ARCHIVED - Canada Communicable Disease Report

Statement on Meningococcal Vaccination for Travellers

Preamble

The Committee to Advise on Tropical Medicine and Travel (CATMAT ) provides the Public Health Agency of Canada (PHAC ) with ongoing and timely medical, scientific, and public-health advice relating to tropical infectious disease and health risks associated with international travel. PHAC 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

Invasive meningococcal disease is a medical emergency, requiring early diagnosis, hospitalization, and effective antimicrobial treatment. At one time, the case-fatality ratio exceeded 50%, but early diagnosis, prompt antimicrobial treatment, and supportive measures have helped to lower the case-fatality rate to 5% to 10% in developed countries^{Footnote 1 Footnote 2}  . Up to 20% of those who survive have permanent neurological sequelae, including hearing loss, neurologic disability, or limb loss^{Footnote 1 Footnote 3} . 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), in which bacteria rapidly disseminate through the bloodstream, is a less common form of meningococcal disease and is characterized by circulatory collapse, haemorrhagic skin rash, and a high fatality rate^{Footnote 1} . This form has been responsible for the high case fatality rate in outbreaks of group C meningococcal disease in Canada^{Footnote 4} .

Meningococcal meningitis is caused by a Gram negative bacterium, Neisseria meningitidis, and accounts for 10% to 40% of endemic bacterial meningitis worldwide. Of the 13 recognized serogroups, groups A, B, C, Y, and W135 most frequently cause disease. Transmission is by direct contact, including respiratory droplets from the nose and throat of infected persons^{Footnote 2} . Most persons who are colonized with meningococcus are asymptomatic carriers^{Footnote 5} , yet meningococcus can be associated with, or impacted by, another infection. 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^{Footnote 6} , and increased incidence has been found following outbreaks of influenza in temperate countries^{Footnote 2} .

Epidemiology

Meningococcal meningitis occurs both sporadically worldwide and in focal epidemics. It is the only form of bacterial meningitis that causes epidemics^{Footnote 7}. Incidence rates in some epidemics in the Americas and Europe have been lower than the endemic incidence in several African countries^{Footnote 7}.

Meningococcal serogroups A, B, and C cause the vast majority of disease worldwide and are responsible for most sporadic cases and outbreaks in Europe and the Americas (see Figure 1). Serogroup A still predominates in Africa and Asia, causing most major epidemics. In sub-Saharan Africa, in a zone stretching across the continent from Senegal to Ethiopia (the African "meningitis belt"), large outbreaks and epidemics occur during the dry season (October–June)^{Footnote 8 Footnote 9} . Worldwide, serogroups Y and W-135 remain relatively uncommon causes of meningococcal infection. However, recent reports of endemic occurrence of group Y meningococcal disease in the United States and Canada^{Footnote 10} , and outbreaks caused by serogroup W-135 strains in Saudi Arabia and sub-Saharan Africa, particularly Burkina Faso, suggest that these serogroups may be on the rise^{Footnote 1} .

Epidemics most often occur during the winterspring 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. In 2000 and 2001, several hundred pilgrims attending the Hajj in Mecca, Saudi Arabia were infected with N. meningitidis W135, importing the disease to their home countries upon return^{Footnote 11 Footnote 12} .

Since 1993, serogroups B and C have been responsible for most of the cases of endemic disease in Canada. Meningococcal outbreaks in Canada are almost exclusively due to serogroup C. Sporadic localized outbreaks and periods of elevated incidence of serogroup C disease occurred during 1989-1993 and 1999-2001. During the 1999-2001 outbreak period, immunization campaigns were undertaken in some regions using serogroup C polysaccharide and conjugate vaccines. Recent data suggest that incidence rates of serogroup C are decreasing; likely as a result of universal childhood conjugate serogroup C meningococcal immunization programs which exist in every Canadian province and territory^{Footnote 13} .

Figure 1: Distribution of predominant N. meningitidis serogroups (A, B, C, Y and W-135)

Sources: United States: Rosenstein NE. J Infect Dis, 1999; Canada: Can Commun Dis Rep CCDR , 2004; Western Europe: EU-IBIS. Annual Report 2001; WHO AFRO Office, 2003; Australia: Commun Dis Intell, 2003; Chile: Ministerio de Salud de Chile (MINSAL ). Boletin de Viligancia en Salud Publica, 2003.

The traditional endemic areas of the world (the "meningitis belt") include the savannah areas of sub-Saharan Africa, from Gambia and Senegal in the west to Ethiopia and western Eritrea in the east (See Table 1 and Figure 2), with an estimated total population of 400 million. Epidemic meningococcal disease remains a major public health challenge in this area, with epidemics classically occurring in the dry season, which varies from country to country between October and June, in cycles that can last 2 to 3 years^{Footnote 1 Footnote 8 Footnote 9} . During year 2 of a cycle, widespread epidemics will often follow local outbreaks, and incidence rates may remain elevated for another 1 to 2 years. Epidemics tend to recur every 8 to 12 years, but since the early 1980s the period between major epidemics has been shorter and more irregular^{Footnote 1} . The estimated number of cases in the meningitis belt in the last 10 years is approximately 700,000, with roughly a 10 % fatality rate. Since the mid-1990s, epidemics in the meningitis belt have occurred on an unprecedented scale, and have spread beyond the usual boundaries (See Table 2). In Burkina Faso, the frequency of epidemic years has increased since 1996^{Footnote 8} . Such increases may be a new characteristic of the epidemiology of meningococcal disease^{Footnote 2} .

Outside the meningitis belt, there is no evidence of a cyclical pattern of epidemics^{Footnote 2} .

Table 1: Countries in the African meningitis belt, 2006* (see Figure 2 for more geographic precision)

Figure 2: Areas in the African meningitis belt, 2006* (*From: CDC Yellow Book: Health Information for International Travel, 2008. URL: http://wwwn.cdc.gov/travel/yellowbook/ch4/menin.aspx#651

Table 2: African countries beyond the meningitis belt borders in which epidemics were reported since 2000*

Angola (2001)
Burundi (2002)
Democratic Republic of the Congo (2007)
Rwanda (2002)
Somalia (2002)
Tanzania (2002)

* From: World Health Organization.

Meningococcal disease in the Democratic Republic of the Congo - 2 February 2007. URL: http://www.who.int/csr/don/2007_02_02/en/index.html ;

Meningococcal disease in the Great Lakes area (Burundi, Rwanda, United Republic of Tanzania) - Update 4 September 2002. URL: http://www.who.int/csr/don/2002_09_12a/en/ ;

Meningococcal disease in Somalia - Update 18 January 2002. URL: http://www.who.int/csr/don/2002_01_18/en/index.html ;

Meningococcal disease in Angola - Update 17 September 2001. URL: http://www.who.int/csr/don/2001_09_17/en/index.html .

Date of access: 28 December 2007.

Meningococcal vaccines

In Canada, six different meningococcal vaccines are licensed: two quadrivalent vaccines containing groups A, C, Y, and W-135, a bivalent A and C vaccine, and three monovalent C vaccines. Because the group B polysaccharide is poorly immunogenic, no vaccine is currently licensed for use against group B strains^{Footnote 14} . In comparison to polysaccharide meningococcal vaccines, the four conjugate meningococcal vaccines available in Canada have demonstrated greater immunogenicity, inducing better immunologic memory. It is hoped that these conjugate vaccines will also lead to decreasing meningococcal carriage and enhanced herd immunity^{Footnote 13} . As well, conjugate meningococcal vaccines do not result in hyporesponsiveness and have been shown to overcome the hyporesponsiveness evident in polysaccharide vaccine usage^{Footnote 13} . The Canadian Immunization Guide (http://www.phac-aspc.gc.ca/publicat/cig-gci/index-eng.php) provides additional information on meningococcal vaccines as do the following National Advisory Committee on Immunization (NACI ) statements:

• Update on the Invasive Meningococcal Disease and Meningococcal Vaccine Conjugate Recommendations, April 2009 (ACS-3) (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/09vol35/acs-dcc-3/index-eng.php)
• "Statement on conjugate meningococcal vaccine for serogroups A, C, Y and W135" May 1, 2007(ACS-3) (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/07vol33/acs-03/index-eng.php) and
• "Meningococcal C conjugate vaccination recommendations for infants" November 2007
  (http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/07vol33/acs-11/index-eng.php)

Table 3 compares all meningococcal vaccines licensed in Canada.

Table 3. Comparison of the meningococcal vaccine products approved for use in Canada*

IM - intramuscularly SQ - subcutaneously CRM₁₉₇ Corynebacterium diphtheriae crossreacting material 197

* From: "Statement on conjugate meningococcal vaccine for serogroups A, C, Y and W135." Canada Communicable Disease Report, Volume 33 (ACS-3 ) 1 May 2007. An Advisory Committee Statement (ACS ): National Advisory Committee on Immunization (NACI )^{Footnote 13} .

Vaccine efficacy

In Canada, two categories of meningococcal vaccine are currently available: polysaccharide vaccines and protein-polysaccharide conjugate vaccines (also referred to as conjugate vaccines). T cell receptors do not recognize polysaccharide vaccines. The T cell independent response to polysaccharide vaccines makes these vaccines poorly immunogenic in children < 2 years of age^{Footnote 13} .

However, conjugate vaccines induce a T cell antibody response, thus generating antibodies with improved functional activity and immunogenicity in young children (including < 2 years old), better immunologic memory, and possibly decreased N. meningitidis carriage^{Footnote 13} . In Canada, three monovalent meningococcal C conjugate products are approved for use in the 2-month to 10-year age group. Trotter et al. showed an effectiveness of 93% (95% CI, 78% to 98%) more than 1 year after vaccination in children vaccinated at 3 to 4 years of age^{Footnote 13 Footnote 15} . As well, Larrauri et al. demonstrated the meningococcal C conjugate vaccine was 94.3% effective (95% CI, 71.2% to 98.8%) more than 1 year after vaccination in children vaccinated at 7 months to 5 years of age^{Footnote 13 Footnote 16} .

Comparing the two available quadrivalent meningococcal vaccines in randomized controlled trials, the conjugate vaccine (Menactra™) was found to be immunologically non-inferior to the polysaccharide vaccine (Menomune^® ) among three age groups: adults 18 to 55 years of age, adolescents 11 to 18 years of age, and children 2 to 10 years of age^{Footnote 13} .

Primary meningococcal immunization when travelling

Beginning in 2002, every Canadian province and territory began routine meningococcal C conjugate immunization programs for children. Programs vary by jurisdiction; further information can be found at http://www.phac-aspc.gc.ca/im/ptimprog-progimpt/. However, immunization against serogroup C alone is not considered adequate for individuals travelling to destinations where other serogroups (such as A and W135) have been reported.

NACI recommends that if meningococcal C conjugate vaccine is given to infants <12 months of age, a booster dose should be given in the second year of life (from 12 to 23 months of age)^{Footnote 17} . Unimmunized children ≥ 1 year, adolescents, and adults require only a single 0.5 mL dose of any of the conjugate C vaccines currently licensed in Canada^{Footnote 13} . Although less data is available for quadrivalent vaccines, by extrapolation these schedules could also be used for the quadrivalent meningococcal conjugate vaccine. In Canada, Menactra™ is only approved for use in children 2 years of age and older. If recommending to children < 2 years of age, it is an "off label" use. Menactra™ is only modestly immunogenic when administered as three doses (2, 4, and 6 months of age) to infants^{Footnote 18} . Hence, NACI recommends that children < 2 years of age who receive Menactra™ should also receive a conjugate C vaccine licensed for this age group to optimize protection against serogroup C^{Footnote 13} .

A single 0.5 mL dose of quadrivalent meningococcal conjugate vaccine (Menactra™) is recommended for travellers >10 to 55 years of age for whom meningococcal vaccine is indicated or required, including pilgrims to the Hajj in Mecca. NACI recommends that children 2-10 years of age, who are at high risk, including travellers, receive not only Menactra™, but also the conjugate C meningococcal vaccine due to its proven effectiveness in this age group and the possibility of lower effectiveness with the quadrivalent vaccine. Menactra™ should be administered first given its broader spectrum of serogroup protection, and there should be at least a 1-month interval between of the administration of each product^{Footnote 13} . It is recommended that children < 2 years receive 3 doses of the conjugate C meningococcal vaccine given at least 4 weeks apart. If possible, vaccination should be completed at least 2 weeks before departure^{Footnote 13} .

For cases where contraindications to conjugate vaccines exist, quadrivalent polysaccharide ACYW135 vaccines may be used for children as young as 3 months who are travelling to regions requiring broad protection^{Footnote 19} . In cases of risk of serogroup A exposure, infants aged 3 to 23 months should receive two doses of quadrivalent polysaccharide vaccine given 2 to 3 months apart^{Footnote 19} .

Repeat doses

Polysaccharide:

Those who have previously received polysaccharide meningococcal vaccine should receive conjugate quadrivalent meningococcal vaccine if travelling to a high-risk destination. For those in whom conjugate vaccines may be contraindicated, reimmunization with polysaccharide vaccine is recommended after a 6-month to ≤ 5-year interval depending on the age at initial vaccination^{Footnote 19} .

Conjugate:

Immune memory has been shown for meningococcal C conjugate vaccines through increases in titres when challenged by polysaccharide or meningococcal C conjugate vaccines. It is not known, however, if immune memory is sufficient to protect against invasive meningococcal disease (IMD ), which has a short incubation period (range 2 to 10 days, commonly 3 to 4 days)^{Footnote 13 Footnote 20} . It is speculated that given the short incubation period, protection requires circulating antibodies. A modeling study by De Wals et al. reported that with a schedule of one dose of meningococcal C conjugate vaccine at 12 months of age, a booster dose would be required if meningococcal C protection waned at 3% or more per year. The authors have noted that 12 years of age would be the optimal age for this booster dose, given the current epidemiology of serogroup C meningococcal disease in Canada^{Footnote 13 Footnote 20} .

Given insufficient data to predict persistence of immunity and long-term effectiveness in quadrivalent conjugate meningococcal vaccine (Menactra™), the need for reimmunization with additional doses is currently unknown. Continued monitoring is required to determine the need for revaccination or booster doses. Individuals travelling to a high-risk meningococcal destination who previously received polysaccharide meningococcal vaccine should now receive conjugate meningococcal vaccine (i.e., Menactra™) unless contraindicated.

Revaccination using a conjugate vaccine (such as Menactra™) after earlier administration of polysaccharide vaccine should be considered:

• 1 to 2 years later if the polysaccharide vaccine was received at 13 to 23 months of age;
• 2 to 3 years later if the polysaccharide vaccine was received at 2 to 5 years of age^{Footnote 13} ; and
• 5 years later if the polysaccharide vaccine was received at ≥ 6 years of age. Given that an adequate response in adults to conjugate C vaccine with a delay of 6 months after immunization with purified polysaccharide vaccine has been documented, this remains the recommended minimum interval to receive Menactra™ after having received a polysaccharide vaccine, until further data are available^{Footnote 13} .

Individuals who have previously received meningococcal C conjugate vaccine can receive quadrivalent meningococcal conjugate vaccine (Menactra ™). Although no data exist, according to expert opinion, a minimum interval of 1 month between products is recommended^{Footnote 13} .

Adverse reactions and contraindications

Local redness or pain occurs frequently, but these are mild reactions, often disappearing within 1 to 2 days. Wheal and flare reactions occur rarely. Systemic adverse reactions are uncommon and not severe. Provided that the booster dose is given as recommended, the incidence of adverse reactions is similar after primary and booster doses of either polysaccharide or conjugate vaccines. Pregnancy is not a contraindication to immunization; however none of the conjugate vaccines, including Menactra™, have been studied in pregnant or breastfeeding women and thus should be used only if the benefits outweigh the risks. In general, local reactions tend to occur more often following administration of quadrivalent meningococcal conjugate vaccine (Menactra™) than quadrivalent meningococcal polysaccharide vaccine (Menomune® ). This may be the result of the diphtheria toxoid carrier protein in Menactra™ or a response to its intramuscular (IM) administration rather than the subcutaneous administration of Menomune®^{Footnote 13} .

The Vaccine Adverse Event Reporting System (VAERS ) in the United States had, as of September 2006, identified 17 cases of Guillain Barré Syndrome (GBS ) occurring within 6 weeks of receipt of Menactra™^{Footnote 21} . GBS cases were significantly clustered at onset intervals of 9-15 days post-vaccination. The rate of GBS in persons aged 11-19 years was 0.20 per 100,000 personmonths, compared to an estimated background rate of GBS of 0.11 per 100,000 person-months. Although the risk of recurrent GBS is unknown, until further data are gathered, Menactra™ should not be administered to an individual with a previous episode of GBS especially when alternate quadrivalent polysaccharide products are available^{Footnote 13} .

Conjugate vaccines and polysaccharide vaccines are contraindicated in people with a known history of anaphylaxis to any component of the vaccine or to a prior dose of conjugate or polysaccharide meningococcal vaccine^{Footnote 19} .

Concurrent administration with other vaccines

There is no published data on the safety and immunogenicity of the concurrent administration of quadrivalent meningococcal conjugate vaccine with other vaccines. Unpublished data from Sanofi Pasteur demonstrates that concurrent administration of Menactra™ and tetanusdiphtheria- acellular pertussis (Tdap - Adacel^® ) vaccine is safe and immunogenic.

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^{Footnote 1} :

• Countries in the meningitis belt of sub-SaharanAfrica (Table 1 and Figure 2). Risk is greatest in the dry season (varies between countries from October to June).
• Areas in sub-Saharan Africa outside of the traditional meningitis belt where recent epidemics have occurred (Table 2).
• The quadrivalent vaccine, (A, C, Y, W-135) is currently required by Saudi Arabia for pilgrims visiting Mecca for the Hajj (annual pilgrimage) or for the Umrah. Outbreaks of meningococcal disease have affected these pilgrims, involving both serogroups A and W135 since 2000.
• Areas with current epidemics or heightened disease activity. For instance, travellers to industrialized countries are exposed to the possibility of sporadic cases. As meningococcal C disease occurs in schools, colleges, military barracks, and other places where large numbers of adolescents and young adults congregate, individuals spending significant time in these higher risk settings may consider receipt of vaccine at least 2 weeks prior to their arrival in those settings. If travelling to an industrialized country with endemic meningococcal disease, travellers should follow the recommendations being used for the residents of that country.

Areas of new and recent activity are identified in frequent travel health notices published by the Public Health Agency of Canada and available at: http://www.phac-aspc.gc.ca/tmp-pmv/pub_e.html

2. Nature and duration of exposure

Long-term travellers and those who will be in close contact with the local population through accommodation, public transport, or work are at higher risk^{Footnote 1} . Medical personnel are at greater risk if they have close, unprotected contact with nasopharyngeal secretions of infected persons^{Footnote 1} . Vaccine is also recommended for those planning to work in a laboratory with meningococcal isolates.

Travellers cannot always anticipate the exact nature of exposure in advance of travel. When uncertainty exists, the health-care provider should weigh the severity of disease and 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. 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^{Footnote 2} .

Since 1985, the overall incidence of invasive meningococcal disease (IMD) has remained at or below 2 per 100,000 per year (range 0.5 to 2.1) in Canada. The incidence rate is highest among children < 1 year of age and declines as age increases; however, a small peak also occurs among those in the age group of 15 to 19 years^{Footnote 19} .

In the African meningitis belt, children 5 to 10 years of age have the highest incidence of disease. In Ghana and Niger, however, surveillance studies showed that the incidence of meningococcal meningitis was similar in all age groups under 20 years of age (average annual incidence: 30-40 cases per 100,000)^{Footnote 2 Footnote 8} .

4. Health of the traveller

Asplenia is a major risk factor for invasive meningococcal disease. Adults and children ≥ 2 years of age with functional or anatomic asplenia should be vaccinated regardless of their potential geographic exposure^{Footnote 19} . Other major risk factors include complement deficiency and immune-suppressing conditions such as HIV infection^{Footnote 22} .

Recommendations

Table 4 presents evidence-based medicine categories for the strength and quality of the evidence for each of the recommendations that follow.

* From: Macpherson DW. Evidence-based medicine. CCDR 1994;20:145-47. http://www.phac-aspc.gc.ca/publicat/ccdr-rmtc/94pdf/cdr2017.pdf (PDF Version)

Recommendation I: Vaccination serogroup coverage

I.1 Travellers to high risk meningococcal destinations (primarily African meningitis belt) require immunization primarily against meningococcal serogroups A and W135. (A-I)

I.2 Individuals who have previously received meningococcal C conjugate vaccine through routine public health programs are not adequately immunized for travel to high risk meningococcal destinations (primarily African meningitis belt). (E-I)

Recommendation II: Vaccination schedules for travellers

Table 5 presents primary and repeat vaccination schedules as recommended in the Canadian Immunization Guide (http://www.phac-aspc.gc.ca/publicat/cig-gci/index-eng.php). The dose for all ages is 0.5mL administered intramuscularly (IM ) for conjugate vaccines and subcutaneously (SC ) for polysaccharide vaccines. Protective immunity is usually established about 7 to 10 days after vaccination with polysaccharide meningococcal vaccines and protective antibody levels are demonstrable within 8 to 28 days after vaccination with conjugate meningococcal vaccines^{Footnote 13 Footnote 19 Footnote 22} . Since conjugate vaccines possess significant advantages over polysaccharide vaccines including better immune memory, longer duration of efficacy, lack of hyporesponsiveness with booster doses, and possible reduction of bacterial carriage rates, travellers may be preferentially offered conjugate over polysaccharide quadrivalent ACYW-135 vaccine.

* Menactra™, is not currently approved for use in children <2 years of age. If using this vaccine in this age group the conjugate C vaccine should also be given to optimize protection against serogroup C.
**Children 2 to 10 years of age should also receive a conjugate C vaccine in addition to the quadrivalent conjugate vaccine^{Footnote 13} .
***Alternative choice to be offered if conjugate vaccine contraindicated.

Recommendation III: Travellers who should receive vaccine

The following individuals should be considered for immunization:

III.1 Persons travelling to an area of epidemic disease, regardless of duration of exposure^{Footnote 2 Footnote 14 Footnote 22} . (A-II)
III.2 Persons travelling to the meningitis belt of sub-Saharan Africa, or to African countries outside the usual boundaries 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;
• may be in close contact with the local population, e.g., through school, accommodation, or public transport.

Risk in these areas is highest in the dry season (which varies between countries from October to June). (A-II)

III.3 Persons travelling to areas (including industrialized countries) where sporadic epidemics (including meningococcal C) have been reported in the last 6 months [check Public Health Agency of Canada (http://www.phac-aspc.gc.ca/tmp-pmv/pub-eng.php) or WHO websites (http://www.who.int/en/) ]. In developed countries, travellers should follow the meningococcal immunization recommendations of the destination country. (C-III)

III.4 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, C, and W135 within the previous 3 years for these visitors^{Footnote 11 Footnote 12} . (A-II)