Carriage meningococcal isolates with capsule null locus dominate among high school students in a non-endemic period, Italy, 2012–2013
Introduction
N. meningitidis is often asymptomatically carried at the mucosal surface of the nasopharynx and transmitted through respiratory secretions (Stephens et al., 2007; Soriano-Gabarró et al., 2011). Carriage status plays an important role in the dynamic of transmission of N. meningitidis (Soriano-Gabarró et al., 2011; Stefanelli and Rezza, 2016).
Many reports have been described that the microbiological traits of carriage isolates together with the age of the subject play a role for the carriage status (Christensen et al., 2010; Harrison et al., 2015). Most of the studies depicts an high incidence rate in 15 to 24 years old individuals (Christensen et al., 2010). In particular, Rønne et al. (1993) reported a prevalence of carriage from 19.8% to 20.4% in subjects between 16 and 20 years of age; moreover, Fraser et al. (1973) estimated a prevalence of carriage of 25.7% in a cohort of young people, 15 to 16 years of age.
In Italy, studies on the prevalence of meningococcal carriage isolates have been carried out in the years (Esposito et al., 2013; Gasparini et al., 2014; Germinario et al., 2010; Stroffolini et al., 1990; Tafuri et al., 2012). A study conducted in subjects 14–22 years of age demonstrated a meningococcal carriage peak of 25.5%, in the years 2011 and 2012 (Gasparini et al., 2014).
Few data are available on meningococcal carriage isolates in Europe, in fact, most of them refer to the local meningococcal epidemiology (Soriano-Gabarró et al., 2011).
Overall, the data reported in a number of carriage studies underline the indirect protection mediated by the immunization programs on carriage status as a key element in the dynamic of IMD (Claus et al., 2005; Maiden et al., 2008; Yazdankhah and Caugant, 2004).
In Italy, the quadrivalent meningococcal conjugate vaccination is currently recommended for adolescents aged 12–18 years (http://www.salute.gov.it/imgs/C_17_pubblicazioni_2571_allegato.pdf). Meningococcal B (MenB) and C (MenC) vaccinations are also recommended for primary vaccination (http://www.salute.gov.it/imgs/C_17_pubblicazioni_2571_allegato.pdf).
In 2012–2013, we conducted a carriage study among undergraduate students in six large cities in Italy in a non-epidemic period and prior to widespread availability of MenB vaccines in the country. Furthermore, carriage meningococcal isolates were characterized with the aim to: i) identify the carrier prevalence and the main serogroup of the carriage isolates; ii) determine their susceptibility against 4 antimicrobials; iii) identify, using Whole Genome Sequencing (WGS), or Sanger sequencing, the Sequence Types (ST), the clonal complex (cc), and the antigens comprised in the meningococcal B vaccines.
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Ethical approval
The study protocol was accepted by the Ethics Committee of the Istituto Superiore di Sanità (reference number CE/11/313). A written informed consent form was obtained from parents of participants aged <18 years old. Participants aged 18 years or above gave their informed consent.
Study design and population
The collection was carried out from June 2012 to July 2013. A total of 1697 healthy teenagers aged between 14–19 years, attending secondary schools in six different Italian cities, were invited voluntary to participate
Prevalence of meningococcal carriage isolates
From the 1697 teenagers enrolled, 120 resulted culture positive for N. meningitidis. In particular, the overall carriage rate was 7% (95% CI, 5.90–8.40), that varied among the collaborating centers: 4.0% in Napoli (12/300) and 4.2% in Padova (11/260), 5.3% (16/300) in Roma, 7.5% (17/225) in Bologna, 9.5% (31/315) in Milano and 11.5% (34/296) in Torino (Fig. 1). The median age of the carriers was 17.5 years (range 14–19 years). Fig. 2 shows the distribution of the carriers by age. The highest
Discussion
Although the rate of IMD in Italy is currently low, outbreak and small clusters have been recently reported (Miglietta et al., 2018; Stefanelli et al., 2018). Meningococcal carriage influences the dynamic of the spread of the disease in particular for specific age group (Caugant and Maiden, 2009).
We aimed to evaluate the carriage rate and the molecular characteristics of carriage isolates from high school students prior to the introduction of MenB vaccines in Italy and in a non-epidemic period (
Competing interests
No competing of interest.
Authors' contributions
AN,CF, PV, performed the microbiological analyses on samples. MPL, LR, LD, IS, collected the swabs at local level and identified Neisseria meningitidis. AC, AA, FL performed the whole genome sequencing on a subsamples of meningococcal isolates. CF, PV, AN contributed in the analysis of carriage isolates and together with PS revised critically the manuscript. PS conceived the study and together with AN wrote the manuscript. All authors have read and accepted the submitted manuscript.
Acknowledgements
The authors are grateful to all students and parents who participated in the study reported in this article.
The authors thanks Antonella Fortunato, Anna Maria Palozzi and Silvia Fillo (Scientific Department, Army Medical Center, Rome, Italy) for the whole genome sequencing; Annapina Palmieri (Department of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy) for the collaboration in the National Surveillance System of Invasive Bacterial Diseases and for the data collection; Fenicia
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