Signs outside of Walgreens and CVS have been advertising the flu vaccine for several weeks now. Even if its effectiveness varies from year to year, I consider it well worth the shot since I work around undergraduates and hospital personnel. Something I don’t expect to see this winter are advertisements for DTaP (diphtheria, tetanus, acellular pertussis) boosters even though they may be just as important for some as flu shots.
Pertussis, also called whooping cough, is caused by a lung infection with the bacterium Bordetella pertussis. It may sound like a nineteenth century disease you’d catch along the Oregon Trail, but whooping cough is a modern issue and can be serious or fatal, especially for newborns. According to Centers for Disease Control, the last few years have brought the largest pertussis outbreak since the 1950’s, reaching over 50,000 cases in 2012 (compared to a low of about 1000 in 1976). So, if we have a vaccine, why are there outbreaks?
In the 1950’s widespread use of the DTP vaccine (diphtheria, tetanus, pertussis) began in the U.S. In a couple of decades, the number of whooping cough cases dropped from about 50,000 to fewer than 1000. The vaccine was effective, but in the late 1970’s and then the 1980’s the vaccine’s side effects took center stage, perhaps as the memory of the disease faded. The DTP vaccine caused some combination of redness, swelling, pain and fever in about half of the children vaccinated. Some more serious reactions, like seizures were reported, but were transiently caused by fever and never led to permanent problems. Concerns that the vaccine caused neurological damage could not be substantiated and throughout the 1980’s, scientists reported that the risk of getting whooping cough outweighed the cost of the side effects.
From our point of view, it may seem brutal to accept such risks, but at the time, DTP was the only option available to prevent a disease that could be much more devastating. Whooping cough is named after the sound that infants make when they try (sometimes unsuccessfully) to take a breath in between coughing fits. The infection destroys structures in our lungs called cilia, which are tiny protrusions that collectively brush out grime from our lungs each day. They are like people in a mosh pit passing unwanted particulates out the door of your airway. When cilia are disabled, mucus collects in the lungs and your body copes by inducing spastic, uncontrollable coughs. Some can be extreme enough to slip vertebral discs or break ribs. The cough can last for months. For infants, the results are much worse because their lungs and airways are small so they have a much harder time catching their breath. This story gives an idea of how helpless parents and doctors can be to help an infant with pertussis.
Back to the 1980’s. Once the fear of the vaccine overcame fear of the disease, a new option had to be explored. The DTP contained whole bacteria that could not cause infection, but was causing inflammation in many vaccine recipients. Inflammation occurs when different types of immune cells gather in large numbers and release proteins that expand blood vessels and recruit more immune cells. Swelling follows and the cells release compounds that are meant to damage bacteria, but can also damage tissue. The process is usually well controlled and only lasts as long as it takes to remove whatever started it all off. The DTP vaccine, it turned out, caused inflammation because of a type of molecule called endotoxin in bacterial membranes. Endoxin non-specifically binds and activates immune cells and causes unchecked inflammation. So work began on a form of the vaccine with individual purified pieces of B. pertussis, called an acellular vaccine. It was approved as a booster by 1991 and the DTaP (diphtheria, tetanus and acellular pertussis) replaced the DTP completely by 1996.
It took about a decade to see the pattern emerge, but it’s starting to become clear that immunity after DTaP immunization does not last as long as immunity conferred by DTP. Since the vaccine requires 5 boosts, one potential cause could be under-immunization, or a failure to complete the whole vaccine course. A 2010 study reported that California kids who tested positive for pertussis were less likely to have received a fifth booster, which suggested that a full course was important for protection. But in the same study, many kids who did get the fifth boost were found in the infected group. These kids were also more likely to have received the last boost over a year prior to the study. That meant that even after five doses, the vaccine seems to wear off after a year. A more recent study done in Minnesota and Oregon also showed that kids’ susceptibility to getting pertussis increased a little more each year after the last booster.
So, under-immunization is not the whole story and although the DTaP vaccine works for about a year, there is something fundamentally different between it and DTP. It’s been suggested that it doesn’t cause enough inflammation or not the right kind of inflammation. So far, there is not enough basic science to support these ideas so researchers are taking a step back to ask simple questions about how the vaccine actually works (More on this in my next post).
Another idea is that B. pertussis is mutating and since DTaP only has a few of the bacteria’s proteins in it, dividing bacteria can start producing fewer or none of those proteins. This possibility is driving some scientists to explore different vaccine designs with more diverse proteins or to go back to a whole bacteria vaccine (like DTP), but without the super-inflammatory endotoxin. These explorations will depend on funding and it will take a long time to show that any new vaccine is effective, safe and cost-effective.
In the meantime, parents and doctors have to decide how best to use the existing vaccine to protect kids from whooping cough. Infants are the most vulnerable to the disease but they can’t be vaccinated for a couple of months after birth. Doctors and public health officials have turned to boosters for adolescents and adults with the idea that if parents and siblings are protected, they will be less likely to pass the infection to a newborn.
In 2005, the CDC recommended a 6th booster called Tdap for adolescents between 10 and 18 years old. One study tested the effectives of this method by comparing observed infection rates among infants to rates that were estimated based on data from previous years. They found that actual rates were significantly lower than the projected ones, bringing hope that cocooning may work. This year, Tdap boosting during pregnancy was deemed safe and was recommended by the CDC. Hopefully another year or two will bring evidence that vaccinating moms during each pregnancy reduces infant pertussis.
While researchers work on finding a happy medium between the inflammatory whole bacteria DTP and the fair-weather DTaP, we are left with rudimentary options: get Tdap boosters, keep kids up to date on their DTaP doses and wash your hands long enough to sing the “happy birthday” song three times.
The Immunization Action Coalition
Nature and rates of adverse reactions associated with DTP and DT immunizations in infants and children. Cody, CL.et al. Pediatrics Nov 1981
Severe reactions associated with diphtheria-tetanus-pertussis vaccine: detailed study of children with seizures, hypotonic-hyporesponsive episodes, high fevers, and persistent crying. Blumberg, DA et al. Pediatrics Jun 1993
“Pertussis Vaccine: Myths and Realities” Gold, R. Can Fam Physician May 1988
Pertussis and pertussis vaccine: further analysis of benefits, risks and costs. Hinman, AR and Koplan, JP. Dev Biol Stand 1985
Association of childhood pertussis with receipt of 5 doses of pertussis vaccine by time since last vaccine does, California, 2010. Misegades, LK et al. JAMA Nov 2012.
Waning immunity to pertussis following 5 doses of DTaP. Tartof, SY et al. Pediatrics Apr 2013
Tetanus, diphtheria, acellular pertussis vaccine during pregnancy: pregnancy and infant health outcomes. Shakib, JH et al. J Pediatrics Nov 2013.