Thursday, February 07, 2013

NEJM: Pertactin Resistant Bordetella Pertussis – United States

Credit CDC Pink Book

# 6913



Technological solutions to biological challenges are often fleeting, as nature’s incredibly prolific experimental laboratory begins work almost immediately to come up with a workaround.


Through random mutation and evolution antibiotic resistant bacteria often thrive while susceptible strains are constrained, viruses that drift antigenically are more likely to succeed, and mosquitoes not repelled by DEET or killed off by pesticides are more likely to live to bite another day.


Hence the old saying that Nature always bats last.


Over the past decade we’ve been watching the re-emergence of an old scourge; Whooping Cough.  A sometimes fatal childhood disease that 30 years ago was all but vanquished in the United States.


The following chart shows the number of Pertussis cases (whooping cough) in California over the past 60 years.


The dramatic drop in Pertussis - which began in the early 1950s – closely follows the introduction of the first whole-cell pertussis vaccine combined with diphtheria and tetanus toxoids (DTP) was introduced in the mid-1940s.


In the 1940s more than 160,000 cases  (and about 5,000 deaths) were recorded annually across the nation, but by 1976 the number of reported cases reached a record-low of 1,010 cases, a decrease of 99%


But over the past decade the number of cases has steadily risen, and in 2012 more than 40,000 cases were reported in the United States.


The reasons behind these increases are complex, and not completely understood, but some factors may include:

  • lower vaccination uptakes
  • the move away from whole cell pertussis vaccines to safer acellular vaccines in the 1990s
  • evolutionary changes in the Bordetella pertussis bacteria.

Today the New England Journal of Medicine published a letter to the Editor that alerts us to the identification of:


Pertactin-Negative Variants of Bordetella pertussis in the United States

N Engl J Med 2013; 368:583-584 February 7, 2013 

DOI: 10.1056/NEJMc1209369

Anne Marie Queenan, Ph.D.Janssen Research and Development, Raritan, NJ 
Pamela K. Cassiday, M.S. Centers for Disease Control and Prevention, Atlanta, GAAlan Evangelista, Ph.D.St. Christopher's Hospital for Children, Philadelphia, PA


Researchers at St. Christopher’s Hospital for Children found that in 11 of 12 isolates of B. Pertussis they examined in 2011-2012, Western blot analysis failed to detect Pertactin.


Pertactin (PRN) is a membrane protein that facilitates the attachment of Bordetella pertussis bacteria to epithelial cells in the trachea, and is one of the prime components of the acellular pertussis vaccine introduced in the 1990s.


The researchers state, "To our knowledge, this finding represents the first reported occurrence of pertactin-negative variants of B. pertussis in the U.S.”


Similar pertactin-negative strains have been reported in Japan, France, and Finland. Pertactin-negative strains reportedly remain infectious in humans, and retain lethality in laboratory testing on mice.


While recent attention has been focused on waning protection afforded by the safer acellular pertussis introduced in the 1990s (see JAMA: Waning Pertussis Vaccine Effectiveness Over Time), another possible cause of the increase in whooping cough cases could be the emergence of a vaccine resistant strain.


Eleven isolates collected in one geographic region of the nation are hardly conclusive evidence of a national trend, so the authors call for:


Isolates of B. pertussis from geographically distinct U.S. regions should be evaluated to determine whether our finding is a local event or represents a more 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


Media reports indicate we may get more on this story later today from the CDC.  If so, I’ll post a link on this blog.

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