Margareta Böttiger

Measles antibody: comparison of long-term vaccination titres, early vaccination titres and naturally acquired immunity to and booster effects on the measles virus

A two-dose vaccination programme, using a combined measles, mumps and rubella vaccine (MMR) and administration at the ages of 18 months and 12 years, was introduced into Sweden in 1982. Since the combined MMR vaccine was introduced, a yearly evaluation of the immunity patterns and seroconversion rates in 12-year-old children has been carried out. This study includes three study groups. All groups consisted of pre- and postvaccination samples from 12-year-old children taken in connection with the MMR immunization. There were 332 paired samples from children who 8-10 years previously had received live measles vaccine. Prevaccination sera from these children represent late postvaccination titres. The postvaccination sera of 49 children seronegative to measles before vaccination, obtained 2 months after vaccination, represent early postvaccination immunity. Ninety-five children who had not been vaccinated earlier and who were seropositive to measles represent naturally acquired immunity. All samples were studied by an enzyme-linked immunosorbent assay (ELISA). Sera from children with late postvaccination immunity had significantly lower titres than children in group 2, who represented early postvaccination sera (p < 0.001). Children with naturally acquired immunity had significantly higher titres than children with vaccine-induced immunity titres (p < 0.001). After revaccination of the previously vaccinated children, a significant booster rise was seen (p < 0.001). After revaccination of children with naturally acquired immunity, no significant booster effect was observed. Sixty-five children of the 332 (20%) previously vaccinated children had no or borderline measles titres prior to the booster. The study suggests that the vaccine-induced measles antibodies decline with time and may fall under the protective level.(ABSTRACT TRUNCATED AT 250 WORDS)

Serological Immunity to Diphtheria in Sweden in 1978 and 1984

Antibody levels in relation to diphtheria toxin were studied in 2409 serum specimens collected from different age-groups in Sweden in 1977-78 and 1983-84. Among children and young adults less than 20 years of age, 46% showed antibody levels considered to be protective (greater than or equal to 0.1 IU/ml). The corresponding percentage among adults was 21%. In the child population, 35% showed a relative degree of protection (less than 0.1-greater than or equal to 0.01 IU/ml), while 19% lacked immunity (less than 0.01 IU/ml). After 40 years of age, only 15% showed protective levels. No difference between males and females was seen in the younger population, while women had a lower prevalence of immunity than men among the adult population. Thus, more than 70% of the adult women lacked immunity, while the figure for the men was 50%.

Antitoxin Antibody Levels and the Outcome of Illness during an Outbreak of Diphtheria among Alcoholics

During an outbreak of diphtheria among alcoholics in Göteborg, Sweden, a study was made of the diphtheria-antitoxin antibodies in serum samples from 8 clinical cases and 36 carriers of toxin-producing Corynebacterium diphtheriae. 33/36 carriers were antibody-positive and had antitoxin titres greater than 0.01 IU/ml, a level which is regarded as relative protective, while only 1/8 clinical cases had such a titre. This patient presented a mild illness with no complications. The results of the study of this outbreak stress the importance of maintaining adequate antibody levels against diphtheria in highly developed societies.

A 15-year surveillance study of antibodies to herpes simplex virus types 1 and 2 in a cohort of young girls

A cohort of 839 young girls at the ages of 14 and 15 years was screened for total antibodies to herpes simplex virus (HSV) and, if positive, for specific antibodies to HSV-2, by means of a sensitive, enzyme-linked immunosorbent assay (ELISA). The cohort was followed from 1972-1987. Blood samples were obtained on six occasions during these 16 years. In total, 2270 blood samples were taken. The number of sero-converting girls was studied in relation to calendar time. Two methods were constructed for the statistical analyses. The first of these gave an estimate of the sero-prevalence at different points in time. This analysis showed that the sero-prevalence which was 23% against HSV-1 in 1972 had increased to 36% in 1976. At the end of the study in 1987, 50% of the cohort had sero-converted against HSV-1. The proportion of girls who had sero-converted against HSV-2 was 0.4% in the 14-15-year-olds and had reached 22% by the end of the study. The second statistical method used all the available information implicit in the observations so as to obtain a maximum-likelihood (ML) estimate of the prevalence. The ML estimates were slightly more precise, but the two estimates did not differ significantly. The observations were further analysed by the Mantel-Haenszel test in order to see if there was any dependence between positivity to HSV-1 and HSV-2 respectively but none was found.

Twenty years' experience of rubella vaccination in Sweden: 10 years of selective vaccination (of 12-year-old girls and of women postpartum) and 13 years of a general two-dose vaccination☆

Two different strategies for the prevention of rubella-induced malformations have now been practised in Sweden, both reaching 90% or more of the target populations. The first was initiated in 1973-1974 and targeted schoolgirls, susceptible women after pregnancy and women at special risk. The second programme-a two-dose measles, mumps, rubella vaccination (MMR) of both boys and girls at the ages of 18 months and 12 years-was introduced in 1982. The percentage of susceptible pregnant women was gradually reduced from 12% in 1975 to 2.8% in 1987 and to just below 2% in 1994. The majority of the non immune are unvaccinated, these being either Swedes born before 1963 or immigrants. Before 1974 on average 14 severely rubella damaged children were reported yearly. Between 1975 and 1985 only a mean of two cases per year were recorded. Since 1985 no child with the rubella syndrome has been registered.

Long-term follow-up study of rubella antibodies in naturally immune and vaccinated young adults

Selective rubella vaccination of 12-year-old schoolgirls was introduced in Sweden in 1973 and at the same time a long-term follow-up cohort study was initiated. In 1982, a two-dose programme with a combined vaccine against measles, mumps and rubella (MMR) was introduced and vaccinations were given at the ages of 18 months and 12 years to both boys and girls. The cohort initially comprised 486 girls. It was followed for between 8 and 16 years. All the girls enrolled were seronegative before vaccination and had seroconverted to a haemagglutination-inhibition (HAI) titre of at least 1:16. On the last test occasion 16 years later, 22% had titre values below 1:16, and 6% lacked detectable antibodies against rubella (< 1:8). A fourfold or greater rise in titre was seen in 36% of the girls during the first 8 years of observation, whereas during the following 8 years only 1% showed a significant increase of titre values. The geometric mean titre declined from 1:110 to 1:34 during the first 8 years and further to 1:18 during the following 8 years. From 1982 to 1990, the seroimmunity to rubella of 18-year-old girls and boys was studied yearly. The number studied was 3308 18-year-old schoolgirls and 6347 18-year-old recruits born between 1964 and 1972. The recruits were divided into two groups, 4610 unvaccinated and born in 1964-1969 and 1737 vaccinated and born in 1970-1972. Seropositive recruits in the first group were thus naturally immune only, while the second group had a mixture of natural and vaccine-induced immunity.(ABSTRACT TRUNCATED AT 250 WORDS)

Screening for HIV-1 antibodies in pregnancy: results from the Swedish national programme.

OBJECTIVE--To determine the effectiveness of a national screening programme for HIV infection in pregnant women. DESIGN--Observational study. SUBJECTS--All pregnant women presenting to antenatal or abortion clinics. SETTING--Sweden, September 1987 to December 1991. MAIN OUTCOME MEASURES--Number and characteristics of infected women. RESULTS--By the end of the study period 510,000 tests had been performed and 54 women with HIV infection identified (1.06/10,000). Of the 33 women identified in Stockholm, 14 women (4.4/10,000) had attended abortion clinics and 19 antenatal clinics (1.8/10,000; p < 0.05). Three women had been intravenous drug users, one was infected through a blood transfusion, and 50 were probably infected sexually. Of the 20 women who attended antenatal clinics early enough to allow an abortion, 12 continued with their pregnancies. CONCLUSIONS--Testing of all women, not just those perceived to be at risk, probably contributed to the high uptake of HIV testing. With high uptake such screening provides valuable data on spread of HIV in the heterosexual population and presents opportunity for preventing transmission of HIV to children and partners.

Polio immunity to killed vaccine : an 18-year follow-up

Two hundred and fifty children born in 1967 and vaccinated with killed polio vaccine in Sweden were followed for 18 years and tested for neutralizing antibodies against polio. All of them had demonstrable antibodies at the age of 18. Sixty-four children were tested in samples collected throughout the years. After a more marked fall of antibody titres during the first few years after vaccination, the decline levelled off to a mean decrease in titre of 0.05-0.10 log10 per year. In half of them, the routine vaccination comprising a fourth dose at 6 years of age was changed and this booster was postponed to the age of ten. The children given the booster dose at ten had significantly higher antibody levels at 18 years of age than those given it at six.

Epidemiology and Immunity to Tetanus in Sweden

An investigation of tetanus antitoxin titres in the Swedish population was carried out in 1985. In Sweden, primary vaccination against tetanus has consisted of 3 doses at intervals of 4-6 weeks, beginning in the 2nd or 3rd month of life. A booster dose is offered to school children at 8-10 years of age. Three levels of antitoxin concentration (0.01, 0.05 and 0.1 U/ml) are used to demonstrate different titre levels. The interpretation is based on the premise that a serum level of 0.01 U/ml is sufficient to protect the subject against clinical tetanus. A protective titre level (greater than 0.01 U/ml) was found in 98-99% of children and young adults. A rapid decrease in the number of children with high titres (0.05-0.1 U/ml) was observed after the age of 1 and was very low in the 4-5-year-old children. An increase in the number with titres of 0.05 and 0.1 U/ml was seen after the booster dose given at school. A protective level was detected in all 21-30-year-old men and in 94% of the women, in 94% of 31-50-year-old men and in 73% of the women in the same age group. 70% of 31-40-year-old men reached antitoxin concentrations of 0.1 U/ml, and 38% of the 41-50-year-olds. The corresponding figures for women were 22% and 16% respectively. In people over 60 years, 80% of the men and 56% of the women reached protective levels of antibodies.

Methods for screening the naturally acquired and vaccine-induced immunity to the measles virus

Since the measles, mumps and rubella (MMR) vaccine was introduced into Sweden in 1982, a yearly evaluation of the immunity patterns and sero-conversion rates in 12-year-old children has been carried out. Since 1977, about half of the pre-school children have been vaccinated against measles. This study includes two study groups. (1) 145 selected pre- and post-vaccination samples tested by the haemolysis-in-gel (HIG) technique and the neutralization test (NT). The selection was made from 1298 12-year-old schoolchildren in 1986 and 1987, whose pre-vaccination sera had shown negative or borderline reactions to the HIG technique. (2) Consecutive pre- and post-vaccination samples obtained from 190 vaccinees in 1988 and 1989. These samples were studied by an enzyme-linked, immunosorbent assay (ELISA) and compared to the NT. The NT and the HIG tests yielded congruent results in early post-vaccination sera from children susceptible to measles prior to vaccination. In late post-vaccination samples, the NT and the HIG tests were discordant, up to 25% of the NT-positive samples being negative by the HIG technique. In no instance did the ELISA produce discrepant results, compared with those of the NT. With both this assays significantly lower antibody levels were detected in late post-vaccination sera (8-11 years) compared to early post-vaccination samples (P less than 0.001) or to sera obtained after natural infection.