MALMO, SWEDEN – A French national study has documented a sharp increase in pneumococcal meningitis since 2015 in children under age 15 years.
The culprit has been identified as serotype 24F, which is not covered by the infant 13-valent conjugate pneumococcal vaccine (PCV13), Naim Ouldali, MD, reported at the annual meeting of the European Society for Paediatric Infectious Diseases.
The rapid emergence of serotype 24F has been accompanied by a disturbing change in its penicillin susceptibility. Indeed, penicillin resistance was present in only 18% of serotype 24F isolates in France during 2000-2014, then jumped to 74% during 2015-2016, according to Dr. Ouldali of René Descartes University in Paris.
“PCV13 has strongly reduced the pneumococcal meningitis burden in children, but its benefit now seems to be jeopardized, at least in France. So serum 24F could become a major concern in the coming years because of its characteristics. And now the question is, is this emergence an epidemic phenomenon or not? And if it’s confirmed in future studies and in other countries, probably it should drive the development of next-generation PCV formulations,” he said.
Dr. Ouldali presented a population-based interrupted time-series analysis of a nationwide prospective survey conducted in France during 2001-2016. He noted that the Cochrane Collaboration has deemed this study design second only to the randomized controlled trial in terms of quality of evidence.
The study, which included 227 French pediatric wards and 168 microbiology departments, identified 1,778 children under age 15 years with pneumococcal meningitis. This is believed to be more than 60% of all cases that occurred in the country during the study years.
The purpose of the study was to determine the impact of implementation of routine PCV13 as part of the national vaccine strategy. Rates of PCV13 coverage in French children are very high: in excess of 90% during 2015 to 2016.
Implementation of PCV13 led to a dramatic 38% reduction in the monthly incidence of pneumococcal meningitis, from 0.12 cases per 100,000 children before PCV13 to a low of 0.07 cases per 100,000 in December 2014. But after that the rate rebounded sharply, by 2.3% per month during 2015-2016, to a high of 0.13 cases per 100,000 per month by the end of 2016. Drilling down into the data, Dr. Ouldali and his coinvestigators learned that the resurgence of pneumococcal meningitis was due largely to the emergence of serotype 24F.
“This serotype is of particular concern because of two characteristics: First, it is already known to have a high disease potential – one of the highest, along with serotype 12F – and second, this rapid emergence was accompanied by a change in its penicillin susceptibility,” he noted.
Most of the French rebound in pneumococcal meningitis has occurred in children under 2 years of age. Of note, German investigators also have recently reported a rebound in invasive pneumococcal disease in German children under 16 years of age. Non-PCV13 serotypes accounted for 84% of all invasive pneumococcal disease during 2015-2016, with serotypes 10A and 24F leading the way. As in France, most of the resurgence has involved children less than 2 years old. However, unlike in France, most of the German increase has been in nonmeningitis forms of invasive pneumococcal disease ().
In response to a question from a concerned audience member, Dr. Ouldali said that while the penicillin susceptibility of serotype 24F has taken a sharp turn for the worse, cephalosporin susceptibility has not.
“To date, we have not seen any cephalosporin-resistant strains. To date, there is no need to use vancomycin,” he said.
Dr. Ouldali said the next step he and his colleagues plan to take is to see if there is a clonal expansion or a particular underlying genetic pattern which could explain the explosive emergence of 24F.
The study was funded by a research grant from Pfizer and by the French Pediatric Infectious Diseases Group.