I’ll never forget the throbbing, pounding headache that heralded the onset of meningococcal meningitis and septicaemia as a 14 year old girl; the complete overwhelm of the horrifying physical sensation that is sepsis. Within two hours I was unconscious – but thanks to a vocal family member advocating their concern for how sick I was, a NETS retrieval to a tertiary unit was swiftly arranged where I was diagnosed with serotype C strain meningococcal disease. I was incredibly fortunate to receive excellent care and survive unscathed.Recently, a surge in (serogroup W135) meningococcal disease has resulted in increased attention towards the quadrivalent vaccine. Many parents are questioning if they should immunise their babies or toddlers and, in a similar vein to the MenB vaccine (another post in itself), why isn’t it part of the National Immunisation Programme for this age group? As we approach the meningococcal peak season of spring, it’s worth looking at the science behind the news headlines.
Who gets meningococcal disease?
Meningococcal disease is a rare yet rapidly progressing and highly fatal infection caused by the gram-negative aerobic bacterium Neisseria meningitidis. There are 13 known serogroups but A, B, C, W135 and Y are the most common to cause disease.
- menigitidis may cause endemic and epidemic infections – the vast majority of the latter occur in low- and middle-income settings where disease control is complicated by poor health infrastructure. The most recent epidemic in the ‘meningitis belt’ of sub-Saharan Africa occurred in 2009 and resulted in the deaths of over 4,000 children due to serotype A disease.
- meningitidis is spread by aerosolised particles and colonises the nasopharynx of a significant proportion of the population. Carriage rates vary by age, from 5% of infants to a peak of 24% in 19 year olds before diminishing to 8% in older adults. The bacteria attaches to the mucosal surfaces of tonsils and adenoids via adhesion proteins; and a very small proportion of these will cross the mucosal barrier to cause invasive meningococcal disease (IMD), which presents as septicaemia and/or meningitis. There are two small peaks in IMD incidence across the age range, which occur in children <5 years and adolescents aged 15-19 years (in whom carriage rates are highest).
While the vast majority of people will simply carry Neisseria asymptomatically, a very small proportion proceed to invasive infection. Factors associated with an increased risk of progressing to IMD include:
- Complement deficiency, due to either a congenital deficiency in a single terminal protein (which will almost always be undiagnosed) or a complement-depleting underlying illness
- Recent or concurrent viral respiratory tract infection, particularly influenza virus
- Living in close confines
- Intimate kissing
- Exposure to either active or passive cigarette smoke (in one study, having a mother who smokes was the strongest independent risk factor for invasive meningococcal disease in children)
- History of preterm birth
How does IMD present?
The clinical presentation of IMD is non-specific with features including sudden-onset fever, a rash (which may be petechial, purpuric or maculopapular); altered LOC, cool peripheries, nausea and vomiting; and photophobia and neck stiffness (with meningitis). The mortality risk is high (between 5 to 10% even with appropriate antibiotic therapy), and of those who survive up to 1 in 3 will suffer long-term consequences (predominantly limb deformities, sensorineural hearing loss and neurological deficits). This high mortality and morbidity burden is secondary to endotoxin-induced vascular collapse induced by N.menigitidis.
Despite media reports often marred by an element of hysteria, IMD remains extremely rare with 1.1 per 100,000 people diagnosed in Australia in 2016 (compare this to the incidence of influenza which occurs in close to 500 per 100,000 Australian children each season, necessitating ICU admission in 6 per 100,000). IMD has seasonal and temporal variations, with peaks seen in Spring each year and multi-year cycles resulting in variable prevalence rates for different serotypes each year. The natural fluctuation in the predominant serogroup over time is only partially attributable to vaccination – a significant decline in the prevalence of serogroup B disease had already begun to occur prior to the current surge in private immunisation rates.
A recent increase in serogroup W135 disease (responsible for 45% of cases in 2016) has boosted interest in immunisation against this serotype. There were 110 cases of W135 in 2016, surpassing serogroup B for the first time since 2002. Concurrently, a small increase in serogroup Y disease (41 cases [16%] in 2016) occurred. Despite causing the highest burden from a global perspective serotype A remains rare in Australia, while serogroup C has dropped from 225 (2002) to 3 notified cases per year (2016; a 99% decline following the national immunisation programme roll-out in 2003).
Part of the concern regarding the increase in W135 disease is that many of these cases have belonged to the hypervirulent ST11 clonal complex, which is associated with an atypical clinical presentation and a higher case fatality rate (8%).
Should we be immunising everyone?
Vaccination for meningococcal is aimed at stopping the transmission between asymptomatic colonised people and those who are susceptible and non-colonised. In light of the recent increase in W135 and Y serotype illness, targeted state-based immunisation programmes were introduced in 2017 for adolescents (targeting 15 – 19 year olds) to protect the age bracket with the highest rates of nasopharyngeal colonisation. For other age groups, the quadrivalent meningococcal vaccine may be provided through private prescription. Vaccination should be recommended for:
- People at increased risk of IMD – those with known complement disorders, functional or anatomical asplenia, and other immunocompromising conditions
- Children in age groups with increased incidence of IMD or high carriage rates of meningitidis – particularly those aged <2 years and adolescents, or those living in close quarters such as boarding school or college accommodation
- Travellers – in particular to the ‘meningitis belt’ of Africa. Proof of immunisation with the 4vMenCV is also a requisite for pilgrims attending the annual Hajj in Mecca.
Which should I prescribe? Are they all the same?
There are two types of quadrivalent meningococcal vaccination – polysaccharide and conjugate vaccines. However, as of early 2017, the polysaccharide vaccines (MPSV4; Mencevax and Menomune) have been discontinued in Australia due to their poorer immunogenicity potential. The available conjugate vaccines (4vMenCV) work by conjugating the antigens of four serogroups (A, C, W135 and Y) to a carrier protein. All are safe and immunogenic. Available 4vMenCV in Australia include:
- Menactra (Sanofi Pasteur)
- Menveo (GSK)
- Nimenrix (Pfizer)
The brand and dosing regimen depends upon the age group you are prescribing for, but for healthy children:
|Age at presentation to commence immunisation course||Recommended brand||Number of doses required||Interval between doses|
|≤ 6 months*||Menveo||3 doses||8 weeks|
|7 – 11 months||Menveo||2 doses||12 weeks|
|12 – 23 months||
|≥2 years||Any||1 dose||–|
*Immunisation is not indicated in children <2/12
A simple rule is to prescribe Menveo for younger age groups opening to broader possibilities with increased age; and the younger the child, the more doses that will be required. Booster doses will be needed in adolescence, and for travellers. The vaccines are not interchangeable, and commencing a course with one brand requires completion of the course with that brand.
But there doesn’t seem to be any quadrivalent vaccines around?
A worldwide shortage of quadrivalent vaccines has impacted the Australian supply, largely driven by a demand increase which was unprecedented by the pharmaceutical companies. The international supply is prioritised to nations that have implemented the vaccination into their national immunisation programmes. Pharmaceutical companies have recognised this, and are trying to increase supply to global demand levels.
The bottom line:
- Up to one quarter of children carry Neisseria meningitidis in their nasopharynx. Risk factors for progression to invasive disease include exposure to cigarette smoke, a recent or concurrent viral illness, living in close confines or immunodeficiency (particularly within the complement pathway)
- Serotype W135 is currently the most common strain causing invasive meningococcal disease in Australia, although disease incidence remains extremely rare
- Vaccination should be encouraged for children in age groups with increased incidence of IMD or high carriage rates of meningitidis, particularly children aged <2 years and adolescents, and those living in close quarters such as boarding school or college accommodation
- Adolescents (aged 15 – 19 years) are currently eligible to receive the quadrivalent vaccine under the national immunisation programme administered via state-based programmes
- Children >2 months can be immunised on a private prescription using one of 3 available conjugate quadrivalent vaccines which require increasing doses when the course is commenced at a younger age. The available vaccines are not interchangeable and a course needs to be completed with the brand in which it was commenced.
 The World Health Organisation; Global Health Observatory Data: Number of suspected meningitis cases and deaths reported (2010); Available: https://www.who.int/gho/epidemic_diseases/meningitis/suspected_cases_deaths_text/en/
 Christensen, H. et al. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infectious Diseases (2010); 10(12) 853-61.
 Ellison, R. et al. Prevalence of congenital or acquired complement deficiency in patients with sporadic meningococcal disease. NEJM(1983),308(16), 913.
 Fischer, M. et al. Tobacco smoke as a risk factor for meningococcal disease. Paediatric Infectious Disease Journal; 1997; 16(10); 979.
 Australian Government Department of Health. Invasive meningococcal disease national surveillance report, with a focus on MenW. 9 January 2017. Available from: ntent/ohp-meningococcal-W.htm (Accessed February 2017)
 Lahra MM, Enriquez RP. Australian Meningococcal Surveillance Programme annual report, 2012. Communicable Diseases Intelligence 2013;37:E224-32
 National centre for immunisation research and surveillance; March 2017.
 Australian Government Department of Health Invasive Meningococcal Disease National Surveillance Report; 12 December 2016
 . Gasparini R, Panatto D. Meningococcal glycoconjugate vaccines. Human Vaccines 2011;7:170-82