Timeline of diphtheria

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This is a timeline of diphtheria, describing major events such as epidemics and medical developments.

Big picture

Year/period Key developments
Ancient times Earliy detailed descriptions of dyphtheria date from ancient Syrian, Egyptian, and Greek writings.[1]
1600s onward Diphtheria infection grows significantly since the 17th century and becomes one of the major causes of death, fuelled by the Industrial Revolution and increasingly crowded urban centers.[2]
1800s Major scientific breakthroughs consolidate the knowledge on diphtheria, which is given its actual name in this century[2]. Bacterium corynebacterium diphtheriae and the diphtheria toxin are discovered.[3][4] Also, the first effective therapeutic serum against diphtheria is developed.[5]
1923 onward After the first diphtheria toxoid vaccine is developed, its subsequent widespread use would lead to a dramatic decrease of diphtheria rates worldwide.[6][7] A more than 90% decrease in number of cases globally results later, between 1980 and 2000.[8]
Recent years Currently most diphtheria cases occur in Sub-Sharan Africa, India, and Indonesia. Globally 4,530 cases were officially reported in 2015, down from nearly 100,000 in 1980.[9][8]

Visual data

Global diphtheria cases reported by the World Health Organization in the period (1980-2015). Local maxima around mid-1990s correlate with large epidemic in the Post-Soviet states.
Diphtheria cases and deaths per year in the United States. Period (1950-2013).
Diphtheria cases and deaths per year in the United States. Period (1950-2013). Logarithmic scale.


Year/period Type of event Event Present time geographical location
5th century BC Scientific development diphtheria is first described by Greek physician Hippocrates.[10][11] Greece
1600s Scientific development Medical reports of a "deadly" strangulation disease first appear early in the century, and emerges as a greater threat with the growth of urbanizations.[2][11]
1613 Epidemic diphtheria epidemic in Spain causes the year to be named "El año de los Garotillos" ("year of strangulations"), due to the many deaths caused by diphtheria suffocation.[12] Spain
1771 Medical development American physician Samuel Bard publishes An Enquiry into the Nature, Cause and Cure, of the Angina Suffocativa, or, Sore Throat Distemper, one of the earliest accurate descriptions of diphtheria as well as one of the first original contributions to pediatrics made by an American.[13] United States
1826 Scientific development French physician Pierre Bretonneau gives diphtheria its official name diphtérite, derived from the Greek word for "leather" or "hide", which describes the pseudomembrane in the throat of the victims.[2][14][12][1]
1856 Epidemic San Francisco doctor Victor Fourgeaud describes an epidemic of diphtheria in California.[8] United States
1883 Scientific development Swiss pathologist Edwin Klebs first observes the bacterium corynebacterium diphtheriae in diphtheritic membranes.[11][12]
1884 Scientific development German bacteriologist Friedrich Loeffler first grows corynebacterium diphtheriae in pure culture.[3][6][11][12] Germany
1888 Scientific development French physicians Pierre Paul Émile Roux and Alexandre Yersin, working at Pasteur Institute, discover the diphtheria toxin.[4][12] France
1890 Medical development Japanese bacteriologist Kitasato Shibasaburo, and German physiologist Emil von Behring, successfully immunize guinea pigs with a heat-treated diphtheria toxin, thus creating the first effective therapeutic serum against diphtheria. In 1901 Von Bering would be awarded the first Nobel Prize in Physiology or Medicine for this work.[5][15][16] Germany (Berlin)
1891 Medical development The first successful therapeutic serum treatment of a child suffering from diphtheria is performed.[5]
1894 Medical development The production and marketing of the diphtheria therapeutic serum begins in Germany.[5] Germany
1894 Medical development American pharmaceutical H. K. Mulford Company of Philadelphia starts production and testing of diphtheria antitoxin in the United States.[17] United States
1901 Medical development Emil von Behring, for the first time, uses a diphtheria inoculation of bacteria with reduced virulence, hoping with this active immunization to help the body also produce antitoxins.[5] Germany
1905 Medical development Franklin Royer publishes a paper urging timely treatment for diphtheria and adequate doses of antitoxin.[8]
1907 Medical development Experiments start using a toxin–antitoxin (TAT) solution to induce protective immunity against diphtheria, under the assumption that the toxin would stimulate immunity and the antitoxin (antibodies) would counteract the toxicity of the toxin and prevent it from causing disease in the recipient.[1]
1907 Campaign Several cities in Europe and the United States begin immunization programs to administer the toxin–antitoxin (TAT) complex.[1] Europe, United States
1913 Medical development Emil von Behring publishes his diphtheria protective agent, T.A. (Toxin-Antitoxin), which contains a mixture of diphtheria toxin and therapeutic serum antitoxin. Designed to provide long-term protection, the new drug would further be tested at various clinics and proven to be non-harmful and effective.[5] Germany
1921 Report A high of 206,000 cases of diphtheria and 15,520 deaths (case-fatality ratio of 7.5%) are recorded in the United States.[18][19] United States
1923 Scientific development French biologist Gaston Ramon, working at Pasteur Institute, develops diphtheria toxoid that could later be used for a toxoid vaccination. The product is licensed; prepared from inactivated bacterial toxin that has lost its toxicity but retaining its antitoxin producing properties. This would be considered the first diphtheria vaccine.[16][8][15] France
1924 Scientific development Gaston Ramon discovers diphtheria and tetanus toxoid, then referred to as anatoxins.[20] France
1926 Medical development British immunologist Alexander Glenny, working at Wellcome Research Laboratories, develops the adjuvant (the substance that enhances the body's immune response to an antigen) for the toxoid vaccine by increasing the effectiveness of diphtheria toxoid when treating it with aluminum salts.[8][16] United Kingdom (London)
1926 Medical development Fluid form of diphtheria toxoid is licensed in the United States.[21] United States
1943 Epidemic Aproximately one million diphtheria cases and 50,000 deaths occur in Europe. A similar number of cases and deaths are believed to occur every year in developing countries at the time.[1]
1947 Medical development Combination diphtheria and tetanus toxoids for pediatric use is first licensed in the United States.[15] United States
1948 Medical development The pertussis vaccine becomes available in combination with diphtheria and tetanus antigens (DTP).[1]
1949 Medical development American Microbiologist, Stephen Dyonis Elek develops the immuno diffusion technique, also called Elek's test. It is used to test for toxigenicity of corynebacterium diphtheriae.[22] United States
1953 Medical development Tetanus and diphtheria toxoids (adult formulation) are first licensed in the United States, after the concentration of diphtheria toxoid is reduced.[15] United States
1964 Policy World Health Organization recommendations for the production and quality control of diphtheria vaccines are first formulated.[23]
1971 Epidemic Seattle experiences the last major diphtheria outbreak in the United States.[24] United States
1974 Policy Diphtheria toxoid combined with tetanus and pertussis vaccines (DTP) is included in the newly incepted World Health Organization Expanded Programme on Immunization.[23][1]
1974 Epidemic Diphtheria epidemic breaks out in Lisbon. 500 persons are involved, and about 40 deaths are recorded.[3] Portugal
1982 Epidemic 5 deaths are recorded in Germany during a diphtheria outbreak.[3] Germany
1990-1998 Epidemic Massive diphtheria epidemic breaks out in the ex-Soviet Union. Starting in Russia, the outbreak reaches the Newly Independent States in 1991. By 1998, the Red Cross estimates as many as 200,000 cases, with 5,000 deaths in the region.[25][26][24] Post-Soviet states
1993 Organization The European Laboratory Working Group on Diphtheria (ELWGD) is formed as a result of the epidemic situation in Eastern Europe.[27]
1996 Medical development Lederle Laboratories licenses diphtheria and tetanus toxoids, and acellular pertussis vaccine Acel-Imune, for use as the first through fifth doses in the series.[15]
1997 Medical development British pharmaceutical company SmithKline Beecham licenses Infanrix (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed), for the first four doses of the series.[15]
1998 Medical development North American Vaccine Inc licenses Certiva (diphtheria and tetanus toxoids and acellular pertussis vaccine adsorbed), for boosting immunization of infants and children.[15]
1999 Medical development Connaught Laboratories licenses diphtheria and tetanus toxoids and acellular pertussis vaccine Tripedia.[15]
2002 Medical development British pharmaceutical GlaxoSmithKline licenses Pediarix, a vaccine combining diphtheria, tetanus, acellular pertussis, inactivated polio, and hepatitis B antigens.[15]
2002 Medical development Aventis Pasteur licenses diphtheria and tetanus toxoids and acellular pertussis vaccine Daptacel.[15]
2004 Medical development Aventis Pasteur licenses vaccine Decavac, indicated for active immunization against tetanus and diphtheria.[15][28]
2005 Medical development Sanofi Pasteur licenses Menactra, the first meningococcal polysaccharide (Serogroups A, C, Y and W-135) diphtheria toxoid conjugate vaccine. This would be the first immunogenic meningococcal vaccine indicated for children younger than 2 years of age.[15]
2007 Report 4,190 cases of diphtheria are reported globally.[18]
2011 Medical development United States Food and Drug Administration approves Boostrix (developed by GlaxoSmithKline) to prevent tetanus, diphtheria, and pertussis in older people.[15] United States
2016 Epidemic Diphtheria reemerges in Venezuela. A cumulative total of 324 diphtheria cases are reported in the country.[29] Venezuela
2017 Report World Health Organization vaccine advisors report diphtheria as a "newly neglected disease that still resides among the cracks of the most privileged health systems."[30]

See also


  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 "State of the world's vaccines and immunization" (PDF). who.int. Retrieved 30 May 2017. 
  2. 2.0 2.1 2.2 2.3 "The strangler". museumofhealthcare.ca. Retrieved 9 May 2017. 
  3. 3.0 3.1 3.2 3.3 KWANTES, W. "Diphtheria in Europe" (PDF). nih.gov. Retrieved 8 May 2017. 
  4. 4.0 4.1 Ladant, Daniel; Alouf, Joseph E.; Popoff, Michel R. The Comprehensive Sourcebook of Bacterial Protein Toxins. 
  5. 5.0 5.1 5.2 5.3 5.4 5.5 "Emil von Behring: The Founder of Serum Therapy". nobelprize.org. Retrieved 9 May 2017. 
  6. 6.0 6.1 "Diphtheria Facts". emedicinehealth.com. Retrieved 9 May 2017. 
  7. "Clinicians". cdc.gov. Retrieved 10 May 2017. 
  8. 8.0 8.1 8.2 8.3 8.4 8.5 "Diphtheria : Clinical Manifestations , Diagnosis , and Role of Immunization In Prevention" (PDF). iosrjournals.org. Retrieved 10 May 2017. 
  9. "Diphtheria reported cases". who.int. Retrieved 12 May 2017. 
  10. "Diphtheria". medscape.com. Retrieved 8 May 2017. 
  11. 11.0 11.1 11.2 11.3 "Corynebacterium diphtheriae" (PDF). cdc.gov. Retrieved 10 May 2017. 
  12. 12.0 12.1 12.2 12.3 12.4 Current Developments in Biotechnology and Bioengineering: Human and Animal Health Applications (Vanete Thomaz Soccol, Ashok Pandey, Rodrigo R. Resende ed.). Retrieved 10 May 2017. 
  13. "Archives & Special Collections Acquires Samuel Bard Work". columbia.edu. Retrieved 11 May 2017. 
  14. "Pierre Bretonneau". historyofvaccines.org. Retrieved 9 May 2017. 
  15. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 15.12 "Vaccine Timeline". immunize.org. Retrieved 8 May 2017. 
  16. 16.0 16.1 16.2 "Diphtheria, Tetanus (Lockjaw), and Pertussis (Whooping Cough) Cases and Deaths, and DTaP Vaccination Rates". procon.org. Retrieved 23 May 2017. 
  17. A Brief History of Pharmacy: Humanity's Search for Wellness (Virgil Schijns, Derek O'Hagan ed.). Retrieved 11 May 2017. 
  18. 18.0 18.1 "Diphtheria: The Plague Among Children". historyofvaccines.org. Retrieved 8 May 2017. 
  19. "Diphtheria. Symptoms and Causative Agent". historyofvaccines.org. Retrieved 10 May 2017. 
  20. Medical Sciences - Volume I (B.P. Mansourian, S.M. Mahfouz, A. Wojtezak ed.). Retrieved 9 May 2017. 
  21. Artenstein, Andrew W. Vaccines: A Biography. Retrieved 26 May 2017. 
  22. "The Plate Virulence Test for Diphtheria". bmj.com. Retrieved 11 May 2017. 
  23. 23.0 23.1 "Diphtheria". who.int. Retrieved 10 May 2017. 
  24. 24.0 24.1 "History in Focus: Diphtheria Epidemic". hampton.lib.nh.us. Retrieved 10 May 2017. 
  25. "Diphtheria". the-medical-dictionary.com. Retrieved 11 May 2017. 
  26. "Diphtheria Outbreak -- Russian Federation, 1990-1993". cdc.gov. Retrieved 10 May 2017. 
  27. Wheeler, Ben S. Trends in Diphtheria Research. Retrieved 12 May 2017. 
  28. "HIGHLIGHTS OF PRESCRIBING INFORMATION" (PDF). vaccineshoppe.com. Retrieved 8 May 2017. 
  29. "Venezuela releases 1st Epi bulletin in a long time: Malaria and diphtheria summary". outbreaknewstoday.com. Retrieved 12 May 2017. 
  30. "WHO vaccine advisors weigh in on polio, cholera, Ebola, diphtheria". umn.edu. Retrieved 12 May 2017.