1 4.10 MENINGOCOCCAL DISEASE

2 4.10.1 Bacteriology 3 Meningococcal disease is caused by a Gram-negative bacterium, , commonly known as 4 meningococcus. There are 13 known serogroups distinguished by differences in surface polysaccharides of the outer 5 membrane capsule. Globally, serogroups A, B, C, W135 and Y most commonly cause disease. Meningococci can be 6 further classified by differences in their outer membrane proteins.1 7 4.10.2 Clinical features 8 N. meningitidis can cause invasive meningococcal disease (IMD) which includes and septicaemia. 9 Septicaemia, either on its own or with meningitis, can be particularly severe. N. meningitidis can also cause other 10 localised , including pneumonia, arthritis and conjunctivitis, but these are less common. 11 The clinical manifestations of meningococcal septicaemia and meningitis may be non-specific and can include sudden 12 onset of fever, rash (petechial, purpuric or maculopapular), headache, neck stiffness, photophobia, altered 13 consciousness, muscle ache, cold hands, thirst, joint pain, nausea and vomiting.1-3 Not all symptoms or signs may be 14 present at disease onset. The characteristic rash of meningococcal disease, which does not disappear with gentle 15 pressure on the skin, is not always present. Meningococcal infections can progress rapidly to serious disease or death in 16 previously healthy persons. The overall mortality risk for IMD is high (between 5 and 10%), despite appropriate 17 antibiotic therapy. Approximately 10 to 30% of children and adolescents who survive develop permanent sequelae, 18 including limb deformity, skin scarring, deafness and neurologic deficits.2,4,5 19 Humans are the only reservoir of N. meningitidis. Meningococcus is transmitted via droplets or direct contact and has 20 an incubation period of between 2 and 10 days, but commonly 3 to 4 days.3 A proportion of the population carry 21 N. meningitidis without developing disease. The prevalence and duration of asymptomatic nasopharyngeal carriage of 22 meningococci vary over time and in different population and age groups. Prevalence of carriage is known to be higher 23 when groups of people occupy small areas of living space.6,7 24 A number of medical conditions are known to increase the risk of an individual developing IMD. The magnitude of the 25 risk varies with the primary underlying condition. Persons with a complement deficiency have an increased risk of 26 meningococcal disease (estimated to range from 5- to 10 000-fold depending on the specific condition), and are also 27 more likely to have a recurrence of .8,9 Persons with an absent or dysfunctional spleen are at a life-long 28 increased risk of severe bacterial infection,10,11 including sepsis attributable to meningococcal disease. Other 29 immunocompromising conditions which increase the risk of IMD include HIV infection12,13 and haematopoetic stem 30 cell transplant. 31 Other individuals at greater risk of meningococcal infection include laboratory workers who handle meningococci, new 32 military recruits14,15 and university students living in residential colleges (particularly in their first year).16-19 Studies 33 have also reported that exposure to smokers (who are more likely to be carriers), intimate kissing with multiple partners, 34 and recent or current viral infection of the upper respiratory tract may also contribute to an individual’s risk of 35 contracting meningococcal disease.1,6,7,20,21 There is no definitive evidence that there is an increased risk of IMD among 36 men who have sex with men (MSM); however, clusters or community outbreaks of serogroup C IMD among MSM 37 have been reported.22-26 38 4.10.3 39 Meningococcal disease may occur sporadically or in epidemics. In Australia a large proportion of cases are reported 40 during winter and early spring, demonstrating a seasonal trend which is also observed in other countries with temperate 41 climates.27 The dominant meningococcal serogroup(s) varies between geographical regions. Serogroup A disease occurs 42 predominantly in low-income countries, particularly countries in sub-Saharan Africa. Meningococcal serogroup B 43 (‘MenB’) is the major cause of sporadic meningococcal disease in many developed countries. In Australia, serogroup B 44 has predominated, particularly since the meningococcal serogroup C (‘MenC’) conjugate program began in 45 2003. Of the 194 cases of meningococcal disease notified in Australia in 2012, for which the serogroup could be 46 determined, 83% were due to serogroup B. The remainder were due to serogroup C (6%), serogroup W135 (4%) and 47 serogroup Y (8%).28 48 Trends in the incidence of meningococcal disease are hard to predict over time due to natural fluctuations in disease. In 49 Australia, notification rates of meningococcal disease have been decreasing, from a peak of 3.5 cases per 100 000 in 50 2001 to 1.1 per 100 000 in 2011. This is due to a decline in serogroup C disease following the national meningococcal 51 C program and also a substantial decline in serogroup B disease.27 In Australia in 2006–2011, the highest 52 incidence of serogroup B disease was in children aged <5 years (5.7 cases per 100 000), particularly infants aged 53 <1 year (14.0 cases per 100 000). There was also a lower, secondary peak in late adolescence and early adulthood (2.8

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1 cases per 100 000 aged 15–19 years). The incidence of serogroup C disease has remained low at <0.3 cases per 100 000 2 since 2009 for all age groups, with no cases reported among those aged <20 years in 2011.27 3 4.10.4 Vaccines 4 Meningococcal available in Australia can be broadly categorised according to their formulation type 5 (conjugate, polysaccharide or recombinant) and the serogroups which they are designed to protect against (A, B, C, 6 W135 and/or Y). There is no single vaccine that offers protection against all meningococcal serogroups. 7 Conjugate meningococcal vaccines

8 Monovalent meningococcal C vaccines (MenCCV)

9 • Meningitec – Pfizer Australia Pty Ltd (meningococcal serogroup C–CRM197 conjugate). Each 0.5 mL pre-filled 10 syringe contains 10 µg Neisseria meningitidis serogroup C oligosaccharide conjugated to approximately 15 µg 11 of non-toxic Corynebacterium diphtheriae CRM197 protein; aluminium phosphate. 12 • Menjugate Syringe – CSL Limited/Novartis Vaccines and Diagnostics Pty Ltd (meningococcal serogroup C– 13 CRM197 conjugate). Lyophilised powder in a monodose vial with a pre-filled diluent syringe. Each 0.5 mL 14 reconstituted dose contains 10 µg N. meningitidis serogroup C oligosaccharide conjugated to 12.5–25 µg of non- 15 toxic C. diphtheriae CRM197 protein; 1.0 mg . 16 • NeisVac-C – Baxter Healthcare (meningococcal serogroup C–tetanus conjugate). Each 0.5 mL pre-filled 17 syringe contains 10 µg N. meningitidis serogroup C polysaccharide conjugated to 10–20 µg of tetanus toxoid; 18 0.5 mg aluminium as aluminium hydroxide. 19 Combination vaccine that contains meningococcal C (Hib-MenCCV) 20 • Menitorix – GlaxoSmithKline (Haemophilus influenzae type b [PRP-T]-meningococcal serogroup C–tetanus 21 toxoid conjugate). Lyophilised powder in a monodose vial with a pre-filled diluent syringe. Each 0.5 mL 22 reconstituted dose contains 5 µg Hib capsular polysaccharide (PRP) conjugated to 12.5 µg tetanus toxoid, and 23 5 µg N. meningitidis serogroup C polysaccharide conjugated to 5 µg of tetanus toxoid; traces of trometamol and 24 sucrose. 25 Quadrivalent meningococcal conjugate vaccines (4vMenCV)

26 • Menactra – Sanofi Pasteur Pty Ltd (meningococcal serogroups A, C, W135, Y–diphtheria toxoid conjugate). 27 Each 0.5 mL monodose vial contains 4 µg each of serogroups A, C, W135 and Y polysaccharides conjugated with 28 a total of approximately 48 µg of a diphtheria toxoid protein.

29 • Menveo – CSL Limited/Novartis Vaccines and Diagnostics Pty Ltd (meningococcal serogroups A, C, W135, Y– 30 CRM197 conjugate). Lyophilised powder containing serogroup A (MenA) in a monodose vial with a pre-filled 31 syringe or vial containing serogroups C, W135 and Y (MenCWY) in suspension. Each 0.5 mL reconstituted 32 dose contains 10 µg of serogroup A and 5 µg each of serogroups C, W135 and Y oligosaccharides individually 33 conjugated with up to 33.3 µg of non-toxic C. diphtheriae CRM197 protein; sucrose.

34 • Nimenrix – GlaxoSmithKline (meningococcal serogroups A, C, W135, Y–tetanus toxoid conjugate). Lyophilised 35 powder in a monodose vial with solvent supplied in a pre-filled syringe or ampoule. Each 0.5 mL reconstituted 36 dose contains 5 µg each of serogroups A, C, W135 and Y polysaccharides conjugated with a total of 44 µg of 37 tetanus toxoid; trometamol; sucrose.

38 Conjugate formulations contain meningococcal serogroup antigens conjugated to a carrier 39 protein. They include vaccines that only offer protection against serogroup C meningococcal disease – monovalent 40 meningococcal C conjugate vaccines (MenCCV) and MenCCV in combination with Hib (Hib-MenCCV) – and 41 vaccines which offer protection against disease caused by four meningococcal serogroups, including meningococcal C 42 (quadrivalent meningococcal conjugate vaccines, 4vMenCV). 43 Monovalent meningococcal C vaccines (MenCCV) 44 Following extensive assessment in clinical studies, MenCCVs are now routinely delivered to infants and young children 45 in a number of countries, including Australia.29 The effectiveness of MenCCV following 1 dose has been estimated to 46 range from 83 to 100%.30,31 The population-wide use of this vaccine in national vaccination programs has resulted in 47 marked reductions in serogroup C invasive disease in the eligible age groups, including in Australia.27,29,30 There is also 48 evidence that meningococcal C vaccination programs have offered indirect protection to older age groups who were not

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1 eligible to receive the vaccine.27,29,32 Although waning of antibody levels has been observed following vaccination with 2 MenCCVs,33-35 current serogroup C meningococcal disease epidemiology in Australia suggests ongoing protection in 3 age groups who were previously vaccinated.27 4 Combination vaccine that contains meningococcal C (Hib-MenCCV) 5 The combination vaccine containing meningococcal serogroup C and Haemophilus influenzae type b antigens (Hib- 6 MenCCV) has been used under the NIP since July 2013. The MenCCV component has similar immunogenicity and 7 safety to monovalent MenCCV.36-41 8 Quadrivalent meningococcal conjugate vaccines (4vMenCV)

9 4vMenCVs are designed to provide protection against four serogroups of meningococci: A, C, W135 and Y. As it is not 10 feasible to assess the efficacy of 4vMenCVs in clinical trials, immunogenicity outcomes have been used as a surrogate 11 measure for vaccine efficacy. Each of the registered 4vMenCV formulations have been shown to be immunogenic in 12 infants, children and adults, inducing serum bactericidal antibodies at levels that correlate with clinical protection 13 approximately 1 month after a vaccine dose.42-52 There is some evidence that the immunogenicity of the different 14 4vMenCV formulations varies among adolescents and adults, but the clinical significance of the differences is uncertain 15 and does not warrant a preference for one formulation over another in this age group.43,53-56 The vaccine effectiveness of 16 a 4vMenCV adolescent vaccination program in the USA, consisting of a single dose, has been estimated at 80 to 85%.57 17 Menveo is the only 4vMenCV which has been assessed in young infants (from 2 months of age). A has 18 shown that protective levels of antibody to serogroups C, W135 and Y are induced in >70% of infants after 2 vaccine 19 doses, at 2 and 4 months of age, with a lower antibody response to serogroup A.49 However, protective levels of 20 antibodies to all serogroups were achieved in >90% of infants after a 3rd dose at 6 months of age.48 21 Protective antibody titres from 4vMenCV have been shown to persist for up to 3 years in clinical trials in children.58 In 22 adolescents and adults, a high proportion of vaccine recipients have been shown to maintain seroprotective antibody 23 titres against most of the vaccine serogroups (except serogroup A) until up to 5 years after primary vaccination.59 24 A few studies have demonstrated a poor immune response to a single dose of meningococcal (either 25 MenCCV or 4vMenCV) in children and adults with asplenia60,61 and in HIV-infected persons.62-64 The immune response 26 to some serogroups improves following a 2nd vaccine dose.60,63-65 27 Meningococcal B vaccine (MenBV)

28 • Bexsero – Novartis Vaccines and Diagnostics Pty Ltd (recombinant multicomponent meningococcal serogroup 29 B vaccine). Each 0.5 mL pre-filled syringe contains 50 µg Neisseria meningitidis serogroup B Neisseria heparin 30 binding antigen fusion protein, 50 µg Neisseria meningitidis serogroup B Neisseria adhesin A protein, 50 µg 31 Neisseria meningitidis serogroup B Neisseria factor H binding protein fusion protein, 25 µg outer membrane 32 vesicles from Neisseria meningitidis serogroup B strain NZ98/254, adsorbed onto aluminium hydroxide; sodium 33 chloride; histidine; sucrose. May contain traces of kanamycin. Tip cap may contain traces of natural rubber latex.

34 MenBV is a recombinant multicomponent vaccine (also known as 4cMenB) designed to provide protection against 35 multiple strains of meningococcal serogroup B. It contains four major protein antigens that are highly conserved across 36 serogroup B strains. This vaccine differs from strain-specific meningococcal B vaccines that have been used in some 37 countries, such as New Zealand, for the control of epidemics dominated by a single serogroup B strain.66 38 As it is not feasible to assess the efficacy of MenBV in clinical trials, immunogenicity outcomes have been used as a 39 surrogate measure for vaccine efficacy. Clinical studies have shown that MenBV induces bactericidal antibodies 40 specific to the four vaccine antigens in infants, children and adolescents at a level that correlates with protection against 41 clinical disease.67-69 There are currently no data on the use of MenBV in persons aged >50 years. MenBV is expected to 42 protect against the majority of circulating meningococcal B strains. Specialised laboratory testing (Meningococcal 43 Antigen Typing System or MATS) has predicted that approximately 76% of all meningococcal B strains that caused 44 disease in Australia from 2007 to 2011 would have been susceptible to effective killing by vaccine-induced 45 antibodies.70 46 The duration of clinical protection afforded by MenBV is currently unknown due to the limited data on persistence of 47 vaccine-induced immunity.71-74 48

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1 Polysaccharide meningococcal vaccines

2 Quadrivalent meningococcal polysaccharide vaccines (4vMenPV)

3 • Mencevax ACWY – GlaxoSmithKline (meningococcal serogroups A, C, W135 and Y polysaccharides). 4 Lyophilised pellet in a monodose vial with separate saline diluent. Each 0.5 mL reconstituted dose contains 5 50 µg of each meningococcal serogroup polysaccharide; 12.6 mg sucrose; 0.1 mg trometamol.

6 • Menomune – Sanofi Pasteur Pty Ltd (meningococcal serogroups A, C, W135 and Y polysaccharides). 7 Lyophilised powder in a monodose vial with separate saline diluent. Each 0.5 mL reconstituted dose contains 8 50 µg of each meningococcal serogroup polysaccharide; 2.5–5 mg lactose.

9 Quadrivalent polysaccharide vaccine formulations (4vMenPV) contain meningococcal polysaccharide antigens for four 10 serogroups: A, C, W135 and Y. Unlike 4vMenCV, the polysaccharide antigens are not conjugated to a carrier protein. 11 This results in a different immunogenicity and efficacy profile to that of the conjugate vaccines. In clinical studies of 12 4vMenPVs, the vaccines were immunogenic in 90% of recipients >2 years of age, but were poorly immunogenic in 13 children <2 years of age. Compared with 4vMenCV, 4vMenPVs are less immunogenic for all vaccine serogroups in 14 children aged 2–10 years47,51,52,58,75 and for some vaccine serogroups in adolescents and adults.44,45,53,76,77 15 Clinical protection following a single dose of 4vMenPV appears to persist for 3 to 5 years in healthy children of school 16 age and adults but with variation between age groups and serogroups. Duration of protection may be shorter for children 17 <10 years of age, particularly for some vaccine serogroups.58 18 Revaccination with polysaccharide meningococcal vaccine formulations has been shown to reduce the antibody 19 response to vaccine serogroups (immunological hyporesponsiveness) compared with the primary immunisation,78-82 20 although a reduction in the clinical effectiveness of 4vMenPV with revaccination has not been demonstrated. This 21 blunting of antibody response is not observed when meningococcal conjugate vaccines are used for the primary 22 immunisation.79 23 4.10.5 Transport, storage and handling 24 For all meningococcal vaccines, transport according to National guidelines: Strive for 5.83 Store at 25 +2°C to +8°C. Do not freeze. Protect from light. 26 Conjugate vaccines 27 Menjugate Syringe must be reconstituted by adding the entire contents of the diluent syringe to the vial and shaking 28 until the powder is completely dissolved. Reconstituted vaccine should be used immediately. 29 Menitorix must be reconstituted by adding the entire contents of the diluent syringe to the vial and shaking until the 30 powder is completely dissolved. Reconstituted vaccine should be used as soon as practicable. 31 Menveo must be reconstituted by adding the entire contents of the liquid MenCWY syringe/vial to the lyophilised 32 MenA vial and shaking until the powder is completely dissolved. Reconstituted vaccine should be used as soon as 33 practicable. 34 Nimenrix must be reconstituted by adding the entire contents of the pre-filled syringe or ampoule of solvent to the vial 35 and shaking until the powder is completely dissolved. Reconstituted vaccine should be used immediately. 36 Polysaccharide vaccines 37 Mencevax ACWY must be reconstituted by adding the entire contents of the diluent container to the vial and shaking 38 until the powder is completely dissolved. Reconstituted vaccine should be used as soon as practicable. If storage is 39 necessary, hold at +2°C to +8°C for not more than 8 hours. 40 Menomune must be reconstituted by adding the entire contents of the diluent container to the vial and shaking until the 41 powder is completely dissolved. Reconstituted vaccine must be used within 24 hours. 42 4.10.6 Dosage and administration 43 Conjugate meningococcal vaccines 44 The dose of all meningococcal conjugate vaccines (MenCCV, Hib-MenCCV, 4vMenCV) is 0.5 mL, to be given by IM 45 injection. 46 MenCCVs and Hib-MenCCV are registered for use in infants from 6 weeks of age.

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1 The recommended age for use of 4vMenCVs varies between vaccine brands. Menactra can be used from 2 years of age, 2 Nimenrix from 12 months of age and Menveo from 2 months of age (see 4.10.13 Variations from product information 3 below). 4 Meningococcal B vaccine 5 The dose of MenBV is 0.5 mL, to be given by IM injection. See Table 4.10.1 for the recommended doses of MenBV for 6 different age groups. 7 MenBV is registered for use from 2 months of age. However, the 1st dose can be given as early as 6 weeks of age to 8 align with the schedule for other routine infant vaccines (see 4.10.13 Variations from product information below). If the 9 1st dose is given at 6 weeks of age, the next scheduled doses can be given at 4 and 6 months of age.

10 Table 4.10.1: Recommended number of doses of MenBV by age group

Number of doses Age at commencement required for Recommended interval Recommended age for single booster of vaccine course primary between primary doses dose immunisation

6 weeks* – 5 months 3 doses 8 weeks 12 months

12 months, or 2 months after previous 6–11 months 2 doses 8 weeks dose, whichever is later

≥12 months 2 doses 8 weeks No booster required†

11 * MenBV is registered for use in persons ≥2 months of age; however, the 1st dose of MenBV can be given as early as 6 weeks of age (see 4.10.13 12 Variations from product information). 13 † The need for a booster dose for this age group is as yet uncertain. 14 15 Polysaccharide meningococcal vaccines 16 The dose of both 4vMenPVs is 0.5 mL, to be given by SC injection. 17 4vMenPVs are registered for use in persons ≥2 years of age. 18 Co-administration with other vaccines 19 Meningococcal vaccines can be administered concurrently with other vaccines (see 4.10.13 Variations from product 20 information below). 21 There is an increased risk of fever following the co-administration of MenBV with other vaccines routinely 22 recommended for children <24 months of age, compared to when these vaccines are given separately (see 4.10.11 23 Adverse events below). Co-administration of MenBV with other routine infant vaccines in this age group is acceptable; 24 however, prophylactic administration of paracetamol to reduce the risk of fever is recommended (see 4.10.10 25 Precautions below). Alternatively, MenBV can be administered separately from other routine infant vaccines, with a 26 minimum interval of 3 days, to minimise the risk of fever. In this circumstance it is important that routinely 27 recommended vaccines are not delayed. 28 The co-administration of MenBV and 4vMenCV in persons who are at increased risk of meningococcal disease is 29 acceptable based on first principles, although there are no specific data on concomitant administration of these vaccines. 30 In persons for whom multiple vaccines (and thus injections) are recommended at one time, and there is a desire to 31 reduce the number of injections given at one visit, MenBV should be administered earlier than 4vMenCV due to the 32 higher incidence of meningococcal serogroup B compared with other serogroups in Australia (see 4.10.3 Epidemiology 33 above). An interval of 4 weeks is recommended in this circumstance. 34 Interchangeability of meningococcal vaccines 35 The different meningococcal vaccine formulations (conjugate, polysaccharide and recombinant) are not 36 interchangeable. 37 The different brands of 4vMenCV are not interchangeable. However, in circumstances where the brand of vaccine used 38 for previous dose(s) is not known or is not available, the use of another brand for the subsequent dose(s) is acceptable.84

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1 4.10.7 Recommendations 2 Meningococcal vaccines are recommended for the following age and risk groups because of their greater risk of IMD. 3 Infants and children 4 Meningococcal C vaccines 5 A single dose of MenCCV is recommended for all children at the age of 12 months. This can be provided as either 6 MenCCV or the combination vaccine Hib-MenCCV. Additional doses of MenCCV are not recommended based on 7 current disease epidemiology in Australia (see 4.10.3 Epidemiology above). 8 Children who missed receiving a dose of MenCCV at 12 months of age should be given a single catch-up dose of 9 MenCCV (see 2.1.5 Catch-up). Similarly, children (without medical risk factors for IMD) who have received a dose(s) 10 of MenCCV at age <12 months, such as migrants from overseas countries where different vaccine schedules are used, 11 should be given a single dose of MenCCV at 12 months of age or 8 weeks after their last dose. (see Section 2.1.5 Catch- 12 up and 4.10.13 Variations from product information). 13 Meningococcal B vaccine 14 MenBV is recommended for infants and young children, particularly those aged <2 years, due to the higher risk of 15 serogroup B meningococcal disease in this age group (see 4.10.3 Epidemiology above). The number of doses required 16 depends on the age at which the vaccine course is commenced (see Table 4.10.1 in 4.10.6 Dosage and administration 17 above). 18 Prophylactic use of paracetamol is recommended with every dose of MenBV in children <2 years of age due to the 19 increased risk of fever following vaccine administration (see 4.10.10 Precautions below). 20 Adolescents and adults 21 Meningococcal B vaccine 22 MenBV is recommended in a 2-dose schedule for all adolescents aged 15–19 years due to their higher risk of serogroup 23 B meningococcal disease compared with other ages (see Table 4.10.1 in 4.10.6 Dosage and administration above). 24 MenBV vaccine is particularly recommended for adolescents and young adults living in close quarters, such as new 25 military recruits and students living in residential accommodation. Vaccination should be given prior to entry to such 26 risk settings or as soon as possible after entry (see 4.10.4 Vaccines). 27 Persons with condition(s) associated with an increased risk of meningococcal disease 28 A number of medical conditions or treatments increase a person’s risk of IMD (see List 4.10.1) and additional doses of 29 4vMenCV and MenBV are recommended for persons with these risk factors.

30 List 4.10.1: Conditions associated with an increased risk of invasive meningococcal disease (IMD) in children 31 and adults 32 • Defects in or deficiency of complement components, including Factor H, Factor D or properdin deficiency 33 • current or future treatment with eculizumab (a monoclonal antibody directed against complement component C5) 34 • functional or anatomical asplenia 35 • HIV infection, regardless of stage of disease or CD4+ count 36 • haematopoietic stem cell transplant 37 38 Meningococcal conjugate vaccines 39 4vMenCV is recommended for persons with conditions in List 4.10.1. The vaccine brand and doses required depend on 40 the age at which the vaccine course is commenced (see Table 4.10.2). 41 Menveo is the only brand of 4vMenCV that should be used in infants <12 months of age. If Menveo is not available, 42 specialist advice should be sought on the most appropriate . 43 Persons who require 4vMenCV due to the presence of underlying at-risk conditions, who have previously received 44 4vMenPV, should receive 2 doses of 4vMenCV as outlined in Table 4.10.2. The first dose of 4vMenCV is

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1 recommended approximately 2 years after the most recent dose of 4vMenPV. Based on limited immunogenicity studies, 2 the minimum interval between the 1st dose of 4vMenCV and the last dose of 4vMenPV is 6 months.78,80,81

3 Table 4.10.2: Recommended use of 4vMenCV by age group for persons with medical condition(s) associated 4 with an increased risk of meningococcal disease

Age at commencement Recommended Primary Recommended interval Timing of of vaccine course brand immunisation between primary doses* booster doses

At age 12–18 months, 2–6 months Menveo 3 doses 8 weeks then 3 years later, then every 5 years thereafter

3 years after the primary doses, 7–11 months Menveo 2 doses 12 weeks then every 5 years thereafter

Menveo or 3 years after the primary doses, 12–23 months 2 doses 12 weeks Nimenrix then every 5 years thereafter

Menactra, 3 years after the primary doses, 2–6 years Menveo or 2 doses 8 weeks then every 5 years thereafter Nimenrix Menactra, Every 5 years after the previous ≥7 years Menveo or 2 doses 8 weeks dose Nimenrix 5 * Refer to 2.1.5 Catch-up for advice on minimum intervals. 6 7 Meningococcal B vaccine 8 MenBV is recommended for persons with conditions in List 4.10.1. For recommended doses of MenBV by age group 9 see Table 4.10.1 in 4.10.6 Dosage and administration above. 10 Travellers 11 A quadrivalent meningococcal vaccine is recommended for persons who are planning travel involving a greater risk of 12 exposure to meningococcal serogroups A, C, W135 and Y. 13 This includes:

14 • individuals who intend to travel to or reside in parts of the world where epidemics of group A, C, W135 or Y 15 meningococcal disease occur, particularly the ‘meningitis belt’ of sub-Saharan Africa 16 • individuals who intend to travel to mass gatherings, for example, pilgrims travelling to the Hajj. In some instances 17 documentation of vaccination is required for country entry visas. 18 The vaccine brand and doses required depends on the age at which the vaccine course is commenced (see Table 4.10.3). 19 Use of 4vMenCV is preferred, particularly in children aged <7 years and travellers of any age who anticipate ongoing 20 or periodic travel-related exposure risk (see 4.10.4 Vaccines). 4vMenPV is suitable, however, when the need for repeat 21 doses is not anticipated. 22 In those with ongoing increased risk due to travel, who have previously received 4vMenPV, 1 dose of 4vMenCV is 23 recommended approximately 2 years after the most recent dose of 4vMenPV, with a recommended minimum interval of 24 6 months, with subsequent 4vMenCV as outlined in Table 4.10.3.

25 Table 4.10.3: Recommended use of 4vMenCV by age group for persons travelling to areas where epidemics of 26 group A, C, W135 or Y meningococcal disease occur or to mass gatherings

Age at commencement Recommended Primary Recommended interval Timing of booster doses of of vaccine course brand immunisation between primary doses* 4vMenCV if required

At age 12–18 months, 2–6 months Menveo 3 doses 8 weeks then 3 years later, then every 5 years thereafter

3 years after the primary doses, 7–11 months Menveo 2 doses 12 weeks then every 5 years thereafter

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Either 2 doses 12 weeks Menveo 3 years after the primary dose(s), 12–23 months then every 5 years thereafter Or 1 dose Not applicable Nimenrix

Menactra, 3 years after the primary dose, 2–6 years Menveo or 1 dose Not applicable then every 5 years thereafter Nimenrix

Menactra, Every 5 years after the previous ≥7 years Menveo or 1 dose Not applicable dose† Nimenrix†

1 * Refer to 2.1.5 Catch-up for advice on minimum intervals. 2 † 4vMenCV is preferred. However, 4vMenPV is a suitable alternative for travellers aged ≥7 years when the need for repeat doses is not anticipated 3 (see ‘Travellers’ above). 4 5 Laboratory personnel who frequently handle Neisseria meningitidis 6 Laboratory personnel who are at occupational risk of exposure to Neisseria meningitidis are recommended to receive 7 immunisation against all vaccine-preventable meningococcal serogroups as listed below. 8 Meningococcal conjugate vaccines

9 4vMenCV is recommended for laboratory personnel to offer protection against serogroups A, C, W135 and Y. Those 10 with ongoing occupational exposure risks are recommended to receive a 4vMenCV booster dose every 5 years. 11 4vMenPV can be used if the risk of exposure is not expected to be ongoing and the need for repeat doses is not 12 anticipated. However, for most laboratory personnel, there will be ongoing exposure risks and anticipated need for 13 repeat doses of the vaccine and, in these instances, 4vMenCV is preferred. 14 In those with ongoing occupational exposure risks who have previously received 4vMenPV, a dose of 4vMenCV is 15 recommended approximately 2 years after the most recent dose of 4vMenPV. Based on limited immunogenicity studies, 16 the minimum interval between the 1st dose of 4vMenCV and the last dose of 4vMenPV is 6 months.78,80,81 17 Meningococcal B vaccine 18 MenBV in a 2-dose schedule is recommended for laboratory personnel to offer protection against meningococcal 19 serogroup B. For recommended doses of MenBV by age group see Table 4.10.1 in 4.10.6 Dosage and administration 20 above. 21 Use of vaccines for close contacts of meningococcal disease cases 22 Advice on the need for meningococcal vaccination of the close contacts (with household or household-like contact) of 23 meningococcal disease cases should be sought from the relevant state or territory public health authority (See 4.10.12 24 Public health management of meningococcal disease below). 25 4.10.8 Pregnancy and breastfeeding 26 Meningococcal vaccines are not routinely recommended for pregnant or breastfeeding women,1,85,86 but can be given 27 where clinically indicated (see 4.10.7 Recommendations above). 28 Refer to 3.3 Groups with special vaccination requirements, Table 3.3.1 Recommendations for vaccination in pregnancy 29 for more information. 30 4.10.9 Contraindications 31 The only absolute contraindications to meningococcal vaccines are: 32 • anaphylaxis following a previous dose of any meningococcal vaccine 33 • anaphylaxis following any vaccine component. 34 Previous meningococcal disease, regardless of the serogroup, is not a contraindication to administration of any 35 meningococcal vaccine. 36 Previous vaccination with the strain-specific meningococcal B vaccine used in New Zealand, MeNZB, is not a 37 contraindication for receiving MenBV.

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1 4.10.10 Precautions 2 Prophylactic use of paracetamol with MenBV vaccination in children aged <2 years 3 Prophylactic use of paracetamol with every dose of MenBV administered to children <2 years of age is recommended 4 due to the increased risk of fever, including high fever, following MenBV67,68 (see 4.10.11 Adverse events below). This 5 is an exception to the general recommendation to not routinely give paracetamol with vaccinations unless it is for relief 6 of fever or pain following immunisation (see 2.3 Post-vaccination). 7 The 1st dose of paracetamol (15 mg/kg per dose) is recommended within the 30-minute period prior to, or as soon as 8 practicable after, vaccination, regardless of the presence of fever. This can be followed by 2 more doses of paracetamol 9 given 6 hours apart, regardless of the presence of fever. A clinical trial has shown that the prophylactic use of 10 paracetamol in infancy reduced the incidence and severity of fever without affecting the immunogenicity of either 11 MenBV or other vaccines given concurrently.87 12 4.10.11 Adverse events 13 Conjugate meningococcal vaccines 14 Meningococcal conjugate vaccines are generally considered safe and well tolerated. Common adverse events are pain, 15 redness and swelling at the site of injection, fever, irritability, drowsiness, decreased appetite and headaches.30,37,39-42,47 16 There are some age-related differences in the type of adverse events following vaccination. For example, headache, 17 anorexia, fever and chills are more likely to be reported in adolescents and adults than in children following 18 administration of 4vMenCV.42,47 Among recipients of 4vMenCV, rash and nausea are common. However, serious 19 general adverse events are rare.42,47 20 The range of adverse events occurring after Hib-MenCCV combination vaccine is similar to that after other childhood 21 vaccines.36 Redness is the most frequently reported local symptom, with irritability the most frequently reported 22 generalised reaction.37,38 Concomitant administration with MMR vaccine is not associated with an increased rate of 23 adverse events for either vaccine.36 24 There is no evidence of an association between meningococcal conjugate vaccines and Guillain-Barré syndrome (GBS). 25 An early report in the United States of a suspected temporal association between Menactra and GBS was followed by a 26 large retrospective cohort study in the United States which found no evidence of an increased risk of GBS with the use 27 of Menactra.84,88 Meningocococal conjugate vaccines can be administered to persons with a history of GBS for whom 28 vaccination is indicated (see 4.10.13 Variations from product information below). 29 Meningococcal B vaccine 30 MenBV has an acceptable safety and tolerability profile based on clinical trial data. In clinical trials, fever was the most 31 notable systemic reaction in infants and young children, particularly those aged 2–12 months. Temperatures were 32 highest 6 hours after vaccination, then decreased on day 2 and generally subsided by day 3.67 More than a quarter of 33 infants who received MenBV alone developed fever ≥38°C and 4 to 8% had a temperature ≥39°C. The frequency of 34 fever was 2-times higher when MenBV was administered with other infant vaccines, specifically DTPa-hepB-IPV-Hib 35 and 7-valent pneumococcal conjugate vaccines.68 Fever in infants given MenBV concurrently with other routine infant 36 vaccines was reduced by prophylactic use of paracetamol.87 (See also 4.10.10 Precautions above). In clinical studies, 37 fever and other systemic reactions were less common after the booster dose of MenBV administered at 12 months of 38 age. 39 Other common adverse events following MenBV included tenderness, swelling and erythema at the injection site, as 40 well as irritability, sleepiness, unusual crying and change in appetite.67 These reactions were reported less often with 41 increasing age. Pain at injection site, malaise and headache were more commonly reported among adolescents and 42 adults.69 43 Polysaccharide meningococcal vaccines 44 Local adverse events after 4vMenPV include erythema, induration, tenderness, pain and local axillary 45 lymphadenopathy. However, these reactions are usually mild and infrequent. Fever and chills occur in approximately 46 2% of young children, and may persist for 48 hours or longer, but significant general adverse events are rare. Studies 47 have indicated no consistently significant differences in adverse events following 4vMenPV and 4vMenCV.52 48 4.10.12 Public health management of meningococcal disease 49 Invasive meningococcal disease is notifiable in all states and territories in Australia. Prompt diagnosis and medical 50 treatment of suspected cases of meningococcal disease is important.

9

1 The state/territory public health authority should be contacted as soon as possible for guidance on the public health 2 management of suspected cases and their contacts (see Appendix 1 Contact details for Australian, state and territory 3 government health authorities and communicable disease control). 4 The need for meningococcal vaccination of close contacts (household or household-like) contacts of a meningococcal 5 case, or in an outbreak of meningococcal disease in an institutional or community setting should be made by the local 6 public health unit and/or the state or territory public health authority, according to the national guidelines.89 7 4.10.13 Variations from product information 8 The product information for meningococcal C conjugate vaccines states that, under the age of 12 months, either 2 9 (NeisVac-C) or 3 (Meningitec and Menjugate Syringe) doses of vaccine are required. The ATAGI recommends instead 10 that meningococcal C vaccination is routinely not recommended before 12 months of age (unless specifically 11 indicated). 12 The product information for Meningitec states that an allergic reaction following a previous dose is a contraindication to 13 further doses. The ATAGI recommends instead that the only contraindication is a history of anaphylaxis to a previous 14 dose or to any of the vaccine components. 15 The product information for NeisVac-C states that this vaccine should not be administered with PRP-OMP 16 Haemophilus influenzae type b vaccine unless ‘medically important’. The ATAGI recommends instead that the vaccine 17 may be administered simultaneously with other vaccines in the NIP. 18 The product information for Bexsero states that this vaccine is indicated for use in persons ≥2 months of age. However, 19 the ATAGI recommends instead that the 1st dose of Bexsero can be given to infants concurrently with other infant 20 vaccines from as early as 6 weeks of age, to align with the routine infant schedule. 21 The product information for Menveo states that this vaccine is indicated for use in persons ≥11 years of age. The 22 ATAGI recommends instead that Menveo can be given to persons aged ≥2 months of age (see 4.10.4 Vaccines). 23 The product information for Menactra states that this vaccine is indicated for use in persons between 2 and 55 years of 24 age. The ATAGI recommends instead that this vaccine can be given to persons greater than 55 years of age. 25 The product information for Nimenrix states that this vaccine is indicated for use in persons between 1 and 55 years of 26 age. The ATAGI recommends instead that this vaccine can be given to persons greater than 55 years of age. 27 The product information for Menactra states that a previous episode of GBS is a contraindication to vaccination with 28 Menactra. The ATAGI recommends instead that any of the available 4vMenCVs can be administered to a person with a 29 history of GBS. 30 The product information for all meningococcal vaccines (MenCCV, 4vMenCV, MenBV and 4vMenPV) states that 31 there are no data on the use of these vaccines in lactating women. The ATAGI recommends that breastfeeding women 32 can be vaccinated. 33 The product information for all 4vMenCVs states that vaccine should be administered as a single dose. The ATAGI 34 recommends that these vaccines can be given in a 2- or 3-dose primary schedule to infants, children and adults who are 35 at increased risk of IMD according to Tables 4.10.2 and 4.10.3. 36 References 37 A full reference list is available on the electronic Handbook or website www.immunise.health.gov.au. 38 1. Granoff DM, Pelton S, Harrison LH. Meningococcal vaccines. In: Plotkin SA, Orenstein WA, Offit PA, eds. 39 Vaccines. 6th ed. Philadelphia, PA: Saunders Elsevier, 2013. 40 2. Apicella MA. Neisseria meningitidis. In: Mandell GL, Bennett JE, Dolin R, eds. Mandell, Douglas, and 41 Bennett's principles and practice of infectious diseases. 7th ed. Philadelphia: Churchill Livingstone, 2010. 42 3. Centers for Disease Control and Prevention (CDC). Meningococcal disease. In: Atkinson W, Wolfe C, 43 Hamborsky J, eds. Epidemiology and prevention of vaccine-preventable diseases. 12th ed. Washington, D.C.: 44 Public Health Foundation, 2011. 45 4. Viner RM, Booy R, Johnson H, et al. Outcomes of invasive meningococcal serogroup B disease in children 46 and adolescents (MOSAIC): a case-control study. The Lancet Neurology 2012;11:774-83. 47 5. Wang B, Clarke M, Thomas N, et al. The clinical burden and predictors of sequelae following invasive 48 meningococcal disease in Australian children. Pediatric Infectious Disease Journal 2014;33:316-8.

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1 6. Robinson P, Taylor K, Nolan T. Risk-factors for meningococcal disease in Victoria, Australia, in 1997. 2 Epidemiology and Infection 2001;127:261-8. 3 7. McCall BJ, Neill AS, Young MM. Risk factors for invasive meningococcal disease in southern Queensland, 4 2000–2001. Internal Medicine Journal 2004;34:464-8. 5 8. Ross SC, Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and 6 consequences of Neisserial and other infections in an immune deficiency. Medicine 1984;63:243-73. 7 9. Figueroa J, Andreoni J, Densen P. Complement deficiency states and meningococcal disease. Immunology 8 Research 1993;12:295-311. 9 10. Holdsworth RJ, Irving AD, Cuschieri A. Postsplenectomy sepsis and its mortality rate: actual versus perceived 10 risks. British Journal of Surgery 1991;78:1031-8. 11 11. Francke EL, Neu HC. Postsplenectomy infection. Surgical Clinics of North America 1981;61:135-55. 12 12. Cohen C, Singh E, Wu HM, et al. Increased incidence of meningococcal disease in HIV-infected individuals 13 associated with higher case-fatality ratios in South Africa. AIDS 2010;24:1351-60. 14 13. Miller L, Arakaki L, Ramautar A, et al. Elevated risk for invasive meningococcal disease among persons with 15 HIV. Annals of Internal Medicine 2014;160:30-7. 16 14. Bergman BP, Hayton JC, Green AD. Effectiveness of the meningococcal vaccination programme for British 17 Armed Forces recruits. Communicable Disease and Public Health 2000;3:298-9. 18 15. D'Amelio R, Molica C, Biselli R, Stroffolini T. Surveillance of infectious diseases in the Italian military as pre- 19 requisite for tailored vaccination programme. Vaccine 2001;19:2006-11. 20 16. Bruce MG, Rosenstein NE, Capparella JM, et al. Risk factors for meningococcal disease in college students. 21 JAMA 2001;286:688-93. 22 17. Froeschle JE. Meningococcal disease in college students. Clinical Infectious Diseases 1999;29:215-6. 23 18. Harrison LH, Dwyer DM, Maples CT, Billmann L. Risk of meningococcal infection in college students. JAMA 24 1999;281:1906-10. 25 19. Neal KR, Nguyen-Van-Tam J, Monk P, et al. Invasive meningococcal disease among university 26 undergraduates: association with universities providing relatively large amounts of catered hall 27 accommodation. Epidemiology and Infection 1999;122:351-7. 28 20. Centers for Disease Control and Prevention (CDC). Updated recommendations for use of meningococcal 29 conjugate vaccines – Advisory Committee on Practices (ACIP), 2010. MMWR Morbidity and 30 Mortality Weekly Report 2011;60:72-6. 31 21. Tully J, Viner RM, Coen PG, et al. Risk and protective factors for meningococcal disease in adolescents: 32 matched cohort study. BMJ 2006;332:445-50. 33 22. Simon MS, Weiss D, Gulick RM. Invasive meningococcal disease in men who have sex with men. Annals of 34 Internal Medicine 2013;159:300-1. 35 23. European Centre for Disease Prevention and Control. Rapid risk assessment: Invasive meningococcal disease 36 among men who have sex with men. Stockholm: ECDC, 2013. Available at: 37 http://www.ecdc.europa.eu/en/publications/Publications/rapid-risk-assessment-invasive-meningococcal- 38 disease-among-MSM.pdf (accessed Sep 2014). 39 24. Marcus U, Vogel U, Schubert A, et al. A cluster of invasive meningococcal disease in young men who have 40 sex with men in Berlin, October 2012 to May 2013. Eurosurveillance 2013;18:20523. 41 25. Schmink S, Watson JT, Coulson GB, et al. Molecular epidemiology of Neisseria meningitidis isolates from an 42 outbreak of meningococcal disease among men who have sex with men, Chicago, Illinois, 2003. Journal of 43 Clinical Microbiology 2007;45:3768-70. 44 26. Tsang RS, Kiefer L, Law DK, et al. Outbreak of serogroup C meningococcal disease caused by a variant of 45 Neisseria meningitidis serotype 2a ET-15 in a community of men who have sex with men. Journal of Clinical 46 Microbiology 2003;41:4411-4. 47 27. NNDSS Annual Report Writing Group. Australia's notifiable disease status, 2011: Annual report of the 48 National Notifiable Diseases Surveillance System Communicable Diseases Intelligence 2013;37:E313-93.

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1 28. Lahra MM, Enriquez RP. Australian Meningococcal Surveillance Programme annual report, 2012. 2 Communicable Diseases Intelligence 2013;37:E224-32. 3 29. Trotter CL, Maiden MC. Meningococcal vaccines and herd immunity: lessons learned from serogroup C 4 conjugate vaccination programs. Expert Review of Vaccines 2009;8:851-61. 5 30. Campbell H, Borrow R, Salisbury D, Miller E. Meningococcal C conjugate vaccine: the experience in England 6 and Wales. Vaccine 2009;27 Suppl 2:B20-9. 7 31. Campbell H, Andrews N, Borrow R, Trotter C, Miller E. Updated postlicensure surveillance of the 8 meningococcal C conjugate vaccine in England and Wales: effectiveness, validation of serological correlates 9 of protection, and modeling predictions of the duration of herd immunity. Clinical and Vaccine Immunology: 10 CVI 2010;17:840-7. 11 32. Chiu C, Dey A, Wang H, et al. Vaccine preventable diseases in Australia, 2005 to 2007. Communicable 12 Diseases Intelligence 2010;34 Suppl:ix-S167. 13 33. Ishola DA, Jr., Borrow R, Findlow H, et al. Prevalence of serum bactericidal antibody to serogroup C 14 Neisseria meningitidis in England a decade after vaccine introduction. Clinical and Vaccine Immunology: CVI 15 2012;19:1126-30. 16 34. Borrow R, Abad R, Trotter C, van der Klis FR, Vazquez JA. Effectiveness of meningococcal serogroup C 17 vaccine programmes. Vaccine 2013;31:4477-86. 18 35. Khatami A, Peters A, Robinson H, et al. Maintenance of immune response throughout childhood following 19 serogroup C meningococcal conjugate vaccination in early childhood. Clinical and Vaccine Immunology: CVI 20 2011;18:2038-42. 21 36. Pace D, Snape M, Westcar S, et al. A new combination Haemophilus influenzae type b and Neisseria 22 meningitidis serogroup C-tetanus toxoid conjugate vaccine for primary immunization of infants. Pediatric 23 Infectious Disease Journal 2007;26:1057-9. 24 37. Schmitt HJ, Maechler G, Habermehl P, et al. Immunogenicity, , and immune memory after 25 primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate 26 vaccine. Clinical and Vaccine Immunology: CVI 2007;14:426-34. 27 38. Pace D, Snape M, Westcar S, et al. A novel combined Hib-MenC-TT glycoconjugate vaccine as a booster dose 28 for toddlers: a phase 3 open randomised controlled trial. Archives of Disease in Childhood 2008;93:963-70. 29 39. Marchant CD, Miller JM, Marshall GS, et al. Randomized trial to assess immunogenicity and safety of 30 Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate 31 vaccine in infants. Pediatric Infectious Disease Journal 2010;29:48-52. 32 40. Tejedor JC, Moro M, Merino JM, et al. Immunogenicity and reactogenicity of a booster dose of a novel 33 combined Haemophilus influenzae type b-Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine 34 given to toddlers of 13–14 months of age with antibody persistence up to 31 months of age. Pediatric 35 Infectious Disease Journal 2008;27:579-88. 36 41. Carmona A, Miranda M, Barrio F, et al. Reactogenicity and immunogenicity of combined Haemophilus 37 influenzae type b-meningococcal serogroup C conjugate vaccine booster dose coadministered with measles, 38 mumps, and . Pediatric Infectious Disease Journal 2010;29:269-71. 39 42. Gasparini R, Conversano M, Bona G, et al. Randomized trial on the safety, tolerability, and immunogenicity of 40 MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered 41 concomitantly with a combined tetanus, reduced diphtheria, and acellular in adolescents and 42 young adults. Clinical and Vaccine Immunology: CVI 2010;17:537-44. 43 43. Jackson LA, Baxter R, Reisinger K, et al. Phase III comparison of an investigational quadrivalent 44 meningococcal conjugate vaccine with the licensed meningococcal ACWY conjugate vaccine in adolescents. 45 Clinical Infectious Diseases 2009;49:e1-10. 46 44. Keyserling H, Papa T, Koranyi K, et al. Safety, immunogenicity, and immune memory of a novel 47 meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine (MCV-4) in 48 healthy adolescents. Archives of Pediatrics and Adolescent Medicine 2005;159:907-13. 49 45. Bermal N, Huang LM, Dubey AP, et al. Safety and immunogenicity of a tetravalent meningococcal serogroups 50 A, C, W-135 and Y conjugate vaccine in adolescents and adults. Human Vaccines 2011;7:239-47.

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1 46. Dbaibo G, Van der Wielen M, Reda M, et al. The tetravalent meningococcal serogroups A, C, W-135, and Y 2 tetanus toxoid conjugate vaccine is immunogenic with a clinically acceptable safety profile in subjects 3 previously vaccinated with a tetravalent polysaccharide vaccine. International Journal of Infectious Diseases 4 2012;16:e608-15. 5 47. Black S, Klein NP, Shah J, et al. Immunogenicity and tolerability of a quadrivalent meningococcal 6 glycoconjugate vaccine in children 2–10 years of age. Vaccine 2010;28:657-63. 7 48. Snape MD, Perrett KP, Ford KJ, et al. Immunogenicity of a tetravalent meningococcal glycoconjugate vaccine 8 in infants: a randomized controlled trial. [erratum appears in JAMA. 2011 Mar 16;305(11):1096]. JAMA 9 2008;299:173-84. 10 49. Perrett KP, Snape MD, Ford KJ, et al. Immunogenicity and immune memory of a nonadjuvanted quadrivalent 11 meningococcal glycoconjugate vaccine in infants. Pediatric Infectious Disease Journal 2009;28:186-93. 12 50. Pina LM, Bassily E, Machmer A, Hou V, Reinhardt A. Safety and immunogenicity of a quadrivalent 13 meningococcal polysaccharide diphtheria toxoid conjugate vaccine in infants and toddlers: three multicenter 14 phase III studies. Pediatric Infectious Disease Journal 2012;31:1173-83. 15 51. Pichichero M, Casey J, Blatter M, et al. Comparative trial of the safety and immunogenicity of quadrivalent 16 (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent 17 polysaccharide vaccine in two- to ten-year-old children. Pediatric Infectious Disease Journal 2005;24:57-62. 18 52. Memish ZA, Dbaibo G, Montellano M, et al. Immunogenicity of a single dose of tetravalent meningococcal 19 serogroups A, C, W-135, and Y conjugate vaccine administered to 2- to 10-year-olds is noninferior to a 20 licensed-ACWY polysaccharide vaccine with an acceptable safety profile. Pediatric Infectious Disease 21 Journal 2011;30:e56-62. 22 53. Jackson LA, Jacobson RM, Reisinger KS, et al. A randomized trial to determine the tolerability and 23 immunogenicity of a quadrivalent meningococcal glycoconjugate vaccine in healthy adolescents. Pediatric 24 Infectious Disease Journal 2009;28:86-91. 25 54. Reisinger KS, Baxter R, Block SL, et al. Quadrivalent meningococcal vaccination of adults: phase III 26 comparison of an investigational conjugate vaccine, MenACWY-CRM, with the licensed vaccine, Menactra. 27 Clinical and Vaccine Immunology: CVI 2009;16:1810-5. 28 55. Gill CJ, Baxter R, Anemona A, Ciavarro G, Dull P. Persistence of immune responses after a single dose of 29 Novartis meningococcal serogroup A, C, W-135 and Y CRM-197 conjugate vaccine (Menveo®) or Menactra® 30 among healthy adolescents. Human Vaccines 2010;6:881-7. 31 56. Baxter R, Baine Y, Ensor K, et al. Immunogenicity and safety of an investigational quadrivalent 32 meningococcal ACWY tetanus toxoid conjugate vaccine in healthy adolescents and young adults 10 to 25 33 years of age. Pediatric Infectious Disease Journal 2011;30:e41-8. 34 57. MacNeil JR, Cohn AC, Zell ER, et al. Early estimate of the effectiveness of quadrivalent meningococcal 35 conjugate vaccine. Pediatric Infectious Disease Journal 2011;30:451-5. 36 58. Vesikari T, Forstén A, Boutriau D, et al. A randomized study to assess the immunogenicity, antibody 37 persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate 38 vaccine in children aged 2–10 years. Human Vaccines and Immunotherapeutics 2012;8:1882-91. 39 59. Jacobson RM, Jackson LA, Reisinger K, et al. Antibody persistence and response to a booster dose of a 40 quadrivalent conjugate vaccine for meningococcal disease in adolescents. Pediatric Infectious Disease Journal 41 2013;32:e170-7. 42 60. Meerveld-Eggink A, de Weerdt O, de Voer RM, et al. Impaired antibody response to conjugated 43 meningococcal serogroup C vaccine in asplenic patients. European Journal of Clinical Microbiology and 44 Infectious Diseases 2011;30:611-8. 45 61. Balmer P, Falconer M, McDonald P, et al. Immune response to meningococcal serogroup C conjugate vaccine 46 in asplenic individuals. Infection and Immunity 2004;72:332-7. 47 62. Siberry GK, Williams PL, Lujan-Zilbermann J, et al. Phase I/II, open-label trial of safety and immunogenicity 48 of meningococcal (groups A, C, Y, and W-135) polysaccharide diphtheria toxoid conjugate vaccine in human 49 immunodeficiency virus-infected adolescents. Pediatric Infectious Disease Journal 2010;29:391-6.

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1 63. Siberry GK, Warshaw MG, Williams PL, et al. Safety and immunogenicity of quadrivalent meningococcal 2 conjugate vaccine in 2- to 10-year-old human immunodeficiency virus-infected children. Pediatric Infectious 3 Disease Journal 2012;31:47-52. 4 64. Bertolini DV, Costa LS, van der Heijden IM, Sato HK, Marques HH. Immunogenicity of a meningococcal 5 serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults. Vaccine 6 2012;30:5482-6. 7 65. Lujan-Zilbermann J, Warshaw MG, Williams PL, et al. Immunogenicity and safety of 1 vs 2 doses of 8 quadrivalent meningococcal conjugate vaccine in youth infected with human immunodeficiency virus. Journal 9 of Pediatrics 2012;161:676-81.e2. 10 66. O'Hallahan J, McNicholas A, Galloway Y, O'Leary E, Roseveare C. Delivering a safe and effective strain- 11 specific vaccine to control an epidemic of group B meningococcal disease. New Zealand Medical Journal 12 2009;122:48-59. 13 67. Vesikari T, Esposito S, Prymula R, et al. Immunogenicity and safety of an investigational multicomponent, 14 recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant 15 and child vaccinations: results of two randomised trials. The Lancet 2013;381:825-35. 16 68. Gossger N, Snape MD, Yu LM, et al. Immunogenicity and tolerability of recombinant serogroup B 17 meningococcal vaccine administered with or without routine infant vaccinations according to different 18 immunization schedules: a randomized controlled trial. JAMA 2012;307:573-82. 19 69. Santolaya ME, O'Ryan ML, Valenzuela MT, et al. Immunogenicity and tolerability of a multicomponent 20 meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, 21 observer-blind, placebo-controlled study. The Lancet 2012;379:617-24. 22 70. Novartis Vaccines and Diagnostics Pty Ltd. Product information: Bexsero® suspension for injection 23 [multicomponent meningococcal group B vaccine (recombinant, adsorbed)]. 2013. Available at: 24 https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/PICMI?OpenForm&t=pi&q=bexsero (accessed Sep 25 2014). 26 71. Snape MD, Saroey P, John TM, et al. Persistence of bactericidal antibodies following early infant vaccination 27 with a serogroup B meningococcal vaccine and immunogenicity of a preschool booster dose. Canadian 28 Medical Association Journal 2013;185:E715-24. 29 72. Snape MD, Philip J, John TM, et al. Bactericidal antibody persistence 2 years after immunization with 2 30 investigational serogroup B meningococcal vaccines at 6, 8 and 12 months and immunogenicity of preschool 31 booster doses: a follow-on study to a randomized clinical trial. Pediatric Infectious Disease Journal 32 2013;32:1116-21. 33 73. McQuaid F, Snape MD, John TM, et al. Persistence of bactericidal antibodies to 5 years of age after 34 immunization with serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age. Pediatric Infectious 35 Disease Journal 2014;33:760-6. 36 74. Santolaya ME, O'Ryan ML, Valenzuela MT, et al. Persistence of antibodies in adolescents 18−24 months after 37 immunization with one, two, or three doses of 4CMenB meningococcal serogroup B vaccine. Human Vaccines 38 and Immunotherapeutics 2013;9:2304-10. 39 75. Knuf M, Kieninger-Baum D, Habermehl P, et al. A dose-range study assessing immunogenicity and safety of 40 one dose of a new candidate meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate 41 (MenACWY-TT) vaccine administered in the second year of life and in young children. Vaccine 2010;28:744- 42 53. 43 76. Stamboulian D, Lopardo G, Lopez P, et al. Safety and immunogenicity of an investigational quadrivalent 44 meningococcal CRM197 conjugate vaccine, MenACWY-CRM, compared with licensed vaccines in adults in 45 Latin America. International Journal of Infectious Diseases 2010;14:e868-75. 46 77. Ramasamy MN, Clutterbuck EA, Haworth K, et al. Randomized clinical trial to evaluate the immunogenicity 47 of quadrivalent meningococcal conjugate and polysaccharide vaccines in adults in the United kingdom. 48 Clinical and Vaccine Immunology: CVI 2014;21:1164-8. 49 78. Granoff DM, Gupta RK, Belshe RB, Anderson EL. Induction of immunologic refractoriness in adults by 50 meningococcal C polysaccharide vaccination. Journal of Infectious Diseases 1998;178:870-4.

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1 79. de Voer RM, van der Klis FR, Engels CW, et al. Kinetics of antibody responses after primary immunization 2 with meningococcal serogroup C conjugate vaccine or secondary immunization with either conjugate or 3 polysaccharide vaccine in adults. Vaccine 2009;27:6974-82. 4 80. Artenstein MS, Brandt BL. Immunologic hyporesponsiveness in man to group C meningococcal 5 polysaccharide. Journal of Immunology 1975;115:5-7. 6 81. Richmond P, Kaczmarski E, Borrow R, et al. Meningococcal C polysaccharide vaccine induces immunologic 7 hyporesponsiveness in adults that is overcome by meningococcal C conjugate vaccine. Journal of Infectious 8 Diseases 2000;181:761-4. 9 82. Borrow R, Andrews N, Goldblatt D, Miller E. Serological basis for use of meningococcal serogroup C 10 conjugate vaccines in the United Kingdom: reevaluation of correlates of protection. Infection and Immunity 11 2001;69:1568-73. 12 83. National vaccine storage guidelines: Strive for 5. 2nd ed. Canberra: Australian Government Department of 13 Health and Ageing, 2013. Available at: 14 www.immunise.health.gov.au/internet/immunise/publishing.nsf/Content/IMM77-cnt (accessed Nov 2013). 15 84. Centers for Disease Control and Prevention (CDC), Cohn AC, MacNeil JR, et al. Prevention and control of 16 meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). 17 MMWR Recommendations and Reports 2013;62(RR-2):1-28. 18 85. O'Dempsey TJ, McArdle T, Ceesay SJ, et al. Meningococcal antibody titres in infants of women immunised 19 with meningococcal polysaccharide vaccine during pregnancy. Archives of Disease in Childhood Fetal and 20 Neonatal Edition 1996;74:F43-6. 21 86. Letson GW, Little JR, Ottman J, Miller GL. Meningococcal vaccine in pregnancy: an assessment of infant risk. 22 Pediatric Infectious Disease Journal 1998;17:261-3. 23 87. Prymula R, Esposito S, Zuccotti GV, et al. A phase 2 randomized controlled trial of a multicomponent 24 meningococcal serogroup B vaccine (I): Effects of prophylactic paracetamol on immunogenicity and 25 reactogenicity of routine infant vaccines and 4CMenB. Human Vaccines and Immunotherapeutics 26 2014;10:1993-2004. 27 88. Velentgas P, Amato AA, Bohn RL, et al. Risk of Guillain-Barré syndrome after meningococcal conjugate 28 vaccination. Pharmacoepidemiology and Drug Safety 2012;21:1350-8. 29 89. Communicable Diseases Network Australia (CDNA). Invasive meningococcal disease: CDNA national 30 guidelines for public health units. Canberra: Australian Government Department of Health, 2014. Available at: 31 http://www.health.gov.au/cdnasongs (accessed Nov 2014). 32

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1 RELEVANT TEXT FROM OTHER CHAPTERS OF THE AUSTRALIAN 2 IMMUNISATION HANDBOOK 10TH EDITION

3 UPDATED TO ALIGN WITH CHANGED RECOMMENDATIONS IN CHAPTER 4.10 4 MENINGOCOCCAL DISEASE

5 6 2.1 PRE-VACCINATION

7 2.1.5 Catch-up 8 Using the catch-up worksheet (Figure 2.1.1) for children <10 years of age

9 Table 2.1.5: Minimum acceptable age for the 1st dose of scheduled vaccines in infants in special 10 circumstances*

Vaccine Minimum age for 1st Action if a vaccine dose is inadvertently administered prior to the recommended minimum dose in special age17 circumstances*

Meningococcal¶ 6 weeks¶ If the 1st dose of either 4vMenCV or MenBV is administered between >28 days and <42 days (6 weeks) of age, the dose does not necessarily need to be repeated; however, expert advice should be sought.

11 ¶ The listed minimum age only applies to the Menveo 4vMenCV brand and MenBV, which can both be used in infants (see 4.10 12 Meningococcal disease). MenCCV is recommended for use in infants at 12 months of age. The ACIR will record MenCCV given at 13 ≥11 months of age as a valid dose for the purposes of calculating immunisation status. It is expected that a single dose of MenCCV 14 provided at ≥11 months (but before 12 months) of age is likely to be immunogenic. As such, doses given in this timeframe may not 15 need to be repeated in all circumstances. 16

17 Table 2.1.7: Minimum acceptable dose intervals for children <10 years of age

Vaccine Minimum interval Minimum interval Minimum interval between dose 1 and 2 between dose 2 and 3 between dose 3 and 4

Meningococcal¶ Minimum acceptable dose intervals vary for the different meningococcal vaccines. Refer to footnote¶ 18 ¶ The recommended schedule for meningococcal vaccines varies for different formulations (see 4.10 Meningococcal disease). The 19 minimum acceptable interval between conjugate vaccines containing meningococcal serogroup C (MenCCV, Hib-MenCCV and 20 4vMenCV) is 8 weeks. The minimum acceptable interval between primary doses of MenBV is 4 weeks for infants aged <6 months. 21 There is no clinical trial data in older children for minimum intervals less than the routinely recommended interval of 2 months. In 22 circumstances where MenBV and 4vMenCV are indicated, and the vaccines are not administered concurrently, a minimum interval of 4 23 weeks between vaccines is recommended. 24 25 Catch-up guidelines for individual vaccines for children <10 years of age 26 Meningococcal C conjugate vaccine 27 Meningococcal C conjugate vaccine (MenCCV) is recommended as a single dose for children at 12 months of 28 age (as either MenCCV or Hib-MenCCV combination vaccine). If a dose has not been given at ≥12 months of 29 age (or if dose(s) were given at <12 months of age), a single dose of MenCCV is recommended (see 4.10 30 Meningococcal disease). 4vMenCV and MenBV are recommended for certain children at increased risk of 31 meningococcal disease due to age and/or other risk factors (see 3.3 Groups with special vaccination 32 requirements and 4.10 Meningococcal disease). 33 34 Catch-up schedules for persons ≥10 years of age 35 For example, a 32-year-old woman (Age) is returning to nursing (Occupation) but has only ever had 1 dose of 36 , 4 doses of the oral poliomyelitis vaccine, 1 dose of MMR vaccine and 2 doses of DTPw 37 vaccine as a child and recently had a splenectomy (Health) following an accident. This person would require:

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1 • 1 dose of dTpa 2 • 2 adult doses of hepatitis B; 1 dose given now and a further dose in 2 months 3 • no further doses of poliomyelitis vaccine (is fully vaccinated against poliomyelitis) 4 • 1 dose of MMR vaccine 5 • 2 doses of if non-immune; 1 dose given now and a further dose in 4 weeks 6 • 1 dose of , and 1 dose annually thereafter 7 • : 1 dose of 13vPCV, followed by 23vPPV approximately 2 months later (because of 8 splenectomy) 9 • 1 dose of (because of splenectomy) 10 • 2 doses of 4vMenCV; 1 dose given now and a further dose in 8 weeks (because of splenectomy) 11 • 2 doses of MenBV; 1 dose given now and a further dose in 8 weeks (because of splenectomy). 12

13 Table 2.1.12: Catch-up schedule for persons ≥10 years of age (for vaccines recommended on a 14 population level)

Vaccine Doses required Minimum interval Minimum interval between dose 1 and 2 between dose 2 and 3

MenCCV‡ 1 dose Not required Not required

15 ‡ 4vMenCV and MenBV are indicated for those at increased risk of meningococcal disease; see recommendations in 4.10 Meningococcal 16 disease and 3.3 Groups with special vaccination requirements. 17 18 19

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1 3.2 VACCINATION FOR INTERNATIONAL TRAVEL

2 3.2.4 Vaccines 3 Routinely recommended vaccines (not specifically related to travelling overseas) 4 Meningococcal disease 5 A single dose of MenCCV is recommended for all children at the age of 12 months (see 4.10 Meningococcal 6 disease). This can be provided as either MenCCV or the combination vaccine Hib-MenCCV. Vaccination 7 against meningococcal serogroup B is recommended for certain age groups who are at increased risk of 8 meningococcal disease (see 4.10 Meningococcal disease). 9 10 3.2.5 Vaccinating the traveller with special risk factors

11 Table 3.2.2: Recommended lower age limits of travel vaccines for children*

Vaccine Lower age limit Dose/route Dosing intervals

Meningococcal ACW135Y (quadrivalent conjugate 4vMenCV) Menveo 2 months 0.5 mL IM Varies by age at time of Menactra 2 years 0.5 mL IM vaccination and vaccine brand. Refer to Table 4.10.3 in 4.10 Nimenrix 12 months 0.5 mL IM Meningococcal disease

Meningococcal ACW135Y (quadrivalent polysaccharide 4vMenPV) Mencevax ACWY ¶ Menomune 7 years 0.5 mL SC Single dose 7 years¶ 0.5 mL SC Single dose

12 ¶ 4vMenCV is preferred. However, 4vMenPV is a suitable alternative for travellers aged ≥7 years when the need for repeat doses is not 13 anticipated (see 4.10 Meningococcal disease). 14

18

1 3.3 GROUPS WITH SPECIAL VACCINATION REQUIREMENTS

2 3.3.2 Vaccination of women who are planning pregnancy, pregnant or breastfeeding, and preterm infants 3 Pregnant women

4 Table 3.3.1: Recommendations for vaccination in pregnancy (see also disease-specific chapters in Part 4)

Vaccines not routinely recommended in pregnancy Inactivated bacterial vaccines Recommendation Comments Meningococcal conjugate vaccines (MenCCV, Hib- Not routinely recommended There are limited data on the safety of meningococcal conjugate vaccines in pregnancy.21 MenCCV or 4vMenCV) Where clinically indicated, meningococcal conjugate vaccine can be given to pregnant Can be given to pregnant women at increased risk of meningococcal disease (see 22 4.10 Meningococcal disease) women. Meningococcal polysaccharide vaccine (4vMenPV) Not routinely recommended Limited available data suggest that it is unlikely that use of meningococcal polysaccharide vaccine in pregnant women has any deleterious effects on pregnancy Can be given to pregnant women at increased risk of meningococcal disease (see 23,24 4.10 Meningococcal disease) outcomes. Where clinically indicated, meningococcal polysaccharide vaccine can be given to pregnant women, although 4vMenCV is preferred.22 Meningococcal B vaccine (MenBV) Not routinely recommended No data are available. Vaccination during pregnancy has not been evaluated, although is Can be given to pregnant women at increased risk of meningococcal disease (see unlikely to result in adverse effects. 4.10 Meningococcal disease) 5 6

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1 3.3.3 Vaccination of immunocompromised persons 2 Solid organ transplant recipients

3 Table 3.3.2: Recommendations for vaccinations for solid organ transplant (SOT) recipients96,98 Vaccine Vaccines recommended before Vaccines recommended after Comment transplantation transplantation, if not given beforehand

Child Adult Child Adult (0–18 years) (≥19 years) (0–18 years) (≥19 years) Neisseria meningitidis (meningococcal disease)

Meningococcal C conjugate Yes Not indicated Yes Not indicated A single dose of meningococcal C conjugate vaccine is recommended at 12 months of vaccine (MenCCV or Hib- age. MenCCV) 4vMenCV is recommended for persons with certain medical conditions or treatments that increase their risk of IMD (see below).

Quadrivalent meningococcal Yes, if ≥2 months of Yes, if defined risk Yes, if ≥2 months of Yes, if defined risk 4vMenCV is recommended for persons with certain medical conditions or treatments that conjugate vaccine age with defined risk factors (see comments) age with defined risk factors (see comments) increase their risk of IMD (see 4.10 Meningococcal disease, List 4.10.1). The vaccine (4vMenCV)* factors (see comments) factors (see comments) brand and doses required depend on the age at which the vaccine course is commenced (see 4.10 Meningococcal disease, Table 4.10.2).

Meningococcal B vaccine Yes, if at risk due to Yes, if defined risk Yes, if at risk due to Yes, if defined risk MenBV is recommended for certain age groups and individuals with specific risk factors (MenBV) age or other defined factors (see comments) age or other defined factors (see comments) placing them at increased risk of IMD (see 4.10 Meningococcal disease). The number of risk factors (see risk factors (see doses varies with age as outlined in Table 4.10.1 in 4.10 Meningococcal disease. comments) comments)

4

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1 Haematopoietic stem cell transplant recipients99,100

2 Table 3.3.3: Recommendations for revaccination following haematopoietic stem cell transplant (HSCT) 3 in children and adults, irrespective of previous immunisation history99,100,107-111

Vaccine Months after HSCT Comments

6 8 12 24

Neisseria meningitidis (meningococcal disease)

Meningococcal B vaccine Yes Yes Not needed Not needed Two doses of MenBV are recommended for (MenBV) (see (see persons ≥6 months of age. Additional doses are comments) comments) required if the vaccine course was commenced before 6 months of age (see 4.10 Meningococcal disease, Table 4.10.1). Quadrivalent Yes Yes† Not needed Not needed Two doses of 4vMenCV are recommended for meningococcal conjugate (see (see persons ≥6 months of age. Additional doses are vaccine (4vMenCV)* comments) comments) required if the vaccine course was commenced before 6 months of age (see 4.10 Meningococcal disease, Table 4.10.2). 4 † The recommended interval between doses is 12 weeks for children who commenced their 4vMenCV course between 7 and 23 months 5 of age as outlined in Table 4.10.2 in 4.10 Meningococcal disease. 6 7 Inactivated (non-live) vaccines 8 • 4vMenCV and MenBV are recommended (see 4.10 Meningococcal disease). A diminished immune 9 response following a single dose of 4vMenCV has been reported in HIV-infected persons; however, this 10 improves for some serogroups following a 2nd dose. There is no clinical data on the use of MenBV in HIV- 11 infected persons; however, vaccination is recommended based on the expected benefit in these individuals. 12 13 Persons with functional or anatomical asplenia 14 Meningococcal vaccination 15 4vMenCV is recommended from 2 months of age. The vaccine brand and doses required depend on the age at 16 which the vaccine course is commenced (see 4.10 Meningococcal disease, Table 4.10.2). 17 MenBV is recommended from 2 months of age for persons with asplenia. The number of doses depends on the 18 age at which the vaccine course is commenced as shown in Table 4.10.1 in 4.10 Meningococcal disease. 19

20 Table 3.3.5: Recommendations for vaccination in persons with functional or anatomical asplenia

Age Recommendations

Meningococcal vaccines ≥2 months‡ 4vMenCV is recommended according to the age at which the vaccine course commenced (see 4.10 Meningococcal disease, Table 4.10.2). MenBV is recommended according to the age at which the vaccine course commenced (see 4.10 Meningococcal disease, Table 4.10.1). 21 ‡ MenBV can be given from 6 weeks of age to align with the schedule for other routine infant vaccines (see 22 4.10 Meningococcal disease). The minimum interval between 4vMenCV and MenBV is 4 weeks (see 2.1.5 23 Catch-up). 24

21

1 3.3.7 Vaccination of persons at occupational risk

2 Table 3.3.7: Recommended vaccinations for persons at increased risk of certain occupationally 3 acquired vaccine-preventable diseases*†

Occupation Vaccine

Laboratory personnel Laboratory personnel handling veterinary specimens or working with Q fever organism (Coxiella burnetii) Laboratory personnel handling either bat tissues or Rabies lyssaviruses (including rabies virus and Australian bat lyssavirus) Laboratory personnel routinely working with these organisms: Bacillus anthracis Anthrax¶ Vaccinia poxviruses Smallpox¶ Poliomyelitis virus Poliomyelitis (IPV) Salmonella enterica subspecies enterica serovar Typhi Typhoid (S. Typhi) Yellow fever virus Yellow fever Neisseria meningitidis Quadrivalent meningococcal conjugate vaccine (4vMenCV)# Meningococcal B (MenBV) Japanese encephalitis virus Japanese encephalitis 4 # 4vMenPV can be used if the risk of exposure is not expected to be ongoing and the need for repeat doses is 5 not anticipated (see 4.10 Meningococcal disease). 6

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