History of Diphtheria

In 1613, Spain experienced an epidemic of diphtheria. The year is known as El Año de los Garrotillos (The Year of Strangulations) in the history of Spain.

In 1735, a diphtheria epidemic swept through New England.

Before 1826, diphtheria was known by different names across the world. In England, it was known as Boulogne sore throat, as it spread from France. In 1826, Pierre Bretonneau gave the disease the name diphthérite (from Greek diphthera “leather”) describing the appearance of pseudomembrane in the throat.

In 1856, Victor Fourgeaud described an epidemic of diphtheria in California.

In 1878, Queen Victoria’s daughter Princess Alice and her family became infected with diphtheria, causing two deaths, Princess Marie of Hesse and by Rhine and Princess Alice herself.

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 the period of time, it was called Microsporon diphtheriticum, Bacillus diphtheriae, and Mycobacterium diphtheriae. Current nomenclature is Corynebacterium diphtheriae. Friedrich Loeffler was the first person to cultivate C. diphtheriae in 1884. He used Koch’s postulates to prove association between C. diphtheriae and diphtheria. He also showed that the bacillus produces an exotoxin. Joseph P. O’Dwyer introduced the O’Dwyer tube for laryngeal intubation in patients with an obstructed larynx in 1885. It soon replaced tracheostomy as the emergency diphtheric intubation method.

In 1888, Emile Roux and Alexandre Yersin showed that a substance produced by C. diphtheriae caused symptoms of   diphtheria in animals. In 1890, Shibasaburo 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.

 Von Behring won the first Nobel Prize in medicine in 1901 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.

On 7 January 1904, Ruth Cleveland died of diphtheria at the age of 12 years in Princeton, New Jersey. Ruth was the eldest daughter of former President Grover Cleveland and the former first lady Frances Folsom.

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.

Between 1910 and 1911, Béla Schick developed the Schick test to detect pre-existing immunity to diphtheria in an exposed person.

Only those who were not exposed to diphtheria were preferably 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.” A vaccine was developed in the next decade, and deaths began declining significantly in 1924.

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. Mulford Company of Philadelphia (manufacturers) paid damages in every case.

In the 1920s, an estimated 100,000 to 200,000 cases of diphtheria occurred per year in the

United States, causing 13,000 to 15,000 deaths per year.  Children represented a largemajority of these cases and fatalities. One of the most infamous outbreaks of diphtheria was in Nome, Alaska; the “Great Race of Mercy” to deliver diphtheria antitoxin is now celebrated by the Iditarod Trail Sled Dog Race.

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 untli the early 1930s.

In 1943, diphtheria outbreaks accompanied war and disruption in Europe. The 1 million cases in Europe resulted in 50,000 deaths. In 1949, 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.

In 1994, the Russian Federation had 39,703 diphtheria cases. By contrast, in 1990, only 1,211 cases were reported.

Between 1990 and 1998, diphtheria caused 5000 deaths in the countries of the former Soviet Union

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 aVt all d’Hebron University Hospita lin Barcelona, Spain. The 6-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” El Mundo” or from 1998, as reported by WHO.

In March 2016, a 3-year-old girl died of diphtheria in the University Hospital of Antwerp, Belgium.

In June 2016, a 3-year-old, 5-year-old, and 7-year-old girl died of diphtheria in Kedah and Malacca, Sabah Malaysia.

In January 2017, more than 300 cases were recorded in Venezuela.

In November and December 2017, an outbreak of diphtheria occurred in Indonesia with more than 600 cases found and 38 fatalities.

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