Anthrax overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]

Overview

Anthrax (Greek Άνθραξ for coal) is an acute infectious disease in humans and animals that is caused by the bacterium Bacillus anthracis and is highly lethal in some forms. Anthrax is one of only a few bacteria that can form long lived spores. When the bacteria s life cycle is threatened by factors such as lack of food caused by their host dying or by a change of temperature, the bacteria turn themselves into a dormant spores to wait for another host to continue their life cycle.

When breathing, ingesting or getting anthrax spores in a cut in the skin, these spores reactivate themselves and multiply in their new host very rapidly. The anthrax spores in the soil are very tough, can live many decades and are known to occur on all continents except Antarctica. Anthrax most commonly occurs in wild and domestic grass eating mammals (ruminants) who ingest or breathe in the spores while eating grass. Anthrax can also infect humans when they are exposed to dead infected animals, eat tissue from infected animals, or are exposed to a high density of anthrax spores from an animal's fur, hide, or wool. Anthrax spores can be grown outside the body and used as a biological weapon. Anthrax cannot spread directly from human to human; but anthrax spores can be transported by human clothing, shoes, among others. If a person dies of anthrax their body can be a very dangerous source of anthrax spores. The word anthrax is the Greek word for coal, the germ's name is derived from anthrakitis, the Greek word for anthracite, in reference to the black skin lesions victims develop in a cutaneous skin infection.

Historical Perspective

Anthrax, caused by Bacillus anthracis, is thought to have originated in Egypt around 1250 BC. Described as being a disease affecting horses, camels and sheep, anthrax had an impact on great civilizations, such as the Greek and Roman. It was described clinically for the first time by Maret in 1752 and Fournier in 1769. In 1877, based upon his studies with Bacillus anthracis, Robert Koch was able to demonstrate what became known as Koch’s postulates. In 1881, Louis Pasteur worked to create a vaccine for anthrax, which he was able to test with success in animals. In 1900, due to the great amount of knowledge gathered during the 1800s, anthrax cases were well documented in the US, UK and Germany. In 1944, penicillin was first used to treat anthrax. The first commercial vaccine to prevent anthrax in humans was created in 1950s. In the past 10 years there have been a few reported cases in the US, specifically in 2006 in NYC, 2009 in Connecticut and in 2011 in Florida. Anthrax has also been used throughout history as a biologic weapon and there has been efforts to create and enforce legislation to avoid disastrous outbreaks of the disease. For that, a Convention on the Prohibition of the Development, Production, and Stockpiling of Biological and Toxin Weapons and on Their Destruction was created and later ratified in April of 1972, with more than 100 nations signing it, including Iraq, the United States, and the Soviet Union.

Pathophysiology

The genetic material of Bacillus anthracis is coded within 1 chromosome and 2 plasmids that are fundamental for its toxicity. The spores of B. anthracis are the infectious form and can remain dormant in the environment for decades. The bacterium causes disease through 2 mechanisms: toxemia and bacterial infection. B. anthracis begins to produce toxins within hours of germination. Protective antigen (PA) and edema factor (EF) combine to form edema toxin (ET), and PA and lethal factor (LF) combine to form lethal toxin (LT). Bacterial toxins have a direct cytotoxic effect by interfering with cellular pathways and they are also responsible for weakening the immune system so thr initial systemic infection may occur. Anthrax lesions at any site are featured by extensive necrosis and confluent exudate containing macrophages and neutrophils. In histopathological specimens or culture media, the presence of large boxcar-shaped Gram-positive bacilli in chains, suggests the diagnosis.

Differentiating Anthrax from other Diseases

The differential diagnosis of anthrax includes a wide range of infectious and non-infectious conditions depending on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation, injection). A history of exposure to contaminated animal materials, occupational exposure, and living in an endemic area is crucial when considering a diagnosis of anthrax. Additional tests that isolate Bacillus anthracis are needed to differentiate anthrax from other differential diagnose and confirm the diagnosis.

Epidemiology and Demographics

Incidence of the natural disease in humans is dependent on the level of exposure to affected animals and, for any one country, national incidence data for non-industrial cases reflect the livestock situation. Human case rates for anthrax are highest in Africa and Central and Southern Asia. While, statistically, in Northern Europe and countries with similar epidemiological situations, there is one human cutaneous case per every 10 livestock carcasses butchered, there can be some 10 human cutaneous and enteric cases per single carcass butchered in Africa, India, and the Southern Russian Federation.

Risk Factors

Risk factors for contracting anthrax include handling of livestock or livestock products, playing animal hide drums, working in a laboratory researching anthrax, and traveling to an endemic region such as Central and South America, Sub-Saharan Africa, Central and southwestern Asia, Southern and eastern Europe, or the Caribbean. Risk factors for anthrax in the setting of bioterrorism are working as a mail handler, military personnel, or response worker.

Natural History, Complications and Prognosis

The natural history of anthrax depends on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation, injection). In cutaneous anthrax, a small painless skin sore develops into a blister and later into a skin ulcer, with a black area at the center. The resolution of the lesion takes several weeks and the time to resolution depends on the size, location and local severity of the lesion. The anthrax lesions might lead to scarring and contractures. Inhalation anthrax is characterized by a mild initial phase of nonspecific symptoms that is followed by the sudden development of dyspnea, cyanosis, disorientation with coma, and death. In oropharyngeal anthrax, the lesion is generally localized in the oral cavity. The illness in oropharyngeal anthrax may progress rapidly, and edema around the lymph node may result in extensive swelling of the neck and anterior chest wall. The gastrointestinal anthrax lesions may occur anywhere within the gastrointestinal tract and they may bleed leading to fatal hemorrhage. Some cases are complicated with massive ascites and this leads to shock and death. The prognosis in anthrax depends on the type of anthrax, how early the anthrax is diagnosed, the strain of the bacteria, and the patient's age and health condition. The pulmonary anthrax is the one with highest mortality rate.

Diagnosis

History and Symptoms

The symptoms of anthrax infection depend on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation, injection). The cutaneous type of anthrax is characterized by a skin blister that evolves into an ulcer with a black center, muscle pains, fever, and vomiting. The gastrointestinal type may include symptoms of fever, chills, sore throat, painful swallowing, and abdominal pain. The symptoms of the inhalation type of anthrax are fever, chills, fatigue, sore throat, and shortness of breath. The symptoms of the injection type are usually similar to those of cutaneous anthrax; however, the disease may spread through the body faster. The symptoms of the injection type of anthrax include fever, chills, skin ulcer, and subcutaneous or muscular abscess.

Physical Examination

The physical findings of anthrax infection depend on the mode of anthrax exposure in the patient (cutaneous, ingestion, inhalation, injection). Common findings associated with cutaneous anthrax infection include fever, tachycardia, skin rash with formation of a typical scar, edema and lymphadenopathy; with gastrointestinal anthrax infection include fever, tachycardia, mucosal ulcer and edema in case of oropharyngeal lesion and edema and pallor in more severe cases; with inhalation anthrax infection includes: fever, tachycardia, bradypnea in severe cases, pallor, cyanosis and decreased heart and lung sounds in the presence of pleural effusion; and with anthrax infection due to injection include fever, typical skin scar at the site of injection, edema and subcutaneous and/or muscular abscess.

Laboratory Findings

When systemic anthrax is present, abnormalities in laboratory tests include anemia, thrombocytopenia, and leukocytosis particularly in the latter stages of the disease. Other laboratory findings are hyponatremia, increased BUN, elevated transaminase levels, hypoalbuminemia, and elevated troponin. Cell cultures from blood, CSF, or pleural fluid can identify the organism and possibly the toxins. In injection anthrax, the typical laboratory finding is an inflammatory pattern with a low CRP. A normal PT/PTT at admission does not exclude coagulopathy nor DIC.

Chest X Ray

Chest X-ray is a sensitive diagnostic test for inhalation anthrax. Chest X-ray abnormalities associated with inhalation anthrax include mediastinal widening, paratracheal fullness, pleural effusions, parenchymal infiltrates, and mediastinal lymphadenopathy.

CT

The chest CT scan findings in anthrax include mediastinal widening, hyperdense lymph nodes, and edema of the mediastinal fat.

Other Diagnostic Studies

Several studies are used for the diagnosis and monitoring of anthrax. The polymerase chain reaction (PCR) test is ordered to confirm the virulence of the organism. In addition, lumbar puncture should be performed on admission when it is not contraindicated to search for the organism in the cerebrospinal fluid (CSF) and to to exclude other alternative diagnoses. Other diagnostic studies include an electrocardiogram and an echocardiogram to assess possible complications of anthrax such as atrial fibrillation and pericardial effusion.

Treatment

Medical Therapy

Medical therapy of anthrax infection includes antibiotic and antitoxin drugs. Patients should be treated with a multiple antibiotic regimen (≥3 drugs) for 60 days to avoid the creation of drug resistant species and ensure the elimination of remaining spores of the bacteria. These patients should be monitored at all times to evaluate the need for supportive care measures, such as hemodynamic support, mechanical ventilation, corticosteroids, procedures, and surgical interventions in certain occasions.