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Surveillance of meningococcal infections in Belgium

1998; Elsevier BV; Volume: 4; Issue: 4 Linguagem: Inglês

10.1111/j.1469-0691.1998.tb00675.x

1469-0691

M. Van Looveren, Françoise Carion, Peter Vandamme, Herman Goossens,

Pneumocystis jirovecii pneumonia detection and treatment

Meningococcal disease remains an important public-health problem in both developing [1.Guibourdenche M H⊘iby EA Riou JY Variane F Joguet C Caugant DA Epidemics of serogroup A Neisseria meningitidis of subgroup III in Africa, 1989–94.Epidemiol Infect. 1996; 116: 115-120Crossref PubMed Scopus (48) Google Scholar] and industrialized countries [2.Ringuette L Lorange M Ryan A Ashton F. Meningococcal infections in the province of Québec, Canada, during the period 1991 to 1992.J Clin Microbiol. 1995; 33: 53-57PubMed Google Scholar]. Before 1990, the annual incidence of meningococcal disease in Belgium fluctuated around one case per 100 000 inhabitants. However, since the early 1990s an increase in the incidence of meningococcal disease has been seen. Meningococci are subdivided into serotypes based on the immunologic properties of several outer-membrane proteins and lipopolysaccharides [3.Frasch CE Zollinger WD Poolman JT Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes.Rev Infect Dis. 1985; 7: 504-510Crossref PubMed Scopus (346) Google Scholar], and development of monoclonal antibodies against those antigens has significantly contributed to a better understanding of the epidemiology of meningococcal disease [3.Frasch CE Zollinger WD Poolman JT Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes.Rev Infect Dis. 1985; 7: 504-510Crossref PubMed Scopus (346) Google Scholar]. In Belgium, serogroup B is the predominant sero-group causing meningococcal disease, followed by serogroup C. No effective vaccine is currently available for protection against group B meningococcal disease, because the B capsular polysaccharide is not immunogenic in humans [4.Romero JD Outschoorn IM Current status of meningococcal group B vaccine candidates: capsular or noncapsular.Clin Microbiol Rev. 1994; 7: 559-575PubMed Google Scholar]. The recent emergence of penicillin-resistant meningococcal strains [5.Blondeau JM Ashton FE Isaacson M Yaschuk Y Anderson C Ducasse G. Neisserin meningitidis with decreased susceptibility to penicillin in Saskatchewan, Canada.J Clin Microbiol. 1995; 33: 1784-1786PubMed Google Scholar, 6.Campos J Trujillo G Seuba T Rodriguez A. Discriminative criteria for Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin.Antimicrob Agents Chemother. 1992; 5: 1028-1031Crossref Scopus (34) Google Scholar] may create additional therapeutic problems. In the present investigation we describe the spread in Belgium of a serogroup B strain which was first reported in The Netherlands in the early 1980s [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. Isolates were characterized by traditional serotyping, and their susceptibility patterns to a panel of antimicrobial agents were determined. Extensive phenotyping (multilocus enzyme electrophoresis) and genotyping (PCR and pulsed-field gel electrophoresis analyses) were performed on these and other strains [8.Van Looveren M, Vandamme P, Hauchecorne M, et al. Molecular epidemiology of recent Belgian isolates of Neisseria meningitidis serogroup B. Submitted.Google Scholar]. Meningococcal infections are notifiable in Belgium. Trends of meningococcal disease have been derived from epidemiologic and laboratory data sets that are complementary but are maintained separately. On the one hand, the Federal Belgian Health Inspection receives physician notifications; data include age, gender, date and location. On the other hand, the Belgian Meningococcal Reference Left at the Scientific Institute for Public Health-Louis Pasteur (Brussels) receives isolates of Neisseria meningitidis from the Belgian diagnostic laboratories for confirmation and determination of serotype, subtype, and susceptibility pattern. Since 1985, the annual number of meningococcal isolates submitted to the Belgian Meningococcal Reference Left has exceeded the number of cases reported [9.Carion F. Meningococci: Surveillance in Belgium by the reference laboratory.in: Program and abstracts of the 11th Seminar on Diagnostics and Surveillance of Infectious Diseases. Institute of Hygiene and Epidemiology, Brussels, Belgium1995: 21-29Google Scholar]. It is generally accepted that the number of submissions to the Belgian Meningococcal Reference Left is highly representative for the number of cases of meningococcal disease in Belgium. From 1990 to 1995, isolates from 769 patients (429 males, 324 females, 16 of unspecified gender; male/female ratio 1.32) were submitted to the Belgian Meningococcal Reference Left. Seven hundred and fifty-three strains were recovered from cerebrospinal fluid or blood, and 16 strains were throat or skin isolates of patients with meningococcal disease. Serogroups were determined by slide agglutination with commercially available rabbit antisera specific for the A, C, X, Y, Z, W135 (Murex Diagnostics, Dartford, UK) and 29E (Diagnostics Pasteur, Marnes-la-Coquette, France) capsular polysaccharides [10.Riou JY Saliou P Guibourdenche M Chalvignac MA Etude bactériologique et sérologique de 358 souches de Neisseria et Branhamella isolées en Haute-Volta.Med Mal Infect. 1980; 10: 430-436Crossref Scopus (10) Google Scholar]. For serogroup B, a monoclonal antibody (Murex Diagnostics, Dartford, UK) was used. Serotyping and subtyping with monoclonal antibodies (J.T. Poolman, National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands) was carried out using an enzyme-linked immunoblot assay [11.Calain P Poolman J. Zollinger W et al.Serological study of meningococcal isolates in Switzerland and France 1980–1986.Eur J Clin Microbiol Infect Dis. 1988; 7: 788-791Crossref PubMed Scopus (5) Google Scholar] or whole cell ELISA [12.Abdillahi H Poolman JT Whole-cell ELISA for typing Neisseria meningitidis with monoclonal antibodies.FEMS Microbiol Lett. 1987; 48: 367-371Crossref Scopus (218) Google Scholar]. In Belgium, an epidemic elevation of the number of cases of meningococcal disease was observed between 1969 and 1975. In 1972, the epidemic reached its peak incidence of 5.3 cases per 100 000 inhabitants [13.De Maeyer S Seba JM Reginster G. Epidemiology of meningococcal meningitis in Belgium.J Infect. 1981; 3: 63-70Abstract Full Text PDF PubMed Scopus (18) Google Scholar]. Afterwards, the incidence of disease decreased and fell to normal inter-epidemic proportions of one case per 100 000 inhabitants per year. Except for a small augmentation in 1980, the incidence has fluctuated around this value. However, during the past 6 years, the incidence of meningococcal disease in Belgium, calculated from the submission of meningococcal isolates to the Belgian Meningococcal Reference Left, has gradually increased from 0.8 cases per 100 000 inhabitants in 1990 to 2.0 cases per 100 000 inhabitants in 1995. This increase is particularly due to a rise in the proportion of serogroup B strains. Serogroup B meningococci always accounted for more than 60% of the cases of meningococcal disease, but in recent years their proportion has increased to up to 80% of the cases. The distribution of serotypes and subtypes of all 568 serogroup B isolates obtained during 1990–95 is shown in Table 1. Amongst the serogroup B strains, the increase of serotype 4 isolates was the most obvious, their relative frequency increasing from 4% in 1990 to 74% in 1995. Serotype 4 strains were mostly associated with subtype P1.4 group B isolates. The proportion of subtype P1.4 increased from 6% in 1990 to 48% in 1995 (Table 1). Strains with phenotype B:4: P1.4 currently cause 32.5% of the cases of meningococcal disease; however, B:non-typeable: P1.4 strains account for an additional 3.5% (total of 36.0%)).Table 1Distribution of serotypes and subtypes among 568 serogroup B meningococci isolated from patients with meningococcal disease in Belgium between 1990 and 1995Year of isolation199019911992199319941995No of isolates tested5377919495158Serotypes (%)1–326242a4321112b63445–4417385374142–22–115910794516–43–––Non-serotypeable757774403414Subtypes (%)P1.1–61–––P1. 1,7––3284P1.213103431P1.2,5––––4P1.462132404548P1.5–––23P1.69––1–2P1.7–1–323P1.7,16––3644P1.9242–31P1.1021101111–P1.12––24–2P1.13–––989P1.14––1315P1. 159267346P1.168105314Non-subtypeable511930784 Open table in a new tab Strains with phenotype B:4:P1.4 were first isolated in The Netherlands in 1980 [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. Until 1984, they were predominantly recovered in the southwestern part of The Netherlands in the vicinity of Rotterdam and Breda. Thereafter, the phenotype dispersed throughout the country, but the incidence remained most pronounced in the southern provinces [14.Caugant DA Bol P H⊘iby EA Zanen HC Fr⊘holm LO Clones of serogroup B Neisseria meningitidis causing systemic disease in the Netherlands, 1958–1986.J Infect Dis. 1990; 162: 867-874Crossref PubMed Scopus (70) Google Scholar]. In Belgium, an increase of meningococcal infections, with B:4:P1.4 and B:non-typeable: P1.4 as predominant phenotypes, was first noticed in the province of Antwerp, near the border with The Netherlands. Later, a similar trend was seen in other provinces of Belgium, particularly East and West Flanders. In 1994, the Walloon provinces were reached, and in 1995 phenotypes B:4:P1.4 and B:non-typeable: P1.4 were encountered in all Belgian provinces (Figure 1). Consequently, dispersion of the Dutch B:4:P1.4 strain in Belgium can be hypothesized. These and other [8.Van Looveren M, Vandamme P, Hauchecorne M, et al. Molecular epidemiology of recent Belgian isolates of Neisseria meningitidis serogroup B. Submitted.Google Scholar] data suggest that the elevated number of meningococcal infections is due to the introduction of a new strain of N. meningitidis (B:4:P1.4/B:non-typeable: P1.4) in Belgium since the beginning of the 1990s. The introduction of a new strain in a susceptible population was previously shown to cause a rise in the number of meningococcal infections [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. In The Netherlands, the incidence of serotype B:4 rose from 11% in 1980 to 43% in 1990, and the incidence of the subtype P1.4 increased from 3% in 1980 to 41% in 1990 [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. However, the highest prevalence of strain B:4:P1.4 was only 21%. As a consequence, B:4:P1.4 alone could not be held responsible for the increase of meningococcal disease in The Netherlands after 1982 [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. Also in England and Wales, B:4:P1.4 strains have become established in the past 5 years and now account for a quarter of all group B infections (25% in 1995) [15.Kaczmarski EB Meningococcal disease in England and Wales: 1995.CDR Rev. 1997; 7: R55-R59Google Scholar]. Meningococcal disease predominates in the age group of 0–4 years, accounting for 38–49% of the annual registered number of cases. From 1990 to 1995, children less than 1 year of age accounted for 13.0%, 17.7%, 15.1%, 18.1%, 17.3%, and 12.5%, respectively, of the cases of meningococcal disease. However, from 1993 onwards, a secondary peak was observed in the age group from 15 to 19 years. The incidence among children aged between 15 and 19 years old increased from 0.9 per 100 000 inhabitants in 1991 (95% confidence interval (95% CI): 0.2–1.7) to 6.2 per 100 000 inhabitants in 1995 (95% CI: 4.2–8.2). This difference of 5.3 was statistically significant (95% CI: 3.2–7.4). A shift in age distribution from younger to older age categories has been observed before and was explained by a coinciding shift of the serogroup and/or serosubtype distribution [7.Scholten RJPM Bijlmer HA Poolman JT et al.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. 1993; 16: 237-246Crossref PubMed Scopus (69) Google Scholar]. Indeed, in Belgium, serogroup B has become more prevalent in recent years, and the introduction of phenotypes not previously encountered has also been seen (B:4:P1.4 and B:non-typeable: P1.4). A random sample of 420 clinical isolates stratified by serogroup and year of isolation was selected for susceptibility testing by E-test (AB Biodisk, Sölna, Sweden). The use of the E-test for determining antibiotic susceptibility of N. meningitidis was validated by Hughes et al [16.Hughes JH Bredenbach DJ Erwin ME Jones RN E-test as susceptibility test and epidemiologic tool for evaluation of Neisseria meningitidis isolates.J Clin Microbiol. 1993; 31: 3255-3259PubMed Google Scholar]. They found that E-test MICs were within ± 1 log2 dilution of the MICs by agar dilution. The susceptibilities to five antimicrobial agents, i.e. penicillin, rifampicin, sulfadiazine, ciprofloxacin and ceftriaxone, were determined. The E-test was performed as previously described by Blondeau and Yaschuk [17.Blondeau JM Yaschuk Y. In vitro activities of ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin against fully susceptible and moderately penicillin-resistant Neisseria meningitidis.Antimicrob Agents Chemother. 1995; 39: 2577-2579Crossref PubMed Scopus (21) Google Scholar]. Definitions of susceptibility were as follows: for penicillin, MIC 0.06 mg/L indicated susceptibility, MIC >0.06–1 mg/L relative resistance, and MIC >1 mg/L resistance [6.Campos J Trujillo G Seuba T Rodriguez A. Discriminative criteria for Neisseria meningitidis isolates that are moderately susceptible to penicillin and ampicillin.Antimicrob Agents Chemother. 1992; 5: 1028-1031Crossref Scopus (34) Google Scholar]; for all other antimicrobial agents, published NCCLS breakpoint definitions were used [18.National Committee for Clinical Laboratory StandardsMethods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M100-S6. NCCLS, Villanova, PA1997Google Scholar]. Although penicillin remains the drug of choice for serious meningococcal disease, the drug appears to be less active because of emerging resistance [17.Blondeau JM Yaschuk Y. In vitro activities of ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin against fully susceptible and moderately penicillin-resistant Neisseria meningitidis.Antimicrob Agents Chemother. 1995; 39: 2577-2579Crossref PubMed Scopus (21) Google Scholar, 19.Sutcliffe EM Jones DM El-Sheikh S Percival A. Penicillin-insensitive meningococci in the UK.Lancet. 1988; i: 657-658Abstract Scopus (70) Google Scholar, 20.Sáez-Nieto JA Lujan R Berrón S et al.E-pidemiology and molecular basis of penicillin-resistant Neisseria meningitidis in Spain: a 5-year history (1985–1989).Clin Infect Dis. 1992; 14: 394-402Crossref PubMed Scopus (120) Google Scholar, 21.Jackson LA Tenover FC Baker C et al.Prevalence of Neissevia meningitidis relatively resistant to penicillin in the United States, 1991.J Infect Dis. 1994; 169: 438-441Crossref PubMed Scopus (62) Google Scholar], The first meningococcal strain isolated in Belgium with a reduced susceptibility to penicillin (0.5 mg/L) was reported in 1993 [22.Brunen A Peetermans W Verhaegen J Robberecht W. Meningitis due to Neisseria meningitidis with intermemate susceptibility to penicillin.Eur J Clin Microbiol Infect Dis. 1993; 12: 969-970Crossref PubMed Scopus (11) Google Scholar]. We observed a reduced susceptibility to penicillin (MIC > 0.06–0.125 mg/L) [16.Hughes JH Bredenbach DJ Erwin ME Jones RN E-test as susceptibility test and epidemiologic tool for evaluation of Neisseria meningitidis isolates.J Clin Microbiol. 1993; 31: 3255-3259PubMed Google Scholar, 17.Blondeau JM Yaschuk Y. In vitro activities of ciprofloxacin, cefotaxime, ceftriaxone, chloramphenicol, and rifampin against fully susceptible and moderately penicillin-resistant Neisseria meningitidis.Antimicrob Agents Chemother. 1995; 39: 2577-2579Crossref PubMed Scopus (21) Google Scholar] for 27 strains (6.4%). The strains showed the following MICs: 0.064 mg/L for 18 isolates, 0.094 mg/L for eight isolates and 0.125 mg/L for one isolate. High-level resistance to sulfadiazine (MIC >256mg/L) was observed in 80 strains (19.0%). No association was found between sulfadiazine resistance and serotype or subtype. All 420 isolates were susceptible to rifampicin, ciprofloxacin and ceftriaxone. In conclusion, we hypothesize that the increase in the incidence of meningococcal disease in Belgium is due to the introduction of a new strain of N. meningitidis (B:4:P1.4) in the susceptible Belgian population since the early 1990s. Phenotype B:4:P1.4 strains were first encountered in The Netherlands, and have caused disease their since the early 1980s. We suggest that these strains dispersed into Belgium from 1990 onwards. We thank Machteld Hauchecorne and Monik Wijdooghe for their excellent technical assistance, Geneviève Ducoffre for her kind help with the figure, and Pierre Van Damme and Jean-Claude Van Der Auwera for statistical advice. PV. is indebted to the Fund for Scientific Research-Flanders for a position as a postdoctoral research fellow. The results of this study were presented in part as a poster at the 8th European Congress of Clinical Microbiology and Infectious Diseases held in Lausanne, Switzerland, 25–28 May 1997 (abstract 414) and at the 4th meeting of the European Monitoring group on Meningococci held in Paris, France, 4–7 June 1997 (abstract 18).