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September 2013

Whooping Cough Vaccination: Not Just for Kids
By Carolyn Gutierrez
For The Record
Vol. 25 No. 12 P. 22

Ignorance and fading vaccine power have contributed to the recent increase in pertussis cases.

Pertussis, commonly known as whooping cough, has experienced an alarming resurgence in the United States over the past three years with the number of cases reaching epidemic proportions in California, Washington, and Vermont.

Although there are other factors in play, infectious disease experts theorize that the recent spike is largely due to the waning immunity of the acellular vaccines that were implemented in 1997. The dearth of adults receiving booster shots to protect themselves and younger family members and the general misdiagnosis of whooping cough in adult populations also may be contributing to the disease’s rampant spread.

A Danger to Infants
A highly contagious disease, whooping cough is caused by exposure to Bordetella pertussis bacteria, which releases toxins into the cilia lining the upper respiratory system and leads to inflammation. Beginning anywhere from about five to 21 days after exposure, symptoms at first are indistinguishable from the common cold, but as the disease progresses, a stubborn cough develops, recognizable in children by a telltale inspiratory “whoop” as the child gasps for breath during paroxysmal coughing episodes.

 The interminable coughing spells impede eating and sleeping, cause vomiting and, in the youngest patients, can lead to pneumonia, seizures, brain damage, and death. Infants with pertussis also may present with pauses in their breathing patterns (apnea).

Also referred to as “the 100-day cough,” pertussis can indeed persist for more than 90 days. During this time, the disease can be transmitted to others through coughing and sneezing. “It’s almost as contagious as measles,” says Ed Marcuse, MD, MPH, a professor of pediatrics and an adjunct professor of epidemiology at the University of Washington and the associate medical director of quality improvement at Seattle Children’s Hospital. “It’s easily communicated. Even contracting the disease does not produce lifelong immunity. We have studies going back to the 1930s showing that if pertussis gets into a household, the attack rate among those who are susceptible approaches 95%.”

Treatment with antibiotics is recommended as early as possible to stem the spread of whooping cough and lessen the symptoms.

Although all age groups are equally susceptible to the disease, infants younger than 6 months old are the most vulnerable because they have the highest mortality rate for pertussis. More than one-half of infants younger than 1 year old who contract whooping cough are hospitalized.

The distinctive whooping sound is more common in younger children with pertussis simply because of the slightness and fragility of their developing respiratory system. “In a baby, the airways are much smaller,” says Jorge Parada, MD, MPH, a professor of medicine and the medical director of the infection control program at Loyola University in Illinois. “The trachea and the bronchi are all much smaller—they are not nearly as firm as in an adult—and they collapse when they are sucking in with negative pressure.”

Adults with whooping cough may not necessarily present with the classic whoop per se—their cough may be paroxysmal—but oftentimes, especially in those previously vaccinated who may have waning immunity to pertussis, a chronic dry cough may be the primary symptom.

“Because the cough takes so long to go away, typically what will happen is that [the adult patient] goes to the doctor and the doctor’s seeing them for the second or third time for the same cough,” Parada explains. “Then, finally, it dawns on the doctor: ‘This might be pertussis, let’s send a test.’ By the time it’s diagnosed, the patient has had the opportunity to cough on all of his friends and family. So the atypical presentation makes for a delayed diagnosis and increased opportunities for the spread of pertussis.”

Pertussis Vaccine: Acellular vs. Whole Cell
Until the late 1990s, infants and children up to the age of 7 were given a whole-cell pertussis vaccine known as DTwP (which also protects against diphtheria and tetanus). Whole-cell vaccines are composed of suspensions of dead B pertussis organisms in their entirety, and although the vaccines were thought to induce stronger immunity, it was found that they gave rise to a host of adverse reactions. The most unsettling concern was whether the whole-cell vaccines were linked to serious long-term complications.

“The big questions, specifically, were whether or not DTwP caused encephalopathy or SIDS [sudden infant death syndrome] or a variety of behavioral disorders,” Marcuse says. “Suffice it to say, when the studies were all done, it became pretty clear that the vaccine did not cause SIDS, and there was no solid, credible evidence that it caused long-term encephalopathy or brain damage. But there was no question that it caused a lot of fevers and local reactions, and a new vaccine was developed.”

Scientists replaced the whole-cell vaccine with an acellular version (DTaP) made from several specific antigens of the pertussis organism in lieu of the entire organism itself. Although the acellular vaccine’s efficacy is just as high as the whole-cell version during the first two years following vaccination, it suffers from diminishing immunity over longer periods. As the patient ages, protection from the vaccine wanes considerably. “It’s taken us some time to recognize just how big an issue this is,” Parada says. “The acellular vaccine doesn’t appear to prime the immune system as effectively as the old vaccine.”

During the recent outbreaks, particularly high rates of pertussis were found in 13- and 14-year-olds. Infectious disease experts suggest that this indicates a direct correlation to the use of acellular vaccines beginning in the late 1990s. Although pertussis in previously vaccinated patients tends to be less severe, it may still serve as a point source for the spread of the bacteria.

Formulating a new vaccine for B pertussis has proven to be a challenge for researchers because of the bacterium’s unusual complexity. “If we want to know whether a measles vaccine or a tetanus vaccine is effective, it’s very easy,” Marcuse explains. “We measure the antibodies to tetanus toxoids or the antibodies to measles virus, and that correlates beautifully with protection. Unfortunately, with pertussis, there is no good correlate. Immunity to pertussis is more complicated. We don’t have a good laboratory marker for it—we don’t have a good laboratory marker for protective immunity—and that makes it harder to develop a vaccine.”

Clearly, the objective is to formulate a pertussis vaccine that retains the safety of the acellular version but has the durability of the whole-cell vaccine. In the meantime, the Centers for Disease Control and Prevention (CDC) maintains, “Vaccination continues to be the single most effective strategy to reduce morbidity and mortality caused by pertussis.”

In the Morbidity and Mortality Weekly Report addressing Washington’s 2012 pertussis epidemic, the CDC noted, “Unvaccinated children have at least an eightfold greater risk for pertussis than children fully vaccinated with DTaP.” Despite waning immunity, acellular pertussis vaccines have been found to provide excellent short-term protection and, in addition to the DTaP infant and childhood vaccination series, the Tdap is strongly recommended as a booster shot for adolescents and adults of all ages.

Giving booster shots to adults may play a significant role in keeping the spread of pertussis at bay. “A lot of people don’t get their boosters because we’re much better at vaccinating children than we are adults,” says Parada. “[With children], there are requirements to go to school—there are not a lot of requirements for adult vaccination.”

Vaccine Safety for Older Adults
Although a Tdap vaccine was licensed in 2011 for people aged 65 and older, it had not been initially licensed for older adults, resulting in limited published information on its safety for the elderly population.

In the study “Safety of a Tetanus-Diphtheria-Acellular Pertussis Vaccine When Used Off-Label in an Elderly Population,” lead author Hung Fu Tseng, PhD, MPH, from Kaiser Permanente’s Southern California department of research and evaluation, examined the EHRs of almost 120,000 adults aged 65 and older to determine whether they had experienced any adverse events following off-label vaccination with Tdap. The results were compared with a similarly large cohort of adults over the age of 65 who had been vaccinated with the tetanus and diphtheria (Td) vaccine, which had previously been deemed safe for use in older populations.

Tseng and his team found that the results were comparable between the two groups. The adverse events, such as local pain and swelling at the injection site, that occurred after Tdap were similar to the adverse events that occurred following the Td vaccination.

“We found that receiving Tdap does not bring additional risk compared with Td,” Tseng says. Additionally, the study noted, “The safety profile of Tdap in the elderly population ≥ 65 years of age in this study is comparable to that in the younger population.”

Although older adults are not particularly at high risk for pertussis, infectious disease experts suggest that the best way to protect those who are most at risk—young infants—is to vaccinate across all generations. “Older people should consider receiving the vaccine given the low risk of possible adverse events,” Tseng says. “By receiving the vaccine they can protect not only themselves, but also the young children in their family.”

A Family Affair
Newborns receive their five-dose vaccination series for pertussis at the ages of 2 months, 4 months, 6 months, 15 to 18 months, and 4 to 6 years. Until an infant’s primary series of shots are completed (typically in the first six months), their immune systems are considered to be at their most vulnerable to disease. According to the CDC, of the 27,550 cases of whooping cough reported in 2010, 3,350 occurred in infants under the age of 6 months, 25 of whom died. The CDC notes that studies identifying the source of pertussis in infants found that the mothers had transmitted 30% to 40% of the infections.

Because of a newborn’s tenuous immune system, the Advisory Committee on Immunization Practices (ACIP) recommends the Tdap vaccine for pregnant women, ideally after 20 weeks gestation for optimal antibody transfer and protection at time of birth. The ACIP notes that the Tdap vaccine has been found to be safe for pregnant women.

For new mothers who were not vaccinated during their pregnancy, the CDC recommends they receive Tdap after delivery and before they are released from the hospital to protect their newborn upon returning home.

But safeguarding the newborn from infection doesn’t stop with inoculating the mother. A strategy known as “cocooning”—making sure that both parents, other children in the household, grandparents, and any other family members or caregivers who are most likely to come in contact with the newborn are all up-to-date with pertussis vaccinations and booster shots—has been recommended by the ACIP since 2005. However, cocooning has had mixed results.

“In theory, [cocooning] should work beautifully because if you are newly boosted and fully vaccinated, the odds of getting pertussis drop dramatically—everyone around this baby won’t be able to catch it and won’t be able to transmit it,” Parada says. “Unfortunately, cocooning hasn’t worked as well as we would like.”

Studies have determined that cocooning has had only limited success in preventing pertussis infection in newborns. Parada notes that, interestingly enough, it is often the father who neglects to complete his vaccination series or does not receive a booster, compromising the household’s protection.

“The other issue is modern life,” Parada says. “So many kids get put in day care, so how do you cocoon? You have day-care centers where they’ll take babies that are relatively young all the way up to 4 years old. A 4-year-old’s parent might not be as worried [about pertussis] anymore. But meanwhile, the 6- or 9-month-old baby who’s in the same center is going to be at high risk.”

Whooping Cough Awareness
Until a few years ago, pertussis was difficult to diagnose. It mainly was detected through clinical presentation. Culturing B pertussis proved to be challenging, and the test’s sensitivity was limited. “It’s only been more recently when we started using molecular diagnostic techniques—polymerase chain reaction and so forth—that we’ve finally been able to get more accurate and rapid tests for pertussis,” Parada says.

More sensitive diagnostic tools analyzing the bacteria’s DNA have enabled clinicians to diagnose milder cases of pertussis, thereby increasing the awareness of how widespread the disease actually is. Infectious disease experts hope that awareness of the resurgence of what was once considered an old-fashioned childhood illness will encourage people in all age groups to consult with their primary care physician to either complete their vaccination series or find out whether they are due for a booster shot.

“There is a tremendous amount of inertia,” Marcuse says. “[Vaccinating for pertussis] has not been part of the adult immunization schedule; that is something new. And I think that the awareness of whooping cough as a common cause of prolonged cough illness in adults is just beginning to be understood, even among my medical colleagues. I think very few thought about pertussis when faced with a 30-, 40-, or 50-year-old with a two-week cough. We simply didn’t look for it.”

Interestingly, studies have shown that when there is extensive vaccination in a particular age group, it can have far-reaching protective results for other age groups in the same community. Parada cites a study that determined children were pneumococcal “amplifiers” who can spread the disease rapidly within a community. Once children received the pneumococcus vaccine, they no longer infected their grandparents and, in turn, the grandparents’ mortality rate from pneumococcal disease decreased.

A similar chain of events occurred with flu vaccines. Although older people and those with comorbid illnesses were encouraged to get the flu shot, “We actually saw a big drop in flu amongst grandparents when we started giving flu shots to the grandkids,” Parada explains. “Pertussis is the reverse example. The adults vaccinate themselves but protect the kids.”

Infectious disease experts underscore the importance of vaccination in a culture that may have selectively forgotten the serious ramifications of childhood diseases such as pertussis.

“Effectively, in this country, only people who don’t want to get vaccinated don’t get vaccinated,” Parada says. “I spent a year in Angola during the civil war there, where people were begging for vaccines, and people were dying from measles and chickenpox. The thing is, here, we’ve benefited from so much improvement in our health care that people have forgotten or have chosen to ignore what infection amongst the naïve patient population can lead to.”

— Carolyn Gutierrez is a freelance writer in New York City.