Pertussis mutations may explain whooping cough epidemic

Pertussis mutations may explain whooping cough epidemics
Pertussis mutations may explain whooping cough epidemics

HealthDay News -- New mutations in Bordetella pertussis may play a role in diminished vaccine efficacy and the rising incidence of whooping cough in the United States, researchers found.

Genetic analyses reveal that 11 of 12 isolates of B. pertussis cultured from specimens from children hospitalized in Philadelphia in 2011 and 2012 were negative for pertactin -- a virulence factor that is a component of the current acellular vaccine -- Alan Evangelista, PhD, of St. Christopher's Hospital for Children in Philadelphia, and colleagues reported in New England Journal of Medicine.

"To our knowledge, this finding represents the first reported occurrence of pertactin-negative variants of B. pertussis in the United States," the researchers wrote.

Strains of pertactin-negative pertussis have also been reported in isolates from France, Finland and Japan. 

Concerns about recent whooping cough outbreaks in several countries have largely focused on waning immunity  associated with the acellular pertussis vaccine (DTaP), which was introduced 15 years ago in this country in an effort to minimize adverse events seen with the whole-cell vaccine (DTwP).

When researchers analyzed pertactin-negative pertussis isolates from Japan and Finland, they found that an allele of the prn gene the encodes pertactin had insertions or deletions, whereas isolates from France had areas of truncation or deletions in a second allele of prn.

To determine if similar mutations were present in U.S. pertussis isolates, Evangelista and colleagues sequenced the full pertactin coding region and performed Western blotting on the Philadelphia isolates.

Insertion sequences at nucleotide 1613 were present in four isolates, and was identical in three. The researchers identified stop codons at amino acid position 425 in the other seven isoltes, all of which were either identical or shared more than 90% of their genetic material. The allele in all 12 cases was the same as those found in the French isolates, but the specific mutations differed.

The researchers called for additional studies of isolates from different parts of the United States to determine whether pertactin-negative pertussis variants are increasing or are a localized development.

In a separate letter to the editor in the same journal, Juventila Liko, MD, MPH, from the Oregon Health Authority in Portland, and colleagues explained findings from their study comparing immunity among children who received either a first-dose of the discontinued whole-cell pertussis vaccine or a first dose of diphtheria-tetanus-acellular pertussis (DTaP) who later received tetanus–diphtheria–acellular pertussis (Tdap) boosters.

From April 1997 through July 2012,  the researchers identified 484 pertussis cases, 402 of which were matched to the Oregon immunization information system ALERT IIS.

The researchers found that the reported rates of pertussis were lower among children who had started the vaccination process with DTwP. Higher rates of reported pertussis were seen for children who underwent priming with acellular versus whole-cell pertussis.

"The balance between vaccine side effects and effectiveness needs to be considered in developing and implementing recommendations on pertussis vaccination, particularly in light of recent outbreaks of pertussis," the researchers wrote.

References

  1. Queenan A et al "Peractin-negative variants of Bordetella pertussis in the United States" N Engl J Med. 2013; 368: 583-584.
  2. Liko J et al. "Priming with whole-cell versus acellular pertussis vaccine." N Engl J Med. 2013; 368:581-582.
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