AT ITS July 2016 meeting, the Pharmaceutical Benefits Advisory Committee (PBAC) urged a significant change in the way older people are vaccinated to prevent pneumococcal disease and pneumonia. Following a price reduction by the manufacturer, the PBAC recommended a switch in the designated vaccine on the National Immunisation Program, from the 23-valent pneumococcal polysaccharide vaccine (Pneumovax 23, Merck) to the 13-valent pneumococcal conjugate vaccine (Prevnar 13, Pfizer).

The PBAC based its recommendation on evidence from the CAPITA trial, which showed the efficacy of Prevnar 13 in an older population. But it also noted a key evidence gap, which was a reliable estimate of the burden of non-bacteraemic pneumococcal pneumonia in Australia. The government has yet to act on the PBAC’s recommendation, but a new systematic review published in the MJA may go some way to bridging that evidence gap.

The review, by researchers from the National Centre for Immunisation Research and Surveillance, pooled data from 12 studies looking at the contribution of pneumococcus to community-acquired pneumonia (CAP) in Australia. It showed that while pneumococcus was the most common cause of CAP, the proportion of pneumococcal CAP cases had declined from 26% in the late 1980s to 14% in 2004–2006. This was probably due to the herd immunity effect of the childhood vaccination program, the authors wrote. Around half of pneumococcal CAP occurred in people over the age of 65 years, and both intensive care unit admission and death were more common in those aged over 85 years and in those with bacteraemia.

Crucially, of 17 bacteraemia cases serotyped, 12 were of serotypes targeted by the Prevnar 13 vaccine, and only three were of additional serotypes targeted by Pneumovax 23. The study authors concluded that if Prevnar 13 did become the designated vaccine, “surveillance to track non-bacteraemic pneumococcal CAP will be essential to evaluate the impact”.

The problem is that such surveillance won’t be easy, according to James Paton, Professor of Microbiology and Director of the Research Centre for Infectious Diseases at the University of Adelaide.

“The diagnosis of the more prevalent non-bacteraemic disease is very problematic, and whatever method you’re using, it will underestimate the true incidence of pneumococcus infection. The only way, at the moment, is with a sputum culture, and that’s not ideal, because you could have asymptomatic carriage in the nasopharynx, which could contaminate the specimen on the way up. But it will give you a minimum estimate for the incidence of pneumococcal pneumonia as a proportion of total cases.”

Professor Paton, who was recently named South Australian Scientist of the Year, said that another way to assess vaccine efficacy might be to look at its impact on nasopharyngeal carriage.

“There are molecular tests now that can very sensitively tell you just which serotypes are being carried, on the basis of DNA segments. Essentially, if you’re not being colonised by pneumococcus, for the vast majority of serotypes, you’re not going to get disease from them. So, if you want to examine vaccine efficacy, a good surrogate might be its impact on nasopharyngeal carriage.”

Professor Paton said that he supported a switch to Prevnar 13 as the designated vaccine for older Australians.

“The efficacy of the old 23-valent vaccine has been open to debate for some time. I think Prevnar 13 is certainly going to be more protective in the older age groups, so they won’t be just relying on herd immunity to get benefit. I think it’s a good move.”

But he added that in general, there was a built-in problem with the conjugate vaccines that was in some ways analogous to the issue of antibiotic resistance.

“If you look at Prevnar 13, there’s a limit to the number of serotypes that you’ll be able include in the conjugate formulation, and we’re probably close to that limit. The problem is that in the parts of the world where the conjugate vaccines have been used the longest, we’re seeing an increase in disease caused by the serotypes that are not included in the vaccine. So, you can get highly successful clones that used to be vaccine serotypes, but they’ve swapped capsule loci so now they can express non-vaccine type capsules.”

He said that some of these vaccine-resistant strains may have been there all along, but in much lower frequencies. However, once the vaccine-type strains are removed, these other strains start to increase in numbers in the nasopharyngeal niche that is now vacated. In the US, Prevnar 13 serotypes currently make up only about 20% of disease-causing strains, Professor Paton noted.

“This is going to be a snowballing thing. Initially, there may only be slight increases in these non-vaccine serotypes, but as they become more commonly carried, they’ll be more frequently transmitted, so more people will be exposed.”

Professor Paton said that the answer is a vaccine that is not dependent on the capture of polysaccharides. He said that using purified pneumococcal protein antigens as vaccines could be one solution, and whole-cell vaccines could be another.

“The protection with either of these probably won’t be as good as for the serotypes included in conjugate vaccines. But they will cover against all other serotypes. So, in the first instance they could be used as adjuncts to conjugate vaccines.”

In the meantime, introducing Prevnar 13 to the older population would be the right decision, he said.

“But if we do this, what’s crucially important is that we have surveillance to monitor the vaccine’s impact on disease.”

Professor Paton is a shareholder and director of GPN Vaccines Pty Ltd, a company involved in vaccine development.

 

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