Seroepidemiology of mumps in Europe (1996-2008): why do outbreaks occur in highly vaccinated populations?

Mumps outbreaks have recently been recorded in a number of highly vaccinated populations. We related seroprevalence, epidemiological and vaccination data from 18 European countries participating in The European Sero-Epidemiology Network (ESEN) to their risk of mumps outbreaks in order to inform vaccination strategies. Samples from national population serum banks were collected, tested for mumps IgG antibodies and standardized for international comparisons. A comparative analysis between countries was undertaken using age-specific mumps seroprevalence data and information on reported mumps incidence, vaccine strains, vaccination programmes and vaccine coverage 5-12 years after sera collection. Mean geometric mumps antibody titres were lower in mumps outbreak countries [odds ratio (OR) 0·09, 95% confidence interval (CI) 0·01-0·71)]. MMR1 vaccine coverage ⩾95% remained protective in a multivariable model (P < 0·001), as did an interval of 4-8 years between doses (OR 0·08, 95% CI 0·01-0·85). Preventing outbreaks and controlling mumps probably requires several elements, including high-coverage vaccination programmes with MMR vaccine with 4-8 years between doses.

Comparative hepatitis A seroepidemiology in 10 European countries.

The WHO recommends hepatitis A virus (HAV) immunization according to level of transmission and disease burden. We aimed to identify susceptible age groups by standardized serosurveys to inform HAV vaccination policy in participating countries: Belgium, Czech Republic, England, Finland, Germany, Italy, Lithuania, Malta, Romania, and Slovakia. Each country tested national serum banks (n = 1854-6748), collected during 1996-2004, for anti-HAV antibodies. Local laboratory results were standardized to common units. Forty-one per cent of those aged <30 years and 6% of those aged ≥30 years were susceptible to HAV in Romania; compared to 70-94% and 26-71%, respectively, elsewhere. Romania reported high HAV incidence in children and young adults. Other countries reported HAV disease primarily in older risk groups. The results suggest low level of HAV transmission in most of Europe. Romania, however, appeared as an area with intermediate transmission. Vaccination of risk groups in countries with high susceptibility of young and middle-aged adults needs to be continued.

Travellers returning with measles from Thailand to Finland, April 2012: infection control measures.

Countries with no autochthonous measles run the risk of the virus being imported by travellers and transmitted to unprotected citizens. In April 2012, two travellers from Finland and one from Estonia were diagnosed with measles after returning from Phuket, Thailand. They were contagious on their return flights and subsequently exposed several individuals, prompting extensive infection control measures. Two secondary cases were detected: one child who had received one vaccine dose and another who was fully vaccinated.

Modelling the impact of varicella vaccination on varicella and zoster.

It has been suggested that the incidence of herpes zoster may increase due to lack of natural boosting under large-scale vaccination with the varicella vaccine. To study the possibility and magnitude of such negative consequences of mass vaccination, we built a mathematical model of varicella and zoster epidemiology in the Finnish population. The model was based on serological data on varicella infection, case-notification data on zoster, and new knowledge about close contacts relevant to transmission of infection. According to the analysis, a childhood programme against varicella will increase the incidence of zoster by one to more than two thirds in the next 50 years. This will be due to increase in case numbers in the 35 years age groups. However, high vaccine coverage and a two-dose programme will be very effective in stopping varicella transmission in the population.

High frequency of cross-reacting antibodies against 2009 pandemic influenza A(H1N1) virus among the elderly in Finland.

Since May 2009, the pandemic influenza A(H1N1) virus has been spreading throughout the world. Epidemiological data indicate that the elderly are underrepresented among the ill individuals. Approximately 1,000 serum specimens collected in Finland in 2004 and 2005 from individuals born between 1909 and 2005, were analysed by haemagglutination-inhibition test for the presence of antibodies against the 2009 pandemic influenza A(H1N1) and recently circulating seasonal influenza A viruses. Ninety-six per cent of individuals born between 1909 and 1919 had antibodies against the 2009 pandemic influenza virus, while in age groups born between 1920 and 1944, the prevalence varied from 77% to 14%. Most individuals born after 1944 lacked antibodies to the pandemic virus. In sequence comparisons the haemagglutinin (HA) gene of the 2009 pandemic influenza A(H1N1) virus was closely related to that of the Spanish influenza and 1976 swine influenza viruses. Based on the three-dimensional structure of the HA molecule, the antigenic epitopes of the pandemic virus HA are more closely related to those of the Spanish influenza HA than to those of recent seasonal influenza A(H1N1) viruses. Among the elderly, cross-reactive antibodies against the 2009 pandemic influenza virus, which likely originate from infections caused by the Spanish influenza virus and its immediate descendants, may provide protective immunity against the present pandemic virus.

[Molecular-epidemiologic characteristic of hepatitis A outbreak among workers of food stores network].

Investigation of hepatitis A (HA) outbreak developed in 2005 among workers of food stores networkwas performed using conventional epidemiologic diagnostics as well as methods of molecular epidemiology. In 14 of 15 ill persons, using polymerase chain reaction, HAV RNA was detected by PCR in serum obtained on 2 - 25 day of illness (mean - 9.3 days). In 10 cases it was possible to determine nucleotide sequence of VP1/VP2 region of HAV genome and perform phylogenetic analysis of obtained isolates. It was determined that all isolates belonged to subgenotype IA, had high degree of homology and grouped in one cluster. These findings demonstrate their descendance from one source of infection, which, with high degree of probability, was the cook who made salads from fresh vegetables. HAV strain, which caused this epidemic outbreak circulates in Saint Petersburg for a long time and was already detected in 2004. Importance of vaccination against HA for persons working in manufacturing and distribution of food and use of molecular epidemiologic methods of surveillance for this infection is underlined.

Serious adverse events after measles-mumps-rubella vaccination during a fourteen-year prospective follow-up.

BACKGROUND: Several disorders have been attributed to measles-mumps-rubella (MMR) vaccination during the past decade. The aim of this prospective follow-up study was to identify serious adverse events causally related to MMR vaccination. METHODS: When the MMR vaccination program was launched in Finland in 1982, a countrywide surveillance system was set up to detect serious adverse events associated with MMR. To obtain detailed case histories vaccinees' clinical charts were reviewed. Serum samples were analyzed to trace concurrent infections. SETTING: All hospitals and health centers in Finland from 1982 through 1996. RESULTS: Immunization of 1.8 million individuals and consumption of almost 3 million vaccine doses by the end of 1996 gave rise to 173 potentially serious reactions claimed to have been caused by MMR vaccination. In all, 77 neurologic, 73 allergic and 22 miscellaneous reactions and 1 death were reported, febrile seizure being the most common event. However, 45% of these events proved to be probably caused or contributed by some other factor, giving an incidence of serious adverse events with possible or indeterminate causal relation with MMR vaccination of 5.3 per 100,000 vaccinees or 3.2 per 100,000 vaccine doses. CONCLUSIONS: Causality between immunization and a subsequent untoward event cannot be estimated solely on the basis of a temporal relation. Comprehensive analysis of the reported adverse reactions established that serious events causally related to MMR vaccine are rare and greatly outweighed by the risks of natural MMR diseases.

Twice vaccinated recipients are better protected against epidemic measles than are single dose recipients of measles containing vaccine.

OBJECTIVE: To study measles risk after revaccination. DESIGN: A population-based case-control study during an epidemic season. MAIN OUTCOME MEASURE: Relative serologically confirmed measles risk. PARTICIPANTS AND METHODS: 153 vaccinated cases, mostly from rural areas, were serologically confirmed as measles at the central laboratory in 1988-89. A randomly selected group of 453 controls from either municipalities of vaccinated cases or from areas where measles attack rate was > 600/10(5), was identified via the population registry. Vaccination and measles histories of cases and controls were determined from official vaccination cards. RESULTS: Once and twice vaccinated had crude relative risk 15.6 and 2.3 compared with thrice vaccinated. When cases who had received their first vaccination at less than 14 months of age were omitted from analysis, once vaccinated had 4.0 (95% CI 1.2, 16.6) times higher age adjusted measles risk compared with twice vaccinated. When, omission was extended to cases from one particular municipality where even revaccinees had high measles risk during an explosive outbreak the corresponding risk ratio was 17.8 (2.8, 67.8). CONCLUSIONS: Twice vaccinated have better protection against epidemic measles compared with single dose recipients.

Epidemiology of rubella in Finland.

Before rubella vaccination programmes began, rubella infection was prevalent in Finnish children. The disease occurred as epidemics at intervals of a few years. Rubella infection was most often contracted between the ages of 2 and 12 years. Vaccinations specifically aimed at eradicating rubella were begun with monocomponent vaccine in the mid-1970s, and the measles, mumps and rubella (MMR) vaccination programme with two injections got underway in 1982. A clear reduction in rubella cases was evident a few years after the launch of the MMR programme. Owing to a sufficiently high vaccination coverage (>95% since 1987), circulation of the indigenous rubella virus in the Finnish population ceased in the late 1990s. Some rubella cases have been imported to Finland since elimination, but they have not caused any secondary cases. This shows unambiguously that protection against rubella continues to be effective, although our cohort studies imply that the vaccine induced antibody levels do decrease with time. The MMR programme has also eliminated congenital rubella syndrome (CRS) from the country. The last CRS case was recorded in 1986. As a result of the high coverage two dose MMR vaccination programme, rubella was successfully eliminated from Finland. How long the acquired protection will last remains to be seen.

[A virological description of serous meningitis in children immunized with vaccine against epidemic parotitis]. / Virusologicheskaia kharakteristika seroznykh meningitov u detei, immunizirovannykh vaktsinoi protiv épidemicheskogo parotita.

The morbidity structure was analyzed in children vaccinated against epidemic parotitis in 1993-2002. Eight children (4 with serous meningitis and 4 with lesions of the salivary glands) underwent virologic and immunologic examinations. The molecular typing of the SH-gene fragment of the parotitis virus showed the process in 7 cases to be provoked by the vaccination strain. Presumedly, progressing vaccine-associated meningitis inhibits antibody formation. The total incidence of vaccine-associated meningitis was shown, according to Saint Petersburg data, to be not high, which testifies to a low reactogenicity of the Russian vaccine strain.

[Characteristics of the manifest and latent components of the hepatitis A epidemic process in cities of Russia]. / Kharakteristika manifestnogo i skrytogo komponentov épidemicheskogo protsessa gepatita A v gorodakh Rossii.

Seroepidemiological study of hepatitis A (HA) morbidity was carried out in three Russian cities, with different levels of HA morbidity. The study included the analysis of HA morbidity for 22 years, the determination of antibodies to HA virus (anti-HAV) in 2,958 healthy persons aged 0-12 months to 40 years and older. In one of the cities 7 isolates of HA virus were obtained from unrelated sources and the genotypes of the virus were determined. The study revealed that the frequency of seropositive cases among persons of different ages correlated with the level and prolonged dynamics of HA morbidity. According to the occurrence of anti-HAV, such cities as St. Petersburg, Rostov-on-Don and Yakutsk may be at present classified as territories, moderately endemic in HA. At the same time in the 90 s the epidemic situation in HA was more favorable in Rostov-on-Don than in two other cities. The suggestion was made that a high proportion of seropositive persons among the population of St. Perersburg was linked with an almost twofold rise in HA morbidity in 1993-1995 caused by genotype 1 of the virus. Seroepidemiological studies in HA during the period of a drop in morbidity acquire special importance in the surveillance and control system of this infection.

Rabies control in Finland: a 12-year experience of human and veterinary surveillance.

Little is known about the public health burden of rabies in rabies-free countries. In these countries, the surveillance of suspected and treated cases serves as a substitute for estimating the risk and burden of human rabies because deaths due to rabies are extremely rare. Suspected rabies exposures among Finnish inhabitants were characterized using data from the National Infectious Disease Registry as well as animal surveillance data from the Finnish Food Safety Authority Evira, 1995-2006. In total, 195 suspected rabies exposures were reported (incidence 3/million inhabitants/year). Exposures were equally common among both genders and the median age was 35 years. Exposures were more common among 20- to 49-year olds than among other age groups. Less than one-third of the exposures occurred in Finland (incidence of indigenous exposures 0.9/million inhabitants/year). Indigenous rabies exposures were most frequently reported in southeastern Finland, with cats and dogs as the main sources. The high prevalence in the Baltic countries and Russia poses a risk for rabies reintroduction. The present control of wildlife rabies appears successful and important. The import of animals from endemic areas, however, remains a risk, which can be reduced by increasing public awareness of the disease, vaccination of imported animals and better rabies control in endemic countries.

The European Sero-Epidemiology Network 2 (ESEN2): standardization of assay results for hepatitis A virus (HAV) to enable comparisons of seroprevalence data across 15 countries.

The European Sero-Epidemiology Network 2 (ESEN2) aimed to compare serological results of vaccine-preventable diseases across Europe. To ensure direct inter-country comparability of hepatitis A virus antibody (anti-HAV) measurements, a standardization panel of 150 sera was developed by a designated reference laboratory and tested by participating national laboratories using assays of choice; each country's results were subsequently regressed against those of the reference laboratory. Quantitatively, the assays were generally highly correlated (R2>0.90). Nevertheless, qualitative comparisons indicated that results obtained with different assays may differ despite the usage of well-established international and local standards. To a great extent standardization successfully alleviated such differences. The generated standardization equations will be used to convert national serological results into common units to enable direct international comparisons of HAV seroprevalence data. The results of this study are expected to contribute to the evaluation and potential improvement of the currently employed immunization strategies for hepatitis in Europe.

A comparison of hepatitis B seroepidemiology in ten European countries.

To inform current and future vaccination strategies, we describe the seroepidemiology of hepatitis B virus (HBV) infection in ten representative European countries using standardized serology that allowed international comparisons. Between 1996 and 2003, national serum banks were compiled by collecting residual sera or by community sampling; sera were then tested by each country using its preferred enzyme immunoassays and testing algorithm, and assay results were standardized. Information on current and past HBV vaccination programmes in each country was also collected. Of the ten countries, six reported low levels (<3%) of antibodies against HBV core antigen (anti-HBc). Of the eight countries testing for HBV surface antigen (HBsAg), the highest prevalence was reported in Romania (5.6%) and in the remaining seven countries prevalence was <1%. Universal HBV vaccination programmes had been established in seven countries as recommended by the World Health Organization, but the seroprevalence of antibodies against HBsAg (anti-HBs) was lower than the reported vaccine coverage in three countries. Regular serological surveys to ascertain HBV status within a population, such as reported here, provide important data to assess the need for and to evaluate universal HBV vaccination programmes.

Parvovirus B19 infection in five European countries: seroepidemiology, force of infection and maternal risk of infection.

We conducted a seroprevalence survey in Belgium, Finland, England & Wales, Italy and Poland on 13 449 serum samples broadly representative in terms of geography and age. Samples were tested for the presence of immunoglobulin G antibody using an enzyme immunoassay. The age-specific risk of infection was estimated using parametric and non-parametric statistical modelling. The age-specific risk in all five countries was highest in children aged 7-9 years and lower in adults. The average proportion of women of child-bearing age susceptible to parvovirus B19 infection and the risk of a pregnant women acquiring B19 infection during pregnancy was estimated to be 26% and 0.61% in Belgium, 38% and 0.69% in England & Wales, 43.5% and 1.24% in Finland, 39.9% and 0.92% in Italy and 36.8% and 1.58% in Poland, respectively. Our study indicates substantial epidemiological differences in Europe regarding parvovirus B19 infection.

Standardization of measles, mumps and rubella assays to enable comparisons of seroprevalence data across 21 European countries and Australia.

The aim of the European Sero-Epidemiology Network is to establish comparability of the serological surveillance of vaccine-preventable diseases in Europe. The designated reference laboratory (RL) for measles, mumps, rubella (MMR) prepared and tested a panel of 151 sera by the reference enzyme immunoassay (rEIA). Laboratories in 21 countries tested the panel for antibodies against MMR using their usual assay (a total of 16 different EIAs) and the results were plotted against the reference results in order to obtain equations for the standardization of national serum surveys. The RL also tested the panel by the plaque neutralization test (PNT). Large differences in qualitative results were found compared to the RL. Well-fitting standardization equations with R2> or =0.8 were obtained for almost all laboratories through regression of the quantitative results against those of the RL. When compared to PNT, the rEIA had a sensitivity of 95.3%, 92.8% and 100% and a specificity of 100%, 87.1% and 92.8% for measles, mumps and rubella, respectively. The need for standardization was highlighted by substantial inter-country differences. Standardization was successful and the selected standardization equations allowed the conversion of local serological results into common units and enabled direct comparison of seroprevalence data of the participating countries.

The comparative sero-epidemiology of varicella zoster virus in 11 countries in the European region.

The European sero-epidemiology network (ESEN2) aims to standardise serological surveillance of varicella zoster virus (VZV) in 11 participant countries. In each country, serum banks were collected between 1996 and 2003 and tested for VZV antibodies. Assay results were standardised so that international comparisons could be made. Age-specific forces of infection were calculated for three age groups (<5, 5-9 and >or=10 years of age) and used to estimate the base reproduction number (R(0)) and the herd immunity threshold (H). Most VZV infection occurred in childhood, but there was a wide variation in transmissibility, with R(0) ranging from 16.9 in the Netherlands to 3.3 in Italy. Herd immunity thresholds varied from 70% in Italy to 94% in the Netherlands. There are substantial differences in VZV sero-epidemiology within the European region, which will need to be taken into account in designing national policies regarding VZV vaccination.

The European Sero-Epidemiology Network 2: standardization of assay results for hepatitis B virus.

The aim of the European Sero-Epidemiology Network 2 was to coordinate and standardize the serological surveillance of vaccine-preventable diseases in Europe. In this study, the standardization of hepatitis B virus (HBV) results is described. The 15 participating national laboratories tested a unique panel of 172 sera established by the Greek reference centre for HBV surface antigen (HBsAg), antibodies to HBsAg (anti-HBs) and/or to the HBV core antigen (anti-HBc) by assay methods of their choice. Country-specific quantitative measurements for anti-HBs and anti-HBc were transformed into common units using standardization equations derived by regressing each country's panel results against the reference centre's results, thus adjusting for interassay and interlaboratory variability. For HBsAg, a qualitative analysis (positive/negative) showed at least 99% agreement with the reference laboratory for all countries. By combining these standardized and qualitative results for the markers mentioned earlier, it was possible to achieve comparable estimates of the proportion of the population susceptible to HBV, vaccinated against HBV, with a past HBV infection, and with a current infection or chronic carrier state. Standardization is a very important tool that allows for international serological comparisons to assess the current vaccination policies and the progress of HBV control in Europe.

Vaccine-induced measles virus antibodies after two doses of combined measles, mumps and rubella vaccine: a 12-year follow-up in two cohorts.

In Finland, a two-dose vaccination programme against measles, mumps and rubella (MMR) was begun in 1982. The programme with high coverage (97-98%) has eliminated these three diseases from Finland. The aim of the present study was to follow up the kinetics of measles virus antibodies in MMR vaccinated cohorts. We have followed the kinetics of measles virus antibody levels induced by vaccination in the same individuals immunized with their first MMR vaccine in 1982. After 12 years 80% of the original children remained available for sampling. Antibodies to measles virus were measured by haemagglutination inhibition (HI) and plaque reduction neutralization (NT) techniques. The primary dose induced 99.4% seroconversion for measles with a geometric mean HI antibody titre (GMT) of 1/269 (+/- 219), equivalent to 4304 mIU (milli-International Units) ml-1 in group A. The 12-year follow-up specimens showed a measles seropositivity rate of 100% as assayed with the HI and NT tests with a mean HI antibody titre of 1/39 (+/- 54), equivalent to 624 mIU ml-1. The vaccination-induced measles virus antibodies decline in the absence of natural booster infections. It is important to follow how long the protection achieved by the present vaccine programme will last after elimination of indigenous measles.