This site is intended for health professionals only

Meningitis vaccine advice for Hajj pilgrims

Carolyn Driver
RGN RM RHV FPCert MSc(TravelMed) FFTM RCPS(Glas)
Independent Travel Health and Immunisation Specialist Nurse Cheshire

The Hajj pilgrimage, which all Muslims are expected to make at least once in their lives, will occur in November 2010. The meningitis vaccine has been a compulsory requirement for pilgrims since 1988, so travel health providers can expect requests for vaccination from those intending to travel to Saudi Arabia to perform the Hajj during September and October. This year, a new quadrivalent meningitis vaccine has been licensed and this means that practitioners will have a choice of products
to offer.

Neisseria meningitidis (N. meningitidis) causes serious disease worldwide (see Box 1). Meningococcus was first isolated in 1887, but epidemics that can be attributed to the organism were described in Europe and the USA in 1805 and 1806. Meningococcal epidemics have been recognised in sub-Saharan Africa for more than 100 years. N. meningitidis is a gram-negative, encapsulated endotoxin-producing bacteria. It only infects humans and at least 13 different serological groups of N. meningitidis have been identified although groups A, B, C, W135, and Y are responsible for almost all cases of disease.

[[Box 1 Hajj]]

The disease mainly affects infants and young children and has a case fatality rate of 10-15%; but cases can occur in older children and young adults. It is thought that as many as 35% of young adults may harbour the organism as a harmless commensal in the nasopharynx and that, at some point in their lives, most individuals are colonised with meningococci. It is still not fully understood as to why some people go on to develop invasive disease.

A further conundrum is the apparent geographical difference in predominant serogroups. Serogoup A, which has a unique capacity for causing large epidemics, has been the most important serogroup in sub-Saharan Africa; although, more recently, W135 has been the cause of outbreaks. In Europe serogroup B now predominates as vaccination has helped to virtually eliminate serogroup C.

Transmission of meningococci requires close contact, as the infection spreads through either direct contact with secretions, or dispersion of droplets from the respiratory tract of an infected person to a susceptible individual. The organism doesn't survive for long in the environment so requires direct person-to-person spread. It is associated with poorer socio-economic groups or where overcrowded living conditions are an issue.

There is also an association with concurrent viral infection of the upper respiratory tract and active or passive exposure to tobacco smoke. In Africa, outbreaks are associated with the dry seasons, whereas in temperate climates, infections peak in winter months. In all countries, disease is most common in the very young, who succumb before they have had a chance to acquire natural immunity to the prevailing serogroups. Outbreaks can occur among groups of older individuals when they encounter new diverse communities, such as military recruits or university "freshers". The communal living and social circumstances of these groups is thought to contribute to transmission in addition to exposure to serotypes not previously encountered.

Primary prevention of meningitis relies on effective vaccination and, initially, the vaccines that were developed contained pure polysaccharide antigens. These were poorly immunogenic in infants under two years of age and induce poor immune memory in older children and adults.

During the 1990s the process of conjugation, where a polysaccharide antigen is attached to a carrier protein, was developed and this enabled much more effective vaccines to be produced. Haemophilus influenza B, meningitis C and, latterly, pneumococcal conjugate vaccines, have all now been added to the primary immunisation programme in the UK. Vaccines have also been developed that protect against A, W135 and Y serogroups but as yet there has been no sustained success with serogroup B.

Currently, with the exception of those who are asplenic or have splenic dysfunction or complement deficiency (see Immunisation Against Infectious Diseases/"The Green Book", chapter 22, updated July 2010) the most common use for the quadrivalent vaccine is for those travelling overseas, principally to the "meningitis belt" (see map) of sub-Saharan Africa or for pilgrims travelling to Mecca in Saudi Arabia.

Why is the meningitis vaccine compulsory for Hajj pilgrims?
Every able-bodied Muslim who can afford to do so is expected to perform the Hajj - the pilgrimage to Mecca (Makkah) in Saudi Arabia - at least once in their lives. The date is set in the Islamic lunar calendar but, because this is 11 days shorter than the Gregorian calendar, it occurs slightly earlier each year.
This year, it is due to fall between 14 and 18 November.

Approximately 2 million pilgrims from all over the world converge on Mecca for this event. The cost for pilgrims from the UK averages £2,500-£3,500 per person and reductions are offered for multiple occupation of standard hotel accommodation. In these cases, five or more people to a room is not unusual. The event may also be an opportunity to meet family members from other countries who may share the accommodation. This mixture of international gathering in overcrowded circumstances enables easy transmission of those diseases associated with close contact such as meningococcal meningitis.

In 1987, a significant outbreak of meningitis occurred in the three Saudi cities most closely associated with the Hajj. Up until this point, only those pilgrims arriving from the "meningitis belt" of Africa were required to have a certificate of vaccination against meningitis (Figure 1). Following the outbreak in 1987, this regulation was changed so that all pilgrims arriving in Saudi Arabia were required to have the meningitis A and C vaccination within the previous three years.

[[Fig 1 Hajj]]

The outbreak in 1987 involved meningococcal serogroup A, which was predominant in Africa at that time. In 2000 and 2001 cases occurred in pilgrims despite vaccination; however, this time the causative organism was W135 serogroup, which had, by now, become more prolific in Africa. These outbreaks not only affected those who attended the pilgrimage but were also associated with cases in the home countries when the pilgrims returned. In the UK there were 51 cases, with eight deaths in 2000 and 33 cases and nine deaths in 2001 - a case fatality rate of 20%, which was higher than the norm.  In 2002 the regulations were altered so that pilgrims now required a certificate to show that they had received the quadrivalent vaccine, which protected against A, C, W135 and Y group organisms.

Umrah is a pilgrimage that can be performed at any time of the year and conditions are not as intensely crowded as during Hajj; however, pilgrims are still arriving from all over the world and so Umrah pilgrims must also be in possession of a certificate of vaccination against meningitis A, C W135 and Y. Vaccination must have been given no fewer than 10 days before, or more than three years before, the date of arrival for both types of pilgrimage.

Which vaccine to use this year?
Until this year, only one type of quadrivalent meningitis vaccine was available in the UK and this was a capsular polysaccharide vaccine. This produces a good immune response in older children and adults, but immune memory will wane after three to five years. In infants there is some short-lasting protection against A, W135 and Y serogroups but very little against serogroup C, and two doses were required with a three-month interval. There has been concern in the past about hypo-responsiveness to subsequent doses of the polysaccharide vaccine and use of the vaccine does not appear to induce herd immunity.

Earlier this year, a new conjugate quadrivalent meningitis vaccine was licensed called Menveo®. The polysaccharide antigens for serogroups A, C, W135 and Y have been conjugated to diphtheria toxoid protein, which confers improved immunogenicity in all recipients, especially those under two years of age. It is also likely to produce robust immunological memory although the need for further boosters has not yet been fully established. The vaccine is licensed in the UK for use in those from the age of 11 years and above.

Studies are ongoing for its use in younger children and infants and it is likely that in the future the product license will be changed to include infants and younger children.

Practitioners advising travellers to this year's Hajj have a choice of vaccines to offer and they should make their choice taking into account the relative merits and disadvantages of each product along with national guidelines. It is important to remember as part of the informed consent process that the traveller should be informed of the options available to them.
This is of particular importance when one product may cost more than another, as the individual will need to be aware of what the benefits may be of the more expensive option.

Practitioners will face an additional challenge if they are advising families taking children under 11 years of age to the pilgrimages. The same potential dilemma will also face those who are advising families taking children to sub-Saharan Africa, particularly if they are visiting friends and family (VFRs). The dilemma is that the very group that will benefit most from this new vaccine are currently those for whom it is not yet licensed. In view of this particular issue, the Joint Committee for Vaccination and Immunisation (JCVI) has taken the unusual step of making significant recommendations for the use of this vaccine "off label".

In the UK the JCVI advises the Department of Health for each devolved country on vaccination policy. This expert committee meets regularly and reviews all available literature on vaccines that are available for use in the UK. The JCVI can make recommendations that go beyond the Summary of Product Characteristics for a given product.

Healthcare practitioners can be assured that even if a recommendation for a vaccine is not covered by the manufacturer's summary of product characteristics (SPC), but it is a recommendation of the JCVI, they will be legally covered to use the product in that way. To this end the manufacturers also include the statement, "The use of this vaccine should be in accordance with official recommendations", in the section on therapeutic recommendations in the SPC.

With regard to Menveo® the JCVI have recommended that, in children under five years of age and infants, it should be used in view of its superior immunogenicity. They also suggest that Menveo® is used in older children and adults because of its better and longer lasting protection.8 Experience with conjugate vaccines already in use has also demonstrated their ability to induce herd immunity by reducing carriage of the organism and so use of the conjugate vaccine in pilgrims should further protect against cases in contacts of returning pilgrims.

Details of these recommendations and schedules are all clearly set out in the updated chapter on meningococcal vaccines in the online version of the "Green Book" (www.dh.gov.uk/greenbook) and are summarized in Box 2. Although Patient Group Directions (PGDs) can be used to administer "off label" use of a product in such circumstances, if the vaccine is being administered privately, in a general practice setting then a patient specific direction should be used as current legislation does not permit the use of a PGD for a privately administered medication in an NHS setting. A private travel clinic may use a PGD (see www.nathnac.org/pro/clinical_updates/pgds_210409.htm).

Conclusion
Meningococcal infection is a serious, life-threatening disease, which is vaccine preventable. Travellers for whom vaccination is recommended should be fully informed about the reasons for the recommendation and the choice of product that is available. National expert guidance should be taken into account especially when advising those travelling with infants and young children.

Resources
Department of Health
W: www.dh.gov.uk/greenbook

NATHNAC
W: www.nathnac.org

Travax
W: www.travax.nhs.uk