ANTHRAX

Bacillus anthracis is a gram-positive spore-forming bacillus that can cause acute infection in both animals and humans. It is primarily a disease of herbivores, which acquire infection after coming into contact with soil-borne spores. In its spore form it can persist in nature for prolonged periods, possibly years. The distribution of anthrax is worldwide.

The disease occurs primarily in three forms: cutaneous, respiratory and gastrointestinal. The incidence of anthrax has decreased in developed countries but it remains a considerable health problem in developing countries.

Historic reference

The earliest known description of anthrax is found in the book of Genesis: the fifth plague (1491 BC), which appears to have been anthrax, was described as killing the Egyptians cattle. There are descriptions of anthrax involving both animals and humans in the early literature of Hindus, Greeks, and Romans. In the 17th century, a pandemic referred to as "the black bane" swept through Europe, causing many human and animal deaths. Later the disease in humans was described as "the malignant pustule".

Several distinguished microbiologists in the 19th century characterized the pathology of the disease and attempted to develop a vaccine because of serious problems with anthrax in the livestock industry. Pasteur developed and field tested in sheep his attenuated spore vaccine in 1881. In 1939, Sterne reported his development of an animal vaccine that is a spore suspension of an avirulent, noncapsulated live strain. This is the animal vaccine currently recommended for use.

Occupational anthrax occurred 18th century in industrial European countries such as England and Germany. Early in this century, in the United States, it occurred in individuals who handled materials that had been woven from contaminated animal fibers.

From the beginning of this century the annual number of cases reported in developed countries has steadily decreased. This decrease is the result of the use of a cell-free anthrax vaccine in humans who are in high-risk industrial groups, decreased use of imported potentially contaminated animal products, improved hygiene in industry, and improved animal husbandry.

Etiology

Pus or tissue from patients suspected to have anthrax should be stained by both Gram stain, to reveal gram-positive bacilli, and polychrome methylene blue, to show the polypeptide capsule. Bacilli are usually abundant in the specimen and easy to culture on standard blood or nutrient agar. In heavily contaminated

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specimens such as Stool it may be necessary to use selective agar or decontamination methods that rely on the resistance of the anthrax spores to heat or ethanol. The colonies are gray-white to white and nonhemolytic. Identification of the isolate depends on biochemical tests, presence of a capsule, lack of motility, catalase positivity, lysis by bacteriophage, penicillin susceptibility, and aerobic endospore production. Commercially available test strips and fluorescent antibody staining can be used to aid identification.

Epidemiology

Anthrax is usually a disease of herbivores and only incidentally infects humans who come into contact with infected animals or their products. Because anthrax remains a problem in developing countries, animal products imported from these areas continue to pose a risk.

Human cases may occur in an industrial or in an agricultural environment. Industrial cases result from contact with anthrax spores that contaminate raw materials that are used in manufacturing processes. In the United States, occasional epidemics occurred in industrial settings, probably related to the processing of batches of highly contaminated imported animal fibers, particularly goat hair. These epidemics were primarily of cutaneous anthrax.

One epidemic was recently reported in Switzerland. Within less than 3 years, 25 workers in one textile factory contracted the disease; 24 cases had cutaneous and one inhalation anthrax. The infection was imported in goat hair from Pakistan. The rarity of the illness contributed to a general lack of experience and therefore hindered recognition of the clinical symptoms. In addition, repeated attempts failed to identify the pathogenic agent conclusively.

Human cases of anthrax in an agricultural environment result from direct contact with animals that are sick or have died from anthrax.

In Africa there have been multiple epidemics of human disease associated with epizootics of anthrax in cattle. The largest reported agricultural outbreak occurred in Zimbabwe, with more than 10,000 cases reported between 1979 and 1985. Endemic cases continue to occur in the involved area. The majority of patients had cutaneous infections located primarily on the exposed parts of the body; some gastrointestinal cases were also reported. Domestic cattle deaths were noted. A similar large outbreak of human and animal anthrax occurred in Chad, mainly in the Department of Chari Baguirmi, from September to December 1988, infecting more than 50 % of donkeys and horses. There were 716 human cases reported, with 88 deaths.

In African wildlife, which cannot easily be vaccinated and in which the other aspects of control are not relevant, the disease remains a major cause of uncontrolled mortality in herbivores.

Organisms can also be transmitted by a common vehicle such as food (meat), although this is more rare. Large outbreaks have been reported in Thailand and Russia. This last outbreak of human anthrax occurred in north central Russia in 1979, in which the government health authorities of the former U.S.S.R. reported

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that the source of infection was contaminated meat. Officially there were 96 cases: 79 of gastrointestinal anthrax and 17 of cutaneous anthrax. However, there is novel evidence concerning the real nature of this anthrax outbreak. Intelligence authorities in the United States had initially reported hundreds of fatalities, including military personnel, and had suspected that an explosion at a secret germ warfare facility in Sverdlovsk had sent deadly anthrax spores airborne. The United States has repeated this allegation, but it never formally accused the former U.S.S.R. of violating the germ warfare treaty or substantiated its charge. The hospital records of the patients affected by this outbreak including the autopsy reports have been unavailable.

Recently two Russian pathologists published hidden secret information describing the necropsy of 42 cases, which consistently revealed pathologic lesions diagnostic of inhalation anthrax. Main features include hemorrhagic necrosis of the thoracic lymph nodes in the lymphatic drainage of the lungs and hemorrhagic mediastinitis. This information underscores the potential use of B. anthracis in biological warfare.

Pathogenesis

The virulence of B. anthracis is determined by the presence of three components: edema toxin, lethal toxin, and capsular material. To exert their effect within cells,both edema and lethal toxin require participation of a common transport protein called protective antigen. The capsule material contains poly-D-glutamic acid, which helps protect the bacillus from ingestion by phagocytes. Production of the toxic factors is regulated by one plasmid and that of the capsular material by a second plasmid.

The effects of anthrax toxin components on human neutrophils have been studied in detail. Phagocytosis of opsonized and radiation killed B. anthracis was not affected by the individual anthrax toxin components. However, a combination of lethal toxin and edema toxin inhibited bacterial phagocytosis and blocked the oxidative burst of polymorphonuclear neutrophils. The two-toxin combination also increased intracellular cyclic AMP levels. These studies suggest that two of the protein components of anthrax toxin increase host susceptibility to infection by suppressing polymorphonuclear neutrophil function and impairing host resistance.

Experiments performed in animals suggest that spores deposited beneath the skin or in the respiratory or intestinal mucosa germinate and the resulting vegetative forms multiply and produce a toxin. The local lesion results from the action of the toxin on the surrounding tissue, which causes tissue necrosis. The toxin or organisms or both may disseminate by the vascular system, causing systemic symptoms and signs of toxicity or bacteremia. Organisms are also often picked up by the lymphatic system, resulting in lymphangitis and lymphadenopathy.

Anatomic pathology

The most significant findings at autopsy are those seen in patients who have died of inhalation anthrax. The classic finding is that of hemorrhagic mediastinitis

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with enlarged, hemorrhagic lymphadenitis. There may be inflammation of the pleura and some pleural effusion. Some patients may have hemorrhagic meningitis, and hemorrhages may be seen in the gastrointestinal tract.

In deaths due to gastrointestinal anthrax there is typically hemorrhagic enteritis, with congestion, thickening, and edema of the intestinal walls. Mucosal ulcers with necrosis may be seen in the terminal ileum and cecum. The regional lymph nodes are enlarged, edematous, and hemorrhagic with some necrosis.

There may be acute splenitis. Peritonitis with ascitic fluid is often present.

Clinical manifestations

Approximately 95 % of anthrax cases in developed counties are cutaneous and 5 % are respiratory: confirmed epidemic cases of gastrointestinal anthrax have often been reported in "Third World" countries.

Cutaneous anthrax. The clinical presentation of cutaneous anthrax is so characteristic that the diagnosis is not often missed by physicians familiar with the disease. Most of the cases occur in exposed skin areas mostly on the arms and hands followed by the face and neck. The infection begins as a pruritic papule that resembles an insect bite. The papule enlarges and within 1 or 2 days develops into an ulcer surrounded by vesicles. The lesion is usually 1-3 cm in diameter and usually remains round and regular. A characteristic black necrotic central eschar develops later with associated edema. The lesion is most often painless and may first be noticed because of pruritus. After 1-2 weeks the lesion dries, and the eschar begins to loosen and shortly thereafter separates, revealing a permanent scar. There may be regional lymphangitis and lymphadenopathy and some systemic symptoms such as fever, malaise, and headache. Antibiotic therapy does not appear to change the natural progression of the lesion itself: however, it will decrease or inhibit development of edema and systemic symptoms. Differential diagnosis include conditions due to potential contact with infected animals such as plague and tularemia.

Respiratory anthrax. Respiratory anthrax shows a bi phasic clinical pattern with a benign initial phase followed by an acute, severe second phase that is almost always fatal. The initial phase begins as a nonspecific illness consisting of malaise, fatigue, myalgia, mild fever, nonproductive cough, and, occasionally, a sensation of precordial oppression.

The illness may cause disorder of upper respiratory tract such as a cold or influenza. After 2-4 days, the patient may show signs of improvement. However, there is then the sudden onset of severe respiratory distress characterized by severe hypoxia and dyspnea. In several cases, subcutaneous edema of the chest and neck has been described. The pulse, respiratory rate and temperature become elevated. Physical examination reveals moist, crepitant rales over the lungs and possibly evidence of pleural effusion. Radiographic examination of the chest may reveal widening of the mediastinum and pleural effusion. Patients soon become hypotensive and septicemia and meningitis may develop. Death occurs in most

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persons with inhalation anthrax within 24 hours after the onset of the acute phase. Inhalation anthrax is very difficult to diagnose early.

Gastrointestinal anthrax. The incubation period of gastrointestinal anthrax is commonly 3-7 days. There are two clinical presentations following ingestion of B. antracis - contaminated food: abdominal and oropharyngeal.

The symptoms of abdominal anthrax are initially nonspecific and include nausea, vomiting, anorexia, and fever. Lesions are frequently described in the cecum and adjacent areas of the bowel. Some reports have described lesions in the large bowel, and rarely in the duodenum. With progression of the disease abdominal pain, hematemesis. and bloody diarrhea develop. With further progression toxemia develops, with shock, cyanosis, and death. The time from onset of symptoms to death has most frequently varied from 2 to 5 days.

In the oropharyngeal form edema and tissue necrosis occur in the cervical area. There are several reports describing the development of an inflammatory lesion resembling a cutaneous lesion in the oral cavity involving the posterior wall, the hard palate, or the tonsils. The main clinical features are sore throat, dysphagia, fever, regional lymphadenopathy in the neck and toxemia. Most of these patients die with toxemia and sepsis.

Meningitis. Meningitis, seen in less than 5 % of anthrax cases, may be a complication of any of the three forms of primary anthrax infection.

Diagnosis

Of importance in considering a diagnosis of anthrax is a source of exposure to the infectious agent. Only rarely cases have occurred for which the source of infection could not be identified. Cutaneous anthrax should be suspected when an individual describes a painless, pruritic papule, sometimes surrounded by vesicles usually on an exposed part of the body. For the detection of anthrax bacillus, sterile swabs should be soaked in the fluid of the vesicles, vesicular fluid should reveal B. anthracis organisms microscopically and on culture. Anthrax bacilli are easily seen on Gram stain smears and cultures from vesicular fluid.

An enzyme-lined immunosorbent assay (EL1SA) has been developed that measures antibodies to the lethal and edema toxins. The diagnosis may be confirmed serologically by demonstrating a fourfold change in liter in acute- and convalescent-phase serum specimens collected 4 weeks apart or by a single titer of greater than 1:32. Although extensive serologic studies have not been conducted, antibody liters in some surveys of exposed individuals suggest some degree of previous subclinical infection.

Differential diagnosis

Includes staphylococcal disease, plague and tularemia. The initial symptoms of inhalation anthrax are nonspecific and resemble those of an upper respiratory tract infection. Characteristically, with the sudden development of the acute phase there is severe respiratory distress, and radiographic examination of the chest should reveal widening of the mediastinum, a typical occurrence with inhalation anthrax.

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In gastrointestinal anthrax, the patient presents with signs and symptoms of gastroenteritis. Organisms may be demonstrable in vomitus and feces from the infected individual. The differential diagnosis includes diseases that cause moderately severe gastroenteritis, such as shigellosis and Yersinia gastroenteritis. In the cervical form, the signs and symptoms might suggest severe pharyngitis, such as is sometimes seen with streptococcal infections.

In anthrax meningitis and in septicemia there should be a primary site of infection. Cerebrospinal fluid (CSF) and blood contain B. anthracis.

Treatment

The basic agents are antibiotics and antianthrax immunoglobulin. Among the antibiotics ciprofloxacin or ofloxacin are preparations of choice. At generalized infection ciprofloxacin is used 0.4 or 0.5 gm twice a day. Course of treatment is 5-10 days. Benzylpenicillini natrium sodium salt 500,000-1 million units is effective, 6-8 times per day. At the generalized form of disease enlarge a daily dose of preparation up to 12-24 million units. It is possible to use semipenicillines -ampicillin or oxacillin. Course of treatment not less than 7-8 days. Alternative preparations can be tetracyclin, levomycetin, streptomycin, gentamicin.

The best results are reached with the combined therapy of antibiotics and antimalignant anthrax immunoglobulin. Last infuse in muscle in a dose from 20 up to 100 mL. Depend on clinical form and degree of gravity of disease. Preliminary make intracutaneous test on sensitivity of organism to horse protein. It is necessary in 1-2 days infuse immunoglobulin repeatedly before clinical improvement. The course dose reaches sometimes 400 mL.

At serious current of disease use infusions of 5 % solution of glucose, reopoliglycin, poliionic solutions, furosemid (lasix), glucocorticoides, oxygenotherapy.

Prophylaxis

Early in this century, as an example of health preventive intervention, a formaldehyde disinfecting station was built by the British government in Liverpool. All "dangerous" imported wool and goat hair were first washed in formaldehyde baths, which successfully reduced contamination of the animal fibers with B. anthracis.

The resistance of the spore form of B. anthracis to physical and chemical agents is reflected in the persistence of the organism in the inanimate environment. Organisms have been demonstrated to persist for years in factories in which the environment became contaminated during the processing of contaminated imported materials of animal origin. Accordingly, they may serve as the source of infection for people who work in the area. Special efforts are required to decontaminate this environment; one method is to use paraformaldehyde vapor, which is successful in killing B. anthracis spores. In the laboratory, surfaces may be decontaminated with either 5 % hypochlorite or 5 % phenol (carbolic acid); instruments and other equipment may be autoclaved.

Employees should be educated about the disease and the recommendations for working in a contaminated environment and for reducing the risk of developing

Infectious diseases

the disease. Medical consultation services should be available to the employees. Adequate cleanup facilities and clothes-changing areas should be available so that workers do not wear contaminated clothes home.

It should be noted that the risk of industrial infection has been reduced significantly as the use of imported animal products decreased because of changing business conditions, the increased use of synthetic materials, and the use of human vaccine.

Gastrointestinal anthrax can be prevented by forbidding the sale for consumption of meat from sick animals or animals that have died from disease. Depending on the circumstances, it may be important to alert individuals who may come in contact with contaminated meat about the disease and about the need to cook all meats thoroughly. Prophylactic penicillin may be used if contaminated food has been ingested.

Animals that graze in areas known as anthrax districts should be vaccinated annually with the animal vaccine. All animals suspected of dying from anthrax should be examined microbiologically: blood or tissue smears can be examined microscopically, and cultures can be set up from these same materials. Necropsies with spillage of contaminated blood with resultant sporulation of organisms should be avoided. All animals that have died with a confirmed diagnosis of anthrax should be thoroughly burned and the remaining bones and other materials buried deeply.

Control of the disease in humans ultimately depends on control of the disease in animals. Effective animal vaccines are available, and all cases should be reported to state veterinary authorities.

Both an attenuated live vaccine and a killed vaccine have been developed. However, the only human vaccine in current use is the killed vaccine derived from a component of the exotoxin. This vaccine* was field tested in employees of four different textile mills in the United States, and an effectiveness of 92.5 % was demonstrated. This vaccine should be used for all employees who may be exposed to contaminated materials or environment. Additionally, anyone who comes into a mill processingB.a/^rac/s- contaminated materials should also be vaccinated. Currently, the vaccine is given parenterally with three doses at 2-week intervals followed by three booster inoculations at 6-month intervals and the annual booster inoculations. Veterinarians and other persons who, because of their occupation, have potential contact with anthrax should also be immunized with the human anthrax vaccine.

Control questions:

•

1. Etiology, epidemiology and incidence of anthrax.

2. Pathogenesis of anthrax.

3. Anatomic pathology of disease.

4. Clinical manifestations of anthrax.

5. Laboratory methods of anthrax diagnosis.

6. Criteria of diagnosis.

7. Differential diagnosis of anthrax.

8. Treatment of anthrax.

9. Prophylaxis of anthrax.

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Date: 2014-12-21; view: 1127