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Cardoso CW  Pinto LL  Reis MG  Flannery B  Reis JN 《Vaccine》2012,30(37):5541-5546
To combat rising incidence of serogroup C meningococcal disease in the city of Salvador, Brazil, the Bahia state immunization program initiated routine childhood immunization with meningococcal C conjugate vaccine (MenC) in February 2010, followed by mass MenC vaccination of city residents 10-24 years of age from May through August 2010. We analyzed trends in incidence of reported cases of meningococcal disease and serogroup distribution among meningococcal isolates identified in hospital-based surveillance in Salvador from January 2000 to December 2011 and estimated vaccine effectiveness using the screening method. Annual incidence of serogroup C meningococcal disease increased from 0.1 cases per 100,000 population during 2000-2006 to 2.3 in 2009 and 4.1 in 2010, before falling to 2.0 per 100,000 in 2011. Estimated coverage of mass vaccination reached 80%, 67% and 41% among 10-14, 15-19 and 20-24 year olds, respectively. Incidence in 2011 was significantly lower than average rates in 2008-2009 among children <5 years, but reductions among 10-24 year olds were not significant. Among 10-24 year olds, a single dose of MenC vaccine was 100% effective (95% confidence interval, 79-100%) against serogroup C meningococcal disease. Low coverage in the population targeted for mass vaccination may have limited impact on ongoing transmission of serogroup C meningococcal disease despite high vaccine effectiveness.  相似文献   

3.
《Vaccine》2017,35(36):4745-4752
BackgroundAdolescents are considered the key transmitters of meningococci in the population. Meningococcal serogroup C (MenC) antibody levels wane rapidly after MenC conjugate vaccination in young children, leaving adolescents with low antibody levels. In this study, we compared MenC immune responses after booster vaccination in adolescence with either tetanus toxoid conjugated MenC (MenC-TT) or MenACWY (MenACWY-TT) vaccine, and aimed to establish an optimal age for this booster.MethodsHealthy 10-, 12-, and 15-year-olds, who received a single dose of MenC-TT vaccine in early childhood, were randomized to receive MenC-TT or MenACWY-TT vaccine. MenC serum bactericidal antibody (rSBA) titers, MenC polysaccharide (PS) specific IgG, IgG1 and IgG2 and MenC-specific IgG and IgA memory B-cells were determined before, one month and one year after the booster. Non-inferiority was tested by comparing geometric mean titers (GMTs) between vaccinees at one year.ResultsOf 501 participants, 464 (92.6%) were included in the ‘according to protocol’ cohort analysis. At one month, all participants developed high MenC rSBA titers (>24,000 in all groups) and MenC-PS-specific IgG levels. Non-inferiority was not demonstrated one year after the booster with higher MenC GMTs after the monovalent vaccine, but 462/464 (99.6%) participants maintained protective MenC rSBA titers. IgG levels mainly consisted of IgG1, but similar levels of increase were observed for IgG1 and IgG2. Both vaccines induced a clear increase in the number of circulating MenC-PS specific IgG and IgA memory B-cells. Between one month and one year, the highest antibody decay rate was observed in the 10-year-olds.ConclusionBoth MenC-TT and MenACWY-TT vaccines induced robust protective MenC immune responses after the booster vaccination, although non-inferiority could not be demonstrated for the MenACWY-TT vaccine after one year. Our results underline the importance of optimal timing of a meningococcal booster vaccination to protect against MenC disease in the long-term.  相似文献   

4.
《Vaccine》2018,36(29):4222-4227
IntroductionIn Tuscany, Italy, where a universal immunization program with monovalent meningococcal C conjugate vaccine (MCC) was introduced in 2005, an outbreak of invasive meningococcal disease (IMD) due to the hypervirulent strain of Neisseria meningitidis C/cc11 occurred in 2015–2016, leading to an immunization reactive campaign using either the tetravalent (ACWY) meningococcal conjugate or the MCC vaccine. During the outbreak, IMD serogroup C (MenC) cases were also reported among vaccinated individuals. This study aimed to characterize meningococcal C conjugate vaccines (MenC-vaccines) failures and to estimate their effectiveness since the introduction (2005–2016) and during the outbreak (2015–2016).MethodsMenC cases and related vaccine-failures were drawn from the National Surveillance System of Invasive Bacterial Disease (IBD) for the period 2006–2016. A retrospective cohort-study, including the Tuscany' population of the birth-cohorts 1994–2014, was carried out. Based on annual reports of vaccination, person-years of MenC-vaccines exposed and unexposed individuals were calculated by calendar-year, birth-cohort, and local health unit. Adjusted (by birth-cohort, local health unit, and calendar-year) risk-ratios (ARR) of MenC invasive disease for vaccinated vs unvaccinated were estimated by the Poisson model. Vaccine-effectiveness (VE) was estimated as: VE = 1-ARR.ResultsIn the period 2006–2016, 85 MenC-invasive disease cases were reported; 61 (71.8%) from 2015 to 2016. Twelve vaccine failures occurred, all of them during the outbreak. The time-interval from immunization to IMD onset was 20 days in one case, from 9 months to 3 years in six cases, and ≥7 years in five cases. VE was, 100% (95%CI not estimable, p = 0.03) before the outbreak (2006–2014) and 77% (95%CI 36–92, p < 0.01) during the outbreak; VE was 80% (95%CI 54–92, p < 0.01) during the overall period.ConclusionsIn Tuscany, MenC-vaccine failures occurred exclusively during the 2015–2016 outbreak. Most of them occurred several years after vaccination. VE during the outbreak-period was rather high supporting an effective protection induced by MenC-vaccines.  相似文献   

5.
《Vaccine》2020,38(14):2995-3002
Meningococcal carriage studies are important to improve the knowledge of disease epidemiology as well as to support appropriate vaccination strategies. We conducted a cross-sectional study to determine the prevalence and genotypic characteristics of meningococci collected from young adults in Salvador, Brazil six years after a meningococcal C conjugate vaccine catch-up campaign. From August through November 2016, oropharyngeal swabs were collected from 407 students aged 1824 years attending a private college in Salvador, Brazil. Neisseria meningitidis was identified by standard microbiology methods and real time PCR. Genetic characteristics of meningococci were assessed by rt-PCR and/or whole genome sequencing. We also investigated potential factors associated with carriage. N. meningitidis was detectable in 50 students, 39 by both culture and rt-PCR, 7 by culture alone and 4 by rt-PCR alone, resulting in an overall meningococcal carriage prevalence of 12.3% (50/407). Carriage was independently associated with male sex (adjusted PR: 1.97; 95% CI: 1.12–3.46; p = 0.018) and attending bars or parties at least once per month (aPR: 3.31; 95% CI: 1.49–7.38; p = 0.003). Molecular tests identified 92% (46/50) N. meningitidis as non-groupable, of which 63% (29/46) had the capsule null genotype; 14 NG isolates contained disrupted capsule backbones and belonged to the following genogroups: 7 B, 3 Z, 3 E and 1 W. One isolate belonged to genogroup C tested only by PCR; 3 isolates contained a complete B capsule backbones, 2 of which were determined to be NG by slide agglutination serogrouping. While most meningococcal carriage isolates were non-groupable, there was a high degree of genetic diversity present in the collection, as evidenced by 25 unique STs being detected. The carriage prevalence of meningococcal serogroup C was low among young adults. Continuous vaccination is important to maintain reduced meningococcal carriage and transmission, inducing herd protection.  相似文献   

6.
BACKGROUND: Increasing numbers of outbreaks of Group C meningococcal disease in teenagers and young adults led to a new policy in the UK in 1999 of vaccinating all new college students. The largest of these outbreaks involved seven students in one university, six of whom were from one hall of residence, and two of whom died. METHODS: Control of the outbreak involved close medical surveillance of resident students, mass chemoprophylaxis and vaccination, and wide dissemination of daily information bulletins. Investigation of the epidemiology of the outbreak involved searching for the network of close contacts between cases, a prevalence survey of carriage of meningogocci and a case control study of risk factors for carriage. RESULTS: Clinical cases could be linked by a discrete network of social contacts within the halls of residence, but the Group C epidemic strain (2a P1.5) was not detected in 454 students (upper 95% confidence interval 0.7%). Carriage of any meningococcal strain (19%) was associated with patronage of the campus bar (OR = 3.0, 0.99-9.1). CONCLUSION: Important factors in the control of the outbreak were rapid institution of mass chemopropylaxis and immunisation of residents, and involvement of student organizations in the dissemination of information about the disease and its control. The role of campus bars in dissemination of the carriage of meningogocci deserves further investigation.  相似文献   

7.
《Vaccine》2020,38(40):6267-6273
The Meningococcal Serogroup C Conjugate Vaccine (MenC) was introduced into the Brazilian Immunization Program in 2010. However, in Salvador, the fourth largest capital in Brazil, an extended catch-up campaign was conducted earlier in that year, which focused on adolescents and young adults aged 10–24 years. To evaluate the long-term impact of MenC vaccination, we analyzed hospital-based surveillance data on cases of meningococcal disease in the Salvador metropolitan region during the pre-vaccine (2005–2009) and post-vaccine (2011–2016) campaign periods. Six years after the introduction of the MenC vaccine, the mean incidence rate decreased from 3.20 to 0.93 cases per 100,000 individuals (71% reduction, 95% CI [58.7–83.3]) in children <4 years. Reductions of 25.6% and 21.1% were also observed for the age groups of 5–9 and 10–14 years, respectively. On the other hand, incidence increased in the 15–24-year age group from 0.72 to 1.11, and from 0.31 to 0.60 in individuals aged >25 years (p < 0.05). At the end of the study period, serogroup C was the most prevalent (65.7%), followed by serogroups B (9.8%), W (2.3%), Y (1.6%) and A (1.0%); serogrouping was not possible in 19.6% of the cases, or adequate material was not available for serogroup identification. The use of real-time PCR from 2010 onwards increased detection rates of meningococcal meningitis by 29.6%. The long-term impact of the MenC vaccination campaign was associated with a significant reduction in MenC disease in children aged 0–4 years, yet no effect was observed in adolescents and adults, as evidenced by increasing trends in infection rates. In addition, the emergence of meningococcal serogroup A was identified, which should serve as an alert to public health officials and deserves further investigation.  相似文献   

8.
Secretor status, smoking and carriage of Neisseria meningitidis   总被引:1,自引:0,他引:1  
A survey of ABO blood groups, secretor status and smoking habits among 389 students and staff of a school in which there was an outbreak of meningococcal disease found no difference in the distribution of the ABO blood groups but a significantly higher proportion of non-secretors (37.6%) in the population examined compared with that reported for previous surveys of the neighbouring population in Glasgow (26.2%) (P less than 0.0005). There was also a significantly higher proportion of non-secretors among carriers of meningococci (47%) compared with non-carriers (32%). Increased carriage of meningococci among non-secretors might contribute to the increased susceptibility of individuals with this genetic characteristic to meningococcal disease observed in previous studies. Although passive exposure to cigarette smoke has been associated with meningococcal disease, there was no association between passive smoking and carriage. There was, however, a significant association between active smoking and carriage.  相似文献   

9.
In a school outbreak of meningococcal disease in Wales, we compared risk factors for the carriage of Neisseria meningitidis B15 P1.16 with carriage of any meningococci. Students had throat swabs and completed a questionnaire. Sixty (7.9%) carried meningococci; risk for carriage was higher in those >14 years of age.  相似文献   

10.
Since the introduction of monovalent meningococcal serogroup C (MenC) glycoconjugate (MCC) vaccines and the implementation of national vaccination programmes, the incidence of MenC disease has declined markedly as a result of effective short-term vaccination and reduction in acquisition of MenC carriage leading to herd protection. Monovalent and quadrivalent conjugate vaccines are commonly used vaccines to provide protection against MenC disease worldwide. Studies have demonstrated that MCC vaccination confers protection in infancy (0–12 months) from the first dose but this is only short-term. NeisVac-C® has the greatest longevity of the currently licensed MCC vaccines in terms of antibody persistence, however antibody levels have been found to fall rapidly after early infant vaccination with two doses of all MCC vaccines – necessitating a booster at ∼12 months. In toddlers, only one dose of the MCC vaccine is required for routine immunization. If herd protection wanes following catch-up campaigns, many children may become vulnerable to infection. This has led many to question whether an adolescent booster is also required.  相似文献   

11.
A population-based study was carried out in Catalonia (Spain) from May 1998 to April 1999 to determine the prevalence of Neisseria meningitidis strains in meningococcal disease (MD) cases and their contacts, as well as the prevalence of meningococci in close contacts of patients with MD, and risk factors for its carriage. A total of 364 close contacts of 87 patients with MD were studied. Throat samples were collected by hospital staff before rifampicin chemoprophylaxis was begun. For each contact, a questionnaire was completed for sociodemographic and epidemiological data. A total of 61 contacts (an overall prevalence of 16.8%) were carriers of meningococcal strains (40 B, 10 C, 1 Z and 10 non-groupable isolates). This prevalence is two to three times higher than in the general population (5-10%). In 33/61 microbiologically confirmed cases (54%) and in 9/26 probable cases (35%), contacts carrying N. meningitidis were found. In 22/33 confirmed cases with carrier contacts, it was possible to study the phenotype of the carrier and patient strains (sero-group, serotype and serosubtype). In 14 cases (64%), both strains were identical, in four cases, only a minor change was observed, in three cases, some strain (from the case or from his contact) was non-serotypable and non-serosubtypable, and in one case, both isolates were completely different. Bivariate analysis identified five statistically significant risk factors for meningococcal carriage: age (5-9 years old), meningococcal A+C vaccination, severe household overcrowding, social class and heavy active smoking (>20 cigarettes a day). Multivariate analysis revealed that of these five variables, only heavy active smoking remained statistically significant when the other factors were controlled.  相似文献   

12.
Emergence of serogroup B meningococci of clonal complex sequence type (ST) 41/44 can cause high levels of disease, as exemplified by a recent epidemic in New Zealand. Multiplication of annual incidence rates (3.1 cases/100,000 population) of meningococcal disease in a defined German region, the city of Aachen and 3 neighboring countries (Greater Aachen) prompted us to investigate and determine the source and nature of this outbreak. Using molecular typing and geographic mapping, we analyzed 1,143 strains belonging to ST41/44 complex, isolated from persons with invasive meningococcal disease over 6 years (2001–2006) from 2 German federal states (total population 26 million) and the Netherlands. A spatially slowly moving clone with multiple-locus variable-number tandem repeat analysis type 19, ST42, and antigenic profile B:P1.7–2,4:F1–5 was responsible for the outbreak. Bactericidal activity in serum samples from the New Zealand MeNZB vaccination campaign confirmed vaccine preventability. Because this globally distributed epidemic strain spreads slowly, vaccination efforts could possibly eliminate meningococcal disease in this area.  相似文献   

13.
Trotter C  Borrow R  Andrews N  Miller E 《Vaccine》2003,21(11-12):1094-1098
Sera from an age-stratified sample of 1689 individuals, submitted to the PHLS Seroepidemiology Unit between 1996 and 1999 were tested for serum bactericidal antibodies to serogroup C meningococci. Titres decreased during infancy, presumably as maternal antibody waned, and increased in older teenagers, the peak age of meningococcal carriage. The prevalence of antibody titres greater than or equal to 8 was highest in adults, with an average of 25% of adults 25 years old or above with titres above this putative protective level. In the absence of vaccination, antibody may be generated from periods of carriage of serogroup C meningococci, from other meningococcal strains sharing non-capsular antigens, and other cross-reactive organisms. The inverse relationship between disease incidence and the prevalence of 'protective' antibody titres as described by Goldschneider et al. appears more consistent with a titre of > or =8 rather than > or =128, although the proportions 'protected' are much lower here than in Goldschneider's study. This study provides baseline antibody levels which will facilitate the evaluation of the meningococcal serogroup C conjugate vaccination programme.  相似文献   

14.
《Vaccine》2020,38(27):4236-4245
The long-term persistence of antibody responses following primary vaccination with quadrivalent conjugate vaccines targeting meningococcal serogroups A, C, W, and Y (MenACWY) and the duration of protection following a booster dose have not been fully elucidated, particularly in children who received primary dosing as toddlers. This review summarizes the findings of one phase 3 and three phase 2 open-label, randomized clinical studies that assessed the long-term antibody persistence of MenACWY conjugated to tetanus toxoid as a carrier protein (MenACWY-TT) in toddlers. Following primary vaccination, antibody responses persisted for approximately 2–3 years and then decreased up to 5 years after vaccination. Geometric mean titers remained elevated for all serogroups up to 5 years after primary vaccination. In children who received a booster dose of MenACWY-TT at 4–5 years after primary dosing as toddlers, antibody responses were documented in >99% of subjects across all serogroups, with minimal decreases in antibody persistence from 2–6 years after booster vaccination. The persistence of meningococcal serogroup C (MenC) antibody responses was similar between MenACWY-TT and MenC vaccine recipients after primary and booster dosing. Together, these findings indicate that antibody responses to primary MenACWY-TT vaccination persist for 2–3 years. Additionally, these findings indicate that in subjects who receive primary MenACWY-TT vaccination as toddlers, the antibody response to booster MenACWY-TT vaccination lasts for up to 6 years and suggest that immune memory is afforded at least into early adolescence, which is an age group at increased risk of invasive meningococcal disease.  相似文献   

15.
《Vaccine》2016,34(36):4278-4284
IntroductionMultiple vaccination visits and administrations can be stressful for infants, parents and healthcare providers. Multivalent combination vaccines can deliver the required number of antigens in fewer injections and clinic visits, while vaccine co-administration can also reduce the number of visits. This non-inferiority study was undertaken to evaluate the feasibility of co-administering a combined measles-mumps-rubella-varicella (MMRV) vaccine with conjugated meningococcal C (MenC) vaccine in a large cohort of healthy Italian toddlers.MethodsHealthy subjects aged 13–15 months were randomized (2:1:1) to receive single doses of either: co-administered MMRV + MenC at the same visit (MMRV + MenC group); or MMRV followed 42 days later by MenC (MMRV group); or MenC followed 42 days later by MMRV (MenC group). Blood samples were collected before and 43 days after vaccination. Antibody titers against MMRV were measured using ELISA. Functional-anti-meningococcal-serogroup activity (rSBAMenC) was assessed using a serum bactericidal test. Solicited local and general reactions were recorded for up to 4 and 42 days post-vaccination, respectively. Non-inferiority of MMRV + MenC to MMRV (post-dose-1 seroconversion rates) and MMRV + MenC to MenC (post-dose-1 seroprotection rates) was achieved if the lower limit (LL) of the 95% confidence interval (CI) for the group difference was ⩾−10% for each antigen.Results716 subjects were enrolled in the study. At 42 days post-vaccination, the MMRV seroconversion rates were 99.3% (measles), 94.5% (mumps), 100% (rubella) and 99.7% (varicella) in the MMRV + MenC group, and 99.4%, 93.2%, 100% and 100%, respectively, in the MMRV group. The seroprotection rates against rSBA-MenC were 98.3% in the MMRV + MenC group and 99.3% in the MenC group. Non-inferiority was reached for all the vaccine antigens. The safety profiles were as expected for these vaccines.ConclusionThe immune responses elicited by co-administered MMRV + MenC were non-inferior to those elicited by MMRV or MenC alone and support vaccination of children with both vaccines at a single visit.Clinical Trials registration: NCT01506193.  相似文献   

16.
A total of 6234 nasopharyngeal swabs was collected during a survey of the population of Stonehouse, Gloucestershire in November 1986 as part of an investigation into an outbreak of meningococcal disease. The overall meningococcal carriage rate was 10.9%. The carriage rate rose with age from 2.1% in the 0- to 4-year-olds to a peak of 24.5% in the 15- to 19-year-olds, and thereafter declined steadily with age. Male carriers outnumbered female carriers of meningococci by 3:2. Group B (or non-groupable) type 15 sulphonamide-resistant strains which had caused the outbreak were isolated from 1.4% of subjects. The age distribution of carriers of these strains was similar to that of other meningococci apart from an additional peak in the 5-9-year age group and a more rapid decline in carriage with increasing age. Variations in the carriage rates of the outbreak strain were seen in children attending different schools and in the residents of different areas of the town. The low carriage rate of these strains in a community during a prolonged outbreak supports the hypothesis that these organisms are less transmissible but more virulent than other strains of pathogenic meningococci. Carriage of Neisseria lactamica, which is thought to be important in the development of meningococcal immunity, was most frequent in children under the age of 5 years and was six times commoner in this age group than carriage of Neisseria meningitidis. In older children and adults female carriers of N. lactamica increasingly outnumbered males in contrast to the male preponderance observed with meningococcal carriage.  相似文献   

17.
《Vaccine》2015,33(1):268-275
ObjectiveAdvisory committees in Canada and the United States have updated recommendations for quadrivalent meningococcal conjugate vaccines against serogroups A, C, W135, and Y. Our objective was to evaluate optimally effective meningococcal vaccination policies using a stochastic dynamic model. Canada was used as an example.MethodsOur stochastic dynamic model of Neisseria meningitidis (Nm) transmission in an age-structured population assumed partial cross-immunity among two aggregated serogroup categories: ‘AWY’ containing A, W135, and Y; and ‘Other’ containing B, C, and ungroupable types. We compared the impact of monovalent C versus quadrivalent ACWY vaccination on Nm carriage and invasive meningococcal disease (IMD). Our model was parameterized with Canadian epidemiological and demographic data and employed probabilistic sensitivity analysis.ResultsRoutine infant immunization at 12 months and boosting at 15 years with a quadrivalent vaccine is projected to have the largest impact on total IMD incidence: a 74% reduction over 40 years. Routine infant immunization with a monovalent vaccine at 12 months only has much less impact and also generates strain replacement appearing after approximately ten years of continuous use.ConclusionsImmunizing infants at 12 months and boosting adolescents at 15 years with an ACWY vaccine is predicted to be most effective at reducing IMD incidence.  相似文献   

18.
Military recruits serving in the armed forces were severelyaffected during the latest serogroup B meningococcal epidemicin Norway. The risk of developing systemic meningococcal disease(SMD) proved highest during the first 12 weeks of service. Adouble-blind, placebo-controlled protection trial with a meningococcalouter membrane vesicle vaccine took place between 1988 and 1991,but the number of proven SMD cases was too low to allow forany conclusions. However, the results of a parallel efficacystudy of the same vaccine among students in secondary school,cross-society examinations for asymptomatic throat carriageof meningococci and recent immunogenicity studies after two-and three-dose vaccination schedules, suggest that a basic immunizationof young teenagers followed by a booster injection at enrolmentwould contribute significantly to preventing SMD in the armedforces.  相似文献   

19.
目的观察国产A C脑膜炎多糖疫苗(A C疫苗)的接种反应和免疫原性。方法以A C疫苗为观察苗、伤寒Vi多糖疫苗(Vi疫苗)为对照苗,采样用整群随机对照的临床试验方法,确定观察人群和对照人群。在已接种的两组人群中,采取整群分层抽样的方法抽取接种反应观察对象,并进行连续3天随访以观察接种反应。采集部分A C疫苗接种对象免前、免后血标本,检测血清抗体IgG4倍增长情况。结果共随访接种反应观察对象1239人,其中接种流脑A C疫苗的771人、接种伤寒Vi疫苗的468人。A C疫苗接种后第1天局部反应发生率为15.06%,第2天的为0.13%,第3天的为0;接种后第1天全身反应的发生率为1.16%,第2天为0.39%和第3天为0.13%。除接种后第1天A C疫苗的局部反应发生率要明显高于Vi疫苗的外,接种后2天、3天的局部反应和第1、2、3天全身反应的发生率,A C疫苗和Vi疫苗无显著性差异。共采集A C疫苗接种对象免前、免后血标本各100份,抗C群脑膜炎球菌抗体4倍增长率达到94%,抗A群脑膜炎球菌抗体仅达到62%。结论A C疫苗和伤寒Vi多糖疫苗一样,接种反应轻微,安全性好;抗C群脑膜炎球菌抗体免疫应答良好。接种前人群血清抗A群脑膜炎球菌抗体平均浓度比抗C群的高2.6倍,抗A群脑膜炎球菌抗体4倍增长率低可能与本底抗A群脑膜炎球菌抗体水平高有关。  相似文献   

20.
Neisseria meningitidis capsular switching has been reported in several countries. In order to establish the genetic relationship within group B and C strains expressing subtypes 2a or 2b, and to evaluate whether C to B capsular switching occurred in Portugal, 64 meningococci (56 serogroup C and 8 serogroup B) isolated from invasive meningococcal disease were typed using molecular methods. The studied phenotypes, 2b:P1.5,2 and 2a:P1.5-1,10-8, were the most frequent among serogroup C, but were uncommon among serogroup B strains. The multi-locus sequence typing (MLST) allelic profile and the pulsed-field gel electrophoresis (PFGE) fingerprints showed that seven serogroup B strains were genotypically identical to C strains, suggesting that capsular switching occurred. Active laboratory surveillance to find evidence of capsule switching is a now priority as MenC was introduced in the Portuguese vaccination schedule in January 2006.  相似文献   

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