An Outline Of The Potential Hazards Associated With Anthrax bacillus (B. Anthracis)

Abstract of an article by: George G. Wright, Ph.D., Fort Detrick, Frederick, Maryland, as presented in Bacterial and Mycolic Infection of Man (edited by Rene Dubos), published by: J.J. Lippincott Co.

The disease has been known from antiquity, and satisfactory descriptions of the typical lesions in animals and man have been available for about 200 years. B.anthracis was the first micro-organism to be established as the etiologic agent of a disease. It was discovered in the blood of infected sheep by Rayer in 1850, and experimental transmission of the disease was demonstrated by Davaine in 1863.

PATHOGENICITY and FACTORS IN INFECTION AND RESISTANCE

Virtually all animals are in some degree susceptible to infection with B.anthracis. Infections have occurred in cattle, sheep, horses, goats, buffaloes, water buffaloes, minks, swine, deer, ostriches and elephants.

Cutaneous anthrax or malignant pustule is the most common form of the disease in man. Frequently, the infection develops at the site of a negligible injury such as a scratch or a minor abrasion. The organism is apparently unable to penetrate the intact skin.

Before the advent of antibiotic therapy, the mortality of cutaneous anthrax over a 20-year period in the United States was 21 percent of the 1,683 reported cases. However, the true mortality of untreated human anthrax is difficult to estimate, because failure to report less severe cases tends to raise the apparent mortality, whereas therapeutic measures doubtless reduced the mortality. It is evident that, in the absence of therapy, an appreciable proportion of cutaneous infections in man would progress to generalized infection and death. Meningitis due to B.anthracis is a relatively rare and almost invariably fatal manifestation of human anthrax, the disease is usually a complication of primary infection elsewhere in the body.

Infection may occur, not only by the cutaneous route, but also via the respiratory and the alimentary tracts.

Inhalation anthrax of man was formerly a relatively common form of industrial anthrax. Improvements in working conditions in industries that deal with contaminated hair and hides have greatly reduced the exposure of workers to spore-bearing-dust, and presumably for this reason, the incidence of inhalation anthrax has declined markedly. Practically the entire respiratory tract is susceptible to infection, but the bronchi and the lungs are most frequently the site of the primary lesion. The mortality of diagnosed cases approaches 100 percent although it is possible that nonfatal cases escape diagnosis. The acute course of the disease is not referable to the pneumonic lesions, which may be minimal, but rather to the rapid generalization of the infection via the lymphatics to the circulation.

Human infection by the oral route is of negligible importance in civilized countries, but significant outbreaks with a high mortality occur in primitive societies in which meat from infected animals is used for human food.

No direct information is available regarding the infective does for man by the various routes, and estimates of human susceptibility must be inferred from indirect evidence.

Only rarely do workers contract recognized inhalation anthrax in environments in which spores may be isolated from the nose and the throat; however, it is possible that the spore-bearing particles in these situations are relatively large.

The course of the infection is determined to a considerable degree by the relative ability of the organism to elaborate aggressins and the host t mobilize bactericidal substances. The encapsulated bacilli are resistant to the phagocytic cells of relatively resistant as well as susceptible animals, and it is probable that phagocytosis is of minor importance in natural immunity to infection with virulent strains.

The mechanism of death in anthrax has aroused the interest of investigators for many years. Sterile extracts of infected tissue were shown to have edema-producing activity in the skin of normal animals, but lethal activity could not be demonstrated.

DIAGNOSIS:
Prompt and accurate diagnosis of cutaneous anthrax in man usually presents no serious difficulty. The characteristic lesion begins as a small red macule which enlarges, and local edema of varying extent gradually develops in the surrounding tissue. A vesicle filled with clear fluid occupies a central position and is soon followed by satellite vesicles. The organism may be easily demonstrated in the early lesion by cultural methods and may frequently be detected in stain smears. Fluid and scrapings from the base of a previously unopened vescile should be used for preparation of slides and of cultures on nutrient or blood agar. Microscopic examination of Giemsa-stained films will frequently reveal the organism and permit a rapid tentative diagnosis. The lesion gradually becomes necrotic, with evolution of the black eschar characteristic of anthrax. At this stage, demonstration of the organism is less certain, and secondary infection may complicate the bacteriological diagnosis. Occasionally, inoculation of mice or guinea pigs will allow isolation of the organism when direct cultural methods fail. Antibiotic therapy usually causes rapid disappearance of the organism, even though evolution of the local lesion continues.

Extension to the regional lymph nodes and to the blood occurs in progressive infections; blood cultures may be positive in advanced infections and, in untreated cases, are invariably positive at death.

Diagnosis of respiratory or intestinal anthrax is a much more difficult problem, because of the mild and nonspecific nature of the early symptoms and the fulminating course of the advanced disease. The organism may be detected in sputum by microscopic examination of stained smears; cultural diagnosis is seldom accomplished during the lift of the patient.

THERAPY:
The anthrax bacillus is susceptible to penicillin, tetracyclines, erythromycin, achromycin and chloromycetin; all have been found to be satisfactory for management of cutaneous anthrax in man. According to Gold (1955), terramycin, achromycin an erythromycin are the drugs of choice. Different strains of the organism may differ somewhat in susceptibility to the antibiotics.

Antibiotics rapidly halt the extension of the disease and sterilize the tissues, but they do not reverse the toxic processes initiated by the infection. The primary lesion usually progresses to formation of the typical eschar despite early therapy.

Little information is available regarding antibiotic therapy of respirator anthrax in man. The early symptoms are mild and nonspecific, and the existence of acute disease is seldom recognized until terminal symptoms appear. Treatment has usually been initiated late in the disease, and the unfavorable results provide no basis for estimating the possible effectiveness of early therapy.

EPIDEMIOLOGY
Although anthrax is primarily a disease of cattle, sheep, horses and goats, virtually all animals show some susceptibility, and the disease has been detected in nearly every country. It is particularly common in the Mediterranean region, Africa, and Asia. Epizootics with heavy loss of livestock occur at intervals in enzootic areas. In Iran during 1945, for example, 1 million of the 15 million sheep were reported to have died of anthrax (Delpy and Kaweh, 1946).

In the United States, scattered outbreaks are widespread, but the disease is not a continuing problem, except in certain areas. During the period of 1945 to 1954, 3,447 outbreaks were reported from 39 states, with loss of 17,600 head of livestock (Stein and Van Ness, 1955). The three important endemic areas are the Gulf coast region of Louisiana and Texas, a portion of eastern South Dakota and Nebraska, and an area in central California. Widespread outbreaks were recorded as early as 1835; presumably, the disease was introduced during early settlement, and the spread to new areas appears to be continuing. Climatic conditions and the nature of the soil evidently determine the establishment of the disease in certain areas and the periodic occurrence of epizootics (Minett, 1952; VanNess and Stein, 1956).

In the United States, approximately 50 cases of human cutaneous anthrax are reported annually; additional unreported cases also occur. The incidence is considerably greater in many countries, and it has been estimated that from 20,000 to100,000 human cases occur annually in the world (Glassman, 1958). Man is infected by contact with infected animals (agricultural anthrax) or contaminated animal products (industrial anthrax). Agricultural anthrax occurs in farmers, veterinarians, and slaughterhouse workers. Industrial anthrax occurs primarily in persons whose work brings them into contact with contaminated hair, wool, or hides, although other products have been responsible for scattered outbreaks. Dock workers are occasionally infected while handling contaminated hair and hides. Extensive outbreaks of intestinal anthrax are reported occasionally from primitive areas in which meat from animals that have died of the disease is used as food, and it is probable that such outbreaks are not uncommon.

CONTROL MEASURES
Major emphasis in the control of human anthrax is placed on minimizing contact of man with infected animals or contaminated animal products.

Measures for the control of industrial anthrax include disinfection of animal products, such as hides and hair, which originate in areas in which the disease is widespread. These materials may be heavily contaminated, and economically feasible methods of disinfection that may be applied routinely without damage to the material are not easy to devise. Observations on sterilization by heat have been reviewed by Schneiter and Kolb (1948). Washing with soap and exposure to warm formaldehyde are effective with hair and wool. Measures to minimize the contact of workers with the contaminated materials are also of major importance. Recent advances in immunization with nonviable preparations give promise that immunization of occupationally exposed workers may become practical in the future.