Decorated initial A

lengthy period of enduring medical difficulty from diagnostic imprecision and resulting confusion preceded the eventual success of the nineteenth-century's new science of Medical Bacteriology, in discriminating and resolving the cruel loss of infant and other lives from the noisy, strident "choking" illnesses loosely termed croup; also in Boston and the American colonies "vulgarly called the throat-distemper", Dickinson (1740); and in London c.1750 "the malignant, ulcerous sore-throat", Huxham (1759). The situation was aptly outlined by German bacteriologist Carl Fraenkel, associate of Koch and the 1880s Berlin group, in the relevant opening remarks to his incisive treatment of "Diphtheria...an affection of infectious origin":

We know quite a number of pathological processes occurring with the formation of croupous or diphtheritic changes of the mucous membranes, and by post-mortem appearances not distinguishable from the processes accompanying diphtheria proper. The former may, however, arise from various causes, while the latter, as a whole and in every part of its course, exhibits so many peculiarities as an entity, that intelligent investigators have always considered it as a disease by itself and attributed its origin to one and the same cause. As its infectious nature is manifested so decidedly and is transmitted most fearfully from [person to person] by direct contagion, it can be readily understood that the specific micro-organism has long been looked for. [Fraenkel, 1887: 311]

The term croup apparently stems from the Proto-Romance and Old French which according to the OED, aroundearly sixteenth century gave the verb croup = to give a hoarse cry, to croak, and then at by 1750 was used to name the characteristic strident hoarseness of the eponymous ailment so distressing in babies and infants. Later terms included the medico-Latin Suffocatio stridula of Davidson (1794) and the Cynanche trachealis of Cheyne (1801). The later term Diphtheria was coined by the French physician Bretonneau (1826), from the Greek diphthera, diphtheris = skin or hide, in an obvious reference to the false membrane which forms in the throat and which may fatally impede respiration.

During the period c.1790-c.1810 important contributions to the complex of ailments subsumed under the loose term croup, emanated from Philadelphia (Davidson, 1794), Edinburgh, London (Cheyne, 1801, passim), and Paris (Schwilgue, 1802; Valentin, 1812). However, a definite pre-eminence of French studies may be seen from c. 1807, prompted by the loss to the disease that year of a nephew of the Emperor Napoleon. By 1808 a group at the École de Médecine in Paris were publishing on La Maladie Strangulatoire, all under the Imperial imprint. The work of Louis Valentin (1812), also published at Paris, appears to have been the first to carefully distinguish croup from pulmonary catarrh, and epidemics from other contagious aspects. Charles Joseph Schwilgue. who had founded the Biblioteque medicale in 1803, was a Member of the Académie de Médecine, and in 1816 became Professor of Medical Law at Paris. In 1812 he proposed advances such as the differential diagnosis of croup and asthma; the use of syrup of ipecacuanha as expectorant and calmant, and a general approach based on prevention. The subsequent work of French physician P. Bretonneau (1826) introduced the modern terms diphtherite, diphtheritis, diphtherie, for croup and a cluster of associated conditions.

Inhalation of iodine and various "vapours"

Inhalation of iodine and various "vapours" was recommended for croup, catarrh, consumption, asthma, and related conditions (Murray, 1829), whilst the popular "Family Catalogue of Drugs" by Butler (1832) included recipes for croup in children under five years of age. Quite different in approach was the introduction by other medical men of surgical interventions such as bronchotomy/tracheotomy, (Coqueret 1834, Porter 1837 and numerous others). In England, Ley (1836) published on Laryngismus stridulus or croup. French physician Antoine Fauvel (1840), whilst still essentially pre-bacteriological, investigated in children the inflammatory tissues of croup bronquique, catarrh suffocant, discovering in the pus abscesses the notable granules de Fauvel. His conclusion, however, was that "les lesions du lobule" were of a nature mecanique, thus missing a potentially classic bacteriological discovery. The latter would await a further four decades and more, before being made by a master of the new histological staining techniques: see Muir & Ritchie (1897: 396, citing Friedrich Augustus Loffler 1884).

Hydropathy (“the water cure”)

The Wasserkur or water cure — that is, hydropathy — was employed against croup by Lauda (1842), together with the recommended use of Quecksilber = liquid mercury.

Topical medications

Topical medications were also the subject of the work of Green (1849), leading to the success of his New York medical-pediatric practice, though his intubation technique was apparently controversial according to Garrison & Morton (1981). Wide interest in croupous conditions occupied medical experts throughout Europe at this time; see Begbie (1856, 1861); Peter (1858) on the occasion of the epidemic at the Paris l'Hopital des Enfants in 1858; the large collection of Memoirs of key workers translated by Semple,1859; the outlines by Slade (1861) at Philadelphia and Jenner (1861) at London; and the many M.D. dissertations and other papers c. 1850-c.1870s in French, English, German, Italian. Special note may be made of the study by Nivet (1865) of the various epidemics, including "angines pseudo-membraneuses et croups", which flourished from 1849-1864 in the Paris arrondisement of Clermont-Ferrand.

The Epidemiology of Diphtheria

The epidemiology of Diphtheritis was studied by Alban (1870). Monti (1875) focussed on the early years of childhood or kindesalter, and the major croupous disease there essayed also formed a special part of the London "Medico-Chirurgical Transactions" of (1879), when the Reports of the Scientific Committees gave due emphasis to the virtually synonymous relations between "Membranous Croup and Diphtheria". Almost on the cusp of the definitive bacteriological account of the contagious and specific nature of diphtheria, Krieger (1880) provided a differential diagnosis/etiology for catarrh, croup and diphtheria, and various authors offered treatments ranging from homeopathic, tinctures and triturations and even mild gargles at the opposite extreme to radical and still dangerous surgery. The important pre-requisite of recognizing the infectious-contagious nature of diphtheria was by now more widely argued, as by paediatrician Abraham Jacobi at the Jacobi Hospital, New York (Jacobi, 1880). Thereafter the relatively new and by then rigorous and confident science of Bacteriology would dominate the scene of Medical Infectious Diphtheria.

Post-1883 and Loffler's Bacillus as the Agent of Diphtheria

Photomicrograph of Gram-positive Corynebacterium diphtheriae bacteria. This photomicrograph depicted a number of Gram-positive Corynebacterium diphtheriae bacteria, which had been stained using the methylene blue technique. Courtesy Wikipedia. Click on image to enlarge it.

Edwin Klebs in 1883 first described the characteristic micro-organism from infected throat-membranes of the developed infection. It was left to Loeffler in 1884 to repeat the observation, with full cultivation of the bacterium and further studies to confirm it as the causative agent of the disease. Presumably from such concerns, the so-called "Klebs-Loeffler bacillus" was preferentially called "Loeffler's bacillus" by both Fraenkel (1887, XVII, 311-17) in Germany, and by Muir & Ritchie (1897, Chap. XVI) in Britain. The eponymous Bacillus diphtheria, later re-named Corynebacterium diphtheria, presents as slender, club-headed rods, which stain well with Loeffler's methylene blue or with Gram's stain. Samples collected from diphtheritic throat membranes may also show some of the organisms enclosed within blood leucocytes. After deaths of infected persons, Loeffler also demonstrated the organism's presence in lung patches, whilst others reported similar results for liver, spleen and other organs. Further organisms were also early detected associated with the specific organism of diphtheria, e.g. streptococci, staphylococci, pneumococcus and even the Bacillus coli of Escherich [now known as E. coli], (Muir & Ritchie: 400).

The contemporary recommended procedure for hand-washing hygiene is of interest, with further application to domestic households both then and now. As noted in the "General Laboratory Rules" of Muir & Ritchie (1897: 89-90), "No label is to be licked with the tongue. Before leaving the laboratory the bacteriologist ought to wash the hands and forearms with 1-1000 mercuric chloride [i.e. 0.1% w/v in water] and then with yellow soap." The yellow soap, of wide household application, was "Wright's Coal-Tar Soap", invented in 1860 by the English wholesale druggist and chemist William Valentine Wright (1826-77), and originally sold as "Sapo Carbonis Detergens", still the enduring Registered Trade Mark. The coal-tar extract - which also gave the aniline dyes of William Perkin; the precursors of acetylsalicylic acid or "Aspirin", and many other Victorian Period commercial and industrial applications — contained phenol and related substances, also sold under the name Lysol as a powerful antiseptic, drain cleaner etc., and served the carbolic acid spray of Lister and subsequent surgeons of the nineteenth-century.

For powers of resistance, Loffler's bacillus offers marked differences to, say, the cholera vibrio. In dry conditions the former is typically very resistant, as in dry throat membranes during difficult respiration. The course of the disease may eventually show the effects of strong toxins produced by the bacteria, and may lead to complete prostration and lower-body paralyses. The diphtheria toxins were early investigated by a number of workers, including Emile Roux & Alexandre Yersin (1888-90) and Brieger & Fraenkel (1890). The late-Victorian years in medicine were to a large extent dominated by the search for and production of antitoxins and antisera for a number of illnesses. In the case of the child-killer diphtheria, vaccination and inoculation were advanced by many talented bacteriologists, including Roux and Yersin, Fraenkel (1890), Sidney Martin (1892), Behring (1893), Ehrlich (1897). Behring and Kitasato in particular have been associated with such later developments, e.g. with "Behring & Kitasato's diphtheria serum". When the Nobel Prize for Medicine was awarded in 1901, however, Emil von Behring alone had been nominated, to the detriment of the very able co-worker Shibasaburo Kitasato.

Loeffler's original papers are unfortunately buried in obscure German science periodicals, making them difficult of access to all but appropriate specialists. In 1887 he founded and edited his own journal, Zentralblatt fur Bakteriologie und Parasitik. In the same year he published the earliest and for a long time the only History of the new science of Bacteriology, viz. Vorlesungen uber die Geschichtlich Entwickelung der Lehre von den Bacterien... [Lectures on the Historical Development of Teaching Derived from the Bacteria. No English edition is available or known to the present brief study]. Brief references to the somewhat neglected Friedrich Loffler may be found at Muir & Ritchie (1897: 662. "Diphtheria"), and in Bulloch (1937).

The proliferation of diphtheria studies appears to have continued strongly c.1900-1910, with an occasional vested interest still even in the by then obsolete treatment with surgical tracheotomy. Antitoxins, inoculations and related preventives by then dominated the scene, to the immense benefit of twentieth-century children and families.

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Last Modified 11 January 2017