menB outbreak in Kent -- more thoughts

Posted some thoughts on the menB outbreak yesterday. Now nine more cases, total at 27.

A few more thoughts today, also after discussing with some others.

A local factor seems necessary. I think pathogen genetics

Even if there was 100% carriage due to massive transmission the rate of meningitis is so low that wouldn’t be enough to explain all of these cases. I would think transmission has been high in similar settings elsewhere, and am struggling to think of a reason why this is happening in Kent without a more invasive strain, or another factor that directly increases invasion risk.

I was pointed to this study from CDC in 1976, which saw a secondary attack rate of 2/330 cases within households. Small numbers but this is around 500x higher than baseline risk from carriage.

One possible example is phase variable regions, e.g. pilus alleles swapping out or frameshifts in poly-A tracts of porA. This rapid genetic change, if it also makes the strain more invasive, could explain locality. (NB: we saw these as consistent mutations within host during meningitis, see table 2.)

So, super-spreading-like transmission of a strain which has just become more invasive?

Phase variation happens rapidly and would switch back again, although this might interact with immunity.

Immunity changes

The outbreak population were vaccinated against menACWY, which is effective at reducing carriage, but not menB. This might have reduced the amount of cross-protection they have against menB. Maybe also less mixing over the past few years, and this is the first menB exposure from contact with older groups.

Doesn’t explain the local outbreak, but would account for increased susceptibility. Would also combine with factors I mentioned yesterday (behavioural, climate etc).

[Another person suggested increased bacterial load: higher inoculum size (perhaps due to immunity) then leading to both more transmission and more likely invasion. I don’t know enough about mening carriage studies to comment on this].

Current hypothesis

Some combination of higher transmission causing higher carriage, host risk from lower immunity to menB and/or dry & cold weather and/or smoking etc, and a strain which is currently more invasive. Together these factors move a distribution so the current outbreak then leads to an extreme of cases, partially by chance: