Caroline L. Trotter

Global epidemiology of meningococcal disease

As reviewed in this paper, meningococcal disease epidemiology varies substantially by geographic area and time. The disease can occur as sporadic cases, outbreaks, and large epidemics. Surveillance is crucial for understanding meningococcal disease epidemiology, as well as the need for and impact of vaccination. Despite limited data from some regions of the world and constant change, current meningococcal disease epidemiology can be summarized by region. By far the highest incidence of meningococcal disease occurs in the meningitis belt of sub-Saharan Africa. During epidemics, the incidence can approach 1000 per 100,000, or 1% of the population. Serogroup A has been the most important serogroup in this region. However, serogroup C disease has also occurred, as has serogroup X disease and, most recently, serogroup W-135 disease. In the Americas, the reported incidence of disease, in the range of 0.3-4 cases per 100,000 population, is much lower than in the meningitis belt. In addition, in some countries such as the United States, the incidence is at an historical low. The bulk of the disease in the Americas is caused by serogroups C and B, although serogroup Y causes a substantial proportion of infections in some countries and W-135 is becoming increasingly problematic as well. The majority of meningococcal disease in European countries, which ranges in incidence from 0.2 to 14 cases per 100,000, is caused by serogroup B strains, particularly in countries that have introduced serogroup C meningococcal conjugate vaccines. Serogroup B also predominates in Australia and New Zealand, in Australia because of the control of serogroup C disease through vaccination and in New Zealand because of a serogroup B epidemic. Based on limited data, most disease in Asia is caused by serogroup A and C strains. Although this review summarizes the current status of meningococcal disease epidemiology, the dynamic nature of this disease requires ongoing surveillance both to provide data for vaccine formulation and vaccine policy and to monitor the impact of vaccines following introduction.

Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction

The meningococcal serogroup C conjugate (MCC) vaccine programme in England has successfully controlled the incidence of serogroup C disease, as a result of high short-term vaccine effectiveness and substantial herd immunity. However, the long-term effectiveness of the vaccine remains unknown. We assessed surveillance data from the 4 years since introduction of the programme. Vaccine effectiveness remained high in children vaccinated in the catch-up campaign (aged 5 months to 18 years). However, for children vaccinated in the routine infant immunisation programme, the effectiveness of the MCC vaccine fell to low levels after only 1 year. The number of individuals in these cohorts remains low, but alternative routine immunisation schedules should be considered to ensure high levels of protection are sustained.

Efficacy of pneumococcal vaccination in adults: a meta-analysis

Background: Clinical trials and meta-analyses have produced conflicting results of the efficacy of unconjugated pneumococcal polysaccharide vaccine in adults. We sought to evaluate the vaccines efficacy on clinical outcomes as well as the methodologic quality of the trials. Methods: We searched several databases and all bibliographies of reviews and meta-analyses for clinical trials that compared pneumococcal polysaccharide vaccine with a control. We examined rates of pneumonia and death, taking the methodologic quality of the trials into consideration. Results: We included 22 trials involving 101 507 participants: 11 trials reported on presumptive pneumococcal pneumonia, 19 on all-cause pneumonia and 12 on all-cause mortality. The current 23-valent vaccine was used in 8 trials. The relative risk (RR) was 0.64 (95% confidence interval [CI] 0.43–0.96) for presumptive pneumococcal pneumonia and 0.73 (95% CI 0.56–0.94) for all-cause pneumonia. There was significant heterogeneity between the trials reporting on presumptive pneumonia (I2 = 74%, p < 0.001) and between those reporting on all-cause pneumonia (I2 = 90%, p < 0.001). The RR for all-cause mortality was 0.97 (95% CI 0.87–1.09), with moderate heterogeneity between trials (I2 = 44%, p = 0.053). Trial quality, especially regarding double blinding, explained a substantial proportion of the heterogeneity in the trials reporting on presumptive pneumonia and all-cause pneumonia. There was little evidence of vaccine protection in trials of higher methodologic quality (RR 1.20, 95% CI 0.75–1.92, for presumptive pneumonia; and 1.19, 95% CI 0.95–1.49, for all-cause pneumonia in double-blind trials; p for heterogeneity > 0.05). The results for all-cause mortality in double-blind trials were similar to those in all trials combined. There was little evidence of vaccine protection among elderly patients or adults with chronic illness in analyses of all trials (RR 1.04, 95% CI 0.78–1.38, for presumptive pneumococcal pneumonia; 0.89, 95% CI 0.69–1.14, for all-cause pneumonia; and 1.00, 95% CI 0.87–1.14, for all-cause mortality). Interpretation: Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended.

Herd immunity from meningococcal serogroup C conjugate vaccination in England: database analysis

In November 1999, the United Kingdom introduced routine meningococcal serogroup C conjugate vaccination for infants. The vaccine was also offered to everyone aged under 18 years in a phased catch-up programme.1 The first to be vaccinated were adolescents, and the entire programme was completed by the end of 2000. On the basis of direct protection provided by the vaccine, 1 2 this catch-up programme was likely to be cost effective.3 Maiden et al described a 67% reduction (from 0.45% to 0.15%) in the prevalence of nasopharyngeal carriage of serogroup C meningococci in adolescents before and after the vaccination programme.4 A fall in meningococcal carriage would be expected to reduce exposure among unvaccinated children and therefore to enhance the effectiveness of meningococcal conjugate vaccine. We present rates of disease in vaccinated and unvaccinated children to provide the first evidence of an indirect effect from meningococcal conjugate vaccine. Since December 1999 we have investigated the vaccination history of all cases of …

Meningococcal carriage by age: a systematic review and meta-analysis.

BACKGROUND Neisseria meningitidis is an important cause of meningitis and septicaemia, but most infected individuals experience a period of asymptomatic carriage rather than disease. Previous studies have shown that carriage rates vary by age and setting; however, few have assessed carriage across all ages. We aimed to estimate the age-specific prevalence of meningococcal carriage. METHODS We searched Embase, Medline, Web of Science, the Cochrane Library, and grey literature for papers reporting carriage of N meningitidis in defined age groups in European countries or in countries with a similar epidemiological pattern (where disease caused by serogroups B and C predominates). We used mixed-effects logistic regression with a natural cubic spline to model carriage prevalence as a function of age for studies that were cross-sectional or serial cross-sectional. The model assessed population type, type of swab used, when swabs were plated, use of preheated plates, and time period (decade of study) as fixed effects, with country and study as nested random effects (random intercept). FINDINGS Carriage prevalence increased through childhood from 4·5% in infants to a peak of 23·7% in 19-year olds and subsequently decreased in adulthood to 7·8% in 50-year olds. The odds of testing positive for carriage decreased if swabs were not plated immediately after being taken compared with if swabs were plated immediately (odds ratio 0·46, 95% CI 0·31-0·68; p = 0·0001). INTERPRETATION This study provides estimates of carriage prevalence across all ages, which is important for understanding the epidemiology and transmission dynamics of meningococcal infection. FUNDING None.

Increasing hospital admissions for pneumonia, England

This rise in recorded incidence from 2001 to 2005 was particularly marked among the elderly.

Updated Postlicensure Surveillance of the Meningococcal C Conjugate Vaccine in England and Wales: Effectiveness, Validation of Serological Correlates of Protection, and Modeling Predictions of the Duration of Herd Immunity

ABSTRACT Meningococcal serogroup C conjugate (MCC) vaccines were licensed in the United Kingdom more than 10 years ago based on correlates of protection that had previously been established for serogroup C-containing polysaccharide vaccines by using the serum bactericidal antibody (SBA) assay. These correlates of protection were subsequently validated against postlicensure estimates of observed vaccine effectiveness up to 7 to 9 months after the administration of the MCC vaccine. Vaccine effectiveness was, however, shown to fall significantly more than 1 year after the administration of a 3-dose course in infancy. Despite this finding, the marked impact on serogroup C disease has been sustained, with the lowest recorded incidence (0.02 case per 100,000 population) in the 2008-2009 epidemiological year, mainly due to the indirect herd immunity effect of the vaccine in reducing carriage. Updated estimates of vaccine effectiveness through 30 June 2009 confirmed high short-term protection after vaccination in infancy, at 97% (95% confidence interval [CI], 91% to 99%), falling to 68% (95% CI, −63% to 90%) more than a year after vaccination. The observed vaccine effectiveness more than 12 months postvaccination was consistent with measured declining SBA levels, but confidence intervals were imprecise; vaccine effectiveness estimates were consistent with SBA titers of 1:4 or 1:8 as correlates of long-term protection after a primary course in infants. Modeling suggested that protection against carriage persists for at least 3 years and predicted the stabilization of serogroup C disease at low levels (fewer than 50 cases per year) up to 2015-2016.

Meningococcal vaccines and herd immunity: lessons learned from serogroup C conjugate vaccination programs

Effective vaccines provide direct protection to immunized individuals, but may also provide benefits to unvaccinated individuals by reducing transmission and thereby lowering the risk of infection. Such herd immunity effects have been demonstrated following the introduction of meningococcal serogroup C conjugate (MCC) vaccines, with reductions in disease attack rates in unimmunized individuals and significantly lower serogroup C carriage attributable to the vaccine introduction. In the UK, targeting teenagers for immunization was crucial in maximizing indirect effects, as most meningococcal transmission occurs in this age group. Questions remain regarding the duration of herd protection and the most appropriate long-term immunization strategies. The magnitude of the herd effects following MCC vaccination was largely unanticipated, and has important consequences for the design and evaluation of new meningococcal vaccines.

Meningococcal carriage in the African meningitis belt

In the African meningitis belt, epidemics of meningococcal disease occur periodically, although unpredictably, every few years. These epidemics continue to cause havoc but new efforts to control the disease, through the use of conjugate vaccines, are being made. Conjugate vaccines are likely to reduce meningococcal carriage, thus generating herd immunity, but to understand their potential impact we need to know more about the epidemiology of meningococcal carriage in Africa. We review published studies of meningococcal carriage in the African meningitis belt. A wide range of carriage prevalences has been reported, from 3% to over 30%, and the serogroup distribution has been variable. Factors influencing carriage include age, contact with a case, and the epidemic/endemic situation; however, season and immunisation with polysaccharide vaccine have little effect. Since the dynamics of carriage within a population are complex, longitudinal carriage studies are of great value; however, few such studies have been done. Carefully designed carriage studies are needed to measure and interpret the impact of meningococcal group A conjugate vaccines in Africa.

Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae

Conjugate vaccines exist that offer protection against disease caused by Haemophilus influenzae type b (Hib), and selected serogroups/serotypes of Neisseria meningitidis and Streptococcus pneumoniae. These vaccines are not only able to prevent serious disease, but they also provide protection against asymptomatic carriage. The resulting herd immunity effects have been striking, and have played an important role in the public health success of conjugate vaccination programmes. The aim of this paper is to review the state of the current evidence on conjugate vaccines and to identify important areas for further study, in order to inform the debate regarding the best use of these vaccines.