L. M. Hesketh

Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years. Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.

Simultaneous IgM reactivity by EIA against more than one virus in measles, parvovirus B19 and rubella infection

BACKGROUND A clinical diagnosis of rash-causing infections is not always possible and reliance has to be placed on serological evidence of infection, especially on the presence of specific immunoglobulin (Ig)M. However, despite the use of modern serological methods and validated commercial kits, reports appear in the literature of simultaneous IgM reactivity against more than one virus in cases of Epstein Barr virus, rubella, cytomegalovirus, human parvovirus B19 (HPV B19) and measles infections, all with implications for the pregnant woman. OBJECTIVES We decided to evaluate the extent of the problem in rubella, measles and HPV B19 infections in a routine diagnostic laboratory. STUDY DESIGN We tested sera from cases with initial clinical and serological evidence of infection with measles, HPV B19 or rubella for evidence of simultaneous IgM reactivity against more than one virus. We confirmed primary infections with specific-IgG antibody avidity tests, and subjected sera with IgM reactivity against more than one virus to avidity tests to identify which, if any, of the three viruses was the cause of the primary infection. Groups of monoreactive IgM sera were randomly selected from the presented sera to demonstrate that the avidity of the IgG specific for the other two viruses would be of high avidity compared with the low avidity of the IgG specific for the virus against which specific IgM had been detected. RESULTS Our results confirm that simultaneous IgM reactivity against more than one virus does occur in these three infections, and that this is unlikely to be caused by the presence of rheumatoid factor. CONCLUSIONS In the absence of seroconversion, reliance on specific IgM results alone for diagnosis of these infections should be avoided and tests such as specific IgG antibody avidity should also be employed. The simultaneous occurrence of IgM reactivity against more than one virus is also important for epidemiological and surveillance reasons as the widespread use of the mumps, measles and rubella vaccine makes its impact on the population. Falsely diagnosed cases of apparent measles or rubella could throw into question the efficacy of the vaccine.

Seroprevalence of antibody to varicella zoster virus in England and Wales in children and young adults.

This is the first large-scale study to investigate the seroprevalence of varicella zoster (VZV) in the general population of England and Wales. The study focused on those aged 1-20 years, that age group in whom most infections occur. Prevalence rose rapidly with age, with 53% of children showing evidence of prior infection by the age of 5 years and most young adults having experienced infection. In addition to using a fixed cut-off recommended by the manufacturer, a mixture modelling technique was also used to define the proportion of the population seropositive in each age group. This was shown to be a more accurate approach to categorizing data from an epidemiological perspective.

The European Sero-Epidemiology Network: standardizing the enzyme immunoassay results for measles, mumps and rubella.

The ESEN (European Sero-Epidemiology Network) project was established to harmonize the seroepidemiology of five vaccine preventable infections including measles, mumps and rubella in eight European countries. This involved achieving comparability both in the assay results from testing in different centres and also sampling methodology. Standardization of enzyme immunoassay results was achieved through the development of common panels of sera by designated reference centres. The panels were tested at the reference laboratory and then distributed to each participating laboratory for testing using their routine methods. Standardization equations were calculated by regressing the quantitative results against those of the reference laboratory. Our study found large differences in unitage between participants, despite all using an EIA method standardized against an international or local standard. Moreover, our methodology adjusted for this difference. These standardization equations will be used to convert the results of main serosurvey testing into the reference country unitage to ensure inter-country comparability.

Interpretation of rubella serology in pregnancy—pitfalls and problems

Clinical and laboratory expertise is essenrial for evaluating rubella specific IgM test results in pregnancy

The seroepidemiology of rubella in western Europe

Most of the countries in western Europe have now implemented mass infant rubella immunization programmes, instead of or in addition to selective vaccination in order to achieve the elimination of congenital rubella syndrome. The European countries Denmark, England and Wales, Finland, France, Germany, Italy and the Netherlands undertook large, national serological surveys collecting several thousand serum specimens during 1994-8. Antibodies against rubella virus were detected by a variety of enzyme immuno-assays. Comparability of the assay results was achieved by a standardized methodology. The age- and sex-stratified serological results were related to the schedules, coverage of rubella vaccination and the incidence in these countries. The results show widely differing levels of immunity to rubella both in the general population and in the specific age groups of males and females. A low rate (< 5%) of susceptibles in childhood and adolescents of both sexes was obtained only in Finland and the Netherlands. Countries such as Italy with only moderate coverage for the infant immunization programme currently have both high susceptibility levels in the general population and in the at-risk population. The likelihood is of continued epidemics of rubella with cases of congenital rubella syndrome. The continued implementation of selective vaccination will help to offset the impact of this ongoing transmission and to protect women on reaching childbearing age.

The seroepidemiology of measles in Western Europe

The European Regional Office of WHO has targeted measles for elimination from the region in 2007. Large national, age and sex stratified serological surveys of measles antibody were conducted in seven Western European countries from 1994-8 as part of the European Seroepidemiology Network. Three patterns were observed in the country-specific measles seroprofiles, ranging from (very) low susceptibility (four countries) to high susceptibility (one country). Susceptibility levels amongst 2-4-year-olds ranged from 2.9 to 29.8%, in 5-9-year-olds from 2.5 to 25% and 10-19-year-olds from 2.1% to 13.9%. A countrys susceptibility profile was highly associated with vaccine coverage for the first dose. First dose coverage ranged from 91 to 97.5% for low susceptibility countries, 75 to 85% for intermediate susceptibility countries and 55% for the high susceptibility country. Only the high susceptibility country still reports epidemic measles. In low susceptibility countries, which have achieved or are very close to measles elimination, the priority will be to maintain high MMR vaccine coverage in all geopolitical units for both vaccine doses. In moderate susceptibility countries there is still some endemic transmission, but also risk of outbreaks as pools of susceptibles accumulate. In the high susceptibility country the priority will be to increase infant vaccine coverage and reduce regional variation in coverage levels.

The prevalence of hepatitis B infection in adults in England and Wales.

Cost effectiveness analyses of alternative hepatitis B vaccination programmes in England and Wales require a robust estimate of the lifetime risk of carriage. To this end, we report the prevalence of infection in 3781 anonymized individuals aged 15-44 years whose sera were submitted in 1996 to 16 microbiology laboratories in England and Wales. One hundred and forty-six individuals (3.9%) were confirmed as anti HBc positive, including 14 chronic carriers (0.37%). The prevalence of infection and carriage was higher in samples collected in London and increased with age. No increased risk of infection was seen in sera from genito-urinary (GUM) clinics. Only 15 sera positive for hepatitis B were also positive for hepatitis C. Our results confirm the low prevalence of hepatitis B in England and Wales, are consistent with previous estimates of carriage and suggest that many infections were acquired while resident outside the UK. Future prevalence studies should determine the country of birth and other risk factors for each individual in order to confirm these findings.

The burden of Helicobacter pylori infection in England and Wales

The prevalence of active infection with Helicobacter pylori in the general population of England and Wales was estimated using high reactivity for specific IgG in serum ELISA as a marker. A total of 10,118 anonymized residues of serum samples collected in 1986 and 1996 from persons aged 1-84 years were used. Estimated prevalence of active infection varied by region and was highest in London. Prevalence was related to decade of birth and increased from 4-3% in those born during the 1980s to 30% in those born before 1940. An estimated total of 7.5 million people living in England and Wales have an active infection and analysis by decade of birth showed no significant difference between samples collected in 1986 and 1996. These data suggest H. pylori infection is becoming less common, is acquired at an early age and is unlikely to be resolved unless suitable antimicrobial treatment is sought.

The changing epidemiological pattern of hepatitis A in England and Wales

Sera from an age-stratified sample of 4188 individuals, submitted for diagnostic purposes to 15 public health laboratories in England and Wales in 1996, were tested for hepatitis A antibody. The serological profiles were consistent with declining incidence in the past. This hypothesis was tested by comparing the serological profiles of Ashford, Leeds and Preston public health laboratories with those from sera collected during a previous study in the same laboratories in 1986/7. A comparison of equivalent 10 year birth cohorts revealed that significant hepatitis A seroconversion had only continued in Ashford. However, it is probable that most seroconversions are due to vaccination and immigration rather than continuing viral transmission. Further population-based surveys collecting more in-depth social and demographic data are needed to confirm the main factors influencing hepatitis A seroprevalence and to explain the regional differences.