Update on Pertussis

BETTER KNOWN BY its descriptive nickname “whooping cough,” pertussis was quite recently on its way to joining smallpox as an extinct disease. However, due to a combination of its own highly contagious nature, its evolving DNA and the increasing influence of anti-vaccine activists, pertussis not only persists, it has made a sadly dramatic comeback in recent years.

Not only can a case of whooping cough be frightening for the patient (and their family members), but in the very young — who are the most likely to contract it, before their immunizations are complete — it can be fatal. One report cites 36,000 deaths in the United States due to pertussis between 1926 and 1930, before the first vaccine was introduced. By 1976, an effective vaccination campaign had brought the total number of pertussis cases in the U.S. down to 1,010.¹

But after an inaccurate 1982 NBC television news report that falsely claimed the pertussis vaccine caused permanent brain damage, the public outcry was so strong that researchers devised a less-powerful vaccine that had fewer side effects. Unfortunately, it also seems to have a much shorter period of effectiveness. By 2012, pertussis infections had grown 40-fold from 1976 numbers to 48,277 cases in the U.S., 1 resulting in 20 deaths,² while globally, there are an estimated 16 million cases per year, resulting in 195,000 fatalities — mostly children.³

What Is Pertussis?

Pertussis is a highly contagious infection of the upper respiratory tract. The bacteria that causes pertussis are inhaled, after which they attach themselves to the cilia along the respiratory tract, where they exude toxins that cause swelling and irritation in nearby tissue.⁴ This irritation causes the violent coughing associated with the disease.

Unlike many other contagious diseases, there is no ancient history of pertussis; the first mention appeared in 1540 in England. In 1578, an epidemic in Paris was recorded. Thomas Sydenham, a British physician, gave the first detailed description of the disease in 1679, also giving it its modern name.⁵

It wasn’t until 1900 that the bacterium that causes the disease was observed microscopically. Jules Bordet and Octave Gengou, working in Paris, identified the species in a patient’s sputum. It took another six years before they isolated a sample.⁶

Causes of Pertussis

Pertussis is caused by the bacteria Bordetella pertussis.⁴ It is distributed through the air by an infected person either through normal breathing or by coughing. The bacteria are very difficult to grow outside the human body, making development of vaccines challenging.

Symptoms and Progression of Pertussis

The early symptoms of pertussis are identical to those of everyday colds:

• Low-grade fever
• Mild, occasional cough
• Runny nose

These early symptoms can last for up to two weeks, and physicians will generally not have reason to suspect pertussis or to test for it based on these symptoms. After one to two weeks, the advanced symptoms of pertussis will manifest:⁷

• Numerous rapid coughs followed by a high-pitched “whoop” as the patient inhales
• Vomiting during or following a coughing spell
• Exhaustion following a coughing spell

These symptoms can last for up to 10 weeks. Indeed, the Chinese call pertussis the “100 day cough.”⁷ Coughing is often more prevalent at night. Gradually, coughing will ease, preceded by the “whoops” disappearing. Subsequent respiratory infections may cause the coughing to resume for up to six months following the initial infection. Patients may be more susceptible to pneumonia during or after whooping cough.⁸

Depending on the severity of coughing fits, patients can suffer secondary symptoms of trauma. These symptoms can include:⁹

• Broken capillaries in the eyes or skin
• Bruised and/or cracked ribs
• Hernias, particularly in the abdomen
• Apnea in infants

Diagnosing Pertussis

Pertussis can be diagnosed either by considering the distinctive late-stage symptoms or by testing a sample of mucus from the patient. A blood test for specific antigens can also be used.¹⁰ X-rays may be appropriate if a secondary infection such as pneumonia is suspected.

Treating Pertussis

Antibiotics can help shorten the infection if started within the first three weeks. If the antibiotic treatment begins before the onset of spasmodic coughing fits, the treatment can also ease the severity of the infection. After three weeks, the bacteria are typically no longer in the body; however, the toxins produced by the bacteria will continue to produce the symptoms for weeks afterward.¹¹ Antibiotics are rarely prescribed after three weeks from onset of infection due to the bacteria already being absent from the patient.

Other treatments to ease symptoms throughout the course of the disease include:¹¹

• Using a mister to help loosen the mucus and reduce the severity of coughing
• Keeping the environment free of dust, smoke and chemicals that can irritate the throat or lungs
• Providing regular liquids to the patient

Infants, particularly those who have not yet completed their immunizations, may require hospitalization¹² so they can be monitored continuously, and so mucus can be removed as it builds up. They may also receive fluids via IV, as well as oxygen to assist their breathing. Up to half of infants under the age of 1 who contract pertussis in Western nations will be hospitalized.

For infants suffering a severe infection, pertussis immunoglobulin (P-IGIV) may prove effective at easing the symptoms caused by pertussis toxin. A 1991 study in Scandinavia showed remarkable improvements in a blind study, with coughing fits cut by two-thirds on average.¹³ A 1999 study of mice in a laboratory environment also showed significant improvement.¹⁴

However, a 2014 follow-up analysis of these and other studies found little correlation between the use of P-IGIV and severity, frequency or length of coughing fits.¹⁵ Still, the authors cautioned that the number of studies was too low to provide conclusive evidence, and the quality of the documentation associated with those studies was often incomplete. They concluded by encouraging additional studies on the efficacy of P-IGIV in treating symptoms of pertussis toxins.

Preventing Pertussis

Pertussis has been preventable by vaccine since the 1940s. Experiments to produce a pertussis vaccine had begun in the 1930s, and a whole-cell vaccine was adopted as the standard in 1944. The vaccine was developed by killing bacteria by solution or heat and then introducing them to the body via injection to stimulate production of antibodies. Side effects of the vaccine were generally mild, but some patients did report convulsions and blacking out,¹⁶ although later studies showed no permanent effects from these episodes.

The efficacy of the vaccine was astonishing. Just 30 years after the pertussis vaccine was introduced, the disease stood on the brink of extinction, with just over 1,000 cases reported in the U.S. in 1976. But six years later, on April 19, 1982, the Washington, D.C., affiliate of the NBC television network aired a program that claimed the pertussis whole-cell vaccine caused permanent brain damage in some infants.¹⁷ Afterward, understandably, parents were reluctant or outright refused to have their children immunized. While that report would eventually be wholly disproved and discredited, the damage was done: Parents did not trust the whole-cell vaccine.

To mitigate the widespread distrust, researchers developed a new vaccine that used broken pieces of the bacterium instead of dead whole cells. The new vaccine is today part of the DTaP vaccine (diphtheria, tetanus and pertussis) given to children in five doses. It is also part of the TDaP booster vaccine given to preteens, teenagers and adults.

Unfortunately, a 2012 study published in the New England Journal of Medicine showed that the acellular vaccine, developed in response to the ill-informed backlash against the whole-cell vaccine, does not provide the same long-lasting protection as the original formulation.¹⁸ Specifically, the study found that immunity to pertussis waned within five years of the last dose of DTaP. Scientific American reported a year later that outbreaks in California were not just occurring among the unvaccinated. (California has among the highest number of children whose parents elect not to have them vaccinated, although a new law will make it almost impossible to opt out in the future.) A majority of children who contracted pertussis in California in 2010 were children who had received the acellular vaccine.¹⁹ And, the U.S. Food and Drug Administration found that while the vaccine prevented those immunized from developing pertussis, it did not necessarily prevent them from being infected — or from passing the infection on to unvaccinated people they encountered.²⁰

While this evidence might seem to add up to a strong medical and scientific argument to return to the whole-cell vaccine, it’s quite possible that the rise of the anti-vaccine political movement would make it very difficult to initiate a quick return to the whole-cell vaccine.¹⁷

Ongoing Research

Researchers are attacking pertussis from a variety of angles. They are looking at ways of crippling the bacteria that cause the disease, as well as ways of stimulating the body’s own defenses to better fight the infection.

Among the promising lines of research are those that involve giving pregnant women the vaccine. Early studies show the vaccine stimulates the mother’s body to produce antibodies that are passed to the child via the placenta. Another study is devoted to introducing minute quantities of pertussis toxins to stimulate the body to build up defenses against the poisons produced by the infectious bacteria. And, yet another study is seeking bioengineering drugs to attack specific molecules in the cell walls of the pertussis-causing bacteria while leaving healthy cells in the patient unaffected.²¹

However, the target is also changing. A recent study offers evidence that Bordetella pertussis has evolved to the point over the last 80 years that the current vaccines may no longer work against it. As the genetic code for the bacteria changes over time, the antibodies stimulated by the current vaccine may not be targeting the current bacteria, leaving many vaccinated children vulnerable.²²

Looking Ahead While the ongoing and unavoidable evolution of Bordetella pertussis may require an update to the vaccine, the largest hurdles to lowering incidences of pertussis outbreaks are political and cultural — not medical.

California’s experience in going from enacting one of the most lenient state “opt-out” laws for preschool vaccinations to adopting one of the strictest for the current school year may offer some guidance. Under the old law and policy, California parents could simply declare a moral opposition to vaccination to have their children exempted. The new law no longer even allows for a formal religious exemption.

Nonetheless, the lingering autism scare of the late 1990s, ignited by British medical journal The Lancet publishing a paper alleging a link between vaccines and autism in young children (later wholly disproved), has made opposition to vaccines a cause célèbre in Western Europe and North America. As pointed out above, reverting to a whole-cell vaccine for pertussis would likely prove effective at stopping the disease and saving lives, but it would also generate tremendous opposition.

And, with fewer than two dozen deaths a year due to pertussis in the U.S., changing vaccines is unlikely to be seen as a critical public health issue. In the rest of the world, with nearly 200,000 children a year still dying from a preventable disease, the issue isn’t political so much as practical: an overt lack of resources to get every child vaccinated. That is perhaps where the focus should and will lie in the years to come.