Mumps

Vaccines

Background

Adverse events following mumps vaccination, July 2003, WHO

Mumps: a resurgent disease with protean manifestations, 2008

Urabe (Pluserix and Immravax)

Background

Sheldon's Vaccines Blog (see end of page)

Some basic facts about meningitis:

• Meningitis (inflamed lining around the brain) is different from encephalitis (brain inflammation), though sometimes infections can cause both problems (meningo-encephalitis)
• Aseptic meningitis from mumps virus is a mild illness, hardly ever associated with long term neurological consequences.
• Natural mumps causes “aseptic meningitis” in around 10% of all cases – so it is quite common, and one source indicates up to 30% incidence.
• Mumps vaccine is a weakened/attenuated live strain of mumps virus, so it might also be expected to cause aseptic meningitis sometimes, albeit a milder form than usual.
• Urabe strain is associated with aseptic meningitis in around 1 in 10,000 shots (ie it is about a thousand times LESS likely to happen than after natural mumps infection).

Encephalitis is more serious but *not* what we are talking about as being caused by Urabe:

• Encephalitis from mumps is rare – it is commoner to get this in measles (and if it happens after MMR is likely to be due to the measles component, not mumps)
• Encephalitis/encephalopathy from natural measles occurs in about 1 case in 1000. (After MMR vaccine it occurs in about one case in 10 million).
• Without MMR vaccination, ALL children will get the natural measles and mumps (ie one in ten of all children will get meningitis, and one in a thousand will get encephalitis).

When MMR was introduced into the UK in October 1988 there were 2 varieties of vaccine in use – one with Urabe mumps strain (Pluserix and Immravax) and another with Jeryl-Lynn mumps strain. The Urabe type was in more common use - JCVI 4 May 1990 minutes at 9.2.b put differential down to "the reputation acquired by the Jeryl-Lynn vaccine of pain at the injection site and the manufacturer's recommendation for a brief "out of the fridge" time for the vaccine".

A report of aseptic meningitis associated with MMR first emerged in Canada in 1986/7. Subsequent cases were reported in Japan in 1988, though other countries reported no problems at that time.

In Canada only a Urabe mumps strain MMR was in use (Trivirix), and they recommended it not be used (but did not withdraw it from production) and to use Jeryl Lynn instead. This was noted in the UK by the Joint Committee for Vaccination and Immunization (JCVI) who were unable to determine at that time whether the problem was specific to Urabe strain or also might affect Jeryl Lynn strain.

The JCVI decided in 1989 to monitor the incidence of reactions in the UK, and 3 cases were reported (all following Urabe MMR vaccine). By May 1990, 2.5 million doses of Urabe and 0.5 million doses of Jeryl-Lynn had been given. The JCVI discussed the reports from Japan at their May meeting, and noted it was unclear from the Japan reports which vaccine was responsible for their increase in cases of meningitis, but Urabe was probably the strain at fault.

An enhanced UK surveillance system was introduced, with the British Paediatric Surveillance Unit (BPSU) reporting on a month to month basis any instances of meningitis or encephalitis following MMR.

By the end of 1991, The BPSU surveillance indication was that the meningitis risk might be as low as one in 270,000 Urabe strain vaccine doses (3.7 per 100,000). The JCVI decided to do a more active surveillance, linking all hospital admissions of possible meningitis with National PHLS laboratory reports and vaccination data. Immunogenicity studies were also being conducted, since it appeared that Urabe was more effective than Jeryl Lynn strain at inducing protective immunity.

In July 1992, data from the PHLS indicated the risk was 1 per 11,000 doses of Urabe, and data from Nottingham indicated that locally the rate could be as high as 1 per 3800 (95% CI of 1 in 2000 to 1 in 19,000)

These data prompted the JCVI to recommend withdrawal of Urabe strain, and use only of Jeryl Lynn strain MMR (Priorix).

Since 2.5 million doses of Urabe had been given over the 2 years 1988 to 1990 in the UK, one would anticipate that there would have been around 250 cases of aseptic meningitis caused in that time by the vaccine (1:10,000).

However, without vaccine, there would have been 800,000 cases of natural mumps, and therefore about 80,000 cases of meningitis, all occurring after childhood mumps infection (1:10).

There would have been no cases of aseptic meningitis if Jeryl Lynn had been the only MMR vaccine available, but as discussed above, there were good grounds for suspecting that Urabe was a superior vaccine in terms of efficacy, and at the time it was unclear whether other non-Urabe MMR vaccines might still cause meningitis. Canada decided early on to act, and they were in retrospect shown to be correct, but their action was rather precipitous and could have backfired badly (had Jeryl Lynn also be shown to cause meningitis).

In Japan, MMR vaccine was withdrawn altogether in 1993 because of meningitis reactions. The folly of this action soon became apparent, as over the next decade there were several major measles epidemics, the one in 2001 causing 265,000 cases of measles (which equates to 250-300 cases of neurologically disabling measles encephalitis and about 50 deaths)

Some other reading

• Risks of Convulsion and Aseptic Meningitis following Measles-Mumps-Rubella Vaccination in the United Kingdom
• Mumps meningitis, possibly vaccine-related--Ontario, Can Dis Wkly Rep. 1988 Nov 19
• Adverse events associated with MMR vaccines in Japan, Acta Paediatr Jpn. 1996 Jun
• JCVI Minutes 1981-1990

Should We Be Worried About This?

Was a dodgy (Urable) mumps strain knowingly included in UK MMR formulations to save money? That's the typical narrative of vaccine sceptics.

Knowing what we know now, and given a choice between Urabe and Jeryl Lynn, it's clearly correct to take the latter.

The question is whether, around 1990, the choice between them was so clear.

As with so many questions around vaccinations, people will line up on different sides depending on the level of trust they have with the establishment view.

A pro-establishment person will point to the studies by the JCVI, and the switch to a Jeryl-Lynn strain once the facts were in, as evidence of a considered evidence-based approach. The JCVI were aware of Canada's 1988 move from Trivirix Urabe-based vaccine, they just didn't see any conclusive evidence to prefer Jeryl-Lynn. Once they had such evidence (by 1992), they switched.

An more sceptical viewer will focus on the 1988 Canada move from Urabe, and say this should have been enough for everyone else to move too.

It's hard for me to get too excited about this one. The worst you can say about Urabe in the UK was that we would have had about 250 extra cases of asceptic meningitis, a condition that is unpleasant for up to a week but has very little evidence around causing long-term issues. At the time there was evidence in Urabe's favour - evidence indicating greater effectiveness. After a *lot* of trials, it now seems clear that if Urabe is more effective (and it does seem to be slightly more so), it's not a big enough win to counteract the downside of the meningitis risk. But this evidence was not present in 1988. The JCVI monitored, got the evidence, made a call when the evidence was in and the whole episode did not cause a great deal of suffering as far as any scientific evidence indicates.

As far as side-effects go, the Pandemrix narcolepsy seems far more serious, even though its UK incidence rate was 5 times lower at 2 in 100,000.