A Study of Bacterial Synergism with Reference to the Etiology of Malignant Diphtheria

Abstract

Malignant, "bull-neck," hypertoxic, or grave diphtheria is differentiated from "ordinary" or milder diphtheria by the presence of marked cervical swelling (hence "bull-neck"), extreme toxemia, albuminuria, frequent development of neuropathies, and a high death rate in spite of early administration of large doses of antitoxin. Epidemics of diphtheria in which the malignant form predominated have been common in Europe, England, and elsewhere within the past two decades as reported by Anderson et al. (1931) and Deicher and Agulnik (1927), but during the same period have been relatively uncommon on this continent. Since 1931 only one such outbreak has been reported (Wheeler and Morton, 1942). However, in Baltimore, after several years of low morbidity and fatality, diphtheria began to increase in 1942 and, as in many other large cities in the United States and Europe during the war years, it attained high levels (Eller and Frobisher, 1945). During the first 6 months of 1944 there were in Baltimore 142 cases, 16 of which were designated as malignant. The malignant cases suffered a 44 per cent mortality (7 cases), whereas the total mortality was only 6 per cent (9 cases). In 1945 there were 352 cases reported and 18 deaths. A considerable number of these were malignant. The disease continued at a relatively high level of incidence and severity throughout 1946. Since the description of gravis and mitis types of diphtheria bacilli by Anderson et al. (1931), malignant diphtheria has been widely believed to be due to the gravis type of diphtheria bacilli, although it has been repeatedly pointed out by Frobisher (1943) and others that the occurrence of this organism, at least that variety of it which is found in Baltimore and elsewhere in the United States, bears no constant relation whatever to malignant diphtheria. Continuous, systematic studies of the types of diphtheria bacilli found in cases of diphtheria in Baltimore since about 1932, including the numerous typical, fatal malignant cases noted above, have revealed during 16 years only 10 or 12 gravis strains, and these rarely in the malignant cases. The mitis or mitis-like form has predominated in cases, contacts, and carriers at all times according to Frobisher (1938, 1940, 1942). This has also been found true, as a general rule, throughout the United States. Obviously, then, malignant diphtheria in Baltimore and the United States during 1 This work was supported in part by funds from The Rockefeller Foundation. 2 Adapted from a dissertation submitted by the senior author to the School of Hygiene and Public Health of The Johns Hopkins University in partial fulfillment of the requirements for the degree of Doctor of Science in Hygiene.