Author(s): Lee Hunter, DVM; Wayne Corbett, VMD, DPH; Carol Grindem, DVM, PhD
Source: From the Veterinary Public Health program, North Carolina Division of Health Services, PO Box 2091, Raleigh, NC 27602-2091 (Hunter), and the Department of Microbiology, Pathology, and Parasitology, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough St, Raleigh, NC 27606 (Corbett, Grindem).
Date: April 15, 1989
This article, from the second edition of Zoonosis Updates published by the American Veterinary Medical Association in 1995, is provided here as a public service due to its potential relevance to bioterrorism. AVMA members may access all Zoonosis Updates by visiting the AVMA Resource Center. Members and nonmembers may contact the AVMA to purchase a print version.
A new series of articles is being prepared under the guidance of the Council on Public Health and Regulatory Veterinary Medicine for publication in the Journal of the American Veterinary Medical Association.
In mid-June, a steer suddenly died on a drought-ridden ranch on the US Gulf Coast. Before its death, the steer had had signs of acute depression and dyspnea. The farmer did not call his veterinarian and no cause of death was determined. Within 1 week, 7 animals (5 cattle, 1 horse, and 1 pig) from 2 adjacent farms had died. Of those, several cattle were found dead a few hours after being checked by the rancher. Others developed fever, dyspnea, and convulsions within 24 hours of their death. Hemorrhage exuded from body orifices at the time the cattle died. The pig and horse died of asphyxia secondary to laryngeal swelling. Anthrax was diagnosed and confirmed by bacteriologic culture at the state laboratory. The epizootic was controlled by vaccination and quarantine.
During the same week, a 35-year-old maintenance worker at a textile plant in a nearby community noticed a red, pruritic papule on his right forearm. Although the man suspected a spider bite, the lesion evolved from a papule into a vesicle, then into a depressed black eschar with surrounding edema. Initially, a physician treated him with a cephalosporin and an antifungal agent; however, his condition worsened and after 24 hours, he was hospitalized with chills, fever, and edema of the right arm extending from the fingers to the axilla. Because anthrax was suspected, blood and wound specimens were obtained for bacteriologic culture. Serum was obtained for anthrax titers. Treatment was changed to IV administration of ampicillin and cephalosporin. The next day, obvious improvement was noticed in the patient's condition, and he was eventually discharged with instructions to continue to take cephalosporin orally. Serum titers were 1:512 to anthrax protective antigen and lethal factor when tested by electrophoretic immunotransblot assay,(1) but Bacillus anthracis was not isolated from the blood or wound.
The patient stated that he had not traveled out of the geographic area during the past year, and had had no exposure to wild or domestic animals, bone meal fertilizer, or animal products other than those used at the textile mill where he worked. He did not recall any wound in the area of infection immediately before developing signs of infection; however, he mentioned that he routinely has trauma to his skin during the course of his job.
The spinning mill makes thread with wool from Australia and New Zealand; with cashmere from China, Afghanistan, and Iran; and with camel hair from China and Mongolia. Samples were taken from raw materials, processed
materials, and dust from various locations in the mill for bacteriologic culture. Bacillus anthracis was isolated from 8 of 59 samples: 6 in Middle Eastern cashmere, and 2 in dust samples.
The patient, his employer, and local farmers affected by the epizootic discussed the cases with state and federal health and agriculture officials.
Farmer: What is anthrax?
Agriculture official: Anthrax is a disease of human beings and animals caused by the encapsulated, spore-forming, large gram-positive rod Bacillus anthracis. The bacteria grows vegetatively within the body tissues of the host; sporulation occurs when the vegetatively growing organism is exposed to the atmosphere.(2,3) As a result, B anthracis is found in soil as a resistant spore that may persist for years.(3) Whether the B anthracis has a saprophytic growth phase in soil is debated(4,5); however, because of observations from related epidemiologic studies, some investigators believe the hypothesis that a growth phase in soil is plausible.
The bacillus produces an exotoxin or exotoxins with at least 3 active fractions: edema factor, lethal factor, and protective antigen. In the host the actions of a combination of these factors cause the destruction of phagocytic cells and capillary permeability, resulting in illness.(3) One study(6) has shown that phagocytosis by human neutrophils is inhibited in the presence of protective antigen and edema factor, potentially increasing the host's susceptibility to disease. There are areas of the world in which anthrax is endemic in animals. This results in chronic environmental contamination with resulting human and animal disease.
Farmer: Where are those geographic areas?
Agriculture official: Bacillus anthracis is found most commonly in areas with neutral to mildly alkaline soil (pH 6 to 8.5), and periods of drought and flooding.(3,7) Flooding allows the bacteria to accumulate at the ground surface in low-lying areas. Subsequent drought affords conditions for exposure of the spores.
Anthrax has been reported in the Middle East, Africa, Central and South America, as well as other areas of the world.(3,8) In the United States, it has been most commonly reported in the southern Mississippi River Valley, but the disease has been reported in nearly every state.(9)
Farmer: How is anthrax transmitted between animals?
Agriculture official: Most animals are infected while grazing in areas that have previously experienced anthrax.(10) After flooding, low-lying areas can become contaminated with a high concentration of spores.(10) The spores are transmitted through the consumption of contaminated water or hay. Also, consumption of inadequately processed, infective feedstuffs of animal origin, such as bloodmeal or bonemeal, has been implicated as a cause of infection.(3,10,11)
Farmer: What clinical signs or stages of the disease are observed in animals?
Agriculture official: Three forms of disease are recognized in animals: peracute, acute/subacute, and chronic.(3,10,12) In the peracute form of anthrax death may occur without any warning, as animals may rapidly develop cerebral anoxia and pulmonary edema. Ruminants, especially cattle, sheep, and goats, are the species most commonly affected with this form of disease.(10)
Fever, depression, convulsions, and dyspnea are associated with acute or subacute anthrax. Animals may hemorrhage from the mouth, nose, and anus. Death occurs approximately 24 hours after the initial signs of illness. Cattle, sheep, and horses are the species most commonly affected with this form of anthrax.(10)
Typical necropsy findings of cattle and sheep dying of acute/subacute anthrax include hemorrhage and edema in any part of the body(12); splenomegaly is evident, with a "blackberry jam" appearance. This sign is not seen in swine dying of anthrax. The blood is dark and will not clot.(9)
Lingual and pharyngeal tissue edema cause the typical clinical signs of chronic anthrax, ie, dyspnea and serosanguineous discharge from the mouth.(10) Death from asphyxia may ensue. This form of illness is reported most often in swine, but has also been seen in horses, dogs, and rarely, cattle.(10) Edema from chronic anthrax may also be seen in other locations of the body. In addition, an intestinal form of chronic anthrax has been reported in swine.(10) Necropsy of animals dying of chronic anthrax will reveal lingual and pharyngeal edema. Hemorrhage may be seen in the pharynx and cervical lymph nodes.(12)
Farmer: How can anthrax be diagnosed in animals?
Agriculture official: The disease is most commonly diagnosed in animals by historic evidence plus examination of blood or edema fluid for characteristic bacteria in short chains.(3,9) Blood should be obtained from the jugular vein or peripheral vessel. Diagnosis is also made by culture or inoculation into laboratory animals.
Bacteriologic cultures from animals may not yield growth if antibiotics were given before sampling. Regardless of the source, testing for B anthracis should be attempted only by a laboratory capable of the containment necessary to prevent accidental laboratory-acquired cases.
A fluorescent antibody test is available to detect capsular production by B anthracis grown on a bicarbonate medium under 5% CO2. Because no other bacillus produces a capsule under these conditions, the sensitivity can be
high when tested by a knowledgeable technician.(13)
Farmer: What is done for a farm in which there is an epizootic of anthrax?
Agriculture official: A quick examination of the entire situation is necessary to remove the source of the bacteria or spores. If circumstances indicate that a new food source may be the cause, it should be removed immediately. Antibiotic treatment should be initiated in survivors. Vaccination against anthrax of the survivors may be of negligible benefit in this scenario. Affected farms should be quarantined for a period extending 2 weeks past the last death from anthrax.
In anthrax-endemic areas or in areas surrounding an epizootic, vaccination of cattle or other livestock may be economically justified. In areas that experience anthrax in sporadic epizootics, it will usually not be
economically justified to vaccinate until there is an epizootic. The Sterne vaccine, an avirulent, nonencapsulated B anthracis vaccine, which is effective in many species, is said to induce immunity within 7 days. Revaccination is recommended yearly where needed. Animals should not receive antibiotics within 7 days of receiving the Sterne vaccine, to prevent killing the live bacteria in the vaccine. Food animals should not be vaccinated within 60 days of slaughter.(9) Animal species in which the vaccine has not previously been used should not be vaccinated unless preliminary testing is done under field conditions.(14)
Milk should be discarded from nonvaccinated, febrile dairy cattle under surveillance in an area experiencing an epizootic. Affected animals should be isolated.(15)
Animals in which anthrax has been diagnosed may be treated with penicillin or oxytetracycline.(9) Treatment should be continued for a minimum of 5 days.
All cases should be reported to the state health department, in addition to the appropriate regulatory authorities.
Farmer: If anthrax has been in an area, how can its recurrence be prevented?
Agriculture official: The best method of preventing future disease is to prevent the release of the organism into the environment. Animals that have died from anthrax should be burned or deeply buried and covered with lime. These animals should not be necropsied in the field because exposure of the vegetative organism to the atmosphere
results in sporulation of the bacteria. "Seeding" of the area with large numbers of spores results in an area of future infectivity. The vegetative anthrax bacteria are destroyed in carcasses that are left unopened.(8,10)
If an animal is necropsied in the field, the carcass should be destroyed as discussed previously. The instruments used should be autoclaved and the surrounding soil should be removed and buried with the animal or decontaminated with a 5% solution of lye.(11)
Vaccination is the method of choice for preventing future cases of anthrax on affected farms.
Mill worker: Was there an association between my infection and that of the animals from the local farms? Can other human cases be prevented?
Health official: Your infection and that of the animals were considered coincidental because you did not have contact with the suspected herds, dead animals, or their products. However, such contact could have resulted in a human infection.
Hair, wool, or skins of animals from endemic areas should be cleaned and tested, preferably before their introduction into the United States, to prevent the seeding of noninfective areas. Contaminated hair and wool may be sterilized by formaldehyde gas.
People at high risk of infection, including textile workers who work with materials from endemic areas, should be vaccinated against anthrax. Vaccination should be used as an adjunct to procedures that reduce environmental contamination, when possible, and access to potentially contaminated areas should be restricted. A cell-free vaccine consisting of the protective antigen is available from the Centers for Disease Control through state health officials.(11)
Mill worker: How is anthrax transmitted to people?
Health official: Bacillus anthracis spores can gain access into the human body through various methods resulting in different manifestations of the disease.(2,10,16) The most common disease form, cutaneous anthrax, generally develops when a penetrating traumatic injury results in deposition of the spore under the skin. Your infection was probably a result of a wound that allowed the bacteria under the skin. People who work with animal-origin products from anthrax-endemic areas are at risk of contracting the disease.(17) Further, bites from flies may mechanically transmit B anthracis, but reported cases are rare and sporadic,(18) and this route of infection is not thought to play a role in epidemics.(9)
A second common form of the disease is caused by the inhalation of spores from contaminated dust, wool, or hair, especially when handled in a confined space.(19) After inhalation, the spores localize in the mediastinal lymph nodes. A septicemic phase follows, with concomitant pulmonary involvement. Despite treatment, death usually follows within 24 hours.(19)
A third form of the disease is intestinal anthrax. Because spores can be found in meat from infected animals, ingestion of raw meat, blood, or inadequately cooked meat from such animals can result in infection. In industrialized nations, intestinal anthrax is less common than the cutaneous or pulmonary form of disease; however, worldwide, intestinal anthrax is much more common than inhalation anthrax.(19) The low prevalence in industrialized nations is presumably attributable to the stringent laws concerning animals allowed into the food chain. Human-to-human transmission is possible but unlikely.
Mill worker: Can you tell me more about the various disease forms?
Health official: Cutaneous anthrax accounts for nearly 90% of all cases. Two to 5 days after inoculation of a spore into a wound, a reddened, papular lesion develops, which commonly is mistaken for an insect bite. Later, there is vesiculation that becomes a depressed, black eschar. Without treatment, septicemia and death may occur
in up to 20% of affected patients. With treatment, death is rare.(11,19)
Initially, inhalation anthrax is associated with signs of mild respiratory disease, ie, mild fever, malaise, and a nonproductive cough. Within 7 days after onset of the signs, the disease becomes more severe, with progressive respiratory distress and cyanosis. Edema of the neck, thorax, and mediastinum signal the beginning of a rapidly
fatal course. Treatment rarely is successful in the advanced stages.(11,19)
A less common clinical form of the disease, intestinal anthrax, is characterized by gastroenteritis with emesis, bloody feces, and signs of septicemia. Death is the usual outcome.(19)
There is an oropharyngeal form of anthrax in people.(19) Those affected develop fever, edema, and cervical or submandibular lymphadenopathy.
Mill worker: Why did the physicians order serologic tests in addition to bacteriologic cultures?
Health official: In human beings, the diagnosis of anthrax is made on the basis of clinical signs as well as results of serologic testing, bacteriologic culture, and inoculation of laboratory animals.(2,11,19) Results of bacteriologic cultures of wound and blood specimens will usually be negative for B anthracis bacillus if antibiotics have been administered,(19) as occurred in your case. Serologic and microbiologic diagnoses are available from state and federal laboratories.
Vesicular fluid is the best source of B anthracis for culture in people with cutaneous anthrax.(19) However, vesicular fluid is often not present when anthrax is suspected.
Farmer: What treatments are most successful in human beings?
Health official: If the disease is not in its advanced stages, antibiotic treatment is effective. Penicillin or ampicillin are drugs of choice in eliminating the bacteria. Presently, in the United States, this organism has not shown resistance to the ß-lactam antibiotics.(19)
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