Anthrax: Symptoms,causative agents,diagnosis and treatment

For centuries, anthrax has been known as a zoonotic disease of herbivorous livestock (sheep, cattle, and goats). It has an important place in the history of medical microbiology because Robert Koch used anthrax as a model for developing his postulates in 1877 and, later, Louis Pasteur used the disease to prove the usefulness of vaccination.

Signs and Symptoms

As just noted, anthrax infection can exhibit its primary symptoms in various locations of the body: on the skin (cutaneous anthrax), in the lungs (pulmonary anthrax), in the gastrointestinal tract (acquired through ingestion of contaminated foods), and in the central nervous system (anthrax meningitis). The cutaneous and pulmonary forms of the disease are the most common.

In all of these forms, the anthrax bacterium gains access to the bloodstream, and death, if it occurs, is usually a result of an overwhelming septicemia. Pulmonary anthrax—and the accompanying pulmonary edema and hemorrhagic lung symptoms—can sometimes be the primary cause of death, although it is difficult to separate the effects of septicemia from the effects of pulmonary infection. In addition to symptoms specific to the site of infection, septicemic anthrax results in headache, fever, and malaise. Bleeding in the intestine and from mucous membranes and orifices may occur in late stages of septicemia.

Causative Agent

Bacillus anthracis is a gram-positive endospore-forming rod that is among the largest of all bacterial pathogens. It is composed of block-shaped, angular rods 3 to 5 micrometers long and 1 to 1.2 micrometers wide. Central spores develop under all growth conditions except in the living body of the host. The genus Bacillus is aerobic and catalase positive, and none of the species are fastidious. Bacillus asa group is noted for its versatility in degrading complex macromolecules, and it is also a common source of antibiotics. Because the primary habitat of many species, including B. anthracis, is the soil, spores are continuously dispersed by means of dust into water and onto the bodies of plants and animals.

 

Pathogenesis and Virulence Factors

The main virulence factors of B. anthracis are its polypeptide capsule and what is referred to as a “tripartite” toxin—an exotoxin “complex” composed of three separate proteins. One of the proteins is called edema factor, an enzyme that acts as an adenylylcyclase, interfering with cellular metabolism by causing the production of high levels of cyclic AMP. Excess cyclic AMP leads to excess cellular secretion and other pathologic effects. Another part of the toxin is protective antigen, so named because it is a good target for vaccination, not because it protects the bacterium or the host directly. It helps the edema factor get to its target site. The third exotoxin is called lethal factor. It also uses enzymatic action to inhibit important cellular processes.

The end result of lethal factor action is massive inflammation and initiation of shock. The B. anthracis exotoxin complex is like other bacterial “A-B toxins,”. Most A-B toxins have two components: a “B” component that binds to host cells and an “A,” or active, component that enters the cell and exerts some toxic effect. B. anthracis is a bit different; its protective antigen is the B component, and both lethal factor and edema factor are A components. The bacteria that cause cholera, shigellosis, pertussis, and diphtheria all use A-B exotoxins. Additional virulence factors for B. anthracis include hemolysins and other enzymes that damage host membranes.

Transmission and Epidemiology

The anthrax bacillus is a facultative parasite that undergoes its cycle of vegetative growth and sporulation in the soil. Animals become infected while grazing on grass contaminated with spores. When the pathogen is returned to the soil in animal excrement or carcasses, it can sporulate and become a long-term reservoir of infection for the animal population. The majority of natural anthrax cases are reported in livestock from Africa, Asia, and the Middle East.

Most recent (natural) cases in the United States have occurred in textile workers handling imported animal hair or hide or products made from them. Because of effective control procedures, the number of cases in the United States is extremely low (fewer than 10 per year). As a result of the terrorist attacks of 2001, anthrax has dominated the public consciousness as never before. The anthrax attack aimed at two senators and several media outlets focused a great deal of attention on the threat of bioterrorism. During that attack, 22 people acquired anthrax and 5 people died.

Culture and Diagnosis

Diagnosis requires a high index of suspicion. This means that anthrax must be present as a possibility in the clinician’s mind or it is likely not to be diagnosed, because it is such a rare disease in the developed world and because, in all of its manifestations, it can mimic other infections that are not so rare. (A very astute public health clinician in Florida first suspected anthrax in the attacks of 2001 and called for the proper tests.) First-level (presumptive) diagnosis begins with culturing the bacterium on blood agar and performing a Gram stain. Further tests can be performed to provide evidence regarding presence of B. anthracis as opposed to other Bacillus species. These tests include motility (B. anthracis is non motile) and a lack of hemolysis on blood agar. Ultimately, samples should be handled by the Centers for Disease Control and Prevention, which will perform confirmatory tests, usually involving direct fluorescent antibody testing and phage lysis tests.

Prevention and Treatment

A vaccine containing live spores and a toxoid prepared from a special strain of B. anthracis are used to protect livestock in areas of the world where anthrax is endemic. Humans should be vaccinated with the purified toxoid if they have occupational contact with livestock or products such as hides and bone or if they are members of the military. Effective vaccination requires six inoculations given over 1.5 years, with yearly boosters. The cumbersome nature of vaccination has spurred research and development of more manageable vaccines.

Persons who are suspected of being exposed to the bacterium are given prophylactic antibiotics, which seem to be effective at preventing disease even after exposure. Carcasses of animals that have died from anthrax must be burned or chemically decontaminated before burial to prevent establishing the microbe in the soil. Imported items containing animal hides, hair, and bone should be gas sterilized.

The recommended treatment for anthrax is penicillin, doxycycline, or ciprofloxacin. During the attacks in 2001, initial treatment of exposed and sick persons was with ciprofloxacin because of fear that the B. anthracis strains used in the attacks could have been penicillin-resistant, either through intentional genetic engineering or due to the natural presence of beta-lactamase genes in the bacterium. Ciprofloxacin treatment continued for the course of the 2001 incident. The CDC is now recommending the use of doxycycline instead of ciprofloxacin, because ciprofloxacin is often used for empirical treatment of all types of infections of unknown etiology. More frequent use of ciprofloxacin could lead to higher levels of antibiotic resistance in bacteria in the U.S. population, which would render ciprofloxacin less effective as an empirical agent.