National and regional differences in meningococcal vaccine recommendations for individuals at an increased risk of meningococcal disease

ABSTRACT

Introduction

Invasive meningococcal disease (IMD) is a severe, life-threatening condition caused by infection with Neisseria meningitidis. Currently available vaccines offer protection against the five most common meningococcal disease-causing serogroups and include monovalent and quadrivalent conjugate vaccines (MenA, MenC, MenACWY vaccines) and outer membrane vesicle- and/or recombinant protein-based vaccines (MenB vaccines).

Areas covered

Country and regional immunization programs target populations susceptible to IMD and typically emphasize the highest-risk age groups (i.e., infants, adolescents/young adults, and the elderly); however, additional groups are also considered at an elevated risk and are the focus of the current review. Specific increased-risk groups include individuals with underlying immunocompromising medical conditions, university/college students, Indigenous people, laboratory workers, military personnel, men who have sex with men, and travelers to areas with hyperendemic IMD. This review compares established meningococcal vaccination recommendations for these vulnerable groups in Europe, the United States, Australia, New Zealand, Israel, Brazil, and Turkey.

Expert opinion

Recommendations should be standardized to cover all groups at increased risk of IMD.

KEYWORDS:

• increased risk
• MenACWY
• MenB
• vaccine
• vaccine recommendations

1. Introduction

Invasive meningococcal disease (IMD) is caused by infection with the bacterium Neisseria meningitidis [1]. IMD is preceded by nasopharyngeal bacterial colonization, which is often asymptomatic but causes disease if the bacteria spreads to the bloodstream or other sterile body sites [2]. Although generally uncommon, IMD is associated with high case fatality rates (CFRs) and can have severe long-term consequences [1]. Globally, the most common meningococcal disease-causing serogroups have historically been A, B, C, W, and Y, although serogroup X has more recently been responsible for outbreaks in Africa [3,4]. However, meningococcal disease is unpredictable, and disease epidemiology including the predominant disease-causing serogroups varies by country/region [3,5], over time [5], during outbreaks [6], or within various risk populations [7].

Meningococcal vaccines are available to prevent infection caused by the most common disease-causing serogroups; these include monovalent (serogroup A [MenA], serogroup C [MenC]) and quadrivalent polysaccharide conjugate vaccines against serogroups A, C, W, and Y (MenACWY), as well as recombinant protein-based serogroup B (MenB) vaccines (Table 1) [8–17]. Polysaccharide protein conjugate vaccines not only result in direct protection of vaccinees but also indirect protection of unvaccinated individuals through a reduction in meningococcal carriage acquisition and transmission [5].

Table 1. Available Meningococcal Conjugate and Protein-Based Vaccines.

Quadrivalent Serogroup A, C, W, and Y Vaccine (Brand)	Serogroup(s) Targeted	Carrier Protein	Manufacturer
MenACWY-DT (Menactra®) [8]	A, C, W, Y	DT	Sanofi Pasteur
MenACWY-CRM (Menveo®) [9]	A, C, W, Y	CRM	GSK
MenACWY-TT (Nimenrix®) [10]	A, C, W, Y	TT	Pfizer
MenACYW-TT (MenQuadfi®) [11]	A, C, W, Y	TT	Sanofi Pasteur
Monovalent Serogroup A or C Vaccine (Brand)	Serogroup Targeted	Carrier Protein	Manufacturer
PsA-TT (MenAfriVac) [12]	A	TT	Serum Institute of India
MenC-CRM (Menjugate®) [13]	C	CRM	GSK
MenC-TT (NeisVac-C®) [14]	C	TT	Pfizer
MenC-TT/Hib-TT (Menitorix®) [15]	C	TT	GSK
Serogroup B Vaccine (Brand)	Recombinant Protein Targets	Other Major Antigenic Components	Manufacturer
MenB-FHbp (Trumenba®) [16]	FHbp subfamily A and B	–	Pfizer
MenB-4C (Bexsero®) [17]	NadA, NHBA, FHbp subfamily B	PorA (present in OMV)	GSK

Note: CRM, cross-reacting material 197 protein; DT, diphtheria toxoid; FHbp, factor H binding protein; HiB, Haemophilus influenzae type b; NadA, neisserial adhesin A; NHBA, neisserial heparin-binding antigen; OMV, outer membrane vesicle; PorA, outer membrane porin protein (serosubtype P1.4); TT, tetanus toxoid.

National and region-specific meningococcal vaccination programs typically target specific individuals considered to be at increased risk of IMD [5]. Risk of IMD varies by age among the general population, with incidence typically highest in infants (because of their immature immune system) followed by peaks in young children (1–5 years of age), adolescents/young adults (because of behaviors increasing relative exposure), and older individuals in some countries [2,5,7,18,19]. Other specific groups may also be at higher IMD risk compared with the general population [6,7,20–31]. ‘At-risk’ typically refers to those with underlying immunocompromising conditions such as HIV infection, complement deficiency (CD), or functional or anatomic asplenia [5]. However, other individuals without an underlying immunocompromising condition are still considered at ‘increased risk’ of IMD; these individuals include university/college students engaging in social behaviors with close physical contact [32], Indigenous or immigrant populations with a high incidence of disease [20], laboratory workers with occupational exposure to N meningitidis [7], military personnel living in communal spaces and/or traveling to countries with hyperendemic serogroups [33], men who have sex with men (MSM) in settings with outbreaks or MSM with HIV infection [28], and travelers to regions with high IMD incidence or mass gatherings [29].

This review will briefly describe recommendations among at-risk individuals with underlying conditions but will then focus mainly on those considered at ‘increased risk of IMD,’ highlighting regional differences in recommendations to identify potential gaps in coverage. Specific countries with established recommendations predominantly available in English that allow for comparison are discussed and include various European countries, the United States, Australia, New Zealand, Israel, Brazil, and Turkey (Table 2). These countries include those with a relevant disease burden, sufficient quality of surveillance systems, and a history of meningococcal vaccination; they were also selected based on authors’ knowledge that they were pertinent to include given their precedent for vaccine advocacy and early vaccine adoption in other therapeutic areas.

Table 2. Current Meningococcal Vaccine Recommendations for At-Risk and Increased-Risk Groups in Different Countries*.

	Underlying Medical Conditions^†	College/University Students	Indigenous People	Laboratory Workers	Military Personnel	Travelers to Areas With Hyperendemic Meningococcal Disease
Australia [40,41]	MenACWY, MenB	MenACWY, MenB	MenB	MenACWY, MenB	MenACWY, MenB	MenACWY
Brazil [42]	MenC, MenACWY			MenC, MenACWY
France [43,44]	MenACWY, MenB, MenC			MenACWY, MenB		MenACWY
Germany [45,46]	MenACWY, MenB	MenACWY, MenB^‡		MenACWY, MenB	MenACWY	MenACWY
Ireland [47–49]	MenACWY, MenB	MenACWY		MenACWY, MenB		MenACWY
Israel [50]	MenACWY, MenB			MenACWY, MenB	MenACWY	MenACWY
Italy^§ [51,52]	MenACWY, MenB
Netherlands [53]	MenACWY					MenACWY
New Zealand [54,55]	MenACWY or MenC^¶, MenB	MenACWY, MenB		MenACWY, MenB	MenACWY, MenB	MenACWY, MenB
Portugal [56]	MenACWY, MenB
Spain [46,57]	MenACWY, MenB				MenACWY	MenACWY
Turkey [58–61]	MenACWY			MenACWY	MenACWY	MenACWY
United Kingdom [46,62–67]	MenACWY, MenB	MenACWY		MenACWY	MenACWY, MenB**	MenACWY
United States[1,68–70]	MenACWY, MenB	MenACWY, MenB^††		MenACWY, MenB	MenACWY, MenB^††	MenACWY

Note: MenACWY, quadrivalent meningococcal vaccine for serogroups A, C, W, and Y; MenB, meningococcal serogroup B vaccine; MenC, meningococcal serogroup C vaccine.

*Vaccine recommendations included here are those in addition to age-based recommendations.

^†Underlying medical conditions include, but are not limited to, cellular immune deficiencies, combined immune deficiencies, complement deficiencies, those for patients who underwent transplantation, those for patients with cancer, hereditary immune deficiencies, and HIV. Recommendations may not apply to all medical conditions; the original source should be referred to for information on specific conditions.

^‡Vaccination of students is recommended only before long-term stays in countries with recommended general vaccination for adolescents or selective vaccination for pupils/students. The type of vaccination given is according to the recommendations of the destination countries.

^§Note that the indicated vaccines are for individuals who are asplenic or hyposplenic; the specific meningococcal vaccine that is recommended in individuals with other underlying medical conditions is not specified.

^¶In high-risk infants aged <9 months, a specific MenACWY vaccine is recommended (but not funded) instead of MenC vaccine.

**Vaccination requirements depend on the military organization, role, and previous vaccination history.

^††Whilst not a recommended vaccine, MenB is available to adolescents and young adults 16–23 years old based on shared clinical decision-making; the individual is not required to be at increased risk of meningococcal disease.

2. At-risk categories and associated recommendations

Certain populations are considered at-risk because of underlying immunocompromising medical conditions; these include individuals with functional or anatomic asplenia (including sickle cell disease), CD/early or late complement pathway disorders, and HIV infection [5,7,26]. Patients with asplenia have an IMD case fatality rate of 40%–70% [25]. Individuals with CD have a 1000–10,000-fold increased IMD risk compared with the general population, whereas those with HIV infection have a 10-fold relative risk [5,7]. An increased risk is also evident in patients taking eculizumab (Soliris®, Alexion Pharmaceuticals, Inc., Boston, MA, U.S.A.) or ravulizumab (Ultomiris®, Alexion Pharmaceuticals, Inc., Boston, MA, U.S.A.) to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, generalized myasthenia gravis, or neuromyelitis optica spectrum disorder [26].

Some medications and immunocompromising medical conditions can also impact vaccine immunogenicity. Reports of meningococcal disease in individuals taking eculizumab who had been recently vaccinated indicate that meningococcal vaccines do not provide complete protection among those receiving complement inhibitors [1,34]. In a recent study of adolescents with juvenile idiopathic arthritis or inflammatory bowl disease, seroprotection after vaccination with a MenACWY conjugate vaccine was significantly lower in patients receiving anti-TNF therapy compared with those not receiving therapy [35]. Asplenic patients and patients with HIV have been shown to have lower immunogenic responses compared with healthy controls after vaccination with MenACWY or MenC conjugate vaccines [36–39]. The lower immune responses to vaccination have led to recommendations that individuals who are immunocompromised receive two vaccine doses or a booster dose of meningococcal vaccines [1,36,38,39]. All countries included in this review recommend meningococcal vaccination for individuals with underlying immunocompromising conditions but differ in the specific medical conditions included and the meningococcal vaccines recommended (Table 2). For example, both MenACWY and MenB vaccines are recommended for HIV-infected individuals in Ireland, New Zealand, and Australia [40,47,54], whereas MenC vaccination only is recommended in France [43] and an unspecified anti-meningococcal vaccine is recommended in Italy [51]. In Germany, MenB vaccination is recommended for individuals living with HIV based on physician assessment [45]. In Turkey, vaccination with MenACWY is recommended for immunocompromised individuals [71] and for children 11–18 years old with HIV infection [72] and the cost is not reimbursed. In Australia, MenB and MenACWY vaccination is funded through the National Immunisation Program for individuals of any age with specific risk factors for IMD [41]. In Brazil, MenC and MenACWY vaccinations are recommended for individuals with underlying immunocompromising conditions, whereas MenACWY vaccination is recommended only for those with paroxysmal nocturnal hemoglobinuria taking eculizumab [42].

Additional medical conditions conferring increased risk for severe complications associated with IMD include diabetes, chronic kidney or liver disease, human papilloma virus infection, hemophilia, autoimmune disorders, severe chronic respiratory disorders, and loss of cerebrospinal fluid [30,73–75]. In Italy, meningococcal vaccination is specifically recommended for individuals with diabetes, kidney disease, and liver disease in addition to individuals with the immunocompromising conditions discussed above [76,77].

3. Increased-risk categories and associated recommendations

3.1. College/university students

Studies across various regions indicate an elevated risk of IMD among college and university students [6,21–23,31]. In the United Kingdom, an analysis of 2014–2015 surveillance data reported a high IMD risk among students 15–24 years old compared with nonstudents of the same age; serogroup B caused 40% and serogroups A, C, W, and Y caused 53% of all IMD cases [21]. In the United States, college students are at similarly increased IMD risk dominated by serogroup B disease, which accounted for approximately 40% of IMD cases in college students in 2021 [31]. Although outbreaks account for >30% of serogroup B disease in US college students, the risk of sporadic serogroup B disease is also elevated in this group compared with that of nonstudents [6]. In France, two clusters of IMD cases caused by serogroup W were reported on two campuses between 2016 and 2017, collectively associated with five cases and three fatalities [23,24]. The increased risk of IMD in college and university students is likely attributable in part to social behaviors involving close physical contact that facilitate pathogen transmission [32].

Of the countries included in this review, the United States and the United Kingdom recommend MenACWY vaccination for college/university students, particularly those in their first year, whereas Australia and New Zealand recommend both MenACWY and MenB vaccinations [40,54,62,68,78] (Table 2). However, it is important to note that while MenB is not a routinely recommended vaccine in the United States, it is available to all adolescents/young adults (age 16–23 years) based on shared clinical decision-making [1,68]. The use of routine adolescent vaccines in some settings may preclude additional recommendations directly concerning college and university students. For example, routine MenACWY vaccination is recommended in adolescents 12–18 years and 11–12 years old in Spain and Brazil, respectively, but vaccination of university students is not specified in these countries, possibly because these individuals are largely included within the recommendation [42,57,79,80]. Also, MenACWY vaccination in Ireland is given to school children in their first year of secondary school, although vaccination of all students and staff against MenC is suggested to help prevent outbreaks among college students [81]. In the United States, college students are at elevated risk of IMD [6,22,31], although routine MenACWY vaccination recommendations in this group [69] may have lowered their risk of IMD caused by vaccine serogroups [1]. Conversely, the lack of formal MenB vaccination recommendations for this group [82] (MenB vaccination is available in the United States based on shared decision-making only [69]) is associated with continued elevated risk of serogroup B disease [6,22,31].

3.2. Indigenous populations

Certain Indigenous populations may be at increased risk of IMD. For example, children of Aboriginal and Torres Strait descent have a higher incidence of serogroup B disease compared with non-Indigenous Australians [20]. This increased risk is most pronounced in children younger than 10 years, with infants having an incidence rate ratio of 3.4 (95% CI: 2.5, 4.5) [20]. In a 1995 report from New Zealand, researchers identified rates of meningococcal disease that were approximately 3 times higher among Māori and Pacific Islander populations compared with New Zealanders of European descent [83]. From 1991 to 2007, a serogroup B strain caused an epidemic mainly affecting infants and children 1–4 years old of Māori and Pacific descent, and this population remains at increased risk of IMD compared with other ethnic groups [54,55]. Immigrant and refugee populations across the globe may also be at increased risk of IMD among other infectious diseases, although no official recommendations exist regarding meningococcal vaccination among these populations [84]. Potential reasons for increased risk among some Indigenous, immigrant, or refugee populations include active or passive exposure to tobacco smoke, poor sanitation conditions, and likelihood of living in close quarters with others [83–85].

In Australia, MenACWY vaccine is provided free to those 12 months and 14‒16 years of age as part of the National Immunisation Program, with catch-up vaccines for those <20 years old [41]; MenB vaccination is also provided for all Aboriginal and Torres Strait Islander children from 6 weeks of age, with a catch-up program for those <2 years of age [41]. In New Zealand, a MenB vaccination program using a tailor-made strain-specific vaccine was conducted from 2004 to 2011 in response to the outbreak, largely with the goal of reducing inequities pronounced in Māori and Pacific Island populations [86]. Other countries included in this review do not have meningococcal vaccine recommendations for Indigenous populations.

3.3. Laboratory workers

The incidence of IMD is 40-fold higher among laboratory workers who routinely handle N meningitidis isolates than those in general age-matched populations [7]. Most countries included in this review recommend meningococcal vaccination for laboratory personnel working with meningococci (Table 2), with Brazil recommending MenACWY or MenC vaccines [42], the United Kingdom recommending MenACWY vaccines [63], and others recommending both MenACWY and MenB vaccines [40,43,45,47,50,54,87].

3.4. Military personnel

Military personnel are at an increased risk of IMD because of their typical age (i.e., 19–25 years), housing in close physical contact (similar to college and university students), and deployment in hyperendemic areas, making them similarly at increased risk of IMD as travelers to such areas [33]. Since MenACWY vaccination was introduced to the US military between 2006 and 2008, overall IMD incidence has decreased and is not different from that in civilians [88]; however, isolated cases of IMD among individual military recruits, including fatal ones, continue to occur [33].

Several of the studied countries have vaccination recommendations specifying military personnel as an increased-risk group (Table 2). In the United States, military members are recommended to receive the same vaccines as the general population based on their age, vaccination history, health, and travel [89]; they are also specifically required to be vaccinated with a MenACWY conjugate vaccine [90].

3.5. Men who have sex with men

Men who have sex with men have been reported to be at increased risk of IMD, and serogroup C in particular [27]. Among 271 IMD cases in US men ≥18 years old during 2015–2016, 18% of cases occurred in MSM [28]. Serogroup C was responsible for a majority of IMD cases in MSM compared with men not known to have sex with men (85% vs 16%) [28]. This increased incidence of IMD in MSM was largely driven by outbreaks; however, in nonoutbreak settings, HIV infection was also identified as a potential risk factor for IMD among MSM [28]. In Europe, an increased risk of IMD caused by serogroup C among MSM was also observed in metropolitan settings [91].

Vaccination recommendations in this group appear to be tied to outbreaks [92,93]. For example, in response to a 2013 outbreak, the New York City Department of Health recommended that all MSM regardless of HIV status be vaccinated against meningococcal disease [92]. That same year, the Israeli Ministry of Health recommended that MSM who were traveling to New York be vaccinated against serogroup C [93]. As a response to an ongoing outbreak of serogroup C meningococcal disease in Florida (from 2021 through 2023), the US Centers for Disease Control and Prevention has expanded recommendations to include vaccination with a MenACWY vaccine for MSM if they live in Florida [94].

3.6. Travelers

Travelers to the African meningitis belt and to large gatherings are at increased risk of IMD, especially given the more recent emergence of the serogroup W cc-11 clone [29,95]. In 2015, 4 cases of serogroup W IMD were confirmed among Europeans returning from the World Scout Jamboree in Japan, an event with >33,000 participants from 162 countries [96]. Travelers to other large gatherings such as the Hajj in Mecca, Saudi Arabia, and their close contacts may be at increased risk of IMD [97]; high carriage rates of up to 27% depending on serogroup and country of origin have been observed among pilgrims [98]. This increased risk is attributed to multiple factors, including congestion, shared accommodations, poor hygiene, air pollution, and presence of elderly individuals who may be more susceptible to infection [29,99]. Therefore, Saudi Arabia requires proof of meningococcal vaccination for Hajj or Umrah pilgrims who are 2 years and older and seasonal or pilgrim workers in these areas, as well as travelers from the African meningitis belt [100]. Most countries included in this review also have meningococcal vaccine recommendations for travelers to areas with hyperendemic disease (Table 2).

4. Meningococcal vaccine implementation and uptake

Available data suggest meningococcal vaccination rates among people with underlying immunocompromising conditions are poor [99,101–104]. A nationwide retrospective US study showed that among patients with functional or anatomic asplenia (excluding sickle cell disease or CD) identified from 2010 to 2018, 28.1% received ≥1 dose of a MenACWY vaccine and 9.7% received ≥1 dose of a MenB vaccine by 3 years after diagnosis [102]. A similar study revealed that 4.6% and 2.2% of patients newly diagnosed with CD in the United States from 2010 to 2018 received ≥1 dose of MenACWY and MenB vaccine, respectively, within 3 years of diagnosis [104]. Also, among patients with HIV infection identified in the United States from 2016 to 2018, 16.3% received ≥1 dose of a MenACWY vaccine by 2 years after diagnosis [103].

Meningococcal vaccination rates among college and university students are also generally low [22,24,31,105]; in certain countries, such as the United States, variability in college/university vaccination requirements [82] may be a contributing factor to vaccination completion rates. MenACWY vaccination is a routine recommendation for US college students [69]; however, only an estimated 53% of colleges/universities require any meningococcal immunization [82]. Among those that require meningococcal vaccination, a higher percentage requires MenACWY vaccination for matriculating students than MenB vaccination (52% vs <1%) [82], which may partly explain the low MenB vaccination completion rates [31]. In the United Kingdom, where MenACWY vaccination is recommended for university students [62], a cross-sectional online survey showed that uptake of MenACWY vaccination was 68% among 401 first-year undergraduate students 18–25 years of age at the University of Liverpool [105]. In South Australia, uptake of a MenB vaccine for 16-year-olds was 77% for 1 dose in the funded program [106]. Although not included in this review, available data suggest that meningococcal vaccination rates among healthcare workers are also poor; for example, vaccine uptake rates among domestic healthcare workers at the Hajj, where vaccination is considered mandatory, have been suboptimal [99,107,108].

Healthcare practitioners can play a substantial role in promoting vaccine knowledge and immunization compliance among their patients, but awareness of vaccination recommendations is lacking [109]. Although MenC vaccination was universally recommended for individuals 12 months to 24 years of age in France, a 2016 survey of general practitioners reported that <52% routinely recommended the MenC vaccine to patients in this age group [110]. Additional barriers to vaccination reported by the study included parents’ lack of awareness of the MenC vaccine, underestimation of the risk of contracting the disease and its seriousness, and concerns about the efficacy and unintended effects of vaccination [110]. These studies suggest that knowledge surrounding meningococcal vaccines is lacking among healthcare providers and parents, which may negatively affect vaccination rates.

5. Discussion

Substantial differences in meningococcal vaccination recommendations for increased-risk groups exist among the countries included in this review. Some countries, such as Australia, Israel, New Zealand, the United Kingdom, and the United States, have more extensive recommendations for these groups; others, such as Brazil, Italy, the Netherlands, Portugal, Spain, and Turkey, have more limited recommendations, although such gaps may be reflective of the availability of predominantly English language publications for inclusion in our review (Table 2).

Several inconsistencies exist in vaccine recommendations among countries as well as in implementation of approved vaccines within countries. In general, recommendations for MenB vaccinations are often lacking compared with those for MenACWY or MenC vaccination (Table 2), despite the fact that serogroup B is responsible for the majority of IMD in the regions reviewed [3]. Some countries, such as the Netherlands, Brazil, and Turkey, only recommend MenACWY or MenC vaccination but not MenB across all risk groups (Table 2). These disparities may be partly explained by the fact that MenC and MenACWY vaccines have been available since 2000 and 2005, respectively, whereas MenB vaccines have only been available since 2013 and at a higher cost [32,111]. In addition, robust surveillance of meningococcal disease is necessary for adaptation of informed immunization strategies. A lack of routine surveillance in some countries may lead to an underestimation of the proportion of serogroup B cases, resulting in lack of understanding of the potential need for MenB vaccination [112]. As of 2022, the World Health Organization (WHO) did not recommend any MenB vaccines for routine immunization, which could impact some countries’ decisions about which vaccines to prioritize [112]. Omission of MenB vaccines from immunization programs may occur in the context of recommendations from national scientific and medical groups. In Brazil, MenB vaccine is not included in the national immunization program despite the availability of privately funded MenB vaccines and recommendations for immunization of children and adolescents by the Brazilian Society of Immunizations and the Brazilian Society of Pediatrics [113].

College and university students and Indigenous populations remain at high risk of IMD [20,22,31,54]; however, vaccination recommendations for these groups are sparse. Of the 14 countries reviewed, several including Australia, Germany, Ireland, New Zealand, the United Kingdom, and the United States recommend MenACWY vaccinations for college and university students (Table 2). By contrast, routine MenB vaccine recommendations in college/university students are almost uniformly lacking in all countries reviewed except Australia and New Zealand [40,54,78]. MenB vaccination programs in adolescents and young adults are beginning to gain traction in Italy [51], New Zealand [54], and Australia [40], possibly leading to future changes in risk among university students in these regions. Regarding Indigenous populations, vaccine recommendations may depend on specific populations in a given country and whether these groups are at heightened risk of IMD. For example, Australia recommends and provides funding for specific higher-risk age groups for MenB vaccine for Aboriginal and Torres Strait Islander individuals, as they remain at higher risk of IMD compared with non-Indigenous populations [20,41,114]. In contrast, although Indigenous populations in Alaska and northern Canada have a greater incidence of IMD compared with non-Indigenous populations [115], there are no specific meningococcal vaccine recommendations for these groups [68,116]. Thus, vaccine recommendations in these groups are in urgent need of an update to address their elevated IMD risk.

Given the rapid onset and progression of disease after exposure to N meningitidis [1], revaccination may be required to maintain protective levels of circulating antibodies [117]. Recommendations with respect to revaccination requirements or booster doses also differ among countries. For example, entry requirements for Saudi Arabia require MenACWY polysaccharide or conjugate vaccination within 3 or 5 years of arrival, respectively [100], indicating visitors must be routinely revaccinated; however, among the countries reviewed, only Australia, Ireland, and the United States recommend booster doses of MenACWY in travelers if the risk is ongoing [40,47,68]. In general, Brazil, Ireland, New Zealand, and the United States recommend booster doses of MenACWY in patients at increased risk every 5 years [1,42,47,54], and New Zealand and the United States recommend booster doses of MenB every 5 and 2–3 years, respectively [1,42,54].

Data suggest that vaccine implementation and completion rates among increased-risk groups are suboptimal, partly because of a lack of knowledge of healthcare providers and parents [73,99,101,107–110]. As one example, a cross-sectional survey of healthcare providers in Italy found that only about a third of respondents had good knowledge of meningococcal disease incidence and mortality rates, common disease-causing serogroups, and underlying conditions conferring increased risk of severe complications from IMD [73]. In the United States, many providers are unaware of specific recommendations for each available meningococcal vaccine and have differing interpretations of the meaning of these recommendations [118]. As such, efforts are needed to educate healthcare providers and the general population on the risks of IMD as well as available vaccines and country-specific guidelines. Additionally, there are notable disparities regarding recommendations for MenACWY and MenB vaccines, with the former being recommended more frequently than the latter in some countries reviewed (Table 2). New combination strategies currently in development, such as pentavalent MenABCWY vaccines (NCT03135834), may help overcome these differences by simplifying vaccination schedules and potentially improving completion rates [119], including those of higher-risk groups, as a result.

6. Conclusion

Overall, there is a pronounced need to update existing meningococcal vaccination recommendations for increased-risk groups to better protect these vulnerable populations from IMD. Such recommendations should be expanded to cover all groups at increased risk and to consider the specific serogroup distribution and risk factors applicable to each country’s epidemiological landscape. In addition, consideration of strategies to improve immunization uptake and introduction of booster dosing may be necessary.

7. Expert opinion

Across all countries included in this review, some disparities were apparent in the specific populations defined as at risk or at increased risk, whether specific meningococcal vaccine recommendations or requirements were in place regarding those populations, and which meningococcal vaccines were recommended (e.g., MenB vs MenACWY vaccines). As described above, recommendations for booster doses also differ across countries. Although it is understandable that different countries have recommendations and requirements unique to their epidemiological landscape, it is important to consider that there are five predominant disease-causing meningococcal serogroups (ABCWY), and the individual prevalence and predominance of these may vary over time in each country [5]. Thus, protection against all five serogroups is essential to prevent or curtail disease emergence.

Of particular concern is that not all countries recommend vaccination to protect against the most predominant disease-causing meningococcal serogroups among the most vulnerable populations within those countries. For example, although a national health database review in France revealed that autoimmune disorders, hemophilia, and severe chronic respiratory disorders were strongly associated with severe complications of IMD, no specific guidelines exist for vaccination among individuals with these conditions [30]. In the United States, MenACWY but not MenB vaccination is routinely recommended among all students attending college or university [1,70], despite MenB being the most common disease-causing serogroup among students [31] and causing all US college outbreaks from 2011 to 2019 [120]. If there existed a clearer international standard for how to develop recommendations based on populations most at risk and serogroups most likely to cause disease, the United States would potentially have recommendations more similar to Australia, which recommends routine vaccination against MenB disease for all university students living in student residences [40].

Several barriers exist that have prevented standardization of meningococcal vaccine recommendations to this point. Differences among countries in vaccine licensure and availability, robust surveillance data including for at-risk and increased-risk populations, knowledge and awareness of meningococcal disease and prevention, prioritization, and cost-effectiveness of meningococcal vaccines may have contributed to the lack of standardization. Additionally, the more recent introduction of MenB vaccines and their requirement for multiple doses [16,17] may have impacted incorporation into the recommendations of some countries. Issues with vaccine uptake and adherence with multiple primary schedule dosing and revaccination/booster schedules also present barriers to successful implementation of recommendations. As described above, novel pentavalent MenABCWY vaccines may help overcome some of these barriers to standardization and uptake of recommendations; these newer vaccines can simplify vaccination schedules while providing protection against all five predominant serogroups with only two doses, and thus potentially improve completion rates [119].

To improve standardization and implementation of vaccine recommendations across countries, wider licensing and availability of vaccines are needed, for greater agreement regarding risk factors, for coordination of recommendations, and for effective strategies to enhance vaccine uptake. In 2020, the WHO launched a global road map with the aim of defeating meningitis by 2030 [121]. Key goals of the road map include (1) eliminating bacterial meningitis epidemics, (2) reducing vaccine-preventable bacterial meningitis cases by 50% and deaths by 70%, and (3) reducing disability and improving quality of life among survivors. Establishment of global policy for use of MenB vaccines and multivalent meningococcal conjugate vaccines was identified as an element of the overarching goal of developing evidence-based policy on vaccination strategies that provide optimal individual protection and, where possible, herd protection (with multivalent vaccines) against the main causative pathogens of bacterial meningitis. Implementation strategies will involve country planning that considers regional specificities, with goal targets prioritized and adapted according to regional and local contexts. Specific implementation frameworks will be developed for each region to ensure that regional needs are met and that regional commitment is promoted. These efforts may potentially improve standardization of meningococcal vaccination recommendations across countries. Additional supernational organizations, such as the Pan American Health Organization (PAHO; in coordination with the WHO) and the North Atlantic Treaty Organization (NATO; for covered military) may also contribute toward improving the standardization of meningococcal vaccine recommendations [46,122].

Article highlights

• Meningococcal vaccination recommendations for groups at an increased risk of invasive meningococcal disease vary considerably worldwide.

• Notable disparities exist between MenB and MenACWY or MenC vaccine recommendations, and country-specific recommendations do not always correspond with the predominant serogroups responsible for disease.

• Updating and standardizing existing recommendations for vaccination against the five major disease-causing serogroups among individuals at increased risk is critical to improve protection of vulnerable populations from meningococcal disease.

Declaration of Interest

Cynthia Burman was an employee of Pfizer at the time of manuscript development and may hold stock or stock options. Jamie Findlow is an employee of Pfizer Ltd and may hold stock or stock options. Helen Marshall is an investigator on vaccine trials sponsored by industry. Her institution has received funding for investigator led research from GSK, Pfizer, and Sanofi Pasteur. She does not receive any personal payments from Industry. Marco Safadi has received grants to support research projects and consultancy fees from GSK, Pfizer Inc, and Sanofi Pasteur.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contribution statement

All authors have substantially contributed to the conception and design of the review article and interpreting the relevant literature; and all authors have been involved in writing the review article or revising it for intellectual content.

Acknowledgments

Editorial/medical writing support was provided by Srividya Ramachandran, PhD, and Kate Russin, PhD (ICON, Blue Bell, PA, USA) and was funded by Pfizer Inc. Helen Marshall acknowledges NHMRC support - Practitioner Fellowship APP1155066.7References

Additional information

Funding

This manuscript was funded by Pfizer Inc.