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WHO Collaborating Centre for Reference and Research on Meningococci

Published Updated


The World Health Organization (WHO) is committed to eliminating meningococcal disease as a public health problem.


WHO logo.
WHO logo.

Meningococcal disease constitutes an enormous public health burden, especially in sub-Saharan Africa where large scale epidemics occur. 

The Norwegian Institute of Public Health (NIPH), which has been an appointed WHO Collaborating Centre for Reference and Research on Meningococci since 1991, contributes to this task.

Meningococcal disease is caused by the bacterium Neisseria meningitidis (the meningococcus). Two clinical forms of meningococcal disease predominate, septicaemia (or blood stream infection) and meningitis which is a serious infection affecting the brain membranes. The disease can lead to severe disability, including hearing loss, mental retardation and epilepsy, and case-fatality rates are around 10 per cent. Meningococcal meningitis is the only form of bacterial meningitis which causes epidemics. In the so-called meningitis belt of sub-Saharan Africa, a region encompassing 21 countries from Senegal in the West to Ethiopia in the East, large epidemics of meningococcal meningitis recur every few years.

The disease is transmitted by air-borne droplets from people who have the bacterium in their throat, but are without symptoms (asymptomatic carriers). Twelve groups of the Neisseria meningitidis have been identified, five of which (A, B, C, W135, and X) can cause epidemics. The large epidemics in the meningitis belt have been mainly caused by strains of serogroup A.

Polysaccharide vaccines against serogroup A, C, W135 and Y have been available since the 1970s, but are sub-optimal as they give only short-term protection and are little effective in children under 2 years of age. There are now several protein-conjugate polysaccharide vaccines available to better protect against disease caused by these four serogroups; but until now, the cost of these vaccines has been prohibitive for Africa.

WHO’s strategy to control disease in the meningitis belt involves epidemic preparedness and response. Preparedness focuses on surveillance, from case detection to outbreak investigation and laboratory confirmation. Response has been based on treatment of the cases and use of polysaccharide vaccines when an epidemic has been confirmed. WHO also regularly provides technical support at the field level to countries facing epidemics.

A WHO-sponsored effort to improve public health response to meningitis outbreaks in Africa resulted in nationwide introduction of a new low price meningococcal A conjugate vaccine, MenAfriVacTM, in Burkina Faso, Mali and Niger in December 2010. It is hoped that all countries in the African meningitis belt will have introduced this vaccine by 2015 and, with high coverage of the target age group of 1-29 years, elimination of meningococcal A epidemics from this region of Africa is expected.

NIPH was designated as a WHO Collaborating Centre 20 years ago because of the expertise and engagement of its employees in the study of meningococcal meningitis globally. Through the years the Centre has supported WHO in contributing to diagnostic and outbreak detection in other countries, in monitoring worldwide spread of virulent strains using molecular methods, and with capacity building, particularly in Africa. The Centre is currently leading a study to monitor the ability of the new vaccine MenAfriVac to reduce carriage prevalence and thus, limit transmission of the meningococcal disease in Burkina Faso.

Responsibilities of the WHO Collaborating Centre:

Analysis

  • Collection of all systemic meningococci isolates from Norway’s medical microbiological laboratories.
  • Reference studies of meningococcal strains from Norway and abroad (serogrouping, serotyping and resistance characterisation).
  • Performance of meningococcal carrier studies around cases/epidemics and in particular population groups. 
  • Monitoring of N. meningitidis strains from various geographical areas and epidemiological situations using the multilocus sequence typing (MLST) technique, as well as other systems for characterisation. Collection & analysis of information on multilocus types & other characteristics are disseminated through WHO-HQ & WHO-RO to the interested countries by an annual report and, if needed, by other means.
  • Genetic studies of culture-negative cerebrospinal fluids and sera from meningitis patients.

Research

  • Development of new genetic-based typing methods. 
  • Research into monitoring variations and extent of virulence properties among meningococci.
  • Research into population genetics and evolution of Neisseria species. 
  • Research related to meningococcal vaccines: characterise meningococcal antigens and study antibody response after vaccination and disease.

Services

  • Maintain a meningococcal strain bank. 
  • Contribute to diagnostic and outbreak detection in other countries (particularly in Africa). 
  • Help to establish quality control of laboratory methods. 
  • Provide reference strains, clinical isolates and other material (e.g. DNA) upon request for eligible parties like: the National Reference laboratories in the allocated countries; European & North American laboratories that are part of the Global Laboratory Network on Meningococcal Diseases. 
  • Production of material for transport (e.g. Trans-Isolate medium) of clinical samples & isolates within & in between countries. 
  • Openness for request to strengthen diagnostic functions in other countries on site.

Reporting 

  • Report results to international collaboration partners. 
  • Responsibility for presenting, together with the other WHO Collaborating Centres for Reference and Research on Meningococci, an annual joint analysis of the meningococcal situation with conclusions and possibilities/problems for the future.

About WHO Collaborating Centres

The WHO Collaborating Centres are institutions, such as research institutes, parts of universities or academies, which are designated by the WHO’s Director-General to carry out activities in support of the Organization's programmes. Currently there are over 800 WHO collaborating centres in over 80 Member States working with WHO on areas, such as nursing, occupational health, communicable diseases, nutrition, mental health, chronic diseases and health technologies. (Source: WHO).

Contact

Head: Prof. Dominique A. Caugant

Tel: (+47) 2107 6311
Fax: (+47) 2107 6518

Division of Infectious Disease Control
Norwegian Institute of Public Health
P.O.Box 222 Skøyen 
0213 Oslo, Norway

Publications

  1. Bårnes, G. K., L. Meyer Næss, E. Rosenqvist, P. J. Guerin, D. A. Caugant and the Fractional Doses Vaccine Study Group. 2011. Avidity of serogroup A meningococcal IgG antibodies after immunization with different doses of a tetravalent A/C/Y/W135 polysaccharide vaccine.Scand. J. Immunol. in press
  2. Kristiansen, P. A., F. Diomandé, S. C. Wei, R. Ouédraogo, L. Sangaré, I. Sanou, D. Kandolo, P. Kaboré, T. A. Clark, A.-S. Ouédraogo, K. B. Absatou, C. D. Ouédraogo, M. Hassan-King, J. Dolan Thomas, C. Hatcher, M. Djingarey, N. Messonnier, M.-P. Préziosi, M. LaForce, and D. A. Caugant. 2011. Baseline meningococcal carriage in Burkina Faso before the introduction of a meningococcal serogroup A conjugate vaccine. Clin. Vac. Immunol. 18:435-443.
  3. Beernink, P. T., D. A. Caugant, J. A. Welsch, O. Koeberling, and D. M. Granoff. 2009. Meningococcal factor H-binding protein variants expressed by epidemic capsular group A, W-135 and X strains from Africa. J. Infect. Dis. 199: 1360-1368.
  4. Caugant, D. A., and M. C. J. Maiden. 2009. Meningococcal carriage and disease – Population biology and evolution. Vaccine 27 (Suppl. 2): B64-B70.
  5. Murphy, E., L. Andrew, K. L. Lee, D. Dilts, P. S. Fink, K. Ambrose, R. Borrow, J. Findlow, M.-K. Taha, A-E. Deghmane, P. Kriz, M. Musilek, J. Kalmusova, D. A. Caugant, T. Alvestad, L. Mayer, X. Wang, C. T. Sacchi, D. Martin, A. von Gottberg, M. du Plessis, K. P. Klugman, A. S. Anderson, K. U. Jansen, G. W. Zlotnick, and S. K. Hoiseth. 2009. Sequence diversity of the factor H binding protein vaccine candidate in epidemiologically relevant strains of serogroup B Neisseria meningitidis. J. Infect. Dis. 200:379-389.
  6. Rose, A. M. C., S. Gerstl, A. E.-H. Mahamane, F. Sidikou, S. Djibo, L. Bonte, D. A. Caugant, P. J. Guerin, and S. Chanteau. 2009. Field evaluation of two rapid diagnostic tests for Neisseria meningitidis serogroup A during the 2006 outbreak in Niger. Plos One 4: e7326.
  7. Thulin Hedberg, S., H. Fredlund, P. Nicolas, D. A. Caugant, P. Olcén, and M. Unemo. 2009. Antibiotic susceptibility and characteristics of Neisseria meningitidis isolates from the African meningitis belt, 2000 to 2006: phenotypic and genotypic perspectives. Antimicrob. Agents Chemother. 53:1561-1566.
  8. Caugant, D. A. 2008. Genetics and evolution of Neisseria meningitidis: importance for the epidemiology of meningococcal disease. Infect. Genet. Evol. 8:558-565.
  9. Guerin, P. J., L. M. Næss, C. Fogg, E. Rosenqvist, L. Pinoges, F. Bajunirwe, C. Nabasumba, R.Borrow, L. O. Frøholm, S. Ghabri, V. Batwala, R. Twesigye, I. S. Aaberge, J.-A. Rottingen, P. Piola, and D. A. Caugant. 2008. Immunogenicity of fractional doses of tetravalent A/C/Y/W135 meningococcal polysaccharide vaccine: results from a randomised non-inferiority controlled trial in Uganda. Plos Neglected Dis. 2: e342.
  10. Norheim, G., A. Aseffa, M. A. Yassin, G. Mengistu, A. Kassu, D. Fikremariam, W. Tamire, Y. Merid, E. A. Høiby, D. A. Caugant, E. Fritzsønn, T. Tangen, B. Melak, D. Berhanu, M. Harboe, J. Kolberg, and E. Rosenqvist. 2008. Specificity of the subcapsular antibody responses in Ethiopian patients following disease caused by serogroup A meningococci. Clin. Vaccine Immunol. 15:863-871.
  11. Rose, A. M. C., J. E. Mueller, S. Gerstl, B. M. Njanpop-Lafourcade, A.-L. Page, P. Nicolas, R. Ouédraogo Traoré, D. A. Caugant, and P. J. Guerin. Meningitis dipstick rapid test: evaluating diagnostic performance during an urban Neisseria meningitidis serogroup A outbreak, Burkina Faso 2007. Plos One 5: e11086.
  12. Caugant, D. A., and P. Nicolas. 2007. Molecular surveillance of meningococcal meningitis in Africa. Vaccine. S1: A8-A11.
  13. Caugant, D. A., G. Tzanakaki, and P. Krizova. 2007. Lessons from meningococcal carriage studies. FEMS Microbiol. Rev. 31:52-63.
  14. Koumaré, B., R. Ouedraogo-Traoré, I. Sanou, A. Yada, I. Sow, P. Lusamba, E. Traoré, M. Dabal, M. Santamaria, M. M. Hacen, A. Kaboré, and D. A. Caugant. 2007. The first large epidemic of meningococcal disease caused by serogroup W135, Burkina Faso, 2002. Vaccine. S1: A37-A41.
  15. Materu, S., H. Cox, P. Isaakidis, B. Baruani, T. Ogaro, D. Caugant. 2007. Serogroup X in meningococcal disease, Western Kenya. Emerg. Infect. Dis.13:944-945.
  16. Nathan, N., A. M. C. Rose, D. Legros, S. R. M. Tiendrebeogo, C. Bachy, E. Bjørløw, P. Firmenich, P. J. Guerin, and D. A. Caugant. 2007. Meningitis W135 outbreak, Burkina Faso, 2002: operational consequences from higher risk in young children. Emerg. Infect. Dis.13:920-923.
  17. Norheim, G., A. Aseffa, M. A. Yassin, G. Mengistu, A. Kassu, D. Fikremariam, W. Tamire, Y. Merid, E. A. Høiby, D. A. Caugant, E. Fritzsønn, T. Tangen, T. Alebel, D. Berhanu, M. Harboe, and E. Rosenqvist. 2007. Serum antibody responses in Ethiopian meningitis patients infected with Neisseria meningitidis serogroup A sequence type 7. Clin. Vaccine Immunol. 14:451-463.
  18. Caugant, D. A., C. Fogg, F. Bajunirwe, P. Piola, R. Twesigye, F. Mutebi, L. O. Frøholm, E. Rosenqvist, V. Batwala, I. S. Aaberge, J.-A. Rottingen, and P. J. Guerin. 2006. Pharyngeal carriage of Neisseria meningitidis in 2-19 years old individuals in Uganda. Proc. Roy. Soc. Trop. Med. & Hyg. 100:1159-1163.
  19. Maiden, M. C. J., and D. A. Caugant. 2006. The population biology of Neisseria meningitidis: implications for meningococcal disease epidemiology and control. In M Frosch & MCJ Maiden (eds). Meningococcal disease, pathogenicity and prevention. Wiley-VCH, Weinheim, Germany. p. 17-35.
  20. Norheim, G., E. Rosenqvist, A. Aseffa, M. A. Yassin, G. Mengistu, A. Kassu, D. Fikremariam, W. Tamire, E. A. Høiby, T. Alebel, D. Berhanu, Y. Merid, M. Harboe, and D. A. Caugant. 2006. Characterization of Neisseria meningitidis isolates from recent outbreaks in Ethiopia and comparison with those recovered during the 1988-89 epidemic. J. Clin. Microbiol. 44:861-871.
  21. Smith, I., D. A. Caugant, E. A. Høiby, T. Wentzel-Larsen, and A. Halstensen. 2006. High case-fatality rates of meningococcal disease in Western Norway caused by serogroup C strains belonging to both the sequence type (ST)-32 and ST-11 complexes, 1985-2002. Epidemiol. Infect. 134:1195-1202.
  22. Tzanakaki, G., K. Kesanopoulos, S. Yazdankhah, S. Levidiotou, J. Kremastinou, and D. A. Caugant. 2006. Conventional and molecular investigation of meningococcal isolates in relation to two outbreaks in the area of Athens. Clin. Microbiol. Infect. 12:1024-1026.
  23. Holst, J., B. Feiring, L. M. Næss, G. Nordheim, P. Kristiansen, E. A. Høiby, K. Bryn, P. Oster, P. Costantino, M.-K. Taha, J.-M. Alonso, D. A. Caugant, E. Wedege, I. S. Aaberge, R. Rappuoli, and E. Rosenqvist. 2005. The concept of “tailor-made”, protein-based, outer membrane vesicle vaccines against meningococcal disease. Vaccine 23:2202-2205.
  24. Kesanopoulos, K., G. Tzanakaki, A. Velegraki, N. Tegos, D. A. Caugant, P. Menounos, J. Kourea-Kremastinou, and S. Levidiotou-Stefanou. 2005. Rapid identification of Neisseria meningitidis isolates by the use of polymerase chain reaction-single strand conformation polymorphism analysis (PCR-SSCP). FEMS Immunol. Med. Microbiol. 45:143-149.
  25. Nicolas, P., N. Ait M’Barek, S. Al-Awaidy, S. Busaidy, N. Sulaiman, M. Issa, J. Mahjour, P. Mölling, D. A. Caugant, P. Olcen, and M. Santamaria. 2005. Pharyngeal carriage of serogroup W135 Neisseria meningitidis in Hajjees and their family contacts in Morocco, Oman and Sudan. APMIS. 113:182-186.
  26. Norheim, G., A. Aase, D. A. Caugant, E. A. Høiby, E. Fritzsønn, T. Tangen, P. Kristiansen, U. Heggelund, and E. Rosenqvist. 2005. Development and characterisation of an outer membrane vesicle vaccine against serogroup A Neisseria meningitidis. Vaccine 23:3762-3774.
  27. Taha, M. K., J.-M. Alonso, S. Clarke, H. Claus, D. A. Caugant, A.-M. Klem, M. Diggle, A. Fox, S. J. Gray, M. Guiver, S. Heuberger, J. Kalmusova, P. Kriz, J. Marsh, P. Mölling, K. Murphy, P. Olcén, O. Sanou,G. Tzanakaki, and U. Vogel. 2005. Interlaboratory comparison of PCR-based identification and genogrouping of Neisseria meningitidis. J. Clin. Microbiol.43:144-149.
  28. Yazdankhah, S. P., B.-A. Lindstedt, and D. A. Caugant. 2005. Use of variable-number tandem repeats to examine genetic diversity of Neisseria meningitidis. J. Clin. Microbiol. 43:1699-1705.
  29. Yazdankhah, S. P., K. Kesanopoulos, G. Tzanakaki, J. Kremastinou, and D. A. Caugant. 2005. Variable number tandem repeats analysis of meningococcal isolates belonging to the sequence type-162 complex. J. Clin. Microbiol. 43:4865-4867.
  30. Nicolas, P., G. Norheim, E. Garnotel, S. Djibo, and D. A. Caugant. 2005. Molecular epidemiology of Neisseria meningitidis isolated in the African meningitis belt between 1988 and 2003 shows the dominance of the sequence type (ST)-5 and ST-11 complexes. J. Clin. Microbiol. 43:5129-5135
  31. Commanducci, M., S. Bambini, D. A. Caugant, M. Mora, B. Brunelli, B. Capecchi, L. Ciucchi, R. Rappuoli and M. Pizza. 2004. NadA diversity and carriage in Neisseria meningitidis. Infect. Immun.72:4217-4223.
  32. McEllistrem, M.C., J. A. Kolano, M. A. Pass, D. A. Caugant, A. B. Mendelsohn, A. G. Fonseca Pacheco, K. A. Shutt, J. Razeq, L. H. Harrison, and the Maryland Emerging Infections Program. 2004. Correlating epidemiologic trends with the genotypes causing meningococcal disease, Maryland. Emerg. Infect. Dis. 10: 451-456.
  33. Norheim, G., E. A. Høiby, D. A. Caugant, E. Namork, T. Tangen, E. Fritzsønn, and E. Rosenqvist. 2004. Immunogenicity and bactericidal activity in mice of an outer membrane protein vesicle vaccine against Neisseria meningitidis serogroup A disease. Vaccine.22: 2171-2180.
  34. Yazdankhah, S. P., and D. A. Caugant. 2004. Neisseria meningitidis: an overview of the carriage state. J. Med. Microbiol. 53:821-832.
  35. Yazdankhah, S. P., P. Kriz, G. Tzanakaki, J. Kremastinou, J. Kalmusova, M. Musilek, T. Alvestad, K. A. Jolley, D. J. Wilson, N. D. McCarthy, D. A. Caugant, and M. C. J. Maiden. 2004. Distribution of serogroups and genotypes among disease-associated and carried isolates of Neisseria meningitidis from the Czech Republic, Greece and Norway. J. Clin. Microbiol. 42:5146-5153.
  36. Wedege, E., B. Kuipers, K. Bolstad, H. van Dijken, L. O. Frøholm, C. Vermont, D. A. Caugant, and G. van den Dobbelsteen. 2003. Antibody specificities and effect of meningococcal carriage in Icelandic teenagers receiving the Norwegian serogroup B outer membrane vesicle vaccine. Infect. Immun.71:3775-3781.
  37. Commanducci, M., S. Bambini, B. Brunelli, J. Adu-Bobie, B. Aricò, B. Capecchi, M. M. Giuliani, V. Masignani, L. Santini, S. Savino, D. M. Granoff, D. A. Caugant, M. Pizza, R. Rappuoli, and M. Mora. 2002. NadA, a novel vaccine candidate of Neisseria meningitidis. J. Exp. Med. 195: 1445-1454.
  38. Leegaard, T.M., E. J. Rønning, D. A. Caugant, L. O. Frøholm, E. A. Høiby, P. Sandven, and J. N. Bruun. 2002. Do HIV-seropositive patients become colonized with resistant microorganisms? Eur. J. Microbiol. & Clin. Dis. 21: 856-863.
  39. Mayer L. W., M. W. Reeves, N. Al-Hamdan, C. T. Sacchi, M.-K. Taha, G. W. Ajello, S. E. Schmink, C. A. Noble, M. L. C. Tondella, A. M. Whitney, Y. Al-Mazrou, M. Al-Jehri, A. Mishkhis, S. Sabban, D. A. Caugant, J. Lingappa, N. E. Rosenstein, and T. Popovic. 2002. The 2000 outbreak of W135 meningococcal disease: not emergence of a new W135 strain, but clonal expansion within the ET-37 complex. J. Infect. Dis. 185:1596-1605.
  40. Ouedraogo-Traore, R., E. A. Høiby , I. Sanou, L. Sangare, N. Kyelem, D. Ye-Ouattara, L. O. Frøholm, and D. A. Caugant. 2002. Molecular characteristics of Neisseria meningitidis strains isolated in Burkina Faso in 2001. Scand. J. Infect. Dis. 34: 804-807.
  41. Ashton, F. E., and D. A. Caugant. 2001. The panmictic nature of Neisseria meningitidis serogroup B during a period of endemic disease in Canada. Can. J. Infect. Dis. 47:283-289.
  42. Caugant, D. A. 2001. From multilocus enzyme electrophoresis to multilocus sequence typing, p. 299-349. In L Dijkshoorn, KJ Towner & M Struelens (eds). New Approaches for the Generation and Analysis of Microbial Fingerprints. Elsevier Science B.V., Amsterdam, The Netherlands.
  43. Caugant, D. A. 2001. Global trends in meningococcal disease, p. 273-292. In AJ Pollard & MCJ Maiden (eds). Methods in Molecular Medicine: Meningococcal Disease. Methods and Protocols. Humana Press, Totowa, New Jersey.
  44. Cimolai, N., and D. A. Caugant. 2001. Gram negative cocci and Moraxellae, p. 499-527. In N. Cimolai (ed). Laboratory Diagnosis of Bacterial Infections. Marcel Dekker Inc., New York.
  45. Paragi, M., A. Kraigher, M. Cizman, M. Gubina, and D. A. Caugant. 2001. Epidemiology of invasive meningococcal infections of children in Slovenia during 1993-1999. Cent. Eur. J. Public Health. 9:79-82.
  46. Van Looveren, M., D. A. Caugant, S. Chapelle, F. Carion, and H. Goossens. 2001. Ongoing increase in the incidence of meningococcal disease in Belgium 1996-1998. J. Med. Microbiol. 50:986-990.
  47. Zhu, P., A. van der Ende, D. Falush, N. Brieske, G. Morelli, B. Linz, T. Popovic, I. Schuurman, R. Adegbola, K. Zurth, S. Gagneux, A. Platonov, J.-Y. Riou, D. A. Caugant, P. Nicolas, and M. Achtman. 2001. Fitgenotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proc. Natl. Acad. Sci. USA. 98:5234-5239.
  48. Frøholm, L. O., A.-B. Kolstø, J.-M. Berner, and D. A. Caugant. 2000. Rearrangement of large DNA regions in the chromosome of Neisseria meningitidis strains of the ET-5 complex. Curr. Microbiol. 40:372-379.
  49. Hilse, R., J. Stoevesandt, D. A. Caugant, H. Claus, M. Frosch, and U. Vogel. 2000. Distribution of the meningococcal insertion sequence IS1301 in clonal lineages of Neisseria meningitidis. Epidemiol. Infect.124:337-340.
  50. Jelfs, J., R. Munro, E. Wedege, and D. A. Caugant. 2000. Sequence variation in the porA gene of a clone of Neisseria meningitidis during epidemic spread. Clin. Diagn. Lab. Immunol. 7:390-395.
  51. Jelfs, J., R. Munro, F. E. Ashton, and D. A. Caugant. 2000. Genetic characterization of a new variant within the ET-37 complex of Neisseria meningitidis associated with outbreaks in various parts of the world. Epidemiol. Infect. 125:285-298.
  52. Rokbi, B., G. Renauld-Mongenie, M. Mignon, B. Danve, D. Poncet, C. Chabanel, D. A. Caugant, and M. J. Quentin-Millet. 2000. Allelic diversity of the two transferrin-binding protein B gene isotypes among a collection of Neisseria meningitidis strains representative of serogroup B disease: implication for the composition of a recombinant TbpB-based vaccine. Infect. Immun.68:4938-47.
  53. Sow, A. I., D. A. Caugant, M. F. Cisse, E. A. Høiby, and A. Samb. 2000. Molecular characteristics and susceptibility to antibiotics of serogroup A Neisseria meningitidis strains isolated in Senegal in 1999. Scand. J. Infect. Dis. 32:185-187.
  54. Vogel, U., H. Claus, M. Frosch, and D. A. Caugant. 2000. Molecular basis for the distinction of the ET-15 clone within the ET-37 complex of Neisseria meningitidis. J. Clin. Microbiol.38:941-942.
  55. Smith, I., A. K. Lehmann, L. Lie, A. Diagranes, D. A. Caugant, E. A. Høiby, L. O. Frøholm, and A. Halstensen. 1999. Outbreak of meningococcal disease in western Norway due to a new C serogroup C variant of the ET-5 clone: effect of vaccination and selective carriage eradication. Epidemiol. Infect. 123:373-382.
  56. Wedege, E., D. A. Caugant, A. Musacchio, N. B. Saunders, and W. D. Zollinger. 1999. Redesignation of a previous P1.15 subtype-specific meningococcal monoclonal antibody as a P1.19 specific reagent. Clin. Diagn. Lab. Immunol. 6:639-642.
  57. Bart, A., I. G. A. Schuurman, M. Achtman, D. A. Caugant, J. Dankert, and A. van der Ende. 1998. Random amplified polymorphic DNA (RAPD) genotyping of serogroup A meningococci yields results similar to multilocus enzyme electrophoresis (MEE) and reveals new genotypes. J. Clin. Microbiol. 36:1746-1749.
  58. Bevanger, L., K. Bergh, G. Gisnås, D. A. Caugant, and L. O. Frøholm. 1998. Identification of nasopharyngeal carriage of an outbreak strain of Neisseria meningitidis by pulsed-field gel electrophoresis versus phenotypic methods. J. Med. Microbiol. 47:993-998.
  59. Caugant, D. A. 1998. Population genetics and molecular epidemiology of Neisseria meningitidis. APMIS 106:505-525.
  60. Fijen, C. A. P., E. J. Kuiper, J. Dankert, M. R. Daha, and D. A. Caugant. 1998. Neisseria meningitidis strains isolated from complement-deficient and complement-sufficient patients in The Netherlands. J. Clin. Microbiol. 36:2342-2345.
  61. Kwara, A., R. A. Adegbola, P. T. Corrah, M. Weber, M. Achtman, G. Morelli, D. A. Caugant, and B. M. Greenwood. 1998. Meningitis caused by a serogroup W-135 clone of the ET-37 complex of Neisseria meningitidis in West Africa. Trop. Med. Int. Health 3:742-746.
  62. Maiden, M. C. J., J. A. Bygraves, E. Feil, G. Morelli, J. E. Russell, R. Urwin, Q. Zhang, J. Zhou, D. A. Caugant, I. M. Feavers, M. Achtman, and B. G. Spratt. 1998. Multilocus sequence typing: A portable approach to the identification of clones within populations of pathogenic microorganisms. Proc. Natl. Acad. Sci. USA 95:3140-3145.
  63. McGee L., H. J. Koornhof, and D. A. Caugant. 1998. Epidemic spread of serogroup A Neisseria meningitidis of subgroup III to South Africa, 1996. Clin. Infect. Dis. 27:1214-1220.
  64. Tønjum, T., D. A. Caugant, S. A. Dunham, M. Koomey. 1998. Repetitive sequence elements are associated with a polymorphic domain of the PilQ pilus biogenesis protein of Neisseria meningitidis. Mol. Microbiol. 29:111-124.
  65. Van Looveren, M., P. Vandamme, M. Hauchecorne, M. Wijdooghe, F. Carion, D. A. Caugant, and H. Goosens. 1998. Molecular epidemiology of recent Belgian isolates of Neisseria meningitidis serogroup B. J. Clin. Microbiol. 36:2828-2834.
  66. Andersen, S. R., J. Kolberg, E. A. Høiby, E. Namork, D. A. Caugant, L. O. Frøholm, E. Jantzen, and G. Bjune. 1997. Lipopolysaccharide heterogeneity and phase variation of Neisseria meningitidis: consequences for vaccine development. Scand. J. Immunol. 45:442.
  67. Andersen, S. R., J. Kolberg, E. A. Høiby, E. Namork, D. A. Caugant, L. O. Frøholm, E. Jantzen, and G. Bjune. 1997. Lipopolysaccharide heterogeneity and escape mechanisms of Neisseria meningitidis: possible consequences for vaccine development. Microbial Pathog. 23:139-155.
  68. Hubert, B., and D. A. Caugant. 1997. Recent changes in meningococcal disease in Europe. Euro Surveillance 2:69-71.
  69. Rokbi, B., M. Mignon, D. A. Caugant, and M.-J. Quentin-Millet. 1997. Heterogeneity of tbpB, the transferrin-binding protein B gene, among serogroup B Neisseria meningitidis of the ET-5 complex. Clin. Diagn. Lab. Immunol. 4:522-529.
  70. Rokbi, B., M. Mignon, G. Maitre-Wilmotte, L. Lissoto, B. Danve, D. A. Caugant, and M.-J. Quentin-Millet. 1997. Evaluation of recombinant transferrin-binding protein B variants from Neisseria meningitidis for their ability to induce cross reactive and bactericidal antibodies against a genetically diverse collection of serogroup B strains. Infect. Immun. 65:55-63.
  71. Varaine, F., D. A. Caugant, J.Y. Riou, M. K. Kondé, G. Soga, D. Nshimirimana, G. Muhirwa, D. Ott, E. A. Høiby, F. Fermon, and A. Moren. 1997. Meningitis outbreaks and vaccination strategy. Trans. Roy. Soc. Trop. Med. Hyg. 91:3-7.
  72. Guibourdenche, M., E. A. Høiby, J.-Y. Riou, F. Varaine, C. Joguet, and D. A. Caugant. 1996. Epidemics of serogroup A Neisseria meningitidis of subgroup III in Africa, 1989-94. Epidemiol. Infect. 116:115-120.
  73. Seiler, A., R. Reinhardt, J. Sarkari, D. A. Caugant, and M. Achtman. 1996. Allelic polymorphism and site-specific recombination in the opc locus of Neisseria meningitidis. Mol. Microbiol. 19:841-856.
  74. Caugant, D. A., E. A. Høiby, L. O. Frøholm, and P. Brandtzæg. 1996. Polymerase chain reaction for case ascertainment of meningococcal meningitis: application to the cerebrospinal fluids collected in the course of the Norwegian meningococcal serogroup B protection trial. Scand. J. Infect. Dis. 28:149-153.
  75. Delvig, A. A., E. Wedege, D. A. Caugant, R. Dalseg, J. Kolberg, M. Achtman, and E. Rosenqvist. 1995. A linear B-cell epitope on the class 3 outer-membrane protein of Neisseria meningitidis recognised after vaccination with the Norwegian group B outer-membrane vesicle vaccine. Microbiology 141:1593-1600.
  76. Ristola, M., M. Jahkola., H. Käyhty, M. Sarvas, P. H. Mäkelä, D. Caugant, and R. Visakorpi. 1995. Meningococcal outbreak in Southern Finland. Euro Surveillance 0-1:2-3.
  77. Wedege, E., J. Kolberg, A. Delvig, E. A. Høiby, E. Holten, E. Rosenqvist, and D. A. Caugant. 1995. Emergence of a new virulent clone within the electrophoretic type 5 complex of serogroup B meningococci in Norway. Clin. Diagn. Lab. Immunol. 2:314-321.
  78. Caugant, D. A., E. A. Høiby, P. Magnus, O. Scheel, T. Hoel, G. Bjune, E. Wedege, J. Eng, and L. O. Frøholm. 1994. Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J. Clin. Microbiol. 32:323-330.
  79. Chaudhuri, A. K. R., N. Banatvala, D. A. Caugant, R. J. Fallon, and K. Whaley. 1994. Phenotypically similar clones of serogroup B Neisseria meningitidis causing recurrent meningitis in a patient with total C5 deficiency. J. Infect. 29:236-237.
  80. Guibourdenche, M., D. A. Caugant, V. Hervé, J. M. Debonne, C. Lanckriet, M. Merlin, C. Mathiot, J. B. Roungou, G. Martet, and J. Y. Riou. 1994. Characteristics of serogroup A Neisseria meningitidis strains isolated in the Central African Republic in February 1992.Eur. J. Clin. Microbiol. Infect. Dis. 13:174-177.
  81. Orren, A., D. A. Caugant, C. A. P. Fijen, J. Dankert, E. J. van Schalkwyk, J. T. Poolman, and G. J. Coetzee. 1994. Characteristics of strains of Neisseria meningitidis recovered from complement-sufficient and complement-deficient patients in the Western Cape Province, South Africa. J. Clin. Microbiol. 32:2185-2191.
  82. Scholten, R. J. P. M., J. T. Poolman, H. A. Valkenburg, H. A. Bijlmer, J. Dankert, and D. A. Caugant. 1994. Phenotypic and genetic changes in a new clone-complex of Neisseria meningitidis causing disease in the Netherlands, 1958-1990. J. Infect. Dis. 169:673-676.
  83. Thiel, W., G. Haas, A. Fox, and D.A. Caugant. 1994. Epidemiology of Neisseria meningitidis in Austria. Antibiotika Monitor 10: 13-15.
  84. Rosenqvist, E., E. A. Høiby, E. Wedege, D. A. Caugant, L. O. Frøholm, B. T. McGuinness, J. Brooks, P. R. Lambden, and J. E: Heckels. 1993. A new variant of serosubtype P1.16 in Neisseria meningitidis from Norway, associated with increased resistance to bactericidal antibodies induced by a serogroup B outer membrane protein vaccine. Microbial Path. 15:197-205.
  85. Scholten, R. J. P. M., H. A. Bijlmer, J. T. Poolman, B. Kuipers, D. A. Caugant, L. Van Alphen, J. Dankert, and H. A. Valkenburg. 1993. Meningococcal disease in the Netherlands, 1958-1990: a steady increase of the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis. Clin. Infect. Dis. 16:237-246.
  86. Wang, J. F., D. A. Caugant, G. Morelli, B. Koumaré, and M. Achtman. 1993. Antigenic and epidemiological properties of the ET-37 complex of Neisseria meningitidis. J. Infect. Dis. 167:1320-1329.
  87. Wedege, E., R. Dalseg, D. A. Caugant, J. T. Poolman, and L. O. Frøholm. 1993. Expression of an inaccessible P1.7 subtype epitope on meningococcal class 1 proteins. J. Med. Microbiol. 38:23-28.
  88. Caugant, D. A., E. A. Høiby, E. Rosenqvist, L. O. Frøholm, and R. K. Selander. 1992. Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol. Infect. 109:241-253.
  89. Kuzemenska, P., D. A. Caugant, L. O. Frøholm, R. K. Selander, and G. Chudackova. 1992. Genotypes of Neisseria meningitidis strains isolated from patients in the Czech Republic. Cesk. Epidemiol. Mikrobiol. Imunol. 41:129-138.
  90. Lomholt, H., K. Poulsen, D. A. Caugant, and M. Kilian. 1992. Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc. Natl. Acad. Sci. USA. 89:2120-2124.
  91. Sacchi, C. T., L. L. Pessoa, S. R. Ramos, L. G. Milagres, M. C. C. Camargo, N. T. Hidalgo, E. A. Melles, D. A. Caugant, and C. E. Frasch. 1992. An ongoing group B Neisseria meningitidis epidemic in Sao Paulo, Brazil due to increased prevalence of a single clone of the ET-5 complex. J. Clin. Microbiol. 30:1734-1738.
  92. Sacchi, C. T., R. C. Zanella, D. A. Caugant, C. E. Frasch, N. T. Hidalgo, L. G. Milagres, L. L. Pessoa, S. R. Ramos, M. C. C. Camargo, and C. E. A. Melles. 1992. Emergence of a new clone of serogroup C Neisseria meningitidis in Sao Paulo area, Brazil. J. Clin. Microbiol. 30:1282-1286.
  93. Wang, J., D. A. Caugant, X. Li, X. Hu, J. T. Poolman, B. A. Crowe, and M. Achtman. 1992. Clonal and antigenic analysis of serogroup A Neisseria meningitidis with particular reference to epidemiological features of epidemic meningitis in China. Infect. Immun. 60:5267-5282.
  94. Ashton, F. E., J. A. Ryan, A. Borczyk, D. A. Caugant, L. Mancino, and D. Huang. 1991. Emergence of a virulent clone of Neisseria meningitidis serotype 2a associated with meningococcal group C disease in Canada. J. Clin. Microbiol. 29:2489-2493.
  95. Caugant, D. A., L. O. Frøholm, and R. K. Selander. 1991. Molecular epidemiology of meningococcal disease. Méd. Mal. Infect. 21:191-194.
  96. Fox, A. J., D. M. Jones, S. J. Gray, D. A. Caugant, N. A. Saunders. 1991. An epidemiologically valuable typing method for Neisseria meningitidis by analysis of restriction fragment length polymorphism. J. Med. Microbiol. 34:265-270.
  97. Frøholm, L. O., D. A. Caugant, E. Holten, E. A. Høiby, E. Rosenqvist, and E. Wedege. 1991. Meningococcal strains isolated from teen-age patients during the serogroup B vaccination trial in Norway: serotyping, serosubtyping, immunotyping and clonal analysis. NIPH Annals (Oslo) 14:139-143.
  98. Mastrantonio P., M. E. Congiu, R. K. Selander, and D. A. Caugant. 1991. Genetic relationships among strains of Neisseria meningitidis causing disease in Italy, 1984-1987. Epidemiol. Infect. 106:143-150.
  99. Riou, J. Y., D. A. Caugant, R. K. Selander, J. T. Poolman, M. Guibourdenche, and E. Collatz. 1991. Characterization of Neisseria meningitidis serogroup A strains, from an outbreak in France, by serotypes and sero-subtypes, multilocus enzyme genotypes and outer membrane protein patterns. Eur. J. Clin. Microbiol. Infect. Dis. 10:405-409.
  100. Wedege, E., D. A. Caugant, L. O. Frøholm, and W. D. Zollinger. 1991. Characterization of serogroup A and B Neisseria meningitidis with monoclonal antibodies and by multilocus enzyme electrophoresis. J. Clin. Microbiol. 29:1486-1492.