Infect Dis Ther (2018) 7:219–234 https://doi.org/10.1007/s40121-018-0196-z REVIEW A Review of Meningococcal Disease and Vaccination Recommendations for Travelers . . . . Lidia C. Serra Laura J. York Amgad Gamil Paul Balmer Chris Webber Received: December 6, 2017 / Published online: March 17, 2018 The Author(s) 2018 international travelers. As vaccination is the ABSTRACT best approach for preventing IMD among trav- elers, currently available meningococcal vac- Abstract: International travel has been steadily cines and corresponding country-speciﬁc increasing since the middle of the twentieth national meningococcal vaccination recom- century, including travel to regions with high mendations, where available, will be summa- levels of endemic meningococcal disease and rized by age and type of vaccine recommended. areas with sporadic or sustained meningococcal The use of the quadrivalent meningococcal outbreaks. Although invasive meningococcal vaccines, speciﬁcally the tetanus toxoid conju- disease (IMD) is relatively rare in travelers since gate vaccine (including MenACWY-TT; Nimen- the advent of quadrivalent meningococcal vac- rix ), as a protective measure against IMD in cines, it remains a serious concern because of its travelers will be emphasized. rapid progression, poor prognosis and out- Funding: Pﬁzer Inc. comes, associated treatment delays, and the potential to precipitate outbreaks. Moreover, Keywords: Adults; Invasive meningococcal fatality occurs in up to 22% of those infected. disease; Meningococcal vaccines; Travelers This review will focus on IMD in travelers, with an emphasis on IMD epidemiology and the geographic regions of potential concern for INTRODUCTION Enhanced content To view enhanced content for this article go to https://doi.org/10.6084/m9.ﬁgshare. Rates of global travel have been increasing since the 1950s. In 2000, 674 million individuals traveled internationally, with the number of L. C. Serra (&) L. J. York P. Balmer travelers in 2010 and 2015 increasing even fur- Pﬁzer Vaccines, Medical Development, Scientiﬁc ther to 950 and 1186 million, respectively . and Clinical Affairs, Collegeville, PA, USA Although invasive meningococcal disease e-mail: Lidia.Olveira@pﬁzer.com (IMD) is relatively rare in travelers, it remains a A. Gamil serious concern because of its rapid clinical Pﬁzer Vaccines, Global Medical Development, course, short time frame for diagnosis, difﬁculty Scientiﬁc and Clinical Affairs, Dubai, United Arab in obtaining timely antibiotic treatment, Emirates potentially poor outcomes, and the ability of C. Webber infection to spread rapidly among a population Pﬁzer Vaccines, Clinical Research and Development, [2, 3]. Even with appropriate medical care, the Pearl River, NY, USA 220 Infect Dis Ther (2018) 7:219–234 case-fatality rate remains high and can reach two of the greatest risks for contracting IMD, 22% , with approximately 20% of survivors there are other regions of particular concern to experiencing debilitating long-term sequelae the global traveler; these are discussed in more that include neurologic impairment, hearing detail below. Importantly, the prevalence of loss, chronic pain, amputation, and skin scar- disease-causing serogroups can vary widely by ring [5–7]. region and year, so, from a preventative stand- Although at least 12 serogroups of N. menin- point, it is important to understand the pre- gitidis have been reported, most cases of IMD are dominant disease-causing serogroups at the caused by serogroups A, B, C, W, X, and Y . time of travel . For instance, the recent Currently, vaccination is the recommended emergence of serogroup W in a number of approach for preventing IMD, with available countries, coupled with its often atypical pre- vaccines targeting single serogroups or a combi- sentation, has made this a serious concern for nation of multiple serogroups; together, international travelers; therefore, more detail these vaccines can provide protection against 5 regarding the emergence of serogroup W by of the 6 major disease-causing meningococcal region is also discussed brieﬂy in the following serogroups (i.e., A, B, C, W, and Y) . Speciﬁcally, sections. various formulations of conjugated quadrivalent ACWY vaccines are commonly used to target The African Meningitis Belt serogroups A, C, W, and, Y and recombinant protein vaccines target serogroup B. Although endemic in various regions across the This review will focus on IMD in interna- globe, the IMD burden is greatest in the 22 tional travelers, with an emphasis on the geo- countries comprising the ‘‘meningitis belt’’ of graphic regions of potential concern and the sub-Saharan Africa, which stretches from Sene- importance of vaccination with quadrivalent gal in the west to Ethiopia in the east . In conjugate vaccines as a preventative strategy for this region, IMD is hyperendemic, with the IMD. Country-speciﬁc national vaccination number of cases approaching 1000 per 100,000 recommendations based on the traveler’s population during the dry season. Epidemics in country of origin will be discussed. Emphasis this region can occur annually and are charac- will be given to the quadrivalent vaccines, terized by a broad distribution across age including the recently approved tetanus toxoid groups. Outside of epidemic situations, the conjugate vaccine (MenACWY-TT, Nimenrix ; highest incidence of IMD in this region typi- Pﬁzer, Sandwich, UK), which is indicated for use cally occurs in young children . in individuals C 6 weeks of age . This review Between 1993 and 2012, the majority of IMD is based on previously conducted studies and in the meningitis belt was due to serogroup A, information obtained from online databases which was the etiologic agent identiﬁed in 80% and did not recruit human participants or uti- of the epidemics with approximately 1 million lize animals. cases and 100,000 deaths . In response to the medical need, a monovalent meningococcal A conjugate vaccine, MenAfriVac (PsA-TT; GLOBAL EPIDEMIOLOGY Serum Institute of India, Pune, India) was OF INVASIVE MENINGOCOCCAL developed and prequaliﬁed for use in children DISEASE IN TRAVELERS and adults aged 1–29 years [14, 15]. In 2010, MenAfriVac was used in prophylactic vaccina- Regional IMD incidence at the traveler’s desti- tion campaigns in three African countries nation is an important consideration when (Burkina Faso, Mali, and Niger) , and by evaluating the overall risk of contracting IMD 2014, no cases caused by serogroup A were and should be taken into account when con- identiﬁed in these countries . In the face of sidering preventative strategies. Although travel declining serogroup A disease, serogroup W to the African meningitis belt and the annual emerged as a predominant pathogen and, by Hajj pilgrimage in Saudi Arabia currently pose Infect Dis Ther (2018) 7:219–234 221 2012, was responsible for 55% of conﬁrmed were reported within the country, and, of these, IMD in the region . Cases of serogroup C 42% occurred in travelers and 58% occurred in were also increasing in the region. From the local population . The majority of these December 2016 to June 2017, Nigeria experi- cases were identiﬁed in children, with 59 and enced a large outbreak of IMD, and, of the 39% occurring in children \ 5 and \ 2 years of 433 conﬁrmed cases, 358 (82.7%) were age, respectively . Together, this suggests that attributable to serogroup C . This outbreak the Hajj pilgrimages of 2000 and 2001 featured may represent the largest global outbreak of an epidemiologic shift from serogroup A to W. serogroup C to date, and a number of factors Information on case-fatality rates among pil- likely contributed to the large number of cases, grims, many of whom are diagnosed upon including procedural and resource allocation returning to their native countries, is not con- inadequacies pertaining to specimen collection sistently reported; however, data available from and identiﬁcation, and delayed access to vac- the 2000 Hajj epidemic suggest a high case- cines . fatality rate associated with that outbreak, with reported rates ranging from 21% among pilgrims from Oman to 60% among pilgrims hospitalized Hajj in Mecca . A number of travel-related meningococcal out- Other Regions breaks have been reported in the literature, and, of these, the largest and the most notable are those associated with the annual Hajj pilgrim- Transient and sporadic increases in IMD have age in Saudi Arabia. The Hajj is the largest also been noted globally in countries outside of annual mass gathering on Earth and attracts the African meningitis belt and Saudi Arabia. more than 2 million pilgrims annually . Hajj Therefore, travelers should be aware of the local pilgrims are geographically diverse, representing IMD epidemiology at any travel destination [ 180 different countries, with many elderly where increases in IMD cases have been docu- participants who commonly have underlying mented. Some of these regions are discussed medical conditions that would predispose them brieﬂy below. to IMD [20–22]. During the 1987 Hajj, an out- break of serogroup A resulted in an incidence Europe rate of 640 cases per 100,000 pilgrims. During Although the IMD incidence in Europe is gen- the 2000 and 2001 Hajj, the majority of cases of erally low, increases have been observed over IMD were not attributable to serogroup A, as the past decade. In 2015, the incidence of IMD expected, but to a hypervirulent strain of in the European Union was 0.6 cases per serogroup W, which before that time was of 100,000 population, slightly down from the 0.7 little epidemiologic concern . cases per 100,000 population in 2010. Countries In 2000, a total of 253 laboratory-conﬁrmed with the highest number of cases per 100,000 IMD cases occurred in Mecca, Medina, and Jed- population in 2015 were Lithuania (1.9), Ire- dah, and, among these, 56% of cases occurred in land (1.5), the United Kingdom (1.4), and Malta travelers . Of the 161 cases for which the (1.2) . Despite low IMD incidence overall, serogroup was identiﬁed, 58% were serogroup W certain serogroups are emerging as a concern in and 37% were serogroup A . This outbreak localized areas. resulted in 70 deaths (case-fatality rate, 28%) and For example, since 2009, a clonal complex the subsequent spread of serogroup W disease to variant of serogroup W (cc11) has been causing at least 16 countries from the pilgrims returning increases in IMD in the United Kingdom . from the Hajj [21, 23]. A retrospective study During the 2013–2014 epidemiologic year, conducted in Saudi Arabia between 1999 and serogroup W accounted for 15% of IMD com- 2002 (encompassing the 2000 and 2001 epi- pared with 1.8% in 2008–2009. This increase demic years) identiﬁed 729 cases of IMD that was due to the expansion of a single strain that 222 Infect Dis Ther (2018) 7:219–234 primarily affected adults C 45 years of age in Middle East In the Middle East, IMD incidence rates were 2009–2010; however, by 2011–2012, cases were distributed across all age groups. highest in Sudan (2006) and Yemen (2005) with 13.26 and 4.74 cases per 100,000 population, Serogroup C also emerged as a concern in Italy in 2015 and 2016, when 43 cases were respectively . In countries that reported reported in Tuscany within the span of outbreaks, most were caused by serogroups A or 13 months; this was a substantial increase W, with the exception of Israel, where outbreaks compared with the 12 and 16 cases reported in were due to serogroups B or C . Recent 2013 and 2014, respectively . Ten of the 43 surveillance data from Kuwait cited a mean cases in Tuscany were fatal, and those infected incidence rate of 0.5 per 100,000 population; the dominant serogroups were W and B, accounting ranged in age from 9 to 82 years. The molecular classiﬁcation of the isolates obtained from these for 80 cases (32% each). Serogroup B accounted for 34% of all cases in children B 14 years, and patients is ongoing . serogroup A accounted for 40% of all adult cases. Three outbreaks in Kuwait in 1987, 1989, and Central and South America 2002 were caused by serogroups A, W, and B, In Central and South America, the annual respectively . incidence of IMD varies considerably, ranging from \ 0.1 cases per 100,000 population in Bolivia, Cuba, Paraguay, and Peru to almost 2 Australia cases per 100,000 population in Brazil. How- In Australia in 2013, the incidence of IMD was relatively low at 0.6 cases per 100,000 popula- ever, it should be noted that surveillance and reporting are not uniform across countries, tion, but beginning in 2014, the number of cases began to increase, and, by 2016, an inci- which may account for the wide range in inci- dence . dence rate of 1.1 cases per 100,00 population Serogroups B, C, Y, and W are all known to was reported . In 2015, serogroup B was cause disease in this region. Although serogroups responsible for 64% of IMD cases, decreasing B and C are responsible for most cases of IMD, from previous years when serogroup B accoun- serogroup W is emerging as a cause of outbreaks ted for 75–88% of cases . The proportion of in several countries [11, 29]. cases due to serogroups W and Y have been rising in recent years, reaching 21% and 13%, The prevalence of disease-causing serogroups varies widely by region and by year . respectively, in 2015 . Although IMD has been decreasing in New Zealand since 2002, the Between 2006 and 2011, serogroups B and C predominated across Central America, the Car- most recent surveillance data in 2013 reports an incidence rate of 1.5 cases per 100,000 popula- ibbean, and Mexico; however, in 2012, most IMD cases were caused by serogroups B and Y tion, which, although still relatively high, is the . In the Andean region (Bolivia, Colombia, lowest annual IMD incidence rate in the last Ecuador, and Venezuela), the proportions of 20 years . The average annual incidence rate serogroup B and C cases increased between 2006 in New Zealand between 2009 and 2012 was 2.5 and 2012 as the relative proportion of serogroup cases per 100,000 population. Y declined . In Brazil between 2006 and 2012, serogroup C caused most cases . In the North America Southern Cone (Argentina, Chile, Paraguay, and In North America, Canada had a peak in IMD Uruguay), serogroup B caused the majority of incidence in 2001 with 1.18 cases per 100,000 IMD in 2006; however, cases caused by population, but, thereafter, incidence rates have serogroup W increased over time so that, by leveled off and, from 2002 to 2011, IMD inci- 2012, it was the predominant serogroup leading dence ranged between 0.45 and 0.75 cases per to IMD . 100,000 population . In the United States, the incidence of IMD decreased from 0.61 to 0.18 cases per 100,000 population over the Infect Dis Ther (2018) 7:219–234 223 10-year period from 2003 to 2013 . In 2016, In Australia, the percentage of meningitis the IMD incidence rate was 0.12 cases per cases due to serogroup W increased from 4 to 100,000 population, with serogroup B being the 30% during the 2-year interval between 2013 most predominant (0.04 cases per 100,000 and 2015 . Of the 22 cases that were repor- population) . ted, 9 cases occurred in adults[ 70 years of age, and the majority of isolates represented a single strain (ST11). An increased prevalence of IMD Emergence of Serogroup W: a Concern due to serogroup W has been noted in Canada for International Travelers between 2009 and 2016, with 18.8% of all cases attributable to serogroup W in 2016; the aver- Although vaccination against serogroup W is age percentage of serogroup W cases over the not broadly recommended for travelers outside time period was 7.1% . In the United States, of Saudi Arabia and the African meningitis belt where an outbreak of serogroup W in , serogroup W, as noted above, is emerging 2008–2009 was linked to 14 cases of IMD in as a global concern. Before 2000, serogroup W Florida, 4 of these were fatal . cases were sporadic ; however, increasing Clinically, serogroup W has not only been incidence rates since the 2000 Hajj have been associated with atypical gastrointestinal presen- observed in a number of countries, including tation but subtle differences in sequelae that dif- England , South America [40, 41], Africa ferentiate it from other IMD-causing serogroups [42, 43], Australia , Canada [45, 46], and the have also been observed, although data are cur- United States . Therefore, vaccination to rently limited . These atypical sequelae asso- prevent serogroup W infection should be an ciated with serogroup W disease include septic important consideration for international arthritis, pericarditis, bacteremia and sepsis, travelers. neonatal sepsis, chronic meningococcemia, In England, the number of serogroup W pneumonia, and peritonitis. Serogroup W has also cases began to increase in 2009 and almost been associated with a high case-fatality rate doubled in a single epidemiologic year, as evi- (16.3%) and infection of older adults (mean age, denced by 95 cases in 2013–2014 compared 53 years) at a higher rate . with 176 cases in 2014–2015 . More recently, serogroup W has been responsible for Other Considerations for Travelers several IMD cases in teenagers, which have been characterized by an atypical gastrointestinal presentation that included nausea, vomiting, Although regional IMD incidence is an impor- and diarrhea . Among 15 cases diagnosed in tant consideration when determining overall teenagers aged 15–19 years between July 2015 risk for international travelers, travelers should and January 2016, 7 had mainly gastrointestinal also consider a number of additional factors. For symptoms, and of these, 5 died within 24 h of example, the traveler’s occupation, length of hospitalization . This marked and stay, and activities undertaken during travel, notable increase in serogroup W cases in Eng- particularly those that involve intensive inter- land was due to a single strain (ST11) that was action with indigenous populations and large also responsible for an increased IMD incidence groups, are also likely to inﬂuence the traveler’s in South America [40, 41]. potential for contracting or spreading IMD. Serogroup W has also been implicated in Some travelers may also be at higher risk for large meningococcal epidemics in Africa IMD due to certain medical conditions, such as [42, 43]. In one epidemic in The Gambia in 2012, inherited deﬁciencies in the complement path- an incidence rate of 1470 cases per 100,000 way, asplenia, previous viral infections, and population (all serogroup W) was observed in chronic underlying illness; smoking and crow- children\ 12 months of age, and a 13% fatality ded living conditions also pose a risk for IMD rate was reported in this age group . . Therefore, in addition to regional IMD epidemiology at the traveler’s destination, these 224 Infect Dis Ther (2018) 7:219–234 items should be considered when evaluating the 4CMenB; GlaxoSmithKline Vaccines, Siena, need for preventative vaccination strategies. Italy) , which includes three recombinant bacterial proteins (including subfamily B FHbp) and an outer membrane vesicle containing PorA AVAILABLE MENINGOCOCCAL , was ﬁrst licensed in Europe in 2013 and is VACCINES now licensed in several geographic regions [59, 60]. AND RECOMMENDATIONS FOR TRAVELERS National Meningococcal Vaccination Recommendations for Travelers Quadrivalent Polysaccharide Conjugate from Their Country of Origin Vaccines Vaccination is the best method for preventing Currently, three different quadrivalent meningococcal infection . Currently, six meningococcal vaccines—each containing cap- countries including Australia , Bahrain , sular polysaccharides conjugated to a carrier Canada , Saudi Arabia , the United protein—are available in various regions for the Kingdom , and the United States  have prevention of IMD caused by serogroups A, C, national recommendations for meningococcal W, and Y (Table 1). MenACWY-DT (Men- vaccination in travelers. Although there is some actra , conjugated to diphtheria toxin; Sanoﬁ variability in country-speciﬁc guidance, speciﬁ- Pasteur, Swiftwater, PA, USA) and MenACWY- cally pertaining to the age of the vaccinees and CRM (Menveo , conjugated to C reactive pro- the type of conjugate vaccine that is recom- tein; Novartis Vaccines and Diagnostics, Sovi- mended (Table 2), there is general consistency cille, Italy) were initially licensed in the United across these guidelines regarding vaccination States in 2005 and 2010, respectively . The for travelers entering high-risk areas. For third quadrivalent vaccine, MenACWY-TT (Ni- instance, all six of these countries recommend menrix , conjugated to tetanus toxoid; Pﬁzer), vaccination with a quadrivalent conjugate vac- was ﬁrst licensed in Europe in 2010 . All cine for travelers entering areas associated with vaccines have been approved for use in multiple an increased incidence of endemic or epidemic countries and are well tolerated and immuno- meningococcal disease that is caused by genic . serogroups contained in the vaccine. Particular emphasis is given to vaccination for those Recombinant Protein Vaccines traveling to the African meningitis belt and to Saudi Arabia for the Hajj and/or Umrah Unlike serogroups A, C, W, and Y, the serogroup [61–64, 66, 67]. The United Kingdom also rec- B polysaccharide is structurally similar to mole- ommends vaccination for backpackers who are cules found on human neuronal cells, and thus traveling in the ‘‘rough’’ and for those who are can be considered a human self-antigen . working with, or spending an extended period Therefore, serogroup B vaccine development has with, indigenous populations . In addition focused on targeting surface-exposed proteins. to quadrivalent ACWY vaccination, the Public Using this approach, two recombinant-protein Health Agency of Canada recommends vac- vaccines are currently available for the preven- cination with a serogroup B vaccine for those tion of IMD due to serogroup B. MenB-FHbp entering areas with an increased incidence of (Trumenba , bivalent rLP2086; Pﬁzer, Philadel- serogroup B infection . phia, PA) , targeting both subfamily A and There are a number of resources available subfamily B variants of the conserved factor H online for travelers documenting global and binding protein (FHbp), was ﬁrst licensed in the country-speciﬁc meningococcal disease epi- United States in 2014 , and, more recently, in demiology and vaccination recommendations Europe , Canada , and Australia . A (Table 3). For example, the World Health second serogroup B vaccine, MenB-4C (Bexsero , Infect Dis Ther (2018) 7:219–234 225 Table 1 Available MenACWY conjugate vaccines Quadrivalent conjugate vaccines MenACWY-TT MenACWY-CRM MenACWY-DT Name Nimenrix Menveo Menactra Company Pﬁzer GSK Sanoﬁ Pasteur Availability European Union International European Union  United States International United States International  [78, 79]  [82, 83]   Age indication, C 6 weeks C 12 months C 2 years C 2 months C 2 months C 9 months C 2 years lower limit a b Age indication, None 55 years None 55 years 55 years 55 years 55 years upper limit Dose schedule C 6 to 12 weeks, 1 dose 1 ? 1 C 2to C 2 to 6 months, C 9to 1 dose 2 ? 1 6 months, 3 ? 1 23 months, 3 ? 1 2 doses C 12 months, 1 C 7 to 23 months, dose C 7to 2 doses C 2to 23 months, 2 e 55 years, 1 C 2 years, 1 dose doses dose C 2 years, 1 C 15 to dose 55 years, booster dose Safety Well tolerated Well tolerated Well tolerated Well tolerated Well tolerated Well tolerated Well tolerated 226 Infect Dis Ther (2018) 7:219–234 Table 1 continued Quadrivalent conjugate vaccines MenACWY-TT MenACWY-CRM MenACWY-DT Co- 6 weeks to 1to \ 2 years: Monovalent and combined DTaP-IPV- DTaP, TT, Hib, MMRV, DT, Typhim administration \ 1 year: HAV, HBV, HAV and HBV, yellow Hib, PCV7, polio, HAV, MMR, V, with other MMR, MMTV, fever, typhoid fever, rotavirus, HBV, PCV7, PCV7, DT, DTaP-HBV-IPV/ h,f vaccines PCV10, seasonal Japanese encephalitis, and MMRV, PCV13, Typhim, Hib, PCV10 inﬂuenza rabies HAV/HBV rotavirus, HAV, 1to \ 2 years: MMRV Daptacel 2nd year: DTaP, HAV, HBV, polio, HBV, Hib AU: DT, MMR, MMRV, Typhim seasonal inﬂuenza, PCV10 2nd year: DTaP, polio, HBV, Hib, PCV13 CRM cross-reactive material, DT diphtheria and tetanus toxoid, DTaP diphtheria and tetanus toxoid with acellular pertussis, HAV hepatitis A virus, HBV hepatitis B vaccine, Hib Haemophilus inﬂuenzae type b, MMR measles, mumps, and rubella, MMRV measles, mumps, rubella, and varicella, PCV7 7-valent pneumococcal conjugate vaccine, PCV10 10-valent pneumococcal conjugate vaccine, PCV13 13-valent pneumococcal conjugate vaccine, TT tetanus toxoid, Typhim typhoid Vi polysaccharide 16 vaccine, V varicella The upper age limit for vaccination in Canada and Australia is 55 years The upper age limit for vaccination in Canada is 55 years In Canada and Australia, booster doses may be administered to those previously vaccinated with an unconjugated polysaccharide meningococcal vaccine A booster dose may be recommended in some individuals In Australia, vaccine may be administered until 55 years of age Concomitant use in clinical vaccines studies Infect Dis Ther (2018) 7:219–234 227 Table 2 Country-speciﬁc meningococcal vaccination rec- Table 2 continued ommendations for travelers Age/population Recommended meningococcal Age/population Recommended meningococcal group vaccines group vaccines 2–55 years MenACWY-CRM or Australia  MenACWY-D 2–6 months MenACWY-CRM C 56 years MenACWY-CRM or 7–11 months MenACWY-CRM (previously MenACWY-D vaccinated) 12–23 months MenACWY-CRM or MenACWY-TT C 56 years MPSV4 (unvaccinated) 2–6 years MenACWY-DT MenACWY- CRM, or MenACWY-TT CRM cross-reactive material, DT diphtheria toxin, TT tetanus toxoid C 7 years MenACWY-DT MenACWY- a Quadrivalent conjugate vaccine is preferred; however, CRM, or MenACWY-TT the quadrivalent polysaccharide vaccine is a suitable alter- Bahrain  native for travelers aged C 7 years when the need for b repeat doses is not anticipated C 2 years MenACWY quadrivalent A single-dose quadrivalent conjugate meningococcal conjugate vaccine vaccine is recommended to citizens at 2 years of age and is recommended for Hajj pilgrims and for travelers to certain Canada  countries; 1 - 2 doses are recommended for individuals C 2 months MenACWY-CRM; 4CMenB with certain hemoglobinopathies, congenital or acquired Saudi Arabia  asplenia, presplenectomy, terminal complement deﬁciency, post bone marrow transplant, or certain cancers after the [ 2 years MenACWY quadrivalent completion of treatment conjugate or polysaccharide For those not previously vaccinated with MenACWY- vaccine CRM or 4CMenB Vaccination with quadrivalent vaccine is required for all United Kingdom  citizens and residents of Medina and Mecca who have not Birth MenACWY-CRM been vaccinated during the past 3 years with a polysac- charide vaccine or during the past 5 years with a conjugate to \ 9 months vaccine; all citizens and residents undertaking the Hajj 9to \ 12 months MenACWY-CRM or who have not been vaccinated during the past 3 years with MenACWY-TT a polysaccharide vaccine or during the past 5 years with a conjugate vaccine; all Hajj workers, including individuals 12 months–2 years MenACWY-TT working at entry points or in direct contact with pilgrims, 2–4 years MenACWY-CRM or who have not been vaccinated in the past 3 years with a MenACWY-TT polysaccharide vaccine or in the past 5 years with a con- jugate vaccine. Visitors from all countries arriving for the C 5 years MenACWY-CRM or purpose of Umrah, pilgrimage (Hajj), or seasonal work MenACWY-TT preferred; must have proof of vaccination C 10 days and \ 3 years MenACWY polysaccharide (polysaccharide vaccine) or C 10 days and \ 5 years vaccine may be considered (conjugate vaccine) before date of entry to Saudi Arabia Even if vaccinated with Hib-MenCY-TT during infancy United States  or childhood 2 months MenACWY-CRM 7–23 months MenACWY-CRM or MenACWY-DT 228 Infect Dis Ther (2018) 7:219–234 Table 3 Links to information pertaining to current meningococcal disease epidemiology and travel-related vaccination recommendations Source Website World Health Organization http://www.who.int/csr/don/archive/disease/meningococcal_disease/en/ International Association for Medical https://www.iamat.org/elibrary/view/id/1359 Assistance to Travelers European Centre for Disease Prevention and https://ecdc.europa.eu/en/meningococcal-disease Control US Centers for Disease Control and https://www.cdc.gov/abcs/reports-ﬁndings/surv-reports.html Prevention New Zealand Ministry of Health https://surv.esr.cri.nz/surveillance/Meningococcal_disease.php Australian Ministry of Health http://www.health.gov.au/internet/main/publishing.nsf/content/cda- pubs-annlrpt-menganrep.htm Recommendations at the Traveler’s Organization maintains a database of meningococcal outbreaks and cases listed by the Destination for Those Entering High-Risk Areas, Primarily Saudi Arabia date of the most recent occurrence and the country of origin . Another useful resource for travelers is the World Immunization Since 2010, the Ministry of Health of Saudi Chart developed by the International Associa- Arabia and the Global Center for Mass Gather- tion for Medical Assistance to Travelers, which ing Medicine has recommended that a quadri- is continually updated and summarizes all glo- valent conjugate meningococcal vaccination be bal vaccination recommendations . administered to individuals 2–55 years of age In addition, a number of societies have made residing in Saudi Arabia, and in 2013, a routine similar recommendations for quadrivalent childhood vaccination program was imple- meningococcal vaccination for travelers enter- mented in that country . However, due to ing high-risk areas, with the African meningitis the high cost, quadrivalent conjugate vaccines belt and Saudi Arabia delineated as areas of were initially recommended but not mandatory potential concern. For example, the Malaysian for international pilgrims . Despite a lack of Society of Infectious Diseases and Chemother- mandatory recommendations, overall vaccine apy recommends vaccination with a conjugate coverage during the 2015 Hajj was high, with meningococcal vaccine for pilgrims attending 91% of all pilgrims having received a quadriva- Hajj or Umrah, all travelers to high-risk areas, lent vaccination, although vaccine coverage was and adults with medical conditions that put \ 70% in some countries . In 2017, the them at high risk for infection (e.g., those with Saudi Arabia Ministry of Health required complement disorders or functional or ana- quadrivalent meningococcal vaccination for all tomic asplenia) . Because numerous soci- Hajj and Umrah pilgrims and for local pilgrims eties put forth recommendations and there is and seasonal workers . no central repository for information, a sum- mary of recommendations from societies is Importance of Recommending Vaccines beyond the scope of the current review; how- that Protect Against Multiple ever, it is advisable for travelers to check all Meningococcal Serogroups recommendations in their country of origin when planning an itinerary. Considering the broad distribution of IMD serogroups worldwide and the presence and/or Infect Dis Ther (2018) 7:219–234 229 emergence of multiple serogroups within geo- 12 months to 55 years [72, 73]. MenACWY-TT is graphical regions, meningococcal vaccines that not currently licensed in the United States. protect against multiple serogroups provide the The immunogenicity and safety of best preventative option for travelers. Currently MenACWY-TT have been established in clinical available quadrivalent ACWY conjugate vac- studies in individuals across all ages compared cines would therefore not only confer protec- with other meningococcal vaccines, using an tion to those traveling globally but would also established correlate of protection . Among be expected to reduce the risk of transmission, toddlers, the percentage of subjects achieving thus reducing the spread of disease at home and seroprotection after 1 dose of MenACWY-TT abroad. However, as noted previously, multiple can reach 100% , but 2 doses may be formulations of quadrivalent ACWY polysac- required to achieve adequate protection in charide conjugate vaccines are currently avail- younger children . In adolescents and able in different regions around the globe. The adults, 80–97% of individuals achieve protec- availability, indication, dosing, co-administra- tive titers against the four serogroups in tion with other vaccines, and safety/immuno- MenACWY at 1 month post-vaccination after a genicity of the conjugate quadrivalent vaccines single dose . Persistence of antibody is set out in Table 1. The text below will sum- responses up to 5 years after administration of marize the clinical data for the most recently the MenACWY-TT primary series has also been approved vaccine, MenACWY-TT. demonstrated across age groups . It has also been demonstrated that MenACWY-TT can be given concomitantly with other commonly Summary of Clinical Datafor MenACWY-TT administered vaccines, including the hepatitis A and B vaccines, the mumps/measles/rubella As evident from the information presented vaccine, the 10-valent and 13-valent pneumo- above, it is imperative that national meningo- coccal conjugate vaccines, the diphtheria/te- coccal vaccination programs for travelers adapt tanus/acellular pertussis vaccine, and the to the variable nature of meningococcal disease combined diphtheria, tetanus, acellular pertus- at the traveler’s destination; however, it is sis/hepatitis B/inactivated polio virus/haemo- equally important that the recommending body philus inﬂuenzae type B vaccine. make informed decisions regarding which vac- MenACWY-TT is generally safe and well tol- cine to recommend when multiple formula- erated across age groups and has demonstrated tions are available. To help inform these an acceptable and consistent safety and reacto- decisions, a brief summary of data available for genicity proﬁle in a pooled clinical study popu- MenACWY-TT is described. lation that included 3079 toddlers (aged The quadrivalent conjugated MenACWY-TT 12–23 months), 1899 children (aged 2–10 years), is licensed in the European Union and 43 2317 adolescents (11–17 years old), 2326 adults additional countries, including Africa (18 (18–55 years old), and 274 older adults countries), Asia (7 countries), Eastern Europe (3 (C 56 years old) . Common local reactions countries), the Middle East (8 countries), North included pain, redness, and swelling at the America (2 countries), Oceania (2 countries), injection site, while common systemic events and South America (3 countries). In some included drowsiness, fatigue, fever, headache, countries, including Europe, a 2-dose infant irritability, and loss of appetite. Safety was also series of MenACWY-TT is indicated for infants demonstrated in 1052 infants receiving C 1 beginning at 6 and 12 weeks followed by a MenACWY-TT dose beginning at 6–12 weeks of booster dose, whereas a single dose is indicated age and in 1008 toddlers (aged 12–14 months) for children aged [ 12 months, adolescents, who received a booster dose . and adults . In Canada and Australia, MenACWY-TT is indicated for individuals aged 230 Infect Dis Ther (2018) 7:219–234 Compliance with Ethical Guidelines. This CONCLUSION review is based on previously conducted studies and information obtained from online data- Outside of Saudi Arabia, the decision of travelers bases and did not recruit human participants or to vaccinate against meningococcal disease rests utilize animals. on country-based recommendations and per- ceived risks. Recent changes in the global epi- Open Access. This article is distributed demiology of IMD, particularly a global increase under the terms of the Creative Commons in serogroup W, have raised concerns in several Attribution-NonCommercial 4.0 International countries worldwide and resulted in updated License (http://creativecommons.org/licenses/ meningococcal vaccination recommendations, by-nc/4.0/), which permits any noncommer- speciﬁcally the addition of conjugated cial use, distribution, and reproduction in any MenACWY vaccine to existing recommenda- medium, provided you give appropriate credit tions. A quadrivalent conjugate vaccine, such as to the original author(s) and the source, provide MenACWY-TT, can provide protection for trav- a link to the Creative Commons license, and elers, especially those traveling to areas where indicate if changes were made. the local meningococcal epidemiology involves multiple predominant serogroups or where the likelihood of epidemic outbreaks is high. REFERENCES ACKNOWLEDGEMENTS 1. 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