Research Paper
Research Paper
Human Vaccines & Immunotherapeutics 10:3, 671–676; March 2014; © 2014 Landes Bioscience
Impact of meningococcal C conjugate vaccination campaign in Emilia-Romagna, Italy Maria Grazia Pascucci1,Valentina Di Gregori2,Gabriella Frasca1, Paola Rucci2, Alba Carola Finarelli1, Laura Moschella 1, Bianca Maria Borrini1, Francesca Cavrini 3,Giovanna Liguori3, Vittorio Sambri3,4, Paolo Bonanni5, and Maria Pia Fantini2,*
Keywords: vaccination campaign, meningococcal disease, serogroups, vaccination strategies, surveillance, vaccination coverage
The incidence of reported meningococcal disease in Italy is among the lowest in Europe. The trend of the disease was increasing up to 2005 and then declined after the gradual introduction of a universal Men C vaccination program in 17/21 Italian regions. Since 2006, in Emilia-Romagna region vaccination against Neisseria meningitidis serogroup C was actively offered free of charge in a single dose to the age groups 12–15 months and 14–15 years, in addition to people with defined epidemiological risk. Our aim was to measure the impact of vaccination on the incidence of meningococcal disease caused by different serogroups among the population of Emilia Romagna Region, Northern Italy (approximately 4.5 million inhabitants) subdivided by age. Using surveillance data, we computed the incidence rates of Neisseria meninigitidis related invasive disease per 100.000 inhabitants for the years 2000 to 2012. In addition, the percentage change in incidence and the mortality rates were calculated. Results indicate a 70.1% decrease in the incidence of meningococcus C-related invasive disease after the introduction of MenC universal vaccination. No case of serogroup C related infection was observed since 2006 in children aged 1–4 years. These findings suggest that the single-dose vaccination strategy against serogroup C N.meningitidis targeted to the age groups 12–15 months and 14–15 years was effective in the EmiliaRomagna population. However, the occurrence of two cases of meningiditis in a 5-month child and in a 9-years child suggests caution and careful consideration in surveillance for the next years.
Introduction Neisseria meningitidis is a gram-negative diplococcus which normally colonizes the pharynx and upper respiratory tract without causing invasive disease. The point-prevalence carriage rate in Europe and the US has been estimated to range from 10 to 35% in young adults.1 In a recent Italian study, meningococcal carriage prevalence was 2% in 583 university students.2 Most isolates were nontypeable and none belonged to serogroup C. Only approximately 2% of students had received MenC conjugate vaccine. However, MenC vaccine coverage in younger children was 60% and the authors considered that a herd effect of vaccination on carriage could not be excluded.2 Despite advances in antibiotic therapy, improvements in intensive care and the increasing use of vaccines, N.meningitidis continues to be a major cause of invasive disease, including meningitis, leading to increased morbidity, mortality, and neurological sequelae. This is particularly evident among young children and adolescents, both in developing and in developed countries.3 The following six serogroups out of the 13 currently identified for N.meningitidis account for up to 90% of the infections: A, B, C, W135, X, and Y. The geographic distribution and epidemic
potential differ according to different serogroups. In Europe, most cases of meningococcal diseases are caused by serogroups B and C and the incidence of laboratory-confirmed disease is 1/100.000 population.4 In sub-Saharan Africa (the so-called Africa meningitis belt) explosive epidemics of meningococcal disease are experienced every 5 to 10 y and are usually caused by serogroup A (http://www.who.int/mediacentre/factsheets/fs141/ en/, accessed October 2013). Between 1999 and 2006, in response to the identification of relatively high endemic rates of serogroup C related disease, the United Kingdom5 and many European countries (Belgium, Iceland, Ireland, Netherlands, and Catalonia, Spain),6-8 introduced meningococcal serogroup C conjugate (MCC) vaccines as part of their national immunization programs. In Germany, Portugal, Switzerland, and France, where the incidence of confirmed and probable cases of meningococcal disease remained low and stable during the 1999–2006 period9 routine vaccination with meningococcal C conjugate vaccines was not initially implemented but has now been introduced into the routine schedule.10 Following the MCC, conjugated tetravalent vaccines, covering serogroups A, C, W135, and Y, were more recently licensed in USA, Canada, and Europe. However, due
*Correspondence to: Maria Pia Fantini; Email:
[email protected] Submitted: 10/31/2013; Revised: 12/10/2013; Accepted: 12/19/2013 http://dx.doi.org/10.4161/hv.27597 www.landesbioscience.com Human Vaccines & Immunotherapeutics 671
©2014 Landes Bioscience. Do not distribute.
1 Regional Health Authority; Bologna, Italy; 2Department of Biomedical and Neuromotor Sciences; University of Bologna; Bologna, Italy; 3Unit of Clinical Microbiology; S. Orsola-Malpighi University Hospital; Bologna, Italy; 4Unit of Clinical Microbiology; Greater Romagna Laboratory; Pievesestina, Cesena, Italy; 5Department of Health Sciences; University of Florence; Florence, Italy
to the rather low incidence of meningococcal disease related to capsular groups A, W135, and Y in Europe, recommendations for the use of quadrivalent conjugate vaccine in Europe are still not uniform across the continent. In Italy, a national monitoring program of invasive meningococcal diseases was set up in 1994. This program was modified in October 2006 to include surveillance of invasive bacterial caused by N. menigitidis, Streptococcus pneumoniae, and Hemophilus influenzae.11 Although Italy has a low endemicity for meningococcal disease, MCC vaccination was recommended under the 2005–2007 National Vaccine Plan and, in 2011 17 out of the 21 regions had introduced universal vaccination.12 Starting from 2003, in Tuscany (a region located in the Central Italy bordering Emilia Romagna with about 3.7 million inhabitants) MCC vaccine was offered to all subjects at risk, and from March 2005 the vaccine was universally offered free of charge to newborns (three doses at 3, 5, and 13 mo of age and in a single dose to unvaccinated children under 6 y of age in a catch-up program). This campaign proved to be successful in preventing meningococcal disease, with no cases observed since 2006 in vaccinated subjects and a herd immunity effect in the unvaccinated age groups.13 Similarly, in Emilia-Romagna, a region located in Northeastern Italy with about 4 million inhabitants, MCC vaccine was offered to people at risk since 2003. Starting from 2006, it has been actively offered free of charge in a single dose to children aged 12–15 mo (together with vaccines against measles, mumps, and rubella) and adolescents aged 14–15 y (in conjunction with anti-diphtheria and tetanus active immunization). No catch-up strategy was implemented. This paper examines the impact of the universal MCC vaccination campaign in Emilia-Romagna, and provides evidence on age-specific vaccine effectiveness.
Results Surveillance data are shown in Figure 1 by infecting N. meningitidis serogroup for the years 2000–2012. From 2001 to 2005, a constant increase in the number of infections was detected, with a peak of 26 cases in 2005 and the main drop occurring soon after the implementation of the vaccine campaign in 2006. This decrement was followed by an increase of notified cases in 2007. This might be partially explained by an increased sensitivity of the surveillance system, that became fully implemented from 2007. The vaccination coverage increased constantly since 2007 and reached 92.2% at 24 mo of age and 80.4% at 15–16 y of age in 2012 (Table 1). The vaccine effectiveness was estimated as 99.0%. Table 2 shows the incidence of N. meningiditis infection before and after the implementation of the vaccination campaign, and the percentage change in incidence between the two periods by age group and by infecting serogroup. The average incidence of meningitis caused by meningococcus declined from 0.54/100.000 (years 2000–2005) to 0.33/100.000 (years 2006–2012). The impact of MCC vaccination on the incidence of serogroup C related disease was remarkable, with a significant decline in the temporal trend since 2006 (Poisson regression, P = 0.038). The total number of notified serogroup C cases dropped from 51 in 2000–2005 to 19 in 2006–2012, corresponding to an overall change in incidence from 0.2/100.000 to 0.06/100.000 (–70.1%). This change reached –100% (no case notified) and -83.1% in the two target age groups 1–4 and 15–24 y. Notably, no case of serogroup C infection was observed after the introduction of the MCC vaccination in the age group 1–4 y. However, after 6 y of herd protection in infants
