Elsevier

Journal of Infection

Volume 59, Issue 2, August 2009, Pages 104-114
Journal of Infection

Molecular characterization of invasive serogroup Y Neisseria meningitidis strains isolated in the Latin America region

https://doi.org/10.1016/j.jinf.2009.06.001Get rights and content

Summary

Objectives

To improve the understanding of serogroup Y invasive meningococcal disease (IMD) in Latin America, particularly IMD molecular epidemiology; 166 Y serogroup isolates received at the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, and Costa Rica during 2000–2006 were characterized by their molecular markers.

Methods

This analysis included serological assays to determine serogroup/serotype/serosubtype, DNA sequencing and genotyping of the porB and/or porA genes, multilocus sequence typing (MLST) and fetA allele determination.

Results

Sixteen different antigenic combinations were observed. Sixty-two (37.3%) isolates were NT:P1.5 and 36 (21.7%) isolates were 14:NST. Thirty-two different STs appeared, but 3 STs (ST-1624, ST-23, and ST-5770) accounted for 69.9% (116) of the strains.

Most of the IMD isolates belonged to the ST-23, ST-167 clonal complexes or the group composed by ST-5770 and related STs.

Conclusions

Isolates obtained in Colombia and Costa Rica were similar to that of the United States, in that most sequence types belonged to the ST-23 clonal complex. IMD isolates found in Argentina appear to be the result of an independent event and did not spread from nearby countries, being the sequence type ST-1624 (ST-167 clonal complex) the most frequently found. We were unable to correlate an antigenic shift of outer membrane proteins with an increase of serogroup Y meningococcal cases in our collection of isolates.

Introduction

Neisseria meningitidis invasive disease can be rapidly fatal or result in a severe neurologic and vascular sequelae in spite of prompt antibiotic therapy. Although the majority of disease worldwide is sporadic, outbreaks and epidemics do occur. In this event, chemoprophylaxis and/or vaccination of the affected population is necessary, although at the early stages of an epidemic, these efforts may be hampered by limited supplies of prophylactic compounds or vaccine.1

N. meningitidis is a diverse bacterial species characterized by more frequent recombination than other bacterial species, and such dynamism may be associated with outbreaks or pandemics.2, 3 It is thought that hypervirulent clones of meningococci and changes in population immunity affect the rates of N. meningitidis disease. Further, the meningococcal polysaccharide capsule is a major virulence factor, and its heterogeneity is the basis for the N. meningitidis serogroup nomenclature.1

Serogroup B is the most frequently observed serogroup in industrialized countries, but no serogroup B vaccine is, as yet, widely available. In some countries, outer membrane vesicle components are used as anti-serogroup B antigens in vaccine formulations. However, vaccine specificity for endemic disease is limited, and a vaccine developed in one country may not be effective in another as a result of serogroup B heterogeneity.1, 4, 5 Further, geographical variations in the distribution of A, C, Y, and W135 serogroups are well known.1 Specifically, epidemic waves of serogroups A and W135 occur in the African Meningitis Belt, and serogroup Y hyperendemic incidence rates are observed among adolescents in North America. A complete understanding of N. meningitidis epidemiology requires monitoring of regional serogroup distributions and their incidence rates over time.2

Recently, the Reference Laboratory of the Instituto Nacional de Salud from Colombia reported a 50% increase in serogroup Y cases in 20066, 7 across all age groups. Slight increases in serogroup Y were also observed in Argentina, Costa Rica, Venezuela and Republica Dominicana.6 In contrast, serogroup Y meningococci has been only reported sporadically in other Latin American countries in close proximity (Brazil and Chile), and no apparent increase in serogroup Y disease has been observed in all of Latin America.6

In January of 2005, a meningococcal vaccine containing polysaccharide serogroups A, C, Y, and W135 conjugated to diphtheria toxoid, MCV4, was licensed for use in 11–55 year olds in the US,8 and in May 2006, Canada licensed the vaccine for use in 2 year olds and above. After initial licensure, vaccine usage was extended to children aged 2 through 10 in the US in October 2007. Eventually, this vaccine will be introduced to additional countries including Latin America. Because rates of serogroup Y diseases fluctuate unpredictably, the collection of baseline molecular epidemiology of N. meningitidis and invasive meningococcal disease (IMD) data is necessary not only to understand these fluctuations but also to improve IMD surveillance in the region.

Therefore, we have performed an antigenic and genetic characterization of serogroup Y isolates collected at the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, and Costa Rica, which were isolated for over a 7-year period (2000–2006). These analyses included serological assays to determine serogroup/serotype/serosubtype, DNA sequencing and genotyping of the porB and/or porA gene,9, 10 and multilocus sequence typing (MLST). MLST is the preferred format for data collection by the global surveillance for N. meningitidis, PubMLST3 (http://www.mlst.net/).

Section snippets

Bacterial isolates

N. meningitidis isolates from patients with invasive disease were collected at the National Reference Laboratories (NRL) of Argentina, Brazil, Chile, Colombia and Costa Rica, as part of national disease surveillance programs. The NRLs received an heterogeneous proportion of the meningococcal isolates in their respective countries: Argentina NRL received 45% of the confirmed cases at the national level, Brazil 25%, Colombia 27%, Chile 65%, and Costa Rica 40%, and this proportion was stable over

Bacterial isolate collection

The collection of N. meningitidis isolates presented here represents 170 isolates collected by the NRLs of 5 Latin American countries (Argentina, Brazil, Chile, Colombia, and Costa Rica). The majority of isolates were collected over a 7-year period (2000–2006) except for those from the Costa Rican NRL, which collected isolates from 2000 through 2004 (Table 1). Four isolates, originally identified as serogroup Y, were subsequently characterized as serogroup B at the Spanish laboratory and

Discussion

This study represents the largest analysis of IMD serogroup Y isolates in Latin American and illustrates the recent capabilities of the SIREVA II surveillance network in Latin America and Caribbean Regions.6 However, the epidemiology of the disease and the molecular epidemiology of N. meningitidis still need to be well defined in this region. The number of cases and relative frequency of serogroups documented in each country indicate trends that need to be further documented with continued

Acknowledgments

We thank all hospitals belonging to the surveillance networks in Argentina, Brazil, Chile, Colombia and Costa Rica for sending the strains to the National Reference Laboratories. We also thank Dr. Elizabeth Castañeda and Olga M. Sanabria from the INS (Colombia) and Ana Paula de Lemos from the Instituto Adolfo Lutz (Brazil) for their contributions to the study.

This study was funded by Sanofi-Pasteur SA, through an institutional agreement with the Institute of Health Carlos III. E.M. and R.L. are

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