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Keywords:

  • meningococcal meningitis;
  • vaccination;
  • carrier state;
  • herd immunity
  • Méningite méningococcique;
  • vaccination;
  • état du porteur;
  • immunité du troupeau
  • Meningitis Meningocócica;
  • Vacunación;
  • Estado portador;
  • Inmunidad de rebaño

Summary

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

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.

Revue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynx

Objectif:  Investiguer l’effet des vaccins méningococciques sur le portage de méningocoques dans le pharynx.

Méthodes:  Revue systématique. MEDLINE et EMBASE ont été recherchés pour des études appropriées. Des essais cliniques contrôlés et des études d’observation basées sur des groupes de comparaison ou sur la comparaison des taux de porteurs avant et après vaccination ont été inclus dans la revue.

Résultats:  29 études ont satisfait aux critères d’inclusion. 25 études rapportaient sur l’effet d’un vaccin polysaccharidique, une étude sur l’effet d’un vaccin conjugué du sérogroupe C et 3 études sur l’impact des vaccins basé sur la membrane externe du sérogroupe B en général et/ou sur les taux de porteurs méningococciques de sérogroupes spécifiques. 10 études sur des vaccins méningococciques polysaccharidiques ont trouvé une réduction du nombre de porteurs de sérogroupes spécifiques; 7 de ces études étaient focalisées sur les groupes à haut risque et sur une courte période de suivi. Seule une étude sur 5 sur des populations civiles en Afrique a révélé une réduction significative du nombre de porteurs. Plusieurs études comportaient des imperfections méthodologiques. La seule étude qui a évalué l’effet d’un vaccin conjugué méningococcique sur les porteurs a révélé un impact significatif. Trois études sur des vaccins de protéine de membrane externe du sérogroupe B n’ont révélé aucun effet sur les porteurs.

Conclusions:  Peu d’essais cliniques bien conçus ont été entreprises sur l’impact des vaccins méningococciques sur les porteurs. De telles études devraient être un composant essentiel de l’évaluation de nouveaux vaccins méningococciques, en particulier ceux introduits pour le contrôle de l’épidémique de maladie méningococcique en Afrique.

Revisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo

Objetivo:  Investigar el efecto de las vacunas frente a meningococo sobre la carga faríngea de meningococo.

Métodos:  Revisión sistemática. Se buscaron estudios relevantes en MEDLINE y EMBASE. Se incluyeron ensayos controlados y estudios observacionales que utilizaron grupos comparables o compararon tasas de carga antes y después de la vacunación.

Resultados:  29 estudios cumplían los criterios de inclusión. 25 estudios reportaban el efecto de una vacuna de polisacárido, 1 el efecto de una vacuna conjugada frente al serogrupo C y 3 el impacto de vacunas de proteínas de membrana externa del serogrupo B, sobre las tasas de carga meningocócica totales y / o serogrupo específicas. En 10 estudios de vacunas de polisacáridos se encontró una reducción de la carga serogrupo-específica; 7 de estas se enfocaron en grupos de alto riesgo y tenían un periodo de seguimiento corto. Solo 1 de 5 estudios en poblaciones civiles de África mostró una carga reducida significativa. Muchos estudios presentaban defectos metodológicos. El estudio que evaluaba el efecto de una vacuna conjugada sobre la carga mostró un impacto significativo. Tres estudios de las vacunas de proteínas de membrana externa del serogrupo B no mostraron efecto sobre el estado de portador.

Conclusiones:  Se han realizado pocos estudios bien diseñados sobre el impacto de las vacunas frente a meningococo. Estos estudios deberían ser un componente esencial de la evaluación de nuevas vacunas frente a meningococo, particularmente aquellas introducidas para el control de la enfermedad meningocócica epidémica en África.


Introduction

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Acute bacterial meningitis continues to be a major cause of mortality and morbidity, especially in the developing world. Three bacteria –Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (the pneumococcus) and Neisseria meningitidis (the meningococcus) account for the majority of cases. Deployment of Hib polysaccharide/protein conjugate vaccines has led to the virtual disappearance of invasive Hib disease in most industrialized countries and in several countries in Africa (Cogwill et al. 2006; Adams et al. 1993; Peltola 2000; Adegbola et al. 2005). Introduction of a seven-valent pneumococcal conjugate vaccine into the routine infant immunization programme has had a dramatic impact on the incidence of invasive pneumococcal disease in both children and adults in the United States (Whitney et al. 2003) and the encouraging results of trials in South Africa, the Gambia and the Philippines (Klugman et al. 2003;Lucero et al. 2006; Cutts et al. 2005) suggest that pneumococcal conjugate vaccines should have a considerable impact on the incidence of invasive pneumococcal disease and pneumonia in developing countries when these vaccines are deployed. However, there has been little progress in containing the epidemics of meningococcal disease that continue to occur across the African meningitis belt, despite the widespread use of polysaccharide vaccines (Chippaux et al. 2002; Greenwood 2006).

It seems probable that the key factor that has led to the dramatic success of Hib and pneumococcal conjugate vaccines is their ability to prevent nasopharyngeal carriage of Hib (Takala et al. 1991; Murphy et al. 1993; Barbour et al. 1995; Adegbola et al. 1998; McVernon et al. 2004) or pneumococci (Obaro et al. 1996; Finkelstein et al. 2003; O’Brien & Dagan 2003; Hammitt et al. 2006) and thus to interrupt transmission, providing indirect protection to non-vaccinated subjects (herd immunity). The failure of widespread immunization with meningococcal polysaccharide vaccines to contain epidemics of meningococcal disease in Africa is often attributed to the apparent inability of these vaccines to reduce pharyngeal carriage of meningococci, and meningococcal conjugate vaccines are developed to overcome this defect. However, there is still some uncertainty about the ability of meningococcal polysaccharide vaccines to prevent pharyngeal carriage and a few well-conducted studies of their impact have been done outside military populations. In this paper, we review the studies that have investigated the impact of meningococcal vaccines of any kind on pharyngeal carriage of meningococci.

Methods

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

In September 2006, we searched the EMBASE (1980–September 2006) and MEDLINE (1966–September 2006) databases for articles on meningococcal vaccination and carriage using Ovid interface. Bibliographies of relevant papers were also hand searched. We used a combination of the following key terms: (meningococc*; Neisseria meningitidis) and (vaccin*) and (carrier state or nasopharyngeal or oropharyngeal carriage or carriage or disease carrier).

The types of studies considered were randomized or quasi-randomized controlled trials or observational studies of meningococcal polysaccharide, conjugate or protein vaccines which used a contemporary control group or which compared carriage rates before and after vaccination. Participants were individuals of any age exposed to meningococcal disease. The outcome of interest was pharyngeal carriage of N. meningitidis. We included studies that reported isolation rates obtained with swabs taken from the nasopharynx or from the oropharynx. In some studies, the method of sample collection was not specified.

Results

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

Description of studies reviewed

The electronic searches identified 189 abstracts (after removing duplicates); of these, 29 studies satisfied the selection criteria. The remainder were excluded because they did not involve vaccination, did not report an effect on carriage, did not refer to meningococcal diseases or were review papers. A vaccine trial in Nigeria (Sanborn et al. 1972) which included a carrier study, was excluded as the vaccine used was reported to be inactive at the time of the trial.

Four studies evaluated a meningococcal serogroup C polysaccharide vaccine (Gotschlich et al. 1969; Artenstein et al. 1970; Devine et al. 1970; Wenzel et al. 1973), four studies evaluated a serogroup A polysaccharide vaccine (Gotschlich et al. 1969; Makela et al. 1975; Wahdan et al. 1977; Sivonen 1981), 17 studies a serogroup A + C polysaccharide vaccine (Greenwood et al. 1978; Bosmans et al. 1980; Blakebrough et al. 1983; Hassan-King et al. 1988; Masterton et al. 1988; Dimartino et al. 1990; Stroffolini et al. 1990; Neal et al. 1998; Smith et al. 1999; Aceitero 2000; Cardenosa et al. 2001; Dominguez et al. 2001; Fernandez et al. 2003; Djibo et al. 2004; Pavlopoulou et al. 2004; Eslami-Nejad et al. 2005; Mueller et al. 2006) and one study evaluated a tetravalent ACYW135 polysaccharide vaccine (Caugant et al. 2006). Only one study has reported on the effect of a meningococcal C conjugate vaccine on carriage (Maiden et al. 2002). Three studies described randomized, controlled trials (RCT) of meningococcal serogroup B outer-membrane vaccines (Bjune 1992; Boslego et al. 1995; Perkins et al. 1998).

The impact of meningococcal polysaccharide vaccines on pharyngeal carriage

We identified 25 studies that addressed the effect of this group of vaccines on carrier status and/or rate of acquisition of carriage. These are summarized in Tables 1–3. We have considered separately the results obtained in military and civilian populations and those obtained in industrialized countries and in Africa.

Table 1.   Summary of studies on the effect of polysaccharide vaccines on meningococcal carriage in military recruits
Study year and countryPopulation for carrier surveyCarriage
Pre-vaccinationPost-vaccination Follow-up (statistics P-value)
  1. NR, not reported.

  2. *Clinical trial.

  3. P-value not reported and was calculated from publication data using Pearson’s chi-squared test.

  4. P-value calculation not applicable.

  5. §P-value statistics relate to pre-post vaccination evaluation.

Intervention studies with a contemporary control group
Gotschlich et al. 1969, USA*Military recruits (≥15 years) from three basic army training camps N = 145 vaccinated with meningococcal C vaccine (Vc) N = 53 vaccinated with meningococcal A vaccine (Va) N = 483 control non-immunized (C) 2 weeks 7 weeks
Overall:  
Vc: 23%Vc: 31% (P = 0.170)†Vc: 46% (P = 0.059) †
Va: 23%Va: 43% (P = 0.383)†Va: 58% (P = 0.575) †
C: 17%C: 37%C: 54%
Serogroup C:  
Vc: 4%Vc: 4% (P < 0.01)†Vc: 13% (P < 0.01)†
Va: 2%Va: 30% (P < 0.01)†Va: 34% (P = 0.782) †
C : 2%C: 13%C: 32%
Devine et al. 1970, USA*Marine recruits from the Infantry Training Regiment§ N = 3018 vaccinated with meningococcal C vaccine (V) N = 3000 control non-immunized (C) 8 weeks
Overall: 
V: 27%V: 40%
C: 25%C: 55%‡
Serogroup C: 
V: 5%V: 8%
C: 4%C: 24% (P < 0.01)†
Artenstein et al. 1970, UK*Army men (≥15 years) recruited from five army training centres N = 155 vaccinated with meningococcal C vaccine (V) N = 557 control non-immunized (C) 8 weeks
Overall: 
NRV: 65%
C: 68% (P = 0.445)†
Serogroup C: 
NRV: 15%
C: 33% (P < 0.01)†
Wenzel et al. 1973, USA*Marine men (17–22 years of age) recruited from the Infantry Training Regiment N = 60 vaccinated with meningococcal C vaccine administered intranasally (V) N = 493 control non-immunized (C) 8 weeks
Overall: 
V: 0V: 46%
C: 29%C: 60% (P = 0.058)† 
Serogroup C: 
V: 0V: 16%
C: 13%C: 21% (P = 0.379)†
Makela et al. 1975, Finland*Army recruits (A meningococci seroprevalent) N = ∼600 vaccinated with meningococcal A polysaccharide vaccine (V) N = ∼600 control non-immunized (C) 4 weeks
Overall: 
35% V and C: 54%‡ 
Serogroup A: 
1.5%V and C: 3.2%‡
Sivonen et al.1981, Finland Half of all new recruits in the Finnish Armed Forces received the polysaccharide A vaccine when entering service. (A meningococci seroprevalent) For the carriage survey: N = 1200 were screened at 4 weeks  4 weeks
Serogroup A: 
V and C: 2.2%V: 9%
C: 24% (P < 0.05)
Aceitero 2000, SpainFollowing a vaccination campaign with group A and C polysaccharide vaccine Healthy military N = 619 military recruits vaccinated (V) N = 166 military unvaccinated control (C) 12 months 
Overall: 
NRV: 8.4%
C: 6.4% (P = 0.398)†
Serogroup C: 
NRV: 0.6%
C: 0%
Serogroup B: 
NRV: 4.8%
C: 3.8% (P = 0.585)†
Before and after vaccination comparisons§
Masterton et al. 1988, UKRoyal Air force trainees (aged 16–18 years) and staff and their families living on site. Meningococcal group A + C polysaccharide vaccine N = 289 (week 4) and 329 (week 8) (V) 2 weeks
Overall: 
V: 4%V: 6% (P = 0.218)†
 8 weeks
Serogroup C: 
V: 19%V < 1%‡
Dimartino 1990, Italy Army recruits in the training centre for army medical officers in Florence: N = 171 vaccinated with meningococcal A + C polysaccharide vaccine (V)  7 weeks
Overall: 
V: 16%V: 12% (P > 0.05)
Serogroup C: 
V: 6%V: 0.6% (P < 0.01)
Stroffolini 1990, Italy Army recruits: N = 98 vaccinated with meningococcal A + C polysaccharide vaccine (V) 3 weeks
Overall: 
V: 32%V: 52% (< 0.01)
Serogroup C: 
V: 9%V: 0%‡
Serogroup Y: 
V: 17%V: 40% (P < 0.01)
Eslami-Nejad 2005, IranSample of military recruits from a military training centre in South-East of Iran who were administered group A and C polysaccharide vaccine after recruitment N = 764 pre-vaccination and N = 692 post-vaccination (V) 8 weeks
Overall: 
V: 11.6%V: 33% (P < 0.01)†
Table 2.   Summary of studies on the effect of polysaccharide vaccines on meningococcal carriage in civilians in industrialized countries
Study year and countryPopulation for carrier surveyCarriage
Pre-vaccinationPost-vaccination Follow-up (statistics P-value)
  1. NR, not reported.

  2. P-value not reported and was calculated from publication data using Pearson’s chi-squared test.

  3. P-value calculation not applicable.

  4. §P-value statistics relate to pre-post vaccination evaluation.

Intervention studies with a contemporary control group
Neal et al. 1998, UK Following a community prophylaxis programme children aged 2 ± 18 years were vaccinated with A + C polysaccharide vaccine and received either rifampicin (ages 2 ± 10 years) or ciprofloxacin (ages 11 ± 18 years) in January 1996 School pupils at secondary schools within an intervention area compared with two schools outside the intervention area but matched for socio-economic status. Aged 11–18 years. N = 1058 and 1296 intervention group (V) at 6 and 11 months follow-up, respectively N = 811 and 1161 control group (C) at 6 and 11 months follow-up, respectively  6 months 11 months
Overall:  
NRV: 2.4%V: 7.4%
C: 8.5% (P < 0.01)C: 7.0% (P > 0.05)
Serogroup C:  
NRV: 0.4%V: 0.08%
C: 0‡C: 0‡
Serogroup B:  
NRV: 0.4%V: 1.9%
C: 2.2% (P < 0.01)C: 1.1% (P > 0.05)
Aceitero 2000, SpainFollowing a vaccination campaign with group A and C polysaccharide vaccine Healthy residents in Extremadura: General population N = 1140 (<19 years of age) vaccinated (V) N = 1193 (≥20 years of age) unvaccinated control (C) 12 months 
Overall: 
NRV: 8%
C: 3.3% (P < 0.05)
Serogroup C: 
NRV: 0.04%
C: 0.1% (P = 0.586)†
Serogroup B: 
NRV: 4.4%
C: 2.3% (P < 0.05)
Cardenosa 2001, SpainFollowing a vaccination campaign with group A and C polysaccharide vaccine Close contacts of cases with meningococcal disease 7–18 months
Overall: 
NRV: 24%
C: 10% (P = 0.003)
Dominguez 2001, SpainFollowing a vaccination campaign with group A and C polysaccharide vaccine Healthy schoolchildren in Catalonia: N = 790 (<19 years of age) vaccinated (V) N = 609 non-vaccinated (C) 12–17 months
Overall: 
NRV: 5.5%
 C: 4.8% (P = 0.55)
Serogroup C: 
NRV: 0%
Before and after vaccination comparisons§
Smith et al. 1999, Norway Following a vaccination campaign with group A and C polysaccharide vaccine targeting all children aged 2–5 years and adolescents aged 13–21 years in February 1996 School pupils aged 13–21 years N = 1120 pre-vaccination and N = 680 post-vaccination (V) 24 months
Overall: 
V: 20.7%V: 19.4%‡
Serogroup C: 
V: 1.6%V: 0‡ 
Serogroup B: 
NRV: 0.4%‡
Fernandez et al. 2003, Spain Following a vaccination campaign with group A and C polysaccharide vaccine targeting all residents in Galicia aged 18 months to 19 years. December 1996–January 1997 Population in high- and low-incidence areas for meningococcal disease. Pre-vaccination (aged 2–19 years): N = 4004 in high (Vh) and N = 3083 in low (Vl) Post-vaccination (aged 5–19 years): N = 4723 in high (Vh) and N = 2659 in low (Vl)  12 months
Overall: 
Vh: 9.6%Vh: 10% (P = 0.751)
Vl: 8.4%Vl: 6.5% (P = 0.053)
Serogroup C: 
Vh: 1.5%Vh: 0.8% (P = 0.037)
Vl: 0.9%Vl: 0.3% (P = 0.149)
Serogroup B: 
Vh: 6.5%Vh: 5.7% (P = 0.404)
Vl: 5.5%Vl: 4.5% (P = 0.145)
Table 3.   Summary of studies on the effect of polysaccharide vaccines on meningococcal carriage in civilians in Africa
Study year and countryPopulation for carrier surveyCarriage
Pre-vaccinationPost-vaccination Follow-up (statistics P-value)
  1. NR, not reported.

  2. *Clinical trial.

  3. P-value not reported and was calculated from publication data using Pearson’s chi-squared test.

  4. P-value calculation not applicable.

  5. §P-value statistics relate to pre-post vaccination evaluation.

Intervention studies with a contemporary control group
Wahdan et al. 1977, Egypt*1. School children (6–15 years of age) = 256 vaccinated with meningococcal A vaccine (V) = 254 control immunized with tetanus toxoid (C) 2. Class contacts of cases of meningococcal meningitis: = 371 vaccinated with meningococcal A vaccine (V) = 470 control immunized with tetanus toxoid (C)Overall: NR1. New acquisitions Per 1000 student-months follow up 
3 months 21 months 
V: 4.9%V: 10.4%
C: 12% (P = 0.081)†C: 10% (P = 0.909)†
2. Class contacts 
8–15 months >19 months 
V: 4.2%V: 10.1%
C: 12.7% (P < 0.01)† C: 10.9% (P = 0.847)†
Greenwood et al. 1978, Nigeria*Household contacts of cases of meningococcal disease identified at hospitals and students of Koranic schools (A meningococci) N = 431 vaccinated with meningococcal A + C polysaccharide vaccine (V) N = 450 control immunized with tetanus toxoid (C) 2 weeks  
Serogroup A:  
V: 4.4%V: 6.7% 
C: 3.3% (P = 0.408)†C: 3.3% (P < 0.05)† 
Serogroup C:  
V: 0.7%V: 1.4 
C: 0.9% (P = 0.747)†C: 1.3% (P = 0.940)† 
Blakebrough et al. 1983, Nigeria*Schoolboys aged 11–20 years enrolled at Government secondary school. N = 85 vaccinated with meningococcal A + C polysaccharide vaccine (V) N = 83 unvaccinated controls (C) 2 months 4 months 
Overall:  
V: 3.5%V: 8.8%V: 13.9%
C: 1.2%C: 4.7% (P = 0.481)†C: 13.5% (P = 0.947)† 
Serogroup A:  
V: 1.2%V: 2.9%V: 11%
C: 1.2%C: 4.3% (P = 0.673)†C: 12% (P = 0.843)†
Hassan-King et al. 1988, the Gambia Pre-vaccination data obtained during the meningitis outbreak from: N = 100 children and young adults (background rate: B) Six months after mass vaccination campaign with serogroup A and C meningococcal polysaccharide vaccine, nasopharyngeal swaps were obtained from: N = 250 subjects aged 2–20 years living in study area and subjects not vaccinated from village across the border. 6 months 12 months
Serogroup A:  
B: 15%V: 12%V: 1%
C: 7%‡ 
Before and after vaccination comparisons§
Bosmans et al. 1980, Rwanda Sample of healthy individuals 2–20 years of age living in Kinigi commune and household contacts of meningitis cases aged 6 months to 2 years vaccinated. N = 219 vaccinated with meningococcal A + C polysaccharide vaccine 3 weeks  
Overall:  
V: 7.3%V: 16% (P < 0.05)† 
Serogroup A:  
V: 2.7%V: 9.8% (P < 0.05)† 
Serogroup B:  
V: 1.4% V: 2.5% (P = 0.43)† 
Caugant et al. 2006, Uganda*Healthy 2–19-year-old individuals in Mbarara enrolled in vaccine study N = 750 vaccinated with tetravalent ACYW meningococcal polysaccharide vaccine 4 weeks  
Overall:  
V: 1.3% V: 1.9% 
Serogroup B:  
V: 0.1%V: 0%‡  
Serogroup W135:  
V: 0%V: 0.3%‡ 

The first trials of the impact of meningococcal polysaccharide vaccines on the prevalence of pharyngeal carriage were conducted in military recruits in the United States who often have very high carriage rates shortly after recruitment. In five of these studies in which a direct comparison was made between vaccinated and control recruits, a statistically significant reduction in the carriage of meningococci of vaccine serogroup was observed (Table 1). The first study of Finnish military recruits showed an increase in the overall carriage of serogroup A after a vaccination campaign but the carriage rate was low overall and too low to allow the rates to be analysed separately in vaccinated and control groups (Makela et al. 1975). However, a subsequent study of Finnish recruits detected a significant difference in the serogroup A carriage rate between vaccinated and control subjects 4 weeks after vaccination (Sivonen 1981). Two studies conducted in Italian recruits also showed a reduction in carriage after vaccination, but these were before and after studies with no control group. Three of four studies which compared carriage rates before and after vaccination reported a significant reduction in the prevalence of serogroup C meningococcal carriage after 2–8 weeks of follow-up. However, not all studies in military recruits showed a positive impact. A study in American marines failed to find a statistically significant difference between vaccinated and control groups, although serogroup C carriage rate was lower in the vaccinees (Wenzel et al. 1973). However, this study differed from the others in that vaccination was administered intra-nasally, and only marines who were not carriers were vaccinated. A study in Spain found no difference between vaccinated and control groups on carriage 1 year after vaccination (Aceitero 2000).

Most studies in military recruits showed an increase in the overall meningococcal carriage at follow-up (ranging from 2 to 8 weeks post-vaccination) in both vaccinated and control recruits, and in some cases this was marked, although usually less in the vaccinees than in the controls. The increase in serogroup C carriage in recruits who received a serogroup A vaccine in the study of Gotschlich et al. (1969) could be interpreted as showing some type of serotype replacement following vaccination. However, an increase in serogroup C carriage was also seen in an unvaccinated control group so the increase was probably just a reflection of the high level of transmission of the dominant serogroup C strain in this community. Military recruits are at high risk of meningococcal infection due to their environment. The results of these trials in the military may, therefore, does not apply to civilian populations. In most military trials, follow-up was limited to a few weeks, except for one study in Spain which assessed the carriage rate 1 year post-vaccination (Aceitero 2000). Only three of the studies undertaken in military recruits reported the method of randomization used for assigning vaccination group while four of the trials did not use randomization or blinding of the investigators to study group. This introduces the possibility of selection bias and uncontrolled confounding in the results. The risk of exposures to infection in the vaccinated and control groups may not have been equivalent. In addition, the level of completeness in follow-up was not reported in several studies which may, therefore, have had a bias in their attrition rates. Lastly, four studies had a before-and-after design without a control group, making it difficult to be certain that the differences seen were the result of the intervention.

In civilian populations in Europe, variable effects of meningococcal polysaccharide vaccination have been observed (Table 2). A mass community study in the United Kingdom, which involved both antibiotic prophylaxis and vaccination, showed a 72% reduction in the carriage of meningococci 6 months after the intervention but not after 11 months (Neal et al. 1998). It is likely that the initial drop in carriage was attributable largely to the antibiotic rather than to the vaccine. Three cross-sectional studies were conducted in Spain following an A + C polysaccharide vaccination campaign (Aceitero 2000; Cardenosa et al. 2001; Dominguez et al. 2001). All showed a higher overall carriage rate in vaccinees than controls (only two statistically significant); one reported a lower carriage rate of serogroup C meningococci 1 year post-vaccination in vaccinees (Aceitero 2000). A before-and-after study of a mass group A + C polysaccharide vaccination campaign conducted in Spain (Fernandez et al. 2003) found a significant reduction in carriage of serogroup C strains in vaccinated children living in a high-incidence area but not in children living in a low-incidence area.

In Africa, only one randomized trial of polysaccharide vaccines has shown a positive impact on carriage (Table 3). In one of the first trials of meningococcal polysaccharide vaccine conducted in Africa, a reduction of serogroup A meningococcal carriage was observed in vaccinated school children in Cairo (Wahdan et al. 1977). Acquisition of serogroup A meningococci was significantly lower among vaccinated contacts of cases than among controls, but this protective effect was not sustained past the first year. New acquisitions also fell in schoolchildren but the effect was not statistically significant. In Nigeria, a polysaccharide vaccine trial conducted in household contacts of cases of meningococcal disease and students of Koranic schools found a significant increase in serogroup A carriage in those vaccinated with an A + C polysaccharide vaccine compared with controls given tetanus toxoid (Greenwood et al. 1978). As observed in some of the military studies, the carriage rate of the epidemic strain increased during the observation period, more markedly in the vaccines than in the controls, indicating the high pressure of infection in an epidemic situation. An individually randomized trial conducted in schoolchildren in Nigeria did not find any impact on the carriage of either serogroup A or serogroup C meningococci (Blakebrough et al. 1983), but the number of children in this trial was relatively small (168) and the study could have missed a modest effect. In the Gambia, the serogroup A meningococcal carriage rate continued to rise for a year after a mass serogroup A + C polysaccharide vaccination campaign that achieved a high level of national coverage and there was no difference between vaccinated and control subjects (Hassan-King et al. 1988). This was not a randomized trial, but it provides some evidence that mass vaccination did not have an immediate effect on carriage rates and was thus unlikely to have had an effect on transmission during the period of an epidemic. Assessment of the impact of a mass vaccination campaign in Rwanda at 3 weeks after vaccination showed no effect on overall or serogroup-specific carriage rates (Bosmans et al. 1980). In Uganda, a field trial of the tetravalent ACYW vaccine did not have an effect on the overall carriage rate 4 weeks post-vaccination (Caugant et al. 2006) but no vaccine-type strains were detected and the overall carriage rate was low (approximately 2%). In Burkina Faso and Niger, studies found carriage of serogroup A meningococci to be unusually low (not detected and <1%, respectively) 1 and 2 years after mass-vaccination campaigns with a serogroup A + C polysaccharide vaccine (Djibo et al. 2004; Mueller et al. 2006).

The impact of meningococcal conjugate vaccines on carriage

Only one study has investigated the impact of a meningococcal conjugate vaccine on pharyngeal carriage of meningococci. Between November 1999 and 2000, all individuals resident in the United Kingdom below the age of 18 years were offered immunization with a serogroup C meningococcal conjugate vaccine and a coverage of 77% in children <5 years and 85% in children 5–17 years was achieved (Trotter et al. 2002). Vaccination provided a high level of protection to children who received the vaccine. Meningococcal disease decreased by 67% [95% confidence interval (CI): 52–77%) among unvaccinated children when figures from 1998/1999 (pre-vaccination) and 2001/2002 (post-vaccination) were compared, suggesting that vaccination had provided herd immunity (Ramsay et al. 2003). The carriage rate of serogroup C meningococci fell from 0.45% to 0.15% in the vaccinated age group but remained constant in older age groups (Maiden et al. 2002). There was no decrease in the carriage of meningococci of other serogroups.

The impact of meningococcal protein vaccines on carriage

Three randomized, controlled trials of outer membrane protein-based serogroup B meningococcal vaccines have not shown any impact on carriage with serogroup B meningococci. The first trial was carried out in 1- to 21-year-old residents of Iquique, Chile (Boslego et al. 1995). During a period of 20 months post-vaccination, the overall meningococcal carrier rate varied from 9.5% to 14% and that for serogroup B meningococci from 1.4% to 1.9%. The carriage rate was threefold higher in those aged 5–18 years than in those aged 1–4 years. No effect of vaccination on serogroup B carriage was found. In Norway, a large-scale, school-randomized, double-blind efficacy trial of a serogroup B meningococcal vaccine that involved 171 800 students showed a direct vaccine efficacy of 71%. Successive carriage surveys showed no differences between vaccinated and control groups and no herd immunity effect was observed (Bjune 1992). Non-vaccinated students within the intervention schools were not at any lower risk of developing disease than students from schools who received placebo. Similarly, a trial in Iceland showed no difference in overall or serogroup B meningococcal carriage rates 1 year post-vaccination between students vaccinated with an outer membrane protein-based serogroup B meningococcal vaccines or with a polysaccharide A and C vaccine (Perkins et al. 1998).

Discussion

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References

The evidence gathered during this review suggests that in high-risk groups in industrialized countries, such as military recruits, meningococcal polysaccharide vaccines can reduce the incidence of carriage, at least for some time. This may assist in preventing or containing outbreaks in military camps. The short duration of protection seen after meningococcal polysaccharide vaccination in these military situations may be linked to the relatively rapid decline in antibody concentrations that follows immunization with polysaccharide vaccines. The situation in civilian populations is much less certain, and most studies have shown little or no impact of polysaccharide vaccination on carriage. However, many of these studies have been opportunistic, often undertaken at the time of an outbreak, and have major methodological weaknesses. For example, several have used before and after observations without a control group; in those who did use a control group, randomization procedures were often sub-optimal. In some studies, swabs were collected from the oropharynx and in others from the nasopharynx, and it is not known how this might have affected the results. It is possible that age could have an influence on the response to vaccination and that the apparently greater success seen in military than in civilian populations could be due in part to the fact that this population is restricted to healthy adults whilst many of the civilian populations in which little effect was seen were undertaken in children or in mixed populations of children and adults. No studies have been undertaken in infants.

In Africa, only one study has reported a positive effect of polysaccharide vaccination on carriage (Wahdan et al. 1977). In Egypt, a transitory effect was reported in about 600 schoolchildren and case contacts, but this was only of borderline statistical significance and had disappeared 19 months after vaccination. In Nigeria, no impact was observed in vaccinated schoolchildren (Blakebrough et al. 1983) and, in the Gambia, high levels of carriage persisted after a national vaccination campaign (Hassan-King et al. 1988). However, no rigorous studies which were well controlled and large enough to detect a modest effect have been conducted in Africa; hence, whether or not polysaccharide vaccines have an impact on carriage in Africa has not been determined definitively. Nevertheless, the evidence provided by the studies considered in this review suggests that if an effect is achieved, it is likely to be only limited, probably of short duration and unlikely to interrupt transmission of an epidemic strain.

Only one study has so far investigated the impact of a meningococcal conjugate vaccine on carriage (Maiden et al. 2002). A marked and highly statistically significant reduction in group C meningococcal carriage was seen in a large-scale trial conducted in school children in the United Kingdom, but this was a before-and-after study and could have been confounded by global changes in the prevalence of the epidemic strain, although this seems unlikely. There was no increase in the prevalence of carriage with meningococci of non-vaccine serogroup in vaccinated children and neither has there been serogroup replacement in invasive disease (Trotter et al. 2006). However, the period of follow-up has so far been relatively short, and serogroup replacement might occur over a longer period, as seen in the case of vaccination with pneumococcal conjugate vaccines remains (Obaro et al. 1996; Dagan et al. 1997; Klugman 2001; Ghaffar et al. 2004; Hammitt et al. 2006; Trotter et al. 2006).

The encouraging results of meningococcal serogroup C vaccination in the United Kingdom (Miller et al. 2001) has stimulated the development of meningococcal conjugate vaccines that could be used to prevent epidemics in Africa. In the African meningitis belt, most major epidemics of meningococcal disease have been caused by meningococci belonging to serogroup A (Greenwood 1999), although epidemics have recently been described that were caused by meningococci belonging to serogroup W135 (Decosas & Koama 2002; Forgor et al. 2005; Traoréet al. 2006) or serogroup X (Gagneux et al. 2002; Djibo et al. 2003; Boisier et al. 2007). Strenuous efforts are being made to develop vaccines that would be effective against serogroup A meningococci, which still account for the majority of epidemics, and which would be affordable by countries in the African meningitis belt. A monovalent serogroup A vaccine is being developed under the auspices of the Meningitis Vaccine Project (MVP), with support from the Bill and Melinda Gates Foundation, and this vaccine is now in clinical trials in the Gambia and Mali (Laforce et al. 2007). In addition, a multivalent DPT/Hib/hepatitis B/group A + C meningococcal conjugate vaccine (Globorix®) has been developed by GlaxoSmithKline (Hodgson et al. 2006) and is being reviewed for licensure. This would be a suitable vaccine for use in routine infant immunization programmes in countries where epidemic meningitis is a threat.

Experience with Hib, pneumococcal and meningococcal serogroup C conjugate vaccines suggests that their impact on carriage has played a key role in their success. Thus, it is important that when meningococcal conjugate vaccines are introduced in Africa, their impact on carriage should be studied and that these studies should be better designed than most of the trials of the impact of meningococcal vaccines on carriage that have been done so far.

References

  1. Top of page
  2. SummaryRevue systématique: Impact de la vaccination méningococcique sur le portage de méningocoques dans le pharynxRevisión sistemática: Impacto de la vacunación frente a meningococo sobre la carga faríngea de meningococo
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. References
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