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Biomedical subjects

M E Ramsay

Publications and source records attributed to M E Ramsay.

At least 19 recordsLinked to original sources

Clusters of meningococcal disease in school and preschool settings in England and Wales: what is the risk?

AIMS: To assess the risk of further cases in educational settings in order to inform policy on managing cases and clusters of meningococcal disease. METHODS: Between 1 April 1995 and 31 March 2001, surveillance in preschool and school settings in England and Wales identified 114 clusters of meningococcal disease. Twenty clusters were reported in preschool settings, 43 in primary, 46 in secondary, and five in independent schools. Seventy three clusters (64%) consisted of two or more confirmed cases, of which 30 had two or more serogroup C cases. Following the introduction of the national meningococcal serogroup C vaccination programme in 1999, no serogroup C clusters were observed between April 2000 and March 2001. RESULTS: The relative risk of further cases in the four weeks after a single case compared with the background rate was raised in all settings, ranging from RR 27.6 (95% CI 15.2 to 39.9) in preschool settings to RR 3.6 (95% CI 2.5 to 4.6) in secondary schools. Absolute risk estimates ranged from 70/100 000 in preschool settings to 3.0/100 000 in secondary schools. The relative risk of clustering was similar for serogroup B and C strains. Most (68%) second cases occurred within seven days of the first case. CONCLUSIONS: Although there was a higher risk of further cases of meningococcal disease in schools and especially in preschool settings, it is not known whether widespread antibiotic use after single cases reduces risk of further cases and if there is a real risk of harm. Evidence of risk reduction is needed to inform public health policy.

Child↗

Risk of vaccine failure after Haemophilus influenzae type b (Hib) combination vaccines with acellular pertussis.

An increase in invasive Hib disease incidence in the UK has coincided with the distribution of combination vaccines that contain acellular pertussis (DTaP-Hib). These vaccines have been associated with reduced immunogenicity of the Hib component, although there is little agreement on the clinical relevance of this finding. We retrospectively compared vaccine formulations given to fully vaccinated Hib cases with those administered to fully immunised age-matched controls using conditional logistic regression. More cases than controls received all three doses of their infant primary course as DTaP-Hib, compared with two or three doses of another Hib vaccine (conditional odds ratio 6.77 [95% CI 3.26-14.07]).

Diphtheria-Tetanus-Pertussis Vaccine↗

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↗

Tetanus in England and Wales, 1984-2000.

A review of national tetanus surveillance in England and Wales during 1984-2000 was undertaken to evaluate the surveillance system and national vaccination policy. Hospital Episode Statistics for tetanus in England for fiscal years 1989/90-1995/6 were also examined to estimate under-reporting. A total of 175 cases of tetanus were reported, giving an annual incidence of 0.20 per million, the lowest levels ever recorded. The highest incidence was in those aged over 64 years (0.66 per million) with no significant sex difference. Twenty (11%) cases were reported in people who were eligible for routine childhood vaccination. Outdoor injuries were the commonest reported exposure risk. Tetanus case under-reporting was estimated as 54-64%. We conclude that GPs should ensure that all their patients are fully vaccinated, targeting those born before 1961. High childhood tetanus vaccination coverage remains a priority. As the disease becomes rarer, enhanced tetanus case surveillance is essential for tetanus immunization policy evaluation.

Adolescent↗

Estimation of the risk of hepatitis B virus, hepatitis C virus and human immunodeficiency virus infectious donations entering the blood supply in England, 1993-2001.

BACKGROUND AND OBJECTIVES: The frequency of hepatitis B virus (HBV), hepatitis C virus (HCV) or human immunodeficiency virus (HIV) infectious donations entering the blood supply in England is too low to monitor using observational studies. The expected frequency of infectious donations can be estimated and these estimates may be used to contribute to monitoring of blood safety and used in the design of strategies to decrease the risk of transfusion-transmitted infections. MATERIALS AND METHODS: The prevalence and incidence of hepatitis B surface antigen (HBsAg), and antibodies to HCV and HIV (anti-HCV and anti-HIV, respectively) in donors in England, between 1993 and 2001, were used together with data about the length of negative 'window-periods' of current assays for each of these markers and data about test performance, to estimate the number of infectious donations that enter the blood supply. The risks were calculated separately for donations from new donors and from repeat donors, and for the three time periods 1993-95, 1996-98 and 1999-01. RESULTS: The estimated frequency of infectious donations entering the blood supply in England, between 1993 and 2001 was 1 in 260,000 for HBV and 1 in 8 million for HIV. For HCV, the frequency of infectious donations was 1 in 520,000 during 1993-98 and fell to 1 in 30 million during 1999-2001 when all donations were tested for HCV RNA. The frequency of HBV- and HCV-infectious donations entering the blood supply fell over these 9 years: the frequency of HIV-infectious donations remained essentially unchanged. The risk from donations from new donors was found to be approximately sevenfold higher than the risk from donations from repeat donors. CONCLUSIONS: The risks of HBV-, HCV- or HIV-infectious donations entering the blood supply in England are very low, and have decreased since 1993. Although the accuracy of these estimates is imperfect, mainly owing to uncertainty in some assumptions and to small numbers of infections, they provide some quantification of the risk of HBV, HCV or HIV transmission by transfusion, and allow comparison of the magnitude of these risks for each infection and over time. The methods we have used have been developed and improved from previously published methods.

Blood Donors↗

Hib vaccination in infants born prematurely.

AIMS: To document the immunogenicity and persistence of antibody to polyribosyl-ribitol phosphate (PRP) as well as the clinical protection against invasive Haemophilus influenzae type b (Hib) disease in premature infants immunised at the routine schedule. METHODS: Blood was obtained at 2, 5, 12, and 64 months of age from a cohort of prematurely born infants (<or=32 weeks gestation). Anti-PRP antibody concentrations were compared with those of a control cohort of infants born at full term and vaccinated at the same schedule. Hib vaccine failures occurring between October 1992 and October 2000 were reported by paediatricians through an active, prospective, national survey in the UK and Republic of Ireland. The number of prematurely born children with vaccine failure was compared with the corresponding number born at term. RESULTS: Twenty seven prematurely born infants were followed to 5 years of age. Compared with term infants they had a significantly lower geometric mean concentration of anti-PRP antibody and/or a significantly lower proportion above one or both of the conventional protective antibody concentrations (0.15 and 1.0 micro g/ml) at all ages. A total of 165 cases of invasive Hib disease were identified over eight years of national surveillance. Eighteen were premature (<37 weeks); approximately 12 would be expected. The relative risk of UK premature infants developing disease compared with term infants was 1.5 (95% CI 0.9 to 2.6). CONCLUSIONS: Premature infants develop lower antibody concentrations than term infants following Hib conjugate vaccination. Premature infants may also have an increased risk of clinical vaccine failure, but interpretation is limited by the small number of premature infants developing invasive Hib disease over eight years of national surveillance. Overall, vaccination with Hib conjugate vaccines affords a high level of protection to premature babies.

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↗

Risk factors, clinical features and genotype distribution of diagnosed hepatitis C virus infections: a pilot for a sentinel laboratory-based surveillance.

Hepatitis C is a global public health problem. A cross-sectional survey was undertaken to determine the frequency of reported risk factors and possible transmission routes in individuals in whom HCV antibody (anti-HCV) was newly detected. Seven public health laboratories in England and Wales reported persons with positive anti-HCV tests over a three-month period (1st November 1996-31st January 1997). A questionnaire was then sent to the clinician or general practitioner (GP) who requested the test. A total of 320 laboratory reports were received from participating laboratories and 221 (69%) questionnaires were received from clinicians and GPs. Of those patients from whom a questionnaire was received (median age 36 years; males 72.9%, females 23.1%), 86% had one or more risk factors for infection reported by the clinician/GP. Injecting drug use (68%) was the main risk factor reported. Reasons for testing included being in a known risk group (65%), liver disease (19%) and blood donation (1.4%). Of the total responders, 67% were asymptomatic, and of those that had had liver function tests 50% were abnormal. The most prevalent HCV genotypes were 3a and 1a. Risk factors for HCV infection can be identified using a simple postal questionnaire to clinicians/GPs who request patient screening.

Adult↗

Rising incidence of Haemophilus influenzae type b disease in England and Wales indicates a need for a second catch-up vaccination campaign.

The incidence of invasive Haemophilus influenzae type b (Hib) disease in the UK fell rapidly following the introduction of routine vaccination in 1992 and the implementation of a catch-up campaign in children under 4 years old in 1992-93. However, since 1999 the number of cases of Hib has been increasing, and in 2002 there were 134 cases in 0-4 year olds (266 in all ages). While still much less than the prevaccine burden of disease (over 800 cases a year in 0-4 year olds), this increase in incidence is worrying and has sparked a range of detailed investigations. In February 2003, the Department of Health announced a second catch-up campaign offering all children between 6 months and 4 years a further dose of Hib vaccine. The epidemiology of Hib disease in England and Wales between 1990 and 2002 is reviewed here to provide a context for this public health response.

Adolescent↗

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.

Adult↗

Enhanced surveillance scheme for suspected meningococcal disease in five regional health authorities in England: 1998.

Enhanced surveillance of meningococcal disease (ESMD) began in five English regions on 1st January 1998. The aims of the scheme were to obtain accurate incidence data and develop a robust surveillance system with which to monitor the impact of a new meningococcal serogroup C conjugate vaccine. During 1998, 2,314 suspected cases of meningococcal disease were identified. The majority (84%) was classified as invasive meningococcal disease, with infection of N. meningitidis confirmed in 66%. Sixteen per cent of suspected cases were subsequently given an alternative diagnosis. Age differences between those classified as meningococcal disease and those not, implied a higher index of suspicion of meningococcal disease in younger children. Regions with high rates of meningococcal disease were due to a higher rate of serogroup C. ESMD increased ascertainment of meningococcal disease and deaths. Cases were 34% greater than identified through statutory notifications, an additional 6.8% confirmed infections were identified than were reported to the PHLS Meningococcal Reference Unit (MRU) and deaths were 24% greater than death registrations. These data were used to inform the national meningococcal serogroup C conjugate vaccination programme in England and Wales. In 1999 ESMD was extended to all regions of England, Wales and Northern Ireland.

Adolescent↗

Estimating the burden of serogroup C meningococcal disease in England and Wales.

In 1999 a new conjugate vaccine for serogroup C meningococcal disease was licensed for use in the UK. In order for an appropriate vaccination strategy to be developed the burden of serogroup C disease in England and Wales needed to be established. This was done using data from an enhanced surveillance scheme alongside routine laboratory reports and a total of 5,052 cases of serogroup C disease in England and Wales between 1993 and 1998 were estimated. Among these, an estimated 398 died and 1,767 were admitted to intensive care units (ITUs). The greatest burden of disease was in young children and teenagers. The current literature identified four studies reporting sequelae following serogroup C meningococcal disease. These provided estimates of sequelae in the range of 6.5% and 45% and presented some evidence of higher levels than occur following serogroup B meningococcal disease. This information was provided to the Joint Committee on Vaccination and Immunisation to inform policy to implement a serogroup C conjugate vaccination programme in the UK. The vaccination programme has since been justified by the dramatic reduction in serogroup C meningococcal cases.

Adolescent↗

Meningococcal serogroup C conjugate vaccination in England and Wales: coverage and initial impact of the campaign.

The UK was the first country to introduce meningococcal serogroup C conjugate vaccination. The vaccine was incorporated into the routine infant immunisation schedule and was offered to all under 18 year olds in a catch-up campaign. The vaccine has been well accepted in infants receiving routine vaccination, with coverage around 89%. Coverage in older children targeted in the catch-up campaign was above 85% up to the age of 14, and was lowest (43%) in 15-17 year olds not in education. The winter of 2000-01 was the first meningococcal season following the offer of the vaccination to all children and adolescents. The incidence of serogroup C disease in the targeted age groups fell by 80%, and the number of deaths in laboratory confirmed cases in 0-19 year olds decreased from 78 to 8 between 1998-99 and 2000-01. The incidence of serogroup B disease in all age groups was slightly higher in 2000-01 than previous years, and there was an increase in the incidence of serogroup C disease in those aged over 20 during the study period, leading to the extension of the vaccination campaign to 20-24 year olds.

Adolescent↗

Efficacy of meningococcal serogroup C conjugate vaccine in teenagers and toddlers in England.

The UK was the first country to use meningococcal serogroup C conjugate (MCC) vaccines, which were licensed on the basis of immunogenicity and safety data but without a formal efficacy study. Increased surveillance during the first 9 months since introduction has shown that short-term efficacy of the MCC vaccine in England was 97% (95% CI 77-99) for teenagers and 92% (65-98) for toddlers. These early results confirm the superiority of MCC over plain C polysaccharide vaccines, which are ineffective in young children.

Adolescent↗

A comparison of oral fluid collection devices for use in the surveillance of virus diseases in children.

Three oral fluid collection devices (OraSure, Omni-SAL and Oracol) were compared in terms of the quality of oral fluid collected by each device for antibody testing and their acceptability to participants. Participants (143 children aged 3.5-5 y from North Hertfordshire, UK, who had recently received DTaP and MMR vaccination) were randomised to use one of the three types of collection device. Oral fluid was collected by a parent who completed a short questionaire recording information on ease of use and willingness to use the device again. A matching serum sample was collected by a nurse. Oral fluid samples were screened for total IgG and IgM by ELISA and for rubella specific IgG and parvovirus specific IgG by radioimmunoassay. Serum samples were screened for rubella specific IgG and parvovirus B19 specific IgG by ELISA. 87.4% (125) of participants provided a matching oral fluid and serum sample. Of these, 100% (125) and 10.4% (13) had serum IgG specific for rubella and parvovirus B19, respectively. The Oracol device provided oral fluid samples with the highest geometric mean titres of total IgG and IgM and with rubella specific IgG results which correlated most closely with those of matching sera. A higher proportion of parents found the Oracol and OraSure devices easier to use than the Omni-SAL (P<0.001) and the proportion who would not take another test was higher for the Omni-SAL than for the Oracol or Orasure. Oral fluid samples collected by each of the devices gave qualitative results acceptable for surveillance and epidemiological studies of rubella and parvovirus B19. The highest quality oral fluid sample for antibody testing in terms of total IgG and IgM concentration and rubella specific IgG concentration was collected by the Oracol. The acceptability to participants of both the Oracol and OraSure was high. As the cheapest device available, the Oracol is the preferred oral fluid collection device for studies involving children in the UK.

Antibodies, Viral↗