A male baby, age 7 days, presented to the Emergency Department with an 11 hour history of reduced feeding. He was afebrile but had a petechial rash, lethargy and poor perfusion. He was born by uncomplicated, term vaginal delivery and went home at 5 days of age with his parents and a fully immunised 2-year-old sister. There were no reports of contacts with unwell persons, and there was no household overcrowding. The number of visitors to the baby in the preceding days was not recorded.
The neonate was resuscitated with intravenous fluids. Cefotaxime, penicillin and gentamicin were administered. He improved somewhat following fluid administration and proceeded to a full septic screen when stable.
Investigations revealed a normal full blood count, coagulation profile, electrolytes and c-reactive protein. Urine showed a high specific gravity (>1.03) indicative of dehydration, with the final negative culture. Cerebrospinal fluid contained 1×106/L leucocytes, 371 × 106/L erythrocytes, protein 1.06 g/L and glucose 2.2 mmol/L (blood glucose 3.2 mmol/L). Nasopharyngeal aspirate was negative, and the chest x-ray was normal.
Due to the infant’s state on presentation, the paediatric team decided to arrange early transfer to a tertiary centre for likely intensive care management. However, while awaiting the arrival of the transfer team, the baby developed irregular breathing, prolonged apnoeas and finally cardiorespiratory arrest. The presence of disseminated intravascular coagulation complicated intubation and ventilation. The baby died despite prolonged cardiopulmonary resuscitation. Cerebrospinal fluid and blood cultures both grew Neisseria meningitides serogroup B.
Meningococcal disease is caused by various strains of the bacterium Neisseria meningitides – strains B and C are the most common in Australia. The disease is spread through close contact and/or sharing of or exposure to respiratory fluids (coughing/sneezing/sharing drink bottles etc) from an infected individual. Up to 10% of the population harbour N. meningitides, primarily in nasal passages, at any one time. This may be the reason for the natural immunity found in most adults. Maternal antibodies, transferred transplacentally in the third trimester, commonly protect very young infants from the disease. Our patient above was sadly not so fortunate.
Invasive disease may result in septicaemia and/or meningitis. Up to one in ten patients with invasive disease will die. One in 30 of the survivors experiences loss of limbs or severe scarring, and another one in 30 suffers severe brain damage.
Around 200 cases of meningococcal disease occur annually in Australia, with the highest incidence in children under 5, and the highest risk of death in children under 12 months. Adolescents are an additional high-risk group.
The only vaccine on the current Australian Immunisation Schedule is the serotype C conjugate vaccine, given at 12 months of age. A quadrivalent vaccine covering serotypes A, C, W123 and Y is available and recommended for some high-risk groups (such as overseas travellers) but immune responses are limited in young children.
The meningococcal B vaccine was slow in development because the capsule of the bacterium has protein marker similarities with human antigen neural-cell adhesion molecules. After many years of research, a Meningococcal B vaccine is now available in Australia for private purchase only.
A little more on Bexsero:
Bexsero is a 4-component, protein-based vaccine (4CMen B) – that means, the vaccine contains 4 antigenic meningococcal B components (identified after whole-genome sequencing of the bacterium).
It was approved on the Australia Register of Therapeutic Goods in August 2013 and can be used in persons over two months of age (although the first dose may be given as early as six weeks of age to suit the current vaccination schedule). It is recommended for children under five, adolescents age 15-19, and immunocompromised/asplenic children and adults.
As per laboratory tests, just under 80% of meningococcal B strains are covered by the vaccine. For infants under six months, three doses of the vaccine plus a booster at 12 months is the current recommendation. Older children and adults need fewer doses. One month after the third dose in infants, 84-100% of patients in clinical trials had achieved an adequate immunological response – following the booster dose, this increased to 95-100%.
Local and systemic reactions are very common – particularly fever (77% of infants, compared to 45% post routine vaccinations). A very small rate of febrile seizures have been attributed to the vaccine. Therefore paracetamol should be given prophylactically prior to and in the 12-24 hours following administration. Some cases of Kawasaki disease were seen in the original cohort, but this has not been replicated in surveillance following Bexsero’s general release. In order to lessen the risk of fever, many infants are being given their vaccines at 3, 5, and 7 months, off-setting with the usual vaccine schedule.
The current cost is AU$140-$150 per vaccine.
The public health ethics in this situation are a little tough to take – it’s so expensive at present that the vaccine is out of reach for many families. Invasive meningococcal disease is rare, but the outcome can easily be devastating, and given the relatively reassuring safety profile of the vaccine so far, it would appear to be a straightforward choice (if not for the financial implications) for most families. Having seen for myself the tragedy of meningococcal B, I won’t be hesitating to vaccinate my own children. It hardly seems fair that families struggling to make ends meet won’t be able to offer the same to their children, at least for now.
The Pharmaceutical Benefits Advisory Committee has so far rejected inclusion of Bexsero in the immunisation schedule due to essentially a limited cost-benefit ratio. They noted that “approximately 272,224 individuals would need to be fully vaccinated to avoid one death”.
Essentially, Bexsero is still yet to prove itself. Lab evidence is one thing, but a measurable reduction in actual cases is what the Committee wants to see.
Other countries, like the UK, are currently funding it on their routine vaccination schedules, but since the vaccine remains in its own infancy, its large-scale impact on morbidity and mortality remains yet to be proven.
The Committee has a fair point. The vaccine does need to prove itself, but whilst an apparently safe vaccine exists, with at least a theoretical 80% protectiveness against a truly horrific disease, it’s going to be very hard to explain to affected families why they have to suffer the consequences of the Committee’s decision.
Smith A, Zehetner A. Early onset neonatal serogroup B meningococcal meningitis and septicaemia. J Paediatr Child Health. 2013;49(2):158-158.
Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D et al. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. The Lancet. 2013;381(9869):825-835.