0
Brief Report |

Effectiveness of a Mass Immunization Campaign Using Serogroup C Meningococcal Conjugate Vaccine FREE

Philippe De Wals, MD, PhD; Geneviève Deceuninck, MD; Nicole Boulianne, MSc; Gaston De Serres, MD, PhD
[+] Author Affiliations

Author Affiliations: Quebec National Public Health Institute and Department of Preventive and Social Medicine, Laval University (Drs De Wals and De Serres and Ms Boulianne), and the Public Health Research Unit, Quebec University Hospital Center (Drs De Wals, Deceuninck, and De Serres and Ms Boulianne), Quebec City, Quebec.

More Author Information
JAMA. 2004;292(20):2491-2494. doi:10.1001/jama.292.20.2491.
Text Size: A A A
Published online

Context Meningococcal polysaccharide vaccines are of limited effectiveness. New protein-polysaccharide conjugate vaccines have yet to be evaluated in field conditions.

Objective To assess the effectiveness of a serogroup C conjugate meningococcal vaccine in an outbreak setting.

Design, Setting, and Participants Population-based observational study of cases of invasive serogroup C meningococcal disease from 1996 through 2002 in Quebec identified from the provincial registry of notifiable diseases and from the provincial reference laboratory. In 2001, a mass immunization campaign with a conjugate vaccine was conducted to control an emerging epidemic. The number of vaccinated individuals was extracted from meningococcal immunization registries.

Main Outcome Measures Incidence of invasive meningococcal disease before and 1 year after the campaign in vaccinated and unvaccinated individuals.

Results Vaccination coverage of those 2 months to 20 years was 82.1%. After the campaign, the number of cases of serogroup C disease decreased from 58 in 2001 to 27 in 2002, and the incidence from 7.8 per million to 3.6 per million. Vaccine effectiveness was found to be 96.8% (95% confidence interval, 75.0%-99.9%). There was no observed increase in the incidence of the other serogroups.

Conclusion The new conjugate vaccine was effective in controlling an emerging epidemic of serogroup C meningococcal disease, as well as providing short-term protection across a wide age range.

Figures in this Article

Serogroup C polysaccharide meningococcal vaccines are not effective in young children, and protection is of short duration in older children and adults.1 In contrast, protein-polysaccharide conjugate vaccines elicit a T-cell dependent immunologic response that is present in young infants and characterized by the production of high levels of high-avidity bactericidal antibodies and the induction of immunologic memory.2 The use of bactericidal assays and possibly other functional tests has been proposed as a standard to license new meningococcal conjugate vaccines, as phase 3 randomized trials aiming at assessing vaccine efficacy would be impracticable.3,4(pp371-393) However, carefully conducted observational studies are of paramount importance to evaluate the effectiveness of these new vaccines.

An increase in the incidence of meningococcal disease was identified in the province of Quebec in 1990, caused by a virulent C:2a ET15 clone.5,6 To control the epidemic, a mass immunization campaign was conducted in the winter of 1992-1993, using polysaccharide vaccines and targeting the population between the ages of 6 months and 20 years.7 Disease incidence decreased markedly in the following years. In February of 2001, several outbreaks caused by a parent clone occurred, mainly in the Quebec City area.8 Localized immunization programs using plain polysaccharide vaccines were conducted that targeted secondary school students. However, the epidemic extended to younger age groups and other regions, generating a high level of anxiety in the population and extensive media coverage. A serogroup C oligosaccharide-CRM197 protein conjugate vaccine (Menjugate, Chiron, Emeryville, Calif) was licensed following a fast-track process and a mass immunization campaign was launched in the Quebec City area from May through June 2001. The campaign was extended to other regions during the autumn of 2001, targeting all residents in the province between the ages of 2 months and 20 years. The vaccine was mainly administered through the local public health units in special clinics and education facilities. This intervention provided a unique opportunity to assess the effectiveness of the conjugate vaccine.

The population targeted for vaccination encompassed all residents in the province of Quebec born between July 17, 1980, and November 30, 2001. The size of the target population and its age distribution on January 31, 2002, was estimated from projections based on the 1996 census. A meningococcal immunization registry was established in the Quebec City region in the spring of 2001 and a provincial registry was established in the fall of 2001. This enabled the processing of immunization records received from vaccine providers, both nurses and physicians, in public health units and private clinics. Data concerning the number of vaccinated individuals and doses administered were extracted from the 2 registries.

Cases of invasive meningococcal disease were identified from the provincial registry of notifiable diseases. Any case suspected or diagnosed by a physician or a laboratory had to be reported to the regional public health department. An investigation was conducted by the public health department to collect additional information, including the clinical presentation and outcome, the vaccination status of the patient, and the results of diagnostic tests. Cases were classified as clinical or confirmed according to standardized criteria.9 Hospital laboratories were asked to transmit samples and/or cultures to the Quebec Public Health Laboratory for confirmation of the bacteriological diagnosis and strain characterization. Polymerase chain reaction and additional strain characterization tests were performed by the Health Canada National Reference Laboratory in Winnipeg.10 The list of cases identified by the Quebec Public Health Laboratory in 1996-2002 was cross-checked against the notifiable diseases file.

Incidence rates for serogroup C disease were calculated as number of cases divided by mid year projections of the population of Quebec based on the 1996 census obtained from the Institut de La Statistique du Quebec. Incidence rates in the total population and target population 2 months to 20 years were compared between the period 1996-2000 (before the mass vaccination campaign), 2001 (during the outbreak), and 2002 (after the campaign). The incidence rates of serogroup B and serogroup Y meningococcal disease were also compared to identify any ecological effect. To assess vaccine effectiveness, the incidence of confirmed serogroup C meningococcal disease during the year 2002 was compared between vaccinated and unvaccinated individuals in the target population. Vaccine effectiveness was defined as 1 minus the relative risk of disease (or the odds ratio).11 Confidence intervals and P values were computed using StatXact software.12P<.05 was considered statistically significant. The study was approved by the Quebec Ministry of Health and Social Services.

The population of Quebec was 7 399 931, while the target population (2 months to 20 years) included 1 919 070 individuals. During the mass campaign, 51 781 doses of plain polysaccharide vaccine were administered, mainly to adolescents in the Quebec City area. A total of 1 606 635 doses of serogroup C congugate vaccine were administered; 1 524 003 individuals received at least 1 dose. The vast majority of vaccines (94.7%) were given before December 31, 2001, and the vaccines administered in 2002 were mostly second and third doses given to young infants. Vaccination coverage was 82.1%; 81.5% were fully immunized. Vaccine coverage was higher in children aged 6 through 16 years than in younger or older age groups (Figure 1).

Figure 1. Immunization Coverage of Target Population
Graphic Jump Location

The number of cases of serogroup C meningococcal disease reported in Quebec from 1996 to 2000 ranged from 3 to 12. In 2001, the number of cases suddenly increased to 58 (Table 1). In 2002, the year following the mass campaign, the number of cases of serogroup C decreased to 27 but was still higher than in the endemic period 1996-2000. The incidence rates were 1.04 per million in 1996-2000, 7.84 in 2001 (P<.001), and 3.63 in 2002 (P<.001 comparing 2001 rates; Table 2). For the age group targeted for vaccination, the incidence increased from 2.90 per million in 1996-2000 to 21.47 in 2001, then decreased to 3.26 in 2002. In contrast, for those 21 years and older, the incidence was similar between 2001 (3.26) and 2002 (3.77; Table 2).

Table Graphic Jump LocationTable 1. Cases of Invasive Meningococcal Disease Reported in the Province of Quebec, According to Serogroup, 1996-2002*
Table Graphic Jump LocationTable 2. Incidence of Serogroup C Meningococcal Disease in the Province of Quebec by Age Group

For serogroup B, the incidence rate in 2002 (4.0 per million) was close to that observed in the period between 1996-2000 (3.8 per million, P = .26). For serogroup Y, the incidence rate in 2002 (0.7 per million) was not significantly different than in the period 1996-2000 (1.2 per million, P = .07).

In the Quebec City area (Figure 2), the number of cases of serogroup C in the population younger than 21 years decreased markedly after the mass campaign. However, sporadic cases continued to occur in individuals exceeding this age bracket. A similar pattern was observed throughout the entire province (Figure 2). A second wave of the epidemic was expected to occur in the winter 2001-2002 but was not observed.

Figure 2. Monthly Number of Cases of Serogroup C Meningococcal Disease in the Quebec City Area and the Province of Quebec, 2001-2002
Graphic Jump Location

In 2002, 7 serogroup C cases were reported among unvaccinated individuals from the target population, and 2 cases of vaccine failure were documented. The first reported case was a 19-year-old man with meningococcemia and meningitis, confirmed by blood culture. He had received a first dose of polysaccharide vaccine in 1993 and a second dose in 2001. The second reported case was a 16-year-old girl with meningitis, confirmed by a polymerase chain reaction test in a blood specimen. She had been treated for an astrocytoma 2 years previously and had received the conjugate vaccine in 2001. Overall, the effectiveness of the conjugate vaccine was 96.8% (95% confidence interval, 75.0%-99.9%).

In Quebec, a mass immunization campaign relying primarily on a serogroup C conjugate vaccine was successful in controlling an emerging epidemic, and a high level of protection was provided over a wide age range of individuals. The 96.8% effectiveness rate measured in the present study is close to the 88% to 96% short-term effectiveness rates observed in the United Kingdom, where 3 different conjugate vaccines have been used for a routine infant immunization program with a catch-up program for older individuals.13,14 In the year following the first mass immunization campaign in Quebec in 1993, the age-adjusted effectiveness rate of the serogroup C polysaccharide vaccine was 74.3% (95% confidence interval, 9.5%-91.6%).1

In industrialized countries, meningococcal diseases are infrequent, even during outbreaks, and confidence intervals for estimates of vaccine effectiveness from observational studies are likely to be wide, even when conducted in large populations. This proved to be a major limitation of our study.

Although selection bias is always possible, in recent years, the increasing use of polymerase chain reaction tests has improved the diagnosis of cases of invasive meningococcal disease.4(pp23-39) This technique is now widely used in Quebec and is included in the case-definition.9 The completeness of reporting of meningococcal disease to public health authorities has been estimated to be 94% in the Montreal, Quebec, area, using hospital records as a reference.15

Similarly, confounding bias is unlikely. Following the 1992-1993 mass immunization campaign in Quebec, polysaccharide vaccine effectiveness was measured in a case-control study, and vaccine effectiveness estimates did not change markedly when potential confounders such as socioeconomic variables were included in the analysis.16 Finally, only short-term protection was assessed. More studies are needed to assess long-term protection, especially for individuals vaccinated before the age of 1 year in whom immunity may wane, as observed in the United Kingdom.17

Corresponding Author: Philippe De Wals, MD, PhD, Département de Médecine sociale et préventive, Université Laval, Pavillon de l'Est, 2180 chemin Sainte-Foy, Québec, Canada G1K 7P4 (Philippe.De.Wals@ssss.gouv.qc.ca).

Author Contributions: Dr De Wals had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: De Wals, Deceuninck, Boulianne.

Acquisition of data: Deceuninck, Boulianne.

Analysis and interpretation of data: De Wals, Deceuninck, Boulianne, De Serres.

Drafting of the manuscript: De Wals, Deceuninck.

Critical revision of the manuscript for important intellectual content: De Wals, Deceuninck, Boulianne, De Serres.

Statistical analysis: De Wals, Deceuninck, De Serres.

Obtained funding: De Wals, Boulianne.

Administrative, technical, or material support: De Wals.

Study supervision: De Wals, Boulianne, De Serres.

Funding/Support: The study was supported by the Quebec Ministry of Health and Social Services.

Role of the Sponsor: The Quebec Ministry of Health and Social Services had no role in the design and conduct of the study; in the collection, management, analysis, and interpretation of the data; or in the preparation, review, and approval of the article.

Previous Presentation: The results of this study have been presented in a poster session at the 12th Interscience Congress on Infectious Diseases, held March 4 through 7, 2004, Cancun, Mexico.

Acknowledgment: Manon Lorange and Louise Ringuette from the Quebec Public Health Laboratory, Diane Audet, and Manale Ouakki from the Quebec Hospital Research Center, and Sylfreed Minzunza from the Quebec Ministry of Health and Social Services provided valuable assistance for the study.

De Wals P, De Serres G, Niyonsenga T. Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec.  JAMA. 2001;285:177-181
PubMed   |  Link to Article
National Advisory Committee on Immunisation.  Statement on recommended use of meningococcal vaccines.  Can Commun Dis Rep. 2001;27:2-36
PubMed
Borrow R, Andrews N, Goldblatt D, Miller E. Serologic basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: revaluation of correlates of protection.  Infect Immun. 2001;69:1568-1573
PubMed   |  Link to Article
Farrington P, Miller E. Meningococcal vaccine trials. In: Pollard AJ, Maiden MCJ, eds. Meningococcal Vaccines (Methods and Protocols). Totowa, NJ: Humana Press; 2001
Lavigne P, Boulianne N, Fortin C, Naccache H, Douville-Fradet M. Meningococcal infections in Quebec—1991-1992.  Can Commun Dis Rep. 1992;18:113-116
PubMed
Ashton FE, Ryan JA, Borczyk A, Caugant DA, Mancino L, Huang D. Emergence of a virulent clone of Neisseria meningitidis serotype 2a that is associated with meningococcal group C disease in Canada.  J Clin Microbiol. 1991;29:2489-2493
PubMed
De Wals P, Dionne M, Douville-Fradet M, Boulianne N, Drapeau J, De Serres G. Impact of a mass immunization campaign against serogroup C meningococcus in the province of Quebec, Canada.  Bull World Health Organ. 1996;74:407-411
PubMed
Squires SG, Deeks SL. Enhanced surveillance of invasive meningococcal disease in Canada: 1 January, 1999, through 31 December, 2001.  Can Commun Dis Rep. 2004;30:17-28
PubMed
Direction générale de la santé publique.  Protocole d’iintervention: Infections Méningococciques. Québec, Québec: Ministère de la santé et des Services sociaux; 1994
Tsang RSW, Squires SG, Tam TWS. Characterization of Neisseria meningitidis strains isolated from invasive meningococcal disease in Canada.  Can J Microbiol. 2003;49:633-638
PubMed   |  Link to Article
Orenstein WA, Bernier RH, Hinman AR. Assessing vaccine efficacy in the field: further observations.  Epidemiol Rev. 1988;10:212-241
PubMed
 StatXact 4 for WindowsCambridge, Mass: CYTEL Software Corp; 1999
Miller E, Salisbury D, Ramsay M. Planning, registration, and implementation of an immunization campaign against meningococcal serogroup C disease in the UK: a success story.  Vaccine. 2002;20:(suppl 1)  S58-S67
Link to Article
Bose A, Coen P, Tully J, Viner R, Booy R. Effectiveness of meningococcal C conjugate vaccine in teenagers in England.  Lancet. 2003;361:675-676
PubMed   |  Link to Article
Rivest P, Sagot B, Bedard L. Evaluation of the completeness of reporting of invasive meningococcal disease.  Can J Public Health. 1999;90:250-252
PubMed
De Wals P, Deceuninck G, De Serres G, Duval B, Remis R, Massé R. Risk factors for serogroup C meningococcal disease and effectiveness of polysaccharide vaccine (poster G-526). In: Proceedings of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 30-November 2, 2004; Washington, DC
Trotter CI, Andrews NJ, Kaczmarski EB, Miller E, Ramsay ME. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction.  Lancet. 2004;364:309-310
PubMed   |  Link to Article

Figures

Figure 1. Immunization Coverage of Target Population
Graphic Jump Location
Figure 2. Monthly Number of Cases of Serogroup C Meningococcal Disease in the Quebec City Area and the Province of Quebec, 2001-2002
Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Cases of Invasive Meningococcal Disease Reported in the Province of Quebec, According to Serogroup, 1996-2002*
Table Graphic Jump LocationTable 2. Incidence of Serogroup C Meningococcal Disease in the Province of Quebec by Age Group

References

De Wals P, De Serres G, Niyonsenga T. Effectiveness of a mass immunization campaign against serogroup C meningococcal disease in Quebec.  JAMA. 2001;285:177-181
PubMed   |  Link to Article
National Advisory Committee on Immunisation.  Statement on recommended use of meningococcal vaccines.  Can Commun Dis Rep. 2001;27:2-36
PubMed
Borrow R, Andrews N, Goldblatt D, Miller E. Serologic basis for use of meningococcal serogroup C conjugate vaccines in the United Kingdom: revaluation of correlates of protection.  Infect Immun. 2001;69:1568-1573
PubMed   |  Link to Article
Farrington P, Miller E. Meningococcal vaccine trials. In: Pollard AJ, Maiden MCJ, eds. Meningococcal Vaccines (Methods and Protocols). Totowa, NJ: Humana Press; 2001
Lavigne P, Boulianne N, Fortin C, Naccache H, Douville-Fradet M. Meningococcal infections in Quebec—1991-1992.  Can Commun Dis Rep. 1992;18:113-116
PubMed
Ashton FE, Ryan JA, Borczyk A, Caugant DA, Mancino L, Huang D. Emergence of a virulent clone of Neisseria meningitidis serotype 2a that is associated with meningococcal group C disease in Canada.  J Clin Microbiol. 1991;29:2489-2493
PubMed
De Wals P, Dionne M, Douville-Fradet M, Boulianne N, Drapeau J, De Serres G. Impact of a mass immunization campaign against serogroup C meningococcus in the province of Quebec, Canada.  Bull World Health Organ. 1996;74:407-411
PubMed
Squires SG, Deeks SL. Enhanced surveillance of invasive meningococcal disease in Canada: 1 January, 1999, through 31 December, 2001.  Can Commun Dis Rep. 2004;30:17-28
PubMed
Direction générale de la santé publique.  Protocole d’iintervention: Infections Méningococciques. Québec, Québec: Ministère de la santé et des Services sociaux; 1994
Tsang RSW, Squires SG, Tam TWS. Characterization of Neisseria meningitidis strains isolated from invasive meningococcal disease in Canada.  Can J Microbiol. 2003;49:633-638
PubMed   |  Link to Article
Orenstein WA, Bernier RH, Hinman AR. Assessing vaccine efficacy in the field: further observations.  Epidemiol Rev. 1988;10:212-241
PubMed
 StatXact 4 for WindowsCambridge, Mass: CYTEL Software Corp; 1999
Miller E, Salisbury D, Ramsay M. Planning, registration, and implementation of an immunization campaign against meningococcal serogroup C disease in the UK: a success story.  Vaccine. 2002;20:(suppl 1)  S58-S67
Link to Article
Bose A, Coen P, Tully J, Viner R, Booy R. Effectiveness of meningococcal C conjugate vaccine in teenagers in England.  Lancet. 2003;361:675-676
PubMed   |  Link to Article
Rivest P, Sagot B, Bedard L. Evaluation of the completeness of reporting of invasive meningococcal disease.  Can J Public Health. 1999;90:250-252
PubMed
De Wals P, Deceuninck G, De Serres G, Duval B, Remis R, Massé R. Risk factors for serogroup C meningococcal disease and effectiveness of polysaccharide vaccine (poster G-526). In: Proceedings of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy; October 30-November 2, 2004; Washington, DC
Trotter CI, Andrews NJ, Kaczmarski EB, Miller E, Ramsay ME. Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction.  Lancet. 2004;364:309-310
PubMed   |  Link to Article
CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 55

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Topics