menB outbreak in Kent -- initial thoughts

A cluster of meningitis cases is currently dominating the UK news. At least five of the cases have been confirmed as serotype B (menB), from what I can tell the others have not yet been analysed.

My PhD was on bacterial meningitis, specifically whether human or pathogen genetics makes meningitis more likely. We mostly focused on pneumococcal meningitis as it is more common, but we did also have data from meningococcal meningitis patients.

The current outbreak made me think back to what I knew about meningitis and about two specific questions:

1. Why is this happening and why now?
2. Is there a broader risk, and what interventions might be effective?

Here are some initial thoughts based on my memories and a bit of reading today.

Basic facts and thoughts

The meningococcus is carried asympotmatically. Estimates always seem to vary quite widely by method (e.g. molecular vs culture) and population, but something like 10-20% seems about right. This paper from 2008-9 found about 30% of these carriage episodes were menB.

Meningitis is a (very) rare outcome of carriage, where the bacteria crosses into the blood (bacteremia) and then the blood-brain barrier into the cerebrospinal fluid. This causes massive inflammation, pressure on the brain, and is very dangerous. Many cases of meningitis lead to permanent disability (e.g. hearing loss), loss of limbs, or death (~10% of cases). Swift administration of antibiotics via spinal tap in hospital are required; possibly also steroids to reduce inflammation (depending on country). The majority of cases are in infants, the elderly, and immunocompromised adults.

I am less aware of literature on carriage duration in meningococcus, but from what I can find some carriage episodes last over a year. The resolution of this study was limited, and going from the pneumococcus I might predict that carriage episodes typically last for around a month, but some are much more prolonged. We assume that onward transmission is equally likely throughout the the carriage episode.

I can’t easily translate this into a serial interval / average time between transmission to a new host. But I would expect at least a week, and longer on average. The long carriage also means one host could cause many transmission. I don’t know if there is evidence for ‘superspreaders’ who may shed more or a lot more, causing more onward episodes of carriage. (many of these cases are linked to one location, a nightclub, which may be indicative of this).

How rare is this?

This is definitely not the first meningitis outbreak at a UK University. Here is a report from 1998 on an outbreak where three students died.

20 cases and 2 deaths over a week does seem unusually high, and quick to me (mostly anecdotally, compared to previous clusters). Some thoughts on why:

Possible explanations

Summary: I am guessing that there is currently a strain circulating in Kent, possibly with higher than usual transmissibility, increasing local carriage. This is probably linked to behavioural pattens (e.g. transmission in a nightclub, new students mixing) that have also led to clusters in Universities previously. A combination of higher exposure, vaccine replacement and one or more of seasonal/coinfection disposition and/or a more invasive strain have led to an unusual spike in cases.

Sequencing the cases, sequencing carriers and mapping transmission, estimating local carriage, and possibly serology would all be useful in ruling in/out possibilities:

Vaccine replacement

Most people in this outbreak will now have been vaccinated against MenA/C/W/Y. MenB is a different vaccine as the serotype target is cross-reactive with human so the factors, vaccine (4CMenB) uses four protein antigen targets.

If more students carried MenB and MenB causes more meningitis, this could partially explain an uptick in cases.

• Likelihood: high (carriage of MenB is surely higher in this group, compared to other serogroups, compared to past years)
• Impact: low (probably not enough to explain this cluster)

Tangential point: the introduction of the MenB vaccine was borderline cost effective by NICE’s guidelines at the times. It’s expensive (~£200 iirc) and prevents only a few rare cases a year. It was agreed to be introduced for infants, but debate over a catchup campaign for teenagers ultimate was not successful.

Host genetic susceptibility

There is evidence that an allele of factor H predisposes to meningococcal meningitis. If people were more susceptibile to meningitis due to their own genetics,

• Likelihood: very low (most Europeans have the allele that is more susceptible)
• Impact: low (low effect size, unlikely that this group would have systematically different genetics)

Bacterial virulence factors: transmission or immunity escape pathogen variants

There are different strains of MenB. The currently circulating one could be some combination of more transmissible or more able to escape prior/vaccine-induced immunity. It could also be more likely to cause invasive disease. The former would cause more carriage cases. The latter would cause (slightly) more carriage cases to develop meningitis.

• Likelihood: medium. We generally haven’t found much evidence for pathogen adaptation along these lines before. More transmission is evolutionarily advantageous. Causing invasive disease is evolutionarily neutral.
• Impact: high. High transmission, high carriage, more invasive would explain the outbreak reasonably well.

I read in one report that the strain has been circulating for five years (I bet this is MLST-based, so not particularly high-resolution, but maybe would pick up high novelty). I also expect that when sequencing this outbreak it will not be straightforward to identify transmission or invasion increasing genetic variation.

High local transmission due to behavioural patterns

Environmental/behavioural patterns in this group such as smoking, kissing, sharing vapes etc could increase transmission. Generally the weather will have an affect (temperature and humidity). Coinfections e.g. with flu, increase inflammation and shedding.

• Likelihood: high. Epidemiological association with a club makes this likely culprit for more carriage (and therefore more invasion).
• Impact: medium. These behaviours happen all over the country, so I think only explain a bump in cases if there is a locally circulating variant.

Stochasticity

Maybe increased carriage rate times a slightly more invasive variant (or even just more menB itself due to vaccine replacement), plus high end of randomness might be enough to explain the size of the outbreak?

• Likelihood: medium. I find this hard to judge without a model but it’s plausible to me.
• Impact: medium. Could explain two deaths. Twenty cases in a short time, not without other factors.

Broader risks

Broader risks to the population are low. Antibiotics are effective, the most vulnerable groups are vaccinated. Transmission and migration across the country will be slow.

I’m a bit surprised vaccines are being given to students given the time taken until protection is reached, and the cost/availability. Vaccines reduce not just invasive disease but carriage and transmission. But if it makes people safer or even just feel safer that’s good. Students should be able to go out and have fun.

Is mass antibiotic prophylaxis sensible? I’m not sure, but probably. I don’t think this will meaningfully increase risk from AMR, when compared to antibiotic consumption generally in the UK. It’s almost certainly cost effective. It could also rapidly stop further transmission if carriage is prevented. Hopefully there is no resistance (I am not sure about meningococcal treatment and resistance frequency, and whether multi-drug resistance is common).