An attempt at an epidemiological explanation - Epib.nl

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Meningococcal disease ill the Netherlands, 1958-1990INTRODUCfIONMeningococcal disease (MD) still poses major health problems in both developingand industrialized countries. Before 1980 the annual incidence of MD in the Netherlandsvaried between 0.7 and 2.0 cases per 100,000 inhabitants, whereas epidemicsthat occurred in 1946 and 1966 were associated with all annual incidence of 9.9 per100,000 and 4.1 per 100,000, respectively." During the 1980s the incidence of MD inthe Netherlands gradually increased and it reached 3.5 per 100,000 inhabitants in1990.Meningococci are classified into serogroups, serotypes and subtypes OD the basis ofantigenic differences in their capsular polysaccharides, class 2/3 outer-membraneproteins (OMPs) and class 1 OMPs, respectively. Studying the serotype and subtypedistribution of meningococci contributes to the understanding of the epidemiology ofMD' The number of monoclonal antibodies used for serosub typing is still growing,thus improving our insight into the spread of MD.' The characterization of thechromosomal genotype of Neisseria meningitidis isolates by multilocus enzymeelectrophoresis is another valu able tool for studying the epidemiology of MD.'Both in Europe and in the Americas, serogroup B is the predominant serogroupcausing MD, followed in freq uency by serogroup C' 7 Currently, no effective vaccineis available for protection against serogroup B MD. The development of such avaccine is primarily focused on class 1 OMPs.69 Experimental vaccines against serogroupB, which to some extent covered the local needs, were tested in Norway, Cubaand Chile. I " 12 The reported efficacy of these vaccines ranged from 51 % to 81%. ITOMP vaccines are to be used for the prevention of serogroup B MD, it becomesessential to monitor the distribution of subtypes over time in order to allow foradaptation of the vaccine to the current circulation of subtypes.Since 1958, meningococcal isolates from blood and/or cerebrospinal fluid (CSF)have been submitted for further classification to the Reference Laboratory fo rBacterial Meningitis (RLBM) in Amsterdam by ahoost all microbiologists in theNetherlands. The strain collection currently comprises of approximately 7000meningococcal isolates. On the basis of this extensive collection, we report thechanging pattern of the serotype and sub type distribution of meningococci in theNetherlands, as determined with the use of monoclonal antibodies against 7 serotypesand 11 subtypes. Our typing results are compared with those obtained with multilocusenzyme electrophoresis in a former survey of strains from patients in the Netherlands13 Special attention is paid to the period 1980-1990, during which the incidenceof MD gradually increased to a subepidemic level. By comparing the results fromtyping in this period with those from the period 1958-1975, we attempt to explain theincreased number of cases. In addition, we describe the shift in the age-distributionand the increase in the recovery of isolates from blood alone - phenomena that wereobserved during ti,e last decade - and discuss tlleir relation to the serogroup andserosubtype distribution.19
Chapter 2MATERIALS AND METHODSBacterial isolatesIsolates of N. meningitidis that were recovered from the blood and/or CSF of patientswith systemic MD in the Netherlands were sent on chocolate-agar slants to theRLBM by regional laboratories. Upon arrival} the isolates were stored at _70°C onglass beads as suspensions in 15% glycerol broth until further processing. Data on thesource of isolation (CSF, blood or both) and on the patient (age and gender) werecollected from the forms supplied by the laboratories. A case was defined assepticemic if N. meningitidis was cultured from blood alone. All isolates submitted tothe RLBM from 1980 to 1990 were included in the general analysis.Grouping and typingUpon receipt of the strains in our laboratory, we performed serogrouping bymeans of Ouchterlony gel diffusion with use of antisera raised in rabbits againstserogroups A, B, C, X, Y, Z, W-135 and 29E.14For detection of changing patterns of serotypes and/or subtypes, all serogroup A, Band C meningococci obtained in 1980, 1983, and 1985-1990 (of which 11 isolates werelost) were serotyped and subtyped by means of a whole-cell ELISA with use ofspecific monoclonal antibodies against class 2/3 and class 1 OMPs of N. meningitidis.'Table 1. Monoclonal antibodies and reference strains used for serotyping and subtyping of meningococcalisolatesIdentification Monoclonal antibody Reference strainSerotypeI MN3C6B MIOSO2. MN2D3F BI6B62b MN20B 29964 MNI4G21.l7 87022714 MN5C8C 53446IS MNI5AI4H6 H44(7616 MN93E 9-1 60ESubtypePl.l MNI4C2.3 MIOSOP1.2 MNI6C13F4 BI6B6 and 2996PI.4 MNZOB9.34 882066Pl.6 MNI9D6.13 M990Pl.7 MNI4CIl.6 H44(76Pl.9 MN5AlOF M982Pl.lO MN20F4.l7 870227P1.l2 MN20A7.1O 53032P1.l4 MN21G3.17 53446Pl.l5 MN3C5C H355Pl.l6 MNSCllG H44(7620
Page 1 and 2: An attempt at an epidemiological ex
Page 3 and 4: VRIJE UNIVERSITEITTHE INCREASED INC
Page 5 and 6: CONTENTSChapter 1 General introduct
Page 7 and 8: Chapter 1Meningococcal disease (MD)
Page 9 and 10: Chapter 1Antigenic variation in the
Page 11 and 12: Chapter 1by electrophoretic typing.
Page 13 and 14: Chapter 1is assumed to be the main
Page 15 and 16: CluJpter 1Study objectives and cont
Page 17 and 18: Chapter 125 Crowe BA. Wall RA. Kuse
Page 19 and 20: Chapter 170 Brandtzacg P, Kicrulf P
Page 21: Chapler 2ABSTRACfIn order to explai
Page 25 and 26: Chapter 2Table 2. An nual number of
Page 27 and 28: Chapter 2the age-distribution to ol
Page 29 and 30: Chapter 2of serotype 4 strains vari
Page 31 and 32: Chapter 2Table 6. Relative distribu
Page 33 and 34: Chapter 2endemicity in the Netherla
Page 35 and 36: Chapter 2REFERENCESde Marie S. Epid
Page 37 and 38: CHAPTER 3PHENOTYPIC AND GENOTYPIC C
Page 39 and 40: Evolution of meningococcal cionesIN
Page 41 and 42: Evolution of meningococcal clonesme
Page 43 and 44: Evolution of meningococcal clonesTa
Page 45 and 46: Evolution of meningococcal clonesli
Page 47 and 48: CHAPTER 4LIPOOLIGOSACCHARIDE IMMUNO
Page 49 and 50: LOS immunotyping of N. meningitidis
Page 57 and 58: LOS immunolyping of N. meningilidis
Page 59 and 60: LOS immunolyping of N. meningilidis
Page 65 and 66: Chapter 5ABSTRACfThe aim of this pr
Page 67 and 68: Chapter 5tive lung disease, chronic
Page 69 and 70: Chapter 5distribution of the clinic
Page 71 and 72: Chapter 5The striking difference in
Page 73 and 74:
Chapter 510-19 and ~50 years, in wh
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Chapter 5REFERENCES1 Andersen BM. M
Page 77 and 78:
Chapter 6ABSTRACfObjectives: To ass
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Chapter 6PATIENTS AND METHODSThis s
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Chapler 6case. In 28 household cont
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Chapter 6rifampicin witb oral contr
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CHAPTER 7GENERAL DISCUSSION ANDRECO
Page 87 and 88:
General discussionexample of the ab
Page 89 and 90:
General discussionPossible changes
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General discussionBrazilian study,
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General discussionIt is very diffic
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General discussionREFERENCES1 Pelto
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SUMMARY
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Summaryemergence of a meningococcal
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Summaryexplains part of the rise. T
Page 103 and 104:
SamenvattingMeningokokkenziekte (me
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Samenvatting57 isolaten was bet imm
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AFFILIATIONS OF CO-AUTHORSHenk A. B
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DaJl /..:woordVele" hebben meegewer
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DanklVoordMijD ouders dank ik voor
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