Epidemiological pattern of meningococcal disease in Valencia, Spain. Impact of a mass immunization campaign with meningococcal C polysaccharide vaccine

The objective of this study was to define the epidemiological pattern of meningococcal disease in the autonomous region of Valencia, Spain, and the impact of a mass immunization campaign against serogroup C meningococcus. Data were obtained from a prospective surveillance program for invasive bacterial diseases in children < 15 y of age that began in the Valencia region on 1 December, 1995. During the period 1996-98, 213 cases of meningococcal disease were detected, representing an annual incidence of 11.3/100,000 children < 15 y. Serogroup C accounted for 31% and 38.5% of cases in 1996 and 1997, respectively (annual incidences of 2.9 and 5.4 cases/100,000 children < 15 y). An immunization campaign with the meningococcal C polysaccharide vaccine, which included all persons between 18 months and 19 y of age, began in late 1997 (vaccination coverage of 86%). In 1998, the annual incidence of meningococcal C disease fell to 1.4 cases per 100,000 children < 15 y of age. These results mirror the increase in the reported incidence of serogroup C meningococcal disease in Spain in the 1990s, a trend that was reversed after the introduction of the mass vaccination campaign. Meningococcal polysaccharide vaccine seems to be an effective public health tool for the management of this serious communicable disease.     

Economics of an adolescent meningococcal conjugate vaccination catch-up campaign in the United States.

BACKGROUND: In June 2005, the Advisory Committee on Immunization Practices recommended the newly licensed quadrivalent meningococcal conjugate vaccine for routine use among all US children aged 11 years. A 1-time catch-up vaccination campaign for children and adolescents aged 11-17 years, followed by routine annual immunization of each child aged 11 years, could generate immediate herd immunity benefits. The objective of our study was to analyze the cost-effectiveness of a catch-up vaccination campaign with quadrivalent meningococcal conjugate vaccine for children and adolescents aged 11-17 years. METHODS: We built a probabilistic model of disease burden and economic impacts for a 10-year period with and without a program of adolescent catch-up meningococcal vaccination, followed by 9 years of routine immunization of children aged 11 years. We used US age- and serogroup-specific surveillance data on incidence and mortality. Assumptions related to the impact of herd immunity were drawn from experience with routine meningococcal vaccination in the United Kingdom. We estimated costs per case, deaths prevented, life-years saved, and quality-adjusted life-years saved. RESULTS: With herd immunity, the catch-up and routine vaccination program for adolescents would prevent 8251 cases of meningococcal disease in a 10-year period (a 48% decrease). Excluding program costs, this catch-up and routine vaccination program would save US$551 million in direct costs and $920 million in indirect costs, including costs associated with permanent disability and premature death. At $83 per vaccinee, the catch-up vaccination would cost society approximately $223,000 per case averted, approximately $2.6 million per death prevented, approximately $127,000 per life-year saved, and approximately $88,000 per quality-adjusted life-year saved. Targeting counties with a high incidence of disease decreased the cost per life-year saved by two-thirds. CONCLUSIONS: Although costly, catch-up and routine vaccination of adolescents can have a substantial impact on meningococcal disease burden. Because of herd immunity, catch-up and routine vaccination cost per life-year saved could be up to one-third less than that previously assessed for routine vaccination of children aged 11 years.     

Meningococcal vaccine in travelers

PURPOSE OF REVIEW: New vaccines to prevent meningococcal disease have been licensed in recent years. It is therefore timely to discuss current vaccine strategies pertinent to international travelers in relation to the changing epidemiology. RECENT FINDINGS: Serogroup W135 achieved epidemic status in Africa in 2002, and then largely disappeared over a short time period. The year 2006 saw a marked epidemic rise in meningitis attack rates across the meningitis belt in Africa. This rise was mainly due to a new serogroup A strain, indicating that a new meningitis epidemic wave is beginning in Africa. Epidemics are also spreading south of the meningitis belt, including the Greater Lakes Area (Burundi, Rwanda, Republic of Tanzania). The new quadrivalent conjugate meningococcal vaccine is now licensed in North America but not elsewhere. In most other industrialized countries, the serogroup C conjugate vaccine is licensed. Plain polysaccharide quadrivalent vaccines are available almost worldwide. SUMMARY: Quadrivalent meningococcal vaccination is a visa requirement for Hajj and Umrah pilgrims to Saudi Arabia. Travelers to the meningitis belt during the dry season should be advised to receive meningococcal vaccine that covers all four serogroups. This recommendation should be extended to the Greater Lake Area, because of recent epidemics. Vaccine choices depend on availability.     

Microbiological epidemiological history of meningococcal disease in Rio de Janeiro,Brazil

The main objectives of the present study were to investigate the clinical and laboratory features of meningococcal disease in the city of Rio de Janeiro, Brazil, during the overlap of 2 epidemics in the 1990s. We conducted a study of a series of cases of meningococcal disease admitted in a Meningitis Reference Hospital. All clinical isolates available were analyzed by means of microbiological epidemiological markers. In 1990, Neisseria meningitidis serogroup B:4,7:P1.19,15, 1.7,1 sulfadiazine-resistant of the ET-5 complex emerged causing epidemic disease. Despite mass vaccination campaign (VaMengoc B+C^®), the ET-5 clone remained hyperendemic after the epidemic peaked. In 1993 to 1995, an epidemic of serogroup C belonged to the cluster A4 overlapped, with a significant shift in the age distribution toward older age groups and an increase of sepsis. Serogroup C epidemics are a recurrent problem in Rio de Janeiro, which can be hindered with the introduction of a conjugate vaccine. We hope the data presented here brings useful information to discuss vaccines strategies and early management of suspected cases.     

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.     

Impact of meningococcal serogroup C conjugate vaccines on carriage and herd immunity

BACKGROUND: In 1999, meningococcal serogroup C conjugate (MCC) vaccines were introduced in the United Kingdom for those under 19 years of age. The impact of this intervention on asymptomatic carriage of meningococci was investigated to establish whether serogroup replacement or protection by herd immunity occurred. METHODS: Multicenter surveys of carriage were conducted during vaccine introduction and on 2 successive years, resulting in a total of 48,309 samples, from which 8599 meningococci were isolated and characterized by genotyping and phenotyping. RESULTS: A reduction in serogroup C carriage (rate ratio, 0.19) was observed that lasted at least 2 years with no evidence of serogroup replacement. Vaccine efficacy against carriage was 75%, and vaccination had a disproportionate impact on the carriage of sequence type (ST)-11 complex serogroup C meningococci that (rate ratio, 0.06); these meningococci also exhibited high rates of capsule expression. CONCLUSIONS: The impact of vaccination with MCC vaccine on the prevalence of carriage of group C meningococci was consistent with herd immunity. The high impact on the carriage of ST-11 complex serogroup C could be attributed to high levels of capsule expression. High vaccine efficacy against disease in young children, who were not protected long-term by the schedule initially used, is attributed to the high vaccine efficacy against carriage in older age groups.     

Prevention of bacterial meningitis: an overview of Cochrane systematic reviews

Acute bacterial meningitis (ABM) is an acute inflammation of leptomeninges caused by bacteria, and has a case fatality rate of 10-30%. Prevention strategies, such as vaccination and prophylactic antibiotics, can prevent ABM and have substantial public health impact by reducing the disease burden associated with it. The aim of this paper is to summarize the main findings from Cochrane systematic reviews that have considered the evidence for measures to prevent ABM. We assessed the evidence available in the Cochrane Library. We found five Cochrane reviews focused on the prevention of ABM; three with use of vaccination and two with prophylactic antibiotics. Polysaccharide serogroup A vaccine is strongly protective for the first year, against serogroup A meningococcal meningitis in adults and children over 5 years of age. Meningococcal serogroup C conjugate (MCC) vaccine is safe and effective in infants. Haemophilus influenzae type b (Hib) vaccine is safe and effective against Hib-invasive disease at all ages. Ceftriaxone, rifampicin and ciprofloxacin are the most effective prophylactic antibiotics against Neisseria meningitidis. There is sufficient evidence to use polysaccharide serogroup A vaccine to prevent serogroup A meningococcal meningitis, MCC conjugate vaccines to prevent meningococcal C meningitis and Hib conjugate vaccine to prevent Hib infections. More studies are needed to evaluate the effects of Hib conjugate vaccine on mortality. Further, studies are required to compare the relative effectiveness of ceftriaxone, ciprofloxacin and rifampicin in chemoprophylaxis against meningococcal infection.     

Advances with vaccination against Neisseria meningitidis

In the last decade, meningococcal serogroup C conjugate vaccination programs have been demonstrated to be hugely successful with a truly impressive public health impact. In sub‐Saharan Africa, with the implementation of an affordable serogroup A conjugate vaccine, it is hoped that a similar public health impact will be demonstrated. Challenges still remain in the quest to develop and implement broadly protective vaccines against serogroup B disease. New, broad coverage vaccines against serogroup B are for the first time becoming available although little is known about their antibody persistence, effectiveness or effect on nasopharyngeal carriage. Enhanced surveillance following any potential vaccine introduction against serogroup B needs to be thoroughly implemented. The future now holds a distinct possibility, globally, for substantially decreasing meningococcal disease, regardless of infecting serogroup.     

Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom

BACKGROUND: The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data. METHODS: All subjects with laboratory-confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory-confirmed case of MenC disease occurring > or =10 days after the subject's last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease. RESULTS: Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1-fold higher for SBA titers [P=.03] and 3.2-fold higher for AIs [P=.001]). CONCLUSIONS: The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long-term protection for MCC vaccines than the ability to generate a booster response on exposure.     

Estimating Haemophilus influenzae type b vaccine effectiveness in England and Wales by use of the screening method

In October 1992, Haemophilus influenzae type b (Hib) conjugate vaccine was introduced to infants in the United Kingdom with a "catch-up" program for those aged <4 years. Initially, the rate of invasive Hib disease decreased dramatically but has been increasing since 1999. To determine possible reasons for this increase, the effectiveness of Hib conjugate vaccine was estimated by use of the screening method. Between October 1993 and December 2001, a total of 443 cases of Hib infection occurred in children eligible for vaccination; 363 (82%) were fully vaccinated. Vaccine effectiveness was estimated to be 56.7% (95% confidence interval, 42.5-67.4). Effectiveness was lower in children vaccinated during infancy, compared with those who were vaccinated during the catch-up campaign (P=.0033), declined with time since vaccination (P=.0008), and was lower in children born during 2000-2002, compared with other children scheduled for infant vaccination (P=.0041). Use of a catch-up vaccination program enhanced the control of Hib infection in England and Wales. Since 1999, however, low effectiveness in infants, declining effectiveness with age, and the use of lower-efficacy vaccines have contributed to increased rates of Hib infection. The potential role of boosters needs to be considered.     

Prospective study of a serogroup X Neisseria meningitidis outbreak in northern Ghana

After an epidemic of serogroup A meningococcal meningitis in northern Ghana, a gradual disappearance of the epidemic strain was observed in a series of five 6-month carriage surveys of 37 randomly selected households. As serogroup A Neisseria meningitidis carriage decreased, an epidemic of serogroup X meningococcal carriage occurred, which reached 18% (53/298) of the people sampled during the dry season of 2000, coinciding with an outbreak of serogroup X disease. These carriage patterns were unrelated to that of Neisseria lactamica. Multilocus sequence typing and pulsed-field gel electrophoresis of the serogroup X bacteria revealed strong similarity with other strains isolated in Africa during recent decades. Three closely related clusters with distinct patterns of spread were identified among the Ghanian isolates, and further microevolution occurred after they arrived in the district. The occurrence of serogroup X outbreaks argues for the inclusion of this serogroup into a multivalent conjugate vaccine against N. meningitidis.     

CRM197-conjugated serogroup C meningococcal capsular polysaccharide, but not the native polysaccharide, induces persistent antigen-specific memory B cells

Neisseria meningitidis is one of the leading causes of bacterial meningitis and septicemia in children. Vaccines containing the purified polysaccharide capsule from the organism, a T cell-independent antigen, have been available for decades but do not appear to provide protection in infancy or immunologic memory as measured by antibody responses. By contrast, T cell-dependent serogroup C protein-polysaccharide conjugate vaccines protect against serogroup C meningococcal disease from infancy onward and prime for immunologic memory. We compared the magnitude and kinetics of plasma cell and memory B-cell responses to a meningococcal plain polysaccharide vaccine and a serogroup C glycoconjugate vaccine in adolescents previously primed with the conjugate vaccine. Plasma cell kinetics were similar for both vaccines, though the magnitude of the response was greater for the glycoconjugate. In contrast to the glycoconjugate vaccine, the plain polysaccharide vaccine did not induce a persistent immunoglobulin G (IgG) memory B-cell response. This is the first study to directly show that serogroup C meningococcal glycoconjugate vaccines induce persistent production of memory B cells and that plain polysaccharide vaccines do not, supporting the use of the conjugate vaccine for sustained population protection. Detection of peripheral blood memory B-cell responses after vaccination may be a useful signature of successful induction of immunologic memory during novel vaccine evaluation.     

Meningococcal serogroup C conjugate vaccine is immunogenic in infancy and primes for memory

The safety, immunogenicity, and immunologic priming of 2 dosages (2 microgram or 10 microgram) of a meningococcal C oligosaccharide-CRM197 conjugate vaccine was evaluated in 114 infants vaccinated at ages 2, 3, and 4 months. Antibody persistence and response to boosting with 10 microgram of meningococcal C polysaccharide were assessed. The meningococcal conjugate vaccine produced fewer local reactions than concurrent routine immunizations. Total serogroup C-specific immunoglobulin geometric mean concentration (GMC) increased from 0.3 microgram/mL before vaccination to 13.1 microgram/mL at age 5 months. Serum bactericidal antibody (SBA) geometric mean titers (GMTs) rose from <1:4 to 1:1057 at 5 months and fell by 14 months to 1:19. Following boosting, anti-C-specific immunoglobulin GMC rose to 15.9 microgram/mL and SBA GMT to 1:495. Antibody responses in the 10-microgram dose cohort were significantly higher at 5 months (P<.01) than in the 2-microgram dose cohort but were lower after polysaccharide boosting (P=.02). This meningococcal conjugate vaccine was well tolerated and immunogenic and induced immunologic memory in infants.     

Meningococcal Disease in Catalonia 1 Year after Mass Vaccination Campaign with Meningococcal Group C Polysaccharide Vaccine

Abstract. Background: The aim of this study was to investigate the clinical and epidemiological characteristics of meningococcal disease in Catalonia (Spain) after vaccination with the polysaccharide vaccine. Patients and Methods: Cases were collected by the Statutory Diseases Reporting System. Results: 176 cases were reported, an overall incidence of 2.9/100,000 persons/year. 60% of cases occurred during winter and spring. The case fatality rate was 6.3%. The highest age incidence was in children under 2 years of age (48/100,000 persons/year). Comparison of the cases detected by the Statutory Diseases Reporting System with those obtained by the Microbiological Reporting System shows that meningococcal disease surveillance in Catalonia was relatively complete (95.7%), with a positive predictive value of 66.3%. 115 cases (65%) were culture-confirmed with a rate of 1.9/100,000 persons/year. 86 (75%) cases were due to Neisseria meningitidis serogroup B and 21 to serogroup C (18%). Conclusion: Although infections due to serogroup C have decreased after mass vaccination with the polysaccharide vaccine, it is likely that the number of infections will decrease further with the conjugate meningococcal group C vaccine.*The Working Group on Meningococcal Disease in Catalonia: A. Domínguez, G. Carmona, A. Martínez, P. Ciruela, P. Garrido, P. Domingo, F. Sánchez, D. Fontanals, A. Retana, N. Camps, N. Follia, C. Casellas, M. Piqué, M. C. Roure, J. Batlle, P. Godoy, A. Artigues, A. Manonelles, A. Nogués, G. Mirada, P. Bach, T. Vallmanya, S. Minguell, N. Escatllar, J. Allué, J. M. Santamaría, M. Olona, J. Rebull, M.M. Pérez, J. S. Escribano, F. Ballester, R. Maldonado, C. Planas,T. Admella, H. Pañella, R.Verdaguer, M. Boronat, A. Martínez, M. Xercavins, M. Dougan, A. Orcau, M. Barahona, A. M. Botia, M. S. Cabello, C. Rodrigo, J. Roca, J. Alvarez, P. Matilla, A. M. Escofet, C. Vila, J. Sitges, J. Cuquet. L. de la Fuente, G. Prats, J. A. Vázquez.     

Meningococcal Disease: Shifting Epidemiology and Genetic Mechanisms That May Contribute to Serogroup C Virulence

During the past decade, monovalent serogroup C and quadrivalent (serogroups A, C, W135, Y) meningococcal vaccination programs have been introduced in multiple industrialized countries. Many of these programs have been successful in reducing the burden of disease due to vaccine-preventable serogroups of Neisseria meningitidis in target age groups. As a result, disease burden in these countries has decreased and is primarily serogroup B, which is not vaccine preventable. Despite the success of these programs, meningococcal disease continues to occur and there is always concern that serogroup C organisms will adapt their virulence mechanisms to escape pressure from vaccination. This review highlights the current epidemiology of meningococcal disease in Europe and United States, as well as genetic mechanisms that may affect virulence of serogroup C strains and effectiveness of new vaccines.     

Measles-rubella mass immunization campaign in Albania,November 2000

In 2000, Albania resolved to eliminate measles by 2007 by use of a four-step program: by conducting a "catch-up" vaccination campaign for all children aged 1-14 years, achieving and sustaining high coverage (>/=95%) among children aged 1 year with the first dose of a measles-containing vaccine, by introducing a routine second dose of measles-containing vaccine for children at age 5 years, and by improving measles surveillance. This catch-up campaign took place in November 2000: 867,000 doses of measles-rubella vaccine were administered for an estimated coverage of 99%. In all, 231 campaign-related adverse events were reported: syncope, 206; allergic reactions, 10; fever, 8; encephalitis/encephalopathy, 2; and aseptic meningitis, seizures, Guillain-Barré syndrome, anaphylaxis, and arthralgia, 1 each. All resolved without sequelae. This report describes the status of measles and rubella/congenital rubella syndrome control in Albania before 2000 and reports on implementation of the catch-up campaign.     

Neisseria meningitidis W-135 carriage during the Hajj season 2003.

During the 2003 Hajj pilgrimage to Mecca, 344 pilgrims of 29 different nationalities were screened by means of a throat swab to detect Neisseria meningitidis carriage. N. meningitidis was isolated from 11 subjects; 2 were serogroup W-135, 1 serogroup B, and 8 were non-groupable. The results indicate a very low colonization rate for N. meningitidis among the tested cohort, with a predominance of non-groupable strains. These results, combined with a review of the published data, warrant a re-evaluation of current recommendations by the Saudi Ministry of Health for the use of ciprofloxacin for Saudi pilgrims departing at the end of the Hajj season. However, vaccination with the meningococcal quadrivalent vaccine, for all pilgrims, should continue to be recommended. The possibility of new strains arising as a cause of future meningococcal outbreaks should be considered, and annual surveillance may give an early warning.     

A critical review of control strategies against meningococcal meningitis epidemics in sub-Saharan African countries

The control strategy of meningitis epidemics in sub-Saharan countries, although reexamined regularly, is based on epidemiological, immunological and logistical considerations put forward at the end of the 1970s. It comprises organizing large-scale vaccinations in the event of a declared epidemic. The obvious failure of this strategy recommended by the World Health Organization (WHO) necessitates evaluation of the emergency vaccination criteria. Despite current controversy on the immunogenicity of the polysaccharide vaccine, its safety, effectiveness in the field and low cost could justify the reopening of a debate on its use in routine vaccination. Routine - or preventive - vaccination could significantly reduce the incidence of meningococcal meningitis and its severity. The conjugate vaccine, when available, will constitute an additional advantage in the prevention of meningococcal meningitis. A strategy combining both polysaccharide and conjugate vaccines according to the population targets and possibilities for funding remain to be defined. Received: January 16, 2002 · Revision accepted: April 23, 2002