Battling the children’s plague
For two hundred years parents watched helplessly as their kids died of diphtheria, said author Perri Klass in Smithsonian Magazine. Then treatments and vaccines turned the tide, in one of medicine’s greatest victories.
EVEN NOAH WEBSTER, that master of words, did not have a name for the terrible sickness. “In May 1735,” he wrote in A Brief History of Epidemic and Pestilential Diseases, “in a wet cold season, appeared at Kingston, an inland town in New-Hampshire, situated in a low plain, a disease among children, commonly called the ‘throat distemper,’ of a most malignant kind, and by far the most fatal ever known in this country.” Webster noted the symptoms, including general weakness and a swollen neck. The disease moved through the colonies, he wrote, “and gradually traveled southward, almost stripping the country of children .... It was literally the plague among children. Many families lost three and four children—many lost all.” And children who survived generally went on to die young, he wrote from his vantage point of more than half a century later. The “throat distemper” had somehow weakened their bodies.
In 1821, a French physician, Pierre Bretonneau, gave the disease a name: diphtérite. He based it on the Greek word diphthera, for leather—a reference to the affliction’s signature physical feature, a thick, leathery buildup of dead tissue in a patient’s throat, which made breathing and swallowing difficult, or impossible. And children, with their relatively small airways, were particularly vulnerable. unprecedented effort, using laboratory investigations to come up with new treatments for struggling, suffocating victims.
In my more than 30 years as a practicing pediatrician, I have never seen a single patient with diphtheria. That’s because vaccination efforts in this country have been so successful. In the 1980s, when I was training, there were only a few cases a year in the United States. Since 2000, there have been only six reported cases in the U.S. that can block a patient’s airway. Friedrich Loeffler, a German bacteriologist, took this microbe and grew it in the lab, to solve the mystery of whether it was indeed the cause of the disease. Loeffler infected guinea pigs, rabbits, horses, and dogs with his labgrown cultures. The bacterium came to be known as the Klebs-Loeffler bacillus (later, Corynebacterium diphtheriae).
Then in 1888, Roux and Alexandre Yersin, medical doctors at the Institut Pasteur in Paris, took another big step when they showed that a substance secreted by the bacteria was the particular culprit. In the lab, researchers grew the bacteria bathed in a broth; after siphoning off the fluid and filtering it to remove any cells, Roux and Yersin found it contained a potent toxin. The scientists mixed the toxin with an iodine solution, which made it far less deadly.
Another step: Behring, working with Shibasaburo Kitasato, a Japanese bacteriologist, discovered that weakened tetanus toxin, given repeatedly to experimental animals, prevented those animals from developing symptoms after they were exposed to tetanus bacteria. The toxin had spurred the animals’ immune systems to recognize and fend off the invading bacteria. Moreover, when lab workers took blood from those immunized animals and removed the blood cells, the remaining serum contained antibodies to tetanus that, when injected into other animals, provided immunity to those animals, too. Behring applied this same principle to diphtheria, creating a serum that could be used to combat the disease in humans. He was recognized for this work in 1901 with the first ever Nobel Prize in Medicine.
they injected horses with weakened diphtheria toxin. They waited for the animals to produce antibodies in response, then bled the animals and collected the serum.
From February to July 1894, at the city’s large Hôpital des Enfants-Malades (or Hospital for Sick Children), Martin, Roux, and Chaillou administered horse serum containing antitoxin to 448 children suffering from diphtheria. Just 109 of them died, giving a fatality rate of 24.3 percent. Meanwhile, at the pediatric Hôpital Armand-Trousseau, where the serum was not used, the fatality rate was 60 percent.
FOR ANY CHILD sick with diphtheria at the very end of the 19th century, the key question was whether the antitoxin would be available. It came to New York City almost immediately. Hermann Biggs, chief inspector of pathology, bacteriology, and disinfection at the New York City
Board of Health, learned about the antitoxin during a trip to Europe in 1894, and he cabled a colleague to start making serum.
But the therapy was distributed unevenly in the United States when the young son of W.E.B. Du Bois got sick. Du Bois, the historian and activist who had been the first African-American to earn a doctoral degree at Harvard, left Philadelphia in 1897 for an academic job in Atlanta. In 1899, his 2-yearold son, Burghardt, came down with diphtheria symptoms. In Du Bois’ classic 1903 book, The Souls of Black Folk, he wrote about his child’s death. “And then one night the little feet pattered wearily to the wee white bed, and the tiny hands trembled; and a warm flushed face tossed on the pillow, and we knew baby was sick,” he wrote. “Ten days he lay there—a swift week and three endless days, wasting, wasting away.”
The night before Burghardt’s death, his father had gone looking for a Black doctor, assuming that no white doctor in Atlanta would treat a Black child. His son would have had more chance of getting antitoxin in other cities. Du Bois’ wife, Nina, believed that if the family had stayed in Philadelphia, the child would have survived.
C. diphtheriae produces a deadly toxin.
noble “von” before his last name) developed a vaccine against diphtheria, the work was hailed as major progress. His vaccine had two components: diphtheria antitoxin, which could battle an active infection, and also an inactivated version of the toxin produced by the bacteria.
WITHIN SEVERAL YEARS of von Behring’s achievement, massive pediatric immunization programs were underway in New York City. School nurses were key in these campaigns. Public health authorities provided information in Yiddish, Italian, and just about every other language that would help the vaccine reach immigrant communities. By 1929, the city was also opening diphtheria immunization stations in parks. cells. The vaccine generates immune reactions that protect against all three diseases.
Despite all the progress preventing and treating the disease, diphtheria has not been eradicated and still flares up around the world, according to a recent analysis of cases by Kristie Clarke, a CDC epidemiologist. She counted almost 9,000 diphtheria cases globally in 2017. Outbreaks tended to occur in places destabilized by population migration and political strife—she cited Bangladesh, Yemen, Nigeria, and Venezuela. Diphtheria emerges, she told me, “when anything disrupts routine vaccination.” And the disease is still a killer; the mortality rate usually cited is 5 to 10 percent, but fatalities can be especially high in areas where medical care is not available. A 2011 outbreak in Nigeria had a case fatality rate of almost 43 percent in children 4 and younger. The antitoxin is still made by injecting horses with weakened diphtheria, though scientists are working to develop newer methods.
At a time when so many Americans are distrustful of vaccines, I often think about the talks I used to have with parents in the 1990s. We were still using the old DTP vaccine, which meant children sometimes experienced side effects, especially fevers and sore arms. The discomfort was not nearly as terrifying as the diseases it inoculated against, but parents had no firsthand experience with the diseases themselves, thanks to years of successful vaccinations. My challenge was to help them understand that when they got their babies vaccinated, they were doing their part in a great triumph of human ingenuity and public health. The whole point was to keep those babies safe.
In a Canadian journal article from 1927, a doctor recalled the years before the antitoxin was available, when he’d had to watch a “beautiful girl of five or six years” choke to death. Later, the doctor’s own daughter came down with diphtheria, but a decade had passed and now the antitoxin was available. “To watch the choking dreadful membrane melt away and disappear in a few hours with complete restoration to health within a few days,” he wrote, “was one of the most dramatic and thrilling experiences of my professional career.”
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