Anthrax is a rare but serious infectious disease caused by an anaerobic gram-positive, rod-shaped bacteria known as “Bacillus Anthracis”. It is a spore-forming bacterium which may affect livestock and humans. Although it is rare, people can get sick if they come in close contact with infected animals or contaminated animal products. We chose to discuss this topic, this month, because of many cases recently discovered in our country, in area like Jeremie, Haiti, where the disease is endemic.
I remember like it was yesterday the first time I saw the manifestations of this disease in a 42-year-old gentleman farmer examined with the Late Raoul Pierre-Louis MD, dermatologist, Dean of the Medical school and chief of the Department of Dermatology. Our group of externs was performing in a mandatory rotation in the external clinic of Dermatology and we were eager to learn. We looked for appropriated gloves to satisfy our curiosity and palpated a painless lesion on the patient’s right forearm. We understood then, that he was constantly in contact with horses and has recently lost two animals without being able to understand the reason behind their death. I was told that the skin lesions were strongly contaminant especially when a “pustule” was present, but it is clear to me that Science has no proof that one could be contaminated by another human being.
The term anthrax comes from the Greek word for “coal” because of the color black of the skin lesions. The black eschar has been the hallmark of the disease in its cutaneous manifestation. The English were the first to coin the word ‘anthrax’ in 1938. but other names have surfaced through the years like “Siberian plaque”, “Cumberland disease”, “Charbon”, “Splenic fever”, “Malignant Edema”, “wool sorter’s disease” and “La maladie de Bradford”.
In Wolsztyn, Poland, a German physician and scientist, Robert Koch, identified a bacterium responsible for the disease in 1875 and he established for the first time, a relation between the clinical symptoms and the infectious agent. He studied the mechanism of the disease, uncovered the lifecycle and the means of transmission. His work awarded him the Nobel Prize in Physiology and Medicine in 1905, for his discovery at a period when scientists were still believing in a “spontaneous generation” theory. Koch went on to study another bacillus related to Tuberculosis, and coined his name to it. Other physicians were more concerned on how to prevent the animals or the humans from catching the disease. John Henry Bell, a physician based in Bradford made the link between the” wool sorters” and the Anthrax disease in 1878. but it was a German bacteriologist, Friederich Wilhelm Eurich who elucidated the problem of industrial anthrax. He was instrumental also in dressing the Anthrax Prevention Act in 1919.
Anthrax is a rare human disease which can be seen in underdeveloped countries like Haiti or any other countries lacking public-health regulations preventing exposure to infected goats, cattle, sheep and horses. The disease can be also seen in dogs and cats. It is most common in Africa and Southern Asia and occasionally can be seen in Southern Europe. The disease is very uncommon in the United States and Northern Europe. Around the world, 2,000 cases a year are reported while only 2 cases have been discovered in the United States.
Drum players, drum makers and their family have been infected by close contact. Veterinarians, farmers, travelers visiting areas where anthrax is endemic, laboratory personnel, mail handlers, military personnel, individual trained in bioterrorist and biological warfare are all at risk to develop the disease when exposed to the bacteria. In bioterrorism, there is an intentional will to release biological agents like viruses, germs or bacteria. Anthrax is one of the disease caused by this intention like botulism, plague, smallpox, brucellosis, ricin toxin poisoning, cholera, epidemic typhus, viral encephalitis, tuberculosis to name only some. Concentrated anthrax spores were used for bioterrorism in 2001 anthrax attacks in the United States and delivered by mailing letters containing the spores to media news offices and two democratic senators. As a result, 22 were infected and 5 died. It seems that only 2 grams of material were used to carry the attack. Now the US Postal Service has installed biohazard detection systems at his major distribution center to scan for anthrax.
Anthrax can infect a host in four ways:
1- Through the skin with the presence of a dark sore.
2- Humans and animals can contract it from carcasses of dead animal previously contaminated with Anthrax. Ingesting the bacteria can cause serious contamination and death.
3- The inhalation of the spores brings the deadliest form of the disease. Once inhaled, they migrate to the lymph nodes in the chest and proliferate and spread in producing toxins causing death.
4- A new form by injection has been described in heroin drug abusers.
Skin infection is the more common manifestation, seen in 95 % of the cases. Without any treatment, the risk of death from a cutaneous anthrax ranges in the 24%, while the risk of death in anthrax involving the gastrointestinal tract ranges in the 25 to 75%. The risk of death in respiratory anthrax is 50 to 75 % even with appropriated treatment. Prior to the 20th century, anthrax infections killed hundreds of people and animals each year but now that the bacillus has been used as a weapon of mass destruction, we would expect the number to grow extensively. Animal eating plants can breathe the spores while grazing and carnivores may ingest meat of an infected animal with the bacteria and contract the disease. Spores can survive in harsh conditions for many years. In such form, it has been found on all continents, included Antarctica.
Occupational exposure to infected animal or their products (skin, wool, meat) is the usual pathway for exposure to a human being. Workers who are exposed to dead animals carrying the disease are at risk for contamination. Anthrax in livestock grazing especially when wild animals are kept together, can happen in the United States or elsewhere. Generally, it is believed that workers dealing with wool are constantly exposed to anthrax spores but the exposure level may not be sufficient for them to develop an Anthrax infection. The inhalation of at least 10.000 to 20,000 spores can result in such infection. In the past, those workers, victims of inhalation of the anthrax spores, were called “wool sorters”, as an occupational hazard. Nowadays, this form is extremely rare because of almost, the absence of animals with anthrax.
It is obvious that one does not find evidence that Anthrax can be transmitted from person to person, but it is possible especially when we know that the skin lesions found in the disease may be contagious at the pustule stage, through direct contact. It is expected that a brake in the texture of the recipient’s skin may allow the penetration of the bacillus, then exceptionally transmit the disease. Anthrax is a life–threatening disease affecting animal’s ruminants like goats, sheep and horses. The bacillus is a Gram positive, anaerobic rod able to survive in a form of spores, very resistant and difficult to destroy. The bacteria were able to secret three toxins in form of proteins: Protective antigen, Lethal factor, and Edema factor which when combined together, present a menace to the one inhaling the spores.
In recent years the bacillus of Anthrax has received a lot of publicity for its involvement in terrorist attacks. In fact, it is little known that the bacillus of Anthrax has been used as a weapon for the last hundred years. In 1916, the Nordic Rebels, supported by the German General Staff used anthrax spores in Finland against the Imperial Army. In the 1930s, the Japanese Kwantung Army, in Manchuria, performed testing on prisoners of war, killing thousands. Anthrax was investigated as “Agent N”, by the allies in 1940. In 1942, Brittish bioweapons trials severely contaminated Gruinard Island. in Scotland with anthrax spores of the” Vollum-14578 strain” until it was decontaminated in 1990. An N-bomb containing dried anthrax spores, and 5 millions of cattle cakes (pellets impregnated with anthrax spores) were prepared for contamination of the cattle in Germany, and expected to be dropped by the Royal Air force in 1944 with “Operation Vegetarian”. They were not used but needed to be incinerated in late 1945. They remained in stock until President Nixon ordered the dismantling of the US bio warfare program in 1969.
We know well the involvement of the CIA in delivering to the anti-Castro rebels, spores of anthrax to start the destruction of the pigs on the island of Cuba. The weapon was delivered on a military base in Panama and transported to the island of La Navase, and then to Guantonamo. The infestation of the pigs was successful necessitating the killing of 200.000 animals was necessary to avoid the propagation of anthrax to the entire island of Cuba. (Reported in AMHE Newsletter # 261: 9-2-19). In 1979, the Rhodesian government used anthrax against cattle and humans to fight the rebels. The Soviet Union created and stored almost 200 tons of anthrax at Kantubekon Vozrozhdeniya island. The project was abandoned in 1992 and the anthrax spores were destroyed in 2002.
In 2001, Anthrax was used for the first time in a mass mail delivery as a powder, in the United States and was spread through many postal service stations, infecting twenty-two (22) postal workers and killing 5. The spores of Anthrax do not spread generally from person to person either. In Sverdlovsk, Russia, an accidental release of anthrax from a biological weapon complex, exposed at least 94 persons on April 2nd 1979. At least 68 people died, some four days after, some a week after. The last fatal case of inhalation in the USA, occurred in California, in 1976 when a home weaver died after working with infected wool in provenance of Pakistan. The deceased person was bagged and transported to UCLA for autopsy. There have been many outbreaks recently in the world notably in Siberia, Russia (2016), killing 2000 reindeer and 13 Siberians. The authorities believed that this localized out brake was due to the fact that an infected reindeer which died 75 years ago, was unburied, causing the release of multiple spores.
The disease has a short period of incubation going from one to five days and rarely may take weeks before the infected individual become sick. Let us review the different types:
Cutaneous anthrax represents 90% of all cases. Some has called this phase “hide-porter disease” and it starts with a red spot that increase in size, presenting signs of inflammation, blistering and hardening. The center of the spot becomes itchy and ulcerated creating a crater with blood-tinged drainage followed by the formation of a black crust called eschar. This eschar is painless and some described it as a bread mold which falls of in weeks. The lymph nodes in the area becomes apparent and swollen. Soon they are painful and infected. The victims accuse then muscle aches and pain, headache, fever, nausea and vomiting. resolving in six weeks. Death may occur if proper treatment with antibiotics is not administered in time. It is the least dangerous form with a low mortality rate with treatment and with a 20% mortality rate without any treatment. This form is generally found when humans handled infected animals and their products. If appropriately treated, this form of anthrax is rarely fatal because the infection is mainly limited to the skin preventing the release of toxins that still can be seen in 20 % of the cases with subsequent toxemia.
Anthrax by inhalation, brings subtle and gradual signs of flu-like with sore-throat and headaches in a first stage and then the illness worsens in a few days into severe respiratory distress with shortness of breath, cough and chest pain. This form of catching the infection is rare. The disease attacks first the lymph nodes causing flu-like or cold symptoms. Soon, patient will demonstrate an increase in temperature, shortness of breath, cough, fatigue and chills. It is important to recognize the disease because fatalities from inhalation anthrax do happen if left untreated. A second stage will manifest with an unusual pneumonia, spreading from the lymph nodes and to the lungs in days following the original inhalation. It is not a true pneumonia. High fever and extreme shortness of breath can be seen. Patient can even cough blood until shock or coma ensues. The macrophages killed the spores or they get transported to the chest lymph nodes and into the lungs. Soon, the entire body is infected. Most affected (85%) at that stage will die if proper antibiotics are not immediately delivered to kill the bacteria but unfortunately not the deadly toxins already released through the body will be controlled.
In the herbivores or humans, the infection by inhalational route, will allow the inhaled spores to be transported to the air passage into the alveoli, in the lungs. The spores are picked up by the macrophages and directed through the lymphatic system into the mediastinum. Damage by the spores and the bacilli causes chest pain and difficulty in breathing. In the lymph nodes, the spores germinate into active bacilli to burst the microphages releasing more bacilli into the blood stream. Once in the blood stream, these bacilli release 3 endotoxins: Lethal Factor, Edema Factor, Protective antigen which in combination are very lethal to the humans while individually they are not offensive. They induced an extensive tissue destruction, bleeding and the death of the host if left untreated. During the 2001 anthrax attack, these considerations were taken on time and the fatality rate fell down to 45%. You need seriously to distinguish pulmonary anthrax from the more common causes of respiratory illness to avoid any delay in delivering the appropriated antibiotics and to improve the outcomes. Anecdotally, in 2008, a drum maker in the United Kingdom who generally works with untreated animal skin, died of anthrax by inhalation.
Gastrointestinal anthrax is the result of absorption of undercooked and contaminated meat with the bacillus. Patient soon becomes symptomatic with nausea, loss of appetite, bloody diarrhea and fever with intense abdominal pain and loss of appetite. Occasionally, bloody vomiting can be seen as well. The bacteria invade through the bowel wall and the infection spreads throughout the entire body via the bloodstream with a deadly toxicity. Lesions have been found in the intestines, the mouth and the throat. Gastrointestinal infections can be treated with appropriated antibiotics but results in fatality in 25 to 60% of the cases. This is the rarest form of transmission of Anthrax. Recent evidence indicates that anthrax targets the endothelial cells that line, the serous cavities such as the pericardium, the pleura, the peritoneal cavity, the lymphatic vessels and the blood vessels causing leakage of fluid and ultimately causes the hypovolemic shock and septic shock. Gastrointestinal anthrax is extremely rare in the United States. Only two cases have been reported. The first one was in 1942 and the second one in 2009. The CDC investigated the second case and found it related an African drum. She became critically ill with the spores hidden in the drum but developed a gastrointestinal form of the disease. She was fully treated and recovered.
A new form of anthrax has been identified in “heroin-injecting-drug-users” in Northern Europe but has not yet been reported in the United States. Symptoms may take days to months prior to surface in an itchy small blister or a bump at the injection site with local inflammation. Fever and chills will accompany the swelling around the sores. A deep abscess may be encountered under the skin or the muscle. Later, a painless skin sore with a black center may appear once the blister dry out. In 2009, such outbreak of the disease was seen among some heroin addicts in the Glasgow and Stirling areas of Scotland, killing 14. The source of the anthrax is believed to be the dilution of the heroin with bone meal from Afghanistan.
The diagnosis is made through the history; One has to take in consideration the type of occupation the victim practices. Smears for Gram stains and cultures may allow the recognition of the bacteria in the skin lesions, throat swabs and sputum may do the same in pulmonary anthrax. As we know already, the bacillus anthracis is a rod-shaped, Gram positive anaerobic, discovered by Robert Koch in 1876, when he took a blood sample from an infected cow. The bacterium normally rest under the form of a spore, in the soil and can survive for decades. Animal grazing can become infected. Once ingested or placed in an open wound, the bacteria begin multiplying inside the host and can kill it in a matter of days or weeks. The spores germinate at the site of entry into the tissues and spread to the circulation via the lymphatics where they multiply. The production of three powerful exotoxins by the bacteria, causes death. Most anthrax bacteria inside the body after death are outcompeted and destroyed by anaerobic bacteria within minutes to hours post mortem. However, anthrax vegetative bacteria that escape the body via oozing blood may form hardy spores as well but they are not contagious but hard to eradicate. Chest X-Rays may show characteristic changes in the lungs or mediastinum. One can also look for excessive fluid or edema in the parenchyma. In disseminated forms, blood cultures will reveal the bacteria responsible for the disease. Anthrax is a mandatory reportable disease. Local and state health agencies must be notified once diagnosed.
Longtime ago, all cases of anthrax would be kept in isolation or in quarantine but since Anthrax does not spread really from an infected human being to another generally, that practice has ceased. Early treatment in the disease, brings cure. Tetracycline, Erythromycin, Ciprofloxacin have all been successful in treating the cutaneous form of the disease. Continuous intravenous antibiotic therapy is lifesaving in the pulmonary form of anthrax. This becomes a medical emergency. A vaccine which has not been available to the public, exist already. This vaccine can be given to personnel employees or other victims who have been exposed to a bioterrorist attack. Four antibiotics have been recommended in individual exposed to aerosolized spores during any bioterrorism attacks: Doxycycline, Ciprofloxacin, Levofloxacin and parenteral procaine penicillin G coupled with a three dose series of anthrax vaccine. If a deceased person is suspected having died from anthrax, precautions should be taken to avoid skin contact with the contaminated body and fluids. The body should be placed in quarantine and blood samples should be collected to ascertain the cause of death and sealed in a container. The body should be incinerated.
The NIH approved a high efficiency respirator and disposable personal protective equipment, rubber gloves, rubber boots to handle such bodies. Preventive antibiotics have been suggested for individuals who have been exposed, as soon as possible. Two months of antibiotics such as Cipro or Doxycycline after exposure can also prevent infection or treat infection with possibly antitoxin. Even if anthrax does not spread directly from person to person, the person’s clothing or the body can be contaminated with anthrax spores. The use of antimicrobial soaps and water will allow a washout and the decontamination the clotting by boiling in water for at least 30 minutes. Formaldehyde and clothes burning are also effective in destroying the spores.
Vaccine against anthrax for use in livestock and in humans is well known in the history of medicine. Louis Pasteur, French scientist developed the first effective vaccine in 1881. The human anthrax vaccine comes from the Soviet Union in the late 1930’s. Later in the US and UK, in the 1950’s. The vaccine was approved by the FDA in 1960’s. These vaccines are different. A live vaccine (Russia) and an acellular vaccine (USA) are both used but present considerable local and systemic reactions like erythema, induration, soreness, fever. In the past, they were administered in 5 doses or in 6 doses with an annual booster but they failed to be effective. A New generation of vaccines is present on the market: Recombinant live vaccines and Recombinant subunit vaccines which have been used routinely to immunize military personnel in the United States and the United Kingdom. There are no public healthcare measures that can be taken to prevent contact with infected animals. The vaccine is also available especially for the one at risk like the veterinarians, laboratory technicians, employees working with goat hairs in the textile industry. Present vaccines have great efficacy and few side effects may develop once given in deep injection to fat or muscle. Finally, an early experimental oral vaccine used on animals, has shown promise. Days are not far when we will be able to use a pill for prevention.
The prognosis depends on the type of Anthrax infection, you are dealing with and the rapid response to an adequate treatment. Anthrax has become a rare disease in the Unites States and the developed countries but remained an endemic disease in all underdeveloped countries especially when they are lacking public health regulations. May I conclude that we have exposed the way Anthrax infects humans and animals: The most common manifestation of the disease is by the cutaneous route and the deadliest form is by inhalation of the spores. The intestinal form remains a rare but serious form of the disease while we are still learning from the “injectable form” discovered in heroin drug addicts. Be vigilant when you are visiting livestock while travelling.
Maxime Coles MD