Neisseria meningitidis group C regularly causes epidemics in schools, universities, and army units, and in the past decade community outbreaks have been reported (1). Since a safe and effective polysaccharide vaccine is available the issue arises repeatedly whether and when vaccination should be offered. Delimitation of the vaccination target group is always difficult as it is an arbitrary process defined by various considerations.

In May 1997, an international football tournament took place in Genk (Belgium), including two teams from Putten (the Netherlands). A Belgian volunteer assistant died from the sequelae of invasive meningococcal disease on the third day after the tournament ended. Inquiries revealed that other cases had occurred among participants after returning home: one in Germany, two in Denmark, and two in the Netherlands (table 1, cases 2 and 3 were respectively, a team supervisor and a participant) (2,3). The Netherlands Reference Laboratory for Bacterial Meningitis (Nederlands Referentielaboratorium voor Bacteriële Meningitis, NRBM) classified the isolated meningococci in the two Dutch cases as serogroup C, type 2a, subtype P1.5 (C:2a:P1.5). The one and only earlier case of invasive meningococcal disease from Putten in 1997 was also caused by N. meningitidis C:2a:P1.5 (table 1, case 1). In July and August 1997, two linked cases of meningococcal disease (table 1, cases 4 and 5) with the same subtype of N. meningitidis occurred. Extensive epidemiological data collection and analysis by the municipal health service (Gemeentelijke Gezondheids Dienst, GGD) failed to identify any relationship between the separate clusters. In all cases, chemoprophylaxis was offered to all household contacts in line with the national guidelines (4).

Table 1 – Dates of onset of disease and epidemiological data of cases

No.

Age / Sex

1st day of illness

Clinical picture

Epidemiological link

School / occupation

N. Meningitidis isolate

Residence

1

18 m

04/05/97

sepsis

sporadic

technical school, Amersfoort

C:2a:P1.5

Putten

2

39 m

11/05/97

sepsis

football tournament

plasterer

C:2a:P1.5

Putten

3

16 m

17/05/97

sepsis

football tournament

secondary school, Ermelo

C:2a:P1.5

Putten

4

15 m

11/07/97

sepsis

?

junior technical school, Hoevelaken

C:2a:P1.5

Putten

5

15 f

03/08/97

meningitis

girlfriend of case no.4's brother

secondary school, Ermelo

C:2a:P1.5

Ermelo

6

13 f

24/12/97

sepsis + meningitis

?

primary school, Putten

C:2a:P1.5

Putten

7

18 m

24/12/97

meningitis

?

carpenter

C:2a:P1.5

Putten

On 25 December 1997, two adolescents from Putten were admitted to hospital with invasive meningococcal disease, strains isolated from both of whom were of type C:2a:P1.5 (table 1, cases 6 and 7). At this point, five mutually unrelated incidents caused by a N. meningitidis of the same subtype had presented in a small town community (population 22 000) in eight months (table 1). Despite thorough investigation of possible contacts and joint activities - sports, recreation, cultural performances, religion - the GGD failed to find a link between the five incidents.

Strains from cases 1 to 4 could not be distinguished after further genotyping with randomised amplification polymorphism DNA (RAP-D) and thus can be regarded as a single clone.

Microbiological laboratories in the Netherlands are sending isolates of N. meningitidis to the NRBM voluntarily. In 1997, 80 isolates appeared to be group C, and 19 of these were classified as C:2a:P1.5. Overall and age specific annual incidences for the Netherlands in 1995, 1996, and 1997 were much lower than in Putten (table 2).

Table 2: Annual incidence of Neisseria meningitidis group C in the Netherlands and in Putten (source: NRMB)

The Netherlands

Putten

1995

1996

1997

1997

95% CI

Total number of cases *

55

56

80

5

Incidence all ages**

0.4

0.4

0.5

23

3-43

Cases in 10-19 years

15

15

21

5

Incidence in ages 10-19 years***

0.8

0.8

1

167

21-313

Incidence in ages 2-19 years***

93

11-174

Putten is a small town in a rural (by Dutch standards) recreational woodland area in the mid east of the country, 66 km away from Amsterdam. The nearest town is Ermelo (26 000 inhabitants) which serves as the town centre, with more shops and several secondary schools. Eight kilometres to the south east lies the village Garderen (2000 inhabitants), and to the south west the town of Nijkerk. For secondary education most pupils from Putten cycle to Ermelo or Nijkerk. Primary school children from Garderen attend schools in Putten.

Communicable disease control in the Netherlands is undertaken by municipal health services. Coordination between the 54 municipal health services and the national service has since 1995, been controlled by Landelijke Coordinatiestructuur voor de Infectieziektenbestrijding (LCI), which draws up guidelines and coordinates outbreak management. LCI consists of a professional advisory team (Outbreak Management Team, OMT, consisting of five permanent members with clinical, microbiological, and public health backgrounds and sometimes other specialists), a board of administrators (Bestuurlijk Afstemmings Overleg, BAO), and a small professional helpdesk (bureau LCI). The OMT advises the Permanent Secretary of Health (Minister van Volksgezondheid, Welzijn en Sport) through the Bestuurlijk Afstemmings Overleg. Local professional clinical, microbiological, and public health staff report data and join in the discussions of the OMT. The BAO check advice for practical feasibility and decide on the policy to be implemented (under responsibility of Minister van Volksgezondheid). The Ministry of Health, the Inspectorate of Health (Inspectie voor de Gezondheidszorg, IGZ), and the Public Health Laboratory (RijksInstituut voor Volksgezondheid en Milieu, RIVM) are represented in BAO as well as representatives of municipal bodies and the health insurance advisory board (Ziekenfondsraad).

In September 1997, with three unrelated cases of meningococcal disease in Putten, the bureau LCI organised a written consultation of OMT members. Adherence to existing national guidelines with regard to chemoprophylaxis (4) was recommended as well as to offer household contacts immunisation against N. meningitidis group C. Enhanced surveillance was regarded as unnecessary, as the public and the medical professions were already on the alert. This was expected to increase notification of meningococcal disease in the statutory notification system (well known for underreporting) to acceptable standards.

In January 1998, immediately after isolates from cases 6 and 7 were typed, the OMT decided to consider vaccination. Geographical clustering in small communities and vaccination as intervention strategy have been described in the United States, Canada, and Australia (1). Delimitation of those who qualify for vaccination must be clear for the authorities and the public alike (5). Experience in this field was not on hand in the Netherlands, despite the fact that an epidemic upsurge with N. meningitidis C:2a:P1.5 had occurred in a south east region in 1992-93 and had spread in various age groups over a considerably larger area (Wijgaarden JK van, Inspectorate of Health, personal communication). Active immunisation was withheld as it seemed impossible to define a group for vaccination.

Although vaccination has no documented effect on carriage (6) it is known to be effective in controlling epidemics (90% effectiveness when used during an outbreak (7,8)) and protects against invasive infections. An adequate antibody response takes 10 to 14 days to develop after vaccination, however, during which invasive infections may still occur. The OMT advised vaccination on the basis of the cumulative incidence in the eight month period of May to December (which accounted for the total annual incidence for the area in 1997). No national threshold level for vaccination had been agreed in the Netherlands, but such thresholds have been established in other countries (9) (table 3). In Putten the annual incidence for the whole population was 23 per 100 000 in 1997, for children and adolescents of 2 to 19 years 93/100 000, for those aged 10 to 19 years 167/100 000.

Table 3: Threshold values for implementation of vaccination in community outbreaks of meningococcal disease in several countries

Country

Criteria

Threshold value for implementation of vaccination

Canada

annual incidence of group C in age group 1-20 yrs*

> 5/100 000

Spain

annual incidence of meningococcal disease (irrespective of Neisseria group and patient’s age)

>10/100 000

United States

3-monthly incidence of group C

>10/100 000

WHO policy for countries at risk for meningitis

weekly incidence group C (all ages)

>15/100 000 in two consecutive weeks

The population at risk was agreed to be the young people aged 2 to 19 years living in Putten. Children from neighbouring places (e.g. Garderen) attending schools in Putten, and their brothers and sisters were also included. Limitation to inhabitants of Putten was decided in spite of the fact that patient 5 came from the neighbouring place Ermelo; it was argued that she had been exposed intensively in Putten. The upper limit was established at 20 years, although patient 2 was 39 years old; he was thought to have been exposed during the Genk football tournament. The lower limit was not set at 12 years (to be expected on the basis of previous cases) but at 2 years, because the chances of transmission to younger siblings were considered realistic. The polysaccharide vaccine available has too little effect in children under the age of 2 years. Children from other villages attending school in Putten were included because of the available knowledge about transmission in schools.

LCI's board of administrators, informed by OMT, accepted the advice and arranged funding of research and intervention. The Ministry of Health requested the NRBM to subject the collected isolates to genotyping and RIVM was asked to design a study into meningococcal carriage. Parallel to the vaccination campaign on 22 and 23 January 1998 in Putten, this study was conducted by the RIVM Centre for Infectious Diseases Epidemiology, the NRBM, the Eemland Hospital, and the GGD.

Immediately after the OMT meeting, the GGD started to draw up scenario. Individual summons to the 5760 targeted people were sent by the GGD in the evening of 19 January, based on dates of birth, after the medical professional groups had been informed officially in a meeting with the District General Practitioners Association. In the morning of 20 January, information brochures were circulated door to door and published in the local media. A telephone helpline was opened and received 1091 inquiries in weeks 4 and 5. Vaccination took place in the next two days with the help of many public health organisations and the municipality of Putten. In total 5939 vaccinations were registered and vaccination coverage was 96.2%. After a catch-up day it increased to 97.5%. Of the 122 children from other places attending school in Putten, 95.9% were vaccinated, as well as 82 of their siblings. Forty youths from Putten who had not received a summons were also vaccinated, as well as 86 from elsewhere indicated for vaccination.

Three cases of bacterial meningitis were notified to the GGD in the month after the intervention. The first was caused by Streptococcus pneumoniae in a 25 year old primary school teacher and the second was caused by N. meningitidis group B in a 1 year old child from the nearby small town of Nunspeet. The third case emerged on 29 January in a boy attending a secondary school in Ermelo (30% of students at this school live in Putten). It had been decided in January not to include the students of this school in the target population. To the policymakers’ relief, the strain isolated was a group B.

The next case of illness caused by a meningococcal group C in Putten was reported in August 1998. It was a man aged 20 years. At the time of the intervention he was over 19 years of age and was therefore not vaccinated. His younger brothers had been vaccinated. The N. meningitidis was typed as C:2a:P1.2,5, and further RAPD-genotyping has not yet been completed. No other cases were reported in 1998.

It will remain a matter of debate whether the chosen intervention was the right one. In retrospect the written consultation in September would have been a better time to decide on vaccination for children and adolescents. The restriction to adolescents of 19 years and younger was in retrospect rather meagre. In community outbreaks elsewhere group C often includes people up to 25 or 30 years of age. No fixed threshold value for vaccination has been established for the Netherlands, every (community) outbreak being managed according its own characteristics. From the discussions in the OMT it is clear however that the Dutch threshold will most likely be close to 40/100 000. This first meningococcal experience shows the accuracy of LCI decision making and will help to improve the speed and quality of decision making in the future. Data from the NRBM are essential for deciding whether or not a cluster can be regarded as an outbreak. The adverse events reporting system installed by the GGD during and after the campaign brought no serious adverse events to light. Further epidemiological and microbiological evaluation is necessary to assess the long term effects of vaccination. Good cooperation between national and local authorities resulted in a successful action. The control and prevention of meningococcal disease remains a challenge for all governmental bodies concerned (10).

1. Jackson LA, Schuchat A, Reeves PhD, Wenger JD. Serogroup C meningococcal outbreaks in the United States. JAMA 1995; 273: 383-9.

2. Van Loock F. Meningococcal disease associated with an international youth football tournament in Belgium. Eurosurveillance Weekly 1997; 1: 970619. (http://www.eurosurv.org)

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