Borna disease virus and mental health: a cross-sectional study.

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.

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.

Ten years of serological surveillance in England and Wales: methods, results, implications and action.

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.

Evaluation of a commercial antibody capture enzyme immunoassay for the detection of rubella specific IgM.

A commercial M antibody capture ELISA kit ( Rubenz M) for the detection of rubella specific IgM was evaluated in comparison with M antibody capture radioimmunoassay. A total of 248 sera were evaluated, including sera from cases of primary postnatal rubella, congenital rubella, infectious mononucleosis, and sera which contained rheumatoid factor. No false positive results were obtained but two high positive sera gave Rubenz M values which were below the value recommended as indicative of a positive result. We therefore propose changes in the criteria used for assessing the significance of the results obtained. These changes improve the accuracy of the assay without loss of specificity.

Rubella-specific IgM detection using Sephacryl S-300 gel filtration.

Sephacryl S-300 has been compared with Sephadex G-200 in the fractionation of sera for the detection of rubella-specific IgM. No difference in sensitivity was found with sera that had low titres of rubella-specific IgM. Sephadex G-200 was apparently more sensitive with some sera which had high titres of rubella-specific IgM due to the contribution of rubella-specific IgA. Sephacryl S-300 offers considerable advantages in ease and speed of preparation, and as it is a more rigid gel higher flow rates can be obtained. Sera may be fractionated in 2.5 hours on Sephacryl S-300 compared with 7-10 hours on Sephadex G-200.

Nature of circulating immune complexes in infective endocarditis.

Two percent polyethylene glycol (PEG) precipitation was found to be a useful method for detecting circulating immune complexes (CIC) and could be used diagnostically to implicate infective endocarditis. Complexes consisting of a least Clq, IgG, and IgA were typically detected in sera from patients with infective endocarditis. Serial studies showed that CIC detection and measurement could be used to monitor clinical progress. Successful clinical improvement was reflected by decreasing CIC levels and the disappearance of rheumatoid factor, and, where increasing amounts of CIC were found, this may indicate situations where treatment was insufficient or inappropriate. There was specific free antibody demonstrable in the serum of six out of nine patients against their own infecting organisms, but attempts to identify the specificity of the complexed antibody as being directed against these organisms or their extracellular products failed. We could not detect any radioactive precipitin arcs, indicative of the free antibody also being in the complex, between the F(ab')2 preparation from the complex and the electrophoresed bacterial antigens in a radio-immunoelectrophoresis system. Eleven out of 13 sera that contained Clq, IgG, and IgA in their complexes also contained rheumatoid factor. Immunisation against the patient's own persisting CIC may explain this phenomenon.

Public Health Laboratory Service IgM antibody capture enzyme linked immunosorbent assay for detecting rubella specific IgM.

A total of 468 sera were selected for the evaluation of the Public Health Laboratory Service's IgM antibody capture enzyme linked immunosorbent assay kit (MACELISA) for detecting rubella specific IgM. The results obtained were compared with those obtained by IgM antibody capture radioimmunoassay (MACRIA). Sera from patients with primary postnatal rubella, congenital rubella, remote rubella, infectious mononucleosis, and recent infection with other agents were included, in addition to sera taken after rubella immunisation and sera containing rheumatoid factor and rubella specific IgG antibody. The assay exhibited a similar ability and comparable specificity to MACRIA for detecting rubella specific IgM antibody. The Public Health Laboratory Service MACELISA can be recommended if, as for all assays that detect rubella specific IgM, all the available clinical and serological data are taken into account when the results are interpreted.

A comparison of three tests for rubella antibody screening.

Sera from 1000 women attending antenatal clinics were screened for the presence of rubella antibody by haemagglutination inhibition (HI), single radial haemolysis (SRH), and enzyme-linked immunosorbent assay (ELISA). With 925 sera concordant results were obtained with all three tests. There were 46 false-negative HI tests due to the necessity of allowing for residual non-specific inhibitors. With SRH there was one false positive and three that were negative by SRH but HI- and ELISA-positive. By ELISA 14 sera gave a false-positive result (OD 405 nm greater than or equal to 0.2). Ten of these could be eliminated by taking an OD 405 nm of 0.5 as the threshold but then another 10 sera became false negatives.

Immunohistological studies of lymphoproliferative lesions in a fatal case of Epstein-Barr virus infection.

A fatal case of infectious mononucleosis occurred in a young adult. Abnormal serological features were noted in his mother, although there was no other family history suggesting an inherited defect of immune response to Epstein-Barr virus (EBV). The cellular infiltrate observed in tissues obtained at necropsy was analysed with a range of specific monoclonal and polyclonal antibodies. Polyclonal plasmacytoid B cell proliferation had occurred in many tissues. These cells were positive for EBV nuclear antigen, but viral particles were not seen on ultrastructural examination, and the virus was not isolated, suggesting a non-permissive infection.

A rationalised virological electron microscope specimen testing policy. PHLS North West Viral Gastroenteritis and Electron Microscopy Subcommittee.

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.

Rubella-specific IgG1 avidity: a comparison of methods.

Two methods of determining the avidity of specific IgG1 were compared with sera from different categories of rubella infection. Both methods were based on an antiglobulin enzyme-linked immunosorbent assay. In one method the absorbances were compared with and without diethylamine (DEA) in the serum diluent over a range of serum dilutions and the difference between the dilution curves measured (DEA-shift). In the other, the absorbances at a single serum dilution were compared with and without urea in the wash fluid used after the antigen/serum incubation (avidity index). Various concentrations of DEA were also assessed in the avidity-index method, as this method is simpler to perform. The DEA-shift method was shown to be more sensitive for diagnosing recent primary rubella or immunization by demonstrating specific IgG1 of low avidity. The avidity-index method, however, was more specific when sera from cases of reinfection or non-specific rubella IgM reactivity were tested. 35 mM DEA was found to be the optimal concentration of DEA when DEA was substituted for urea in the avidity index method.

A comparison of Rubazyme-M and MACRIA for the detection of rubella-specific IgM.

One-hundred and eighty-six carefully selected sera were tested for rubella-specific IgM by Rubazyme-M (Abbott Diagnostics) and an M-antibody capture radioimmunoassay (MACRIA). Eleven of these sera were from cases of infectious mononucleosis, six of which gave positive results in MACRIA, while one gave a positive result in Rubazyme-M. Of the remaining 175 sera, 158 gave concordant results whilst 17 sera gave discordant results; these 17 were also tested by serum fractionation. Problems were encountered with all assay systems used. It is therefore recommended that the results of all tests for rubella-specific IgM should be interpreted with caution.

Persistence of specific IgM and low avidity specific IgG1 following primary rubella.

Persistence of specific IgM in sera following primary rubella infection was compared with the maturation of the specific IgG1 response. 206 sera, from 171 patients with primary rubella, taken 1 day to 2.5 years after onset of illness, were tested. Rubella-specific IgM was detected by M-antibody capture radioimmunoassay in 100% of sera taken 15-28 days after onset, but in only 9% taken 3-4 months after onset. However, using the diethylamine (DEA) shift value (DSV) method, low avidity specific IgG1 was detected in 91% sera taken at 3-4 months and at 5-7 months 21% of sera remained positive. Using an avidity index method, with urea in the wash buffer, none of the sera were positive for low avidity specific IgG1 beyond 3 months after onset. With DEA in the wash buffer, the number of sera positive rose to 38% at 3-4 months. Thus, the DSV method for detecting low avidity specific IgG1 is a useful additional test for confirming or refuting a diagnosis of primary rubella and is of particular value for assessing pregnant patients.

An evaluation of nine commercial EIA kits for the detection of measles specific IgG.

Nine commercial EIAs for measles-specific IgG were compared with haemagglutination inhibition (HI) and plaque reduction neutralization (PRN). A total of 174 sera selected, to give approximately half of the sera without measles antibody by HI, were tested by all EIAs and HI. However, there was sufficient volume of only 101 samples for testing by PRN. A dilution curve of the British Standard measles antibody serum was also tested by each EIA. Assays were evaluated qualitatively against a consensus EIA result, HI and PRN: Gull, Melotest and Behring EIAs performed best. Quantitative evaluation was by assessment of the characteristics of the standard dilution curve, and by plotting differences with PRN against mean: Gull and Melotest EIAs were best.

Problems in management of health care workers exposed to HBeAg positive body fluids.

A young Asian male was admitted to hospital suffering from severe lower limb and facial injuries. He was subsequently found to be a carrier of hepatitis B virus and HBeAg positive. The management of 38 health care workers with significant blood and body fluid exposure involving this patient is discussed.

The role of environmental contamination with small round structured viruses in a hospital outbreak investigated by reverse-transcriptase polymerase chain reaction assay.

In May 1994 an outbreak of vomiting and diarrhoea occurred in a 28-bed long-stay ward for the mentally infirm. The predominant symptoms were vomiting, diarrhoea, malaise and abdominal pain lasting for approximately 12 h in most cases. The attack rate was 62% (13/21) for patients and 46% (16/35) for staff members. Infection control measures were implemented (containment of infectious individuals, hand hygiene among staff and environmental decontamination) and the ward was closed to admissions. Affected staff were excluded from contact with patients and their food until asymptomatic for 72 h. The outbreak lasted for 17 days. Faecal samples from nine symptomatic persons were negative for bacterial enteric pathogens, Giardia, Cryptosporidium and group A rotavirus. Electron microscopy of 12 faecal samples and one sample of vomitus revealed small round structured virus (SRSV) particles in one faecal sample. A further 30 faecal samples and seven vomitus samples were tested by reverse transcription polymerase chain reaction (RT-PCR) for SRSV of which 12 (40%) and 1 (14%) were positive respectively. Twenty-eight throat swabs from symptomatic and asymptomatic patients were collected, three (9.5%) of which were positive for SRSV by RT-PCR. Thirty-six environmental swabs were collected on the affected ward, and 11 (30%) were positive by RT-PCR. Positive swabs were from lockers, curtains and commodes and confined to the immediate environment of symptomatic patients. The distribution of contamination supports the rationale of cohorting sick patients.

Zoonotic illness--determining risks and measuring effects: association between current animal exposure and a history of illness in a well characterised rural population in the UK.

STUDY OBJECTIVES: To recruit a representative sample of farmworkers, accurately quantify the range and extent of their animal exposures, and measure the associated risks of illness. DESIGN: Inception cohort. SETTING: The study was undertaken among farmworkers living in five local authority areas in the catchment of Hereford and Preston Public Health Laboratories, England. PARTICIPANTS: A quota sample of 404 people on 255 agricultural holdings took part. The holdings were selected at random from the Ministry of Agriculture, Fisheries and Food register. Altogether 58% of eligible subjects approached agreed to participate. MEASUREMENTS AND MAIN RESULTS: The sample had the same sex distribution as the 1991 census for those giving their occupation as agriculture. The mean age was significantly (p < 0.01) higher (44.6 years v 42.2 years) than that of those giving their occupation as agriculture, forestry or fishing in the census, although the modal range (45-59 years) was the same. At enrollment interviews, subjects individually reported contact with up to nine animal species (mode 4) out of 26 reported in all. Based on the numbers contacted and the frequency and intimacy of contact, scores on a ranked ordinal scale from 0-5 were constructed for each species and frequencies for each score were plotted. Subjects also reported past operations and serious illness. A history of pneumonia was significantly (p < 0.05) associated with a pigeon loft on the farm (relative risk (RR) 7.3) and attending farrowing pigs (RR 6.6), and one of leptospirosis with a rat problem on the farm (RR 28.1). Cattle contact was associated with a significantly lower likelihood (protective) of glandular fever (RR 0.19) and rheumatic or scarlet fever (RR 0.12). These effects were significantly related to rankings of the extent of exposure. CONCLUSIONS: It is possible to recruit a representative sample of farmworkers and measure their animal exposures in great detail. Among these exposures, associations with plausible risk factors for pneumonia and leptospirosis and apparently protective factors for glandular fever, scarlet fever, and rheumatic fever have been demonstrated, which further show a relationship between the extent of exposure and response. These findings can be tested further by examining the relationship of exposures to serological evidence of illness or by further prospective follow up of this and similarly well characterised cohorts, or both.

Clinically apparent rubella reinfection.

We report two cases of rubella reinfection in apparently immunocompetent young women. In both cases rubella-specific IgG had been detected on two occasions prior to an illness clinically diagnosed as rubella. Rubella-specific IgM was detected by various techniques in samples of serum collected at the time of the illness.

Clinical rubella reinfection--a case of arthropathy.

We describe a case of arthropathy due to rubella reinfection. Clinical rubella reinfection with rash and lymphadenopathy has been reported but as far as we are aware this is the first report of a case with arthropathy as the sole presentation. Rubella IgG subclass and avidity tests confirmed the reinfection.

The prevalence of hepatitis C in England and Wales.

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.