P. Bol

Dysfunctional properdin in a Dutch family with meningococcal disease.

DEVELOPMENT of systemic infections with Neisseria meningitidis can usually be ascribed to the absence of protective IgM or IgG antibodies, or to the presence of IgA antibodies that block serum bact...

The incidence of bacterial meningitis in the Netherlands—A comparison of three registration systems, 1977–1982

Data on the incidence of bacterial meningitis (BM) in the Netherlands are important for a cost-benefit analysis of new effective vaccines. During the period 1977-1982 we compared the notifications of meningococcal meningitis, diagnoses on discharge from hospital of all causes of BM (Stichting Medische Registratie, Medical Registration Foundation; SMR) and bacteriological data (Netherlands Reference Laboratory for Bacterial Meningitis; RBM). Notifications of meningococcal meningitis were 42% lower than SMR-data. RBM-registration of meningococcal, haemophilus and pneumococcal meningitis was 20% lower than SMR. Reviewing patient-records we found that these diseases had not been reported in 16% (RBM) and 11% (SMR) of cases. We estimate the incidence of BM during an endemic period at 8.0 per 100 000 population per year, to which the meningococcus contributes 20-25%. In children under 5 years of age the age-specific incidence of haemophilus meningitis is 22/100 000.

HAEMOPHILUS INFLUENZAE TYPE B STRAINS OF OUTER MEMBRANE SUBTYPES 1 AND 1c CAUSE DIFFERENT TYPES OF INVASIVE DISEASE

Of 275 consecutive Haemophilus influenzae type b (Hib) strains isolated from children with invasive disease in Finland in 1985-86, 74% were of the common European outer membrane protein (OMP) subtype 1 and 22% were of OMP subtype 1c, which is usually rare. Strains of subtype 1c caused proportionately more meningitis and less epiglottis than did strains of subtype 1c. Furthermore, children with disease due to strains of subtype 1c were younger than those with disease due to strains of subtype 1. The significant difference in association between subtype and the diagnosis of epiglottitis or meningitis remained even when the strong influence of age was accounted for. This finding may suggest a true difference in the virulence between these subtypes not previously demonstrated for Haemophilus influenzae type b.

Types and subtypes of 73 strains of Haemophilus influenzae isolated from patients more than 6 years of age with meningitis in The Netherlands

Strains of Haemophilus influenzae isolated in The Netherlands between 1975 and 1984 from patients with meningitis were analysed in order to determine whether older patients are infected with particular types or subtypes of the organism. Of 1154 patients with H. influenzae meningitis 73 (6.3%) were more than 6 years of age. Thirty-one strains (42%) were of serotype b, one strain was of serotyped, one strain was of serotype f and 40 strains (55%) were non-typable. Twenty-eight type b strains were available for subtyping by analysis of the major outer-membrane proteins by sodium dodecylsulphate (SDS)-polyacrylamide gel electrophoresis (PAGE), by serotyping of their lipopolysaccharides and by biotyping. Twenty-one strains were outer-membrane protein subtype 1,24-lipopolysaccharide serotype 1 and 24 biotype I. Seventeen strains (61%) combined these characteristics. This percentage did not differ significantly from the percentage found for strains isolated from patients of all age groups (80%). The 32 non-typable H. influenzae strains analysed had different outer-membrane protein patterns as seen by SDS-PAGE. Five biotypes were found, among which biotype II was predominant (21/32). The results indicated that (i) patients more than 6 years of age were infected by subtypes of H. influenzae b strains which were not significantly different from the strains isolated from younger patients, (ii) non-typable strains of H. influenzae were much more common (55%) in the older age group than in the younger (1.2%) and (iii) that these non-typable strains were not of a particular subtype.

Epidemiology of Haemophilus influenzae meningitis in patients more than 6 years of age

Haemophilus meningitis was found to be rare in those more than 6 years of age in The Netherlands (incidence: 1/10(6)/year). Persons of this age account for only 6-7% of all cases. The histories of a representative sample of 35 of 73 patients over the age of 6 years with Haemophilus influenzae meningitis were reviewed and correlated with the characteristics of the causal strains. Altogether, these patients had suffered 51 episodes of purulent meningitis. Sequelae were found after five of the 35 H. influenzae episodes studied (14%) but none of the patients died during one of these episodes. Of all the patients, 54% had severe predisposing factors, mainly CSF leaks following road traffic accidents or operations, which often led to recurrent bouts of meningitis; these patients were predominantly males. In the patients aged 15-64 years, predisposing factors were present in 74%. Predisposed patients were infected mainly by unencapsulated strains and, as far as type b strains were involved, by uncommon subtypes. Unencapsulated strains were hardly ever able to invade the bloodstream, primarily or secondarily. Careful review of the patients history is important in this rare disease, because, in many patients, the presence of a CSF fistula may become evident and surgery is likely to prevent recurrences.

Meningococcal disease in The Netherlands, 1959–1981: The occurrence of serogroups and serotypes 2a and 2b of Neisseria meningitidis

By means of a filter radioimmunoassay and the use of monoclonal anti-2a and anti-2b antibodies, we have serotyped 3164 of 3688 strains of Neisseria meningitidis isolated from patients in The Netherlands between 1959 and 1981. Serotypes 2a and 2b were distributed differently among the major serogroups A, B, C, and W-135. Neither of the types was found among group A strains. Type 2b strains of serogroup B emerged in 1965, causing a country-wide epidemic which reached a peak incidence in March and April of 1966 and continued to predominate within group B until 1979. Type 2a strains of serogroup C were responsible for a substantial number of sporadic cases over a long period without any association with outbreaks or with a shift in the pattern of the serogroup. After the appearance of group W-135 in 1971, W-135 strains caused a small non-focal epidemic wave. The upsurge of disease due to virulent sub-populations of strains B:2b and C:2a appeared to be closely related to a basic pattern of regular cyclical waves with peak intervals which differed for serogroups A, B, and C. In recent years both serotype 2a and 2b strains within the different serogroups fell to insignificant numbers. Our results show that retrospective large-scale serotyping of collected strains provides insight into the epidemiological patterns of endemic meningococcal disease.

Non-neonatal meningitis due to less common bacterial pathogens, the Netherlands, 1975-83.

In the Netherlands, case histories of 160 patients aged more than 1 month, with meningitis due to bacteria other than Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae were reviewed in order to look for associations between the bacteriological data and the course of disease. The incidence of such cases was about 0.8/100,000/year. Escherichia coli and Listeria monocytogenes each accounted for about 15% of the cases. The case-fatality rate was 18.8% (Gram-negative bacteria, 25%; Gram-positives, 15%) and sequelae occurred in 13.3% of the surviving patients (14 and 13% Gram-negative and Gram-positive, respectively). Hearing loss was the most prevalent sequela (5.0%). Predisposing factors were present in 70% of patients (69 and 71% respectively), especially in meningitis due to enteric Gram-negative bacteria (except for salmonella) and due to staphylococci. Surveillance is important because the incidence of meningitis due to these micro-organisms is likely to increase and because the problems in antibiotic treatment have not yet been solved.

Comparison of antibiotic resistant and sensitive strains ofHaemophilus influenzae type b in The Netherlands by outer-membrane protein subtyping

The percentage ofβ-lactamase producingHaemophilus influenzae strains from patients with meningitis in The Netherlands increased from 0% in 1975/1976 to 4.6 % in 1985/1986 (n=1559). Twenty-three isolates resistant to ampicillin, penicillin, chloramphenicol, rifampicin and/or tetracycline were subtyped to determine if one resistant strain was spreading. (Sub)typing was performed by capsular typing, analysis of the major outer membrane protein patterns on sodium dodecylsulfate gels (SDS-PAGE subtypes), lipopolysaccharide serotyping and biotyping. The (sub)types of the resistant strains were similar to those of sensitive strains, thus indicating that antibiotic resistant strains develop at random.

Meningitis and the Evolution of Dominance of Righthandedness

In bacterial meningitis, forced deviation of the head and/or the eyes towards either the left or the right side reflects an ipsilateral focal inflammation of the brain. Also, the symptom of forced deviation is associated with a high fatality and sequelae rate. In this study it was observed that, among 2124 Dutch patients with bacterial meningitis, forced deviation was significantly more often to the right than to the left. Because the right hemisphere is dominant for motor functions in natural lefthanders, it was concluded that bacterial meningitis might have been a selection mechanism favouring the evolution of a dominance of righthandedness.

Differences in subtype distribution of Haemophilus influenzae type b from carriers in the general population and patients with meningitis

Twenty-four Haemophilus influenzae type b strains from 836 children and young adults in an open population were subtyped by outer-membrane-protein (OMP) analysis on sodium dodecyl sulphate-polyacrylamide gels, lipopolysaccharide serotyping and biotyping. The results were compared with those obtained with H. influenzae type b strains from 97 patients with meningitis in the same city (Amsterdam). OMP subtype 1 was significantly more common among the CSF isolates than in carrier strains (82% vs 50%; p less than 0.002). The other OMP subtypes found among carriers were rarely isolated from patients. The lipopolysaccharide serotype and biotype distribution did not differ between the two groups. The combination of OMP subtype 1, lipopolysaccharide 1, biotype I was much more common in isolates from patients than in those from carriers (71% vs 42%; p less than 0.01). The data suggest that various H. influenzae type b subtypes are less virulent than those commonly isolated from invasive infections.