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Biomedical subjects

N J Andrews

Publications and source records attributed to N J Andrews.

At least 19 recordsLinked to original sources

Modelling the hepatitis B vaccination programme in prisons.

A vaccination programme offering hepatitis B (HBV) vaccine at reception into prison has been introduced into selected prisons in England and Wales. Over the coming years it is anticipated this vaccination programme will be extended. A model has been developed to assess the potential impact of the programme on the vaccination coverage of prisoners, ex-prisoners, and injecting drug users (IDUs). Under a range of coverage scenarios, the model predicts the change over time in the vaccination status of new entrants to prison, current prisoners and IDUs in the community. The model predicts that at baseline in 2012 57% of the IDU population will be vaccinated with up to 72% being vaccinated depending on the vaccination scenario implemented. These results are sensitive to the size of the IDU population in England and Wales and the average time served by an IDU during each prison visit. IDUs that do not receive HBV vaccine in the community are at increased risk from HBV infection. The HBV vaccination programme in prisons is an effective way of vaccinating this hard-to-reach population although vaccination coverage on prison reception must be increased to achieve this.

Adolescent↗

Survival of a national cohort of hepatitis C virus infected patients, 16 years after exposure.

The aim of this study was to describe the natural history of HCV after 16 years of infection, in a cohort of individuals who acquired their infections on a known date in the United Kingdom. A total of 924 HCV-infected transfusion recipients (cases) and 475 anti-HCV negative transfusion recipients (controls) were eligible for inclusion in the study. Survival was compared between cases and controls to see if there was any excess mortality attributable to HCV. The results show that all-cause mortality was not significantly different between cases and controls (hazard ratio 1.17, 95% CI 0.92-1.49, P=0.21). However, the risk of death directly from liver disease was higher in cases than controls (hazard ratio 2.71, 95% CI 1.09-6.75, P=0.03). Nearly 30% of those HCV-infected cases who died directly from liver disease were known to have consumed excess alcohol.

Adolescent↗

The seroepidemiology of Bordetella pertussis infection in Western Europe.

High titres of pertussis toxin (PT) antibody have been shown to be predictive of recent infection with Bordetella pertussis. The seroprevalence of standardized anti-PT antibody was determined in six Western European countries between 1994 and 1998 and related to historical surveillance and vaccine programme data. Standardized anti-PT titres were calculated for a series of whole-cell and acellular pertussis vaccine trials. For the serological surveys, high-titre sera (> 125 units/ml) were distributed throughout all age groups in both high- (> 90%) and low-coverage (< 90%) countries. High-titre sera were more likely in infants in countries using high-titre-producing vaccines in their primary programme (Italy, 11.5%; Western Germany, 13.3%; France, 4.3%; Eastern Germany, 4.0%) compared to other countries (The Netherlands, 0.5%; Finland, 0%). Recent infection was significantly more likely in adolescents (10-19 years old) and adults in high-coverage countries (Finland, The Netherlands, France, East Germany), whereas infection was more likely in children (3-9 years old) than adolescents in low-coverage (< 90%; Italy, West Germany, United Kingdom) countries. The impact and role of programmatic changes introduced after these surveys aimed at protecting infants from severe disease by accelerating the primary schedule or vaccinating older children and adolescents with booster doses can be evaluated with this approach.

Adolescent↗

Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland.

BACKGROUND: Primary human herpesvirus-6 and -7 (HHV-6/-7) infections cause febrile illness sometimes complicated by convulsions and rarely encephalopathy. AIMS: To explore the extent of such HHV-6 and -7 induced disease in young children. METHODS: In a three year prospective study in Britain and Ireland, 205 children (2-35 months old) hospitalised with suspected encephalitis and/or severe illness with fever and convulsions were reported via the British Paediatric Surveillance Unit network. Blood samples were tested for primary HHV-6 and -7 infections. RESULTS: 26/156 (17%) of children aged 2-23 months had primary infection (11 HHV-6; 13 HHV-7; two with both viruses) coinciding with the acute illness; this was much higher than the about three cases expected by chance. All 26 were pyrexial; 25 had convulsions (18 status epilepticus), 11 requiring ventilation. Median hospital stay was 7.5 days. For HHV-6 primary infection the median age was 53 weeks (range 42-94) and the distribution differed from that of uninfected children; for HHV-7, the median was 60 weeks (range 17-102) and the distribution did not differ for the uninfected. Fewer (5/15) children with primary HHV-7 infection had previously been infected with HHV-6 than expected. CONCLUSIONS: Primary HHV-6 and HHV-7 infections accounted for a significant proportion of cases in those <2 years old of severe illness with fever and convulsions requiring hospital admission; each virus contributed equally. Predisposing factors are age for HHV-6 and no previous infection with HHV-6 for HHV-7. Children with such neurological disease should be investigated for primary HHV-6/-7 infections, especially in rare cases coinciding by chance with immunisation to exclude misdiagnosis as vaccine reactions.

Child, Preschool↗

Antibody to Haemophilus influenzae type b after routine and catch-up vaccination.

Since 1999, the number of cases of Haemophilus influenzae type b (Hib) disease in the UK has risen. We investigated the role of population immunity in this change by testing more than 2600 serum samples from children aged 1-15 years. After the introduction of the routine Hib conjugate vaccination programme for infants, median antibody titres rose significantly in 1-year-olds. Individuals who received their first dose of vaccine at age 1-4 years in the original catch-up campaign initially had much higher concentrations of antibody than those who had been immunised in infancy. A second catch-up campaign in children aged 6 months to 4 years should be highly effective in boosting immunity and reducing disease in the short term.

Adolescent↗

Deaths from variant Creutzfeldt-Jakob disease in the UK.

In 2002, 17 people died from variant CJD (vCJD) in the UK, compared with 20 in 2001 and 28 in 2000. We analysed data for deaths from vCJD since 1995 and estimated the underlying trend in mortality. The trend had a quadratic component (p=0.005), suggesting that the increase was not exponential, and that the previously increasing trend is slowing down. The death rate peaked in 2000. These findings are encouraging, but mortality might increase again in the future.

Adolescent↗

Measurement of IgG antibodies to Chlamydia trachomatis by commercial enzyme immunoassays and immunofluorescence in sera from pregnant women and patients with infertility, pelvic inflammatory disease, ectopic pregnancy, and laboratory diagnosed Chlamydia psittaci/Chlamydia pneumoniae infection.

BACKGROUND: Screening for Chlamydia trachomatis specific antibodies is valuable in diagnosing asymptomatic pelvic inflammatory disease (PID) and tubal damage following repeated episodes of PID. The assays in current use are unsuitable for screening large numbers of samples so there is a need to develop more suitable assays. AIMS: To compare the performance of several commercial C trachomatis enzyme immunoassays (EIAs) (SeroCT, C tracho(pep), Medac p-EIA, Vircell and Labsystems C trachomatis IgG EIAs) using major outer membrane protein (MOMP), an inactivated organism EIA (Genzyme Virotech EIA), and a genus specific EIA (Platelia Chlamydia IgG) with the whole cell inclusion immunofluorescence (WIF) assay. In addition, to adapt, using time resolved fluorescence technology, the assay showing the highest correlation with WIF. METHODS: Ninety sera from patients presenting with ectopic pregnancies, 187 sera from those with a variety of types of infertility, 33 sera from cases of PID where a fourfold rise in WIF titre occurred, and 90 sera from antenatal clinic attenders were tested. A panel of 36 sera from laboratory diagnosed cases of Chlamydia psittaci/Chlamydia pneumoniae infection was also tested. RESULTS: The Genzyme Virotech EIA showed the highest rank correlation coefficient (0.82) with WIF, particularly at high WIF titres. The MOMP specific assays varied in their correlation with WIF, with rank correlation coefficients ranging from 0.70 (Medac p-EIA) to 0.80 (Vircell EIA). The Genzyme Virotech assay showed poor specificity (5.6%; 95% confidence interval (CI), 0.68% to 18.7%)--it was reactive with 34 of the panel of 36 C psittaci/C pneumoniae positive sera. The MOMP based EIAs showed high specificity, particularly the Medac p-ELISA (97.2%; 95% CI, 85.5% to 99.9%)--only one serum was reactive. In view of the good correlation between WIF and the Genzyme Virotech EIA, a time resolved fluorescence immunoassay (TRFIA) was developed using the Genzyme Virotech antigen. Using an appropriate cut off the TRFIA assay showed excellent correlation with WIF. CONCLUSIONS: The TRFIA assay may be useful as a screening assay, possibly in conjunction with one of the highly specific EIAs studied (for example, Medac p-EIA) to confirm the antibody specificity of sera selected by the screening assay.

Antibodies, Bacterial↗

A national survey of genitourinary medicine clinic attenders provides little evidence of sexual transmission of hepatitis C virus infection.

OBJECTIVE: To determine the prevalence and genetic diversity of hepatitis C virus in genitourinary medicine clinic attenders and to assess the extent of sexual transmission of the virus. METHODS: A cross sectional, unlinked, anonymous survey in 14 genitourinary medicine clinics situated in England, Wales, and Northern Ireland. Serum specimens from genitourinary medicine clinic attenders, retained as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP) serum archive, were tested in small pools, for the presence of antibody to hepatitis C virus (anti-HCV). The main outcome measures were prevalence of antibodies to hepatitis C virus and identification of hepatitis C virus genotypes. RESULTS: Testing of 17,586 specimens from 1995 showed an adjusted prevalence of anti-HCV in genitourinary medicine clinic attenders of 1.03% (95% CI: 0.89 to 1.16) overall and 0.65% (95% CI: 0.51 to 0.78) among those who did not report injecting drug use. Prevalence in injecting drug users attending genitourinary medicine clinics was 36.9% in both 1995 and 1996. Heterosexual injecting drug users had a higher prevalence of anti-HCV than homosexual/bisexual injectors. The most common hepatitis C genotypes were types 3a and 1a. There was a high degree of concordance between genotype and serotype. CONCLUSIONS: The low prevalence of anti-HCV in genitourinary medicine clinic attenders who deny injecting drugs suggests that the majority of hepatitis C infections have been acquired in adult life, mostly by injecting drug use, and that the hepatitis C virus is rarely transmitted sexually. The use of needle exchanges may explain the relatively low prevalence observed in the injecting drug users.

Adult↗

Exposure to varicella boosts immunity to herpes-zoster: implications for mass vaccination against chickenpox.

We present data to confirm that exposure to varicella boosts immunity to herpes-zoster. We show that exposure to varicella is greater in adults living with children and that this exposure is highly protective against zoster (Incidence ratio=0.75, 95% CI, 0.63-0.89). The data is used to parameterise a mathematical model of varicella zoster virus (VZV) transmission that captures differences in exposure to varicella in adults living with and without children. Under the 'best-fit' model, exposure to varicella is estimated to boost cell-mediated immunity for an average of 20 years (95% CI, 7-41years). Mass varicella vaccination is expected to cause a major epidemic of herpes-zoster, affecting more than 50% of those aged 10-44 years at the introduction of vaccination.

Adolescent↗

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.

Adolescent↗

Statistical assessment of the association between vaccination and rare adverse events post-licensure.

Once a new vaccine has been licensed and is in widespread use, it is important to be able to detect and investigate adverse events which may be associated with the vaccine. This is particularly important for rare events which may have been missed in pre-licensure studies. Recent studies investigating adverse events following vaccination have used either a population or a sample of the population (cohort studies), cases matched to controls (case-control studies), or just information on the cases themselves (self-controlled case-series studies). In this paper, the three methods are reviewed and compared and examples are given of recent applications. The effects of potential sources of bias are demonstrated using a data set on MMR vaccine and convulsions.

Case-Control Studies↗

A model to assess the infection potential of jet injectors used in mass immunisation.

Jet injectors are needleless injectors that penetrate skin with high-pressure fluid. They have potential advantages over needles and syringes in mass immunisation programs, but concerns over their capacity to transfer blood-borne viruses have been a barrier to acceptance. Hepatitis B infection can transmit in 10 pl of blood; detection of such low volumes presents severe difficulties to such assessments. A model to assess jet injector safety was developed using injection of an inert buffer into calves and assaying the next injector discharge, representing the next dose of vaccine, for blood using a highly sensitive ELISA. Four injectors were tested: two with reusable heads and direct skin contact, one with single-use injector heads and one where the injector head discharged at a distance from the skin. All injectors tested transmitted significant (over 10 pl) volumes of blood; the volumes and frequency of contamination varied with injector. The source of the contamination was consistent with contamination by efflux of injected fluid and blood from the pressurised pocket in tissue that is formed during injection. This insight should inform the design of safe jet injectors.

Animals↗

Time resolved fluorometric immunoassay, using europium labelled antihuman IgG, for the detection of human tetanus antitoxin in serum.

A time resolved fluorometric immunoassay (TRFIA) has been developed and compared with an in house enzyme linked immunosorbent assay (ELISA) and commercial ELISA (Bindazyme) for the detection of tetanus antitoxin in human sera. A panel of 132 sera submitted for routine testing was used. Scatterplots showed a high degree of correlation between all three assays, although some divergence of results was apparent for low titre sera when comparing in house ELISA results with Bindazyme ELISA and TRFIA results. The TRFIA appeared to be more sensitive than the in house ELISA, and the Bindazyme assay compared well with the TRFIA. The intra-assay precision of all three assays, in terms of percentage coefficient of variation (%CV), was between 2.0% and 4.0%. The interassay precision ranged from 5% to 8% for the in house ELISA, 13% to 19% for the Bindazyme assay, and 11% to 13% for TRFIA. Both Bindazyme and TRFIA assays were simple to perform, accurate, reproducible, and amenable to automation. A particular benefit of the TRFIA was its large dynamic range, enabling tetanus antitoxin values of 0.01 IU/ml to 50 IU/ml to be measured with just one dilution of serum. TRFIA appears to be a useful serological technique worthy of further development.

Confidence Intervals↗

Immunity to diphtheria and tetanus in England and Wales.

The immunity profile of the English and Welsh population to diphtheria and tetanus has been determined by measuring diphtheria and tetanus antitoxin levels for 3088 and 3142 sera, respectively. Time-resolved fluorimetric immunoassay - DELFIA was used to measure diphtheria antitoxin levels and an in-house, indirect ELISA to measure tetanus antitoxin levels. More than 80% of those aged between 2 and 20-24 years had protective diphtheria antitoxin levels of 0.01 IU/ml, or greater, and more than 80% of those aged between 4 and 35-39 years had protective tetanus antitoxin levels of 0.1 IU/ml, or greater. Only 29% and 53% of those aged 60 and over were protected against diphtheria and tetanus. Two increases of diphtheria antitoxin levels greater than 0.1 IU/ml and tetanus antitoxin levels greater than 1.0 IU/ml were apparent, starting at 4 and 14 years of age, which correspond with the policy of giving a diphtheria and tetanus toxoid booster on school entry and a tetanus plus low-dose diphtheria toxoid (recently introduced) booster to school leavers. This is the first comprehensive study of diphtheria and tetanus immunity in the English and Welsh population and shows that the accelerated schedule of immunisation, introduced in 1990, has effectively primed immunological memory against both these antigens and that boosting at school entry and at school leaving is effective in increasing levels of immunity.

Adolescent↗

Incidence of variant Creutzfeldt-Jakob disease in the UK.

The number of deaths from variant CJD (vCJD) in the UK increased in the last quarter of 1998, although numbers were lower in subsequent quarters. We analysed the numbers of definite and probable (living and dead) vCJD cases since 1994 to assess trends in incidence. We estimated that the number of onsets increased by 23% per year for 1994-2000 (p=0.004), and that deaths increased by 33% for 1995-2000 (p=0.005). The absolute number of cases in the UK is still low, but such an increase should be a matter of concern.

Creutzfeldt-Jakob Syndrome↗

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.

Adolescent↗

Bordetella pertussis surveillance in England and Wales: 1995-7.

Available data sources on disease due to Bordetella pertussis, including notifications, hospital admissions, deaths, and an enhanced laboratory-based surveillance system commenced in January 1994, were reviewed for the period 1995-7. Pertussis notifications continued their approximately 3-year cycle although at historically reduced levels. A slight seasonal increase in late summer/early autumn existed over and above a relatively constant background rate. Over time, the proportion of pertussis cases in younger, unvaccinated children, and to a lesser extent, adolescents and young adults, is increasing. There is a continuing significant and underreported mortality associated with pertussis in the very young age group. Disease due to serotype 1,2 is on the increase despite persistent high vaccination levels and this serotype causes more severe disease. The provision of preventative antibiotics prior to disease onset reduced the severity of the disease but its use remains uncommon in England and Wales. While overall levels of pertussis notifications have declined in recent times, vaccination efficacy wanes with increasing age, and pertussis remains a significant cause of mortality and severe morbidity in the very young. This could be reduced by timely booster vaccination and increased recognition of mild disease in older cases followed by early antibiotic therapy for the very young household contacts.

Adolescent↗