Discovery and science Records of Diphtheria begin as early as the 5th century BCE in the writings of
Hippocrates. Epidemics were first described by
Aëtius of Amida in the 6th century. In 1883,
Edwin Klebs identified the bacterium causing diphtheria, and named it
Klebs–Loeffler bacterium. The club shape of this bacterium helped Edwin to differentiate it from other bacteria. Over time, it has been called
Microsporon diphtheriticum,
Bacillus diphtheriae, and
Mycobacterium diphtheriae. Current nomenclature is
Corynebacterium diphtheriae. In 1884, German
bacteriologist Friedrich Loeffler became the first person known to cultivate
C. diphtheriae. Löffler found that the bacteria were always present in the mucous membranes of the larynx and trachea of patients with diphtheria. In the process of finding the bacteria, he isolated the organism, cultured it, and reproduced the disease in susceptible animals (guinea pigs and rabbits), and then recovered the same bacillus from the diseased animal, thus fulfilling
Koch's postulates. He believed there was a toxin that was made by the bacteria that caused the disease symptoms, and subsequently showed that some animals are immune to diphtheria. In 1885,
Joseph P. O'Dwyer introduced the O'Dwyer tube for laryngeal intubation in patients with an obstructed larynx. It soon replaced
tracheostomy as the emergency diphtheric intubation method. In 1888,
Emile Roux and
Alexandre Yersin showed that a substance (
exotoxin) produced by
C. diphtheriae caused symptoms of diphtheria in animals. In 1890,
Shibasaburō Kitasato and
Emil von Behring immunized guinea pigs with heat-treated diphtheria toxin. They also immunized goats and horses in the same way, and showed that an "
antitoxin" made from
serum of immunized animals could cure the disease in non-immunized animals. Behring used this antitoxin (now known to consist of
antibodies that neutralize the toxin produced by
C. diphtheriae) for human trials in 1891, but they were unsuccessful. Successful treatment of human patients with horse-derived antitoxin began in 1894, after production and quantification of antitoxin had been optimized. In 1901, Von Behring won the first
Nobel Prize in medicine for his work on diphtheria. In 1895,
H. K. Mulford Company of
Philadelphia started production and testing of diphtheria antitoxin in the United States.
Park and
Biggs described the method for producing serum from horses for use in diphtheria treatment. In 1897,
Paul Ehrlich developed a standardized unit of measure for diphtheria antitoxin. This was the first ever standardization of a biological product, and played an important role in future developmental work on sera and vaccines. In 1901, 10 of 11 inoculated
St. Louis children died from contaminated diphtheria antitoxin. The horse from which the antitoxin was derived died of
tetanus. This incident, coupled with a tetanus outbreak in
Camden, New Jersey, played an important part in initiating federal regulation of biologic products. In 1905, Franklin Royer, from Philadelphia's Municipal Hospital, published a paper urging timely treatment for diphtheria and adequate doses of antitoxin. In 1906,
Clemens Pirquet and
Béla Schick described
serum sickness in children receiving large quantities of horse-derived antitoxin. Schick and Pirquet reported that children treated for diphtheria with very large doses of horse-derived antitoxin frequently developed delayed symptoms, including swelling, fever, rash, and joint pain. It is now understood that these reactions occur because the human immune system recognizes the foreign antibodies in horse serum as antigens, triggering a cascade of immune responses. In the clinical experience of Pirquet and Schick, these reactions were self-limited rather than life-threatening, and children who survived diphtheria were not permanently harmed by the antitoxin treatment. Between 1910 and 1911, Béla Schick developed the
Schick test to detect pre-existing immunity to diphtheria in an exposed person. Only those who had not been exposed to diphtheria were vaccinated. A massive, five-year campaign was coordinated by Dr. Schick. As a part of the campaign, 85 million pieces of literature were distributed by the
Metropolitan Life Insurance Company, with an appeal to parents to "Save your child from diphtheria." In 1914,
William H. Park investigated the use of carefully calibrated mixtures of diphtheria toxin and antitoxin to induce active immunity in experimental animals and later humans. Building on earlier antitoxin work, he systematically adjusted the relative concentrations to identify formulations that produced durable protective immunity while minimizing adverse reactions to the toxin–antitoxin complex. This mixture, TAT (for toxin-antitoxin), became the first vaccine against diphtheria. In 1919, in
Dallas, Texas, 10 children were killed and 60 others made seriously ill by toxic antitoxin, which had passed the tests of the
New York State Health Department. The manufacturer of the antitoxin, the
Mulford Company of Philadelphia, paid damages in every case. In 1926, Alexander Thomas Glenny increased the effectiveness of diphtheria
toxoid (a modified version of the toxin used for vaccination) by treating it with aluminum salts. Vaccination with toxoid was not widely used until the early 1930s. In 1939, Dr.
Nora Wattie, who was the
Principal Medical Officer (Maternity and Child Welfare) of Glasgow between 1934– 1964, introduced immunisation clinics across
Glasgow, and promoted mother and child health education, resulting in virtual eradication of the infection in the city. Widespread vaccination pushed cases in the United States down from 4.4 per 100,000 inhabitants in 1932 to 2.0 in 1937. In
Nazi Germany, where authorities preferred treatment and isolation over vaccination (until about 1939–1941), cases rose over the same period from 6.1 to 9.6 per 100,000 inhabitants.
List of epidemics • In 1613,
Spain experienced an epidemic of diphtheria, referred to as (The Year of Strangulations). • In 1705, the
Mariana Islands experienced an epidemic of diphtheria and
typhus simultaneously, reducing the population to about 5,000 people. • In 1735, a diphtheria epidemic swept through
New England. Then known as "throat distemper," in one New Hampshire town, 32% of children under 10 died. Of the persons known to have acquired diphtheria, nearly 40% died.
Noah Webster wrote: "It was literally the plague among children. Many families lost three of four children—many lost all." • In 1856,
Victor Fourgeaud described an epidemic of diphtheria in
California. • In 1925, in
Nome, Alaska; the
"Great Race of Mercy" to deliver diphtheria antitoxin is now celebrated by the
Iditarod Trail Sled Dog Race. During the 1920s, an annual estimate of 100,000 to 200,000 diphtheria cases and 13,000 to 15,000 deaths occurred in the United States. • In 1943, diphtheria outbreaks accompanied war and disruption in
Europe. The 1 million cases in Europe resulted in 50,000 deaths. • During 1948 in
Kyoto, 68 of 606 children died after diphtheria immunization due to improper manufacture of aluminum phosphate toxoid. • In 1974, the
World Health Organization included
DPT vaccine in their
Expanded Programme on Immunization for
developing countries. • In 1975, an outbreak of cutaneous diphtheria in
Seattle, Washington, was reported. • After the breakup of the former
Soviet Union in 1991, vaccination rates in its constituent countries fell so low that an explosion of diphtheria cases occurred. In 1991, 2,000 cases of diphtheria occurred in the USSR. Between 1991 and 1998, as many as 200,000 cases were reported in the
Commonwealth of Independent States, resulting in 5,000 deaths. • In early May 2010, a case of diphtheria was diagnosed in
Port-au-Prince,
Haiti, after the devastating
2010 Haiti earthquake. The 15-year-old male patient died while workers searched for antitoxin. • In 2013, three children died of diphtheria in
Hyderabad, India. • In early June 2015, a case of diphtheria was diagnosed at
Vall d'Hebron University Hospital in
Barcelona,
Spain. The six-year-old child who died of the illness had not been previously vaccinated due to parental
opposition to vaccination. It was the first case of diphtheria in the country since 1986, as reported by the Spanish daily newspaper
El Mundo, or from 1998, as reported by the WHO. • In March 2016, a three-year-old girl died of diphtheria in the University Hospital of
Antwerp,
Belgium. • In June 2016, a three-year-old, five-year-old, and seven-year-old girl died of diphtheria in
Kedah,
Malacca, and
Sabah,
Malaysia. • In January 2017, more than 300 cases were recorded in
Venezuela. • In 2017, outbreaks occurred in a
Rohingya refugee camp in Bangladesh, and amongst children unvaccinated due to the
Yemeni Civil War. • In November and December 2017, an outbreak of diphtheria occurred in
Indonesia, with more than 600 cases found and 38 fatalities. • In November 2019, two cases of diphtheria occurred in the
Lothian area of
Scotland. Additionally, in November 2019, an unvaccinated eight-year-old boy died of diphtheria in
Athens,
Greece. • In July 2022, two cases of diphtheria occurred in northern
New South Wales,
Australia. • In October 2022, there was an outbreak of diphtheria at the former
Manston airfield, a former
Ministry of Defence (MoD) site in
Kent,
England, which had been converted to an
asylum seeker processing centre. The capacity of the processing centre was 1,000 people, although about 3,000 were living at the site, with some accommodated in tents. The
Home Office, the government department responsible for asylum seekers, refused to confirm the number of cases. • In December 2023, there was an outbreak at a school in
Luton, in the United Kingdom.
UK Health Security Agency (UKHSA) issued a statement saying specialists have been providing public health support following confirmation of the diphtheria case at a primary school in Luton. The agency said it is working closely with local and national partners "to ensure all necessary public health measures are implemented" following the discovery of the new case. The statement added: "We have conducted a risk assessment and close contacts of the case have been identified, and where appropriate, vaccination and advice will be given to prevent the spread of the infection."
Notable deaths On April 8, 1861,
Elisha Graves Otis died from diphtheria at age 49. In December 1863, Eliza Arabella Garfield, the eldest daughter of
James A. Garfield, died from diphtheria at the age of three, right before Christmas. In 1878,
Princess Alice (
Queen Victoria's second daughter) and her family became infected with diphtheria; Princess Alice and her four-year-old daughter,
Princess Marie, both died. Their deaths caused the Sanitary Journal to warn readers of the “kiss of death” that may have spread the disease through the royal family. On December 7, 1892,
Eleanor Roosevelt's mother,
Anna Hall Roosevelt, died of diphtheria at age 29. Five months later, Elliott Roosevelt Jr., Eleanor's younger brother, died of the disease. On January 7, 1904,
Ruth Cleveland died of diphtheria at age 12 in
Princeton, New Jersey. She was the eldest daughter of former
President Grover Cleveland and the former
First Lady,
Frances Folsom. ==References==