A mixture modelling technique is applied to age-specific frequency distributions of quantitative results from serological surveys for measles, mumps and rubella using samples collected across the age range in England and Wales in 2000. In accordance with previous studies the analysis suggests that the antibody response to natural infection is stronger than that produced by vaccination, that vaccine-induced antibody levels wane with time and that levels of vaccine-induced antibody response vary for each virus infection being strongest for rubella and weakest for mumps. The current mumps epidemic in the United Kingdom is focused in cohorts born during 1982-1987 who were too old to have received routine MMR vaccination. In the cohort born in 1981-1985 the model estimates that 7.5% have no evidence of mumps specific IgG and 24.9% have the lowest level of detectable antibody. The similar proportions of mumps antibody in these categories among cohorts with opportunity for 1 or 2 doses of vaccine is a concern, as the degree to which these individuals are protected is unclear. Investigations into the efficacy of two doses of a mumps containing vaccine should be a priority during the current epidemic.

Background: Borna disease is an infectious neurological disease of horses, sheep and possibly other animals.A role for Borna disease virus (BDV) in human neurological and psychiatric illness has been proposed, but this hypothesis remains controversial.Aim: To investigate the epidemiology of BDV in UK farming communities.Design: Retrospective cohort study.Methods: We measured the seroprevalence of BDV in the PHLS Farm Cohort, a representative sample of those employed in agriculture in the UK, and investigated the clinical significance of our findings by comparing the prevalence of symptoms of neurotic psychopathology in those found seropositive and seronegative.Results: Seroprevalence was 2.3% (95%CI 1.3-4.0%) in 1994, 3.1% in 1996 (95%CI 1.9-5.0%)and 2.6% in 1999 (95%CI 1.5%-4.6%).Those living or working on livestock farms had higher seroprevalence (2.6%) than those on mixed (2.3%) or arable (1.6%) farms, but this was not statistically significant.Exposure to horses, sheep and cats did not increase risk of seropositivity.Seropositives were no more likely to report symptoms of psychiatric morbidity.Discussion: UK farming populations appear to be exposed to Borna disease virus.However, we found no evidence that exposure to BDV was associated with morbidity in this healthy occupational cohort.

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.

Vaccination is one of the most cost-effective measures for preventing morbidity and mortality that modern medicine has to offer (1). Measles, mumps, and rubella are three viral infections causing significant morbidity for which an effective vaccine is available. Otitis media (5 percent of cases), pneumonia or bronchitis (4 percent), and neurologic complications (1 percent), including subacute sclerosing panencephalitis, are associated with cases of measles (2), while mumps is recognized as a common cause of aseptic meningitis and can cause orchitis in adult males (3). Rubella infection in pregnancy, especially during the first trimester, can cause miscarriage or congenital rubella syndrome, which is characterized by a pattern of congenital abnormalities including nerve deafness, cataracts, cardiac abnormalities, and mental retardation

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.

The aim was to carry out a population‐based sero‐prevalence survey of Epstein‐Barr virus (EBV) across a wide age range in England and Wales and to identify any associations between EBV and herpes simplex virus types one and two (HSV‐1 and 2). Sera from an age‐stratified sample of 2,893 individuals, submitted for diagnostic purposes to 15 public health laboratories in England and Wales in 1994, were tested for immunoglobulin G (IgG) antibody to EBV. The samples had been tested previously for IgG antibody to HSV‐1 and HSV‐2. The serological profile of EBV was consistent with an endemic infection with peaks in transmission in those less than 5 years old and in young adults. An age adjusted analysis found a significant association between EBV and HSV‐1 seropositivity that is most likely explained by similarities in their mode of transmission. The very low seroprevalence of HSV‐2 in this sample complicated the comparisons of EBV and HSV‐1 with HSV‐2. Any associations were most likely explained by chance. Given the association between EBV and HSV‐1, it is likely that recently documented epidemiological changes in HSV‐1 also apply to EBV. Continuing surveillance of these herpes viruses is necessary as the predicted changes could have a significant public health impact, especially in the young adult population. J. Med. Virol. 67:522–527, 2002. © 2002 Wiley‐Liss, Inc.

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.

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.

Objectives: To estimate the background population prevalence of hepatitis C in England and Wales, observe the prevalence over time and assess the extent of infection outside of known risk groups.Methods: Sera from residual specimens from adult patients submitted to laboratories in England and Wales were tested for anti-HCV. Testing was carried out using a cost-effective pooling strategy.Results: Although the prevalence of anti-HCV was highest in 1986 (1.07%), in the multivariable analysis, prevalence did not vary significantly between the 3 periods 1986, 1991 and 1996 (P=0.14). The prevalence of infection was higher in males than in females (P=0.0013). An age-period-cohort analysis revealed a cohort effect due to a lower HCV prevalence in the most recent birth cohorts, that is, those born between the calendar years 1971-1975 and 1976-1980.Conclusions: The majority of HCV infections in England and Wales were probably acquired before 1986. Infections in younger males identified in 1996 may signify more recent acquisition by injecting drug use. (C) 2002 The British Infection Society. Published by Elsevier Science Ltd. All rights reserved.

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 Sero-epidemiology 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 country's 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 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.

The techniques of enzyme-linked immunosorbent assay (ELISA) and immunoblotting were used to examine a total of 1667 sera, from apparently healthy members of rural communities in England, for antibodies to the lipopolysaccharide (LPS) of Escherichia coli O157 and Verocytotoxins (VT). Twenty-nine sera from 22 individuals were shown to have antibodies specific for E. coli O157 LPS. Some of these lived on livestock farms and had occupational contact with cattle, suggesting that personnel working with farm animals may produce serum antibodies to the O157 LPS antigens. Fifteen people had IgG class antibodies to O157 LPS, suggesting long-term exposure to E. coli O157 and five people had serum antibodies on more than one occasion showing evidence of persistent antibodies to O157 LPS. Thirteen sera from 12 of 22 individuals also contained antibodies to VT1, VT2 or both toxins. Ten sera contained antibodies to VT1 and VT2, three sera contained antibodies to VT2 only.

BACKGROUND:The first age-stratified serological survey of antibody to measles, mumps and rubella in the UK was conducted in 1986/87 prior to the introduction of MMR vaccine into the immunization programme. Serum collection and testing have continued annually, allowing trends over time to be monitored. These sera have also been available for ad hoc surveys of other infections.METHODS:Residual sera are collected in participating laboratories and sent to a central store where they are irrevocably unlinked from identifying data. A unique identity number is assigned to each serum and details of age and sex are collated on a database. The sera are accessed for testing as required.RESULTS:The results of recurring and other surveys performed over the last ten years are presented. These demonstrate that opportunistic serum samples are an ideal resource for serological surveillance programmes.CONCLUSIONS:The serological surveillance programme has provided past exposure profiles for many infections. These data have resulted in a number of national policy changes and have been instrumental in shaping the UK vaccination programme.

An association of enterovirus infection with endemic cardiomyopathy (Keshan disease [KD]) and outbreaks of myocarditis in selenium-deficient rural areas of southwestern China has been established. Enteroviruses have been isolated from patients with KD or during outbreaks of myocarditis in last two decades. Six of these isolates grew readily in cell lines (Vero or HEp-2) and were investigated by a novel molecular typing method apart from serotyping and pathogenicity. A neutralization assay identified two isolates from KD as coxsackievirus serotype B2 (CVB2) and two isolates from myocarditis as coxsackievirus serotype B6 (CVB6) but failed to type the remaining two isolates, also from myocarditis. Direct nucleotide sequencing of reverse transcription-PCR products amplified from the 5' nontranslated region (5'NTR) of these viruses confirmed that they belong to a phylogenetic cluster consisting of coxsackie B-like viruses, including some echovirus serotypes. Sequence analysis of the coding region for viral capsid protein VP1 showed that two isolates serotyped as CVB2 have the highest amino acid sequence homology with CVB2 and that the remaining four isolates, two CVB6 and the two unknown serotypes, are most closely related to the sequence of CVB6. Sequences among these isolates varied from 82.3 to 99% in the 5'NTR and from 69 to 99% in VP1, indicating no cross contamination. The pathogenicity of these viruses in adult and suckling mice was assessed. None caused pathologic changes in the hearts of adult MF-1 or SWR mice, although pancreatitis was evident. However, the four CVB6-like viruses caused death in suckling mice, similar to a virulent coxsackievirus group B3 laboratory strain. In conclusion, the sequence data confirm that coxsackievirus group B serotypes are predominant in the region in which KD is endemic and may be the etiological agents in outbreaks of myocarditis. VP1 genotyping of enteroviruses is accurate and reliable. Animal experiments indicate that isolates may differ in pathogenicity.

OBJECTIVE:To measure the burden of infection with herpes simplex type 1 (HSV-1) and herpes simplex type 2 (HSV-2) in the general population of England and Wales and to assess temporal changes in the incidence of HSV-1 infection in childhood.METHODS:4930 residual blood samples taken from people aged 0-69 years and submitted to 15 public health laboratories in England and Wales between January 1994 and June 1995, and 500 samples taken from people aged 10-14 years between November 1986 and December 1987, were screened for IgG antibody to HSV-1 and HSV-2 using type specific ELISA assays.RESULTS:The prevalence of antibody to HSV-1 in 10-14 year olds declined from 34% in samples collected in 1986-7 to 24% in samples collected in 1994-5 (p < 0.001). HSV-1 antibody prevalence in adults increased with age and was higher in females than males, reaching 54% in females aged 25-30 years in 1994-5. In samples collected in 1994-5 from people aged 16-69 years HSV-2 antibody was detected in sera from 3.3% of men and 5.1% of women.CONCLUSIONS:The incidence of HSV-1 infection in childhood is falling in England and Wales. The prevalence of HSV-2 infection in the general population is low, with the rate of infection significantly lower than that described for the general population in the United States and developing countries. The falling rate of HSV-1 infection in childhood may be one factor contributing to the increasing incidence of genital HSV-1 infection.

We recruited a representative population-based sample of 606 farmers, farmworkers,and their families from three areas of England. By defining and measuring animalexposure (type, frequency, and species range) we were able not only to measure theincidence and prevalence of markers of exposure to zoonotic organisms in this sentinelgroup, but also to determine the risk of exposure to zoonotic organisms associated witha variety of defined occupational exposures. Prevalence of antibodies to Coxiella burnetii(the cause of Q fever) (29.2%) and toxoplasma (50.2%) were high; whereas, prevalenceof antibodies to Borrelia burgdorferi (the cause of Lyme disease) (0.2%), leptospira(0.2%), and brucella (0.7%) were low. The cohort was also exposed to hantavirus(seroprevalence 4.7%), orthopoxvirus (0.7%), parapoxvirus (4.5%), Bartonella spp.(2.0%) Ehrlichia chaffeensis (0.2%), human granulocytic ehrlichiosis agent (1.5%), andEchinococcus granulosis 3/202 (1.5%). Coxiella seropositivity was associated withexposure to dairy cattle (odds ratio: 1.48, 95% confidence interval: 1.03-2.12); cowpoxwith exposure to rats (odds ratio: 18.7, 95% confidence interval: 1.7-201.8). Self-reportedclinical orf (contagious pustular dermatitis) was associated with exposure tosheep (risk ratio: 7.64, 95% confidence interval: 1.93-30.26) and rats (risk ratio 4.54,95% confidence interval: 1.16-17.70); ringworm (dermatophytosis) with cattle (riskratio: 1.76; 95% confidence interval: 1.17-2.64).

The aim of this project was to produce guidance for a rationalised virological electron microscopy specimen testing policy for PHLS North West, to facilitate centralisation of a groupwide diagnostic electron microscopy service on a single site. Careful specimen selection to limit numbers and the groupwide use of commercially available enzyme immunoassays has allowed PHLS North West to reduce the number of specimens prepared for electron microscopy. The rationalised virological electron microscopy specimen testing policy has enabled a diagnostic electron microscopy service to be provided from a single site with a manageable workload. Implementation of this specimen testing policy by PHLS North West has been successful and may be applicable to other laboratories (or groups of laboratories) to maximise the use of expensive electron microscopy facilities.

Orf is a zoonotic skin disease which is commonly self-diagnosed by those who tend sheep and goats. This paper reports the prevalence, incidence and risk factors associated with the infection in a cohort of farmworkers from three areas of England, derived from the results of self-reporting and serology. Twenty-three per cent of those employed or living on a sheep farm reported ever having had orf, and the antibody serological profiles indicated a prevalence of 4 per cent and an annual incidence of 2.8 per cent. The main risk factors associated with the infection were contact with sheep, the size of the sheep flock, and contact with dogs.

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.