1. Anthrax Human anthrax is typically an ulcerative sore on an exposed part of the body. Constitutional symptoms are minimal, and the ulcer usually resolves without complications. If anthrax spores are inhaled, a fulminant pneumonia may lead to respiratory failure and death.

2. EPIDEMIOLOGY Anthrax is primarily a disease of herbivores such as horses, sheep, and cattle who acquire it from spores of B. anthracis contaminating their pastures. Humans become infected through contact with these animals or their products.

3. PATHOGENESIS B. anthracis spores introduced into the body by abrasion, inhalation or ingestion are phagocytosed by macrophages and transported from the site of infection to regional lymph nodes, where the spore germinate and vegetative bacteria multiply. The bacilli then enter the bloodstream causing septicaemina, with upto 10 8 colony forming units/mL of blood. The antiphagocytic properties of the capsule aid in survival, eventually allowing production of large enough amounts of the exotoxins to cause disease. The adenylate cyclase activity is believed to correlate with the striking edema seen at infected sites.

4. Virulence factor The pahogenicity of the of B. anthracis depends primarily on two major virukence factors: 1. The poly-D-glutamic capsule 2. The toxin complex comrising three proteins: the protective antigen, oedema factor and lethal factor Capsule increases virulence by preventing phagocytosis. The tree componets of the tripartite toxin combine to form binary toxins, the oedema toxin and lethal toxin, formed by the association of the protective antigen with the oedema factor and lethal factor respectively. In each case the protective antigens binds to host cells and facilitates the entry of the associated oedema and lethal factor.

5. Virulence factor Oedema factor is a calmoduli-dependent adenylate cyclase that catalyzes the production of intracellular cyclic adensine monophosphate (cAMP), inducing interleukin-6(IL-6) and inhibiting tumor necrosis factor-α (TNF- α) in monocytes. In addition to disrupting cytokine responses, the oedema toxin may also increase hos susceptibility to infection by impairing neutrophil functions. However, it is the lethal toxin that is believed to play major role in damage to the host and death.

6. The lethal factor is a Zinc metalloprotease that inactivate nitrogen-activated protein kinase, particularly in macrophages. The lethal toxin stimulates macrohages to produce IL-1β and TNF- α. During infection IL-1β accumulates in the macrophages and TNF- α is released. As the concentration of the lethal toxin increases later in the infection process, macrophages lysis produces a sudden release of IL-1β causing shock and death.

8. A N T H R A X : C L I N I C A L A S P E C T S Cutaneous anthrax usually begins 2 to 5 days after inoculation of spores into an exposed part of the body, typically the forearm or hand. The initial lesion is an erythematous papule, which may be mistaken for an insect bite. This papule usually progresses through vesicular and ulcerative stages in 7 to 10 days to form a black eschar (scab) surrounded by edema.

9. Pulmonary anthrax is contracted by inhalation of spores. In the pulmonary syndrome, 1 to 5 days of nonspecific malaise, mild fever, and nonproductive cough lead to progressive respiratory distress and cyanosis. Massive spread to the bloodstream and CNS follow rapidly. If untreated, progression to a fatal outcome is usually very rapid once bacteremia has developed.

10. DIAGNOSIS Culture of skin lesions, sputum, blood, and CSF are the primary means of anthrax diagnosis. Blood cultures are positive in most cases of pulmonary anthrax.

11. TREATMENT Antimicrobial treatment has little effect on the course of cutaneous anthrax but does protect against dissemination. Almost all strains of B. anthracis are susceptible to penicillin, which remains the treatment of choice for all forms of anthrax. Doxycycline or ciprofloxacin are alternatives and are also recommended for chemoprophylaxis in the case of known or suspected exposure.

12. PREVENTION The most important preventive measures are those that eradicate animal anthrax and limit imports from endemic areas. Vaccines are also useful. Pasteur’s vaccine used a live strain attenuated by repeated subculture that resulted in the loss of a plasmid encoding toxin production. Proof of the efficacy of the vaccine in humans is neither practical nor ethical.