Canada Communicable Disease Report
Vol. 25 (ACS-5)
15 September 1999

An Advisory Committee Statement (ACS)
Committee to Advise on Tropical Medicine and Travel (CATMAT)* +

STATEMENT ON MENINGOCOCCAL VACCINATION FOR TRAVELLERS

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Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT) provides Health Canada with ongoing and timely medical, scientific, and public-health advice relating to tropical infectious disease and health risks associated with international travel. Health Canada acknowledges that the advice and recommendations set out in this statement are based upon the best current available scientific knowledge and medical practices, and is disseminating this document for information purposes to both travellers and the medical community caring for travellers. Persons administering or using drugs, vaccines, or other products should also be aware of the contents of the product monograph(s) or other similarly approved standards or instructions for use. Recommendations for use and other information set out herein may differ from that set out in the product monograph(s) or other similarly approved standards or instructions for use by the licensed manufacturer(s). Manufacturers have sought approval and provided evidence as to the safety and efficacy of their products only when used in accordance with the product monographs or other similarly approved standards or instructions for use.

Introduction

Meningococcal disease is a medical emergency, requiring early diagnosis, hospitalization, and effective antimicrobial treatment. Even under optimal conditions, the case-fatality rate is 5% to 10%, and it may exceed 50% in untreated cases⁽¹⁾. Fifteen to 20% of survivors, especially infants and young children, may have persistent neurologic defects^(1,2). Meningococcal meningitis is characterized by a short incubation period (2 to 10 days, but often < 4 days), followed by sudden onset of symptoms: intense headache, fever, nausea, vomiting, photophobia, and stiff neck. Infants may have illness without sudden onset and stiff neck. Meningococcal septicemia (meningococcemia) is a less common but often fatal form of the disease characterized by rapid circulatory collapse and a hemorrhagic rash⁽¹⁾. This form has been responsible for the high case fatality rate in outbreaks of group C meningococcal disease in Canada⁽³⁾. Meningococcal meningitis accounts for 10% to 40% of endemic bacterial meningitis. It is caused by a Gram negative bacterium, Neisseria meningitidis. Of the 13 recognized serogroups, groups A, B, and C most frequently cause disease. Transmission is by direct contact, including respiratory droplets from the nose and throat of infected persons⁽²⁾. Most infections are subclinical, and many infected persons become asymptomatic carriers; however, there is no constant and close relationship between the carrier rate and the incidence of disease⁽⁴⁾. In a case-control study in Chad in 1988, patients with meningococcal disease were 23 times more likely than controls to have concurrent respiratory infections⁽⁵⁾, and increased incidence has been found following outbreaks of influenza in temperate countries⁽²⁾.

Culture of N. meningitidis from cerebrospinal fluid, blood, or petechial scrapings is required for diagnosis. Treatment is by antibiotics, usually penicillin G, ampicillin, chloramphenicol, or ceftriaxone⁽¹⁾.

Epidemiology

Meningococcal meningitis occurs sporadically worldwide and in focal epidemics. It is the only form of bacterial meningitis that causes epidemics⁽⁶⁾. Serogroups B and C are the most frequent causes of sporadic cases^a and outbreaks^b in Europe and the Americas (Figure 1). An epidemic is defined as "...an unacceptable incidence rate requiring emergency measures", and refers to different conditions throughout the world⁽⁷⁾. For example, incidence rates in recent epidemics in the Americas and Europe have been lower than the endemic incidence in several African countries⁽⁷⁾. Serogroup A has historically been the main cause of epidemic disease worldwide and still dominates in Africa and Asia. Epidemics most often occur during the winter-spring period in temperate regions and in the dry season in tropical regions. Incidence is highest in areas of poverty and overcrowded living conditions. Travel and migration facilitate the circulation of virulent strains within a country and among countries. A large outbreak associated with the 1987 Hajj in Saudi Arabia caused a pandemic in Africa when pilgrims returned to their home countries⁽²⁾.

The traditional endemic, or hyperendemic, areas of the world (the "meningitis belt") include the savannah areas of sub-Saharan Africa extending from Gambia and Senegal in the west to Ethiopia and Western Eritrea in the east (Table 1and Figure 2). This region can have a disease rate > 1,000 per 100,000 population during epidemics⁽⁸⁾, which typically occur in the dry season (December to June) in cycles that can last 2 to 3 years⁽¹⁾. Widespread epidemics often follow local outbreaks during the second year of the cycle, and incidence rates can remain elevated for the following 1 to 2 years. Epidemics tend to recur every 8 to 12 years, but since the beginning of the 1980s the intervals between major epidemics have become shorter and more irregular⁽¹⁾. Since the mid-1990s, epidemics in the meningitis belt have occurred on an unprecedented scale, and have spread beyond the usual boundaries (Table 2). This may be a new characteristic of the epidemiology of meningococcal disease⁽²⁾. The number of deaths from meningococcal meningitis in Africa in 1996 was the highest ever reported to the World Health Organization (WHO) during a single year⁽⁹⁾.

Outside the meningitis belt, no evident cyclic pattern of epidemics has been found⁽²⁾.

Table 1 Countries in the African meningitis belt*

Table 2 African countries outside the usual boundaries of the meningitis belt in which epidemics were reported in the late 1980s through the 1990s*

In sporadic outbreaks, children are at greatest risk, with peak incidence occurring in children < 2 years of age. Since 1986, the rate of group C disease in Canada has increased relative to group B, with a disproportionately high number of cases among adolescents⁽³⁾.

In epidemics, the age range is broader and includes older children, adolescents, and young adults⁽²⁾.

Figure 1 Distribution of predominant N. meningitidis serogroups (A, B, C), 1996-1997*

* From: Tikhomirov E, Santa Maria M, Esteves K. Meningococcal disease: public health burden and control. World Health Stat Q 1997;50:171.

Meningococcal vaccines

Meningococcal vaccines contain purified capsular polysaccharides. Two products are licensed in Canada: a quadrivalent vaccine containing groups A, C, Y, and W-135, and a bivalent A and C vaccine. No vaccine is currently licensed for use against group B strains, because the group B polysaccharide is poorly immunogenic⁽¹⁰⁾. Conjugated meningococcal vaccines have been shown to be more immunogenic, but are not yet licensed in Canada.

Vaccine efficacy

Vaccine efficacy is age related. Among adults and children >= 2 years of age, group A and C vaccines have generally been shown to be >= 90% effective in preventing meningococcal disease caused by constituent groups during outbreaks in both civilian and military populations⁽¹¹⁾. The overall field efficacy against group C disease in Quebec (1992-1993) was 79%; it was higher in adolescents (93%) and lower in those < 5 years of age (70%)⁽¹²⁾. No cross-protection occurs between serogroups.

Vaccine is least effective in very young children. In two studies, age-specific immunogenicity against group A in children aged 3 to 5 months was poor 3 months after receiving two doses of monovalent vaccine; serum antibodies to group A polysaccharide were < 2 µg/mL and < 1 µg/mL in 36% and 60%, respectively^(13,14). Although the protective level is unknown, an antibody response of 1 µg/mL to 2 µg/mL is generally accepted as indicative of immunity^(13,14). In a more recent report following a 1991-1992 vaccination program in Ottawa, antibodies were measured in 50 children aged 6 to 12 months. One month after vaccination, a very modest antibody response was seen to group A: 0.13 µg/mL (pre) to 1.58 µg/mL (post)⁽¹⁵⁾. In addition, other researchers reported a poor correlation between bactericidal activity (which indicates protection against disease) and antibody levels to group C in children < 18 months of age⁽¹⁶⁾.

Both children and adults produce antibodies in response to vaccines containing groups Y and W-135, but the degree of protection against disease has not been established⁽¹¹⁾.

Primary immunization

A single dose of vaccine is indicated for individuals >= 2 years of age. When there is a risk of exposure to Group A disease, infants aged 3 months to 23 months should receive two doses of vaccine given 2 months to 3 months apart. When there is risk of exposure to Group C disease, infants aged 6 months to 23 months may be given a single dose of vaccine depending on the age-related occurrence of the disease. Quadrivalent vaccine should be used unless the risk of exposure is known to be limited to a specific serogroup for which monovalent or bivalent vaccine is available⁽¹¹⁾.

Repeat doses

There is little research on which to base recommendations for repeat doses of vaccine. The persistence of serum antibody following group A or C vaccine is limited and age related. Protection against serogroup A disease has been shown to decline rapidly in children immunized with a single dose of vaccine at < 4 years of age; vaccine efficacy at 1, 2, and 3 years post-vaccination was 100%, 52%, and 8%, respectively. Similar transient responses to polysaccharide A have been shown with the quadrivalent vaccine in children aged 2 years to 8 years at 1-year follow-up^(14,17,18).

Clear evidence of boosting has been demonstrated for Group A vaccine in North American children. Antibody titres against Group A polysaccharide increased significantly following booster immunizations at 15 months to 18 months and 4 years to 6 years of age and persisted until age 10, even when primary immunization occurred as early as 3 months of age⁽¹⁴⁾. However, African children between the ages of 1 year to 4 years who received the primary immunization witha single dose of bivalent A and C vaccine had a decline of antibody titres directed against group A at both 2 years and 5 years after vaccination that was not influenced by a booster dose given 2 years after primary immunization⁽¹⁹⁾.

Group C vaccine does not prime even North American children for a booster response. Furthermore, recent research has shown that Canadian toddlers who received two primary doses of group C vaccine had lower antibody titres after a 1-year booster than a control group of children vaccinated for the first time. This hyporesponsive state was still present 12 months later⁽²⁰⁾.

Little is known about the duration of protection following group Y and W-135 vaccines⁽¹¹⁾. North American authorities do not agree fully on the timing of repeat doses, particularly regarding group C vaccine in children < 5 years of age^(10,11,21). In a joint statement, the American Academy of Pediatrics and the Canadian Paediatric Society have recommended repeat doses after 1 year for this age group⁽¹⁰⁾, whereas the National Advisory Committee on Immunization recommends repeat doses after 5 years or sooner in special circumstances⁽¹¹⁾.

Adverse reactions and contraindications

Local redness and/or pain occur frequently, but these reactions are not severe and usually disappear within 1 to 2 days. Immediate wheal and flare reactions occur rarely. Systemic adverse reactions are uncommon and not severe. The incidence of adverse reactions is similar after primary and booster doses of vaccine, provided that the booster dose is given as recommended. Pregnancy is not a contraindication to immunization⁽¹¹⁾.

Assessing risk of meningococcal disease in travellers Vaccine should be considered for individuals travelling to a region of increased meningococcal disease caused by one of the serogroups represented in the vaccine. The decision to recommend vaccination should be based on a careful assessment of risk, taking into account the following four factors: destination, nature and duration of exposure, age of the traveller, and health of the traveller.

1. Destination

Where geographic risk exists, travellers to remote areas without immediate access to reliable medical care are at highest risk. These areas are as follows:

• Countries in the meningitis belt of sub-Saharan Africa (Table 1and Figure 2). Risk is greatest in the dry season (December to June).

• Areas in sub-Saharan Africa outside of the traditional meningitis belt in which recent epidemics have occurred within the last 2 to 3 years (Table 2).

• Areas with current epidemics or heightened disease activity
  
  Areas of new and recent activity are identified in frequent updates published by the Laboratory Centre for Disease Control (LCDC), Health Canada, and by WHO. LCDC: FAXlink Service (613-941-3900), Health Canada Web site. WHO: Outbreak News Web site.

2. Nature and duration of exposure

Higher risk exists for long-term travellers and those who will be in close contact with the local population through accommodation, public transport, or work⁽¹⁾. Medical personnel are at greater risk if they have close, unprotected contact with nasopharyngeal secretions of infected persons⁽¹⁰⁾.

Travellers can not always anticipate the exact nature of exposure in advance of travel. When uncertainty exists, the health-care provider should weigh the severity of disease against the potential risk of exposure. Since severe adverse reactions to the vaccine are uncommon, and the disease is one that can have a fatal outcome within a very short period, it may be prudent to proceed with vaccination when the traveller is uncertain about the exact nature of exposure.

3. Age of the traveller Age

is a major determinant of host immunity to meningococcal disease. Over 80% of Canadians have acquired natural antibodies against serogroups A, B, and C by the age of 20 years⁽³⁾. The very young have the highest disease risk. In non-epidemic conditions in developed countries, 50% to 60% of cases occur in children 3 months to 5 years old, but cases are also seen in adolescents and young adults < 25 to 30 years old⁽²⁾. In 1996, the overall attack rate in Canada was 0.9 per 100,000. Age-specific incidence was twice this rate in adolescents aged 15 to 19 years, over three times as high in children aged 1 to 4 years, and 12 to 13 times as high in infants < 1 year of age⁽²²⁾. Similar data have been reported from the United States⁽²¹⁾. In the meningitis belt, incidence is highest among children 5 to 10 years of age. During epidemics in this region, older children, adolescents, and young adults are also affected⁽²⁾.

4. Health of the traveller

Asplenia is a major risk factor. Adults and children >= 2 years of age with functional or anatomic asplenia should be vaccinated regardless of geographic exposure⁽¹¹⁾. Complement deficiency is another major risk, and other immune-suppressing conditions, including HIV infection, may also increase risk⁽²¹⁾.

Figure 2 African meningitis belt*

* From: World Health Organization. Control of epidemic meningococcal disease. WHO practical guidelines. 2nd ed. Geneva: World Health Organization, 1998. WHO/EMC/BAC/98.3:6.

Recommendations Table 3 presents evidence-based medicine categories for the strength and quality of the evidence for each of the recommendations that follow.

Table 3 Strength and quality of evidence summary sheet*

Recommendation I: Vaccination schedules for travellers

Table 4 presents primary and repeat vaccination schedules as recommended in the Canadian Immunization Guide. Group A schedules should be used, unless the risk of disease is known to be group C only. The dose for all ages is 0.5 mL administered sub-cutaneously. Protective immunity is usually established about 7 to 10 days after vaccination⁽²¹⁾.

I.1    Primary schedules as per Table 4. (A-II)

I.2    Repeat schedules as per Table 4. (C-III)

Table 4 Schedules for primary and repeat doses of meningococcal vaccine*⁺

Recommendation II: Effectiveness of vaccine in children < 2 years of age

II.1 Parents of young children should be informed that protection from vaccine is not long lasting, and that only a limited number of young children receive protection, particularly against group C disease. Serogroup A vaccine may be less than fully effective in children 6 months to 12 months of age. Serogroup C vaccine has not conclusively been shown to be effective in children < 2 years of age^(13-16). (A-II)

II.2 If direct contact with a case occurs, chemoprophylaxis with  rifampin or ceftriaxone is recommended for these  children⁽¹⁰⁾. (A-III)

Recommendation III: Travellers who should receive vaccine

The following individuals should be considered for immunization:

III.1 Children, adolescents, and young adults (up to 25 years to 30 years old) who are in, or will be travelling to, an area of epidemic disease, regardless of duration of exposure^(2,10,21). (A-II)

III.2 Individuals going to the meningitis belt of sub-Saharan Africa, or to African countries outside the usual boundries of the meningitis belt where epidemics have occurred in the past 2 to 3 years (Figure 2, Table 1, and Table 2), who:

• will be living or working there⁽¹⁾
• may be in close contact with the local population, e.g. through accommodation or public transport⁽¹⁾
• will travel in remote areas where medical care is not readily available
• Risk in these areas is highest in the dry season (December to June)⁽²⁾. (A-II)

III.3 Individuals travelling to other remote areas where sporadic epidemics have been reported in the last 6 months (check Health Canada or WHO Web sites) and medical care is not readily available. (C-III)

III.4 Individuals working in hospitals, health care, field epidemiology, research, international aid, or refugee camps in areas of hyperendemic or epidemic meningococcal disease. (A III)

III.5 Individuals who travel extensively and unpredictably, e.g. military and intelligence personnel, flight attendants, and cabin crews. (B-III)

III.6 Travellers to Saudi Arabia for purpose of "Umra" or the Hajj pilgrimage, or for seasonal work. Saudi Arabia requires evidence of vaccination against serogroups A and C within the previous 3 years for these visitors⁽²³⁾.

Recommendation IV: Travellers not needing vaccine

Vaccination is not routinely recommended for adults who are travelling for < 3 weeks on business or holiday (including safaris) to areas of heightened meningococcal activity (sporadic outbreaks or meningitis belt areas) if they will have little exposure to local populations in crowded conditions. When doubt about the nature of exposure exists, it may be prudent to offer vaccination. (C-III)

References

1. World Health Organization. Epidemic meningococcal disease. URL: <http://www.who.int/inf-fs/en/fact105.html>. Date of access: 21 June 1999.

2. Tikhomirov E, Santa Maria M, Esteves K. Meningococcal disease: public health burden and control. World Health Stat Q 1997;50:3-10.

3. Gold R. Meningococcal disease in Canada:1991-92. Can J Public Health 1992;83:5-8.

4. Broome, CV. The carrier state: Neisseria meningitidis. J Antimicrob Chemother 1986;19(Suppl):25-34.

5. Moore PS. Meningococcal meningitis in sub-Saharan Africa: a model for the epidemic process. Clin Infect Dis 1992;11:515-25.

6. World Health Organization. Control of epidemic meningococcal disease. WHO practical guidelines. 2nd ed. Geneva: World Health Organization, 1998. WHO/EMC/BAC/98.3:1.

7. Ibid:3.

8. Ibid:31.

9. World Health Organization. Interagency appeal to control epidemic meningitis in Africa. URL: <http://www.who.int.archives/inf-pr-1997/en/pr97-11.html>. Date of access: 21 June 1999.

10. American Academy of Pediatrics and Canadian Pediatric Society. Meningococcal disease prevention and control strategies for practice-based physicians. Pediatrics 1996;97:404-12.

11. National Advisory Committee on Immunization. Canadian immunization guide. 5th ed. Ottawa Ont.: Health Canada, 1998:125-29. (Minister of Public Works and Government Services Canada, Cat. no. H49-8/1998E.)

12. De Wals P, Dionne M, Douville-Fradet et al. Impact of a mass immunization campaign against serogroup C meningococcus in the province of Quebec, Canada. Bull World Health Organ 1996;74:407-11.

13. Peltola H, Makela PH, Kayhty H et al. Clinical efficacy of meningococcus group A capsular polysaccharide vaccine in children three months to five years of age. N Engl J Med 1977;297:686-91.

14. Gold R, Lepow ML, Goldschneider I et al. Kinetics of antibody production to group A and C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children. J Infect Dis 1979;140:690-97.

15. King J, MacDonald N, Ashton F et al. Immunogenicity of quadrivalent meningococcal polysaccharide vaccine (Menomune) during a mass vaccination campaign. Pediatr Res 1993;33:90A. Abstract 525.

16. King J, MacDonald N, Wells G et al. Total and functional antibody response to a quadrivalent meningococcal polysaccharide vaccine among children. J Pediatr 1996;128:196-202.

17. Reingold AL, Broome CV, Hightower AW et al. Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine. Lancet 1985;2:114-18.

18. Lepow ML, Beeler J, Randolph M et al. Reactogenicity and immunogenicity of a quadrivalent combined meningococcal polysaccharide vaccine in children. J Infect Dis 1986;154:1033-36.

19. Ceesay S, Allen SJ, Menon A et al. Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of effect of booster immunization. J Infect Dis 1993;167:1212-16.

20. MacDonald N, Halperin S, Law B et al. Induction of immunologic memory by conjugated meningococcal polysaccharide vaccine in toddlers. JAMA 1998;180:1685-89.

21. Advisory Committee on Immunization Practices. Control and prevention of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46 (RR-5):1-9.

22. Deeks S, Kertesz D, Ryan A et al. Surveillance of invasive meningococcal disease in Canada, 1995-1996. CCDR 1997;23:121-25.

23. World Health Organization. Health conditions for travellers to Saudi Arabia:Pilgrimage to Mecca (Hajj). Wkly Epidemiol Rec 1999;74:6-7.

^a Sporadic cases: Single cases of invasive disease in a community in which no evidence exists of an epidemiologic link by person, place, or time (From: American Academy of Pediatrics and Canadian Paediatric Society. Meningococcal disease prevention and control strategies for practice-based physicians. Pediatrics 1996;97:404).

^b Outbreak: An increase in the number of sporadic cases in a population (Adapted from: Ibid).

*  Members: Dr. B. Ward (Chairman); Dr. K. Kain (Past Chairman); H. Birk; M. Bodie-Collins (Executive Secretary); Dr. S.E. Boraston; Dr. H.O. Davies; Dr. K. Gamble; Dr. L. Green; Dr. J.S. Keystone; Dr. K.S. MacDonald; Dr. J.R. Salzman; Dr. D. Tessier.

Ex-Officio Members: Dr. E. Callary (HC); Dr. M. Cetron (CDC); R. Dewart (CDC); Dr. E. Gadd (HC); Dr. C.W.L. Jeanes (retired, formerly with HC); Dr. H. Lobel (CDC); Dr. A. McCarthy (DND); Dr. M. Parise (CDC).

Liaison Representatives: Dr. R. Birnbaum (CSIH); S. Kalma (CUSO); Dr. V. Marchessault (CPS and NACI); Dr. H. Onyette (CIDS); Dr. R. Saginur (CPHA); Dr. F. Stratton (ACE).

⁺ This statement was prepared by H. Birk and approved by CATMAT.

[Canada Communicable Disease Report]