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Oropharyngeal meningococcal carriage in children and adolescents, a single center study in Buenos Aires, Argentina

  • Angela Gentile ,

    Contributed equally to this work with: Angela Gentile, Maria Paula Della Latta, Cecilia Sorhouet Pereira, Maria del Valle Juarez, Adriana Efron

    Roles Conceptualization, Methodology, Resources, Supervision, Writing – review & editing

    Affiliation Epidemiology Division, Dr Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina

  • Maria Paula Della Latta ,

    Contributed equally to this work with: Angela Gentile, Maria Paula Della Latta, Cecilia Sorhouet Pereira, Maria del Valle Juarez, Adriana Efron

    Roles Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Writing – original draft

    Affiliation Epidemiology Division, Dr Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina

  • Mercedes Bloch ,

    Roles Conceptualization, Investigation, Methodology, Supervision

    ‡ These authors also contributed equally to this work.

    Affiliation Epidemiology Division, Dr Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina

  • Luisina Martorelli ,

    Roles Investigation, Methodology, Validation

    ‡ These authors also contributed equally to this work.

    Affiliation Clinical Microbiology Service, INEI-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina

  • Barbara Wisner ,

    Roles Investigation, Methodology

    ‡ These authors also contributed equally to this work.

    Affiliation Clinical Microbiology Service, INEI-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina

  • Cecilia Sorhouet Pereira ,

    Contributed equally to this work with: Angela Gentile, Maria Paula Della Latta, Cecilia Sorhouet Pereira, Maria del Valle Juarez, Adriana Efron

    Roles Formal analysis, Methodology, Supervision, Writing – original draft

    Affiliation Clinical Microbiology Service, INEI-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina

  • Mabel Regueira ,

    Roles Investigation, Project administration

    ‡ These authors also contributed equally to this work.

    Affiliation Clinical Microbiology Service, INEI-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina

  • Maria del Valle Juarez ,

    Contributed equally to this work with: Angela Gentile, Maria Paula Della Latta, Cecilia Sorhouet Pereira, Maria del Valle Juarez, Adriana Efron

    Roles Data curation, Formal analysis, Methodology, Writing – original draft

    Affiliation Epidemiology Division, Dr Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina

  • Veronica Umido ,

    Roles Investigation, Methodology

    ‡ These authors also contributed equally to this work.

    Affiliation Epidemiology Division, Dr Ricardo Gutiérrez Children’s Hospital, Buenos Aires, Argentina

  • Adriana Efron

    Contributed equally to this work with: Angela Gentile, Maria Paula Della Latta, Cecilia Sorhouet Pereira, Maria del Valle Juarez, Adriana Efron

    Roles Conceptualization, Formal analysis, Funding acquisition, Investigation, Supervision, Writing – original draft

    Affiliation Clinical Microbiology Service, INEI-ANLIS Dr. Carlos G. Malbrán, Buenos Aires, Argentina



Neisseria meningitidis (Nm) pharyngeal carriage is a necessary condition for invasive disease. We present the first carriage study in children in Buenos Aires, Argentina, considering 2017 as a transition year. Aims: to assess the rate of Nm carriage, to determine genogroup, clonal complex and outer membrane protein distribution, to determine carriage risk factors by age.


Cross-sectional study including children 1–17 yrs, at Ricardo Gutiérrez Children’s Hospital in Buenos Aires 2017. Oro-pharyngeal swabs were taken and cultured within a short time after collection. Genogroup was determined by PCR and clonal complex by MLST. Categorical variables were analyzed.


A total of 1,751 children were included. Group 1: 943 children 1–9 yrs, 38 Nm were isolated; overall carriage 4.0%. Genogroup distribution: B 26.3%, W 5.3%, Y 2.6%, Z 5.3%, other groups 7.9% and capsule null (cnl) 52.6%. Participating in extracurricular activities was the only independent predictor of Nm carriage. Group 2: 808 children 10–17 yrs, 76 Nm were isolated; overall carriage 9.4%. Genogroup distribution: B 19.7%, C 5.3%, W 7.9%, Y 9.2%, Z 5.3%, other groups 7.9% and cnl 44.7%. Independent predictors of carriage: attending pubs/night clubs and passive smoking (adjusted OR: 0.55, 95%CI = 0.32–0.93; p = 0.025).


Overall carriage was higher in 10–17 yrs. The isolates presenting the cnl locus were prevalent in both age groups and genogroup B was the second most frequent.


Neisseria meningitidis (Nm) is a leading cause of invasive diseases such as meningitis and septicaemia. Twelve different serogroups have been defined based on chemical composition and immunological specificity of capsular polysaccharides (A, B, C, E, H, I, K, L, W, X, Y, Z); most cases of invasive disease are caused by serogroups A, B, C, W, X and Y. Meningococci can be subdivided into serotypes and serosubtypes based on outer membrane proteins PorB and PorA respectively. In addition, immunotypes have been described dependant on the antigenic composition of the lipopolysaccharide [1]. Different groups of related sequence types, known as clonal complexes (CC) and hypervirulent lineages have been identified using molecular biology techniques [24].

While humans are the only known reservoir of Nm, meningococci are generally commensal organisms colonizing the nasopharynx, a phenomenon known as carriage, which can be transient or evolve into invasive meningococcal disease (IMD). Carriage is necessary for IMD to occur [5]. Some studies report asymptomatic carriage triggers an immune response providing protection [6]. Better understanding of factors influencing carriage is crucial to clarify disease dynamics like occur with conjugate polysaccharide vaccines, that can impact carriage and contribute to population immunity. Carriage prevalence increases with age, rates ranging from 4.5% in children to 23.7% in adolescents have been reported worldwide; children over 10 years of age, adolescents and young adults are the main reservoirs of Nm and are mostly responsible for transmission [7,8].

Meningococcal carriage rates are higher in closed or semi/enclosed communities (military personnel, university students), and in close contacts of patients with IMD. Several risk factors have been associated with carriage including cigarette smoking, exposure to passive smoking, intimate kissing and certain social behaviours such as frequenting pubs or nightclubs [911].

Global incidence of IMD in Argentina ranges from 0.4 to 0.7 cases per 100,000 population per year, mainly affecting children under the age of 5 years. Highest rates are observed in infants under 12 months (13.2 cases per 100,000), 64% of whom are under 9 months. The incidence of IMD in Argentine, does not increase in adolescents [12].

Genogroups B and W are the main cause of invasive disease in the country, and corresponded to 91% of all clinical isolates between 2012 and 2015. Genogroup B proportion has increased substantially in recent years accounting for 57% of all samples analysed at the National Reference Laboratory (NRL) for Meningitis and Acute Bacterial Respiratory Infections INEI-ANLIS C. G. Malbrán in 2017. Other common genogroups were W (25.3%), C (11.4%) and Y (6.3%) [1315].

In January 2017, the quadrivalent meningococcal conjugate vaccine MenACYW (conjugated to the non-toxic CRM197 derivative of diphtheria toxin) was included in the National Immunization Program (NIP), as a combined strategy targeting both infants (2+1 doses at 3, 5 and 15 months) and adolescents (single dose at 11 years). We consider 2017 as a transition year, since in that moment the strategy began with infants aged 3 and 5 months and in adolescents coverage was less than 50%. This study was carried out before local regulatory authorities had approved meningococcal B vaccine use [16].

The aim of this study was to assess Nm oropharyngeal carriage rates in children and adolescents attending a public, tertiary children’s hospital in the city of Buenos Aires, analyse risk factors in different age groups and determine circulating serogroups, clonal complexes and outer membrane protein distribution.

Materials and methods

Between March and December 2017, we carried out an observational, cross-sectional study in 1751 children and adolescents aged 1 to 17 years old at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires city. Participants were distributed into two age groups: 1 to 9 years (group 1, n = 943) and 10 to 17 years old (group 2, n = 808). The sample size was chosen based on an estimated meningococcal carriage rate of 2.5% (95% confidence interval (CI) 1.5–3.5) for the 1 to 9 year-olds and 5% (95% CI 3.5–6.5) for the older children. At the moment of the design of our study, we hoped to obtain at least 100 Nm samples positive to be analysed. Based on previous Nm carriage studies carried on in Argentina, we calculated to need 1740 samples to get this 100 Nm to study.

Inclusion criteria

Children and adolescents aged 1 to 17 years attending the outpatient clinic at the Ricardo Gutiérrez Children’s Hospital in Buenos Aires.

Exclusion criteria

Subjects with fever at the time of swab collection, immunodeficiency disorders (congenital, acquired, or secondary immune disorders due to treatment, cancer, Down Syndrome), prior meningococcal conjugate vaccination and patients receiving antimicrobial treatment at the time of the study or in the past 24 hours were excluded.

Subject recruitment

A convenient sampling was carried out. Every subject attending to the hospital was invited to participate in the study, and asked to sign an informed consent/assent form before swabs were collected. In all cases, children were enrolled in the presence of their parents or guardians, who also signed an informed consent/assent form.

Data collection

A questionnaire was used to collect data on: demographics (age, gender, place of residence); crowded housing conditions; maternal educational level (partial or complete primary studies; partial or complete secondary studies; partial or complete university studies); cigarette smoking; exposure to passive smoking; school attendance (kindergarten, school); extracurricular activities (frequent -2 or more days in a week- contact with other children in sports/arts or other activities outside the school); pub/nightclub attendance. (S1 File).

Participants were considered carriers when nasopharyngeal swab cultures were positive for Nm (excluding other Neisseria sp). Data were collected anonymously, privacy rights of patients were observed in all cases in accordance with local legislation and the World Medical Association Declaration of Helsinki International Code of Ethics for experiments involving humans. The protocol and informed consent form were approved by the Ricardo Gutierrez Children Hospital Independent Committee on Ethics in Investigation.

Isolation and characterization of N. meningitidis

Oro-pharyngeal swab samples were obtained through the mouth from the posterior wall of the oropharynx by trained staff, and immediately placed in Amies-Charcoal transport medium (Britania, Argentina). Samples transferred to the NRL within 5 hours of collection were plated onto modified Thayer-Martin medium (Britania, Argentina), incubated at 37°C in a humid atmosphere containing 5% CO2 and examined after 24 and 48 hours. Colonies characteristic of Neisseria sp. were sub-cultured on blood agar medium for species identification by Gram staining, oxidase reaction (Britania, Argentina), gamma-glutamyl aminopeptidase reaction (ROSCO, MEDICA-TEC) and Bruker Biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

Isolates identified as N. meningitidis were confirmed by PCR using specific primers for detecting crgA gene, capsular transport gene ctrA and genogroups A, B, C, E, W, X, Y and Z [1719]. Isolates negative for crgA and ctrA PCR were re-tested by PCR for presence of the capsule null region (cnl) [20].

To determine sequence type (ST) and clonal complex (CC), Multilocus Sequence Typing (MLST) was performed as previously described by Maiden et al., using primers listed on the Neisseria PubMLST website ( [3].

For the characterization of PorA genotype, Factor H-binding protein (fHbp) and neisserial heparin-binding antigen (NHBA), PCR amplification of variable region gene fragments followed by standard DNA sequencing was performed [2124]. The assignment of genotype, variant family and peptide variant respectively was achieved using the blast tool of the website ( [3]. The nomenclature scheme for fHbp peptide according to Novartis was used. For NHBA the peptides variants designations from Bexsero Antigen Sequence Typing (BAST) was the chosen nomenclature for show the results.

The presence of neisserial adhesion A (NadA) gene was determined by PCR amplification as previously describe [25].

All the primers used in this study for PCR and sequence analyses are listed in S1 Table.

Statistical analysis

Categorical variables were analysed using the χ2 test with Yates correction and the Wilcoxon test was applied for median age comparison. Odds ratio (OR) with 95% CI was used for association analysis; a bivariate analysis was performed initially to identify significant associations and multivariable logistic regression subsequently carried out to establish independent predictors of Nm carriage. P values < 0.05 were considered statistically significant. STATA/SE version 13 was used for the analysis. A logistic regression model was constructed to identify predictors of Nm carriage. Variables significantly associated with carriage in the crude analysis and/or those considered clinically relevant, were added one at a time to the multivariable model and only those showing significant association with the outcome in the multivariable context (Wald test) were retained in the final model. Changes in coefficients were examined to find confounding variables. Model calibration and discrimination were evaluated using Hosmer-Lemeshow goodness-of-fit test and area under the ROC curve.


A total of 1751 children were enrolled, 943 1–9 years (Group 1) and 808 10–17 years (Group 2). Demographics and epidemiologic characteristics of each group are shown in Table 1.

Table 1. Characteristics of patients according to age groups (Group 1: 1–9 years and Group 2: 10–17 years).

Nm carriage rate was 4% (n = 38) in group 1 and 9.4% (n = 76) in group 2 (S1 Fig). Nm carriage percentage increased with age (S2 Fig).

Multivariable analysis showed participating in extracurricular activities was associated with Nm carriage in group 1 (OR: 2.25; 95% CI: 1.16–4.36; p = 0.016). In group 2, visiting pubs/nightclubs was carriage associated (OR: 3.37; 95% CI: 1.39–9.98; p = 0.009), whereas passive smoking was not carriage associated (OR: 0.51; 95% CI: 0.30–0.89; p = 0.018) (Table 2). We performed a stratified analysis by age, dividing Group 2 into two subgroups. The cut-off point was established at 13 years, which is the age from which adolescents can go to pubs. In the subgroup aged 13 to 17 years (n = 343), the OR for the variable of attendance at pubs was 3 (CI 95% 1.1–8.4 p = 0.036).

Table 2. Results of multiple logistic regression: Independent predictors of Nm carriage according to age group.


The isolates harboring the cnl locus were predominant in both age groups followed by genogroup B. A total of 38 isolates were identified in Group 1: cnl 52.6% (20), B 26.3% (10), other groups 7.9% (3), W 5.3% (2), Z 5.3% (2), and Y 2.6% (1). In group 2, 76 isolates were found: cnl 44.7% (34), B 19.7% (15), Y 9.2% (7), W 7.9% (6), other groups 7.9% (6), C 5.3% (4), and Z 5.3% (4).

Clonal complexes

Clonal complexes were determined in 32 of 38 Nm isolates in group 1 and in 73 of 76 isolates in group 2. In both age groups, ST-198 and ST-1136 CCs were identified only among cnl isolates, ST-865 and ST-32 were identified only among genogroup B and ST-11 only among genogroup W. ST 41–44 was most often associated with genogroup B (S3 and S4 Figs).

Outer membrane protein sequencing

PorA was identified in 87 out of 105 isolates; one variable region sequence was determined in 13 isolates. Due to the high degree of heterogeneity among genogroups, differentiation by age group was not possible. The isolates presenting cnl locus were mainly associated with porA 22,14 (13/47) (S5 Fig). As regards genogroup B, the number of isolates was too low to identify any porA predominance (S6 Fig). In the ST-198 CC, porA 22,14 predominated (12/31), in ST-35 CC porA 22–1,14 predominated (8/11), in ST-865 only porA 21,16–36 was identified (3/3), and ST-11 was only associated with porA 5,2 (3/3).

We were able to identify fHbp peptides variant in 22 isolates belonging to group 1 (68.8%) and in 65 belonging to group 2 (89.0%); fHbp variant family 2 predominated in both. ST-198 CC was only associated with fHbp variant family 1; ST-41/44 and ST-865 CCs were associated with fHbp variant family 2. A single group 2 isolate expressed fHbp variant family 3 (ST-461, genogroup C) (S7 and S8 Figs).

NHBA was determined in 67 isolates, 14 in group 1(43.8%) and 51 in group 2 (69.9%). A high degree of variability in NHBA variants was found, 23 different peptides were identified. ST-198 was associated with peptide 10 (4/7 group 1 and 18/24 group 2), ST-35 with peptide 21 (1/3 group 1 and 6/8 group 2), ST-1136 with peptide 145 and ST-175 with peptide 9.

NadA was identified in 10.5% (n:4) of isolates in group 1 (B:2, W:1, Z:1) and in 9.6% (n:7) of isolates in group 2 (Y:3, B:2, W:1, NG:1).

The isolate information of molecular data is provided in S2 Table.


This was the first study of Nm oropharyngeal carriage in children and adolescents conducted in Argentina before introduction of the quadrivalent meningococcal conjugate vaccine to the NIP. Collecting baseline data is crucial to make decisions based on the local epidemiology, since carriage of serogroups and CCs varies by geographic regions [26]. Impact of immunization on invasive disease and carriage rates after introduction of new conjugate vaccines is also important to measure. In the United Kingdom, two years after MenC conjugate vaccine was used in the national immunization program, carriage prevalence in adolescents were reduced from 0.98% to 0.5%, confirming vaccine vaccine effect on acquisition of carriage strains [27].

Carriage prevalence varies with age, epidemiology of circulating Nm and local vaccination policies. In Europe and in USA, rates of carriage are very low in infants and young children increasing substantially in adolescents [28]. Several studies conducted in Latin America have shown varying results between countries. In Cuba, Martinez et al found highest Nm carriage rates in children over the age of 9 years, peaking in 11 year-olds (36.4%) [7]. In Brazil, carriage prevalence in 2015 was 9.9% in adolescents between 11 and 19 years of age [29]. Rates reported in Mexico were lower, 1.9% in children and 2.9% in adolescents [30].

In this study, the population was divided into two age groups, below or above the age of 10 years, based on evidence that carriage was higher in adolescents and taking into account that the classification of WHO, define the beginning of the adolescence at this age. We found a higher prevalence rate in adolescents (9.4%), similar to those reported in a recent meta-analysis of Nm carriage in the American continent (approximately 9% prevalence in this age group in the Southern Cone region) [26].

Several risk factors have been associated with meningococcal carriage including male gender, number of individuals living together, parental educational level, exposure to cigarette smoke, attending pubs/nightclubs [11,26,31,32]. In our study, pub/nightclub visits in adolescents and participation in extracurricular recreational activities in 1–9 year-olds were significantly associated with increased risk of being a carrier, a finding consistent with existing knowledge that close personal contact is linked to carriage risk. No association was found between other risk factors (high number of household members, parental educational level, school attendance, history of recent antibiotic use) and carriage.

Although passive smoking is often associated with carriage, we found mixed evidence for the effect of passive smoking on carriage [10,33]. Smoke exposure is a known risk factor for developing IMD, however the relationship with carriage is less clear since some studies have not found an association between passive smoking and carriage [34]. Several microbiological hypotheses help explain the mechanisms by which cigarette smoke damages the nasopharyngeal mucosa, thus affecting carriage. Smoke inhibits neutrophil phagocytic activity, dampens natural killer cell cytotoxicity, reduces immunoglobulin A secretion, induces oxidative stress and has a negative effect on immune response including response to vaccination. Passive coating of the oropharyngeal mucosa with tobacco smoke components can potentially enhance binding of pathogenic bacteria, including meningococci [33,35,36].

Some authors believe that increased risk of carriage in children exposed to passive smoking is due to close contact with the smoker rather than to effects of the smoke per se [29]. However, studies are often biased as information is provided by parents and may be incorrect; further investigations measuring nicotine levels are needed to clarify this issue.

In concordance with other similar regional reports, cnl meningococci was the most common isolate identified [26,38]. Genogroup B was the second most prevalent as our previous study [38]. Predominance of cnl strains has been widely reported in healthy carriers [37]. Clonal complexes associated with cnl isolates were ST-198, as previously described in healthy carriers in Argentina, and to a lesser degree ST-1136, which were only found in 1–9 year-olds [38]. On analysing the antigenic composition of ST-198 CC, we observed a homogeneous distribution of surface proteins variants.

Genogroup B was the second most predominant genogroup in both age groups, coinciding with reports of prevalent genogroup causing meningococcal disease in the country [1315]. Clonal complexes among genogroup B meningococci from carriage samples were the same CCs as those identified in IMD in Argentina in previous studies [39,40]. This genogroup harbored various CCs and outer membrane proteins. This variability reflects local epidemiological conditions characterised by a low number of cases per year and diverse antigenic profile of circulating disease isolates [39].

In a prior study carried out in Argentina, genogroup B ST-865 CC was prevalent in IMD; even if this CC was found to cause sporadic cases of meningococcal disease in other countries, in our country it behaves as predominant for many years (2006–2011) in genogroup B [39,40]. The situation remains the same for the period 2012–2014 (unpublished data). In this study, only three isolates belonging to this CC were identified, two in the younger age group and one in the older group.

All three isolates presented characteristic surface proteins, porA 21,16–36 and fHbp variant family 3, and did not exhibit NadA. Eight isolates belonging to ST-41/44, six belonging to ST-35, and 5 belonging to ST-32 were found, antigenic profiles were heterogeneous. ST-41/44 and ST-32 complexes exhibited a high diversity of porA antigens, whereas ST-35 presented mainly porA 22–1,14, as found in isolates from IMD. With regard to fHbp peptides, all three CCs harbored variant family 2 exclusively. NadA gene was found solely in ST-32 CC. Finally, although NHBA presence was variable, ST-35 CC presented mainly peptide 21. Antigenic diversity of genogroup B in healthy carriers coincided with endemic IMD epidemiology in Argentina.

Genogroup W carriage rate was low and the hypervirulent, hyperinvasive ST-11 CC was detected, only 1 isolate in group 1 and 2 isolates in group 2 (3.1% and 2.7% respectively). In Chile, an extensive carriage study was recently conducted after an outbreak of serogroup W meningococcal disease with high case-fatality rate. Although overall prevalence of genogroup W carriage was low, hyperinvasive ST-11 was the only clone identified [41,42]. In this study, genogroup W showed a variable antigenic profile; less than half of isolates belonged to ST-11, and harboured porA 5.2, fHbp variant family 2 and the NadA gene, similar to strains isolated from invasive disease cases in the country [39]. The remaining genogroup W isolates belonged to various CCs, mainly-ST-35 which was also found in genogroup B.

The B:ST-865 clone and the hyperinvasive W: ST-11clone were already found in a low proportion in previous studies [38]. The reason why these clones are found in low proportion in healthy carriers is still unclear. It may be due to their virulent characteristics, but further studies would be necessary to answer this question.

Despite not being able to analyse 100% of the sequences of the most relevant protein antigens, we believe that these results, although partial, enrich the knowledge of the description of the clones present in carriage in our environment. For future studies it would be very useful to have more tools for the performance of the characterization of the isolates.

Other genogroups were isolated in lower numbers, namely C, Y and Z, showing variable CCs and outer membrane proteins. Although genogroup Z is not a cause of IMD in Argentina, this strain was identified in healthy carriers. Circulating CCs associated in carriers with genogroup Y were different to those found in isolates causing IMD, in which ST-167 predominated [39,43].

Isolates of genogroup C were heterogeneous as seen in prior carriage and invasive disease studies; no group C carriage was observed in young children, but 5% in older children [38,39]. Only one isolate of clonal complex ST-103 was detected, although this clone is the main cause of invasive disease in neighbouring Brazil [29,44].

One of the main limitations to this study is the fact that the population included children attending an outpatient clinic at a public tertiary children’s hospital in Buenos Aires City, which may not be representative of country population. To minimize this bias, we only selected participants without the previously described immunosuppressing disorders. Other limitation was that the sample size did not allow stratified analysis within the defined groups. We must mention that the heterogeneity within the groups could be a limitation because the groups contain a large number of age groups with different social, immunological and developmental stages, and therefore there may be confounding factors. Other measures to minimize the bias of detection were taken: samples were plated promptly, PCR was used to identify genogroups, vaccinated children were excluded and herd immunity had not yet been achieved during the year of the vaccine introduction (2017).

In conclusion N. meningitidis carrier rates were higher among 10 to 17 year olds. The isolates containing the cnl locus were predominant in both age groups and genogroup B was the most common capsulated strain. Extracurricular activities in children and frequenting pubs/nightclubs in adolescents showed positive correlation with Nm carriage. Association between CC and outer membrane proteins in genogroups B and W coincide with those of IMD for the country. Genogroup Z was detected, although no cases of invasive disease have been reported in this country.

Supporting information

S1 Fig. Distribution of Neisseria species according to age group.


S2 Fig. Samples (Nm positive, Nm negative) and Nm carriage percentage by age.


S3 Fig. Distribution of clonal complexes by genogroup in the 1–9 year old group.


S4 Fig. Distribution of clonal complexes by genogroup in the 10–17 year old group.


S5 Fig. Distribution of PorA types in cnl isolates.


S6 Fig. Distribution of PorA types in genogroup B isolates.


S7 Fig. Distribution of fHbp variant families by clonal complex in the 1–9 year old group.


S8 Fig. Distribution of fHbp variant families by clonal complex in the 10–17 year old group.


S1 Table. Oligonucleotides used in N. meningitidis molecular typing.



  1. 1. Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB, Jolley KA, et al. Emerging Infectious Diseases • Vol. 19, No. 4, April 2013.
  2. 2. Caugant DA. Population genetics and molecular epidemiology of Neisseria meningitidis. APMIS 1998 May;106(5):505–25. pmid:9674888
  3. 3. Maiden MC, Bygraves JA, Feil E, Morelli G, Russell JE, Urwin R, et al. Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 1998 Mar 17;95(6):3140–5. pmid:9501229
  4. 4. Yazdankhah SP, Kriz P, Tzanakaki G, Kremastinou J, Kalmusova J, Musilek M, et al. Distribution of serogroups and genotypes among disease-associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece, and Norway. J Clin Microbiol 2004 Nov;42(11):5146–53. pmid:15528708
  5. 5. Olsen SF, Djurhuus B, Rasmussen K, Joensen HD, Larsen SO, Zoffman H, et al. Pharyngeal carriage of Neisseria meningitidis and Neisseria lactamica in households with infants within areas with high and low incidences of meningococcal disease. Epidemiol Infect 1991 Jun;106(3):445–57. pmid:1904825
  6. 6. Kremastinou J, Tzanakaki G, Pagalis A, Theodondou M, Weir DM, Blackwell CC. Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica. FEMS Immunol Med Microbiol 1999 May;24(1):73–8. pmid:10340715
  7. 7. Martinez I, Lopez O, Sotolongo F, Mirabal M, Bencomo A. [Carriers of Neisseria meningitidis among children from a primary school]. Rev Cubana Med Trop 2003 Sep-Dec;55(3):162–8. pmid:15849920
  8. 8. Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 2010 Dec;10(12):853–61. pmid:21075057
  9. 9. Olcen P, Kjellander J, Danielsson D, Lindquist BL. Epidemiology of Neisseria meningitidis; prevalence and symptoms from the upper respiratory tract in family members to patients with meningococcal disease. Scand J Infect Dis 1981;13(2):105–9. pmid:6797052
  10. 10. Stanwell-Smith RE, Stuart JM, Hughes AO, Robinson P, Griffin MB, Cartwright K. Smoking, the environment and meningococcal disease: a case control study. Epidemiol Infect 1994 Apr;112(2):315–28. pmid:8150006
  11. 11. MacLennan J, Kafatos G, Neal K, Andrews N, Cameron JC, Roberts R, et al. Social behavior and meningococcal carriage in British teenagers. Emerg Infect Dis 2006 Jun;12(6):950–7. pmid:16707051
  12. 12. Argentina, Ministerio de Salud de la Nación. Fundamentos de la introducción de la vacuna tetravalente (ACYW) conjugada contra Meningococo al Calendario Nacional de Inmunizaciones. 2017 [cited 10 March 2019];
  13. 13. Efron A, Gagetti P, Sorhouet Pereira C, Maldonado M, Gaita L, Moscoloni M, et al. Vigilancia Laboratorial Nacional de Serogrupos y Resistencia Antimicrobiana de aislamientos de Neisseria meningitidis causantes de enfermedad invasiva en Argentina 2009–2015 CAM-ALAM. Rosario Argentina, 2016.
  14. 14. Gagetti P, Efron A, Faccone D, Santos M, Moscoloni MA, Red Laboratorial de Vigilancia de Nme en Argentina, Regueira M, Corso A. Vigilancia Nacional de Resistencia a los Antimicrobianos y Serogrupos en Aislamientos de Neisseria meningitidis causantes de Enfermedad Invasiva en Argentina: Actualización 2014–2017. VIII Congreso de SADEBAC 2018. CABA, Argentina. 6–9 de noviembre de 2018.
  15. 15. Informe Regional SIREVA 2017, Argentina.
  16. 16. Argentina, Ministerio de Salud de la Nación. Fundamentos de la introducción de la vacuna tetravalente (ACYW) conjugada contra Meningococo al Calendario Nacional de Inmunizaciones. 2016 [cited 10 March 2019];
  17. 17. Taha MK. Simultaneous approach for nonculture PCR-based identification and serogroup prediction of Neisseria meningitidis. J Clin Microbiol 2000 Feb;38(2):855–7. pmid:10655397
  18. 18. Bennett DE, Mulhall RM, Cafferkey MT. PCR-based assay for detection of Neisseria meningitidis capsular serogroups 29E, X, and Z. J Clin Microbiol 2004 Apr;42(4):1764–5. pmid:15071043
  19. 19. Guiver Malcolm, Borrow Ray, Marsh John, Gray Stephen J., Kaczmarski Edward B., Howells David, Boseley Paul, Andrew J. FoxEvaluation of the Applied Biosystems automated Taqmanpolymerase chain reaction system for the detection of meningococcalDNA.FEMS Immunology and Medical Microbiology 2000 28 173–179. pmid:10799809
  20. 20. Claus H, Maiden MC, Maag R, Frosch M, Vogel U. Many carried meningococci lack the genes required for capsule synthesis and transport. Microbiology 2002 Jun;148(Pt 6):1813–9. pmid:12055301
  21. 21. Maiden M. C., Bygraves J. A., McCarvil J., and Feavers I. M. 1992. Identification of meningococcal serosubtypes by polymerase chain reaction. J Clin Microbiol 30:2835–41. pmid:1452652
  22. 22. Saunders N. B., Zollinger W. D., and Rao V. B. 1993. A rapid and sensitive PCR strategy employed for amplification and sequencing of porA from a single colony-forming unit of Neisseria meningitidis. Gene 137:153–62. pmid:8299943
  23. 23. Suker J., Feavers I. M., Achtman M., Morelli G., Wang J. F., and Maiden M. C. 1994. The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation. Mol Microbiol 12:253–65. pmid:8057850
  24. 24. Jacobsson S., Thulin S., Molling P., Unemo M., Comanducci M., Rappuoli R., and Olcen P. 2006. Sequence constancies and variations in genes encoding three new meningococcal vaccine candidate antigens. Vaccine 24:2161–8. pmid:16321460
  25. 25. Lucidarme J, Comanducci M, Findlow J, Gray SJ, Kaczmarski EB, Guiver M, et al. Characterization of fHbp, nhba (gna2132), nadA, porA, sequence type (ST), and genomic presence of IS1301 in group B meningococcal ST269 clonal complex isolates from England and Wales. J Clin Microbiol 2009 Nov;47(11):3577–85. pmid:19759227
  26. 26. Moreno J, Hidalgo M, Duarte C, Sanabria O, Gabastou JM, Ibarz-Pavon A. Characterization of Carriage Isolates of Neisseria meningitidis in the Adolescents andYoung Adults Population of Bogota (Colombia). PLoS ONE 2015; 10(8):e0135497. pmid:26322796
  27. 27. Jeppesen C, Snape M, Robinson H, Gossger N, John T, Voysey M, et al. Meningococcal carriage in adolescents in the United Kingdom to inform timing of an adolescent vaccination strategy. Journal of Infection (2015) 71, 43–52. pmid:25709085
  28. 28. Claus H, Maiden MC, Wilson DJ, McCarthy ND, Jolley KA, Urwin R, et al. Genetic analysis of meningococci carried by children and young adults. J Infect Dis 2005 Apr 15;191(8):1263–71. pmid:15776372
  29. 29. Cassio de Moraes J, Kemp B, de Lemos AP, Outeiro Gorla MC, Lemes Marques EG, Ferreira Mdo C, et al. Prevalence, Risk Factors and Molecular Characteristics of Meningococcal Carriage Among Brazilian Adolescents. Pediatr Infect Dis J 2015 Nov;34(11):1197–202. pmid:26222063
  30. 30. Espinosa de los Monteros LE, Aguilar-Ituarte F, Jimenez-Rojas LV, Kuri P, Rodriguez-Suarez RS, Gomez-Barreto D. Prevalence of Neisseria meningitidis carriers in children under five years of age and teenagers in certain populations of Mexico City. Salud Publica Mex 2009 Mar-Apr;51(2):114–8. pmid:19377737
  31. 31. Bogaert D, Hermans PW, Boelens H, Sluijter M, Luijendijk A, Rumke HC, et al. Epidemiology of nasopharyngeal carriage of Neisseria meningitidis in healthy Dutch children. Clin Infect Dis 2005 Mar 15;40(6):899–902. pmid:15736029
  32. 32. Weckx LY, Puccini RF, Machado A, Goncalves MG, Tuboi S, de Barros E, et al. A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1–24 years in the city of Embu das Artes, Sao Paulo, Brazil. Braz J Infect Dis 2017 Nov—Dec;21(6):587–95. pmid:28711456
  33. 33. Stuart JM, Cartwright KA, Robinson PM, Noah ND. Effect of smoking on meningococcal carriage. Lancet 1989 Sep 23;2(8665):723–5. pmid:2570968
  34. 34. Blackwell CC, Weir DM, James VS, Todd WT, Banatvala N, Chaudhuri AK, et al. Secretor status, smoking and carriage of Neisseria meningitidis. Epidemiol Infect 1990 Apr;104(2):203–9. pmid:2323355
  35. 35. Rashid H, Booy R. Passive smoking, invasive meningococcal disease and preventive measures: a commentary. BMC Med 2012 Dec 10;10:160. pmid:23228079
  36. 36. Huttunen R, Heikkinen T, Syrjanen J. Smoking and the outcome of infection. J Intern Med 2011 Mar;269(3):258–69. pmid:21175903
  37. 37. Dolan-Livengood JM, Miller YK, Martin LE, Urwin R, Stephens DS. Genetic basis for nongroupable Neisseria meningitidis. J Infect Dis 2003 May 15;187(10):1616–28. pmid:12721942
  38. 38. Efron A, Gaita L, Sorhouet Pereira C, Regueira M, Vizzoti C, Morriconi L, Bolino P, Ibarz Pavón A. Asymptomatic carriage of Neisseria meningitidis (Nm) among 18–21 year old students attending the Universidad Nacional de la Plata (UNLP)-Buenos Aires- Argentina between September 2012 and March 2013. XIXth International Pathogenic Neisseria Conference (IPNC). Ashville USA, 2014.
  39. 39. Sorhouet-Pereira C, Efron A, Gagetti P, Faccone D, Regueira M, Corso A, et al. Phenotypic and genotypic characteristics of Neisseria meningitidis disease-causing strains in Argentina, 2010. PLoS One 2013;8(3):e58065. pmid:23483970
  40. 40. Neisseria meningitidis serogroupB (NmB) clones circulating in Argentina: impact on vaccination strategies. Sorhouet Pereira C; Efron A; Gaita L; Regueira M;Mollerach M;Taha M-K; Ibarz-Pavón AB. XIXth International Pathogenic Neisseria Conference (IPNC). 12 al 17 de octubre de 2014, Ashville U.S.A.
  41. 41. Diaz J, Carcamo M, Seoane M, Pidal P, Cavada G, Puentes R, et al. Prevalence of meningococcal carriage in children and adolescents aged 10–19 years in Chile in 2013. J Infect Public Health 2016 Jul-Aug;9(4):506–15. pmid:26819097
  42. 42. Araya P, Fernandez J, Del Canto F, Seoane M, Ibarz-Pavon AB, Barra G, et al. Neisseria meningitidis ST-11 clonal complex, Chile 2012. Emerg Infect Dis 2015 Feb;21(2):339–41. pmid:25625322
  43. 43. Abad R, Agudelo CI, Brandileone MC, Chanto G, Gabastou JM, Hormazabal JC, et al. Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region. J Infect 2009 Aug;59(2):104–14. pmid:19576638
  44. 44. Safadi MA, Carvalhanas TR, Paula de Lemos A, Gorla MC, Salgado M, Fukasawa LO, et al. Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010. Emerg Infect Dis 2014 May;20(5):806–11. pmid:24751156