PubMed Health⌕ Search

Biomedical subjects

P T Heath

Publications and source records attributed to P T Heath.

At least 19 recordsLinked to original sources
PubMed2006

Changes in ascertainment of Hib and its influence on the estimation of disease incidence in the United Kingdom.

Enhanced surveillance for Hib infection, initially covering Wales and five English regions, began in 1990 and in 1995 was extended to the whole of England and Wales. To determine whether changes in the ascertainment of Haemophilus influenzae may have affected estimates of Hib disease incidence, data from January 1990 to December 2003 were analysed. A total of 8887 and 4020 (45%) cases of H. influenzae and Hib respectively were reported. The proportion of isolates that were serotyped increased over time, and therefore reported incidence may have underestimated the true incidence in the early years of the study. Adjusting for this under-ascertainment, the incidence in children aged <5 years declined from a peak of 28.3/100,000 in 1991 to 0.97/100,000 in 1998 and increased to 3.8/100,000 in 2003. Following the implementation of universal vaccination a dramatic decline in the true incidence of invasive Hib disease occurred. The observation of the subsequent resurgence was real but the highest incidence reached was 85% below the corrected incidence in the pre-vaccine era. Continued high-quality surveillance is needed in order to accurately monitor and detect changes in disease incidence.

Bacterial Capsules↗
PubMed2006

Conjugate vaccines for preventing meningococcal C meningitis and septicaemia.

BACKGROUND: Meningococcal polysaccharide (MPLS) vaccines protect against Serogroup C disease, but do not produce an immune response in infants less than two years of age. This limitation can be overcome by linking C polysaccharide to carrier proteins ('conjugating'), to create meningococcal serogroup C conjugate (MCC) vaccines. In the absence of trial data, the immune response to vaccination has been considered to be a reasonable surrogate for vaccine protection. OBJECTIVES: To assess the immunogenicity, safety and efficacy of MCC vaccines for preventing meningitis and septicaemia. SEARCH STRATEGY: We searched the Cochrane Central Register Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2005); MEDLINE (1966 to September, Week 1 2005); and EMBASE (1990 to June 2005) and references of studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in humans comparing MCC vaccines against a control vaccine or none. In the absence of any trials on vaccine efficacy, population-based observational studies about effectiveness were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened the results of the literature searches, selected eligible studies, extracted the data and evaluated the quality of them. MAIN RESULTS: The studies showed that MCC vaccine was highly immunogenic in infants after two and three doses, in toddlers after one and two doses and in older age groups after one dose. In general higher titres were generated after MCC than after MPLS vaccines. Immunological hypo-responsiveness seen after repeated doses of MPLS vaccine may be overcome with MCC. Observational studies have documented a significant decline in meningococcal C disease in countries where MCC vaccines have been widely used. The timing of the vaccinations schedules, the specific conjugate used, and the vaccines given concomitantly or combined, may be important. AUTHORS' CONCLUSIONS: The MCC vaccine appears to be safe, immunogenic and able to induce immunological memory in all age groups. Observational studies strongly suggest that MCC is clinically effective.

Humans↗
PubMed2006

Immunisation of premature infants.

Premature infants are at increased risk of vaccine preventable infections, but audits have shown that their vaccinations are often delayed. Early protection is desirable. While the evidence base for immunisation of preterm infants is limited, the available data support early immunisation without correction for gestational age. For a number of antigens the antibody response to initial doses may be lower than that of term infants, but protective concentrations are often achieved and memory successfully induced. A 2-3-4 month schedule may be preferable for immunisation of preterm infants in order to achieve protection as early as possible, but an additional dose may be required to achieve persistence of protection. This update focuses on the use of routine childhood vaccines in premature infants.

Child↗
PubMed2005

Neonatal sepsis: an international perspective.

Neonatal infections currently cause about 1.6 million deaths annually in developing countries. Sepsis and meningitis are responsible for most of these deaths. Resistance to commonly used antibiotics is emerging and constitutes an important problem world wide. To reduce global neonatal mortality, strategies of proven efficacy, such as hand washing, barrier nursing, restriction of antibiotic use, and rationalisation of admission to neonatal units, need to be implemented. Different approaches require further research.

Cross Infection↗
PubMed2003

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↗
PubMed2003

Neonatal meningitis.

Twelve years ago an annotation was published in Archives of Disease in Childhood regarding the antibiotic treatment of suspected neonatal meningitis. The authors recommended the use of cephalosporins rather than chloramphenicol and advocated intraventricular aminoglycoside treatment in selected cases. They noted the absence of clinical trials with third generation cephalosporins that showed an improvement in mortality or neurological outcome.

Anti-Bacterial Agents↗
PubMed2002

Treatment of infections due to resistant organisms.

Antibiotic resistance remains rare in paediatric community-acquired pneumonia in the UK, but is more common in hospital-acquired pneumonia and in patients with chronic lung diseases. It should also be considered in children arriving from countries with a high prevalence of antibiotic resistance, children with previous heavy antibiotic exposure, those who are immunosuppressed, and those who are not responding to conventional therapy. The most frequent bacterial cause of paediatric pneumonia is Streptococcus pneumoniae and globally there are major concerns about the increasing resistance of this organism to penicillin. Intermediate resistance may be overcome with conventional doses of parenteral penicillin and there is as yet no convincing evidence that intermediate/high level resistance is associated with a worse clinical outcome. Continued vigilance and research is required. The recently introduced pneumococcal conjugate vaccines offer great promise as they are likely to prevent cases of disease due to penicillin-resistant serotypes.

Bacterial Vaccines↗
PubMed2002

The UK Hib vaccine experience.

Haemophilus influenzae type b (Hib) is an important pathogen in children <5 years of age. The Hib conjugate vaccines were the first polysaccharide-protein conjugate vaccines to be used in routine childhood schedules. Their introduction in the UK in 1992 has resulted in the near elimination of Hib disease. The UK Hib vaccine programme has a number of unique features including an accelerated schedule, absence of a booster dose, and the inclusion of a catch up component at the beginning of the programme. Collaboration between UK paediatricians, microbiologists, and public health physicians has allowed active national surveillance of Haemophilus influenzae disease and enabled important conclusions to be drawn. These include high vaccine effectiveness, the presence of herd immunity, and the frequency of risk factors in cases of vaccine failure and in cases of invasive disease due to non-b H influenzae. Parallel studies have shown the immunogenicity, induction of immunological memory, and persistence of immunity following vaccination at the UK schedule, as well as measuring the impact of vaccination on pharyngeal Hib carriage. Cases continue to occur and complacency is ill advised, particularly as other vaccines and combinations are introduced. Surveillance of H influenzae disease in the UK remains important.

Carrier State↗
PubMed2001

Non-type b Haemophilus influenzae disease: clinical and epidemiologic characteristics in the Haemophilus influenzae type b vaccine era.

BACKGROUND: As a result of the decline in Haemophilus influenzae type b (Hib) disease caused by the widespread use of conjugate vaccines, non-type b H. influenzae will become a more important cause of H. influenzae (Hi) disease. Characterization of the clinical and epidemiologic features of non-b Hi disease is needed in the Hib vaccine era. METHODS: A prospective active surveillance study of invasive Hi disease involving pediatricians in the United Kingdom and Republic of Ireland. For the first phase of the study (October 1, 1992, to October 31, 1995) pediatricians were asked to report any child who had invasive Hi disease and who had received Hib conjugate vaccine. For the second phase of the study (November 1, 1995. To December 31, 1998) pediatricians were asked to report any child with invasive Hi disease regardless of vaccination status. RESULTS: During the study period 102 cases of invasive non-type b Hi disease and 106 cases of invasive Hib disease were reported in children who had been fully vaccinated against Hib. Children with non-type b disease were younger (16 vs. 22 months of age, P = 0.08), less likely to have meningitis and epiglottitis (P < or = 0.001) and more likely to have pneumonia and bacteremia (P < or = 0.001) than children with type b disease. For the last 2 years of the study invasive Hi disease occurring in a fully vaccinated child was more likely to be caused by a non-b strain than by a type b strain (58 vs. 38). In 1998 the incidence of non type-b Hi disease in all children <5 years of age in the UK was 1.3/100,000 as compared with an incidence of Hib disease of 0.6/100,000. The majority (88%) of non-b strains isolated in children were nontypable strains. CONCLUSIONS: Non-b Hi is a rare cause of disease in children, but in the Hib vaccine era it has become more common than type b as a cause of Hi disease in fully vaccinated children.

Age Factors↗
PubMed2001

Pneumococcal disease in childhood.

Streptococcus pneumoniae is the most common cause of serious bacterial infections in children worldwide. Problems with antibiotic resistance have lead to changes in antibiotic policies for children with possible pneumococcal disease. Demonstration of the efficacy of a pneumococcal conjugate vaccine has lead to consideration of its inclusion in routine infant vaccination schedules.

Aged↗
PubMed2000

Antibody concentration and clinical protection after Hib conjugate vaccination in the United Kingdom.

CONTEXT: The schedule for Haemophilus influenzae type b (Hib) vaccination of infants in the United Kingdom consists of 3 doses given at 2, 3, and 4 months of age. Many countries include a fourth dose (booster) of Hib vaccine in the second year of life on the basis of declining Hib antibody concentrations after the primary series. Few data are available to show that this fourth dose is actually necessary. OBJECTIVE: To evaluate long-term clinical protection against Hib disease and Hib antibody concentrations following primary Hib vaccination without a booster dose. DESIGN, SETTING, AND SUBJECTS: Clinical protection study conducted between October 1992 and March 1999 in the United Kingdom, in which children developing invasive Hib disease despite vaccination in infancy with 3 doses of Hib conjugate vaccine were reported by pediatricians through an active, prospective, national survey. Separate antibody studies were conducted among 2 cohorts of children (n = 153 and n = 107) vaccinated at 2, 3, and 4 months of age with Hib conjugate vaccine and followed up to 43 and 72 months of age. MAIN OUTCOME MEASURES: Age-specific vaccine effectiveness, derived from the observed number of true vaccine failures after 3 Hib vaccine doses compared with the number of cases expected based on the age-specific rates of invasive Hib disease obtained prior to the introduction of Hib vaccines; and proportion of children in the 2 cohorts with Hib antibody concentrations of less than 0.15 and less than 1.0 microg/mL. RESULTS: Ninety-six true vaccine failures occurring after 3 vaccine doses were detected. During the study period, an estimated 4,368,200 infants in the United Kingdom received 3 doses of vaccine; therefore, the vaccine failure rate was 2.2 per 100,000 vaccinees (95% confidence interval, 1.8-2.7 per 100,000). Although vaccine effectiveness declined significantly after the first year of life (P<.001), it remained high until the sixth year of life (99.4% in children aged 5-11 months vs 97.3% in those aged 12-71 months). The proportion of cohorts 1 and 2 with anti-PRP antibody levels of less than 0.15 microg/mL increased between 12 and 72 months of age (6% at 12 months, 8% at 43 months, and 32% at 72 months; chi(2)(1) = 18.25; P<.001 for trend). CONCLUSIONS: Our results suggest that anti-PRP antibody levels and clinical protection against Hib disease wane over time after Hib vaccination at 2, 3, and 4 months of age without a booster dose at 2 years of age. The decline in clinical protection is minimal, however, suggesting that a booster dose of Hib vaccine following infant vaccination is not essential. JAMA. 2000;284:2334-2340.

Antibodies, Bacterial↗
PubMed2000

Clinical and immunological risk factors associated with Haemophilus influenzae type b conjugate vaccine failure in childhood.

Haemophilus influenzae type b (Hib) conjugate vaccines have proved extremely efficacious in healthy children. True Hib vaccine failures are rare. Hib conjugate vaccines were introduced for routine immunization in the United Kingdom and the Republic of Ireland in 1992. Coincident with this, active prospective and national surveillance via pediatricians, microbiologists, and public health physicians was commenced to assess the clinical and immunological factors associated with vaccine failure. During the 6 years of the study, 115 children with true vaccine failure were reported. Of the children who were vaccinated before 12 months of age, a clinical risk factor was detected in 20%, an immunological deficiency was detected in 30%, and one or both were detected in 44%. Children who were vaccinated after 12 months of age were more likely to have one or both factors (67%). Thirty percent (33 of 105) of children with true vaccine failure had a low Hib antibody response (concentration, <1.0 microg/mL) after disease, but the majority then responded to a further dose of Hib vaccine. Children who develop Hib disease despite vaccination deserve further clinical and immunological evaluation.

Adolescent↗
PubMed2000

Safety, immunogenicity, and induction of immunologic memory by a serogroup C meningococcal conjugate vaccine in infants: A randomized controlled trial.

CONTEXT: Neisseria meningitidis is a common cause of meningitis and septicemia in infants worldwide. Whether a meningococcal C conjugate vaccine protects infants against the serogroup C strain is unknown. OBJECTIVES: To determine whether a meningococcal C conjugate vaccine is safe and immunogenic and induces immunologic memory in infants. DESIGN: Single-center, double-blind, randomized controlled trial in 1995 and 1996. SETTING: Community, Oxfordshire, England. PARTICIPANTS: One hundred eighty-two healthy infants. INTERVENTIONS: Participants were randomly assigned to receive vaccination with 0. 5-mL doses of 1 of 2 lots of meningococcal C conjugate vaccine (groups 1 and 2; n=60 in each group) or a hepatitis B control vaccine (group 3; n=62), administered with routine immunizations at 2, 3, and 4 months of age. Approximately half of each group received meningococcal C conjugate vaccine and half received plain meningococcal polysaccharide vaccine (MPS) at 12 months of age. MAIN OUTCOME MEASURES: Serum antibodies to meningococcal C polysaccharide, assayed by enzyme-linked immunosorbent assay, and serum bactericidal activity (SBA), at 2, 3, 4, 5, 12, and 13 months of age; local and systemic reactions, recorded for 6 days after each vaccination, compared by intervention group. RESULTS: Meningococcal C conjugate vaccine was well tolerated. After 3 doses, children in groups 1 and 2 achieved significantly higher meningococcal C IgG geometric mean concentrations (21 and 17 U/mL, respectively, vs 0.20 U/mL; P<.001) and SBA titers (629 and 420, respectively, vs 4.1; P<. 001) than controls. At 12 months, antibody concentrations had decreased in all groups but remained significantly higher in children vaccinated with meningococcal C conjugate vaccine (SBA, 24 and 16 in groups 1 and 2, respectively, vs 4.2 in group 3; P<.001). Following vaccination with MPS at 12 months of age, SBA in the meningococcal C conjugate vaccine group was significantly higher than in controls (SBA, 789 vs 4.5; P<.001). CONCLUSIONS: Our data indicate that meningococcal C conjugate vaccine is safe and immunogenic and results in immunologic memory when given with other routinely administered vaccines to infants at 2, 3, and 4 months of age. JAMA. 2000;283:2795-2801

Analysis of Variance↗
PubMed2000

Epidemiology and bacteriology of bacterial pneumonias.

An understanding of the epidemiology and bacteriology of pneumonia in childhood is frustrated by the difficulties in making an aetiological diagnosis in young children. Incidence figures for community-acquired pneumonia are derived from the 1970s and 1980s and suggest that the incidence is higher in young children than in older children: approximately 40/1000/year <5 years of age and 15/1000/year aged 5-14 years. Certain pathogens are associated with pneumonia in different age groups, Mycoplasma pneumoniae and Chlamydia pneumoniae are more commonly implicated in older age groups and viruses in younger age groups. The most common bacterium, Streptococcus pneumoniae is less influenced by age. The mortality from community-acquired pneumonia in developed countries appears to be very low. The range of potential bacterial pathogens associated with nosocomial pneumonia and with pneumonia in the immunosuppressed child is wider with Gram-negative aerobic bacilli the most frequent isolate.

Adolescent↗
PubMed1999

The Hib immunization programme in the Oxford region: an analysis of the impact of vaccine administration on the incidence of disease.

In May 1991 an immunization programme against Haemophilus influenzae type b (Hib) infection began within the Oxford region. We validate a deterministic mathematical model of Hib by comparison with the incidence of disease in the Oxford region, 1985-97. The comparison of model results with observed outcome allows an exploration of some of the poorly understood properties of the immunization programme. Model results and observed incidence are consistent with a vaccine that blocks the acquisition of carriage. Similarly, the data suggest that factors other than experience of Hib carriage are likely to have generated acquired immunity to Hib disease prior to the introduction of vaccination. Hence it is unlikely that waning of vaccine-derived protection will result in a resurgence of disease. The inclusion in the immunization schedule of a booster dose, as used in other countries, would have provided very little extra benefit.

Carrier State↗
PubMed1998

Mathematical models of Haemophilus influenzae type b.

A review of empirical studies and the development of a simple theoretical framework are used to explore the relationship between Haemophilus influenzae type b (Hib) carriage and disease within populations. The models emphasize the distinction between asymptomatic and symptomatic infection. Maximum likelihood methods are used to estimate parameter values of the models and to evaluate whether models of infection and disease are satisfactory. The low incidence of carriage suggests that persistence of infection is only compatible with the absence of acquired immunity to asymptomatic infection. The slight decline in carriage rates amongst adults is compatible with acquired immunity, but could be a consequence of reduced contacts. The low rate of disease observed in adulthood cannot be explained if protection from disease is a product of previous detectable exposure to Hib alone. We estimate an R0 of 3.3 for Hib in developed countries, which suggests that current immunization programmes may eliminate the infection. Analysis of the disease data set suggests the absence of maternal immunity and increased susceptibility to disease in the oldest age classes.

Adolescent↗