Immune status of the population to poliovirus infection in Singapore

Bulletin of the World Health Organization, 65 (1): 83-86 (1987) i World Health Organization 1987 Immune status of the population to poliovirus infection in Singapore K. T. GOH' & S. YAMAZAKI2 A seroepidemiological survey conducted after two decades of mass immunization against poliomyelitis in Singapore showed a high level ofherd immunity in the population to all three types of human poliovirus. Neutralizing antibodies to poliovirus 1, 2 and 3 were detected in 93.9-96.7% of the population between 6 months and over 40 years old. Adults above 30 years of age had a relatively high level of susceptibility to poliovirus infection, with 10.2-12% in the over-30-year age group possessing no neutralizing anti- body against poliovirus 1, 14.3% in the 40+ age group against poliovirus 2, and 14% in the 30-39-year age group against poliovirus 3. The geometric mean titres showed a general decline among the older age groups. There were no statistically significant differences in the immune status by sex and by ethnic groups (Chinese, Malays and Indians). The impor- tance of maintaining a high coverage of immunization, monitoring the herd immunity of the population to identify high-risk groups, and advising adults travelling to the endemic areas to be immunized against poliomyelitis was stressed. Poliomyelitis used to be a major public health problem in Singapore during the immediate post-war period (after 1945). In 1958, mass administration of Sabin type-2 attenuated poliovirus vaccine to chil- dren was demonstrated to be effective in aborting an epidemic caused by poliovirus 1 (1, 2). The national childhood immunization programme against polio- myelitis was introduced in March 1962. The compre- hensive coverage of this programme, in which more than 85% of infants and 95% of primary school entrants were immunized every year, has led to the elimination of paralytic poliomyelitis in the country (3-5). Seroepidemiological surveys to determine the sus- ceptibility level of the childhood population against the three types of poliovirus and to evaluate the effi- cacy of the initial phases of the immunization pro- gramme were conducted in the early 1960s (4). A 1976 study on the seroimmunity of a population group born between 1955 and 1958 and not immun- ized against poliomyelitis showed that 35.4/o of them remained susceptible to poliovirus infection (6). The findings gave rise to considerable concern, as it was ' Head, Quarantine & Epidemiology Department, Ministry of the Environment, Environment Building, 40, Scotts Road, Singa- pore 0922, Singapore. Requests for reprints should be sent to this author. 2 Director, WHO Serum Reference Bank, Central Virus Diag- nostic Laboratory, National Institute of Health, Gakuen, Musashimurayama, Tokyo, Japan. not certain whether the immunization programme should be extended to cover the adult population. In 1982, the Expert Committee on the Immunization Programme in Singapore decided that a comprehen- sive seroepidemiological survey should be conducted to assess the immune status of the population against the three types of poliovirus, to identify high-risk groups, and to determine if there was a need to modify the existing programme (7). The study was implemented in collaboration with the WHO Serum Reference Bank at the National Institute of Health, Tokyo. MATERIALS AND METHODS It was realized from the beginning that it would be extremely difficult to organize a survey involving collection of random blood samples that would be representative of the whole population. Therefore, samples had to be obtained from selected groups of healthy children and adults between 6 months and 40 + years of age. They included blood donors, national servicemen, students and young children admitted to Singapore General Hospital for paed- iatric surgery. A sample of 1-3 ml whole blood was collected from each selected individual using dispos- able needles and syringes. The sample size for each age group was in accordance with WHO's recom- mendation for serological surveys (8). The sera were 4754 -83- K. T. GOH & S. YAMAZAKI separated, transferred to properly-labelled 1.5 ml Teflon tubes and then kept in a freezer at the Depart- ment of Pathology, Singapore General Hospital. Information recorded for each individual included date of birth, sex, ethnic group, and previous immun- ization history. When blood collection had been com- pleted, the samples were transferred and packed in a polystyrene foam box, kept frozen in dry ice, and then dispatched together with the individual record forms by air to Japan for the analyses. Titration for neutralizing antibody against Sabin poliovirus 1, 2 and 3 was carried out by the micro cell culture method using Vero cells at the Central Virus Diagnostic Laboratory, National Institute of Health, Tokyo. The antibody titre was expressed as the reciprocal of serum dilutions. A titre of > 1:4 was regarded as seropositive (immune). Geometric mean titres were calculated from the antibody positive sera. RESULTS A total of 425 blood samples were collected and analysed. Of these, 399 (93.9%) had neutralizing antibodies to poliovirus 1, 410 (96.5%) to poliovirus 2, and 411 (96.7%) to poliovirus 3. Adults above 30 years of age had a relatively higher level of suscepti- bility to all three types of poliovirus. For poliovirus 1, 6 (12.0%) of 50 adults in the 30-39 age group and 5 (10.2%) of 49 in the 40 + age group had no neutraliz- ing antibody. In the case of poliovirus 2, 7 (14.3%) of 49 adults in the 40 + age group were non-immune. As for poliovirus 3, 7 (14.0%) of 50 adults in the 30-39 age group possessed no neutralizing antibody. There was a general decline in the geometric mean titre (GMT) among the older age groups (Fig. 1). Further analyses of the data based on 276 persons between 6 months and 19 years of age revealed that all those who had completed the primary course of immunization against poliomyelitis were seropositive against all three types of human poliovirus. Unim- munized children were also found to develop an anti- body response to Sabin poliovirus 1, 2 and 3 (Table 1). There was no significant difference in the sero- immunity level against the three types of poliovirus between males and females (Table 2), or among the three major ethnic groups in Singapore (Table 3). DISCUSSION It must be stressed that the groups selected for the survey were not random samples of the population. Therefore, the results obtained and the conclusions drawn may not be representative of the whole population. Nevertheless, the survey confirmed the high level of herd immunity which had been acquired by active immunization of the childhood population Poliovirus type 1 t. t t t i - rv C.) t- v Cb C~ Poliovirus type 2 t 0 / / / Ii1 Poliovirus type 3 t t tV 4' / / / *i Age (years) Fig. 1. Immune status of the population and neutralizing antibody levels, by age group, against poliovirus 1, 2 and 3 in Singapore, 1982-84. The arrows indicate when immunizations were given: primary course at 3-5 months and boosters at 18 months, 6+ years and 1 5+ years. (Solid line: immune persons with neutralizing antibody level > 1:4. Dotted line: geometric mean titres.) 100 r 80 60 C 0 CL E 0. m 40 20 0 180 150 120 . 90E .2 E608 30 .~ ~~~~~~~~~ ~~~ I 84 IMMUNE STATUS TO POLIOVIRUS INFECTION 85 Table 1. Immune status of the population between 6 months and 19 years of age against human poliovirus 1, 2 and 3 by history of immunization, Singapore, 1982-84 No. immune' to poliovirus Age No. No. group tested immunized Type 1 Type 2 Type 3 6 months-4 years 123 119 (96.7)" 120 (97.6) 119 (96.7) 122 (99.2) 5-9 years 53 38(71.7) 51 (96.2) 52(98.1) 52(98.1) 10-14 years 50 50 (100) 46 (92.0) 50 (100) 50 (100) 15-19 years 50 50 (100) 48 (96.0) 50 (100) 49 (98.0) Total 276 257 (93.1) 265 (96.0) 271 (98.2) 273 (98.9) a Neutralizing antibody titres of A 1:4 are considered immune. bFigures in parentheses are percentages. against poliomyelitis over the past two decades. The majority of those who, in the period before the immunization programme was started, had not been immunized must have acquired natural immunity from the wild virus circulating in the community at that time. The periodic increases in GMT to polio- virus 1, 2 and 3 from infancy to adulthood were the result of the administration of Sabin boosters or of reinfection by the vaccine-derived strains circulating naturally in the environment. Sabin poliovirus strains excreted in the environment appeared to be adequate in stimulating antibody production in the unimmun- ized children and in potentiating herd immunity. Although the relatively high-risk groups were those above 30 years of age, more than 85% of them were immune to all three types of human poliovirus. The high immunity level induced by the Sabin vaccine which provides both local gut immunity and serum humoral immunity conferred double protection against disease outbreaks caused by the wild strain. However, there is no ground for complacency. Outbreaks of paralytic poliomyelitis have occurred in poorly or non-immunized subgroups within other- wise well-vaccinated populations (9, 10). In the Table 2. Immune status of the population against human poliovirus 1, 2 and 3 by sex, Singapore, 1982-84 No. immune' to poliovirus No. Sex tested Type 1 Type 2 Type 3 Male 323 300 (92.9)b 308 (95.4) 309 (95.7) Female 102 99 (97.1) 102 (100) 102 (100) Total 425 399 (93.9) 410 (96.5) 411 (96.7) Neutralizing antibody titres of > 1:4 are considered immune. Figures in parentheses are percentages. recent outbreak in Finland where more than 900/ of the population were immunized, there was evidence indicating that the Finnish poliovirus strains had undergone antigenic evolution because the virus was found to be poorly neutralized by antibodies to the classical poliovirus type 3 vaccine strain (11). Therefore, every effort has to be made to achieve as near 100% coverage as possible and, at the. same time, seroepidemiological surveys should be carried out periodically to monitor the changing pattern of the immunity of the population to the three types of poliovirus. In a country where indigenous paralytic poliomyelitis caused by the wild strain has not been reported since 1973, relying on disease notification and immunization coverage can be misleading. As Singapore is situated in a tropical region which is still endemic for poliomyelitis, wild virus strains will continue to be introduced into the country by foreign workers and other visitors (12). It is very important to ensure that the antibodies induced by the Sabin strains will neutralize or confer protection Table 3. Immune status of the population against human poliovirus 1, 2 and 3 by ethnic group, Singapore, 1982-84 No. immune' to poliovirus Ethnic No. group tested Type 1 Type 2 Type 3 Chinese 269 254 (94.4)b 256 (95.2) 262 (97.4) Malay 101 96 (95.0) 99 (98.0) 99 (98.0) Indian 47 41 (87.2) 47 (100) 44 (93.6) Others 8 8 (100) 8 (100) 6 (75.0) Total 425 399 (93.9) 410 (96.5) 411 (96.7) Neutralizing antibody titres of A 1:4 are considered immune. Figures in parentheses are percentages. 86 K. T. GOH & S. YAMAZAKI against the wild strains isolated from the imported cases reported from time to time in the country. Adults who have not been immunized and have not acquired natural immunity are at risk of contracting the disease when travelling to endemic countries; they have therefore been advised to be immunized prior to departure. In view of the low antibody titres among the older age groups, it would also be advisable for young adults to receive booster doses once every ten years. ACKNOWLEDGEMENTS We thank the Expert Committee on the Immunization Programme, Singapore, for their encouragement and support, and Dr K. Miyamura, Dr T Ogino, Dr H. Tanaka, and Dr E. T. Utagawa of the Central Virus Diagnostic Laboratory, National Institute of Health, Tokyo, for carrying out the laboratory analyses. We would also like to express our gratitude to the medical and nursing staff of the Ministry of Health and Ministry of the Environment for their assistance. RtSUME ETAT IMMUNITAIRE DE LA POPULATION ENVERS LES INFECTIONS A POLIOVIRUS A SINGAPOUR Une enquete seroepidemiologique etendue a e effectuee A Singapour pour evaluer l'etat immunitaire de la popu- lation envers les poliovirus, pour identifier les groupes A haut risque et pour savoir s'il fallait modifier le programme de vaccination antipoliomyelitique chez les enfants, instaure en 1962. Le titrage des anticorps neutralisants envers les poliovirus des types 1, 2 et 3 a e effectue, par la micro- m6thode de culture cellulaire utilisant les cellules Vero, A la Banque de serums de reference de l'OMS A Tokyo. 11 a ete observe que, dans la population Ag&e de 6 mois A 40 ans et plus, les pourcentages de sujets immunises 6taient de 93,9% envers le poliovirus 1, 96,5% envers le poliovirus 2 et 96,7% envers le poliovirus 3. Les adultes de plus de 30 ans avaient une sensibilite relativement plus 6lev6e envers les trois types de virus; ainsi, les anticorps neutralisants faisaient defaut (titre inferieur A 1:4) chez 10,2% A 12% du groupe 30 A 40 ans envers le poliovirus 1, chez 14,3% du groupe d'Age 40 ans et plus envers le poliovirus 2 et chez 14% du groupe d'Age 30-39 ans envers le poliovirus 3. Les titres moyens geometriques diminuaient progressivement dans les groupes d'Age plus eleves bien que des doses de rappel ulterieures aient suscit6 une reponse anamnestique de type secondaire. D'autres analyses des donn6es n'ont pas montre de differences statistiquement significatives dans les taux d'im- munite suivant le sexe et suivant l'appartenance a un des trois groupes ethniques principaux de Singapour (Chinois, Malais et Indiens). L'enquete a confirme l'efficacite du programme national de vaccination pour eliminer la polio- myelite du pays. Cependant, etant donne la constante intro- duction de virus sauvage due a I'afflux de travailleurs &trangers et d'autres visiteurs provenant de regions d'endemie, la couverture vaccinale 6lev6e obtenue pendant les deux dernieres d6cennies devra etre maintenue et il faudra proceder periodiquement a des enquetes epid6mio- logiques pour surveiller l'immunite collective de la popu- lation. De plus, il faudrait conseiller aux adultes non immuns se rendant dans des regions d'end6mie de se faire vacciner contre la poliomyelite. REFERENCES 1. HALE, J. H. ET AL. Large-scale use of Sabin type 2 attenuated poliovirus vaccine in Singapore during a type I poliomyelitis epidemic. British medical journal, 1: 1541-1549 (1959). 2. KNOWELDEN, J. ET AL. Measurement of the protective effect of attenuated poliovirus vaccine. British medical journal, 1: 1418-1420 (1961). 3. LEE, L. H. ET AL. Prevention of poliomyelitis in Singapore by live vaccine. British medical journal, 1: 1077-1080 (1964). 4. LEE, L. H. & LIM, K. A. Eradication of poliomyelitis in Singapore. Singapore medicaljournal, 18: 34-40(1977). 5. LEE, L. H. ET AL. The poliomyelitis immunisation pro- gramme in Singapore. Singapore medical journal, 6: 89-95 (1965). 6. LEE, L. H. ET AL. Seroimmunity of national servicemen in Singapore to poliomyelitis. Singapore medical journal, 22: 262-265 (1981). 7. GOH, K. T. The national childhood immunisation programme in Singapore. Singapore medical journal, 26: 225-242 (1985). 8. WHO Technical Report Series, No 454, 1970 (Multipurpose serological surveys and WHO Serum Reference Banks: report of a WHO Scientific Group). 9. Poliomyelitis surveillance, Netherlands. Weekly epidemiological record, 53 (25): 187 (1978). 10. KIM-FARLEY, R. J. ET AL. Outbreak of paralytic polio- myelitis, Taiwan. Lancet, 2: 1323-1324 (1984). 11. COMMUNICABLE DISEASE SURVEILLANCE CENTRE, U.K. Outbreak of poliomyelitis in Finland. Communicable disease report, No. 6, p. 3 (1985). 12. GOH, K. T. Imported communicable diseases in Singa- pore. Annals of the Academy of Medicine, Singapore, 13: 127-135 (1984).