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Biomedical subjects

R T Mayon-White

Publications and source records attributed to R T Mayon-White.

At least 19 recordsLinked to original sources

Diagnosis of viral infections of the central nervous system: clinical interpretation of PCR results.

BACKGROUND: Standard laboratory techniques, such as viral culture and serology, provide only circumstantial or retrospective evidence of viral infections of the central nervous system (CNS). We assessed the diagnostic accuracy of PCR of cerebrospinal fluid (CSF) in the diagnosis of viral infections of the CNS. METHODS: We examined all the CSF samples that were received at our diagnostic virology laboratory between May, 1994, and May, 1996, by nested PCR for viruses associated with CNS infections in the UK. We collected clinical and laboratory data for 410 patients from Oxford city hospitals (the Oxford cohort) whose CSF was examined between May, 1994, and May, 1995. These patients were classified according to the likelihood of a viral infection of the CNS. We used stratified logistic regression analysis to identify the clinical factors independently associated with a positive PCR result. We calculated likelihood ratios to estimate the clinical usefulness of PCR amplification of CSF. FINDINGS: We tested 2233 consecutive CSF samples from 2162 patients. A positive PCR result was obtained in 143 patients, including 22 from the Oxford cohort. Logistic regression analysis of the Oxford cohort showed that fever, a virus-specific rash, and a CSF white-cell count of 5/microL or more were independent predictors of a positive PCR result. The likelihood ratio for a definite diagnosis of viral infection of the CNS in a patient with a positive PCR result, relative to a negative PCR result, was 88.2 (95% CI 20.6-378). The likelihood ratio for a possible diagnosis of viral infection of the CNS in a patient with a negative PCR result, relative to a positive PCR result, was 0.10 (0.03-0.39). INTERPRETATION: A patient with a positive PCR result was 88 times as likely to have a definite diagnosis of viral infection of the CNS as a patient with a negative PCR result. A negative PCR result can be used with moderate confidence to rule out a diagnosis of viral infection of the CNS. We believe that PCR will become the first-line diagnostic test for viral meningitis and encephalitis.

Adolescent

A study of 42 episodes of overwhelming post-splenectomy infection: is current guidance for asplenic individuals being followed?

Individuals without a spleen have an increased risk of overwhelming post-splenectomy infection (OPSI). Improved awareness in recent years has stimulated increased efforts to prevent OPSI. Published guidelines have described policies for immunization, chemoprophylaxis and other measures considered beneficial to asplenic patients, yet OPSI episodes continue to occur. In an attempt to investigate why serious infections are still being seen, we have conducted a nationally based survey of recent OPSI episodes, using mainly a network of medical microbiologists. Data including clinical background to both splenectomy and OPSI episode, immunization and chemoprophylaxis history have been collated. Forty-two cases of overwhelming infection were reported by June 1996. Patients of all ages were affected with OPSI occurring up to 59 years after splenectomy. A mortality rate of 45% was seen. Pneumococcal infection caused at least 37 of 42 episodes, but only 12 patients had received pneumococcal vaccine. Four cases were possible vaccine failures. Only 22% of individuals had taken any chemoprophylaxis since splenectomy, and only one carried a medical alert card. Much more needs to be done to ensure that asplenic patients are warned of the risks of infection, and given at least pneumococcal vaccine. The role of antibiotics for either continual prophylaxis or as a reserve supply for self-prescription at appropriate times also needs greater discussion. Further work on improving pneumococcal vaccine response together with suitable programmes for revaccination are required. Surveillance should continue until the incidence of OPSI reaches an irreducible minimum.

Adult

Meningococcal vaccines for the United Kingdom.

New meningococcal vaccines are needed in the United Kingdom with some urgency. Almost all Neisseria meningitidis disease in this country is caused by serogroups B and C. Infants have the highest attack rates, but also make the poorest immunological responses to potential vaccines. The development of vaccines that protect infants is a significant challenge. A capsule-based serogroup B vaccine is unlikely to be successful in infants because the capsule is poorly immunogenic and the polysaccharide molecule mimics a human epitope. Without completely discounting capsule as an immunogen, alternate antigens are being considered for immunisation: outer membrane proteins (OMP), iron regulating proteins, and lipopolysaccharide. Vaccines based on OMP have been used in several phase 3 trials in South Africa, Cuba, Brazil, Norway, and Chile, in which two doses of vaccine were given. The Cuban and Norwegian vaccines have been compared in phase 2 trials in Iceland and Chile. Potential limitations are epitope heterogeneity and the theoretical ability of N. meningitidis to adapt even to hosts who have received polyvalent vaccines. A phase 2 trial of a hexavalent class 1 OMP vaccine is under way in Gloucester, with 100 babies receiving injections at 2, 3, and 4 months. Serogroup C vaccines have been developed from capsular polysaccharide but, unconjugated, these vaccines do not protect those under 2 years of age. Conjugate vaccines with C and AC polysaccharides are immunogenic in infants, but antibody titres may wane quickly.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Vaccines

The impact of conjugate vaccine on carriage of Haemophilus influenzae type b.

Conjugate vaccines against Haemophilus influenzae type b (Hib) may modify Hib pharyngeal colonization. Hib colonization was compared in 371 infants and their families. In Oxfordshire, infants received PRP-T (polyribosylribitol phosphate conjugated to tetanus toxoid) and in Buckinghamshire they did not (controls). Infants were followed at 6, 9, and 12 months of age. Also, 6 unvaccinated Hib carriers were vaccinated and followed for 6 weeks. Hib acquisition was lower in vaccinees than controls (P < .01). During surveillance, 1.5% of vaccinees and 6.3% of controls carried Hib (P = .04). Among those with family Hib exposure, the carriage rates were 8.7% and 38.5% (P = .07), respectively. Hiv carriage rates were lower among vaccinees' unvaccinated siblings. Giving conjugate vaccine to a child carrying Hib did not rapidly terminate carriage. Thus, a primary means by which herd immunity to Hib is induced in a vaccinated population may be through reduction or delay in the initial acquisition of Hib.

Bacterial Capsules

Efficacy of Haemophilus influenzae type b conjugate vaccine PRP-T.

Efficacy of the Haemophilus influenzae type b (Hib) conjugate vaccine PRP-T (Pasteur-Merieux) was evaluated in a controlled community intervention study in the Oxford region, UK. PRP-T was offered to infants from May 1, 1991 in three of the region's eight districts and from July 1, 1991, in a fourth district. It was given by separate injection in addition to the standard diphtheria, tetanus, and pertussis vaccine according to an accelerated 2, 3, and 4 month schedule without a booster dose in the second year of life. By October 1, 1992, more than 90% of infants in vaccine districts had received at least one dose of PRP-T. None of the infants given three doses had developed Hib infection, whereas 11 infections occurred in the control population (vaccine efficacy 100%, 95% CI 80-100%). Intention-to-treat analysis also showed a high estimate of efficacy for the vaccine (90%, 50-99%). Follow-up of study children until November 1, 1993, has shown only 1 vaccine failure in an infant, and no invasive infections in those older than 1 year (average age 22 months). PRP-T vaccine had high protective efficacy with an accelerated immunisation schedule. Furthermore, the vaccine appears to remain protective through the second year of life without a booster dose. These findings provide encouragement for use of PRP-T in the Expanded Programme of Immunisation.

Child, Preschool

Tempting fate: control of communicable disease in England.

Recent changes in the NHS have left many defects in the systems for the control of communicable diseases and infection and their surveillance and the management of outbreaks. Clear, explicit legislation is needed, placing the responsibilities on health authorities. New teams led by consultants need to be set up to investigate and manage outbreaks of communicable diseases of all types.

Communicable Disease Control

An improved antiserum agar method for detecting carriage of Haemophilus influenzae type b.

Enriched Columbia medium was tested against Levinthal medium for the isolation of Haemophilus influenzae type b. In both media, Haemophilus influenzae type b recovery and antigen-antibody precipitation halos were equivalent. Haemophilus influenzae type b colony size and iridescence were superior on enriched Columbia medium. Enriched Columbia medium is inexpensive, simply prepared and easily standardised.

Agar

Hospital bed usage by people with HIV disease: experience in a provincial setting.

In order to describe hospital bed usage by people with HIV disease in a provincial setting, a retrospective analysis of admissions to hospital wards in Oxford was undertaken for people admitted to hospital with all HIV-related illnesses or complications of HIV-related treatment. A total of 83 people were identified as having been admitted to hospital between January 1986 and the end of August 1990. Average length of hospital stay, the number of admissions per observed person-year and the in-patient days per observed person-year decreased. Of the 2,446 days spent in hospital, 913 were by people with an AIDS diagnosis; 1,533 days were spent by people who did not fulfil the World Health Organisation/Centers for Disease Control (WHO/CDC) classification for AIDS but who were admitted because of their HIV disease. AIDS is an end-point of infection with HIV. Pre-AIDS morbidity, a spectrum of illness of increasing severity from minor illness up to the point of WHO/CDC level AIDS, is a major determinant of hospital care and has previously been underestimated. In order to calculate the best estimates of hospital care needed, HIV disease should be regarded as a single entity and the artificial barrier dividing HIV illnesses from AIDS should be discarded.

Adolescent

Invasive Haemophilus influenzae type b disease in the Oxford region (1985-91).

For a seven year period (1985-91) clinical and epidemiological data were prospectively collected on children aged < 10 years with microbiologically confirmed invasive Haemophilus influenzae type b infection in the Oxford region to study the epidemiology of the disease and determine the potential impact of early primary immunisation in infants. Computer records of primary immunisations given to these cases were retrospectively analysed and, where necessary, hospital and general practitioner records were searched to determine the immunisation history. Over the seven year period, 416 cases of invasive H influenzae type b disease were reported. Widescale immunisation against H influenzae type b began in 1991 as part of a regional trial. The estimated annual incidence for invasive disease between 1985 and 1990 was 35.5 cases per 100,000 children aged less than 5 years; for H influenzae type b meningitis it was 25.1 per 100,000 children aged less than 5 years. The cumulative risks for invasive disease and meningitis by the fifth birthday were one in 560 and one in 800 respectively. The majority of disease (71%) occurred in children less than 2 years of age with the peak monthly incidences at 6 and 7 months of age. The overall mortality was 4.3% and 50% of these deaths occurred suddenly. Most (91%) of the children had received at least one primary immunisation against diphtheria, tetanus, and pertussis before H influenzae type b infection and there was only one case of parental refusal of immunisation. None had received H influenzae type b immunisation. Given a vaccine uptake of 90% by 5 months of age it is estimated that at least 82% of the H influenzae type b infections could have been prevented. Extrapolated nationally, 1150 cases of infection and 50 deaths could be prevented each year by routine primary immunisation.

Age Factors