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.

An evaluation of three commercial kits for use as screening methods for the detection of leptospiral antibodies in the UK.

AIMS: To compare three commercial screening tests--the PanBio leptospiral IgM enzyme linked immunosorbent assay (ELISA), the Biolisa leptospiral IgM ELISA, and the indirect haemagglutination assay (IHA)--with the microscopic agglutination test (MAT) and two "in house" ELISAs--urease and horseradish peroxidase (HRP)--for the detection of leptospiral antibodies in a local UK and Eire population. METHOD: Two hundred sera submitted for a differential diagnosis of leptospirosis were tested by all methods. A further 142 sera from patients with antibodies to toxoplasma, Epstein-Barr virus (EBV), hepatitis A virus, rheumatoid factor, Borrelia burgdorferi, Mycoplasma pneumoniae, syphilis, cytomegalovirus, and Q fever were tested for crossreactivity. RESULTS: Compared with the MAT, sensitivity and specificity were found to be: PanBio, 90%/94%; Biolisa with sorbent, 100%/85%; and IHA, 54%/95%. Seven of 200 trial sera gave false negative results with PanBio; 14 of 200 trial sera gave false positive results with Biolisa with sorbent, as did a further 25 of the 142 sera tested for potential crossreactivity. Two of 142 sera gave crossreactions with PanBio and IHA (one each). CONCLUSIONS: The degree of false positivity seen with the Biolisa suggests that the recommended positive value of > or = 26 Eu/ml should be reassessed using pools of sera from local populations. When the cut off value was reassessed, using a value of > or = 40 Eu/ml, a sensitivity and specificity of 96% and 94%, respectively, was achieved. Even the modified Biolisa appears to be over sensitive and to show a high degree of non-specificity. The IHA, although specific (95%), lacked sensitivity in this study. The PanBio appeared to be the most suitable as a screening test for leptospiral IgM in the UK, although it would be advisable for all positive test results to be confirmed by a different enzyme immunoassay and the MAT.

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.

How is the source of food poisoning outbreaks established? The example of three consecutive Salmonella enteritidis PT4 outbreaks linked to eggs.

Three consecutive outbreaks of Salmonella enteritidis PT4 occurred in Wales in 1989 in which epidemiological and microbiological investigation established eggs as the likely source although kitchen inspection and food preparation histories suggested other vehicles of infection. This paper examines the contribution of analytical epidemiology in attributing causation, with particular reference to those limitations which are regarded as inherent in epidemiological evidence. Such evidence, implicating eggs in the three outbreaks, fulfilled 6/7 widely accepted criteria for causation; data to assess the seventh were lacking. Collaboration between different agencies and professionals in investigating outbreaks is very important.

The public health laboratory service (PHLS) and its role in the control of zoonotic disease.

The aetiology of zoonotic infections embraces organisms from every branch of the microbial world. In addition, zoonoses must be considered as a truly global problem, both in terms of their distribution and the measures required for their control. Within the UK, zoonotic disease is considered to be less frequent than in some less developed parts of the world. However, its contribution to overall morbidity and mortality within the UK population is not well established. In an attempt to define the impact of zoonotic infection more accurately, a multicentre prospective study of disease in farmers in England and Wales was initiated by the PHLS in 1992. The study involved the completion by participants of annual questionnaires dealing with their own health and the range and health of their livestock. Our results confirmed that some infections occur frequently in farmers. For example, ringworm and Q fever were associated with contact with cattle and orf with the handling of sheep. Some findings were unexpected; the incidence and prevalence of leptospirosis, for example, were far lower in the farmers than had been anticipated, whilst there was a higher than expected incidence and prevalence of hantavirus infection. The success of the project was largely due to the adoption of a multidisciplinary approach and the continuity of funding which enabled the study of the same cohort to continue for 7 years.

Orf (contagious pustular dermatitis) in farmworkers: prevalence and risk factors in three areas of England.

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 cen. The main risk factors associated with the infection were contact with sheep, the size of the sheep flock, and contact with dogs.

Diabetes in mice after Coxsackie B 4 virus infection.

The intraperitoneal inoculation of CD(1) mice with Coxsackie virus B(4) resulted in the raising of blood sugar levels to diabetic values 12 days after the administration of the virus. Serum insulin remained inappropriately low. Light microscopy changes in the islets of Langerhans showed mononuclear cell infiltration of the islets and marked degranulation of the beta cells. The acinar tissue appeared to be little changed. It is concluded that Coxsackie B(4) virus may cause a diabetic state compatible with islet cell damage.

Risk factors for Neisseria meningitidis carriage in a school during a community outbreak of meningococcal infection.

As part of the management of an outbreak of meningococcal infection, 119 school contacts of an index case were swabbed for nasopharyngeal carriage. In a cohort study, risk factors for Neisseria meningitidis carriage were ascertained by means of a questionnaire, completed by 114 (96%) of those swabbed. Twenty five (21%) cultures were identified as "neisseria positive'; of which there were 18 (15%) Neisseria meningitidis isolates, 2 (2%) Neisseria lactamica isolates and 5 (4%) showed contaminants only. Two (2%) carriers were identified as harbouring the implicated outbreak strain. Single variable analysis identified six statistically significant risk factors for meningococcal carriage; increasing age, female sex, manual social class, personal smoking, regular attendance at a discotheque and rhinorrhoea. Multivariate analysis, using logistic regression modelling, found that of these six variables only age, sex and social class remained statistically significant when the other factors were controlled for. Nevertheless the role of smoking, social events and respiratory/viral infections in nasopharyngeal carriage, and other plausible mechanisms whereby age, sex and social class might exert their effect, could usefully be investigated further.

How well do viruses survive during transport?

Centralisation of viral diagnostic services offers the potential for cost saving in laboratories, but incurs costs for transporting specimens. In a trial of 326 paired specimens, isolation rates of viruses sent by overnight post and a more expensive same-day courier service were similar.

Adverse events and antibody response to accelerated immunisation in term and preterm infants.

A study was performed to compare adverse events and antibody response in term and preterm children vaccinated with diphtheria, tetanus, and pertussis vaccine at 2, 3, and 4 months of age. A total of 124 children were recruited and grouped according to gestational age: 37 weeks or more (n = 52), 34 to 36 weeks (n = 40), and less than 34 weeks (n = 32). Study nurses followed up children 24 hours after each vaccination to record temperature, redness, and swelling at the injection site and any systemic symptoms. Proportions of children experiencing adverse events did not differ between groups. Blood samples were obtained six weeks after the vaccination course at which time all children had protective levels of diphtheria and tetanus antitoxins. Geometric mean antibody titres (95% confidence interval) to pertussis toxin were 2754 (2042 to 3715), 5495 (4074 to 7413), and 3690 (2951 to 4677), to filamentous haemagglutinin were 541 (282 to 1023), 951 (537 to 1698), and 614 (426 to 1023), and to agglutinogens 2 and 3 were 12,106 (6918 to 21,380), 21,330 (13,183 to 34,674), and 22,387 (15,136 to 33,113) in children born at a gestational age of less than 34 weeks, 34 to 36 weeks, and 37 weeks or more respectively. These findings support the current recommendations that preterm children are vaccinated at chronological age according to the national schedule.

Antibody responses and reactions to the whole cell pertussis component of a combined diphtheria/tetanus/pertussis vaccine given at school entry.

To measure the clinical effect of adding a whole cell pertussis component to diphtheria/tetanus vaccine (DT) given as a pre-school booster, 190 children aged 4-5 years were randomised by a double-blind method to receive either diphtheria/tetanus/pertussis (DTP) or DT vaccine in a 1:1 ratio at selected clinics in England. The geometric mean antibody titres to each of the three pertussis antigens were at least sixfold higher in the DTP than the DT vaccine group and equalled or exceeded those in infants immediately after primary immunisation with DTP vaccine. There were no significant differences between DTP and DT vaccinated children in their diphtheria and tetanus antitoxin levels. The frequency of large local reactions and systemic symptoms such as crying and a disturbed night was 2-3-fold higher in the DTP vaccinees than in the DT vaccinees. Medication was given to 44% of DTP and 23% of DT vaccinees (p = 0.006). Although the change to whole cell DTP vaccine at school entry would result in good pertussis antibody titres, the 2-3-fold increase in reactogenicity that would be caused may be unacceptable at a time when whooping cough is not circulating widely. Evaluation of acellular DTP vaccines given as a pre-school booster in children vaccinated under the accelerated schedule is planned.

Low rates of ehrlichiosis and Lyme borreliosis in English farmworkers.

To determine the occupational significance of tick-borne zoonoses we sought serological evidence of Lyme borreliosis, human monocytic ehrlichiosis (HME) and human granulocytic ehrlichiosis (HGE) in a representative sample of farmworkers. Although around 20% reported ticks on their domestic and companion animals, few (< 2% per year) reported being bitten by ticks. Seroprevalence of Lyme borreliosis (0.2%), HME (0.2%) and HGE (1.5%) was low. Those seropositive for HGE were no more likely to report tick bites nor more likely to report ticks on their animals. This study provides evidence that farmworkers in England are exposed to tick-borne zoonoses but that they are uncommon. Since the severity of these diseases is linked to delays in diagnosis and treatment, clinicians should be aware of these diagnoses in patients from rural communities, with or without a self-reported history of tick bite.

The risk of acquiring Q fever on farms: a seroepidemiological study.

OBJECTIVES: To determine the occupational risk of Q fever. DESIGN: Cohort study. SETTING: Community: five English local authority districts. SUBJECTS AND METHODS: Prevalence and incidence of immunoglobulin G (IgG) specific antibody to Coxiella burnetii phase II antigen was measured in a representative (study) cohort of farm workers in the United Kingdom, and detailed exposure data were collected. Also seroprevalence of Q fever in a (control) cohort of police and emergency service personnel was measured. RESULTS: Prevalence was significantly (P < 0.01) higher in the study cohort (105/385 v 43/395). During the first 12 month period after enrollment no seroconversions were found (upper 95% confidence limit: 1318/100,000/year). During the second 12 month period after enrollment two seroconversions were found, equalling an incidence of 813/100,000/year (95% confidence interval (95% CI) 98-2937/100,000/year). No association was found between seroprevalence and age. In the study cohort, extent of total contact with farm animals seemed more important than exposure to any specific animal: full time employees were more than four times more likely to be antibody positive than part time employees (P < 0.05). Exposure to cattle, but not sheep, goats, cats, raw milk, and hay (all reported sources of Q fever) was associated with being positive to Coxiella burnetii IgG by univariate analysis but this association was not independent of total farm animal contact. CONCLUSIONS: The risk of Q fever on livestock farms is related to contact with the farm environment rather than any specific animal exposure. The absence of an increasing prevalence with age suggests that exposure may occur as clusters in space and time (outbreaks).

Evidence of persisting serum antibodies to Escherichia coli O157 lipopolysaccharide and Verocytotoxin in members of rural communities in England.

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.

Mental health of British farmers.

AIMS: To estimate the prevalence of neurotic symptoms in a sample of British farmers, to investigate whether farming characteristics are associated with psychiatric morbidity, and to test the hypothesis that British farmers have a higher prevalence of depression and thoughts of life not worth living than the British household population. METHODS: A total of 425 farmers from Hereford, Norwich, and Preston completed the Revised Clinical Interview Schedule (CIS-R) by computer between March and July 1999. The comparison cohort consisted of 9830 private householders aged 16-64 from the Office of Population Censuses and Surveys National Psychiatric Morbidity Surveys of Great Britain carried out in 1993 in which the CIS-R was administered. All analyses used the commands developed specifically for survey data available in Stata version 6.0. RESULTS: Taking a threshold of an overall score of 12 or more on the CIS-R, only 6% of farmers reported clinically relevant psychiatric morbidity. Psychiatric morbidity was not significantly associated with farm type or size in this study. Farmers reported a lower prevalence of psychiatric morbidity than the general population but were more likely to report thinking that life is not worth living, particularly after the low prevalence of psychiatric morbidity had been taken into account (odds ratio 2.56, 95% CI 1.39 to 4.69). When restricting the comparison to only rural or semirural householders, this increased risk was even more pronounced (odds ratio 3.26, 95% CI 1.51 to 7.02). CONCLUSIONS: The relation between depression and suicidal ideation seems to be quite different among farmers and the general population and warrants further investigation. We have shown it is possible to measure mental health systematically in a sample of British farmers. This study should be repeated in the aftermath of the foot and mouth crisis.

Detection of rubella-specific IgM in subclinical rubella reinfection in pregnancy.

Seven cases of asymptomatic rubella reinfection in early pregnancy are described. In each, there was a history of exposure to a rubelliform illness and low levels of rubella-specific IgM subsequently appeared in the serum. Four of the women had been immunised, after having been shown to be susceptible to rubella, one had been immunised at school without previous antibody screening, and two were uncertain about immunisation. One pregnancy was terminated and rubella virus was not isolated from the products of conception. Six pregnancies went to term and the infants showed no evidence of intrauterine infection. In a further case it was impossible to discriminate between reinfection and primary infection, and termination of pregnancy was offered.