Diphtheria

• 1. Introduction

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  Diphtheria killed an estimated million people a year before the 1980s, yet most listeners today have never seen a case. In 1735, a throat illness swept through New England so ferociously that in one New Hampshire town, 32 percent of children under ten died. Noah Webster wrote at the time: "It was literally the plague among children. Many families lost three of four children - many lost all." That epidemic was already ancient by the time scientists figured out what caused it, and older still by the time anyone had a vaccine. The story of diphtheria is not simply a story of a disease. It is a story about how humanity slowly, imperfectly, learned to fight something invisible - and what happens when that fight is abandoned. The questions worth holding as you listen: what makes this bacterium so lethal, how did the world's first standardized biological treatment come to be, and why did a disease declared nearly extinct in the twentieth century keep reappearing in the twenty-first?

• 2. The Membrane That Kills

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  Pierre Bretonneau named the disease diphtheria in 1826, drawing on the Greek word for leather, diphthera. That choice of word was not poetic. It was anatomically precise. Within two to three days of infection, dead tissue forms a thick grey coating in the throat - a pseudomembrane - that can extend from the nose across the tonsils, voice box, and all the way into the lungs. Patients develop what historical texts called a barking or brassy cough, similar to croup. The neck swells as lymph nodes enlarge, a presentation historically called a "bull neck." Breathing becomes a struggle against a membrane that behaves like a growing leather plug. In the worst cases the airway closes entirely, and the patient strangles.

  The pseudomembrane is only the visible part of the danger. The bacterium Corynebacterium diphtheriae releases an exotoxin that travels through the blood to attack the heart, nerves, and kidneys. Myocarditis - inflammation of the heart muscle - can produce fatal arrhythmias, either early in the illness or weeks after the throat has apparently healed. The toxin can also cause paralysis in the eyes, neck, throat, and respiratory muscles. Among untreated patients, roughly 40-50 percent die. Even among those who do receive treatment, death occurs in 5-10 percent of diagnosed cases. In children under five and adults over forty, the fatality rate can reach 20 percent.

  The toxin's mechanism is remarkable in its precision. It is produced only when C. diphtheriae is itself infected by a particular bacteriophage - a virus that parasitizes bacteria. Once that phage integrates its tox gene into the bacterial chromosome, the bacterium becomes a toxin factory. The toxin protein, which weighs 60 kDa, splits into two fragments after entering a human cell. Fragment A shuts down protein synthesis by blocking a molecule called elongation factor EF-2, which is essential for building new proteins. A cell that cannot make new proteins cannot survive. Researchers have found that very high doses of nicotinamide - a form of vitamin B3 - can reverse this effect in laboratory conditions, because the reversal reaction is driven by product concentration.

• 3. The Scientists Who Named It

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  Edwin Klebs identified the bacterium in 1883 and named it Klebs-Loeffler bacterium after himself and his collaborator. The club shape of the organism was the diagnostic clue that distinguished it from other microbes. German bacteriologist Friedrich Loeffler became the first person known to culture C. diphtheriae in 1884. Loeffler did more than grow the bacteria in a laboratory; he fulfilled Koch's postulates by isolating the organism from patients, reproducing the disease in guinea pigs and rabbits, and then recovering the same bacillus from the infected animals. He also suspected early on that a toxin - not the bacteria themselves - was causing the symptoms, and he showed that some animals appeared naturally immune.

  Emile Roux and Alexandre Yersin confirmed the toxin hypothesis in 1888, demonstrating that a substance produced by C. diphtheriae caused the disease's symptoms in animals even without live bacteria present. Two years later, in 1890, Shibasaburo Kitasato and Emil von Behring took the next step: they immunized guinea pigs, goats, and horses with heat-treated diphtheria toxin, then showed that serum from those animals could cure the disease in non-immunized animals. Behring tried the antitoxin on human patients in 1891 without success. Successful human treatment using horse-derived antitoxin began in 1894, after production methods were refined. In 1901, Emil von Behring won the first Nobel Prize in medicine for this work.

  Standardization of the antitoxin became the next challenge. In 1897, Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin - the first standardization of any biological product in history. That foundational work shaped how sera and vaccines would be measured and regulated for generations. Then in 1914, William H. Park built on the antitoxin research to create the first diphtheria vaccine, a carefully calibrated mixture of toxin and antitoxin known as TAT, by systematically adjusting concentrations to produce durable immunity with minimal adverse reactions.

• 4. When the Cure Caused Harm

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  Antitoxin derived from horse serum was the first tool that could actually stop diphtheria from killing, but it came with its own dangers. In 1901, ten of eleven children in St. Louis who received contaminated diphtheria antitoxin died. The horse that had provided the antitoxin had died of tetanus, and the contaminated batch went undetected. That same period saw a tetanus outbreak in Camden, New Jersey, also linked to biological products. Together, these events helped trigger the first federal regulation of biological products in the United States.

  In 1906, Clemens Pirquet and Bela Schick described what they called serum sickness - a delayed reaction in children who received large quantities of horse-derived antitoxin. Patients developed swelling, fever, rash, and joint pain, sometimes weeks after treatment. Pirquet and Schick found these reactions were self-limited rather than life-threatening, and that children who survived diphtheria were not permanently harmed. The underlying cause, now understood, is that the human immune system recognizes foreign horse antibodies as antigens and mounts its own response against them.

  In 1919, in Dallas, Texas, ten children died and sixty others became seriously ill from toxic antitoxin that had already passed testing by the New York State Health Department. The manufacturer, the Mulford Company of Philadelphia, paid damages in every case. And in 1948, in Kyoto, Japan, 68 of 606 children died after diphtheria immunization due to improperly manufactured aluminum phosphate toxoid. Each of these disasters revealed gaps in manufacturing quality and regulatory oversight, and each in its own way forced improvements that made later vaccination programs safer.

• 5. Building Immunity at Scale

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  Bela Schick developed the Schick test between 1910 and 1911, a method for detecting whether a person already had immunity to diphtheria. Only those without pre-existing immunity were vaccinated. Schick then coordinated a massive five-year public awareness campaign, during which the Metropolitan Life Insurance Company distributed 85 million pieces of literature appealing to parents to protect their children.

  Alexander Thomas Glenny increased the effectiveness of the diphtheria toxoid in 1926 by treating it with aluminum salts. The toxoid vaccine - an inactivated form of the toxin rather than live bacteria - triggers antitoxin immunity without causing the disease. Widespread use of the toxoid did not follow immediately; vaccination was not widely adopted until the early 1930s. In the United States, cases fell from 4.4 per 100,000 inhabitants in 1932 to 2.0 per 100,000 in 1937 as vaccination spread. In Nazi Germany over the same period, where authorities favored treatment and isolation over vaccination until roughly 1939-1941, the rate climbed from 6.1 to 9.6 per 100,000.

  In Glasgow, Dr. Nora Wattie, who served as Principal Medical Officer for Maternity and Child Welfare between 1934 and 1964, introduced immunization clinics across the city in 1939 and promoted health education for mothers and children. The result was the virtual eradication of diphtheria in Glasgow. By 2015, reported cases worldwide had fallen to 4,500, down from nearly 100,000 in 1980. Today, the vaccine is administered as part of combination vaccines - DTaP for children, and Tdap or Td boosters recommended every ten years for adults. Pentavalent vaccines, which protect against five diseases simultaneously including diphtheria, tetanus, pertussis, Hepatitis B, and Haemophilus influenzae type b, are used extensively in developing countries by organizations including UNICEF.

• 6. Outbreaks After Neglect

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  The pattern repeated itself throughout the twentieth and twenty-first centuries: wherever vaccination rates fell, diphtheria returned. After the breakup of the Soviet Union in 1991, vaccination rates in the newly independent countries collapsed. In 1991, around 2,000 cases were recorded in the USSR. Between 1991 and 1998, as many as 200,000 cases were reported across the Commonwealth of Independent States, resulting in 5,000 deaths. In 1994 alone, the Russian Federation recorded 39,703 cases.

  In 1925, Nome, Alaska, faced a diphtheria outbreak in an era when antitoxin still had to be transported by sled dog. The race to deliver that antitoxin is now commemorated by the Iditarod Trail Sled Dog Race. During the 1920s, the United States recorded an estimated 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths annually. Between June 1942 and February 1943, 714 cases and 112 deaths occurred at Sham Shui Po Barracks in Hong Kong because the Imperial Japanese Army refused to release supplies of anti-diphtheria serum.

  In 2015, a six-year-old child died of diphtheria in Barcelona, Spain - the first case in Spain since either 1986 or 1998, depending on the source. The child had not been vaccinated because of parental opposition. In 2017, outbreaks occurred among Rohingya refugees in Bangladesh and among children unvaccinated because of the Yemeni Civil War. In November and December 2017, more than 600 cases and 38 deaths were recorded in Indonesia. As recently as May 2026, an outbreak in Australia's Northern Territory reported 133 cases and one death, spreading into aboriginal communities in South Australia, the Kimberley region of Western Australia, and Queensland. The disease currently occurs most often in sub-Saharan Africa, South Asia, and Indonesia, and in the United States only 57 cases were reported across the entire span from 1980 to 2004.

• 7. Notable Deaths

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  Diphtheria moved through all levels of society with indifference to rank or wealth. On the 8th of April 1861, Elisha Graves Otis, the inventor of the safety elevator, died from diphtheria at age 49. In December 1863, Eliza Arabella Garfield, the three-year-old eldest daughter of James A. Garfield, died of the disease just before Christmas.

  In 1878, Princess Alice - Queen Victoria's second daughter - and members of her family contracted diphtheria. Both Princess Alice and her four-year-old daughter Princess Marie died. The Sanitary Journal warned readers of what it called the "kiss of death" - the belief that the disease had spread through the royal family through physical affection.

  On the 7th of December 1892, Anna Hall Roosevelt, mother of Eleanor Roosevelt, died of diphtheria at age 29. Five months later, Eleanor's younger brother Elliott Roosevelt Jr. also died of the disease. On the 7th of January 1904, Ruth Cleveland died in Princeton, New Jersey, at age 12. She was the eldest daughter of former US President Grover Cleveland and First Lady Frances Folsom. Each of these deaths - from the inventor who changed urban architecture, to the children of presidents and queens - illustrates the reach of a disease that is still, today, circulating in unvaccinated populations around the world.