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.

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.

Overview: epidemiology, surveillance, and population biology.

A combination of data obtained by classical epidemiological techniques with insights gained from the analysis of the population biology of Neisseria meningitidis have proved to be critical in understanding the spread of menin-gococcal disease. This is a consequence of the natural history and evolution of this bacterium, which, despite its fearsome reputation as an aggressive pathogen (1), is ordinarily a harmless commensal inhabitant of the nasopharynx of adult humans (2). Further, it has been established that "natural," (that is to say, carried) populations of meningococci are highly diverse, with a minority of genotypes (the "hyperinvasive lineages") being responsible for the majority of disease (3). Finally, it is known that distinct hyperinvasive lineages tend to be associated with particular epidemiological manifestations of meningococcal disease (4) and some are especially associated with severe disease (the "hyper-virulent" lineages) (5). These complexities have important implications for public-health interventions, as different disease epidemiologies, caused by genetically diverse meningococci, require distinct approaches to public-health management. For example, the public-health response necessary to combat large-scale meningococcal-disease outbreaks in Africa (6) is different from that required during an institutional disease outbreak in Europe and North America, and prolonged geographical outbreaks in these countries require a different response again (7). In recognition of the importance of the multi-disciplinary approach necessary to establish these insights, this section contains chapters ranging from outbreak management through surveillance and isolate characterization techniques to phylogenetic methods. Together the chapters provide the methodologies necessary for monitoring, understanding, and reacting to the spread of meningococcal disease.

Induction of immunological memory in UK infants by a meningococcal A/C conjugate vaccine.

The induction of immunological memory to serogroup A and C polysaccharides in UK infants immunized with three doses of a meningococcal A/C oligosaccharide CRM197 conjugate vaccine was investigated. Forty UK infants vaccinated previously with three doses of a meningococcal A/C oligosaccharide-CRM197 conjugate vaccine at 2, 3 and 4 months of age, were revaccinated at a mean age of 145.6 weeks with either a 10 or 50 microg dose of licensed meningococcal A/C polysaccharide vaccine. Serogroup-specific antibody and serum bactericidal antibody (SBA) responses were measured by enzyme-linked immunosorbent assay and serum bactericidal assays, respectively. Following challenge, anti-serogroup A and C polysaccharide antibody levels rose from pre-booster geometric mean concentrations (GMC) of 3.1 and 2.1 microg/ml respectively to 19.6 and 21.0 microg/ml 1 month post-booster. Serum bactericidal antibody geometric mean titres (GMTs) for serogroups A and C increased 156- and 113-fold from 2.1 and 7.1 pre-booster respectively to 327.4 and 800.7 post-booster. A serogroup A control group of 45 children received a 10 microg dose of licensed meningococcal A/C polysaccharide vaccine (with no prior history of serogroup A vaccination) had serogroup A SBA GMTs of 2.3 pre-vaccination rising to 8 post-vaccination with corresponding GMCs of 0.8 and 10.8 microg/ml. These rises in SBA following serogroup A/C conjugate vaccination are indicative of immunological priming.

Salivary antibodies following parenteral immunization of infants with a meningococcal serogroup A and C conjugated vaccine.

Bacterial and viral salivary antibody testing is proving sensitive and specific, useful for epidemiological studies, and is simple and non-invasive. Salivary serogroup C polysaccharide-specific (SC PS-S) IgA and IgG were determined as a proportion of total salivary IgA and IgG in a group of UK infants who were recipients of a conjugated A/C meningococcal PS vaccine. Geometric mean concentrations (GMCs) of salivary SC PS-S IgG per mg of total IgG (microg/mg) were 0.1 pre-vaccination, rising to 8.2 post first, 16.1 post second and 29.3 post third dose of vaccine. For IgA, the corresponding GMCs in ng/mg were 0.1, 82.8, 69.6 and 91.2. Significant correlations (P < 0.0001) were found between serum Ig and salivary IgG SC PS-S antibody for pre-vaccine and 1 month post each dose of vaccine suggesting that SC PS-S IgG in saliva was largely derived from serum. Of the five infants whose sera were analysed for isotype-specific responses, only traces of IgM and IgA were measurable suggesting that the SC PS-S IgA was locally produced. These findings suggests that the widespread use of meningococcal conjugate vaccines is likely to reduce nasopharyngeal carriage and may thereby induce herd immunity in the vaccinated population.

Control of diphtheria: guidance for consultants in communicable disease control. World Health Organization.

These guidelines for the control and management of diphtheria are intended for consultants in communicable disease control and regional epidemiologists in England and Wales. They are intended to complement existing guidance from the World Health Organization. The guidelines cover the immediate steps to be taken following identification of a case, what is required to confirm the diagnosis, steps to be taken to minimise the likelihood of further linked cases, and what should be done to disseminate information after a case.

Antibody responses and symptoms after DTP and either tetanus or diphtheria Haemophilus influenzae type B conjugate vaccines given for primary immunisation by separate or mixed injection.

The safety and immunogenicity of two conjugate Haemophilus influenzae type B (Hib) vaccines administered either mixed with, or in separate limbs to, a whole-cell DTP vaccine, was compared in infants vaccinated at 2, 3 and 4 months of age. Antibody titres to purified polyribosylribitol phosphate, diphtheria, and to pertussis antigens between infants who received the Hib and DPT vaccines in separate limbs or in the same limbs were similar (P > 0.1) while antibody titres to tetanus toxoid were higher in the later group (P < 0.05). This study demonstrated that both Hib vaccines can be mixed with whole-cell DTP vaccine without reducing immunogenicity of either vaccine or increasing the incidence of adverse reactions.

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.

A collaborative case control study of sporadic hepatitis A in England.

A case control study of sporadic hepatitis A was carried out in 201 districts in England from July 1990 to June 1991. The aims were to determine the risk factors associated with the infection and to identify individuals or groups who might benefit from prophylactic measures, such as human normal immunoglobulin or hepatitis A vaccine. Factors associated with risk of hepatitis A included travel abroad (odds ratio (OR) 19.8; 95% confidence interval (CI) 4.87-80.6), a household contact with hepatitis A (OR 13.5; 95% CI 6.49-28.0) and sharing a household with a child aged 3 to 10 years (OR 1.57; 95% CI 1.1-2.22). This study provided no clear evidence of increased risk in health care workers, teachers, or other occupational groups. A non-significant trend towards an increased risk in nursery nurses and child minders aged 20 to 29 years was observed. Pre-exposure prophylaxis with hepatitis A vaccine may be considered for people who travel frequently to areas where hepatitis A is highly or moderately endemic. Post-exposure prophylaxis with human normal immunoglobulin should be given to contacts of known cases in accordance with national guidelines. Immunoglobulin alone has been recommended in outbreaks, but the use of vaccine alone or combined with immunoglobulin should be evaluated.

Pneumococcal bacteraemia and meningitis in England and Wales 1982 to 1992.

In the 11 years from 1982 to 1992, microbiology laboratories in England and Wales reported 22,567 episodes of serious illness in which Streptococcus pneumoniae was isolated from blood and 3500 in which it was isolated from cerebrospinal fluid. Half of the reported cases of bacteraemia occurred in people of over 65 years (11,299 cases). A predisposing cause was seldom reported. Annual totals of reports of pneumococcal bacteraemia and meningitis have risen in parallel with other serious infections. The rates of pneumococcal infections reported in very young and elderly people have risen much more rapidly and, although this observation may be artefactual, it may be associated with an observed increase in reports of antibiotic resistance. The proportion of pneumococcal isolates resistant to penicillin rose from 0.3% in 1989 to 1.9% in 1992 (p < 0.05). We suggest that the role of pneumococcal vaccination should be re-evaluated.

Antibody response and viral excretion after live polio vaccine or a combined schedule of live and inactivated polio vaccines.

A randomized controlled trial was performed in infants undergoing routine immunization in North Hertfordshire. Ninety-six children received a single dose of inactivated polio vaccine, followed by two doses of live attenuated oral polio vaccine and 97 children received three doses of live attenuated oral polio vaccine at 2, 3 and 4 months of age. Blood samples were taken by study nurses 6 weeks after vaccination and stool samples were collected by parents weekly for 4 weeks after each dose of vaccine. Follow-up was completed for 92 of 96 (96%) children in the combined schedule group and 92 of 97 (95%) in the control group. After vaccination the proportions of children with detectable antibody to poliovirus serotypes 1, 2 and 3 were high and similar between groups and geometric mean titers (95% confidence interval) to poliovirus types 1, 2 and 3 were 264 (200 to 347), 375 (311 to 450) and 189 (144 to 250) in the combined schedule group and 369 (290 to 469), 401 (321 to 498) and 206 (145 to 293) in the live vaccine group, respectively. The only significant difference between groups in rates of viral excretion was observed after the second dose of live attenuated oral polio vaccine, when excretion of type 3 poliovirus was reduced in those children who had received prior inactivated polio vaccine (P = 0.05). This study suggests that, compared with the current schedule, a combined schedule of inactivated and live poliovaccines is likely to produce equivalent individual protection against poliomyelitis and is unlikely to substantially alter circulation of poliovirus in the community.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunoprophylaxis at extremes of age.

Many infections that occur at the extremes of age are preventable by active or passive immunization. The immune response to vaccines in neonates and the elderly may be diminished when compared with other age groups, however this is usually outweighed by the benefits of providing protection at the age when the need is greatest. Immunoprophylactic agents used at birth include BCG vaccine, oral polio vaccine, varicella-zoster immunoglobulin and hepatitis B vaccine and immunoglobulin. In the elderly, influenza, pneumococcal and tetanus vaccines are often indicated, although the uptake in this age group is poor in comparison with neonates.

Antibody response to accelerated immunisation with diphtheria, tetanus, pertussis vaccine.

From May, 1990, a new schedule of immunisation against diphtheria, tetanus, and pertussis (at 2, 3, and 4 months) replaced the previous more widely spaced schedule. A report that children had lower concentrations of diphtheria and tetanus antibodies a month after an accelerated schedule led us to undertake a controlled study to assess antibody response and the persistence of antibodies a year after immunisation in children receiving vaccine according to widely spaced and accelerated schedules. Concentrations of antibodies to diphtheria and tetanus toxoids and to Bordetella pertussis filamentous haemagglutinin (FHA) were measured by solid-phase radioimmunoassay (SP-RIA). We studied 57 children who received accelerated immunisation at median ages of 11, 16, and 21 weeks and two control cohorts (total n = 82) who received vaccine at median ages of 15, 21, and 45 weeks. 6-8 weeks after the third dose the accelerated-schedule group had lower (p < 0.0001) geometric mean concentrations of antibody to tetanus (0.522 [95% CI 0.383-0.710] vs 3.43 [2.45-4.81] IU/mL), diphtheria (0.266 [0.179-0.396] vs 2.39 [0.616-3.53] IU/mL), and FHA (0.044 [0.030-0.063] vs 0.270 [0.196-0.374] units/mL) than the longer-schedule group. 12 months after the third dose the differences between the groups had narrowed (tetanus 0.197 vs 0.341 IU/mL, p = 0.29; diphtheria 0.100 vs 0.131 IU/mL, p = 0.64; FHA 0.014 vs 0.016 units/mL, p = 0.72). At that time all children had tetanus antibody concentrations above protective levels (0.01 IU/mL); only 2 of 31 in the accelerated-schedule group and 3 of 31 in the longer-schedule group had diphtheria antibody concentrations below the protective level. The use of an accelerated schedule of diphtheria, tetanus, and pertussis vaccination is unlikely to lead to an increase in the proportion of children unprotected against these diseases before the preschool booster.