Tuesday, November 27, 2012

The comeback of whooping cough

October issue of Microbe, published by ASM.

I read a very interestingand somewhat alarmingarticle in the October issue of the journal Microbe (formerly ASM News). In this article, Merry Buckley explains that whooping cough (aka pertussis), a childhood disease that has strongly declined since the introduction of a vaccine in the 1940s, is now on the rise again. We even see epidemics! says Buckley.

In 2012, in the USA, the number of pertussis cases is expected to be the highest in fifty years, approaching 40,000. Other countries such as Australia and the Netherlands also have high incidence of the diseasein the Netherlands, 6,000 cases were reported in 2009, against only 30 cases in 1980. The causes of this comeback are not fully understood, but scientists have gathered many clues.

Whooping cough is caused by Bordetella pertussis, a Gram negative bacterium belonging to the group beta Proteobacteria. It infects the respiratory system, causing a characteristic ‘whoop’ sound in sick children. Teens and adults can also be infected, although the symptoms are milder than in small children. In the prevaccine era, pertussis was a terrible threat, killing on average 5,000 children a year during the 1920s and 30s in the USA alone. At this period, the epidemics peaked following a cyclic pattern of a couple of years.

When the vaccine, which consisted of killed B. pertussis bacteria, became in use (together with the diphteria and tetanus vaccines), the number of pertussis cases sharply dropped down. During the 1980s, however, the trend was reversed and more cases were reported in the US, this despite the fact that 95% of the children were vaccinated. In 1991 a new pertussis vaccine, which was based on antigens only, was implemented, and it is this one that is in use today. But the introduction of a new vaccine did not stop the climb initiated in the 1980s, and since 2000 we have seen again the cyclic pattern of epidemics peaking every five years or so. The only positive note is that, despite the increase in the disease incidence, the number of fatal cases remains low.

So why is pertussis on the rise? One reason is waning immunity. More adult and teens become infected and, even though they don’t risk much for themselves, these carriers become a source of infection for children. This decrease in the vaccine protection overtime may possibly be linked to the use of the acellular vaccine. But it is not sufficient to explain the present situation: genetic changes in the populations of Bordetella pertussis likely are part of the story. In particular, researchers point at variations in the promoter of the gene encoding the pertussis toxin, and at the virulence factor pertactin. New variants that express more toxic (via changes in the promoter) and that have a pertactin that is not recognized by the immune system seemingly contribute to the rise of pertussis in Europe and Australia. The situation is somewhat different in the US, where a different traitthe production of a certain type of fimbriaeis associated with the rise of the disease. In both cases, however, it is a serious possibility that vaccination has helped select for these more dangerous variants. 

What can be done to counter this situation? Well, the clinicians working on pertussis suggest that the current vaccine should be carefully reviewed and, possibly, replaced by a more up-to-date version. 


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