Impact of the meningococcal C conjugate vaccine in Spain: an epidemiological and microbiological decision

The new meningococcal C conjugate vaccine became available in Spain and was included in the infant vaccination schedule in 2000. A catch-up campaign was carried out in children under six years of age. As a consequence, the incidence of meningococcal disease caused by serogroup C has fallen sharply during the last three epidemiological years in Spain. The risk of contracting serogroup C disease in 2002/2003 fell by 58% when compared with the season before the conjugate vaccine was introduced. There was also an important decrease in mortality. Three deaths due to serogroup C occurred in the age groups targeted for vaccination in 2002/2003, compared with 30 deaths in the same age groups in the season before the launch of the vaccine campaign. In the catch-up campaign the vaccine coverage reached values above 92%. For the 2001, 2002 and 2003 routine childhood immunisation programme coverage values ranged from 90% to 95%. During the past three years a total of 111 cases of serogroup C disease have been reported in patients in the vaccine target group. Most of the vaccination failures occurred during the epidemiological year 2002/2003. Eight (53%) vaccine failures occurred in children who had been routinely immunised in infancy, and could be related to a lost of protection with time since vaccination. The isolation of several B:2a:P1.5 strains (ST-11 lineage) is noteworthy. These may have their origin in C:2a:P1.5 strains which, after undergoing genetic recombination at the capsular operon level, express serogroup B. These strains could have relevant epidemic potential.     

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.     

Incidence, serogroups and case-fatality rate of invasive meningococcal infections in a Swedish region 1975-1989.

In a retrospective study of invasive meningococcal infections in Greater Gothenburg, Sweden, 213 cases of culture-verified meningitis or septicaemia were identified during the 15-year period 1975-1989. The annual incidence was 2.0/100,000. Cases were seen in all age-groups with the highest rates in the 0-4 and 15-19 year-old groups, 9.5 and 6.2/100,000 respectively. 20% of the patients were less than 2 years. 91% of the patients had no known risk factors. In only 10 cases (5%) was contact with another case of meningococcal infection known. The main clinical manifestations were meningitis (57%), septicaemia with no sign of focal infection (25%) and septic shock (17%). The case-fatality rate for all the patients was 6.6% and did not change during the 15-year period. One-third of the patients who presented with septic shock died. The serogroup was known for strains from 192 patients. 51% of the strains belonged to serogroup B, 10% to group A and 23% to group C. In conclusion, the incidence of meningococcal infection was low but the relatively high case-fatality rate warrants a search for effective prophylaxis. About 30% of the cases were potentially preventable by the currently available tetravalent (A, C, Y and W135) polysaccharide vaccine, which is immunogenic in children greater than 2 years. Widespread use of antibiotic prophylaxis to close contacts of known cases would not lower the incidence markedly.     

Emergence of serogroup C meningococcal disease associated with a high mortality rate in Hefei, China

ABSTRACT: BACKGROUND: Neisseria meningitidis serogroup C has emerged as a cause of epidemic disease in Hefei. The establishment of serogroup C as the predominant cause of endemic disease has not been described. METHODS: We conducted national laboratory-based surveillance for invasive meningococcal disease during 2000--2010. Isolates were characterized by pulsed-field gel electrophoresis and multilocus sequence typing. RESULTS: A total of 845 cases of invasive meningococcal disease were reported. The incidence increased from 1.25 cases per 100,000 population in 2000 to 3.14 cases per 100,000 in 2003 (p < 0.001), and peaked at 8.43 cases per 100,000 in 2005. The increase was mainly the result of an increase in the incidence of serogroup C disease. Serogroup C disease increased from 2/23 (9%) meningococcal cases and 0.11 cases per 100,000 in 2000 to 33/58 (57%) cases and 1.76 cases per 100,000 in 2003 (p < 0.01). Patients infected with serogroup C had serious complications more frequently than those infected with other serogroups. Specifically, 161/493 (32.7%) cases infected with serogroup C had at least one complication. The case-fatality rate of serogroup C meningitis was 11.4%, significantly higher than for serogroup A meningitis (5.3%, p = 0.021). Among patients with meningococcal disease, factors associated with death in univariate analysis were age of 15--24 years, infection with serogroup C, and meningococcemia. CONCLUSIONS: The incidence of meningococcal disease has substantially increased and serogroup C has become endemic in Hefei. The serogroup C strain has caused more severe disease than the previously predominant serogroup A strain.     

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 disease and control in China: Findings and updates from the Global Meningococcal Initiative (GMI)

The Global Meningococcal Initiative (GMI) is a global expert group, including scientists, clinicians and public health officials from a wide range of specialities. The goal of the GMI is to prevent meningococcal disease worldwide through education, research, and co-operation. The Chinese GMI roundtable meeting was held in June 2017. The GMI met with local experts to gain insight into the meningococcal disease burden in China and current prevention and vaccination strategies in place. China experienced five epidemics of serogroup A meningococcal disease (MenA) between 1938 and 1977, with peak incidence of 403/100,000 recorded in 1967. MenA incidence rates have significantly declined following the universal introduction of the MenA polysaccharide vaccine in China in the 1980s. Further, surveillance data indicates changing meningococcal epidemiology in China with the emergence of new clones of serogroup B from serogroup C clonal complex (cc) 4821 due to capsular switching, and the international spread of serogroup W cc11. The importance of carriage and herd protection for controlling meningococcal disease was highlighted with the view to introduce conjugate vaccines and serogroup B vaccines into the national immunization schedule. Improved disease surveillance and standardized laboratory techniques across and within provinces will ensure optimal epidemiological monitoring.     

Impact of Non-routine Vaccination on the Incidence of Invasive Haemophilus influenzae Type b (Hib) Disease: Experience in the Autonomous Region of Valencia, Spain

OBJECTIVE: This study assessed the impact of non-routine vaccination against invasive Haemophilus influenzae (Hib)disease before the introduction of universal childhood Hib vaccination. METHODS: Data were obtained from a prospective surveillance program for invasive bacterial diseases in children <15 years of age that was begun in the Autonomous Region of Valencia on 1 December 1995. RESULTS: An incidence of 15.5 cases of invasive Hib disease per 100,000 children <5 years of age was reported in the first year of the surveillance program (from 1 December 1995 to 30 November 1996), when Hib vaccination coverage was estimated to be 32.5%. An increase in vaccination coverage to 44% in the second year (1 December 1996 to 30 November 1997) was associated with a reduction in disease incidence to 3.3 cases per 100,000. After the initiation of universal vaccination in December 1998, only two cases were reported. The effectiveness of non-routine vaccination was 71% in 1997. CONCLUSIONS: These results show that before the introduction of routine childhood Hib vaccination, widespread use of the vaccine can dramatically reduce the occurrence of invasive Hib disease.     

Epidemiology of serogroup B invasive meningococcal disease in Ontario, Canada, 2000 to 2010

ABSTRACT: BACKGROUND: Invasive meningococcal disease (IMD) caused by serogroup B is the last major serogroup in Canada to become vaccine-preventable. The anticipated availability of vaccines targeting this serogroup prompted an assessment of the epidemiology of serogroup B disease in Ontario, Canada. METHODS: We retrieved information on confirmed IMD cases reported to Ontario's reportable disease database between January 1, 2000 and December 31, 2010 and probabilistically-linked these cases to Public Health Ontario Laboratory records. Rates were calculated with denominator data obtained from Statistics Canada. We calculated a crude number needed to vaccinate (NNV) using the inverse of the infant (<1 year) age-specific incidence multiplied by expected vaccine efficacies between 70 % and 80 %, and assuming only direct protection (no herd effects). RESULTS: A total of 259 serogroup B IMD cases were identified in Ontario over the 11-year period. Serogroup B was the most common cause of IMD. Incidence ranged from 0.11 to 0.27/100,000/year, and fluctuated over time. Cases ranged in age from 13 days to 101 years; 21.4 % occurred in infants, of which 72.7 % were <6 months. Infants had the highest incidence (3.70/100,000). Case-fatality ratio was 10.7 % overall. If we assume that all infant cases would be preventable by vaccination, we would need to vaccinate between 33,784 and 38,610 infants to prevent one case of disease. CONCLUSIONS: Although rare, the proportion of IMD caused by serogroup B has increased and currently causes most IMD in Ontario, with infants having the highest risk of disease. Although serogroup B meningococcal vaccines are highly anticipated, our findings suggest that decisions regarding publicly funding serogroup B meningococcal vaccines will be difficult and may not be based on disease burden alone.     

Features of a large epidemic of group A meningococcal meningitis in Khartoum, Sudan in 1988

A large epidemic (February-August 1988) of group A sulphonamide resistant, clone III-1 meningococcal meningitis in Khartoum, Sudan is described. A total of 10,099 cases were admitted to treatment centers with 8,397 cases during March and April, corresponding to an annual incidence of 1,679/100,000 inhabitants during this period. The age profile showed a high morbidity in adults (31% of the cases greater than or equal to 20 years). The male dominance was marked especially in the adult cases with a proportion of 3.2:1. The epidemic started during the hot and dry season and declined when the clouds came, humidity rose, temperature fell and a mass vaccination campaign had been implemented together with other epidemic precautions. Vaccination with a combined group A/C polysaccharide vaccine had been given 4 weeks-1 year before hospitalization to 11% of the children, 80% of whom were greater than 18 months of age. The estimated case fatality rate was 6.3%. Since 47% of the cases came from periurban and rural areas, the actual mortality during the epidemic might have been higher when considering those who may have died before reaching any of the treatment centres. Fatal cases had a short history of acute illness and a septic condition. Septicaemia was rare and seen in only 3.7% of the cases, the rest had acute purulent meningitis. Hearing loss/impairment and hemiplegia was diagnosed in 2-3% of the cases. The epidemiology, based on detailed typing/subtyping and restriction enzyme patterns of meningococcal strains, was apparently associated with the Mecca outbreak in August 1987.     

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.     

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.     

Surveillance of invasive meningococcal disease in the Czech Republic

Routine notification of invasive meningococcal disease has a long tradition in the Czech Republic: mortality data are available from 1921 and morbidity data from 1943. The collection of Neisseria meningitidis strains kept in the NRL for Meningococcal Infections in Prague dates from 1970 onwards, and represents more than 3500 strains isolated from invasive disease and their contacts, from healthy carriers and from respiratory infection. Analysis of these strains showed that the Czech meningococcal population is different from that seen in western Europe. In 1993, the incidence serogroup C meningococcal disease increased and was associated with the emergence of the hypervirulent complex Neisseria meningitidis C, ST-11, ET-15/37, and caused an increase in the incidence of invasive meningococcal disease which peaked in 1995 (2.2/100,000). A vaccination strategy targeting the part of the population at highest risk of invasive meningococcal disease was adopted in the country.     

Influence of prior meningococcal C polysaccharide vaccination on the response and generation of memory after meningococcal C conjugate vaccination in young children.

To determine whether the immunological hyporesponsiveness induced by meningococcal AC polysaccharide (MACP) vaccines can be overcome by meningococcal C conjugate (MCC) vaccine in young children, serum bactericidal antibody (SBA) serogroup C-specific IgG and IgG avidity indices were measured in young children who received MACP vaccine, followed 7 months later by MCC vaccine, and their responses were compared with those in age-matched MACP-naive control children, who received a single dose of MCC vaccine. For children <1 year of age at MACP vaccination, the SBA geometric mean titer (GMT) after MCC vaccination was lower (P=.022) and proportions with SBA titers <8 (P=.0083) or <128 (P=.0091) were higher than those in the control children. For older children, there was no difference in the SBA GMTs between the study and control groups (P>.5) or in the proportion with SBA titers <8 (P=1.00) or <128 (P=.98). No increase in avidity occurred after MACP vaccination, whereas avidity increased significantly 1 month after MCC vaccination, with a further increase at 6 months, which indicates that the induction of immunological memory was not impaired.     

Systematic review: Impact of meningococcal vaccination on pharyngeal carriage of meningococci

Objective To investigate the effect of meningococcal vaccines on pharyngeal carriage of meningococci. Methods Systematic review. MEDLINE and EMBASE were searched for relevant studies. Controlled trials and observational studies which used comparison groups or compared carriage rates before and after vaccination were included in the review. Results Twenty‐nine studies satisfied the inclusion criteria. Twenty‐five studies reported the effect of a polysaccharide vaccine, one the effect of a serogroup C conjugate vaccine and three the impact of serogroup B outer‐membrane vaccines on overall and/or serogroup‐specific meningococcal carriage rates. Ten studies of meningococcal polysaccharide vaccines found reduced serogroup‐specific carriage; seven of these focussed on high‐risk groups and had a short follow‐up period. Only one of five studies of civilian populations in Africa showed a significantly reduced carriage. Many studies had methodological shortcomings. The one study which assessed the effect of a meningococcal conjugate vaccine on carriage showed a significant impact. Three studies of serogroup B outer‐membrane protein vaccines showed no effect on carriage. Conclusions A few well‐designed trials of the impact of meningococcal vaccines on carriage have been undertaken. Such studies should be an essential component of the evaluation of new meningococcal vaccines, particularly those introduced to control epidemic meningococcal disease in Africa.     

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.     

Meningococcal carriage, meningococcal disease and vaccination

Group A meningococcal carriage rates were determined 6 months before and 6 and 18 months after a mass vaccination campaign with a combined group A and group C meningococcal polysaccharide vaccine in a rural area of The Gambia. During the first pre-vaccination survey, performed during an outbreak of meningococcal disease, the carriage rate was high (16%). The carriage rate remained high during a second survey made 6 months after a vaccination campaign that covered approximately 90% of the study population. A year later very few group A meningococcal carriers were found. Membrane protein patterns of isolates obtained before and after vaccination were similar. We conclude that vaccination had little influence on the carriage rate of group A meningococci but that this was influenced by changes in herd immunity or by other unidentified factors.     

Epidemiology of invasive streptococcus pneumoniae infections in children in Spain, 1996-1998

BACKGROUND: Streptococcus pneumoniae is a significant cause of meningitis and septicemia in early infancy, being associated to a high case-fatality rates and serious sequelae. OBJECTIVE: To investigate the burden of invasive disease caused by S. pneumoniae in Valencia, Spain, during a three-year period (1996-1998). METHODS: Hospital-based prospective active surveillance program for invasive bacterial diseases in children < or = 15 years of age in Valencia, from December 1, 1995 to January 1999. RESULTS: A total of 94 cases of invasive pneumococcal disease were detected in patients < or = 15 years of age. The overall annual incidence of invasive pneumococcal disease was 4.6/100,000 persons, < or = 15 years of age. The incidence of invasive disease and meningitis was higher among children younger than 2 years of age (16.8 and 3.8, respectively). Serotypes 19, 14 and 6 accounted for 83% of the isolates. CONCLUSIONS: The age distribution of invasive pneumococcal disease and meningitis shows a peak in the first two years of life and a decline thereafter. Serotypes 19, 14 and 6 are those primarily responsible for invasive pneumococcal disease in children of this region of Spain.     

Epidemiology of meningococcal disease in Denmark 1980-1988.

Based on epidemiological data of notified cases of meningococcal disease (MD) in Denmark during the period 1980-88 the recommendations for prophylaxis are evaluated. In 1986 the incidence of MD increased about 60% to 5.5 per 100,000 population. The clinical diagnosis of MD was verified by culture of Neisseria meningitidis in 79% of notified cases. About 40% of all patients were less than 4 years of age. The mortality in 1988 was found to be 10%. Serogroup B disease accounted for about 80% of the cases. Two co-primary and 28 secondary cases were registered. Two major outbreaks of serogroup C disease occurred in 1984 and 1986, respectively. In small clusters of 2-3 cases within socially well-defined groups the recommendations for prophylaxis are sufficient. But for the new pattern of clusters spread over months to years in certain geographical areas or open social groups, especially among teenagers, the existing recommendations are insufficient. The occurrence of localized clusters of serogroup B disease emphasises the need for a vaccine against serogroup B disease.