Tuesday, February 12, 2013

Bordetella Pertussis Mutations may Reduce Vaccine Effectiveness

A recent report by the Centers for Disease Control (CDC) has discovered that mutations in a particular gene may be partially responsible for the increase in B. pertussis or whooping cough cases. CIDRAP reports that B. pertussis isolates in some children in the U.S. have been tested and found to have gene mutations in the coding region for Pertactin.
In the US study, researchers looked at pertactin genes from 12 isolates of B pertussis from children hospitalized in Philadelphia in 2011 and 2012. Most of the patients were younger than 2 years old, but the group also included a 9-year-old and 14-year-old.

They analyzed the pertactin genes from the specimens and amplified and sequenced the coding region. They determined the pulsed-field gel electrophoresis (PFGE) patterns and detected pertactin using Western blotting with antiserum and a strain from the World Health Organization (WHO) as the pertactin-positive reference.

Eleven of the 12 pertussis strains they tested were negative for pertactin. The pertactin allele in all isolates was pm2, but the mutations were different than pertactin-negative pm2 isolates from France, according to the report. (Variants in Japan and Finland had insertion sequences in the pm1 allele.)
Pertactin is a virulence factor for B. pertussis which is an adaptation of the organism that enables it to colonise its host.  Pertactin is an adhesin that promotes adhesion of B. pertussis bacteria to the tracheal epithelium of humans.  Pertactin (Prn) is one of the antigens in the acellular vaccine along with inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and fimbriae types 2 and 3 (Fim).  The U.S. group, as reported in NEJM, found both insertions and stop codons that prevented the B. pertussis bacterium from expressing pertactin although the virulence of the pertactin negative strains was the same as pertactin positive strains.

Japan and France have also found pertactin negative strains but with different insertions and deletions in a different allele than what has been found in the U.S. although the net result is the same. The current theory is that these mutations have occurred through selective adaptations against the acellular vaccines.  The pertactin negative strains may not be as virulent as the pertactin positive strains although more research would be necessary to confirm this.
The only significant difference (p = 0.29) was that the time between the beginning of the cough and hospitalization was longer for infants infected with a PRN– isolate; this finding might reflect less severe disease in this group.
Note: I believe that the reported p-value of 0.29 is a typo and perhaps should have been 0.029.

The vaccines still remain effective for attenuating disease severity even with fewer than the age-appropriate dosing schedule of three by six months old.
Vaccination was associated with less severe clinical symptoms (Table 2): the proportion of hospitalizations in intensive care units was significantly lower in the vaccinated group (p = 0.001). Clinical symptoms, such as apnea, syncope, cyanosis, and deterioration of general condition, were also less frequent in the vaccinated group (Table 2). This confirms previous findings (12) indicating that infants who receive 1 or 2 doses of pertussis vaccine are protected to some extent.
Pertussis vaccination introduced in the U.S. in the 1940s (as a whole-cell vaccine) and around the world at various times after that have undoubtedly saved millions of lives.  This finding does not negate the necessity of infants receiving the full series and older children and adults remaining current on boosters in order to prevent widespread morbidity and mortality.  What these findings do is highlight the importance of developing more effective pertussis vaccines while maintaining a high safety profile.


  1. For some more information refer to my emails to Professor Lyn Gilbert and Professor Ruiting Lan (forwarded in December 2012) re the Journal of Infectious Diseases Brief Report re the Australian pertussis epidemic in 2008-2010: http://users.on.net/~peter.hart/Whooping_cough_enquiry.pdf

    I conclude my email to Professor Lan with the following questions:

    Q. Professor Lan can you please clarify for me how increasing the number of 'boosters' of the existing vaccine protects against the new strain?

    Q. Also, how is vaccination "still the best way to reduce transmission of the disease and reduce cases" particularly if "vaccine-induced selection could contribute to the expansion of cluster I"?

    As yet I have not received any response to my emails.

    Elizabeth Hart

    1. As yet I have not received any response to my emails.
      I suggest you get used to that. We're busy people and don't, as a matter of course, cater to the whims of nutter anti-vaxxers like yourself. So don't mistake their non-answer for unable to answer.

    2. She has been told before there is a reason for not getting answers to her queries. Not that she should complain because she refused to answer questions directed towards her at the Bad Science Forum: Elizabeth, I've lost my patience with you. You've had ten months, and now you've got a week to answer the questions put to you by pipsqueak, on that thread, even if they're "dunno". If you answer them then the conversations around this can continue in good faith, which is good. If you don't answer them then I'm going to ban you for being a spammer, which is bad, because we like engagement and open discussion here.

  2. You could have answered that yourself Ms. Hart with a modicum of work on your part. It is obvious from the epidemiology that the vaccine series and boosters for older children and adults still protects from disease otherwise we would see millions of infant cases/year in the U.S. alone. Continued use of the current vaccines will most likely keep contributing to the selective pressure but until a better vaccine is developed, the alternative will usher in unthinkable morbidity and mortality.

  3. You've hooked a "live one" Science Mom.

    The drive-by poster Elizabeth Hart has been making the rounds of other science blogs:


  4. @ Anonymous: Have you any, er, comments about Science Mom's blog...or are you just trolling?

  5. It was just Thingy again crawling out of her rock. Her comments have gone into the spam bucket and any others' quoting hers went too. I can return the responses if you like.

  6. Paul Offit had some choice words yesterday regarding Queenan et al. (http://www.nejm.org/doi/full/10.1056/NEJMc1209369):

    - Could draw an analogy to pertactin-negative variant paper and Wakefield MMR-autism hypothesis.
    - Both papers raised hypothesis but supplied no evidence in support of the hypothesis.
    - Can’t reasonably expect the media or the public to differentiate between a study and a hypothesis.


  7. Thanks for the information Mr. Rolloson. I can't say I agree with him though, particularly when these findings have surfaced in other countries.