Reference Laboratory for Bacterial Meningitis

Bacterial meningitis is a life-threatening infectious disease with a reported case-fatality rate from 3% to 30% depending on the pathogen isolated, of which Neisseria meningitidis, Streptococcus pneunomiae and Haemophilus influenzae type b are most common, and age at which the meningitis occurs.

Already in 1959, Charlotte Ruys, professor Bacteriology, Epidemiology and Immunity at the Laboratory of Hygiene of the University of Amsterdam started to collect Neisseria meningitisisolates from patients with meningitis. The expert research activities on meningococci were soon recognized and the depertment became known the Reference Laboratory for Bacterial Meningitis albeit that this status was informal.

In 1975, the Netherlands Reference Laboratory for Bacterial Meningitis was officially established as a cooperation between the Department of Medical Microbiology of the University of Amsterdam and the Institute of Public Health and Evironmental Protection (RIVM) in Bilthoven. From than on, the Reference Laboratory collected and still collects isolates from cerebrospinal fluid (CSF) and blood from patients with proven meningitis (CSF and possibly blood culture positive) or with bacteraemia and suspected meningitis (blood culture positive only). The Netherlands Reference Laboratory has one of the largest and oldest meningococcal isolate collection in the world as well a large collection of isolates form patients with pneumococcal meningitis and Haemophilus meningitis. The vast majority of these isolates can be linked to patients’ data available in the archives of the Reference Laboratory.

Annual report
2005 2006 2007 2008
2009 2010 2011 2012
2013 2014 2015

Haemophilus influenzae

In 2014 total, 161 Haemophilus isolates were submitted to the Reference Laboratory. This number is higher than that of the last years. Twenty-one strains were isolated from CSF (or CSF and blood), and 140 from blood only. Thirty percent of the isolates were H. influenzae type b. From 1999 to 2004, the number of H. influenzae type b isolates received by the Reference Laboratory increased.The higher number of H. influenzae type b isolates was mainly due to an increase of H. influenzae type b cases among elderly people.

Six cases of H. influenzae type b invasive disease were observed among children younger than 2 years of age. In total 117 non-typable H.influenzae were received; 15 isolated from CSF (or CSF and blood) and 102 isolated from blood only. Non-typable strains were isolated more frequently than type b isolates.

For more information about H. influenzae and all other isolates, download our last annual report.

Neisseria meningitidis

In 2014, the Reference Laboratory received 73 Neisseria meningitidis isolates, of which 32 were isolated from CSF (or CSF and blood) and 42 from blood only. This means that 58% of cases of meningococcal disease concerned patients with a positive blood culture only, either because no meningitis was present or because no CSF specimen was obtained.

Serogroup B accounted for 73% of all isolates and group Y for about 17%.The proportion of serogroup Y isolates is gradually increasing since 2008, partly due to a decrease in the number of serogroup B isolates and to a small increase in the number of serogroup Y isolates.The remaining 10% of the isolates were of the rare serogroups C, W, or E. The serogroup distribution observed during the whole collection period 1959 - 2014 shows that in 2012 the number of group B isolates was the lowest since 1983.

The proportion of group C isolates was 24% in 1991, decreased to about 10% in 1994 and was since then increasing, with a sharp rise from 19% (105 cases) in 2000 to 40% (276 cases) in 2001. In June 2002, vaccination against serogroup C was included in the National Immunization Program. Since then, the number of serogroup C isolates received by the Reference Laboratory decreased rapidly to only a few isolates per year; in 2014 only 3 serogroup C isolates were received.

Download our last annual report for more details about N. meningitidis.

Streptococcus pneumoniae

The Reference Laboratory received 769 S. pneumoniae isolates in 2014. Of these, 142 were isolated from CSF or from CSF and blood. A steep increase in the number of pneumococcal blood isolates had occurred between 1994 (312 isolates) and 2003 (1471 isolates). This increase can be explained by the increasing use of automated blood culture devices by the contributing laboratories and by a real increase in the number of cases of pneumococcal bacteremia due to pneumonia among patients of the increasing cohort of the elderly and a more complete submission of isolates by the laboratories.

The number of isolates from blood sent to the Reference Laboratory decreased from 1471 in 2003 to 627 in 2014. This was due to a change in policy: from 2003 onwards, we asked only nine selected laboratories, evenly distributed over the country, to send pneumococcal blood isolates. Thus, the numbers of S. pneumoniae from blood only are incomplete.

This policy has been changed to monitor the effect of the introduction of the 7-valent conjugate pneumococcal polysaccharide vaccine by June 1st , 2006. From 2006 onwards, all laboratories are requested to send all invasive pneumococcal isolates from patients in the age group 0-4 year, while from patients older than 4 year only isolates from CSF are requested. Again, from nine selected laboratories we ask all invasive pneumococcal isolates from all patients.

Download our last annual report for more details about S. pneumoniae.

Vaccination prospects

N. meningitidis

In the Netherlands, vaccination against serogroup C meningococcal disease has been introduced in June, 2002. All children born on or after June 1st, 2001 are vaccinated at the age of 14 months as part of the regular national vaccination programme. In addition, between June, 2002 and October, 2002 children and adolescents from 14 months to 19 years have been vaccinated. In 2014, 3 (4.1%) cases of meningococcal disease were due to serogroup C meningococci. All three patients were not vaccinated. Two because of age and one because of nationality. This indicates that the vaccination programme has been successful.

A PorA-based protein vaccine composed of six different genosubtypes (1.5-1,2-2; 1.19,15-1; 1.7,16; 1.7-2,4; 1.5-2,10; 1.12-1,13), if available, would have prevented 49 cases (93%) of serogroup B meningococcal disease and 61 (84%) of all cases of meningococcal disease.

H. influenzae

The existing H. influenzae vaccine consists of the type b polysaccharide conjugated to a protein, tetanus toxoid. Since July 1993, children born after the first of April 1993 are vaccinated with the PRP-T vaccine at the age of 3, 4, 5, and 11 months, and since 1999 at the age of 2, 3, 4 and 11 months. The number of H.influenzae meningitis cases gradually decreased since the introduction of the vaccine, while the number of meningitis cases caused by H. influenzae non-type b did not alter. In 2014, the number of invasive isolates of H. influenzae type b, received from patients that should have been vaccinated (<21 years of age) decreased from 14 to 12 in 2014. Of those 12 patients, six had received all doses and onde received only three doses of the vaccine. Four patients (5 cases) were not vaccinated.

S. pneumoniae

The pneumococcal conjugated polysaccharide vaccine contains 7 serotype-specific polysaccharides linked to inactive diphtheria toxin (7-valent polysaccharide conjugate vaccine. PCV7). Since July 2006, children born after the first of April 2006 are vaccinated with this vaccine at age of 2, 3, 4 and 11 months. In April 2011 the 10-valent vaccine (PCV10) was introduced for all newborns born since March 1, 2011. In 2014, Five percent of the CSF isolates were of a serotype covered by this hepta-valent conjugate polysaccharide vaccine, while 13% of the isolates were covered by the 10-valent vaccine. The proportion of CSF isolates with a PVC7 serotype from te last year was lower than in previous years (2014:5% 2003: 52%), most probably as a result of the vaccination. There were 7 patients with an invasive disease due to S. pneumoniae with a vaccine serotype. One case of serotype 19F invasive pneumococcal disease, was 6 years of age and received all doses of PCV7. The remaining 6 cases were not vaccinated because of age. There was one child with an invasive disease due to S. pneumoniae with a (PVC10) vaccine serotype (7F). This child received four doses of PVC10. The beneficial effect of vaccination is partly abrogated by an increase of the number of cases due to non-vaccine types

The pneumococcal non-conjugated polysaccharide vaccine contains 23 serotype-specific polysaccharides. Seventy-three percent of the CSF isolates were of a serotype which is represented in this vaccine.



Visiting address
Location L1-114
Meibergdreef 9
1105 AZ Amsterdam
the Netherlands

Postal address
Academic Medical Center
Department of Medical Microbiology
Postbus 22660
1100 DD Amsterdam
the Netherlands

Tel.: +31(0)20-566 4852