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Scientists comment on the latest Meningitis case numbers and a UK Health Security Agency (UKHSA) technical briefing.
Prof Andrew Smith, Professor and Honorary Consultant Microbiologist, University of Glasgow, said:
“The technical briefing provides useful genomic data for the serogroup B meningococcus (MenB) from the Kent outbreak. It provides us with new evidence that this strain is similar to but slightly different to other MenB strains isolated in the UK. One of the differences is in some surface proteins called Porins that are used to identify different strains. This will help in public health investigations aimed at understanding how the disease was spread.
“Very detailed genomic information (from the whole bacterial genome) is only currently available for one isolate. Interrogation of this data has shown that there are some changes in the make-up of a bacterial gene that codes for other surface features that can affect the infection behaviour of this bacteria, however, we still need to know more about the meaning of these changes, so it is too early to understand this finding. More isolates need to be sequenced and further laboratory work is required to understand the clinical significance. The whole genome data has provided information that predicts this strain is covered by both the MenB vaccines (Bexsero and Trumenba). These strains are also sensitive to antibiotics used for treatment or prevention of meningococcal infection.
“The drivers for this outbreak remain as the biological properties of the outbreak strain, population immunity to the outbreak strain, social factors such as kissing and environmental factors. The bacterial genomic data is helping stitch some parts of the narrative together. Having access to molecular testing (PCR) to enable analysis of MenB genetic fragments in samples where MenB has not grown and the full genome where it has been grown is assisting diagnosis, understanding of disease spread and vaccine antigen coverage.
“The Scottish Meningococcal Reference Laboratory service based at Glasgow Royal Infirmary has been routinely performing whole genome sequencing on invasive meningococcal isolates since 2018, so is well positioned to monitor any changes in meningococcal strains. Laboratory meningococcal infection surveillance is integrated with Public Health Scotland team monitoring infection and vaccine deployment.”
Prof Martin Maiden, Professor of Molecular Epidemiology, University of Oxford, said:
“It’s important to emphasise that the report is based on only one meningococcal isolate – we need more data to be sure. But assuming that it is representative, this strain belongs to a meningococcal ‘family’ (clonal complex) that usually causes ‘hyperendemic disease’, which is elevated levels of disease over a protracted period in a given population (like the Stroud outbreak in the 1980s). However, in Kent it is casing a ‘localised outbreak’ – albeit a large one. It therefore is behaving differently than what we’d normally expect for this meningococcal family, although other families regularly cause such outbreaks. The isolated bacterium that has been sequenced is very closely related to other meningococci we have seen before, but it is distinct. If you think of Russian dolls, this is a unique Russian doll inside other known Russian dolls. It is so very similar to the others that we need whole genome sequencing to see the differences (see Figure 4 in the UKHSA technical briefing), though that can’t give us all the answers at this stage.
“The close relatives of this isolate have caused disease in the UK since 2020, but this the first big outbreak. Other than the size of the outbreak, the meningococcus is behaving consistently with what we know about meningococci: (i) teenagers and young adults are a high-risk group; (ii) the meningococcus is normally carried inside lots of people’s throats and rarely cause disease; (iii) higher carriage can lead to more disease, and it’s well known that pubbing, clubbing and kissing can all increase carriage; (iv) University outbreaks do occur, although they are normally restricted in scope, and this one is a bit bigger than we would normally expect; (v) we know outbreaks are caused by certain types of bacteria and this is one of those types – although normally this type is associated with longer-term lower level outbreaks rather than the large outbreak we have seen.
“Meningitis bacteria are constantly walking a tightrope – they need to persist and grow in the human throat in the face of immune responses, but if they are too aggressive and invasive, they cause disease, which will limit their persistence (because a person who is very unwell will transmit less), so causing disease isn’t an adaptive trait. One explanation is that variability in outbreaks is due to diversity in pathogenicity of meningitis bacteria – some are more likely to cause disease than others. Clubbing happens all over the country all the time, but we have only seen this one outbreak. Hopefully, this outbreak will be one of those rare chance events we don’t see again for a while – but we can’t be sure yet. Another option is that this outbreak variant does spread further, which has been judged as possible but unlikely in the UKHSA technical briefing.
“There is still a lot of uncertainty, but I am cautiously optimistic that this will turn out to be a rare, chance, event. So far, we haven’t seen secondary cases unlinked with the club (Figure 3 shows all cases so far appear to be linked to the club). But we need to remain aware of the possibility of further cases. We have the technology to monitor the situation, and the HSA can tailor the public health response – the science and the genomics have been really helpful for that.”
Prof Paul Hunter, Professor in Medicine, The Norwich School of Medicine, University of East Anglia, said:
“Firstly the number of cases as of today are now 23 or which 20 are confirmed meningococcal group B. This is down from a report of 34 a few days ago primarily because probable cases that were included in previous days’ summaries have now been excluded as the disease was not confirmed.
“The technical briefing provides valuable additional insights into the nature of the meningococcal outbreak in Kent. There is a lot of information in the briefing. This briefing represents a considerable amount of work by UKHSA staff and they should be commended for getting this much data together so quickly. I would like to comment on a number of issues:
“1. The strain causing the outbreak has been around for about 5 years, but we now know that there are several differences (mutations) from the strain that was first seen in 2020. But whether these differences contributed to this outbreak is currently not clear.
“2. It is still not known with any great degree of confidence what factors or combination of factors made this outbreak so explosive. It remains the case that the drivers of this outbreak may be a combination of the nature of the outbreak strain, inadequate immunity in the people affected and behavioural factors but only a low confidence in this conclusion.
“3. At present it appears to be the case that all affected people acquired their infection in Kent but it is likely that we will see some cases where the infection will have been acquired outside Kent from contact with people who were contacts of cases. The risk of acquiring the infection from this route is very low but not zero.
“4. The briefing states that historically the risk to university students from any invasive meningococcal disease has been about 11 times greater that in those of the same age and not going to University. This relative risk is rather greater than I would have guessed. JCVI have been asked to review their advice on whether the meningococcal type B vaccine should be offered to adolescents. To my mind this relative risk is sufficient that JCVI should model not only giving the vaccine to all adolescents but also model giving it to first year university students.
“5. Of the 29 confirmed and 2 probable cases with exposure data (figure 2) all but 3 attended club chemistry. That two confirmed and one probable case did not attend the club shows that there has been secondary transmission. Secondary transmission after a case of meningococcal disease does occur, hence the need for antibiotics in contacts, but the risk is generally quite low about 1 in 300 household contacts. It is not clear to me whether the 2, possibly 3, secondary cases identified so far represents a real increased risk of secondary transmission than would normally be the case.
“6. Figure 2 is the first graph showing when people became unwell. One became unwell on Monday 9th March, 3 on Tuesday, 4 on Wednesday, 2 on Thursday, 5 on Friday, 3 on Saturday 1 on Sunday and 3 (only 1 confirmed so far) on Monday 16th. If, as has been reported, UKHSA were first notified on Friday 13th, this seems to me to be a long gap between cases presenting and UKHSA being notified unless cases were ill for a few days before admission to hospital.
“7. There have been no new cases becoming ill since Monday 16th so it is likely that the initial outbreak has now ended. However, there remains a risk albeit low of additional secondary cases so the need remains to be vigilant and if people become ill with relevant symptoms get them medical advice as soon as possible.
“8. We know 2 have died. We also know that at least 9 – about a half – have been admitted to intensive care. It is not clear whether the deaths were in people who are also included in the intensive care numbers. This illustrates how severely ill many of the affected students were.
“9. The vaccine in use is a pretty good match for the outbreak strain.
“10. UKHSA are already planning further work that will hopefully increase our understanding of how this outbreak happened and what lessons could be learned to reduce the risk of something like this happening again.”
Dr Michael Head, Senior Research Fellow in Global Health, University of Southampton, said:
“The latest technical briefing provides a very useful overview of what we do, and do not know, about the outbreak so far. The laboratory investigations have shown very clearly that this is a known serogroup of meningitis B bacteria, but with novel distinctions in the subtype. We do not know if these changes in the bacteria genome have contributed to the initial infection and the transmission of cases. There are other known environmental and behavioural risk factors present, such as unvaccinated populations and a likely poorly-ventilated environment as the probable source of the first cases. The technical briefing makes clear that all of the cases were not eligible for the routine meningitis B vaccine rollout and thus would likely have not been offered the vaccination previously.
“Meningitis is often alas a very severe illness. Therefore, despite some of the novelty around the bacterial genome, we are not seeing anything obviously different about the severity of the clinical presentation here.
“It does appear as though we are in the tail-end of the outbreak. There is though still the possibility that new linked cases could emerge.”
Declared interests
Prof Andrew Smith: “The only COI I have is being a local PI on some of the meningococcal carriage studies pre-COVID (main recipients of funding was Oxford Uni) and co-authorship on a number of publications with University of Oxford but I don’t have any paid (or in kind) COI with industry and other funders.”
Prof Martin Maiden: “I am a member of the Invasive Meningococcal Disease Technical Group that put together the UKHSA technical briefing. I have conduced commercial consultation on behalf of Oxford University in this area in the past, but I have no current active funding conflicts of interest.”
Prof Paul Hunter: “No CoI.”
Dr Michael Head: “No COI.”