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Anthrax

Ragpicker's disease, Wool sorter's disease, Black Baine, Malignant edema, Malignant pustule, Siberian Plague

Overview

Anthrax is an infection caused by the bacterium Bacillus anthracis. It can occur in four forms: skin, lungs, intestinal, and injection. Symptoms begin between one day and two months after the infection is contracted. The skin form presents with a small blister with surrounding swelling that often turns into a painless ulcer with a black center. The inhalation form presents with fever, chest pain, and shortness of breath. The intestinal form presents with diarrhea which may contain blood, abdominal pains, and nausea and vomiting. The injection form presents with fever and an abscess at the site of drug injection.

Anthrax is spread by contact with the bacterium's spores, which often appear in infectious animal products. Contact is by breathing, eating, or through an area of broken skin. It does not typically spread directly between people. Risk factors include people who work with animals or animal products, travelers, postal workers, and military personnel. Diagnosis can be confirmed based on finding antibodies or the toxin in the blood or by culture of a sample from the infected site.

Anthrax vaccination is recommended for people who are at high risk of infection. Immunizing animals against anthrax is recommended in areas where previous infections have occurred. Two months of antibiotics such as ciprofloxacin, levofloxacin, and doxycycline after exposure can also prevent infection. If infection occurs treatment is with antibiotics and possibly antitoxin. The type and number of antibiotics used depends on the type of infection. Antitoxin is recommended for those with widespread infection.

Although a rare disease, human anthrax, when it does occur, is most common in Africa and central and southern Asia. It also occurs more regularly in Southern Europe than elsewhere on the continent, and is uncommon in Northern Europe and North America. Globally, at least 2,000 cases occur a year with about two cases a year in the United States. Skin infections represent more than 95% of cases. Without treatment, the risk of death from skin anthrax is 24%. For intestinal infection, the risk of death is 25 to 75%, while respiratory anthrax has a mortality of 50 to 80%, even with treatment. Until the 20th century, anthrax infections killed hundreds of thousands of people and animals each year. Anthrax has been developed as a weapon by a number of countries. In plant-eating animals, infection occurs when they eat or breathe in the spores while grazing. Carnivores may become infected by eating infected animals

Symptoms - Anthrax

Most often, anthrax bacteria enter your body through a wound in your skin. You can also become infected by eating contaminated meat or inhaling the spores. The symptoms that occur because of anthrax depend on the way you're infected.

Cutaneous anthrax

In this form of anthrax, the spores enter your body through a cut or other sore on your skin. Cutaneous infections generally form within the site of spore penetration between 2 and 5 days after exposure. Unlike bruises or most other lesions, cutaneous anthrax infections normally do not cause pain. It's by far the most common form of the disease. It's also the mildest — with appropriate treatment, cutaneous anthrax is seldom fatal. Symptoms of cutaneous anthrax include:

  • A raised, itchy bump resembling an insect bite that quickly develops into a painless sore with a black center
  • Swelling in the sore and nearby lymph glands

Gastrointestinal anthrax

You contract this form of anthrax by eating undercooked meat from an infected animal. Signs and symptoms include:

  • Nausea
  • Vomiting, which is often bloody in the later stages of the disease
  • Loss of appetite
  • Fever
  • Severe, bloody diarrhea in the later stages of the disease
  • Sore throat and difficulty swallowing
  • Swollen neck

Inhalation (pulmonary) anthrax

Inhalation anthrax (also known as Woolsorters' or Ragpickers' disease) develops when you breathe in anthrax spores. It's the most deadly form of the disease and even with treatment is often fatal. Initial signs and symptoms of inhalation anthrax include:

  • Flu-like symptoms, such as sore throat, mild fever, fatigue and muscle aches, which may last a few hours or days
  • Mild chest discomfort

As the disease progresses, you may experience:

  • High fever
  • Trouble breathing
  • Shock
  • Meningitis — a potentially life-threatening inflammation of the brain and spinal cord

The most serious complication of anthrax is a fatal inflammation of the membranes and fluid covering the brain and spinal cord, leading to massive bleeding (hemorrhagic meningitis).

Causes - Anthrax

Anthrax is caused by an infection with the spores of a bacterium called Bacillus anthracis. The bacterium multiplies within the host and produces during this process the deadly anthrax toxin. Killing the bacteria through antibiotics at an early state of the infection is vital, otherwise too much of anthrax toxin is produced in the body of the patient, which leads to organ failure and death.

Bacillus anthracis is a rod-shaped, Gram-positive, aerobic bacterium that is about 1 by 9 micrometers in length. Like many other members of the genus Bacillus, Bacillus anthracis can form dormant endospores, which are able to survive in harsh conditions for decades or even centuries. The spores can remain dormant for years until they find their way into a host — usually wild or domestic livestock, such as sheep, cattle, horses, goats and camels. Although rare in the United States, anthrax is still common throughout the developing world, especially sub-Saharan Africa.

Viable bacteria hatch out of these spores as soon as they encounter a suitable environment. This can also mean an infection with Bacillus anthracis, if the spores are inhaled, ingested, or come into contact with a skin lesion.

Herbivores are often infected whilst grazing or browsing. Anthrax commonly infects wild and domesticated herbivorous mammals, but humans can contradict anthrax by direct contact (e.g. inoculation of infected blood to broken skin) or consumption of a diseased animal's flesh. Once ingested or placed in an open cut, the bacterium begins multiplying inside the animal or human and typically kills the host within a few days or weeks. The endospores germinate at the site of entry into the tissues and then spread via the circulation to the lymphatics, where the bacteria multiply.

The infection of herbivores (and occasionally humans) via the inhalational route normally proceeds as follows: once the spores are inhaled, they are transported through the air passages into the tiny air particles sacs (alveoli) in the lungs. The spores are then picked up by scavenger cells (macrophages) in the lungs and are transported through small vessels (lymphatics) to the lymph nodes in the central chest cavity (mediastinum). Damage caused by the anthrax spores and bacilli to the central chest cavity can cause chest pain and difficulty breathing. Once in the lymph nodes, the spores germinate into active bacilli which multiply and eventually burst the macrophages, releasing many more bacilli into the bloodstream to be transferred to the entire body. Once in the blood stream, these bacilli release the three compound anthrax toxin.

The anthrax toxin consists out of the three proteins named lethal factor, edema factor and protective antigen. All three are non-toxic by themselves, but the combination is incredibly lethal to humans. Protective antigen combines with these other two factors to form lethal toxin and edema toxin, respectively. These toxins are the primary agents of tissue destruction, bleeding, and death of the host. If antibiotics are administered too late, even if the antibiotics eradicate the bacteria, some hosts will still die of toxemia. This is because the toxins produced by the bacilli remain in their system at lethal dose levels.

Protective antigen binds to two surface receptors on the host cell. A cell protease then cleaves the protective antigen into two fragments: PA20 and PA63. PA20 dissociates into the extracellular medium, playing no further role in the toxic cycle. PA63 then oligomerizes with six other PA63 fragments forming a heptameric ring-shaped structure named a prepore. Once in this shape, the complex can competitively bind up to three edema factor or lethal factor forming a resistant complex. Receptor-mediated endocytosis occurs next, providing the newly formed toxic complex access to the interior of the host cell. The acidified environment within the endosome triggers the heptamer to release the lethal factor and/or edema factor into the cytosol.

It has been shown that lethal toxin suppresses proinflammatory cytokine production in macrophages by inhibiting transcription of cytokine messenger RNA, even at extremely low levels of lethal toxin. Thus, one way lethal toxin causes the disease anthrax is by suppressing the inflammatory response. Another action of lethal toxin is to lyse macrophages, which are one of the body's important defense mechanisms against invading organisms. Lethal factor is a zinc-binding protein with metalloproteinase activity. The MAP kinase kinases Mek1 and Mek2 are macrophage proteins that interact with it. Lethal factor cleaves Mek1 and Mek2 and an additional related factor MKK3.

To contract anthrax, you must come in direct contact with anthrax spores. This is more likely if you:

  • Are in the military and deployed to an area with a high risk of exposure to anthrax
  • Work with anthrax in a laboratory setting
  • Handle animal skins, furs or wool from areas with a high incidence of anthrax
  • Work in veterinary medicine, especially if you deal with livestock
  • Handle or dress game animals — in the United States, seasonal outbreaks of anthrax are common among livestock and game animals, such as deer

Prevention - Anthrax

Antibiotics are recommended to prevent infection in anyone exposed to the spores. Ciprofloxacin and doxycycline are approved by the Food and Drug Administration for post-exposure prevention of anthrax in adults and children. Levofloxacin is also approved for use in adults.

Anthrax vaccine

An anthrax vaccine for humans is available, but it's not 100 percent effective. The vaccine doesn't contain live bacteria and can't lead to infection, but it can cause side effects, ranging from soreness at the injection site to more-serious allergic reactions. The vaccine isn't recommended for children, pregnant women or older adults.

Traditionally, vaccination has consisted of three shots given two weeks apart, followed by three additional shots given at six, 12, and 18 months. But some research has shown that a less stringent schedule may be equally effective with fewer side effects.

The vaccine isn't intended for the general public. Instead, it's reserved for military personnel, scientists working with anthrax and people in other high-risk professions.

Avoiding infected animals

If you live or travel in a country where anthrax is common and herd animals aren't routinely vaccinated, avoid contact with livestock and animal skins as much as possible. Also avoid eating meat that hasn't been properly cooked.

Even in developed countries, it's important to handle any dead animal with care and to take precautions when working with or processing imported hides, fur or wool.

Diagnosis - Anthrax

Your doctor will first want to rule out other, more common conditions that may be causing your signs and symptoms, such as flu (influenza) or pneumonia. You may have a rapid flu test to quickly diagnose a case of influenza. If other tests are negative, you may have further tests to look specifically for anthrax, such as:

  • Skin testing. A sample of fluid from a suspicious lesion on your skin or a small tissue sample (biopsy) may be tested in a lab for signs of cutaneous anthrax.
  • Blood tests. You may have a small amount of blood drawn that's checked in a lab for anthrax bacteria.
  • Chest X-ray or computerized tomography (CT) scan. Your doctor may request a chest X-ray or CT scan to help diagnose inhalation anthrax.
  • Endoscopy and stool samples. To diagnose intestinal anthrax, your doctor may examine your throat or intestine with an endoscope — a thin, flexible tube with a tiny camera at its tip. In some cases, a sample of your stool may be checked for anthrax bacteria.
  • Spinal tap (lumbar puncture). In this test, your doctor inserts a needle into your spinal canal and withdraws a small amount of fluid. A spinal tap is usually done only to confirm a diagnosis of anthrax meningitis.

 

Prognosis - Anthrax

A prognosis is a medical opinion as to the likely course and outcome of a disease, or the chance that a patient will recover. Many factors affect a person's prognosis.

The doctor may speak of a favorable anthrax prognosis if the condition is likely to respond well to anthrax treatment. The anthrax prognosis may be unfavorable if the anthrax is likely to be difficult to control. It is important to keep in mind, however, that a prognosis is only a prediction. The doctor cannot be absolutely certain about the outcome for a particular patient.

The anthrax prognosis will depend on a number of factors, including:

  • The type of anthrax (see Types of Anthrax)
  • How early the anthrax is diagnosed
  • The strain of anthrax bacteria (Bacillus anthracis)
  • The patient's age and general health.

Early anthrax treatment for all anthrax types improves the anthrax prognosis.

Cutaneous Anthrax Prognosis

Cutaneous anthrax is usually cured with anthrax treatment. The cutaneous anthrax death rate is 20 percent without antibiotic treatment and less than 1 percent with it.

Inhalation Anthrax Prognosis

There have not been enough cases of inhalation anthrax to know the specific anthrax prognosis. Although death rates for inhalation anthrax are based on incomplete information, the rate is extremely high, approximately 75 percent, even with all possible supportive care including appropriate antibiotics.

Gastrointestinal Anthrax Prognosis

For gastrointestinal anthrax, the death rate is estimated to be 25 to 60 percent. The impact of early antibiotic treatment on the anthrax death rate is unknown.

Treatment - Anthrax

Anthrax cannot be spread directly from person to person, but a person's clothing and body may be contaminated with anthrax spores. Effective decontamination of people can be accomplished by a thorough wash-down with antimicrobial soap and water. Waste water should be treated with bleach or another antimicrobial agent. Effective decontamination of articles can be accomplished by boiling them in water for 30 minutes or longer. Chlorine bleach is ineffective in destroying spores and vegetative cells on surfaces, though formaldehyde is effective. Burning clothing is very effective in destroying spores. After decontamination, there is no need to immunize, treat, or isolate contacts of persons ill with anthrax unless they were also exposed to the same source of infection.

Antibiotics

Early antibiotic treatment of anthrax is essential; delay significantly lessens chances for survival.

Treatment for anthrax infection and other bacterial infections includes large doses of intravenous and oral antibiotics, such as fluoroquinolones (ciprofloxacin), doxycycline, erythromycin, vancomycin, or penicillin. FDA-approved agents include ciprofloxacin, doxycycline, and penicillin.

In possible cases of pulmonary anthrax, early antibiotic prophylaxis treatment is crucial to prevent possible death.

In recent years, many attempts have been made to develop new drugs against anthrax, but existing drugs are effective if treatment is started soon enough.

Monoclonal antibodies

In May 2009, Human Genome Sciences submitted a biologic license application (BLA, permission to market) for its new drug, raxibacumab (brand name ABthrax) intended for emergency treatment of inhaled anthrax. On 14 December 2012, the US Food and Drug Administration approved raxibacumab injection to treat inhalational anthrax. Raxibacumab is a monoclonal antibody that neutralizes toxins produced by B. anthracis. On March, 2016, FDA approved a second anthrax treatment using a monoclonal antibody which neutralizes the toxins produced by B. anthracis. Obiltoxaximab is approved to treat inhalational anthrax in conjunction with appropriate antibacterial drugs, and for prevention when alternative therapies are not available or appropriate.

Resources - Anthrax

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