Increase of Neisseria meningitidis W:cc11 invasive disease in Chile has no correlation with carriage in adolescents

Abstract

Neisseria meningitidis is a human exclusive pathogen that can lead to invasive meningococcal disease or may be carried in the upper respiratory tract without symptoms. The relationship between carriage and disease remains poorly understood but it is widely accepted that decreasing carriage by immunization should lead to a reduction of invasive cases. Latin America has experienced an increased incidence of serogroup W invasive cases of Neisseria meningitidis in the last decade. Specifically in Chile, despite low total incidence of invasive cases, serogroup W has become predominant since 2011 and has been associated with elevated mortality. Expecting to gain insight into the epidemiology of this disease, this study has used molecular typing schemes to compare Neisseria meningitidis isolates causing invasive disease with those isolates collected from adolescent carriers during the same period in Chile. A lower carriage of the serogroup W clonal complex ST-11/ET37 than expected was found; whereas, the same clonal complex accounted for 66% of total invasive meningococcal disease cases in the country that year. A high diversity of PorA variable regions and fHbp peptides was also ascertained in the carrier isolates compared to the invasive ones. According to the results shown here, the elevated number of serogroup W invasive cases in our country cannot be explained by a rise of carriage of pathogenic isolates. Overall, this study supports the idea that some strains, as W:cc11 found in Chile, possess an enhanced virulence to invade the host. Notwithstanding hypervirulence, this strain has not caused an epidemic in Chile. Finally, as genetic transfer occurs often, close surveillance of Neisseria meningitidis strains causing disease, and particularly hypervirulent W:cc11, should be kept as a priority in our country, in order to prepare the best response to face genetic changes that could lead to enhanced fitness of this pathogen.

Fig 1. Distribution of NM isolates according to age.

All isolates were grouped by age and serogroups were stacked within bars with different patterns from a) carriers (N = 184, 9–19 year olds) or b) IMD (N = 119, any age).

Fig 2. Distribution of NM isolates 2013 by serogroups and clonal complexes.

a) Isolates arranged by serogroup percentages show diversity among carriers whereas serogroups W and B account for almost all IMD isolates (N.G. = non-groupable). b) Isolates arranged by clonal complexes percentages resulting from MLST analysis presented a separation of serogroup B, both carriers and IMD isolates, into cc41/44 and cc32. Most NG isolates belonged to cc198, whereas all serogroup W isolates belonged to cc11. (Total number of samples: Carriers = 184 (9–19 yrs); IMD = 119 (any age)).

Fig 3. Distribution of PorA subtypes among NM isolates 2013.

a) PorA profiles from carrier isolates presented as percentages b) PorA profiles from carrier isolates were differentiated by colors within clonal complexes resulting from minimum spanning tree analysis of MLST. c) PorA profiles percentages from IMD isolates. d) PorA profiles from invasive isolates indicated by colors within clonal complexes as in b). (*ND = non-determined). Compare the dominance of P1.5,2,36 subtype among invasive isolates and the diversity among carrier isolates.

Fig 4. Distribution of fHbp peptides among NM isolates 2013.

FHbp peptides for all isolates were arranged by modular groups as previously described [32]. Percentages from total are displayed on respective bars. a) fHbp peptides from carrier isolates (N = 184) or b) fHbp peptides from IMD isolates (N = 119). Modular group VI and I predominated among carrier isolates, whereas modular group III did among invasive isolates.

Fig 5. Distribution of fHbp peptides within clonal complexes of NM isolates 2013.

fHbp peptides were differentiated by colors within clonal complexes arranged as minimum spanning trees. a) fHbp peptides distribution within carrier isolates (N = 184) b) fHbp peptides distribution within invasive isolates (N = 119).