{"id":5533,"date":"2025-10-09T20:41:09","date_gmt":"2025-10-10T02:41:09","guid":{"rendered":"https:\/\/allphasepharma.com\/dir\/?p=5533"},"modified":"2025-10-10T18:03:14","modified_gmt":"2025-10-11T00:03:14","slug":"about-diphtheria","status":"publish","type":"post","link":"https:\/\/allphasepharma.com\/dir\/2025\/10\/09\/5533\/about-diphtheria\/","title":{"rendered":"About DIPHTHERIA"},"content":{"rendered":"

\"\"<\/a>The early work on the organism and the toxoid vaccine reads like the \u2018Who Is Who\u2019 of microbiology: Klebs, Loeffler, Koch, Roux, Yersin, Behring, Kitasato, Schick, and T. Smith were all involved in bringing this deadly disease under control.<\/p>\n

In those days bacteria and diseases were referred to by the names of researchers, discoverers, and clinicians.\u00a0 Corynebacterium diphtheriae was referred to as the Klebs-Loeffler bacillus.\u00a0 TB was known as Morbus Koch and leprosy as Morbus Hansen.\u00a0 This tradition has been fading into oblivion esp. as the etiology has become clearer, but we still call Crohn\u2019s disease, Sjogren\u2019s syndrome and Behcet\u2019s by their eponyms.\u00a0 Other names have become obsolete; few would nowadays associate Morbus Boeck with sarcoidosis or Morbus Bechterev with ankylosing spondylitis.<\/p>\n

After Klebs discovered the diphtheria bacillus, Loeffler developed a specific growth medium now called Loeffler medium and recognized that it was this particular bacillus that causes diphtheria.\u00a0 He also made some very astute observations: having found the organism only in the diphtheric membranes but nowhere else in the bodies of infected children, he suggested the systemic disease manifestations were being caused by a bacterial product, the toxin later identified by Behring and his coworkers.<\/p>\n

As vividly described by Paul de Kruif, Behring had to kill a lot of guinea pigs in his lab to prove that protection against the diphtheria toxin can be generated and a toxoid preparation can induce long-lasting immunity in humans.[1]<\/a> \u00a0De Kruif’s book chapter on Roux and Behring has the subtitle \u201cMassacre the Guinea Pigs\u201d describing the travails of researchers introducing a new treatment, in this case an inactivated vaccine for a deadly disease.<\/p>\n

In those days there was no FDA, CDC, GCP, or ICH, no governmental oversight over human testing.\u00a0 None of these gentlemen had training in research ethics. Diphtheria antitoxin was first given to a child in 1891, equivalent to a 2-3 year development timeline!<\/p>\n

The vaccine made a huge impact on morbidity and mortality worldwide.<\/p>\n

Diphtheria research is not finished.\u00a0 We know a lot about the toxin\u2019s structure and MoA.\u00a0 It is an A\/B type peptide consisting of 2 chains: B for cellular binding and A for disruption of intracellular protein synthesis.\u00a0 Peptide A binds to EF2, blocks its action,\u00a0<\/p>\n

\"\"<\/a><\/p>\n

and leads to cell death.\u00a0 This is an abbreviated explanation for a very unusual interaction between DT and a post-translationally modified histidine on EF2 called diphthamide.\u00a0 It is the A-toxin of C. diphtheriae that modifies diphthamide on EF2 by ADP-ribosylation.\u00a0 This inactivates EF2, blocks protein synthesis and leads to cell death.[2]<\/a><\/p>\n

Clinicians wondered early on why the diphtheria toxin has such a profound effect on the heart.[3]<\/a>\u00a0 Effects on the vagus nerve, conduction system, and myocardial cells in general were considered.\u00a0 The most common findings of conduction abnormalities were documented in many cases (as in the ECG below) and histopathology pointed towards a toxic myocarditis.<\/p>\n

\"\"<\/a>
ECG with conduction abnormalities<\/figcaption><\/figure>\n

We did not find studies that would explain the particular sensitivity of the heart for EF2 blockade by diphtheria toxin.\u00a0 If any of you have an explanation, please share it with our readers.<\/p>\n

Last, a bit of trivia:<\/p>\n

Friedrich Loeffler, was a German microbiologist and a \u201cmicrobe hunter whose mustache was so militaristic he had to keep pulling it down to see through the microscope\u201d.[1]<\/a> \u00a0Indeed, he had an impressive beard!<\/p>\n

\"\"<\/a>
Friedrich Loeffler<\/figcaption><\/figure>\n

In contrast, Wilhelm L\u00f6ffler (note the different spelling!) was a Swiss clinician known for studies on eosinophilic myocarditis and tropical eosinophilic pneumonia.[4]<\/a>\u00a0 Pictures show him with a moustache but never a full beard, making it easy not to confound him with his namesake.\u00a0 We do not know whether his moustache got in the way when studying eosinophils under the microscope.<\/p>\n

\"\"<\/a>
Wilhelm L\u00f6ffler<\/figcaption><\/figure>\n

ABBREVIATIONS
<\/strong>DT\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 diphtheria toxin
EF2\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0\u00a0 elongation factor 2<\/p>\n

REFERENCES
<\/strong>[1] \u00a0<\/a>De Kruif, P.\u00a0 Microbe Hunters. 1926
[2]<\/a> Su, X.\u00a0 The biosynthesis and biological function of diphthamide. Crit Rev Biochem Mol Biol, 2013; 48: 515, 2013
[3]<\/a> Marvin H.\u00a0 The effect of diphtheria on the cardiovascular system.\u00a0 Am J Dis Children. 29: 433, 1925
[4]<\/a> L\u00f6ffler, W. \u00a0Endocarditis parietalis fibroplastica mit Bluteosinophilie. \u00a0Ein eigenartiges Krankheitsbild.\u00a0 Schweizerische Medizinische Wochenschrift 66: 817, 1936<\/p>\n\n","protected":false},"excerpt":{"rendered":"

The early work on the organism and the toxoid vaccine reads like the \u2018Who Is Who\u2019 of microbiology: Klebs, Loeffler, Koch, Roux, Yersin, Behring, Kitasato, Schick, and T. Smith were all involved in bringing this deadly disease under control. In those days bacteria and diseases were referred to by the Continue reading About DIPHTHERIA<\/span>→<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":5537,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"jetpack_post_was_ever_published":false,"_jetpack_newsletter_access":"","_jetpack_dont_email_post_to_subs":false,"_jetpack_newsletter_tier_id":0,"_jetpack_memberships_contains_paywalled_content":false,"_jetpack_memberships_contains_paid_content":false,"footnotes":"","jetpack_publicize_message":"","jetpack_publicize_feature_enabled":true,"jetpack_social_post_already_shared":true,"jetpack_social_options":{"image_generator_settings":{"template":"highway","default_image_id":0,"font":"","enabled":false},"version":2}},"categories":[140,227,3,18],"tags":[1271,403,2479,2483,2493,2494,2484,2486,2489,2485,2488,2487,2491,1583,2480,2474,2476,2475,2490,2492,2477,2481,2482,2478],"class_list":["post-5533","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-interesting_facts","category-recent_literature","category-the_news","category-the_viewpoint","tag-allphase-pharma-consulting","tag-antibiotic-blog","tag-behring","tag-c-diphtheriae","tag-cardiac-conduction","tag-diphthamide","tag-diphtheria","tag-diphtheria-cardiac-toxicity","tag-diphtheria-toxin","tag-diphtheria-vaccine","tag-ef2","tag-elongation-factor-2","tag-eosinophilia","tag-harald-reinhart","tag-kitasato","tag-klebs","tag-koch","tag-loeffler","tag-loffler","tag-myocarditis","tag-roux","tag-schick","tag-smith","tag-yersin"],"jetpack_publicize_connections":[],"jetpack_featured_media_url":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/10\/Diphtheria-SLIDER.jpg?fit=640%2C180&ssl=1","jetpack_shortlink":"https:\/\/wp.me\/p4KWFr-1rf","jetpack_sharing_enabled":true,"jetpack-related-posts":[{"id":4782,"url":"https:\/\/allphasepharma.com\/dir\/2025\/07\/22\/4782\/much-ado-about-nothing-covid-19-vaccination-for-healthy-children\/","url_meta":{"origin":5533,"position":0},"title":"MUCH ADO ABOUT NOTHING: Covid-19 Vaccination for Healthy Children","author":"Harald","date":"July 22, 2025","format":false,"excerpt":"Oh, what a disaster: all the ACIP members were replaced for no good reason, the best and the brightest.\u00a0 Now children will die as incompetence rules supreme.\u00a0 The CDC\u2019s guidance on Covid vaccination of healthy kids is being ignored, being made light of and challenged.\u00a0 We are looking at governmental\u2026","rel":"","context":"In "Recent Literature"","block_context":{"text":"Recent Literature","link":"https:\/\/allphasepharma.com\/dir\/category\/recent_literature\/"},"img":{"alt_text":"","src":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/image-7.png?resize=350%2C200&ssl=1","width":350,"height":200,"srcset":"https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/image-7.png?resize=350%2C200&ssl=1 1x, https:\/\/i0.wp.com\/allphasepharma.com\/dir\/wp-content\/uploads\/2025\/07\/image-7.png?resize=525%2C300&ssl=1 1.5x"},"classes":[]},{"id":2596,"url":"https:\/\/allphasepharma.com\/dir\/2016\/07\/07\/2596\/is-laiv-dead-or-just-on-laiv-support\/","url_meta":{"origin":5533,"position":1},"title":"Is LAIV Dead or Just on LAIV-Support?","author":"Harald","date":"July 7, 2016","format":false,"excerpt":"Very recently we came across several studies in which small differences in design\u00a0had a major\u00a0impact on outcomes. 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