Meningitis prevention

Introduction

The case definitions used are described here.

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Contents 1 Introduction 1.1 Contacts who should be offered chemoprophylaxis 2 Identification and notification of cases 2.1 Checklists 2.1.1 Why it is important to confirm cases, and to identify group and sub-type wherever possible 3 Prevention 3.1 Prevention (meningococcal disease) 3.1.1 Vaccination 3.1.1.1 Traditional meningococcal vaccines 3.1.1.1.1 Conjugate vaccine 3.1.1.1.2 Polysaccharide vaccines 3.1.1.2 Novel meningococcal vaccines 3.1.1.2.1 Recommendations for group B meningococcal vaccine use in the UK 3.1.2 Chemoprophylaxis 3.2 Prevention (pneumococcal disease) 4 See also 5 External links 6 References

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Contacts who should be offered chemoprophylaxis

Prophylaxis comprising chemoprophylaxis and vaccination should be offered to the following contacts of confirmed or probable cases (and usually to no others):

• Contacts who were living in the same ‘household’ as the case during the seven days before the case became ill.
• Sexual partners and "kissing contacts" (which refers people with whom the case had had intimate contact - "snogging" or "wet kissing") during the seven days before the case became ill.
• Medical or nursing staff only require prophylaxis if:

• They have given mouth to mouth resuscitation to the case during the seven days before the case became ill; or
• Their mouth or nose has been directly contaminated (clearly felt) with respiratory droplets/¬secretions from a probable or definite case around the time of admission; or
• They develop conjunctivitis within 10 days of contact with a confirmed or probable case.

(US guidance differs from UK guidance.^[1][2][3])

See Chemoprophylaxis for details.

Identification and notification of cases

Checklists

A useful checklist can be found at Meningitis checklist

Why it is important to confirm cases, and to identify group and sub-type wherever possible

Identification of the causative organism is important for:

• The management of cases and contacts.
• Outbreak identification, in order to be able to intervene promptly when outbreaks arise, and to know when cases of possible meningococcal disease that are linked time and place are not linked cases (e.g. because they are different groups or sub-types, or not meningococcal disease at all).

It is also important to confirm cases, wherever possible, for the following reasons:

• Surveillance, in order to understand the epidemiology of the disease, and to plan and monitor vaccination programmes.
• Research, in order to better understand – and hence to prevent and treat – the disease.

In order to be sure of making the diagnosis wherever possible, the correct samples (see below) need to be taken at the earliest possible opportunity. If the clinician has any doubt, they should discuss the sampling requirements with the hospital microbiologist or with HPU.

The ‘gold standard’ is to culture N meningitidis from blood, cerebrospinal fluid (CSF), or other normally sterile site. When parenteral penicillin has been given before admission, the yield from blood culture is low, and CSF may not always be taken because of the dangers of lumbar puncture. The diagnosis may be confirmed in other ways: these include culture from throat swabs or rash aspirates, antigen detection, serodiagnosis, and polymerase chain reaction (PCR) testing on blood and CSF.

The yield of meningococci from throat swabs in cases is about 50% and is unaffected by prior administration of antibiotic; meningococcal strains isolated may be assumed to be the same as the invading strain. Positive microscopy or culture may be obtained from needle aspiration of an area of meningococcal skin rash. Serological testing for antibody response ideally requires paired specimens of serum. Tests to establish the presence of meningococcal infections and characterise the invading strain, based on PCR, are being evaluated at the meningitis reference unit (MRU).

Meningococcal strains isolated from throat swabs of household contacts are likely to be the same as the case strain, especially if the index case is a child.

Where there has been a recent case, and there is a possibility that this is the second case in a cluster, it is particularly important to isolate the germ wherever possible. In this situation HPU may advise that throat or pernasal swabs should be taken from close household contacts before they receive chemoprophylaxis, as it is likely that, if they are carrying a meningococcus there, it will be the same group and strain as that affecting the index case.

Prevention

Prevention (meningococcal disease)

Vaccination

See the Green Book (chapter 22) for more detail.

Meningococcal vaccine is recommended for people who have been in contact with a case of vaccine-preventable meninogococcal disease, and who meet the criteria for chemoprophylaxis; and for people travelling to areas where they may be at risk.

Meningococci are encapsulated bacteria. Traditional vaccines are based on antigens from the polysaccharide capsule. The antigen for group B meningococci does not work safely and effectively as a vaccine, so novel vaccines have been created which are not yet (March) included in routine vaccine programmes.

Traditional meningococcal vaccines

Conjugate vaccine

In the UK a conjugate vaccine is available that works in infancy, and provides long-term (possibly life-long) protection against group C meningococcal disease. This vaccine is offered to all babies in the UK. It should also offered routinely to anybody below the age of 23 who has not yet been vaccinated, and to people above that age who enter higher or further education for the first time.

Certain at risk groups (including people with asplenism or hyposplenism should receive this vaccine.

Various"MCV4" conjugate vaccines which provide protection against A, C, W135, and Y meningococcal disease are in development or have been licensed. Menactra™, from Sanofi Pasteur, has been licensed in the USA since, and recommended for all teenagers since and some other groups since. ^[4][5] Menveo™, from Novartis, was licensed in Europe in March. Another MCV4 vaccine from GSK is expected to be licensed shortly, if it hasn't already been licensed.

Formal advice on the use of Menveo™ in the UK has not yet been published, but the minutes of the JCVI meeting on 14 October^[6] refer to advice from a subgroup as follows:

The subgroup also advised on the use of the MenACWY conjugate vaccine Menveo® when it is licensed and the use of the currently licensed MenACWY polysaccharide vaccine. The subgroup advised that:

• There should be no alteration to the current Green Book indications for the use of MenACWY vaccines for travel.
• There is good evidence for the efficacy of both the polysaccharide vaccine and Menveo® in individuals aged 11 years and older. When Menveo® is licensed, both vaccines can be used in individuals aged 11 years and older, but individuals should be advised that that Menveo® is likely to provide longer lasting immunity.
• When licensed, Menveo® should be used for children under five years of age ‘off label’, as the benefits of protection outweigh the risks of vaccination. Polysaccharide vaccine has limited immunogenicity in this age group and in children under the age of two, it has been shown to produce antibody hypo-responsiveness. Data on Menveo® demonstrates that this vaccine is safe and immunogenic in children.
• When licensed, Menveo® can be used for children aged five and up to 10 years of age ‘off label’. Polysaccharide vaccine can also be used in this age group, but individuals should be advised that that Menveo® is likely to provide longer lasting immunity.
• In preference, Menveo® vaccine should not be administered at the same time as other conjugate vaccines (for example, the conjugates Hib/MenC and PCV that are administered at 12 -13 months) until further data are available on concomitant administration of these vaccines. This advice is not based on

Polysaccharide vaccines

Polysaccharide vaccines available that provide protection against group A, or against groups A, C, W135, and Y meningococcal disease. As they are polysaccharide vaccines, however, they are less effective in younger children (little or no efficacy in under-twos; efficacy rising with age, and becoming equivalent to conjugate vaccine only in the mid teens). The immunity provided is relatively short-lived (two-three years), and there is no immune memory.

Novel meningococcal vaccines

Because the polysaccharide antigens for group B meningococcal disease are not useful for vaccination, novel approaches were applied to identify other parts of the bacteria which would be effective as vaccine antigens. At the time of writing (March two products (Bexsero®, generic name "4CMenB", originally from Novartis, and Trumenba (US marketing page) from Pfizer) are licensed and available (at least in some parts of the world); but neither is yet included as part of the routine vaccination schedule.

The classification of meningococci into serogroups A, B, etc. is based on the polysaccharide antigens. Since the antigens used to get around the problems with group B meningococci are independent of this classification, the vaccines are likely to be effective against meningococci of all serogroups: although they are marketed as vaccines for group B, this is only because other vaccines are effective against other strains. In fact, some of the antigens identified may not be unique to meningococci, Neisseria meningococcus. They may also be found in other Neisseria species. It is not yet clear whether the vaccines are at all effective against, for example, Neisseria gonorrhoeae: if they are this would be a huge benefit, since gonorrhoea is rapidly becoming resistant to most antibiotics.

Recommendations for group B meningococcal vaccine use in the UK

The problems that decision-makers encounter with these vaccines is that they are expensive (developing the products took decades and was hugely expensive; and the cost of manufacturing is also considerable), yet the number of cases of disease is not all that large. It is true that group B disease has been the commonest cause of meningococcal disease in the UK for decades - even at the time when group C conjugate vaccine was introduced in the 1990s. Yet the burden of disease preventable by these vaccines may not be sufficient to justify their cost. Whereas the conjugate vaccines are extremely effective against the serogroups they cover, the "group B" vaccines are likely to prevent two-thirds to three-quarters of disease. It is even possible that serogroup replacement (as vaccine pressure eliminates vaccine preventable strains, other strains may become more common as they occupy the same ecological niche) may further reduce their efficacy over time. This may be unlikely to happen quickly or to a significant extent; but it is another cause for uncertainty.^[7]

Another cause of uncertainty is our ability to measure accurately the burden of disease. It's relatively straight-forward to measure the short term direct costs to the NHS, and the mortality, from such diseases. But meningococcal disease has long term sequelae for many survivors. Many are left with sensory or intellectual impairment, or with amputations. The long term costs to the economy - which include direct health care costs, but also the costs to the economy from the underperformance and contribution to the economy that the person would have made had they not been impaired by this infection - are harder to measure.

With no country in the world having introduced these vaccines we have to rely on modelling; and cost-effectiveness models (such as this one^[8]) can always be improved when more real-world data become available.

The UK's Joint Committee on Vaccination and Immunisation produced a position statement on the use of meningococcal B (MenB) vaccine in the UK in March:

"The Joint Committee on Vaccination and Immunisation (JCVI) position statement includes a recommendation to offer the Bexsero MenB vaccine to children at 2, 4 and 12 months. This recommendation depends on securing a cost effective price for the Bexsero vaccine."

Negotiations between vaccine manufacturers and the government are usually secret ("commercial in confidence"), with the criteria for decision making not being in the public domain, even after the event. (Government argues that the "cons" in terms of reduced transparency and accountability are outweighed by the "pros" in terms of the low cost to the exchequer that they are able to achieve this way.) So we cannot know how exactly negotiations are going. Some information has leaked - or been leaked - to the press, such as allegations that the government has accused the manufacturers of "holding the government to ransom" with the high prices it demands; but we should be wary of reading too much into these leaks, as they may well amount to little more than posturing by one or other side for commercial or political benefit.

At the time of writing this section (March) no agreement has been reached, despite the best efforts of pressure groups, and the vaccine has not been included in the national vaccine schedules. It is, however, recommended in "certain groups at high risk of developing invasive meningococcal disease (see ‘Children and adults with asplenia, splenic dysfunction or complement disorders’), laboratory workers working with meningococci and in the management of outbreaks of meningococcal disease". (Green Book, Chapter 22.)

Chemoprophylaxis

• Prophylaxis of contacts is only indicated when meningococcal or Hib disease (rare) is the "probable" (most likely) or "confirmed" diagnosis (see Meningitis case definitions). It is not necessary in e.g. suspected viral cases being treated "just in case". Always discuss with CCDC/Public Health. Prophylaxis is not necessary in pneumococcal and viral meningitis.

See Meningitis Chemoprophylaxis for more details.

Prevention (pneumococcal disease)

Chemoprophylaxis is not required for cases of pneumococcal meningitis or their contacts.

When there is a case of invasive pneumococcal disease (including meningitis) in a child under five years of age, the child should (according to the November edition of the Immunisation "Green Book") be offered vaccination with the pneumococcal polysaccharide vaccine.

See also

• Meningitis
• Bacterial meningitis
• Meningitis case definitions
• Meningitis charities
• Meningitis checklist
• Meningitis chemoprophylaxis
• Meningitis prevention
• Viral meningitis

External links

• Information from the Health Protection Agency on meningitis here.
• Information from the Meningitis Research Foundation here.
• Information from the Meningitis Trust here.

References