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Biomedical subjects

P Morgan-Capner

Publications and source records attributed to P Morgan-Capner.

At least 37 records · Page 2Linked to original sources

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.

Adolescent↗

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.

Aged↗

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.

Cross Infection↗

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.

Adult↗

Childhood infection with hepatitis A and B viruses in England and Wales.

Infection with hepatitis B and A viruses during childhood was studied using serum specimens collected from children aged 13 and 14 years by 12 public health laboratories in England and Wales from 1986 to 1995. Six of the 2025 specimens tested for markers of hepatitis B infection showed evidence of earlier resolved infection, one specimen showed evidence of recent infection, and hepatitis B surface antigen (HBsAg) was detected in three specimens. The HBsAg carriage rate of 0.15% (3/2025) was consistent with that expected from vertical transmission before the introduction of antenatal screening and neonatal hepatitis B vaccination, for which the children in our study would not have been eligible. Five of the six children with earlier resolved hepatitis B infection also showed evidence of hepatitis A infection, whose coexistence raises the possibility that both infections were acquired abroad in areas of high endemicity. At present, by adolescence, about one in 200 children has at some time been infected with hepatitis B virus. The current practice of screening pregnant women for HBsAg and selectively vaccinating neonates at high risk of acquiring hepatitis B infection may reduce this rate in the future. Immunisation of all infants against hepatitis B would prevent very few more childhood infections than the current policy. The incidence of hepatitis A infection has fallen in the past decade, suggesting the potential for an epidemic resurgence in the future as more of the population becomes susceptible. The average annual incidence of hepatitis A infection in children aged 0 to 14 years from 1986 to 1995 was 800 per 100 000, fifty times higher than the reported incidence of laboratory confirmed disease in this age group. Most hepatitis A infections in this age group are therefore likely to be subclinical or very mild.

Adolescent↗

The epidemiology of measles in England and Wales since the 1994 vaccination campaign.

The incidence of measles in England and Wales has fallen since the national vaccination campaign in November 1994, in which 92% of children aged 5 to 16 years were vaccinated. A total of 148 confirmed cases with onsets in the 18 months from January 1995 to June 1996 have been ascertained. Notified cases did not provide a reliable measure of incidence: 11,343 suspected cases were notified in the same period, 6426 (57%) of whom were tested for salivary antibody. Only 90 (1.4%) of cases tested were confirmed. Many confirmed cases occurred in small clusters; 12 imported cases were identified. The pattern of small, local clusters is what would be expected from the introduction of imported cases into a population with herd immunity. Serological surveillance showed that the campaign produced a significant fall in the proportion of 5 to 16 year old children with low levels of measles antibody: the proportion with levels < 50 mIU/ml fell from 8.4% to 2.1%; the proportion with levels < 100 mIU/ml fell from 15.7% to 6.6%. About 15% of 2 to 4 year old children had antibody levels < 100 mIU/ml before and after the campaign. The addition of a routine second dose of measles vaccine (as measles, mumps, and rubella vaccine) to the vaccination schedule will provide another opportunity to immunise these children before they start school. The two dose vaccination programme should maintain the herd immunity of the population and the elimination of endemic measles transmission.

Adolescent↗

Mumps surveillance in England and Wales supports introduction of two dose vaccination schedule.

Sentinel surveillance in general practice and laboratory reports to the PHLS Communicable Disease Surveillance Centre show that the incidence of mumps has fallen to very low levels since vaccination against measles, mumps, and rubella was introduced in 1988. Hospital admissions for mumps show a 92% decline compared with the prevaccination era, to a rate of 0.2 per 100,000 population per year. Serological surveillance has shown an increase in the proportion of school age children who have no detectable antibody to mumps, which is consistent with the reduction in mumps virus transmission. The proportion of children aged 11 to 15 years with no detectable antibody is expected to peak at 19% in 1997. Mathematical models suggest that this increase in susceptibility is unlikely to allow a large resurgence of mumps in the short term but that school outbreaks may become more common. Outbreaks in universities and military establishments are possible in the medium term. Analysis of efficacy data for mumps vaccine indicates that mumps is unlikely to be eliminated with a single dose of vaccine at current coverage rates. A second dose of vaccine, which is now being offered to preschool children, will reduce morbidity and should eventually eliminate mumps if coverage is high enough.

Adolescent↗

The epidemiology of rubella in England and Wales before and after the 1994 measles and rubella vaccination campaign: fourth joint report from the PHLS and the National Congenital Rubella Surveillance Programme.

The national immunisation campaign carried out in the United Kingdom in November 1994 was designed to give children aged 5 to 16 years of age a single dose of a combined measles and rubella vaccine. Its main objective was to prevent an epidemic of measles predicted in school age children. The rubella component of the vaccine was included in order to reduce the high level of susceptibility to rubella in young adult males and thus reduce the risk of transmission from this group to pregnant women. Susceptibility to rubella in children aged 5 to 16 years has fallen from 15.7% to 3.4% since the measles and rubella campaign. Despite this the incidence of laboratory confirmed rubella rose substantially in 1996, largely on account of cases among males aged 17 to 24 years, who were not vaccinated in the 1994 campaign and about 16% of whom are susceptible. The impact of the resurgence on the incidence of infection in pregnancy has been relatively limited, due to the low level of susceptibility in the antenatal population (2% in nulliparous and 1.2% in parous women for 1994/5). No cases of congenital rubella arising from administration of measles and rubella vaccine during the campaign have been identified. The numbers of babies born with congenital rubella and terminations of pregnancy for rubella arising from the 1996 resurgence are expected to be similar to those that followed the 1993 resurgence. The reduction in susceptibility in future cohorts of young men who received measles and rubella vaccine in the 1994 campaign should prevent future resurgences after the year 2000. If a second dose of measles, mumps, and rubella (MMR) vaccine had not been introduced, susceptibility levels in the school age population would have risen to about 12% in the future. The effect of the second dose of MMR vaccine introduced for children aged 4 to 5 years in October 1996 will be assessed through serological surveillance.

Adolescent↗

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.

Antibodies, Viral↗

Zoonotic and viral infection in fetal loss after 12 weeks.

One hundred and thirty-six women from an urban, rural and farming community were recruited to a study of infectious causes of midtrimester miscarriage (n = 85), stillbirth (n = 32), or termination for developmental (n = 17) or chromosomal (n = 2) abnormalities. No woman had evidence of acute infection with toxoplasma, listeria, leptospira or Chlamydia psittaci (ovine enzootic abortion). One woman had midtrimester miscarriage associated with primary cytomegolovirus infection and five women had evidence of parvovirus B19 infection, although fetal infection was not proven. Zoonoses were not identified as a cause of fetal loss or malformation in this at-risk population, but parvovirus B19 was a significant cause of midtrimester fetal loss.

Abortion, Induced↗

Coxsackievirus B3-induced myocarditis. Characterization of stable attenuated variants that protect against infection with the cardiovirulent wild-type strain.

Coxsackievirus B3 (CVB3) is the enterovirus most frequently involved in human myocarditis or dilated cardiomyopathy. Attenuated variants were derived from a cardiovirulent CVB3 reactivated from a sequenced, full-length cDNA clone. The prophylactic potential of these variants was assessed in SWR/Ola (H-2q) mice. Animals immunized with attenuated variants of CVB3 were protected from myocarditis when challenged subsequently with the cardiovirulent wild-type virus. In contrast to nonimmunized controls, the wild-type virus was not isolated from myocardium of protected mice, nor was viral RNA detected in myocardium by reverse transcription nested polymerase chain reaction. Specific antibody to CVB3 was demonstrated by virus neutralization assay and by indirect immunofluorescence. The attenuated phenotype of one variant, p14V-1, remained stable throughout 20 consecutive passages in SWR mice and induced a markedly lower level of autoantibody against mouse cardiac myosin heavy chain than the cardiovirulent wild type. These data demonstrate that attenuated strains protect against CVB3-induced myocarditis in mice, that the attenuated phenotype is stable, and that they do not persist in myocardium nor induce a significant level of anti-heart anti-body against myosin heavy chain. These attenuants may be the basis of a live vaccine against CVB3 in the prevention of enteroviral heart muscle disease.

Animals↗

Evaluation of 15 commercial enzyme immunoassays for the detection of rubella-specific IgM.

BACKGROUND: Detection of rubella-specific IgM is a critical investigation in the diagnosis of recent or congenital rubella for which many commercial enzyme immunoassays (EIAs) are now available. OBJECTIVES: To evaluate 15 commercially-available EIA kits for the detection of rubella-specific IgM. STUDY DESIGN: A panel of 229 sera was established comprising 72 sera from cases of primary rubella, re-infection, congenital rubella and primary immunization in which rubella-specific IgM had been detected by M-antibody capture radioimmunoassay (MACRIA); 80 sera, negative by MACRIA and no evidence of recent illness; 77 sera from recent illness with a number of other microbial agents, sera containing rheumatoid factor, and sera previously shown to give non-specific reactivity by MACRIA. These sera were tested in 15 commercial EIA kits for rubella-specific IgM according to the manufacturers' instructions. Sensitivity and specificity for each assay was established. RESULTS: Specificities ranged from 82-98%, improving to 88-100% if the previously established non-specific reactive sera were excluded. Sensitivities ranged from 63-92%. Although only two sera from congenital rubella were tested, for one serum only four assays detected specific IgM. CONCLUSION: Some commercial EIAs for rubella-specific IgM now give an acceptable balance of sensitivity and specificity, but all assays may give reactivity with occasional sera where there is no supporting evidence for recent primary rubella or rubella reinfection.

Journal Article↗

Differential maturation of avidity of IgG antibodies to gp41, p24 and p17 following infection with HIV-1.

We have evaluated solid-phase ELISA IgG antibody avidity studies as a means of identifying cases of recent HIV-1 infection. Although separate studies on the avidity of anti-gp41 and anti-p24 antibodies in seroconvertors have been reported, a comparison of the ability of patients to simultaneously mature their immune response to more than one HIV antigen immediately following seroconversion appears to be lacking. We have demonstrated a maturation in anti-gp41 avidity which reflects the time since seroconversion in all cases. In contrast, however, only some patients produced high-avidity anti-p24 or anti-p17 antibodies during the same time span. While the avidity of anti-gp41 antibodies remained high in cases of non-recent HIV infection, even in the face of advanced disease, we have confirmed the findings of others that the avidity of anti-p24 falls before the onset of ARC or AIDS. Therefore, whilst the avidity of anti-gp41 antibodies could reliably be of value in identifying cases of recent HIV infection, the avidity of anti-p24 or anti-p17 antibodies could not, but may be of prognostic value, even at an early stage. The time taken to reach maximum anti-p17, anti-p24 and anti-gp41 titres was variable, but anti-gp41 titres, like anti-gp41 avidity, remained high. In contrast, anti-p24 titres fell, even during the early followup period in some seroconvertors. Anti-p24 antibody avidity, however, appeared to be a better predictor of disease progression in 'remote' cases than anti-p24 titre. The avidity and titres of these antibodies are presented in relation to the clinical details, p24 antigen status, CD4 and CD8 counts where these are known.

Adult↗

A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines.

We describe a new method for active post-marketing surveillance of vaccine safety based on patient records. We studied the association between diphtheria/tetanus/pertussis (DTP) vaccination and febrile convulsion, and between measles/mumps/rubella (MMR) vaccination and febrile convulsion and idiopathic thrombocytopenic purpura (ITP) in five district health authorities in England by linking vaccination records with computerised hospital admission records. We found an increased relative incidence for convulsions 0-3 days after DTP vaccination. The effect was limited to the third dose of vaccine for which the attributable risk (all ages) was 1 in 12,500 doses. Completion of vaccination by 4 months instead of 10 months after the change in the UK to an accelerated immunisation schedule may have resulted in a 4-fold decrease in febrile convulsions attributable to DTP vaccine. 67% of admissions for a convulsion 6-11 days after MMR vaccination were attributable to the measles component of the vaccine (risk 1 in 3000 doses). An excess of admissions for a convulsion 15-35 days after MMR vaccination was found only for vaccines containing the Urabe mumps strain (1 in 2600 Urabe doses). There was a causal association between MMR vaccination and ITP resulting in admission 15-35 days subsequently; there was no evidence of a mumps strain-specific effect. The estimated absolute risk of 1 in 24,000 doses was 5 times that calculated from cases passively reported by clinicians. This finding emphasises the need for active surveillance of adverse events. The record linkage method that we used is an effective way to identify vaccine-attributable adverse events.

Diphtheria-Tetanus-Pertussis Vaccine↗

A single amino acid substitution in the capsid protein VP1 of coxsackievirus B3 (CVB3) alters plaque phenotype in Vero cells but not cardiovirulence in a mouse model.

We previously described a large plaque attenuant (p14V-1) derived from a cardiovirulent Coxsackievirus B3 (CVB3) and showed that there were no major determinants of either attenuation or plaque phenotype in the 5' nontranslated region (5'NTR). Part of the region encoding the last 124 amino acids of VP3 and the first 106 amino acids of VP1 of the attenuant was then sequenced and compared to the wild-type. Three nucleotide changes were found in the VP1 coding region: a silent single base change at nucleotide position 2467 (C to U) and a double-base change at position 2690-1 (AA to GT), which leads to a change from lysine to serine at amino acid position 80. This mutation maps to the begining of B-C loop of the three-dimensional structure of VP1 of CVB3, where a distinct surface projection is formed. Two infectious chimeric cDNA clones were constructed, based on a cardiovirulent cDNA construct. In one construct, the 5'NTR and the VP3-VP1 region were from p14V-1 and in the other, only the VP3-VP1 region was from this attenuant. Both chimeric viruses produced large plaques on Vero cell monolayers, similar to p14V-1 but larger than the prototypic cardiovirulent virus. In vivo experiments showed that both chimeric viruses induced myocarditis in a murine model, similar to wild-type virus. We conclude that mutation serine-80 in capsid protein VP1 of p14V-1 is a determinant of the large plaque phenotype but is not responsible for attenuation.

Amino Acid Sequence↗

Antibodies to measles, mumps and rubella in UK children 4 years after vaccination with different MMR vaccines.

Persistence of antibodies 4 years after vaccination with measles, mumps and rubella (MMR) vaccine from three different manufacturers was compared in 475 children who received a single injection of vaccine when aged 12-18 months. Antibodies to measles and mumps were measured using a plaque reduction neutralisation assay; rubella antibodies were measured by radial haemolysis and latex agglutination. Children given MMR vaccine containing the Urabe mumps strain were less likely to be antibody negative than those given the Jeryl Lynn mumps strain (39/266, 15% vs 39/204, 19%, p = 0.048). However, the relatively high proportions in both groups without detectable mumps neutralising antibody suggests the probable need for a second dose in order to achieve mumps elimination. No significant differences were found in the proportions with detectable antibody to measles between vaccines containing the Schwarz and the Enders-Edmonston strains. Overall, only 3% of vaccinees were without detectable measles antibody, although a further 28% had a level below 200 mille International Units, the putative protective level for clinical measles. Geometric mean titres (GMTs) to measles were twofold higher in girls vaccinated after than before 14 months of age; GMTs in boys were intermediate and showed no age effect. Over 99% of vaccinees were seropositive to rubella, confirming the excellent immunogenicity of the RA 27/3 rubella strain and the potential for elimination of rubella with a single dose strategy.

Antibodies, Viral↗