by Dr. Andreas Lambrianides
General Surgeon, Brisbane, Australia
The genus Bacillus consists of Gram-Positive, aerobic, spore bearing rods. There is only one species pathogenic to man, Bacillus anthracis, the cause of anthrax. The capsule of bacillus anthracis, which consists of poly-D-glutamic acid, and the toxin are the principal virulence factors of the organism.

Anthrax is primarily a disease of herbivorous animals and infects humans only incidentally when they come into contact with infected animals and their products.

The disease anthrax occurs primarily in three forms: cutaneous, gastrointestinal and respiratory.

The earliest description of anthrax is found in Exodus Chapter Nine, 1-7: " Let my people go so that they may worship me, if you refuse to let them go, and continue to hold them back, the hand of the Lord will bring a terrible plague on your livestock in the field - and your horses and donkeys and camels and on your cattle and sheep and goats ------ And all the Livestock of the Egyptians died".. And again, Exodus Chapter Nine 8-12: ".Festering boils broke out on men and in animals."

The classic studies Robert Koch, established that Bacillus anthracis, was the cause of anthrax. This was the first demonstration of a single organism causing a single disease. Pasteur developed and tested in sheep his attenuated spore vaccine in 1881. Sterne in 1939 developed an animal vaccine that is a spore suspension of an avirulent non-encapsulated strain.

Bacillus anthracis itself is a large, square ended non-motile encapsulated bacillus measuring five to eight micrometers times one to one point five micrometers. In the tissues it occurs singly or in pairs but in culture the bacilli adhere end to end to produce long chains.

Bacillus anthracis is a spore forming bacterium. Some bacteria have this ability to pass into a highly resistant resting phase by production of thick walled spores. Spore formation is characteristic of two genera: the spore bearing aerobes (Bacillus) and the spore bearing anaerobes (Clostridium). The spores in bacillus anthracis are the same width as the bacteria or slightly narrower and do not produce a bulge in the contour of the cell.

Sporulation depends on the depletion of some particular nutrient at a time when conditions for growth are otherwise unfavorable. It does not occur in the tissues. An in growth of cytoplasmic membrane cuts off a portion of the cells cytoplasm and nuclear material, the spore primordium, or forespore, which later develops a thick cortex and a tough spore coat. The mature spore is a round or oval body, which stains with difficulty. It is first contained in the cell, but finally the rest of the bacterium disintegrates and the spore is set free. The most important property of spores is their extreme resistance to drying, heating and disinfections and the fact that they remain viable and a potential danger for long periods.

Bacillus anthracis spores have been used as a biological warfare agent. Countries such as Japan, The United Kingdom, Iraq, The United States and the Soviet Union have all developed anthrax as a biological warfare agent.

Anthrax spores have several characteristics suitable for a biological weapon such as high potency, accessibility, easy delivery and low visibility. A millionth of a gram of anthrax spores constitutes a lethal inhalation dose. A kilogram has a potential to kill thousands of people in a metropolitan area. Because the incubation period of inhalation anthrax may last a few days, the impact of terrorist exposure could be reduced by early diagnosis.

It is certain that scientists are now capable of inserting the Bacillus anthracis gene into other bacilli using plasmid biotechnologies, against which the present available vaccine is ineffective. In addition vaccines may not be affective against rare strains of Bacillus anthracis. Antibiotic resistant strains have also been developed which makes the thread of pathogenicity highly significant.

For diagnosis, specimens of patients are stained with both the Gram stain to reveal the Gram-positive bacilli and polychrome methylene blue to show the polypeptide capsule.

Bacilli are easy to culture on standard blood or nutrient agar. A twenty-four hour culture on blood agar produces the characteristic medusa's head colonies on the surface. Inoculation of Bacillus anthracis will kill guinea pigs in twenty-four hours and the organism can be recovered from the left ventricle. Insertion of a needle contaminated with the beast into gelatin, gives a characteristic inverted fir tree appearance. Identification of the isolate depends on the presence of a capsule, lack of motility, catalase positivity, lysis by Gama bacteriophage, penicillin susceptibility and aerobic endospore production. The indirect microhemagglutination test has detected antibodies in 93% of patients and in none of the controls. It is useful in confirming the diagnosis.

The pathogenesis of the bacterium depends on the production of a toxin, which in the case of Bacillus anthracis is composed of three proteins: protective antigen, edema factor, and lethal factor. The protective factor binds to specific receptors on the cell surface and mediates entry of the edema factor and lethal factor into the cell. The edema factor is a calmodulin dependent adenyl cyclase, and together with the protective antigen forms the edema toxin. Lethal factor and protective antigen together form the lethal toxin that is the dominant virulence factor and is the major cause of death.

Approximately 95% of anthrax cases in developed countries are cutaneous and 5% respiratory epidemic cases of gastrointestinal anthrax have also been reported. Most of the cases of cutaneous anthrax occur in exposed skin areas on the arms and hand followed by the face and neck. The lesion begins as a small pruritic papule, which enlarges within a day or two to develop into an ulcer surrounded by haemorrhagic vesicles. The vesicles are one to three cm in diameter and remain round and regular. There is a characteristic black central necrotic area. The edema is a striking feature in cutaneous anthrax and it commences around the original lesion and spreads extensively where ever the sub-cutaneous tissue is lax. The skin may retain its normal color or become intensely red. The lesion is surprisingly painless and is initially noticed, because of the pruritus. After about two or three weeks, the lesion dries, the eschar separates, leaving a deep ulcer which fills with granulations tissue and eventually produces a permanent scar. Regional lymphadenopathy and systemic disturbance such as fever, malaise and headache may occur.

Ingestion of contaminated meat products can produce gastrointestinal anthrax. The incubation period is three to seven days. There are two clinical presentations following ingestion of contaminated food: Abdominal and Oropharyngeal. Initial symptoms of abdominal anthrax are non-specific and include nausea, vomiting, anorexia and fever. Lesions are frequently described in the caecum, and adjacent areas. With progression, abdominal pain haematemesis and bloody diarrhea occur. Eventually toxemia develops leading to shock, cyanosis and death. The time from the onset of symptoms to death ranges from two to five days. In the Oropharyngeal form the main clinical features are sore throat, dysphagia, fever, lymphadenopathy and toxemia. There is edema and tissue necrosis in the cervical area.

Respiratory anthrax, also known as "woolsorters" disease, is a highly fatal disseminated infection characterized by cyanosis, dyspnoea, mediastinitis and haemoptysis. The illness is bi-phasic and initially consists of an insidious onset of mild fever, malaise fatigue, myalgia, non-productive cough and a feeling of sub sternal oppression. This phase lasts several days before the acute onset of a second stage consisting of dyspnoea cyanosis, stridor and shock. Plural effusions and widening of the mediastinum are characteristic. These changes follow the inhalation of the bacillus spores. The inhaled spores do not secrete the toxin before germination and cause little inflammatory reaction. The spores germinate into bacilli as they are transported to the hilar and mediastinal lymph notes, where they cause haemorrhagic necrosis and edema. As the haemorrhagic necrosis extends to the pleura, bloody pleural effusions occur.

Less than 5% of anthrax cases may be complicated by meningitis, which can occur after any of the forms of anthrax infection.

The drug of choice is intravenous penicillin and therapy should be continued for two weeks. For the penicillin allergic patients ciprofloxacin or doxycycline is a satisfactory alternative.

If there is a suspicion that spores are being used in biological warfare, prophylaxis with ciprofloxacin or doxycycline may be given to susceptible non-immunized patients.

Both attenuated live vaccine and a killed vaccine have been developed. The vaccine used in the United States is a sterile filtrate of cultures from an avirulent non-encapsulated strain that incorporates the protective antigen. Effectiveness is around 93%. Since 1998 the United States armed forces have been vaccinated against anthrax.

The mortality rate from cutaneous anthrax in the absence of antibiotic treatment is 10% to 20%. In contrast, the mortality from inhalation anthrax is approaching one hundred percent and treatment is usually not successful. The mortality for treated gastrointestinal disease is about 50%. Anthrax meningitis is usually fatal.