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I’m certain by now many of our readers have come across news of the current pertussis, aka whooping cough, epidemic in California.  Beginning this February and accelerating dramatically through May and June, California has so far seen a ~500% increase in pertussis cases compared to last year, and only two days ago announced the death of a sixth baby from infection.  Public health officials in California are currently working to control its spread and determine the factors that allowed this outbreak to occur, unfortunately, at this time the available data is very rough.

The number of confirmed cases as of 6/30/2010 is growing rapidly (1,377), with an additional ~700 cases pending investigation.  General geographic location, ages, and ethnicity have been identified, and general vaccination rates and exemption rates are known, but other important demographic and epidemiologic data, including vaccination status of infected children and adults, has yet to be fully described.  Lack of data notwithstanding, I have read equally hasty stories and comments blaming the outbreak on vaccine refusal, a large immigrant population, an inadequate adult vaccination program, and normal cyclical variation in pertussis incidence, among other factors.  Finding where the system has broken down enough to allow this resurgence is exceedingly important, but in this situation pointing fingers is not as important as taking action.

Pertussis

A bit of background first.  Pertussis is a highly contagious infection of the respiratory tract by a bacteria Bordetella pertussis.  After an incubation period of 7-10 but up to 42 days, the disease progresses through three stages.  The catarrhal stage is often indistinguishable from the symptoms of the common cold, with runny nose, mild cough, and lasts 1-2 weeks.  During the second or “paroxysmal” stage infected people will have fits or “paroxysms” of uncontrollable rapid-fire coughing.  Examples can be seen here (caution, may be disturbing to watch). At the end of these paroxysms people take a large, rapid intake of breath through raw and often partially closed vocal cords, producing a high-pitched “whoop.”  The paroxysmal stage can last anywhere from 1-6 weeks.  The final stage is one of prolonged convalescence with a persistent dry cough lasting weeks to months (this is where pertussis got its other name, the “hundred day cough”).

A persistent cough isn’t the worst of pertussis.  60% of children under 6 months of age infected with pertussis need to be hospitalized, 5-10% get pneumonia, 1 in 125 have seizures, and 1 in 1000 suffer from an encephalopathy (inflammation of the brain) that frequently causes permanent brain damage.  And of course pertussis can kill.  Children under 3 months of age are at the greatest risk, and make up 84% of all pertussis related deaths.

Treatment is possible, but limited in utility.  Even though pertussis is bacterial and we have multiple antibiotics that reliably kill it, treatment after the first stage (when it becomes clear someone has more than a cold) only limits the ability of a person to spread it to others, it does not reduce the severity or length of the disease.  Once symptoms start, we are forced to ride out the illness.  Prevention is far better than treatment.  And speaking of prevention…

The Vaccine

The first vaccine to prevent pertussis was licensed in the US in the 1940s.  At that time we had an average yearly of 157 per 100,000 people, though this is likely to be a low-ball figure, given the state of medicine at the time and under-reporting.  From its release through the 1970s we saw a steady drop in cases from the pre-vaccination rate of 157 down to <1 infection per 100,000 people per year.  Though effective, the original vaccine had multiple side effects, including inducing a febrile seizure in 1 in 10,000 children.  These serious complications were enough to begin to undermine the public trust in the vaccine in the US, and to prompt several countries to stop pertussis immunization entirely.

In the 1980s and 90s several countries ceased or severely curtailed their use of DTP, including Japan, Sweden, and the UK.  Each of them saw a sharp and immediate rise in pertussis incidence to levels 10-100 times that of countries that continued to have high rates of vaccination with DTP.  This is a pattern we see repeated time and again when vaccines are withdrawn; it represents one of the best and most tragic demonstrations of vaccine efficacy you could ask for.

Effectiveness aside, the original DTP vaccine had legitimate problems, so a new vaccine was developed, tested, and eventually licensed for use.  By 1997 DTaP had fully replaced the original DTP vaccine.  Subsequent testing confirmed that it was just as effective as its predecessor, and induced significantly fewer side effects.  DTaP replaced DTP in the US before significant outbreaks could occur, and when instituted in countries that had stopped vaccination with DTP, quickly brought pertussis back under control.

DTaP, like all vaccines, continues to be studied, and is holding up very well to scrutiny.  Just this month, a self-controlled case series study in Pediatrics including 433,654 children and 7191 seizure events failed to find any significant association between DTaP and febrile seizures.

That the current pertussis vaccine is effective is beyond any serious contention, and its safety profile is excellent, but it’s not perfect.  The immune response the vaccine generates is relatively weak, necessitating multiple doses at 2, 4, 6, 15-18 months and 4-6 years to generate an adequate response (this isn’t unique to the vaccine; natural pertussis infection isn’t capable of providing long-lasting immunity either), and protection wanes after 5-10 years.

These characteristics predispose the vaccine, when used exclusively in childhood, to leave a couple of populations susceptible to infection.  First, the children most at risk of death from pertussis, those under the age of 3 months, have little to no direct protection from the vaccine or from maternal antibodies; this population relies heavily on herd immunity for protection.  The second vulnerability is that since neither the childhood vaccine nor natural infection provides lasting immunity, adults can become repeatedly infected, and serve as the primary reservoir of disease.  This is grimly illustrated by the fact that infants are most frequently infected not by other children, but by their parents.

Of course, this has been known for some time, and the vaccination schedule isn’t focused exclusively on early childhood.  A late childhood booster dose of TDaP (a reformulation of DTaP) at 11-18 years has been recommended since 2005, and adults are supposed to receive TDaP once between the ages of 19-64 to address this very problem.  Unfortunately, these doses are infrequently given for a variety of reasons, creating vulnerable populations to act as reservoirs for pertussis.

Though I may wish to have a vaccine that is somewhat less burdensome to use, it’s hard to complain about the current pertussis vaccine’s safety record, and properly administered, it’s capable of controlling and preventing epidemics (some even optimistically speculate the possibility of eradication).  To be fully effective though, it requires the dedicated support of both public health officials and the community.

The California Epidemic

Without a doubt, the relatively high-maintenance vaccination schedule contributes to our inability to fully control pertussis, but even if we had a vaccine capable of inducing lifelong immunity from birth onward, we would still have sections of the population that remain vulnerable to infection.  An embarrassingly large fraction of our fellow citizens lack access to health care.  Some immigrant populations may not have had the benefit of a modern medical system and immunization before arriving in the US, and some again lack access to health care after arrival.  A relatively small number of people are unable to be vaccinated or are immunocompromised due to medical conditions.  Finally, there are people who utilize California’s notoriously lax Personal Belief Exemption (PBE) policy to opt out of vaccination.

To what degree each of these factors is to blame for the current epidemic is not yet clear.  While it is true that some of the counties with the highest attack rates also happen to be counties where PBEs are common and vaccination rates low, other counties with reasonable vaccination rates are also being heavily affected.  (The attack rates of individual California counties can be found here.)  We simply do not yet have the entire epidemiologic picture, and it appears likely that several, if not all of these factors are in play.  That doesn’t mean, however, that we don’t know what action needs to be taken.

The California Department of Public Health is approaching this problem in the right way by addressing all of these elements at once, educating the public and expanding their TDaP program (TDaP program FAQ here, CDPH’s current activities and news releases here, and local California public health services here), though I think they may need to be even more aggressive.  In particular, I’d like to see a heavy revision of California’s PBE policy to make PBEs more difficult to obtain.

At the beginning of this post I said that in this pertussis epidemic, pointing fingers isn’t as important as taking action; to some this may have sounded hasty, but I hope you now understand my rationale.  An increase in size of any of any vulnerable group pushes the population as a whole closer to that nebulous cliff where herd immunity can no longer prevent an outbreak from becoming an epidemic.  No matter what the underlying cause(s) turns out to be, the single best intervention to control the spread of the current epidemic is the same: Vaccination. There may be multiple reasons for an outbreak of pertussis… but in our society there really is no excuse for it.

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Posted by Joseph Albietz