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Pertactin-negative B. pertussis isolates discovered in US
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Eleven of 12 isolates of Bordetella pertussis tested by Western blotting in one area of the United States did not show pertactin, according to a report published online.
Anne Marie Queenan, PhD, of Janssen Research and Development, Raritan, N.J., and colleagues said that they believe their report was the first one showing pertactin-negative variants of B. pertussis in the United States. However, data from other countries have shown similar trends, including France, Finland and Japan.
“Sequencing revealed that in four of these isolates, the insertion sequence (IS) 481 disrupted the pertactin coding region and that in seven isolates there was a stop codon truncating the protein,” the researchers wrote in a letter to the editor in a recent New England Journal of Medicine. The letter was co-authored by Pamela K. Cassiday, MS, from the CDC and Alan Evangelista, PhD, from St. Christopher’s Hospital for Children, Philadelphia.
Queenan and colleagues said that because their isolates were only recorded in one part of the country – Philadelphia during 2010 and 2011– more data are needed from other US regions. This would help determine if this finding is a local event or represents a widespread shift in B. pertussis strains.
“An understanding of the epidemiology and virulence of pertactin-negative variants is crucial to developing the next generation of pertussis vaccines,” the researchers concluded.
Disclosure: Queenan reports no relevant financial disclosures.
Perspective
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Nicola Klein, MD, PhD
This letter by Queenan and colleagues describing gene variants in B. pertussis isolates is intriguing. As described in this report, they cultured 12 B. pertussis isolates and found that 11 of the 12 isolates did not express the pertactin protein, which is one of the components of acellular pertussis vaccines. They then sequenced the pertactin gene from these 12 isolates and found that 11 of the 12 had sequence mutations which caused the pertactin gene not to be expressed.
As the authors note, there has been concern that B. pertussis has adapted due to vaccine selection pressure. Pertactin-negative variants have been identified in Japan, Finland and France. This study now demonstrates that there are pertactin-negative B. pertussis variants in the United States and raises the issue that variants may be contributing to ongoing pertussis epidemics.
However, an important consideration in this report is that of the 12 isolates, only two derived from patients aged older than 6 months, and seven of the 12 were cultured from infants aged 2 months and younger. As the majority of these pertactin-negative isolates was obtained from infants too young to have been vaccinated (or at most had received one dose of acellular pertussis vaccine), it is not clear from this study whether a pertactin-negative variant of B. pertussis is more likely to cause disease in unvaccinated or undervaccinated populations.
In addition, it will be important to understand whether pertactin-negative variants of B. pertussis are more likely than non-variant isolates of B. pertussis to cause disease in individuals who have been recently fully vaccinated with acellular pertussis vaccines and in individuals with waning immunity to acellular vaccines.
As this study shows, we will need to be vigilant in monitoring for genetic variants of B. pertussis. At this point, only time will tell what and how much of an impact pertactin-negative gene variants will have on the persistence of ongoing pertussis outbreaks.
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