Waning antibody levels and avidity: implications for MMR vaccine-induced protection.

BACKGROUND: The measles-mumps-rubella (MMR) vaccine is effective in eliciting a good antibody response. In addition to the amount of antibodies, the avidity of these antibodies might be important in protecting against disease. METHODS: The amount of circulating antibodies for measles, mumps, and rubella was measured with enzyme immunoassays, and the avidity of these antibodies was determined by urea dissociation. Three groups of twice-MMR-vaccinated individuals and 1 group of naturally infected individuals were studied. One vaccinated group (n = 71) was studied 6 months and 20 years after a second MMR vaccination. RESULTS: The antibody avidity indexes were high for measles and rubella but low for mumps. Twenty years after a second MMR vaccination, antibody levels for all 3 viruses waned. Also, the mean avidity index decreased by 8% for measles, 24% for mumps, and remained unchanged for rubella. Antibody avidity correlated with antibody concentration for measles. There was partial correlation for rubella and no correlation for mumps. CONCLUSIONS: Measles and rubella induced high-avidity antibodies and mumps induced low-avidity antibodies after both vaccination and natural infection. Waning of both the concentration as well as the avidity of antibodies might contribute to measles and mumps infections in twice-MMR-vaccinated individuals.

MMR vaccination and disease elimination: the Finnish experience.

Measles, mumps and rubella (MMR) vaccinations have been included in Finland's national vaccination program as a two-dose schedule since 1982. Owing to the high (>95%) coverage of vaccinations, indigenous MMR diseases were eliminated from Finland by the mid-1990s. In 1982, the incidence of measles, mumps and rubella was 105, 43 and 64 per 100,000 population, respectively, but declined to 0.1 per 100,000 population for all MMR diseases in 1995. Since then, the few cases of measles, mumps and rubella imported annually have not caused any outbreaks. Several research projects that started along with the vaccination campaign have provided important support throughout the program. The vaccine was proven to be safe, immunogenic and effective. Antibody follow-up has revealed that MMR vaccine-induced antibodies wane over time, and concerns have arisen about the continuation of this good situation. High vaccination coverage, enhanced surveillance and preparedness to administer additional doses when needed are key factors for future success. Here we present an overview of MMR vaccinations and the Finnish experience of the MMR disease elimination process, and we describe surveillance activities in the era following elimination in Finland.

Factor V Leiden as risk factor for unexplained stillbirth--a population-based nested case-control study.

INTRODUCTION: Stillbirth is a relatively uncommon pregnancy complication in developed countries yet causing strong emotional burden. Thrombophilia has been associated with stillbirth but population-based studies are few. We assessed selected genetic and acquired parameters for the risk of unexplained stillbirth, including FV Leiden. MATERIALS AND METHODS: We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and accepted according to strict criteria after checking their medical records. Stillbirth was defined as intrauterine fetal death > or =22weeks of gestation. We excluded stillbirths due to lethal congenital developmental conditions, umbilical cord complications, and infections. We studied 44 cases of unexplained stillbirth and 766 controls. RESULTS: FV Leiden was associated with 3.8-fold (95% CI 1.2-11.6) risk for unexplained stillbirth, 3.9-fold (95% CI 1.1-13.9) risk for unexplained late stillbirth (> or =28weeks of gestation), and 10.8-fold (95% CI 2.1-55.3) risk for unexplained stillbirth with placental lesions. The same figures for singleton pregnancies were 3.1-fold (95% CI 0.9-10.9), 4.3-fold (95% CI 1.2-15.3), and 10.6-fold (95% CI 2.1-54.3). Slightly increased risk associated with blood group O was not statistically significant. We found a trend for increased risk in advanced maternal age and smoking during pregnancy. High pre-pregnancy BMI was not associated with increased risk, nor was low educational level or first pregnancy. CONCLUSIONS: Our population-based study from a country with comprehensive prenatal care confirms the association between FV Leiden and unexplained stillbirth.

Blood group AB and factor V Leiden as risk factors for pre-eclampsia: a population-based nested case-control study.

INTRODUCTION: Pre-eclampsia is an important cause of maternal morbidity and mortality. Its etiology is still unknown. Clinical symptoms correlate with activation of coagulation and inherited thrombophilia has been associated with pre-eclampsia. ABO blood group has been associated with thrombotic disorders and pre-eclampsia. We assessed ABO blood group, seven thrombophilia associated polymorphisms, and anti-beta2-glycoprotein I antibodies as risk factors for pre-eclampsia. MATERIALS AND METHODS: We performed a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers and medical records were reviewed. We studied 248 cases fulfilling strict criteria for pre-eclampsia and 679 controls. Severe pre-eclampsia, early pre-eclampsia, and pre-eclampsia with intra-uterine growth restriction (IUGR) were analyzed separately. RESULTS: Blood group AB increased the risk for pre-eclampsia as a whole (OR 2.1, 95% CI 1.3-3.5), and in the three subgroups (OR 2.3, 3.8, 3.4; 95% CI 1.3-3.9, 2.0-7.1, 1.6-7.1). FV Leiden increased the risk as a whole (OR 1.7, 95% CI 0.8-3.9), and in the three subgroups, although not statistically significantly. Anti-beta2-glycoprotein I antibodies were not associated with pre-eclampsia. High body mass index, diabetes, first pregnancy, and twin pregnancy increased the risk from 1.5-fold to 8.2-fold. CONCLUSIONS: Our results confirm and extend the prior observation of blood group AB being a risk factor for pre-eclampsia. ABO blood group is known from all pregnant women. The value of blood group as risk factor for pre-eclampsia should be further assessed in prospective studies. In this study, FV Leiden was not statistically significant risk factor.

Measles, mumps, and rubella in Finland: 25 years of a nationwide elimination programme.

A nationwide programme to eliminate indigenous measles, mumps, and rubella, mainly by vaccinating children twice, was launched in Finland in 1982. Strong scientific methods to examine the immunological, clinical, and epidemiological variables have accompanied the programme. Measles was eliminated in 1996, and mumps and rubella in 1997. Now, 25 years from the start of this programme, Finland is facing new challenges. Since elimination, eight, 32, and six cases of measles, mumps, and rubella, respectively, have been reported. Of those, seven cases were failures of mumps vaccinations and one case was a rubella vaccination failure. Although outbreaks have been averted, the risks are increasing because the unvaccinated population is growing, epidemics occur in nearby countries, breakthrough cases arise, and declining antibodies suggest waning immunity. The chances for natural boosters are now at a minimum, and individuals are increasingly protected solely by vaccination. To maintain the absence of these diseases, the adopted policy should continue, but the country should also be prepared for prompt supplementary vaccinations in the case of epidemic outbreaks.

Mumps outbreaks in Canada and the United States: time for new thinking on mumps vaccines.

Mumps epidemics in Canada and the United States prompted us to review evidence for the effectiveness of 5 different vaccine strains. Early trials with the Jeryl Lynn vaccine strain demonstrated an efficacy of approximately 95%, but in epidemic conditions, the effectiveness has been as low as 62%; this is still considerably better than the effectiveness of another safe strain, Rubini (which has an effectiveness of close to 0% in epidemic conditions). The Urabe vaccine strain has an effectiveness of 54%-87% but is prone to cause aseptic meningitis. Little epidemiological information is available for other vaccines. The Leningrad-Zagreb vaccine strain, which is widely used in developing countries and costs a fraction of what vaccines cost in the developed world, seems to have encouraging results; in 1 study, the effectiveness of this vaccine exceeded 95%. Aseptic meningitis has also been reported in association with this vaccine, but the benign nature of the associated meningitis was shown recently in Croatia. Also, the Leningrad-3 strain seems to be effective but causes less-benign meningitis. No mumps vaccine equals the best vaccines in quality, but the virtually complete safety of some strains may not offset their low effectiveness. Epidemiological data are pivotal in mumps, because serological testing is subject to many interpretation problems.

An unfavorable combination of Factor V Leiden with age, weight, and blood group causes high risk of pregnancy-associated venous thrombosis: a population-based nested case-control study.

INTRODUCTION: Hereditary and acquired risk factors increase the risk for thrombosis among pregnant women. Few risk estimates are, however, well established. The aim of the present study was to assess risk for pregnancy-associated venous thrombosis of factor V Leiden (FVL), FII G20210A, FV A4070G, MTHFR C677T, TFPI C536T, PROC T38853G, FXIII V34L, blood group, age, and body mass index (BMI), and their interactions and public health impact. MATERIALS AND METHODS: Study design is a population-based nested case-control study of 100,000 consecutive pregnancies in Finland. Cases and controls were identified by combining national registers. Thirty four cases with objectively diagnosed venous thrombosis and 641 controls were studied. RESULTS: FVL (OR 11.6, 95% CI 3.6-33.6), age >35 vs. <25 (OR 6.3, 95% CI 1.7-23.1), and BMI >30 vs. <25 (OR 5.6, 95% CI 2.3-13.9) were associated with thrombosis. Overall absolute risk of a FVL carrier was 1 in 314. FVL interacted with age, BMI, and blood group. Population attributable risk proportion was 19% for FVL, 23% for age >35, 33% for BMI >25, and 35% for non-O blood group. Unexpectedly, the prevalence of FVL increased with age in controls. CONCLUSIONS: FVL appeared as a strong risk factor for pregnancy-associated venous thrombosis. Especially in elderly overweight mothers, FVL may cause a substantial thrombosis risk. Further studies are needed to confirm the increased prevalence of FVL in elderly mothers with normal pregnancies.

IgG avidity to distinguish secondary from primary measles vaccination failures: prospects for a more effective global measles elimination strategy.

The nearly 40-year long debate on the relevance of secondary measles vaccination failure has been inconclusive because a feasible method for the assessment of the duration of immunity has been lacking. Even if a two-dose measles vaccination policy is now universally endorsed, WHO still officially adheres to the view that a single successful measles vaccination, without natural boosters, induces a lifelong immunity and deems secondary failures epidemiologically irrelevant - in the belief that the latter are rare and do not participate in the transmission chain. A recently published study on measles-IgG avidity, which allows for separation of secondary from primary vaccination failures, tentatively showed that the official view does not necessarily hold true. The results may have wide implications on global measles eradication efforts. The potential of IgG avidity measurement in complex postvaccination measles epidemiology is discussed.