The first set of writings describing a diphtheria-like illness in Egypt dates back to the second millennium BC. Famous Greek writers, including Hippocrates, Aretaeus, and Aëtius, presented more details about the disease in their writings during the 5th century BC, 2nd century AD, and 6th century AD, respectively.
In 1613, Spain experienced a diphtheria epidemic so devastating that the year became known as ‘El Año de los Garotillos’ — the “Year of Strangulations.” Outbreaks continued to occur in many parts of Europe every 12 years during the 18th century, especially in southwestern Europe .
In 1683, the ‘Father of Microbiology,’ Antonie van Leeuwenhoek discovered microorganisms. He termed them ‘animalcules’ or ‘little animals’ at the time. He also fashioned the first microscope based on lens-making skill. After this pioneering work, the field of microbiology progressed considerably. Many other scientists began identifying and classifying previously unknown bacteria, viruses, and parasites, leading to a greater understanding of diseases.
In 1826, Pierre Bretonneau, a French physician, identified the C.diphtheriae bacterium and gave it an official name, diphtérite – a Greek word for leather. The term describes the leathery coating that appears in the throat of a person infected by C.diphtheriae . In 1883, the bacterium was observed for the first time in diphtheritic membranes by a German-Swiss microbiologist named Edwin Klebs. It was then cultivated for the first time by Friedrich Löffler, a German bacteriologist, a year later .
In 1888, two doctors in Paris, Roux and Alexandre Yersin isolated the toxin produced by the bacterium. They demonstrated that this toxin was responsible for the bacterial infection.
Around the same time, there was a breakthrough in the fight against diphtheria. Emil von Behring, a German doctor, collaborated with a Japanese bacteriologist Kitasato Shibasaburo and discovered ‘antitoxins.’ They induced passive immunity from a disease in healthy animals by injecting them with the blood serum of an infected animal. While their first focus was tetanus, they eventually achieved stellar results against diphtheria as well. For this landmark achievement, Behring received the first-ever Nobel Prize for Physiology or Medicine in 1901 [10,28]
In 1907, Theobald Smith, an American epidemiologist, bacteriologist, pathologist, and professor, was the first to observe the immune response against diphtheria in guinea pigs that were vaccinated with diphtheria toxin and antitoxin. This combination was later used to immunize children living in big cities in Europe and the US.
In 1926, the first alum-precipitated diphtheria toxoid was licensed in the US. This was developed by Alexander Thomas Glenny, a British immunologist. A year later, Ramon and Zoeller combined the diphtheria toxoid with the tetanus toxoid. In 1943, thanks to the groundbreaking work on pertussis (whooping cough) by Grace Eldering and Pearl Kendrick, the pertussis vaccine was added to the diphtheria-tetanus mixture to create a combined DTP (Diphtheria-Tetanus-Pertussis) vaccine .
Cases gradually decreased after the World Health Organization (WHO) began the universal childhood immunization program in 1974 . As the vaccination program gained momentum, the demand for DTP shots skyrocketed. In 2006, around 500 million DTP vaccine doses were produced globally, with pharmaceutical giants like Sanofi Pasteur and GSK accounting for almost 20% of the overall production .
In 2018, data from countries that actively participated in the immunization program showed that almost 90% of children received at least one dose of the diphtheria vaccine, and around 86% of them received three doses and at least one dose of the Measles-Containing Vaccine (MCV). Despite all the immunization efforts, only 129 of 194 member countries of WHO reached the target of vaccinating over 90% of the population .