The Daily Express reported today that “hundreds of thousands of children may need booster injections against meningitis after the discovery of three new “superbug” strains of the disease”. It says that the meningitis vaccine, previously thought to be 100% effective, is “powerless against the highly evolved strains”. The Daily Mirror reported that the strains are not out in the community, but if they do get a foothold they could undermine the vaccine.
The news articles are based on a laboratory study in which researchers identified three strains of meningitis C that were resistant to the immune response raised by vaccination. When they analysed these strains they found a particular mutation, which resulted in more capsule, the protective layer of the meningitis bacterial cell, being produced. This in turn reduced the immune response. This is an important study, and the results warrant further investigation.
The meningococcal C vaccine has been successfully used for many years with no reports of emerging resistance. The impact of the findings outside of the laboratory are at present unclear.
Where did the story come from?
Dr Maria Jose Uria and colleagues from Imperial College London, the Institute of Health Carlos III in Spain, the National Institute of Biological Standards and Control, JEOL UK, and the Manchester Royal Infirmary carried out the research. The study was funded by Meningitis UK, the Medical Research Council, and the Wellcome Trust. The study was published in the peer-reviewed medical journal Journal of Experimental Medicine.
What kind of scientific study was this?
The authors of this laboratory study were interested in assessing whether strains of meningitis C in samples taken from patients were developing resistance to the standard meningitis C vaccination. They examined blood samples from 109 patients, all of whom had proven meningococcal disease and had never had the meningitis vaccine.
Each of the 109 samples was mixed with the separated blood (sera) from three people who had been vaccinated and therefore had high levels of bacterial antibodies. The researchers then identified the strains of meningitis that showed heightened resistance to the meningitis C vaccination.
The resistant strains were profiled and examined. The cell capsules of the bacteria - the outer protective layer - were purified and the polysaccharides were extracted for further examination. The researchers were looking for particular modifications to the lipopolysaccharides or polysaccharides that make up the capsule. They also assessed whether it was these changes that produced the resistant strains.
The researchers then examined the genes responsible for producing the capsule and used techniques to amplify (repeat many times) the gene sequences in the areas they were particularly interested in. This allowed them to identify whether particular gene sequences were present in the resistant strains.
Finally, they used special techniques to assess the precise composition of the polysaccharides in the bacterial capsules, and looked at the immune mechanisms linked to the enhanced resistance.
What were the results of the study?
Of the 109 strains of meningitis C that were tested, three were resistant to the immune response caused by the meningitis C vaccine. Although they found no modifications to the lipopolysaccharides and the polysaccharides, later experiments confirmed that something in the capsule was responsible for resistance.
DNA investigation revealed that in all three resistant strains, a particular gene sequence (IS 1301) was being inserted into the region of the DNA responsible for generating the capsule. Further investigation suggested that this insertion did not change the overall structure of the capsule, but it resulted in more capsule being produced.
What interpretations did the researchers draw from these results?
The researchers say that their study has identified strains of meningitis C, which have increased resistance against the most critical aspect of immunity that protects against meningitis C infection. They conclude that it is not clear whether ‘strains with this change will compromise the efficacy of meningococcal vaccines’. The vaccines have been used for over 30 years with no reports of emerging resistance to date.
What does the NHS Knowledge Service make of this study?
This laboratory study used recognised methods to examine the molecular features of the resistant strains of meningitis C that were identified, and to compare them with strains that are susceptible to the immune response raised by vaccination. The results will be of interest to the scientific and medical communities and warrant further research.
- The study was small, profiling only three isolates of bacteria. Confidence in the results would be greater if the findings were replicated in larger studies.
- It is important to point out the success to date of the meningitis C vaccine. Since routine use in 1999, it has reduced the prevalence of the infection by 90% in people under 20. To date there have been no reports of resistant strains, so it is unclear whether these findings represent a real concern to the population at large.
More studies into the genetic changes behind vaccine-resistant meningitis C will be needed to ensure that these preventative vaccines remain effective for this disease.
Sir Muir Gray adds...
Cunning little beasts; that’s why we need a public health service to keep an eye on the enemy, which will evolve, as will our defences.
Analysis by Bazian
Edited by NHS Website
Links to the headlines
Daily Mirror, 9 June 2008
Mail on Sunday, 8 June 2008
Links to the science
The Journal of Experimental Medicine, Vol. 205, No. 6, 1423-1434