Recent outbreaks highlight the risks of bacterial meningitis – and the need to vaccinate

Outbreaks of bacterial meningococcal disease in England^[1] and recent cases in students in New Zealand^[2] have raised awareness of this serious and life-threatening disease.

The disease is caused by the bacterium Neisseria meningitidis and presents as meningitis or blood poisoning (septicaemia)^[3].

Meningitis is an inflammation of the membranes that cover the brain and spinal cord (meninges), while septicaemia affects the whole body through the presence of bacteria in the blood stream.

Both can be also be caused by other infectious agents, but bacterial meningococcal disease is the most severe form.

Infants, children and young adults are at higher risk. While the disease is largely preventable through vaccination, only one vaccine is currently on the national immunisation schedule^[4] in Aotearoa New Zealand.

As part of ongoing research to explain the recent cases, we compared the meningococcal strains involved in both countries and explored the significance of people who carry the bacterium but don’t develop symptoms or disease.

There are several strains of Neisseria meningitidis and most belong to six groups (named A, B, C, W, X and Y). All have an extraordinary ability to swap genetic material between them and switch genes on and off through a process known as phase variation^[5].

This can change the surface of the bacterium, enabling it to escape the body’s immune system.

The strains responsible for both the UK and recent Dunedin cases belong to Group B meningococci. However, the similarity ends there. The UK outbreak strain is known as ST485^[6], while the Dunedin cases were caused by different strains. They differ from the UK strain as well as from each other, suggesting more than one chain of transmission was involved.

The Bexsero vaccine^[7] is used to protect people against bacterial meningitis caused by group B strains. It was designed to recognise components in the outer membrane and on the surface of the bacteria.

The strain that caused the UK outbreak is likely covered by the Bexero vaccine^[8] because it matches exactly one of the protein antigen sequences used in the vaccine.

But genomic sequencing of the bacteria responsible for one of the Dunedin cases is still pending, while the other case did not yield a bacterial culture.

The importance of genome sequencing

Although meningococcal disease can appear as scattered and apparently unrelated cases, these can occasionally build into larger outbreaks.

Strain typing and genome sequencing can help to determine if an apparent outbreak is due to the emergence of a particular strain or a cluster of cases that are genetically unrelated.

Both scenarios can occur if cases share a common risk factor, such as increased close contact and mixing in educational settings such as schools and universities.

Past genomic surveillance in New Zealand has shown the emergence of outbreak strains and helped identify likely resistance to antibiotics^[9]. For example, a W group strain variant caused rising numbers of meningococcal disease between 2016 and 2019 in New Zealand and an outbreak in Northland in 2018.

Genome sequencing showed this strain was different from the W strain causing disease in Europe at the time, and the specific 2015 variant also has increased resistance to penicillin^[10].

Healthy people can be carriers

Despite its ability to cause severe disease, the bacterium causing meningococcal disease is often found in people’s throat, without causing symptoms.

About 5% to 30% of the global population are carriers^[11], and most don’t experience any symptoms or disease. We don’t yet fully understand the factors that determine whether disease develops.

Genome sequencing has shown that some highly virulent strains which are associated with outbreaks are rarely identified in samples from healthy carriers. But as yet, attempts to find genomic explanations for differences in bacteria found in outbreaks and healthy carriers remain inconclusive^[12].

The likelihood whether people carry the bacterium is age dependent^[13]. It is low in younger children and older people, but high in teenagers and young adults.

The high carriage rate in young adults makes university students a high-risk group for developing the disease. Crowded living conditions also contribute to the high carriage rate, exacerbating the risk.

In New Zealand, both the Bexsero (against group B) and MenQuadfi (against ACWY) vaccines are available to young people moving into boarding school or university halls the first time. In contrast, only one vaccine (against ACWY) is currently funded for university students in England^[14].

Both vaccines are needed to have maximum protection. Conjugate ACWY vaccines may reduce carriage and therefore transmission^[15]. Bexsero does not reduce carriage^[16] but protects against development of the disease.

Impact of COVID measures on transmission

Lockdowns and border controls introduced during the COVID pandemic reduced transmission of the SARS-CoV2 virus. But they also had a major effect on other diseases, including influenza^[17] and other respiratory viruses^[18].

Cases of meningococcal disease were also dramatically reduced^[19] during the COVID response, most likely due to reduced contact between individuals and because fewer infected people entered the country.

The rebound in cases following relaxation of these strict measures was expected.

This highlights how important it is to be aware of the risks associated with large gatherings, particularly of young people, and the need to vaccinate with the Bexsero vaccine as part of the immunisation schedule^[22] as well as MenQuadfi for high-risk groups.

References

1. ^{^} bacterial meningococcal disease in England (www.gov.uk)
2. ^{^} recent cases in students in New Zealand (www.rnz.co.nz)
3. ^{^} meningitis or blood poisoning (septicaemia) (www.meningitis.org)
4. ^{^} national immunisation schedule (www.healthnz.govt.nz)
5. ^{^} phase variation (doi.org)
6. ^{^} ST485 (www.gov.uk)
7. ^{^} Bexsero vaccine (immune.org.nz)
8. ^{^} covered by the Bexero vaccine (www.gov.uk)
9. ^{^} antibiotics (wwwnc.cdc.gov)
10. ^{^} increased resistance to penicillin (wwwnc.cdc.gov)
11. ^{^} carriers (academic.oup.com)
12. ^{^} remain inconclusive (doi.org)
13. ^{^} age dependent (pubmed.ncbi.nlm.nih.gov)
14. ^{^} England (www.theonlinegp.com)
15. ^{^} may reduce carriage and therefore transmission (pubmed.ncbi.nlm.nih.gov)
16. ^{^} does not reduce carriage (academic.oup.com)
17. ^{^} influenza (www.researchsquare.com)
18. ^{^} other respiratory viruses (rdcu.be)
19. ^{^} dramatically reduced (www.thelancet.com)
20. ^{^} Data extracted from the PHF Science notifiable disease dashboard for meningococcal disease (www.phfscience.nz)
21. ^{^} CC BY-SA (creativecommons.org)
22. ^{^} immunisation schedule (cdn.prod.website-files.com)