PubMed Health⌕ Search

Biomedical subjects

M P Slack

Publications and source records attributed to M P Slack.

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↗
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↗
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

Epidemiological studies of large resistance plasmids in Haemophilus.

The distribution of large conjugative Haemophilus influenzae plasmids in the nasopharyngeal haemophili of a group of people and in a large collection of 541 H. influenzae type b (Hib) isolates was studied. A newly developed PCR-based assay was used to detect the plasmids. The target sequences were chosen from sequence analysis of part of p1056, a large multiresistance plasmid isolated from a clinical Hib isolate, 1056. Fifty-nine per cent of people were found to carry beta-lactamase-positive (beta-lac(+)), ampicillin-resistant (ampR) haemophili with detectable plasmid sequences. Of these, 83% were in Haemophilus parainfluenzae and 17% were in H. influenzae. In the collection of 541 Hib, antibiotic resistance [beta-lac(+)ampR, beta-lac(+)ampR plus tetracycline resistance (tetR) or tetR] was highly correlated with large plasmids. It was found that 2.3% of the isolates contained large cryptic plasmids (i.e. these isolates were susceptible to antibiotics). The distribution of plasmids between invasive and carried Hib did not differ significantly (25 of 245 and 23 of 276, respectively). Isolates with large plasmids occur at high frequency in the nasopharynx of the normal human population and consist of two populations in Hib, one associated with specific antibiotic resistance traits and the other cryptic. These plasmids do not appear to influence the invasiveness of Hib.

Adult↗
PubMed1998

Enhanced surveillance of invasive Haemophilus influenzae disease in England, 1990 to 1996: impact of conjugate vaccines.

We report an enhanced prospective survey of invasive Haemophilus influenzae infections that has defined the pattern of invasive disease in five English regions for 2 years before and 4 years after the introduction of the H. influenzae type b (Hib) vaccination program. During the prevaccination period the majority of cases of invasive H. influenzae were caused by type b; most (89%) of these infections occurred in children <5 years of age and the most common presentation was meningitis. Since the introduction of routine immunization of infants with conjugate Hib vaccine, there has been a 16-fold reduction in the annual attack rate of invasive Hib disease recorded in children <5 years of age. This reduction is of a magnitude similar to that observed in other countries with Hib vaccination programs. The number of infections caused by non-type b H. influenzae has shown a small but progressive increase over the same period, emphasizing the need for continued surveillance. There was no increase in the number of infections caused by other serotypes. Diagnostic category varied with both age and serotype but was not affected by vaccine introduction; meningitis was the most common presentation overall but pneumonia and bacteremia were more common in adults and with noncapsulated isolates.

Adolescent↗
PubMed1997

Vaccine failures after primary immunisation with Haemophilus influenzae type-b conjugate vaccine without booster.

BACKGROUND: Diseases of early childhood associated with Haemophilus influenzae type b (Hib) can now be prevented by vaccination. The rapid implementation of routine infant vaccination with Hib polysaccharide-tetanus protein conjugate (PRP-T) vaccine has allowed us to assess whether an accelerated 2, 3, and 4 month schedule can protect in the longer term without a booster dose and whether carrier priming influences protective efficacy. The degree of protection afforded by a catch-up programme with Hib oligosaccharide conjugate (HbOC) for older children was also assessed. METHODS: Paediatricians and microbiologists in the UK were asked to report all cases of invasive H influenzae infection in children who had received at least one dose of Hib-conjugate vaccine. Serum samples from convalescent children were obtained and the isolate was verified. Efficacy was estimated by comparing observed rates of Hib disease in those who had been vaccinated with rates predicted by age adjustment of disease rates from the prevaccine era. FINDINGS: Of 164 reports of invasive infection between Oct 1, 1992, and Oct 1, 1995, 43 were considered true vaccine failures. The estimated overall efficacy for three doses of PRP-T was 98.1% (95% CI 97.3-98.7%). Efficacy in infants aged 5-11 months was 99.1%, 12-23 months 97.3%, and 24-35 months 94.7%. In infants aged 3-11 months, who received their first dose of PRP-T after tetanus toxoid vaccination, disease was unlikely from 1 week after one dose of PRP-T vaccine (88.6% protection in the second to fourth weeks [66.8-97.7%]). The disease rate in vaccinated infants aged 2 months has declined year on year. In children aged 13 months to 2 years given HbOC, as a catch-up vaccine, the estimated efficacy was 94.0% (84.7-98.4%). INTERPRETATION: A high degree of efficacy has been observed with PRP-T vaccine given as a three-dose schedule in infancy and with HbOC as a single dose in older children. Efficacy of PRP-T appears to be enhanced by carrier priming. Although with increasing age there was a small decline in efficacy of PRP-T, Hib disease is now close to being eliminated in the UK, and we suggest that a booster is not necessary in the second year of life.

Age Factors↗
PubMed1995

Haemophilus influenzae: then and now.

Haemophilus influenzae has long been recognised as a major cause of serious infection and mortality in children less than 5 years old. Prior to the introduction of Haemophilus influenzae type b (Hib) immunisation, the incidence of a child suffering an invasive Haemophilus infection was 20-50/100,000 in industrialised countries and up to ten times higher in developing regions. The introduction of a Hib vaccine programme results in a rapid and dramatic decline in the incidence of Hib infection in the susceptible childhood population. For example, within two years of the introduction of routine Hib vaccination of infants in the UK, the risk of serious Hib infection had fallen from 1:600 to 1:30,000 by 5 years of age. Many other European countries have introduced, or are in the process of introducing, a routine Hib immunisation programme. Because the epidemiology of Haemophilus influenzae infection is changing so dramatically, it is opportune to review Haemophilus influenzae as it was perceived in the pre-vaccine era (the past) and during vaccine implementation (the present), and how its role may change in the post-vaccination era (the future). This review will summarise the historical landmarks that have led to our present-day understanding of Haemophilus influenzae pathogenicity, the concerns about antibiotic resistance, the features of the host immune response to Haemophilus influenzae, and the introduction of the Hib vaccine. Furthermore, the possible importance of this organism in the future will be discussed.

Haemophilus Infections↗
PubMed1995

Epidemiology of invasive Haemophilus influenzae infections in England and Wales in the pre-vaccination era (1990-2).

This survey defined the pattern of invasive Haemophilus influenzae infections during 1990-2 in six regions in England and Wales during the pre-vaccination era providing a baseline against which any changes in patterns of disease due to the introduction of the Haemophilus influenzae type b vaccination programme can be monitored. A total of 946 cases of invasive Haemophilus influenzae were recorded during the survey period of which almost 90% were due to type b and most of the remainder were non-typeable. Type b infections occurred predominantly in children less than 5 years of age (88%) with the highest attack rate in male infants in the 6-11 month age group. Diagnostic category varied with both age and serotype; meningitis was the commonest presentation overall but pneumonia and bacteraemia were more common in adults and non-typeable isolates. Mortality was highest in neonates and the elderly (over 65 years of age) who were more likely to have an underlying predisposing condition than older children and adults. Children under 5 years of age had a higher case fatality rate for non-typeable than for type b infections. Ampicillin resistance was 15% and there were no cefotaxime resistant type b isolates.

Adolescent↗
PubMed1994

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↗
PubMed1993

Population-based study of non-typable Haemophilus influenzae invasive disease in children and neonates.

The extent of non-capsulate, non-serotypable Haemophilus influenzae (NST) as a cause of serious invasive disease in children has not been fully defined. We describe the epidemiology of these childhood infections from cases identified during a continuing prospective survey of invasive H influenzae disease in the Oxford region, UK. 408 strains of H influenzae were isolated from cases of invasive disease. 383 (94%) were H influenzae type b (Hib), 24 (6%) were NST strains, and 1 was a type f strain. 3 of the NST strains were non-capsulate type b mutants (b-), but the remaining 21 strains were from the phylogenetically distinct and heterogeneous population of non-capsulate H influenzae (NC). 10 of the NC strains were isolated from neonates with sepsis; crude mortality rate was 40%, with an incidence of 4.6 cases per 100,000 livebirths. 11 NC strains were isolated from children after the neonatal period and under 10 years of age, 4 (36%) of which had severe, unrelated, predisposing conditions. The incidence of NC invasive diseases in these children was 0.5 per 100,000 per year. The attributable mortality for these infections was 10%. Infections due to these H influenzae strains are, after the implementation of Hib vaccines, likely to persist and represent a substantial proportion of the serious infections caused by this species.

Blotting, Southern↗