patients at the nine university clinics was not noticeably different from that at the other clinics. No polioviruses or other enteroviruses were found, but an untyped adenovirus was isolated from four patients.

 

Discussion

Several important conclusions can be drawn from this study.

First, it seems possible to interest clinical wards in an ad hoc retrospective reporting system, and to obtain a satisfactory level of coverage in a matter of national importance, even if this is of no immediate practical value to the wards themselves. It is worth noting that the total number of reports returned over the 12-month period was 415, of which more than 75% represented null reporting.

Second, it may have been important to our success that we tried to make the reporting as easy as possible by defining the reportable cases through clinically relevant diagnoses rather than using the term AFP, and by sending partly completed reporting forms together with pre-paid envelopes to the contact persons in the hospitals every month. Nevertheless, despite the good reporting coverage, epidemiological investigations of the individual AFP cases did not necessarily occur in the structured way recommended by WHO. To guarantee this, we would have needed resources that are beyond the capacity of our laboratory.

Third, the apparent incidence of AFP patients referred to hospitals in Finland is “satisfactory”. Furthermore, the cases reported comprised the expected number of patients with Guillain–Barré syndrome, the most common component of the working diagnosis AFP. The apparent incidence of Guillain–Barré syndrome in Finland based on this study (0.80 per 100 000) is similar to that (0.82 per 100 000) noted for the 1980s (9). This suggests that almost all the relevant cases during the period were reported, a view supported by comparison with the national hospital discharge data.

Notably higher rates of both AFP and Guillain–Barré syndrome in both children and adults have been reported previously from some other countries (e.g. 8, 10, 11). In the USA, the incidence of Guillain–Barré syndrome alone was reported to be 1.5 per 100 000 among children under 15 years of age (10). We do not know the reason for the observed variations between countries (11) but they may reflect differences in demographic background, environmental factors and, most likely, different diagnostic practices. We do know that in Finland, about 10% of hospital discharges registered as Guillain–Barré syndrome do not fulfil the international criteria for this syndrome, and that definite cases are also registered under other codes (9). In addition, repeated treatment periods are not easily distinguishable in raw discharge register data, and may result in falsely high numbers unless properly corrected. Significant variation can be expected to occur in the interpretation of the rather “soft” definition of AFP, wherein Guillain–Barré syndrome is the major but not the only diagnosis. A further problem is the annual variation in Guillain–Barré syndrome (9) – and possibly of other components of AFP – which limits the usefulness of short-term AFP incidences as surrogates of the quality of surveillance in small populations (< 10 million). These confounding factors do not necessarily call into question the use of longitudinal trends of AFP incidence in poliomyelitis surveillance, but are a major obstacle in assessing the real significance of the initially obtained “accepted” level of 1 per 100 000.

The fourth conclusion relates to the value of feedback in improving the quality of case investigation. While 9 out of 10 children with AFP were properly examined for potential enteroviral etiology, the corresponding proportion of all AFP patients was less than half. A low percentage of virologically investigated cases is a common problem of recently established AFP surveillance systems (10, 12, 13). Despite repeated feedback, this proportion did not improve during the study period. The apparent discrepancy between the high reporting level and the low diagnostic activity is most probably because the contact persons working with us were responsible for retrospective reporting, but did not necessarily have primary responsibility for determining which laboratory tests should be carried out on individual patients. A wider and more intensive information campaign would have been needed to ensure the adherence of all the clinicians working on the relevant wards. Even then, attempts to establish a virological diagnosis for patients in these clinical categories might not be considered worth while by many clinicians, since this study confirmed previous experience in Finland in which reported diseases, including AFP, are not commonly associated with enterovirus infections. No enteroviruses were found in the specimens investigated. This is not uncommon in Finland in relation to the clinical diagnoses specifically followed in this study. It is likely that most of the non-polio enterovirus isolations from AFP patients in recently endemic countries are irrelevant to the disease itself and reflect the silent transmission of these viruses, known to be facilitated by poor hygiene and a high population density.

These results suggest that the apparent added value of suboptimally performing AFP surveillance in monitoring the circulation of wild poliovirus in Finland would be limited. The main evidence for the absence of poliovirus circulation must be based on other approaches, such as the continuous monitoring of the environment for polioviruses (5, 14) and the careful analysis of virus strains isolated from faecal specimens collected for any reason (enterovirus surveillance). About 25% of the Finnish population have been covered by regular environmental surveillance since 1985 and not one poliovirus has been found in the sewage specimens. The approach used appears to be able to detect poliovirus in a single sewage specimen if the prevalence of poliovirus excretion is as low as 1 per 5000 people, or even less. Regularly repeated sampling is further increasing the population sensitivity (T. Hovi et al., unpublished results, 2000). The frequency of faecal specimens examined annually for cytopathic viruses in Finland corresponds to the random screening of about 1 per 5000 Finns for poliovirus excretion (1 per 1200 in children under 15 years of age) every year (National Report for Regional Certification Commission, filed at KTL). Together, these approaches are very likely to reveal the circulation of silent poliovirus in Finland. Based on several years’ experience, isolation of any poliovirus from any specimen by other laboratories in the country would have been immediately notified.

In conclusion, although it was possible to establish a functioning network of centres for modified AFP surveillance, and the number of reported cases appeared satisfactory, levels of virus diagnosis in patients remained unsatisfactorily low despite repeated reminders to the contact persons. The 10 children with AFP were examined properly, but not the adults. Consequently, other approaches must be used for poliovirus surveillance in Finland.

 

Acknowledgements

The contact persons at all the neurological and paediatric neurological units in Finland are acknowledged for preparing the monthly reports. Dr A. Salmi, Dr M. Färkkilä, and Dr H. Saxén made useful suggestions for the design of the study. Mr S. Pelanteri kindly provided the hospital discharge data. We are grateful to Ms R. Hallivuori for secretarial assistance, and to Ms E. Penttilä and Ms E. Lamminsalo for skilful assistance in the laboratory work.

 

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Correspondence
T. Hovi
Department of Virology, National Public Health Institute
Mannerheimintie 166
00300 Helsinki, Finland T. Hovi
E-mail: tapani.hovi@ktl.fi