The Granuloma inguinale is an indolent granulomatous and ulcerative disease usually • localized to the genitalia and caused by a pleomorphic coccobacillus, Donovania granulomatis, the so-called “Donovan body.” When grown on an artificial medium, the organism develops a large capsule that reacts immunologically, with klebsiella capsular material: Donovania granulomatis also resembles pneumoniae in morphology. Presumably, the infection is customarily transmitted during coitus or another close bodily contact- and the degree of communicability appears to in relatively low. The lesion tends to be Owen and may rarely appear on surfaces of time fisdiFculture, it inhibits protein synthesis. So-called nonvirulent strains of C. diphtheriae fail to produce this toxin. Freeman (1951) and others have shown that the ability to produce toxin is frequently associated with infection of the bacterial cell with a lysogenic bacteriophage that under proper conditions can convert an avirulent-don-toxin-producing strain into a fully virulent toxin-producing one.
Three types of diphtheria are recognized, largely on the basis of their characteristic colonial formation on potassium tellurite medium and their distinctive fermentation reactions. All three types, gravis, mitis, and intermedius, produce the same toxin and the same clinical picture. The original hypothesis that gravis strains were more frequently associated with epidemic diphtheria remains unproven. Epidemiology and Immunity. Corynebacterium diphtheriae is essentially on the obligate parasite of man; hence, the human host represents the only significant reservoir of diphtheritic infections.
The GRANULOMA INGUINALE organisms may be transmitted directly or indirectly from one person to another. As the usual habitat of the organism is the upper respiratory tract, droplet infection is probably the most common method of spread, although contamination of the hands, handkerchiefs, and similar objects may play an important role. Discharges from extra respiratory sites of infection (such as superficial ulcers of the skin) are infectious. Al-though the organism may survive for a brief period outside the human body, the spread of infection by contaminated dust appears to be a rare occurrence. A few milk-borne outbreaks have been reported.
The GRANULOMA INGUINALE Invasion and infection of the human body by the diphtheria bacillus is not always followed by the development of the clinical disease. More frequently, the organism multiplies in the mucous membrane linings of the air passages for a shorter or longer period without causing signs of illness. Presumably, in such a case, the “carrier” possesses a preexisting immunity of a greater or lesser degree, which, although it does not prevent the actual implantation of the organism, does limit the amount of damage to the host’s cell so that no clinical manifestations develop.
The GRANULOMA INGUINALE Immunity against the clinical disease depends primarily upon the presence of antitoxin in the blood of the infected person. Although it is probable that upon occasion antibacterial mechanisms play a role in preventing the diphtheria bacillus from actually establishing itself in the throat of the human subject, nothing i known concerning the nature or specificity of the reaction. On the other hand, recovery from an attack of clinical diphtheria is associated with the appearance of appreciable amounts of antitoxin in the blood.
This antitoxin is formed in response to the direct stimulation of diphtheria toxin. It has the characteristics of a true antibody: it may be formed in response to either clinical or subclinical infection or as a result of artificial active immunization. Although it is produced relatively slowly in response to the primary stimulation it appears rapidly and in large amounts following secondary stimuli, even though little or no antitoxin can be demonstrated at the time of the secondary stimulation. The antibody may be transferred to other persons (naturally, by tranplacentaI passage in utero; artificially, by transfusion), thereby conferring temporary passive immunity upon the recipient.
Although the accurate determination of anti-toxin levels is a laboratory procedure, the Schick test will usually yield valuable information concerning the immune status of a person. This test is performed by injecting into the skin of the forearm 0.1 ml. of diluted highly purified diphtheria toxin. A positive reaction is characterized by the development of a variable area of redness at the site of inoculation over a period of 72 to 120 hours. The reaction reaches its height about the fifth day; after this it gradually fades, leaving an area of brownish pigmentation that may persist for some weeks. Such a positive reaction is associted with an antitoxin level in the circulating blood of less than 0.03 unit of antitoxin per milliliter and is interpreted to mean that the patient is susceptible to the clinical disease. A negative Schick reaction signifies that the blood antitoxin level exceeds 0.3 unit per milliliter and that the subject’s chances of contracting clinical diphtheria are comparatively slight. The occasional negative reactor who does develop clinical illness usually has a mild attack.
In actual practice, the diluted toxin is injected in one forearm, while the other forearm is injected with a similar amount of the same material that, however, has been heated to 60° C. for 30 minutes in order to destroy the toxin. This control is necessary in order to detect pseudo-Schick reactions, reactions caused by-products of growth of the diphtheria bacillus other than the toxin itself. Thus, some workers recommend the use of highly purified toxoid as control material. The pseudo-Schick reaction is char-bacterize by the development of erythema at the site of inoculation about 18 hours after injection. This increases to reach its maximal intensity at 24 to 36 hours and then fades gradually to disappear completely within the next 72 hours. Such a reaction connotes allergy to some component of the injected- material rather than the absence of circulating antitoxin in quantities adequate to confer immunity. Thus, four types of reaction are possible, as indicated in the accompanying table.
Babies born to immune mothers will give negative Schick reactions at birth, owing to the transplacental transfer of anti-toxin. This passive immunity wears off rapidly, and by the sixth month, in the absence of artificial immunization, nearly all infants are susceptible to the disease as evidenced by the demonstration of a positive Schick reaction. From this point on there is a gradual rise in the proportion of persons giving Schick-negative reactions as a result of natural immunization, usually following subclinical, infection. In the absence of continued contacts with the diphtheria bacillus, the antitoxin level gradually falls to a point where the person is again susceptible to the disease. Pathogenesis.
The usual habitat of the diphtheria bacillus is the upper respiratory tract of man. In a susceptible person, the organism multiplies in the superficial epithelial cells of the pharynx, elaborating and secreting the specific toxin in the process. The absorption of this toxin by neighboring cells initiates a process of tissue necrosis, which furnishes conditions favorable to the growth of the organism, which in turn produces more of the toxin. As the process continues,’, it stimulates an inflammatory reaction on the part of the body, leading to the formation of the typical diphtheritic membrane.