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Genomic surveillance of Neisseria meningitidis serogroup W in Portugal from 2003 to 2019

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Abstract

In recent years, a change in the epidemiology of meningococcal disease caused by Neisseria meningitidis serogroup W (MenW) has been observed worldwide, with the emergence of new sublineages associated with a higher rate of fatal cases. The present study intends to describe the epidemiology of invasive meningococcal disease (IMD) due to MenW in Portugal between 2003 and 2019, and to genetically characterize population structure. Despite MenW has a low incidence in Portugal, having almost disappeared from 2008 to 2015, since 2016, the number of MenW cases has been steadily increasing at a rate of ~ twofold per year, with more than 80% of the characterized isolates belonging to clonal complex 11 (cc11). Core-genome phylogeny of 25 Portuguese (PT) MenW isolates showed a strain clustering mainly either with the Original UK or the UK 2013 sublineages. Our study also reported for the first time the presence of distinct prophages with a notable overrepresentation of an ~ 32–35-kb PS_1-like prophage found in MenW cc11 genomes. The presence of the PS_1-like prophage in almost all 4723 cc11 genomes selected from Neisseria PubMLST database regardless of the capsular group they belong to suggests an ancestral acquisition of this mobile element prior to capsular switching events. Overall, by mimicking the scenario observed worldwide, this study reinforces the importance of a close monitoring of MenW disease, especially from cc11, in order to promptly adapt the vaccination plan for IMD control in Portugal. Moreover, future studies are needed to understand the putative contribution of prophages to fitness and virulence of PT MenW strains.

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Data availability

Raw sequence reads used in the present study were deposited in the European Nucleotide Archive (ENA) under the study accession number PRJEB36474.

References

  1. Christensen H, May M, Bowen L, Hickman M, Trotter CL (2010) Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 10(12):853–861. https://doi.org/10.1016/S1473-3099(10)70251-6

    Article  PubMed  Google Scholar 

  2. World Health Organization (2015) Meningococcal meningitis fact sheet #141 2015. http://www.who.int/mediacentre/factsheets/fs141/en/ Accessed 11 Apr 2019

  3. Pace D, Pollard AJ (2012) Meningococcal disease: clinical presentation and sequelae. Vaccine 30(SUPPL. 2):B3-9. https://doi.org/10.1016/j.vaccine.2011.12.062

    Article  PubMed  Google Scholar 

  4. Maiden MCJ, Bygraves JA, Feil E et al (1998) Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci 95(6):3140–3145. https://doi.org/10.1073/pnas.95.6.3140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bratcher HB, Corton C, Jolley KA, Parkhill J, Maiden MCJ (2014) A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes. BMC Genomics 15(1). https://doi.org/10.1186/1471-2164-15-1138

  6. Parikh SR, Campbell H, Bettinger JA et al (2020) The everchanging epidemiology of meningococcal disease worldwide and the potential for prevention through vaccination. J Infect 81:483–498. https://doi.org/10.1016/j.jinf.2020.05.079

    Article  PubMed  Google Scholar 

  7. European Centre for Disease Prevention and Control (2019) Invasive meningococcal disease. In: ECDC. Annual epidemiological report for 2017. ECDC, Stockholm

  8. Aguilera J-F, Perrocheau A, Meffre C, Hahné S (2002) Outbreak of serogroup W135 meningococcal disease after the Hajj pilgrimage, Europe, 2000. Emerg Infect Dis 8(8):761–67. https://doi.org/10.3201/eid0808.010422

    Article  PubMed  PubMed Central  Google Scholar 

  9. Centers for Disease Control and Prevention (CDC) (2000) Serogroup W-135 meningococcal disease among travelers returning from Saudi Arabia--United States, 2000. MMWR 49(16);345–6. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4916a2.htm

  10. Taha MK, Achtman M, Alonso JM et al (2000) Serogroup W135 meningococcal disease in Hajj pilgrims. Lancet 356(9248):2159. https://doi.org/10.1016/S0140-6736(00)03502-9

    Article  CAS  PubMed  Google Scholar 

  11. Mayer LW, Reeves MW, Al-Hamdan N et al (2002) Outbreak of W135 meningococcal disease in 2000: not emergence of a new W135 strain but clonal expansion within the electophoretic type–37 complex. J Infect Dis 185(11):1596–1605. https://doi.org/10.1086/340414

    Article  PubMed  Google Scholar 

  12. Koumaré B, Ouedraogo-Traoré R, Sanou I et al (2002) The first large epidemic of meningococcal disease caused by serogroup W135, Burkina Faso. Vaccine 25(SUPPL:1):37-41. 2007. https://doi.org/10.1016/j.vaccine.2007.04.038

    Article  Google Scholar 

  13. Taha M-K, Parent du Chatelet I, Schlumberger M et al (2002) Neisseria meningitidis serogroups W135 and A were equally prevalent among meningitis cases occurring at the end of the 2001 epidemics in Burkina Faso and Niger. J Clin Microbiol 40(3):1083–1084. https://doi.org/10.1128/JCM.40.3.1083-1084.2002

    Article  PubMed  PubMed Central  Google Scholar 

  14. Abad R, López EL, Debbag R, Vázquez JÁ (2014) Serogroup W meningococcal disease: global spread and current affect on the Southern Cone in Latin America. Epidemiol Infect 142(12):2461–2470. https://doi.org/10.1017/S0950268814001149

    Article  CAS  PubMed  Google Scholar 

  15. Ladhani SN, Beebeejaun K, Lucidarme J et al (2015) Increase in endemic Neisseria meningitidis capsular group W sequence type 11 complex associated with severe invasive disease in England and Wales. Clin Infect Dis 60(4):578–585. https://doi.org/10.1093/cid/ciu881

    Article  CAS  PubMed  Google Scholar 

  16. Knol MJ, Hahné SJM, Lucidarme J et al (2017) Temporal associations between national outbreaks of meningococcal serogroup W and C disease in the Netherlands and England: an observational cohort study. Lancet Public Health 2(10):e473-82. https://doi.org/10.1016/S2468-2667(17)30157-3

    Article  PubMed  Google Scholar 

  17. Eriksson L, Hedberg ST, Jacobsson S, Fredlund H, Mölling P, Stenmark B (2018) Whole-genome sequencing of emerging invasive Neisseria meningitidis serogroup W in Sweden. Mellmann A, ed. J Clin Microbiol 56(4). https://doi.org/10.1128/JCM.01409-17

  18. Lucidarme J, Hill DMC, Bratcher HB et al (2015) Genomic resolution of an aggressive, widespread, diverse and expanding meningococcal serogroup B, C and W lineage. J Infect 71(5):544–552. https://doi.org/10.1016/j.jinf.2015.07.007

    Article  PubMed  PubMed Central  Google Scholar 

  19. Lucidarme J, Scott KJ, Ure R, et al (2016) An international invasive meningococcal disease outbreak due to a novel and rapidly expanding serogroup W strain, Scotland and Sweden, July to August 2015. Eurosurveillance 21(45). https://doi.org/10.2807/1560-7917.ES.2016.21.45.30395

  20. Moreno G, López D, Vergara N, Gallegos D, Advis MF, Loayza S (2013) Caracterización clínica de los casos de enfermedad meningocóccica por serogrupo W135 confirmados durante el año 2012 en Chile. Rev Chil infectología 30(4):346–349. https://doi.org/10.4067/S0716-10182013000400002

    Article  Google Scholar 

  21. Campbell H, Parikh SR, Borrow R, Kaczmarski E, Ramsay ME, Ladhani SN (2016) Presentation with gastrointestinal symptoms and high case fatality associated with group W meningococcal disease (MenW) in teenagers, England, July 2015 to January 2016. Eurosurveillance 21(12):30175. https://doi.org/10.2807/1560-7917.ES.2016.21.12.30175

    Article  Google Scholar 

  22. Guiddir T, Gros M, Hong E et al (2018) Unusual initial abdominal presentations of invasive meningococcal disease. Clin Infect Dis 67(8):12220–12227. https://doi.org/10.1093/cid/ciy257

    Article  Google Scholar 

  23. Campbell H, Saliba V, Borrow R, Ramsay M, Ladhani SN (2015) Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015. Eurosurveillance 20(28). https://doi.org/10.2807/1560-7917.ES2015.20.28.21188

  24. Knol MJ, Ruijs WLM, Antonise-Kamp L, de Melker HE, van der Ende A (2018) Implementation of MenACWY vaccination because of ongoing increase in serogroup W invasive meningococcal disease, the Netherlands, 2018. Eurosurveillance 23(16). https://doi.org/10.2807/1560-7917.ES2015.20.28.21188

  25. Krone M, Gray S, Abad R, Skoczyńska A, Stefanelli P et al (2019) Increase of invasive meningococcal serogroup W disease in Europe, 2013 to 2017. Euro Surveill 24(14):1800245. https://doi.org/10.2807/1560-7917.ES.2019.24.14.1800245

    Article  PubMed Central  Google Scholar 

  26. World Health Organization (2011) Laboratory methods for the diagnosis of meningitis caused by Neisseria meningitidis, Streptococcus pneumonia and Haemophilus influenza. WHO manual, 2nd Edition. World Heal Organ. Published online http://www.cdc.gov/meningitis/lab-manual/

  27. Bettencourt C, Nunes A, Correia AM, Gomes JP, Simões MJ (2020) Lung abscess due to Neisseria meningitidis serogroup X—unexpected virulence of a commensal resulting from putative serogroup B capsular switching. Eur J Clin Microbiol Infect Dis 39(12):2327–2334. https://doi.org/10.1007/s10096-020-03977-7

    Article  CAS  PubMed  Google Scholar 

  28. Llarena A, Ribeiro-Gonçalves BF, Nuno Silva D et al (2018) INNUENDO: a cross-sectoral platform for the integration of genomics in the surveillance of food-borne pathogens. EFSA Support Publ 15(11):v. https://doi.org/10.2903/sp.efsa.2018.EN-1498

    Article  Google Scholar 

  29. Bolger AM, Lohse M, Usadel B (2014) Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 30(15):2114–2120. https://doi.org/10.1093/bioinformatics/btu170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Bankevich A, Nurk S, Antipov D et al (2012) SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 19(5):455–477. https://doi.org/10.1089/cmb.2012.0021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Walker BJ, Abeel T, Shea T et al (2014) Pilon: an integrated tool for comprehensive microbial variant detection and genome assembly improvement. Wang J, ed. PLoS One 9(11):e112963. https://doi.org/10.1371/journal.pone.0112963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Aziz RK, Bartels D, Best AA et al (2008) The RAST Server: rapid annotations using subsystems technology. BMC Genomics 9(1):75. https://doi.org/10.1186/1471-2164-9-75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kwong JC, Gonçalves da Silva A, Stinear TP, Howden BP, Seemann TTP, Howden BP, Seemann T (2017) Meningotype: in silico typing for Neisseria meningitidis. GitHub. https://github.com/MDU-PHL/meningotype

  34. Jolley KA, Maiden MC (2010) BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 11:595. https://doi.org/10.1186/1471-2105-11-595

    Article  PubMed  PubMed Central  Google Scholar 

  35. Bratcher HB, Corton C, Jolley KA, Parkhill J, Maiden MCJ (2014) A gene-by-gene population genomics platform: de novo assembly, annotation and genealogical analysis of 108 representative Neisseria meningitidis genomes. BMC Genomics 15(1). https://doi.org/10.1186/1471-2164-15-1138

  36. Zhou Z, Alikhan NF, Sergeant MJ et al (2018) GrapeTree: visualization of core genomic relationships among 100,000 bacterial pathogens. Genome Res 28(9):1395–1404. https://doi.org/10.1101/gr.232397.117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Joseph B, Schwarz RF, Linke B et al (2011) Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome. Ahmed N, ed. PLoS One 6(4):e18441. https://doi.org/10.1371/journal.pone.0018441

  38. Arndt D, Grant JR, Marcu A et al (2016) PHASTER: a better, faster version of the PHAST phage search tool. Nucleic Acids Res 44(w1):W16-21. https://doi.org/10.1093/nar/gkw387

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Francisco AP, Bugalho M, Ramirez M, Carriço JA (2009) Global optimal eBURST analysis of multilocus typing data using a graphic matroid approach. BMC Bioinformatics 10(1):152. https://doi.org/10.1186/1471-2105-10-152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ribeiro-Gonçalves B, Francisco AP, Vaz C, Ramirez M, Carriço JA (2016) PHYLOViZ Online: web-based tool for visualization, phylogenetic inference, analysis and sharing of minimum spanning trees. Nucleic Acids Res 44(W1):W246–W251. https://doi.org/10.1093/nar/gkw359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. European Commission, 2018 Official Journal of the European Union https://eur-lex.europa.eu/legal-content/EN/TXT/PDF/?uri=CELEX:32018D0945 Accessed 26 June 2019

  42. Booy R, Gentile A, Nissen M, Whelan J, Abitbol V (2019) Recent changes in the epidemiology of Neisseria meningitidis serogroup W across the world, current vaccination policy choices and possible future strategies. Hum Vaccin Immunother 15(2):470–480. https://doi.org/10.1080/21645515.2018.1532248

    Article  PubMed  Google Scholar 

  43. Hong E, Barret AS, Terrade A et al (2018) Clonal replacement and expansion among invasive meningococcal isolates of serogroup W in France. J Infect 76(2):149–58. https://doi.org/10.1016/j.jinf.2017.10.015

    Article  PubMed  Google Scholar 

  44. Leo S, Lazarevic V, Girard M et al (2019) Genomic epidemiology of Neisseria meningitidis serogroup W in Switzerland between 2010 and 2016. J Infect 79(3):277–287. https://doi.org/10.1016/j.jinf.2019.05.014

    Article  PubMed  Google Scholar 

  45. Bille E, Zahar JR, Perrin A et al (2005) A chromosomally integrated bacteriophage in invasive meningococci. J Exp Med 201(12):1905–1913. https://doi.org/10.1084/jem.20050112

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Bille E, Meyer J, Jamet A et al (2017) A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation Shafer WM, ed. PLOS Pathog 13(17):e1006495. https://doi.org/10.1371/journal.ppat.1006495

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Brynildsrud OB, Eldholm V, Bohlin J, Uadiale K, Obaro S, Caugant DA (2018) Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa. Proc Natl Acad Sci 115(21):5510–5515. https://doi.org/10.1073/pnas.1802298115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Masignani V, Giuliani MM, Tettelin H, Comanducci M, Rappuoli R, Scarlato V (2001) Mu-like prophage in serogroup B Neisseria meningitidis coding for surface-exposed antigens. Barbieri JT, ed. Infect Immun 69(4):2580–88. https://doi.org/10.1128/IAI.69.4.2580-2588.2001

  49. Mustapha M, Marsh J, Krauland M, Fernandez J et al (2016) Genomic investigation reveals highly conserved, mosaic, recombination events associated with capsular switching among invasive Neisseria meningitidis serogroup W sequence type (ST)-11 strains. Genome Biol Evol 8(6):2016. https://doi.org/10.1093/gbe/evw122

  50. Simões, MJ, Martins, JV (2016) Doença invasiva meningocócica em Portugal Vigilância epidemiológica integrada, 2007–2016. Instituto Nacional de Saúde Doutor Ricardo Jorge. http://hdl.handle.net/10400.18/7024

  51. Letunic I, Bork P (2021) Interactive Tree of Life (iTOL) v5: an online tool for phylogenetic tree display and annotation. Nucleic Acids Res 49(W1):W293–W296. https://doi.org/10.1093/nar/gkab301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the colleagues from the Unit of Technology and Innovation of the National Institute of Health Doutor Ricardo Jorge and the pathologists and clinicians contributing to the Portuguese surveillance system of invasive meningococcal disease.

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Author notes

  1. Célia Bettencourt and Alexandra Nunes contributed equally to this work

Authors and Affiliations

  1. National Reference Laboratory for Neisseria meningitidis, Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal

    Célia Bettencourt & Maria João Simões

  2. Bioinformatics Unit, Department of Infectious Diseases, National Institute of Health Doutor Ricardo Jorge, Lisbon, Portugal

    Alexandra Nunes & João Paulo Gomes

  3. CBIOS – Universidade Lusófona Research Center for Biosciences & Health Technologies, Lisbon, Portugal

    Alexandra Nunes

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  1. Célia Bettencourt
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  2. Alexandra Nunes
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Contributions

CB performed laboratory work and data analysis. AN performed computational study. CB and AN wrote the original draft preparation and reviewed the manuscript. JPG and MJS wrote and reviewed the manuscript. MJS and AN designed and coordinated the study.

Corresponding authors

Correspondence to Célia Bettencourt or Alexandra Nunes.

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Supplementary Fig. 1

Phylogeny of MenW cc22 isolates based on a dynamic gene-by-gene approach using the cgMLST schema V1.0, with 1605 N. meningitidis core-loci. The Minimum spanning tree was constructed using the goeburst algorithm implemented in the PHYLOViZ Online platform and was based on the number of core-loci shared by 100% of the 268 validated isolates. Filled circles (nodes) represent unique allelic profiles and are colored according to isolates’ isolation country. The size of the circles is proportional to the number of isolates it represents. For better visualization, nodes were collapsed when they exhibited allelic distances <=20. (426 KB)

High resolution image (TIF 88.5 KB)

Supplementary Fig. 2

PS_1-like prophage ORFs content. Annotation was based on Phaster analysis and further confirm by RAST. (823 KB)

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Supplementary Table S1

(1.58 MB)

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Bettencourt, C., Nunes, A., Gomes, J.P. et al. Genomic surveillance of Neisseria meningitidis serogroup W in Portugal from 2003 to 2019. Eur J Clin Microbiol Infect Dis 41, 289–298 (2022). https://doi.org/10.1007/s10096-021-04371-7

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  • DOI: https://doi.org/10.1007/s10096-021-04371-7

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