Introduction: spore form which can release toxins into the

Introduction:The Bacillus Anthracis bacterium is commonly found in soil and infectsgrazing animals such as cattle. The bacterium has the potential to causedisease through the spores producing toxins. The zoonotic disease is calledAnthrax and is a virulent disease with the potential to be used in aerosol formas a biological warfare.

Characterization:  Bacillus anthracis is a gram-positive, rod-shaped bacterium1. It is anon-motile, spore forming bacteria that is non-hemolytic on blood agar4.It can be grown in aerobic and anaerobic conditions, making it a facultativeanaerobe. The bacterium is 1-1.2mm in width and 3-5mm in length4.There are two forms of cellsthat Bacillus Anthracis exists in.

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Thevegetative cells which are inside of the host, and dormant, endospore formcells4. The hard coating of the bacteria helps these spores survivefor long periods of time in harsh and extreme conditions. These spores areextremely resistant to different outside factors such as UV radiation, nutrientdepletion, and extreme heat4. The ability of the spores to be protectedincreases the survival of the spores for decades4.The moreinfectious form of the bacteria is the spore form which can release toxins intothe body after germination2.

Germination requires an abundance ofnutrients that is found in the tissue and blood of the host1. TheBacillus Anthracis bacterium has twomain virulence features, the poly-g-D-glutaminc acid capsule and tripartite toxin4.The capsule is produced by the bacteria in order to mask itself from themacrophages in order to invade the immune system4. The bacteriumproduces three proteins that form the combination of toxins that causes thedangerous effects of the disease1. Bacillus Anthracis has an A-B toxin in which the B, binding,subunit binds to gain entrance for the A, active, subunit into the host cell6.The protective antigen, also known as PA is the B subunit for the two differenttypes of active subunits. In the exotoxins, there is the Edema Factor(EF) andthe Lethal Factor(LF)6. The EF has adenylate cyclase activity whichcauses the cells to secrete a large amount of fluid6.

The LF hasprotease activity that interferes with the immune system’s inflammatory system6.The etiologic agent of the zoonotic disease anthrax, is a genetically monomorphicspecies7. The first plasmid on the different strains is pX01 whichencodes the different toxins while the pX02 encodes the genes needed for capsulesynthesis4. Three of the most well known strains are theAmes, Sterne, and Vollum4.

  TheAmes strain carries both of the plasmids which makes it the most virulentstrain that’s known from the species4. The Sterne strain is lessvirulent and lacks the plasmid pX02 which codes for the capsule for protection;this strain is used for vaccine research and is from Canada4. The Vollumstrain is also used for research and lacks the pX01 which codes for the toxins4. Clinical Description:  BacillusAnthracis is the agent responsiblefor Anthrax which is a zoonotic disease that has been around for centuries4.

The typical symptoms of the Bacillusanthracis usually appear between 1 day after infection to more than 2months after. The severity of the symptoms depends on the ability to seektreatment in a timely manner with the possibility of serious illness or death2.The most common form of the disease is cutaneous anthrax and is also the leastdangerous.

Cutaneous anthrax occurs when the spores enter the body throughbroken skin and reproduce vegetative cells that release exotoxin6. Cutaneousanthrax begins showing symptoms 2-5 days after the initial exposure10.These symptoms typically include small itchy blisters or bumps, swelling aroundthe sore, and painless skin sores like an ulcer with a black center called a Eschar5.The sores are found mostly on the hands, face, neck, or arms of the infectedindividual2. These lesions tend to heal after weeks and end upleaving scars10. The different modes of transmission also affect thetype of symptoms that an infected patient will encounter.

Another form of thedisease is inhalation anthrax. The most dangerous form and most fatal even iftreatment is provided in a timely manner8. The case-fatality is67%-88% even when antibiotic treatment and infection typically develops in 1-7days but can take up to 2 months after the exposure to appear2. Thisform of anthrax is at risk of becoming a biological weapon because it causesthe most harm and would be easier to infect a larger group of people if made intoan aerosol. Inhalation anthrax, also known as woolsorters’ disease, occurs whenthe Bacillus Anthracis producesendospores and these spores are inhaled; attaching to the lung tissue and begingermination8. The germination process destroys the lung tissue,eventually entering the blood system and traveling to other vital organs8.One complication that can arise from all forms but especially inhalation is thedevelopment of anthrax meningitis; this factor also affects the type of antibioticsand antitoxin prescribed2.

For inhalation anthrax, some symptomsinclude common flu-like symptoms such as fever, shortness of breath, headache,confusion/ dizziness, and vomiting2. As the disease progresses, lifethreatening symptoms include septic shock, breathing difficulties, andmeningitis- inflammation of the brain and spinal cords8. The third form of the disease is gastrointestinalanthrax which is obtained from ingesting uncooked meat that is infected withspores from cattle and other herbivore animals. Typically, symptoms appear 1-7days after the exposure. Gastrointestinal symptoms include sore throat, bloodyvomiting, stomach pain, severe, bloody diarrhea, swelling of the abdomen,fainting, and red eyes2.

Once inside the body, the spores can reachthe blood stream, making the mortality rate around 50%6. Lastly, themore recent form is injection anthrax, which is only found in Europe andassociated with heroin drug users2. Injection of anthrax can causefever, groups of small blisters from the injection, swelling around the sore,and abscesses that are deep under the skin near and around the injection site2.Cutaneous and injection anthrax display similar symptoms but the injectionanthrax can be more dangerous since it spreads faster and it more difficult totreat2.  Thereare a variety of treatments for the anthrax disease depending on the type ofillness.

The first for cutaneous anthrax includes a skin testing from a fluidsample of a lesion or small tissue sample8. A blood sample will alsobe taken and tested in a special lab8. After the identification ofanthrax, the patient begins a 60-day antibiotic course using ciprofloxacin,etc.8. When a person is suspected of being exposed to the spores,they are put on a post- exposure prophylaxis before symptoms are even shown inorder to prevent the progression of disease2. The sooner theinfected person receives medical treatment, the increased chance of a betterrecovery9. The spread of activated spores throughout the body isresponsible for the produced toxins and poisons that cause illness9.Once the toxins have spread throughout the body; the only treatment is anantitoxin9.

While the spores cause great harm to the body,especially if left untreated, it is not contagious, meaning it can’t be passedfrom person to person contact2.Theinfectious dose for inhalation anthrax is very high due to the clearing ofmicrobes from the various mechanisms of respiratory deposition. The averageinfective dose is estimated to be between 8,000-50,000 spores6.

Fromcurrent search by the Department of defense, in order to make an aerosolcapable of causing inhalation anthrax, 2,500-55,000 spores are needed for thelethal dose6. Portals of entry include the respiratory,gastrointestinal tracts, mucous membranes, and the skin.  Epidemiology and transmission: Thebacteria were first made known through the work from Robert Koch who discoveredthe spores and benefits that are provided to the bacteria in survival3.He was able to grow and isolate a pure culture of the bacteria and thenproceeded to inject it into an animal3.

Through his research, hedeveloped the research that described the relationship between the anthraxdisease and bacillus anthracisbacterium. This research method became known as Koch’s postulates3. Afterstudying the research of Koch, Louis Pasteur worked to develop a vaccine fromhis own research of injecting the vaccine and then exposing the animals to thebacterium and recording the results3. The effects of the vaccinehelped lower the rate of infection in United States, specifically thevaccination of animals to prevent transmission to humans. After developing avaccine for animals, the 1950s saw the first human vaccine that created 92.5% effectiverate in preventing cutaneous anthrax3. This vaccine was thenreplaced with the current one that is given to military personal from a limitedsupply3.

A majority of the cases of anthrax has come from people whoare handling animal skins such as drum makers. The ability to spread thebacillus spores through inhalation has created the potential to become abiological weapon. In a recent attack, 2001, letters were sent to U.S.Senators’ offices and media agencies that contained Bacillus Anthracis spores3. The route of transmission, inhalation,allowed it to spread before being identified, a total of 22 people got sickfrom the bacteria and 43 people tested positive from being exposed to thespores3. The Ames strain of the spores was used and it highlightedthe ability of the pathogen to be used as a biological weapon1.

TheBritish in the 1940s worked to develop a type of bomb that could release anaerosol of Bacillus Anthracis sporesand they tested it on islands near Scotland1. They also worked toproduce cattle cakes that were infected with the spores in order to decreasethe meat supply in Germany during the war1. Thebacterium and the disease it causes are more common in larger, warmeragricultural areas such as Africa, southern Asia, southern Europe, and CentralAmerica2. Other outbreaks occur sporadically in other parts of theworld with only a few in the last couple decades in the United States. Sincethe 1960’s in the United States, there have been less than 10 cases of anthraxreported each year, with 95% of them being the cutaneous form and the other 5%being inhalation6. The majority of cases are naturally causing fromagricultural workers and a couple from laboratory infections. In previousresearch, strains have been isolated from dead animals after reports of themconsuming other infected animals6.

The prevalence in the UnitedStates is extremely small, only limited to periodic outbreaks in areas ofcattle6. People who work in these areas and agricultural workers areat an increased risk of coming in contact with the bacteria throughoccupational exposure2. The risk of contracting the bacteria anddevelop the disease also increases when contacting products from infectedanimals2.  Themain modes of transmission revolve around contact with infected animals orproducts. Exposures such as contact with infected tissues of dead animals,consumption of contaminated uncooked meat, contact with hides, or wool frominfected animals, and consumption of illegal drugs that have been contaminatedwith the bacterium increase an individual’s risk of becoming infected with thepathogen in one of the four different forms6. The main reservoirs ofthe bacterium are farm and herbivorous animals. Some examples include cattle,deer, sheep, and even goats. The main hosts include humans and mammals7.

  Environmental:  The bacterium are normally found in the soil, livingin inactive spore forms4. The inactive form lives in the groundundisturbed but regularly infects wild animals after ingestion of the spores.The spores can be transported by different herbivores and domestic farm animalssuch as cattle, goats, and deer4. In areas of common infection, animalshave regular vaccination to prevent outbreaks and there is an increased risk oftransmission between the people that encounter these animals along with theskins, mead, and bones of the animals4. In order for the cells togerminate without a host, it needs optimal conditions such as alkaline pH, highorganic and moisture levels in addition to warmer tmeperatures4. Different factors can enhance the density ofspores in a particular area. Some factors include increased rainfall, andwarmer temperatures. Increased rainfall after a drought in particular increasesthe movement of the bacteria and can deposit the Bacillus Anthracis spores into a new area such as a pasture forcattle or sheep.

Vultures are also known to carry the spores after harvestingon an infected carcass and help spread the endospores to other parts of theworld. The spores can live in the soil for decades and once they have become establishedin an area, its almost impossible to remove them1. The bacteriumhave become resistant to different types of disinfectants which increases therisk of coming in contact with a herbivorous animal or occupational worker. Thebacteria usually live in the endospore form when exposed to differentenvironmental elements until they find a host that provided them with optimalconditions.

A temperature between 8 and 45 degrees Celsius, pH of 5-9,increased humidity and adequate nutrients will begin the germination process ofthe spores6. There has been increasing amounts of research regardingthe survival of anthrax spore in the permafrost in Artic regions from centuriesago as the increase in climate change thaws the regions, unveiling new possibleoutbreaks.             The main preventative measure is a vaccine that isnot available to the public. The vaccine is given to military personnel in theUnited States only with some exceptions for medical officials in the time of ananthrax emergency6. There is a pre-exposure vaccination that isrecommended for agricultural workers with risk of coming in contact withcontaminated animals.

The vaccination is also recommended for workers inlaboratories that are concentrating on the strains in a BSL 2 or higher lab,and veterinarians that are at a high risk of being infected throughoccupational exposures in various countries6. Ifthere was a health hazard bioterrorist threat in the form of inhalationanthrax, the Center of Disease Control has plans of action to isolate theinfected and prevent additional infections. The use of monitoring systemsthroughout the United States would be one of the first methods of detecting thespores after the release2. The other method of surveillance would bethe reporting by doctors when patients start exhibiting symptoms and labtesting is ordered. The response would be to send the sample through theLaboratory Response network and educating other health care professionals onthe issue along with the general public2. Once confirmed, medicineand additional supplies from the Strategic National Stockpile would bedispersed in the designated locations2. These preventative stepswould prevent further infections from the virulent bacteria and protect the atrisk populations.