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Biomedical subjects

J M Stuart

Publications and source records attributed to J M Stuart.

At least 19 recordsLinked to original sources
PubMed2006

Effectiveness of different policies in preventing meningococcal disease clusters following a single case in day-care and pre-school settings in Europe.

National policies for chemoprophylaxis after single cases of meningococcal disease in day-care or nursery settings vary across Europe. We carried out a multi-national retrospective study to compare the effectiveness of different policies. Countries were divided into those recommending chemoprophylaxis only to close contacts (policy A, close) and those recommending chemoprophylaxis for all children in the same nursery (policy B, mass). Country-specific relative risk (RR) of a cluster was defined as the ratio of the number of clusters observed to the number of clusters expected by chance. In total, 37 clusters were identified between 1 January 1993 and 31 December 2002. After adjusting for marked heterogeneity in RR by country, the ratio of RR between countries suggested possible benefit from mass prophylaxis (RR ratio 3.8, 95% CI 0.7-22.0), although the difference was not statistically significant (P=0.22). The costs of this approach and the low risk of clustering need to be taken into account when deciding national policy.

Child↗
PubMed2006

Changing epidemiology of bacterial meningitis among adults in England and Wales 1991-2002.

We examined the epidemiology of community-acquired bacterial meningitis among adults in England and Wales between 1991 and 2002. Among 3169 cases, meningococcal infection was predominant among young adults and pneumococcal meningitis among older adults. Whilst infection due to most causes decreased, the incidence of tuberculous (TB) meningitis doubled over the 12 years. The mortality rate among meningococcal and pneumococcal infections fell from 0.45/10(5) to 0.31/10(5) (P=0.0001). This study demonstrates important changes in the epidemiology of bacterial meningitis among UK adults. Improvements in clinical management, childhood vaccination programmes and the re-emergence of tuberculosis are likely to be drivers of these changes.

Adolescent↗
PubMed2006

Quality of in-hospital care for adults with acute bacterial meningitis: a national retrospective survey.

BACKGROUND: Most adults with bacterial meningitis and meningococcal septicaemia present to junior doctors who have limited experience of these conditions. In contrast to paediatric practice, data from industrialized countries with regard to current hospital management practice are lacking. AIM: To examine whether current practice meets recommended standards in hospital management of community-acquired bacterial meningitis and meningococcal septicaemia among adults. DESIGN: National audit of medical records. METHODS: We conducted a survey of all patients with acute bacterial meningitis and meningococcal septicaemia admitted to 18 randomly selected acute hospitals in England and Wales between 1 January 2000 and 31 December 2001. All stages of care, including pre-hospital management, initial hospital assessment, record keeping, and ongoing hospital and public health management, were assessed. RESULTS: We identified 212 cases of bacterial meningitis and meningococcal septicaemia; 190 cases remained in the final analysis. Clinical record keeping did not meet acceptable standards in 33% of cases. Parenteral antibiotics were given within 1 h of hospital arrival in 56% of cases, increasing to 79% among those with an initial differential diagnosis that included bacterial meningitis or meningococcal septicaemia. A full severity of illness assessment was made in 27%. The quality of clinical practice varied widely between hospitals. This was most pronounced in the timeliness of consultant review (p < 0.0005). DISCUSSION: The quality of adult clinical practice for bacterial meningitis and meningococcal septicaemia needs improvement. This study provides a tool for developing targeted interventions to improve quality of care and outcome among adults with life-threatening infections, both in the UK and in other countries.

Adolescent↗
PubMed2006

Cryptosporidium outbreak linked to interactive water feature, UK: importance of guidelines.

A need for national guidelines relating to interactive water features was highlighted following three outbreaks of cryptosporidiosis in the United Kingdom, all of which were related to public water features. In August 2003 the Health Protection Agency South West of England was notified of an outbreak of cryptosporidiosis associated with an interactive water feature designed for water play within an adventure park. The water feature was implicated following samples with a high coliform count and the presence of faecal coliforms. A case was defined as any child (younger than 16 years of age) who had visited the park during August and who subsequently had gastrointestinal symptoms and a faecal sample positive for cryptosporidium. Seventy one children were identified in the cohort. This outbreak of cryptosporidiosis was characterised by a very high attack rate (89%), relatively severe in duration (median 8 days) and had a relatively high hospital admission (16% of cases). The epidemic curve was consistent with a point source of infection, which corresponded to the date 80% of the cohort visited the park. This outbreak has similarities to two other cryptosporidiosis outbreaks reported in England in 2003 that involved public water features. These outbreaks raise issues about the operation and maintenance of water-based recreational attractions that very often involve children. The paper reflects on the basic control measures that can be taken and highlights the need for guidelines, especially since such attractions are becoming increasingly common. The Pool Water Treatment Advisory Group in United Kingdom has now produced guidelines.

Child↗
PubMed2006

Case-control study for risk factors for Q fever in southwest England and Northern Ireland.

Q fever (Coxiella burnetti) is thought to account for 1% (700 cases) of community acquired pneumonia in the United Kingdom each year, and can result in serious complications such as endocarditis. Although outbreaks have frequently been reported worldwide, the causes are often not clearly identified and there have been few studies of risk factors in sporadic cases. We conducted a matched case-control study. Cases of acute Q fever in people aged over 15 years in southwest England and Northern Ireland were identified from January 2002 to December 2004. Controls were matched for age, sex and the general practice at which they were registered. Questionnaires asking about contact with animals, and leisure and work activities, were posted to cases and controls. Questionnaires were completed by 39/50 (78%) of the cases and 90/180 (50%) of the controls. In the single variable analysis, occupational exposure to animals or animal products was the only risk factor associated with cases at the 5% level (P=0.05, odds ratio (OR) 3.4). Long term illness appeared to be significantly protective (P=0.03, OR 0.3). In multivariable analysis the strength of association between occupational exposure and illness remained high (OR 3.6, 95% confidence interval (CI) 0.9 to 14.8) and smoking emerged as a possible risk factor. This is the first case-control study to identify occupational exposure to animals or animal products as the most likely route of infection in sporadic cases as opposed to outbreaks.

Adult↗
PubMed2005

HTLV-1 induced molecular mimicry in neurological disease.

As a model for molecular mimicry, we study patients infected with human T-lymphotropic virus type 1 (HTLV-1) who develop a neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a disease with important biological similarities to multiple sclerosis (MS) (Khan et al. 2001; Levin et al. 1998, 2002a; Levin and Jacobson 1997). The study of HAM/TSP, a disease associated with a known environmental agent (HTLV-1), allows for the direct comparison of the infecting agent with host antigens. Neurological disease in HAM/TSP patients is associated with immune responses to HTLV-1-tax (a regulatory and immunodominant protein) and human histocompatibility leukocyte antigen (HLA) DRB1*0101 (Bangham 2000; Jacobson et al. 1990; Jeffery et al. 1999; Lal 1996). Recently, we showed that HAM/TSP patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), a neuron-specific autoantigen (Levin et al. 2002a). Monoclonal antibodies to tax cross-reacted with hnRNP A1, indicating molecular mimicry between the two proteins. Infusion of cross-reactive antibodies with an ex vivo system completely inhibited neuronal firing indicative of their pathogenic nature (Kalume et al. 2004; Levin et al. 2002a). These data demonstrate a clear link between chronic viral infection and autoimmune disease of the central nervous system (CNS) in humans and, we believe, in turn will give insight into the pathogenesis of MS.

Antibodies, Monoclonal↗
PubMed2005

Invasive group A streptococcal disease: should close contacts routinely receive antibiotic prophylaxis?

Group A streptococci (Streptococcus pyogenes) causes a wide range of illnesses from non-invasive disease--eg, pharyngitis--to more severe invasive infections--eg, necrotising fasciitis and toxic shock-like syndrome. There remains uncertainty about the risk of secondary cases of invasive disease occurring among close contacts of an index case and how best to manage that risk. We do not consider that currently available evidence justifies the routine administration of chemoprophylaxis to close contacts. We suggest that the appropriate response should be to routinely inform all household contacts of a patient with invasive group A streptococcal disease about the clinical manifestations of invasive disease and to seek immediate medical attention if they develop such symptoms.

Anti-Bacterial Agents↗
PubMed2004

Efficacy of modified recombinant type II collagen in modulating autoimmune arthritis.

OBJECTIVE: Previous studies have shown that an analog peptide of the immunodominant T cell determinant of type II collagen (CII), i.e., CII(256-276)(N(263), D(266)), was able to suppress the immune response to CII and the development of arthritis in DR1-transgenic mice. The present study tested the hypothesis that introduction of the same amino acid substitutions into full-length CII might improve the efficacy of the mutant collagen in achieving suppression of autoimmune arthritis. METHODS: Using recombinant technology, full-length CII was modified, while the native conformation was retained. Two point mutations were introduced within the immunodominant T cell determinant to convert the F(263) to N and E(266) to D, using a baculovirus expression system that has previously been utilized in the production of recombinant CII (rCII). RESULTS: The mutant rCII(N(263), D(266)) was capable of reducing the incidence and severity of arthritis as well as the antibody response to CII when administered to DR1-transgenic mice that display susceptibility to collagen-induced arthritis. More importantly, it was significantly more effective than the synthetic analog peptide, CII(256-276)(N(263), D(266)). Its mechanism of suppression may be explained by the secretion of predominantly Th2 cytokines by the T cells immunized with rCII(N(263), D(266)). Administration of rCII(N(263), D(266)) was ineffective in suppressing arthritis in IL4(-/-) mice, suggesting that the profound suppressive effects of rCII(N(263), D(266)) were mediated through the production of interleukin-4. CONCLUSION: These findings describe a promising specific immunotherapy for patients with DR1-mediated autoimmunity to CII.

Adjuvants, Immunologic↗
PubMed2004

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↗
PubMed2003

Investigation of an outbreak of E. coli O157 infections associated with a trip to France of schoolchildren from Somerset, England.

A retrospective cohort study was conducted after 2 confirmed and 8 probable cases of VTEC 0157 occurred in a schoolgroup from Somerset following a trip to France. The strain of the 2 confirmed cases was vero-cytotoxin type 2, phage type 34. Despite its low statistical power due to small numbers, this study suggested the most likely vehicle of infection was cucumber salad (crude RR=4.3, 95%CI [0.6-29], adjusted OR=107, 95%CI indeterminate, p=0.08). The cucumbers were purchased from Belgium but it was not possible to trace them back to source. The international nature of this outbreak emphasises the importance of close collaboration between organisations in the management of outbreaks, of ensuring international standards in food safety, and of agreeing a common standard in VTEC typing across Europe.

Adolescent↗
PubMed2002

The role of IL-4 in regulation of murine collagen-induced arthritis.

Collagen-induced arthritis (CIA) is a murine model of autoimmune-mediated polyarthritis. CIA can be prevented by the administration (intravenously) of CII, inducing regulatory CD4+ T cells which produce Th2 cytokines. However, the relative importance of IL-4 in suppressing arthritis remains unclear. To address this question, a neutralizing monoclonal antibody to IL-4 was given to mice treated with tolerized, CII-specific cells. The antibody significantly reversed the expected suppression of arthritis. Moreover, CII administered intravenously to DBA/1 IL4-/- mice (developed by backcrossing C57B1/6 IL4-/- to wild-type DBA/1 mice) was completely ineffective in suppressing disease. These data support the importance of IL-4 in the regulation of autoimmune arthritis. Compensatory increases in mRNA message for other Th2 cytokines were observed, but they did not restore suppression of arthritis. Antibodies to CII, mostly IgG2a, were increased in IL4-/- mice. These studies represent a unique opportunity to analyze the role of IL-4 and its absence on an autoimmune murine model of arthritis.

Animals↗
PubMed2002

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↗
PubMed2002

Socioeconomic inequality and meningococcal disease.

Incidence of meningococcal disease was associated with socioeconomic deprivation across a rural English region. In young children the incidence was twice as high in the most deprived compared with the least deprived electoral wards. By addressing social inequalities the incidence of this serious infection could be reduced.

Child↗
PubMed2001

A gene expression map for Caenorhabditis elegans.

We have assembled data from Caenorhabditis elegans DNA microarray experiments involving many growth conditions, developmental stages, and varieties of mutants. Co-regulated genes were grouped together and visualized in a three-dimensional expression map that displays correlations of gene expression profiles as distances in two dimensions and gene density in the third dimension. The gene expression map can be used as a gene discovery tool to identify genes that are co-regulated with known sets of genes (such as heat shock, growth control genes, germ line genes, and so forth) or to uncover previously unknown genetic functions (such as genomic instability in males and sperm caused by specific transposons).

Algorithms↗
PubMed2001

Risk factors for meningococcal disease in university halls of residence.

A retrospective ecological study was undertaken to identify social and environmental factors associated with increased incidence of meningococcal disease in university halls of residence. A standardized questionnaire was sent to UK universities and colleges of higher education outside London, for distribution to halls containing at least 50 students. Incidence rate ratios of invasive meningococcal disease were obtained for a range of social and environmental variables. Multi-variable Poisson regression analysis identified 3 factors as having a strong association: a high proportion of first year undergraduate residents (P = 0.0008), decreasing smokiness of the hall bar (P < 0.0001), and opening of hall bar before 1990 (P = 0.0001). The inverse relationship between disease incidence and smokiness of bars was an unexpected finding, and may be due to confounding factors. Universities should continue to promote awareness of meningococcal disease, encourage vaccination of first year students against serogroup C disease, and where appropriate, take measures to reduce overcrowding.

Adult↗
PubMed2001

Risk of laboratory-acquired meningococcal disease.

Five probable secondary cases of meningococcal disease were identified in microbiology laboratory workers in England and Wales during a 15-year period. All cases had prepared suspensions of Neisseria meningitidis outside a safety cabinet upto seven days before onset of illness. Relative risk in laboratory workers compared with the background adult population was 184 (95% CI 60-431). In view of the potentially serious outcome from this infection, a safety cabinet should always be used when preparing or working with suspensions of meningococci. Vaccination policy for microbiology laboratory workers should be reviewed.

Adult↗