Ενημερωτικό Δελτίο ΚΕΕΛΠΝΟ Φεβρουάριος 2015

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Μηνιγγιτιδοκοκκική νόσος στην Ελλάδα, 2004-2014Κλινική Εικόνα – Επιδημιολογικά δεδομένα - Μοριακή Επιδημιολογία - Θεραπεία και Πρόληψη

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  • 3-5, , 15123, 210 5212000 2015.49/ 5ISSN 1792-9016http://www.keelpno.gr, info@keelpno.gr

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    M - - . Neisseria meningitidis (-), Gram . - 13 . - , . - - . . - -, . , - -. - , 10% - , 11-19% - , ,

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    , 2004-2014: - -

    - - . - - . - , , b - , Gram (-) [1,2]. , - b 75% - 90% [1]. - - , - . , - 50 ( ) [2]. , , - - , - [1,2]. - . , -, , 10% 25% [3].

    - , - . ( ). , . () (, ), , -, , . 30-60% . - >5 , , , , , . -, Brudzinski Kernig . - 30%. - , . . (

  • 3

    . - , , - . . - , , (occult bacteremia). - , - , . -, - . , , . -, . - PCR. O -, , , - . - - Y W135. H - - . . 6-10% - , -, , , , , . - - . 10%. - 11-19% - , -, , .

    , - ( ) -. - , - , . - - (, .) (EKAM), . , - . - , (, , ), - . , , , -, , -, , - .

    2004-2014 863 - , 55 108 0,71 100.000 ( 1). , - - 2007 2010 [4] .

  • 4

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    - 2004-2014, - - 92,1% (795/863). - - 76,1% (657/863) / Neisseria meningitidis, 572/657

    (87,1%) (A, B, C, W135, Y) - . 77% (505/657) - , - , - , 2 C ( 3).

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    ABCYW135N. Gr.

    , , - . - , . (Polymerase Chain Reaction, PCR), , - - , -- - . - 1998 (multiplex PCR) -

    [5,6]. - (: 44.4% (1998), 94% (2014). , - (82%) - PCR, - (18%).

    Neisseria meningitidis , 11 (2004-2014), C, - 1997-1998, - . ,W-135 ( 4), - . - (2009-2012) [7,8].

  • 6

    4. N.meningitidis , , 2004-2014

    - (sequencing) . - :

    1. (Multilocus Sequence Typing, MLST)

    N. meningitidis - -.

    PCR, - , - -. MLST (sequence types, ST) 2004-2014 ST-269 (14,7%), ST-32 (10,5%), ST-162 (5,7%), ST 41/44 (5,6%) ( 5) ST-269, ST 41/44 ST-32 - - (4CmenB) [9].

    5. (Sequence types) N. meningitidis, , 2004-2014

  • 7

    2. porA.

    porA, - , - -. , 19-1, 15-11 36 1, 2 , o N. meningitidis . - -, .

    3. (Variable Tandem Repeat Analysis- VNTR)

    DNA - (tandem repeats). (motif) - - - N. meningitidis, - . , , - , - , - , [10, 11].

    4. (fHbp, NHBA, NadA).

    : fHbp (factor H binding protein ),

    -, - , NHBA: Neisserial heparin-binding antigen - ), , - , , NadA: (eisserial adhesion A), - . , MATS (Meningococcal Typing System), - 78,4% - NHBA, 52,7% fHbp (0,7%) NadA. - , - - 89,2%. [12].

    5. Whole Genome Sequencing (WGS). DNA (next generation sequencing -NGS), (-) DNA - - - DNA, (Whole Genome Sequencing -WGS) . - () -. Neisseria meningitidis - - , , [13]. - Neisseria meningitides - , -, - - [14].

  • 8

    - 2004-2014 49 , 5,68%. - 2012 (11,11%), 2011 (1,82%). 2004-2014 0,40 - 100000 .

    - - 3 , . - () < 0,1g/ml, . 0,1 g/ml, 3 . - - , -. ( 64 g/ml). , -, 2-3% . - . -, - shock , - , . - - . , b , - .

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  • 10

    -, . fHbp (factor H binding protein) Nad A (Neisserial adhesin A) (Neisseria Heparin Bind-ing protein A) z Por A. MATS (Meningococcal Antigen Typing System), - (), -. , -

    -, . - . (2, 4, 6 + 1 ). . -. FDA - fHBP 10-25 . - .

    1. American Public Health Association. Control of communicable diseases manual, 19th edition. Heymann DL ed. 2008; p. 414-426.

    2. Tunkel A, Scheld M. Acute meningitis In: Mandell G, Bennett J, Dolin R (eds). Mandell, Douglas, and Bennetts principles and practice of infectious diseases. 6th edition. Philadelphia, PA Elsevier/ Churchil Livingston. 2005: 1083-1126.

    3. Woods CR. Neisseria Meningitidis (Meningococcus). In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF eds. Nelson textbook of pediatrics. 18th ed. Philadelphia: Saunders Elsevier. 2007; p: 1164-1169.

    4. Georgakopoulou T, Menegas D, Tzanakaki G, Pipa E, Vernardaki A, Mavraganis P, Theodoridou M, Kremastinou J. Epidemiology of Bacterial Meningitis in Greece, in the Era of Conjugate Vaccines: A 7 years review 2005-2011. 52nd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), San Fransisco, USA, 9-12 Sep 2012.

    5. Tzanakaki G,Tsopanomichalou M, Kesanopoulos K, Matzourani R, Sioumala M, Tabaki A, Kremastinou J and Simultaneous single-tube PCR assay for the detection of N. meningitidis, H. influenzae type b and streptococcus pneumoniae. ClinMicrob Infect 2005; 11:386-390.

    6. Xirogianni A, Tzanakaki G, Karagianni E, Markoulatos P, Kourea-Kremastinou J. Development of a single-tube polymerase chain reaction assay for the simultaneous detection of Haemophilus influenzae, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus spp. directly in clinical samples.Diagn Microbiol Infect Dis. 2009 Feb;63(2):121-6

    7. Broker M, Jacobsson S, Kuusi M, Pace D, Simones MJ, Skoczynska A, Taha MK, Toropainen M, Tzanakaki G. Meningococcal serogroup Y emergence in Europe: update 2011 . Hum Vaccin Immunother 2012; 8 (12)

    8. Brker M, Bukovski S, Culic D, Jacobsson S, Koliou M, Kuusi M, Simes MJ, Skoczynska A, Toropainen M, Taha MK, Tzanakaki G. Meningococcal serogroup Y emergence in Europe: High importance in some European regions in 2012. Hum Vaccin Immunother. 2014 Mar 7;10(6).

  • 11

    9. Read R, Baxter D, Faust D, Finn A, Gordon S et al. Effect of quatrivalent meningococcal ACWY glyconconjugate or a serofropu B meningococcal vaccine on meningococcal carriage: an observer-blind, phase 3 randomized clinical trial. The Lancet 2014, 384:2123-2131.10. Tzanakaki G, Kesanopoulos K, S. Yazdankhah, Levidiotou S, Kremastinou J and Caugant DA. Conventional and molecular investigation of meningococcal isolates in relation to two outbreaks in the area of Athens, Greece.Clin Microbiol Infect 2006; 12(10):1024-611. Kesanopoulos K, Tzanakaki G, Sioumala M, Kourea-Kremastinou J Direct application of variable number tandem repeats polymerase chain reaction in clinical samples obtained from patients with meningococcal disease.Diagn Microbiol Infect Dis. 2010 (66): 124-27.12. Tzanakaki G, Hong E, Kesanopoulos K, Xirogianni A, Bambini S, Orlandi L, Comanducci M, Muzzi A, Taha MK.Diversity of greek meningococcal serogroup B isolates and estimated coverage of the 4CMenB meningococcal vaccine. BMC Microbiol. 2014 Apr 29;14(1):111.13. Jolley KA, Hill DM, Bratcher HB, Harrison OB, Feavers IM, Parkhill J, Maiden MC. Resolution of a meningococcal disease outbreak from whole-genome sequence data with rapid Web-based analysis methods. J Clin Microbiol. 2012 Sep;50(9):3046-53.14. Bratcher H, Kesanopoulos , Tzanakaki G, Maiden MCJ. Genomic comparison of Neisseria meningitidis isolates of patients and their close family contacts using gene-by-gene analysis.:XIXth International Pathogenic Neisseria Conference (IPNC), October 2014, Asheville, NC, USA (poster presentation).15. Anderson MS, Glode MP, Smith AL. Meningococcal infections. In: Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL eds. Textbook of Pediatric Infectious Diseases, 6th edition. Saunders Elsevier. 2009; pp: 1350-1366.16. CDC. Epidemiology and Prevention of Vaccine-Preventable Diseases (The Pink Book). Atkinson W, Wolfe S, Hamborsky J, eds. 12th ed, 2nd printing. Washington DC: Public Health Foundation, 2012.17. CDC. Prevention and control of meningococcal disease. 1. MMWR 2005;54(RR-7):117.18. MacNeil J, Cohn A. Meningococcal disease. In: Roush SW, McIntyre L, Baldy LM eds. CDC. Manual for the surveillance of vaccine-preventable diseases. (5th ed) Centers for Disease Control and Prevention, Atlanta, GA, 201119. Broome CV. The carrier state: Neisseria meningitidis. J Antimicrob Chemother 1986; 18 (suppl. A):25-34. 20. Dworzack DL, Sanders CC, Horowitz EA, et al. Evaluation of single-dose ciprofloxacin in the eradication of Neisseria meningitidis from nasopharyngeal carriers. Antimicrob Agents Chemother 1988; 32:1740-1. 21. Schwartz B, Al-Tobaiqi A, Al-Ruwais A, Fontaire RE, Aashi J, Hightower AW, Broome CV, Music SI. Comparative efficacy of ceftriaxone and rifampin in eradicating pharyngeal carriage of group A Neisseria meningitidis. Lancet 1988; 2:1239-42.22. Gardner P. Prevention of meningococcal disease. N Engl J Med 2006; 355:1466-73.

    23. Rappuoli R. Reverse vaccinology. Curr Opin Microbiol 2000; 3(5);445-50.

    24. Moxom ER, siegrist CA. The next decade of vaccine: societal and scientific challenge

  • 12

    25. Gorringe AR, Pajon R. Bexsero: a multicomponent vaccine for prevention of meningococcal disease. Hum Vaccines Immunother 2012; 8(2): 174-83.

    26. Vesikari T, Esposito S, Prymoula R, Ypma E, Kohl I, Toneatto D et al. Immunogenicity and safety of an investigational multicomponent, recombinant meningococcal serogroup B vaccine (4C MenB) administered concomitantly with routine infant and child vaccinations: results of two randomized trials. Lancet 2013;381(9869): 825-35.

    27. Tzanakaki G, Hong E, Kesanopoulos K, Xirogianni A, Bambini S, Orlandi L, Comanducci M, Muzzi A, Tahamk. Diversity of Greek meningococcal serogroup B isolates and estimated coverage of the 4CMenB meningoccal vaccine. BMC Microbiol 2014: 14;111.

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  • 13

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    0 0 0 0 2 1 0 7 0 0 0 1 3 8 1 30 0 0 0 0 - 0 0 0 0 2 1 0 10 0 0 0 0 0 0 0 0 3 0 0 4 A 5 10 1 25 , & HBsAg(+) < 12 1 8 2 15

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    0 0 0 0 / 0 0 0 5 29 44 29 59 0 0 0 0

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    3. () , , - 01/01/2015 31/01/2015 ( : , : ).

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  • 17

    1. Meningococcal serogroup Y emergence in Europe High importance in some European regions in 2012:Michael Brker, Suzana Bukovski, Davor Culic, Susanne Jacobsson, Maria Koliou, Markku Kuusi, Maria Joo Simes, Anna Skoczynska, Maija Toropainen, Muhamed-Keir Taha, Georgina Tzanakaki.Human Vaccines & Immunotherapeutics 10:6, 14; June 2014

    O M , , 13 , , , C, W135 . . , - , , [1]. , - C , 4 A, C, W Y.

    2. Diversity of Greek meningococcal serogroup B isolates and estimated coverage of the 4CMenB meningococcal vaccine.Tzanakaki G, Hong E, Kesanopoulos K, Xirogianni A, Bambini S, Orlandi L, Comanducci M, Muzzi A, Taha MK.BMC Microbiol. 2014 Apr 29;14:1

    4CMenB . , NadA, fHbp PorA - . , . 4CMenB , . 148 MATS (Meningococcal Antigen Typing System) [2]. NHBA , fHbp (52,7%), PorA (8,1%) NadA (0,7%). - ST-162, 44,6% - e 86.4 %.

    http://www.ncbi.nlm.nih.gov/pubmed/24779381http://www.ncbi.nlm.nih.gov/pubmed/24779381

  • 18

    3. Molecular and serological diversity of Neisseria meningitidis carrier strains isolated from Italian students aged 14 to 22 years.Gasparini R, Comanducci M, Amicizia D, Ansaldi F, Canepa P, Orsi A, Icardi G, Rizzitelli E, De Angelis G, Bambini S, Moschioni M, Comandi S, Simmini I, Boccadifuoco G, Brunelli B, Giuliani MM, Pizza M, Panatto D.J Clin Microbiol. 2014 Jun;52(6):1901-10

    4CMenB, . Gasparini . - 14 22 -, , PorA, fHbp, NHBA NadA 4CMenB [3]., 18,5% , , 5 . (34.4%) - - , 28.1% . Fhbp NHBA - NadA 5% . . 4CMenB , .

    B , ,

    http://www.ncbi.nlm.nih.gov/pubmed/24648565http://www.ncbi.nlm.nih.gov/pubmed/24648565http://www.ncbi.nlm.nih.gov/pubmed/24648565

  • 19

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    () 0,50 / 100000 , , . , 10 - 1000 100000 (WHO 1998).

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  • 20

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  • 21

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    1. K A M ().

    2. Rosenstein NE, Perkins BA, Stephens DS, Popovic T, Hunghes JM. Meningococcus disease. N. Engl J Ned. 344(18): 1378-88, (2001).

    3. Feigin RD, Cutrer WB, Textbook of Pediatric infectious Diseases. Bacterial Meningitis beyond the neonatal period Saunders 6th edition 439-471, (2009).

    4. Stephens DS. Conquering the meningococcus. FEMS Microbiol Rev. 31(1):3-14. Review (2007).

    5. Overturt GD. Indications for the immunological evaluation of patients with meningitis. Clin. Infect. Dis 36(2): 189-94, 2003.

    6. Coen PG, Tally I, Stuart JM, Ashby D, Viner RM, Booy R. Is it exposure to cigarette smoke or to smokers which increases the risk of meningococcal disease in teenagers? Int J Epidemiol 35(2) 330-6, 2006.

    7. Brouwer MC, Mcintyre P, de Gans J, Prasad K, van de Beek D. Corticosteroids for acute bacterial meningitis. Cochrane Database Sust Rev (9): CD004405, 2010.

    , - ,

  • 22

    2015

    17-21, 2015

    : 16 : : -

    : : : Abu Dhabi National Exhibition Centre : +33 1 44 32 03 60: http://www.wctoh.org/

    30- 3, 2015

    : 25 & : ; ;

    : ...: : Manchester Grand Hyatt : +785-865-9402: http://www.healthpromotionconference.com

    ,

  • 23

    2015

    Ebola [1] Ebola . 25 - 2015 23729 (, , ), - 9604 , , , , (, ), , , , , . ( ).

    MERS [1, 2] 26 2015, 1030 MERS-CoV, 381 . .

    (79) [1, 2] 2013 23 2015 602 -, 227 . - . .

    1. World Health Organization (WHO). Global Alert and Response (GAR). : http://www.who.int/csr/disease/ [ 1 2015]

    2. European Centre for Disease Control and Prevention (ECDC). Communicable disease threats report. : http://ecdc.europa.eu/en/publications/_layouts/forms/ [ 1 2015]

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