Outbreak of paralytic poliomyelitis in Finland: widespread circulation of antigenically altered poliovirus type 3 in a vaccinated population.

An outbreak of 9 cases of paralytic poliomyelitis and 1 non-paralytic case occurred in Finland between August, 1984, and January, 1985, after two decades of freedom from the disease attributable to a successful immunisation programme. During the outbreak poliovirus type 3 was isolated from the patients, from about 15% of healthy persons tested, and from sewage water. At least 100 000 persons were estimated to have been infected. With 1.5 million extra doses of inactivated poliovirus vaccine to children under 18 years of age and an oral poliovirus vaccine campaign covering about 95% of the entire population in February-March, 1985, the outbreak was halted in February, 1985. Impaired herd immunity to the epidemic strain of poliovirus type 3, which differed from the type 3 vaccine strains in both immunological and molecular properties, was important in the emergence of this outbreak. The inactivated poliovaccine that had been used in the vaccination programme was relatively weakly immunogenic, especially as regards the type 3 component. Whether continuous antigenic variation of poliovirus type 3 has wider epidemiological implications is not known.

Elimination of poliomyelitis in Finland.

In Finland paralytic poliomyelitis has disappeared after immunization programs carried out exclusively with inactivated poliovirus vaccine (IPV). A sharp decrease in the number of patients with poliomyelitis occurred after mass vaccination in 1960-1961, when 51% of the population had received the complete primary vaccination. Immunity is maintained by continuous vaccination of infants, whose vaccination rate is close to 98%. Intensive poliovirus surveillance in 1972-1974 revealed that dissemination of the virus has also virtually ceased. Serologic surveys indicate that greater than or equal to 90% of individuals older than 15 years of age possess antibodies to all viral types, but in the younger age groups the proportion with antibodies to types 1 and 3 is lower, a finding that is alarming, especially in the case of type 3. Revaccination of seronegative children and conscripts has induced rapid booster-like responses, indicating that fully vaccinated individuals, although without demonstrable antibodies, are protected against poliomyelitis. The new, improved IPV developed in Holland induces satisfactory antibody titers in all vaccinees, with two injections--or perhaps even one--leading to long-lasting immunity.

Etiology of mild acute infectious myocarditis. Relation to clinical features.

The etiology of mild myocarditis, diagnosed on the basis of serial ECG changes during an acute infection, was studied in 126 consecutive conscripts. A fourfold rise in the antibody titers in the paired serum samples was required for a positive etiologic diagnosis. An etiologic diagnosis was made probable in 47% of the patients. Adenovirus was incriminated in 19 patients, vaccinia in 12, influenza A in eight, beta-hemolytic Streptococcus in six, mononucleosis in five and Mycoplasma in three. Chlamydia, influenza B and Coxsackie B4 were each found in two patients; parainfluenza, mumps and adult Still's disease were each found in one patient. The incidence of vaccinia myocarditis was 1/10000 smallpox vaccinations. Clear-cut myopericarditis was usually noted during vaccinia, mononucleosis, Mycoplasma, Chlamydia and Coxsackie B4 infections. Adenovirus and influenza A myocarditis was most often subclinical, being mostly detected only because of ECG screening of patients without cardiac symptoms. Frequent recent ventricular extrasystoles were most often triggered by a beta-hemolytic Streptococcus infection. The etiology of infectious myocarditis seems to reflect the overall profile of viruses and other infective agents in the study population at that particular time. Cardiotrophic viruses such as Coxsackie B only rarely cause myocarditis outside epidemics.

Coxsackie B virus antibodies in myocardial infarction.

Evidence for the association between Coxsackie B virus infections and myocardial infarction was studied in a prospective follow-up examination. Using the micro neutralization test, 9 (15%) of 59 patients with acute myocardial infarction and 1 (2.6%) of 38 control patients showed a fourfold, or higher, antibody increase in paired serum samples against Coxsackie B1-5 viruses. This difference is significant (p less than or equal to 0.05). None of the patients or controls revealed symptoms of a viral infection during the blood sampling. Virus isolation from throat and feces was negative in all patients and controls. This finding agrees with some previous studies suggesting that the Coxsackie B group may in some cases have a causal role in myocardial infarction, or may act as a triggering factor.

Antigen content of inactivated poliovirus vaccine for use in a one- or two-dose regimen.

The immunologic response to inactivated poliovirus vaccine following one and two doses has been studied in infants in developing and developed countries using vaccine prepared at the Rijks Instituut voor de Volksgezondheit, The Netherlands. Virus was grown in microcarrier cultures of monkey kidney cells, purified, concentrated, and inactivated with formalin. The vaccines used contained different quantities of D-antigen units for each of the three types. The data reveal that both antibody and immunologic memory (booster-type responsiveness) were induced in virtually all individuals following a single dose of a sufficient quantity of antigen. Immunologic memory was readily revealed by the booster-type response following a second dose given six months after the first. The degree of booster-type response to a second dose is linked primarily to the quantity of antigen used for primary immunization, and secondarily to the quantity of antigen used for the booster dose. The data base is presented for formulating the antigen content of an inactivated poliovirus vaccine that can be relied upon to be protective after the first dose when given alone or when incorporated with combinations of other antigens (diphtheria-per tussis-tetanus) that may require two or more doses.

Potency test of inactivated polio vaccines in guinea pigs.

A trial with five different inactivated polio vaccines offered an opportunity to compare children's antibody titres with the antibody responses in guinea-pigs elicited by the same batches of vaccines. The potency test in guinea-pigs was carried out according to the European Pharmacopoeia. Polio antibodies were determined by the neutralization test in Vero cell tubes. In our experience the potency test according to the European Pharmacopoeia is suitable for comparing different batches of vaccines manufactured in the same laboratory, but not for comparing vaccines prepared by different manufacturers.

Experiences with polio vaccination and herd immunity in Finland.

Since the mass vaccination in 1960, infants have been vaccinated systematically with inactivated polio vaccine. By school entry 97% of children have received complete primary vaccination. Since 1964 no case of poliomyelitis has been found in Finland. An intensified search for polioviruses among patients with polio-like diseases, among preschool children and in sewage did not reveal any polioviruses, giving evidence of their disappearance. Studies on immunity showed unexpectedly large numbers of preschool children without detectable antibodies to type 1 and especially to type 3. Their response to a booster dose revealed a secondary type reaction, indicating immunity. Thus, antibodies in low or even undetectable titres protect individuals from polio infection and furthermore may eliminate polio viruses from the country.

Theoretical and practical considerations in the application of killed poliovirus vaccine for the control of paralytic poliomyelitis.

This paper contains a summary of the principles upon which the preparation and use of killed poliovirus vaccine (KPV) are based, as well as a summary of earlier and more recent work suggesting the feasibility of formulating a KPV preparation that would be fully and durably effective in a one- or two-dose regimen. The essential factor in the preparation of such a vaccine is the inclusion of a sufficient mass of the immunizing antigen, for each of the three antigenic types of poliovirus, to induce the formation of humoral antibody and/or immunologic memory after the first dose. The results of a series of studies carried out in West African and Scandinavian countries are summarized, which suggest that such a vaccine should contain 40, 8, and 32 D-antigen units for types I, II and III, respectively. If the D-antigen unit measurement is to be used as a guide to KPV standardization, the details of the method of manufacture are important; in this regard, the method of vaccine preparation used at the Rijks Instituut voor de Volksgezondheid should serve as a reference standard for the preparation of vaccines expected to produce the effects described.

Inactivated poliovaccine: adverse reactions and antibody responses.

Adverse reactions and antbody responses after inactivated poliovaccine were studied in 380 children. Fever reaction (greater than or equal to 37.5 degree C rectally) was recorded in 14% of children after the first poliovirus vaccination and in 19% after the second. Restlessness was reported in 15% and 14% of the chidren. Fever reaction exceeding 38.5 degree C was seen in 5% of the vaccines. Before the first vaccination at the age of six month 29% of the 48 children had antibodies against poliovirus type 1 and 2 and 43% against type 3. The first vaccination induced no significant changes in antibody titers. After the second vaccination antibody responses were low and 35%, 9%, and 35% remained seronegative to types 1, 2 and 3, respectively. After the third vaccination at the age of two years the respective geometric mean titers were 1:67, 1:335 and 1:48. No measurable antibodies were found to type 1 in 23%, to type 2 in 2%, and to type 3 in 10%. Only one child was triplenegative. All seronegative children were revaccinated and in all vaccinees a seroconversion ocurred two weeks after the booster dose. The combination of inactivated poliovaccine to DPT (Diphtheria, Tetanus, Pertussis) vaccine induced no significant change in poliovirus antibodies or in adverse reactions.

Infections and other maternal factors as risk indicators for congenital malformations: a case-control study with paired serum samples.

An obstetric population of 48,000 individuals was prospectively followed up for evidence of possible teratogenic factors that might be associated with congenital malformations. Serum samples from 274 mothers of defective children and from paired controls were collected during early pregnancy and approximately one month after delivery and tested for antibodies against ten different viruses, Mycoplasma pneumoniae, and Toxoplasma. These data were supplemented with clinical information on infections, other diseases, drug intake, and other potentially teratogenic factors during pregnancy. Mothers of defective children had more seroconversions (fourfold or greater increase in titer) than the controls, 123 vs. 86. This difference was mainly due to an increase in herpes simplex viruses 1 and 2, cytomegalovirus, varicella-zoster virus, and Toxoplasma titers. In addition, the number of reported diseases during the pregnancy, the intake of drugs (especially analgesics and hormones), and the number of earlier abortions were greater in the mothers of the defective children than in the controls.

The efficacy of polio vaccination in Finland.

The inactivated polio vaccine has eliminated not only the disease but also polioviruses from Finland. The last endemic cases of poliomyelitis were seen in 1961, and two were imported in 1964. To check whether polioviruses were still circulating in Finland, an intensified search for polioviruses was carried out in 1972-1974 in sewage, among patients with polio-like diseases and among healthy preschool children. Viruses, mostly Coxsackie B viruses, were isolated from sewage in 67% of the samples, but no polioviruses. The etiology of aseptic meningitis and other polio-like diseases was explained in 52% of the cases, but without isolation of any polioviruses. Faeces samples from 4878 different preschool children were examined: 15.7% of them excreted viruses, but not polioviruses.

Polio antibodies and HLA antigens in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal, progressive disease of the central nervous system. Its possible association with poliomyelitis was studied by measuring neutralizing antibodies against polio virus types 1, 2 and 3 in the sera and cerebrospinal fluids of 11 ALS-patients, but antibody titers did not markedly differ from those of the controls. The HLA antigens of 12 ALS patients were also determined, in order to reveal any possible genetically-determined susceptibility to the disease. Possible association of ALS with HLA-Bw40 was noted. In addition, the Bw40 antigen seemed to be associated with milder progression of the disease. The lymphocytes of the ALS patients seemed defective in their capacity to stimulate allogenic lymphocytes, possibly due to a relative decrease of B cells in the peripheral blood. Joint efforts of study groups of neuroepidemiology, immunology and genetics should be mobilized to reveal the true nature of these findings.