Web article review

The purpose of this review is simply to identify a pertinent story of recent anthrax that could be found in our media today. Recently, an article on CBC news was written titled "Anthrax scare at Atlanta laboratory puts 75 scientists at risk" (2014). This report was actually written on the 19 of Jun so it is very recent. As the title may imply the article (2014) explains, "As many as 75 scientists working in U.S. federal government laboratories in Atlanta may have been exposed to live anthrax bacteria and are being offered treatment to prevent infection" (p.1). The article explains that the event was carried out after a failure in proper transfer procedures failed to inactivate samples of the bacteria. They then transferred these new samples to subsequent CDC labs which were "not equipped to handle live anthrax" (p.1). The exposure occurred on June 13th to which the CDC immediately began preventative treatment. To since the writing of this article, no symptoms have been seen of the illness. As with any upper class bacteria, the FBI launched a full investigation but found, "no evidence of wrongdoing"(p.1). The treatment of these individuals is not different from the typical course of treatment that we have discussed earlier in this blog sequence. The article (2014) reports that, "Around 75 individuals are being offered a 60-day course of treatment with the antibiotic ciprofloxacin as well as an injection with an anthrax vaccine" (p.1). I would have thought that at this point most CDC members who would be at high risk for exposure to these diseases would have already gotten their vaccines but I digress. Dr Paul Meechan, the director of the environmental health and safety compliance office at the CDC had reported that all employees involved in the transfer process and inactivation process were "tier one select agent approved" (p.1). This means that they had already undergone their security checks and were  deemed to be fully capable to cary out such an important task. The biggest issue now it seems (besides insuring treatment) is to ensure that a mishap like this will never happen again. It is far to risky to have this botched transfer occur. While I want to cut them slack and say, "everybody makes mistakes", this mistake may have cost the lives of over 70 people.  As we see, Anthrax remains a prominent discussion in today's media and  its stigma to bioterrorism will make us think twice about a little mistake such as this.

References: 

CBC News (2014, June 19). Anthrax scare at Atlanta laboratory puts 75 scientists at risk - World - CBC News. Retrieved June 20, 2014, from http://www.cbc.ca/news/world/anthrax-scare-at-atlanta-laboratory-puts-75-scientists-at-risk-1.2681388

Media retrieved from: http://blog.copdfoundation.org/copdf-points-to-cdc-report-showing-declines-in-copd-hospitalizations-and-mortality-rate/

Literature Review

It is the goal of this Literature Review to outline the summary of the Article “Bioterrorism-related inhalational anthrax: the first 10 cases reported in the United States” (2001) by John A. Jernigan, et al,. This will be conducted in order to achieve a better understanding of the function of the disease and to take a look at the actual field examples of the illness. I will examine and summarize the factors most important to the disease that I feel are pertinent based on the criteria beset within the patient at the time of illness. I will discuss three out of the 10 cases presented in the study.

This case study looks to examine, individually, 10 separate cases (rightly the 10 first cases) of inhalational anthrax due to bioterrorism in the U.S. The method of dispersal for these agents was found to be in the form of powdered Bacillus anthracis. Of the 10 cases, 7 were seen in the employees of the postal service. The geographic distribution found that patients were spread across New Jersey, the District of Columbia, Florida and New York. B. anthracis is able to be the determined the causative agent through gamma phage lysis, capsule confirmation, cell-wall antigens and a specific B. anthracis polymerase chain reaction. The most identifiable test is the PCR test in which the genetic material for the B. anthracis is compiled and analyzed to provide a template for identification. This is known as a BLAST nucleotide test.

Case #1

The initial case (#1) had an apparent onset on October 2, 2011. It was a 63-year-old Caucasian male who worked at a Florida newspaper. His symptoms were nausea, vomiting, and confusion. Prior to this he was feeling ill on September 27 during a trip to North Carolina. The symptoms of the initial illness were characterized by malaise, fatigue, fever, chills, and sweats. It is important to note that with this case there was no history of a headache, cough, chest pain, dyspnea, diarrhea, or skin lesions.

Treatment:

Day 1: He reported to the hospital not oriented to person place or time. While he did not report chest pain or other symptoms indicative of a pleural edema, when the chest x-ray did come back it showed a prominent superior mediastinum and small left pleural effusion. The hospital diagnosis of the anthrax did not come until they looked at the cerebrospinal fluid (CSF). They were able to isolate B. anthracis from CSF after 7 hours of incubation. During day one, a full diagnosis of meningitis and antibiotic treatment ensued. After admission on day 1 he began to have seizures and was intubated for airway protection.

Day 2: Penicillin G, levofloxacin, and clindamycin were administered and previous antibiotic treatments were halted. The patient’s condition deteriorated as renal failure began. The patient died on October 5. The cause of death was hemorrhagic mediastinal lymphadenitis because the B. anthracis had spread throughout his body.

Summary:  On Oct 2, PT was taken to emergency room. PT had an onset of initial symptoms on Sep27. Day one of the hospital showed treatment with multiple wide spectrum antibiotics on OCT 2. Day two of hospital treatment saw additional antibiotic treatment and witnessed more rapid patient deterioration on Oct 3. On Oct 5^th, the patient died and the bacteria were found to be in multiple organs. This case shows the short potential incubation period of the disease and how quickly an infection is able to desaturate a patient.

Case #4:

On October 16, a 56 y/o African-American male postal worker noted a constant mild headache. Over the time of three days the headache became more prominent and was now accompanied by a low grade fever, chills, sore throat, nausea , photophobia(light sensitivity), and blurred vision. These neurological symptoms were accompanied with difficulty breathing, a dry cough, and chest pain.

Treatment:

Day 1: On October 20, the Pt reported to the hospital as afebrile (without his fever) and with decreased breath sounds. Blood draws were shown to contain an increase in bilirubin and hepatic enzymes, low albumin, and hypoxia. It is reported that no organisms were seen on Gram stain of the patient’s Cerebrospinal fluid and the CSF culture did not gro. A chest X-ray showed pleural effusions and diffuse mediastinal edema. The confirmation of B. anthracis was made when blood cultures grew the bacteria within 15 hours of admission to the hospital. Antibiotic treatment immediately ensued and included Ciprofloxacin, rifampin, and clindamycin. 

Day 3: On October 22, worsening respiratory distress was noted

Day 4: on October 23, the patient underwent therapeutic thoracentesis. This is an attempt to drain the fluid that is inside of the lungs. After this treatment his condition improved. He was given a second thoracentesis and given corticosteroids for bronchospasm.

Day 17: Patient is discharged from hospital

Summary: Besides the obvious contrast with Case #1 that this patient survived, it appears that the treatment with initial antibiotics and early diagnosis (within one day) of the bacteria was not enough to halt the complication that the disease caused. In this case it was combined with interventional therapy in the form of a thoracentesis to remove the fluid. After sever positive responses with this procedure, the patient’s status improved greatly.

Case #6:

On October 16, a 47 y/o African- American male postal service employee who is affiliated with the same work center as case number 4 reported initial mild cough, nausea, vomiting and stomach cramps. On Oct 20 the patient passed out at church (syncope) but failed to seek medical treatment.

Treatment:

Day 1: Early on October 21 the patient checked into an emergency department with a chief complaint of vomiting and profuse sweating. He had a history of renal complications and asthma. He did not report with an initial fever. The chest X-ray was initially read as normal, but late the review had discovered a small margin of an increased density. The patient was discharged after receiving I.V fluids with no antibiotic treatment.

Day 2: In the morning of October 22 the patient again returned to the emergency department. He reported with chills, dyspnea, vomiting and another syncopal episode (fainted). At this point his blood pressure was 76/48 mm Hg. HR was 152 min and respiratory rate was 32 min. He was in respiratory distress with bilateral wheezing, tachycardia, and a distended abdomen. At this point a full lab work up revealed an infection and penicillin; ceftriaxone, rifampin, and levofloxacin were administered. The patient’s respiratory rate continued to be inhibited and required intubation and mechanical ventilation. A second X-ray shows mediastinal edema and bilateral pleural effusions. The patient died within 6 hours of admission. The Gram- positive bacilli were visible on the buffy coat blood smear and blood cultures grew B. anthracis within 18 hours. Cause of death was hemorrhagic mediastinal lymphadenitis.

Summary: We learn from this case that the delay of initial antibiotic treatment and identification of infection resulted in the increase degradation of the patient and ultimately resulted in death. This case shows how critical it is to 

Conclusion:

Overall this research was very informative about the mechanisms of action for this type of bacteria. As we hear of forms of bioterrorism in the world today we need to understand just what it is that is affecting us. The critical knowledge gained from this study will prove to be essential for the identification of the disease again because, as in this case, time is critical. The case studies seen here were compiled forms of the original study by John A. Jernigan, et al,. (2001). This review was meant to be a brief educational explanation of what my interpretation of the cases where and how they affect the prevention and treatment of Anthrax for the future. Due to the compiled nature of this review much information was omitted. To view the full study, please click on the following link.

References:

Jernigan, J. A., Stephens, D. S., Ashford, D. A., Omenaca, C., Topiel, M. S., Galbraith, M., . . . Perkins, B. A. (2001). Bioterrorism-Related Inhalational Anthrax: The First 10 Cases Reported in the United States. Emerging Infectious Diseases, 7(6), 933-944. doi:10.3201/eid0706.010604

Media References (in order of appearance):

http://science.howstuffworks.com/anthrax2.htm

http://en.wikipedia.org/wiki/Pleural_effusion

http://www.skinsight.com/atlas/anthrax.htm

History, Etiology, Symptoms and Treatment

Anthrax is a disease that is almost always associated

with bioterrorism. Outside of this light though, many do not know just what it is or where it comes from. Many people today think that Anthrax only recently came about as it is portrayed in the media. This belief is not true and as we will find, it has a history that spans many hundreds of years.

1250 BC- To truly understand Anthrax we will have to travel back, some say, as far as the time when Moses brought the 10 plagues to Egypt. According to the Center for Disease Control (Nov 2013), “ Anthrax is thought to have originated in Egypt and Mesopotamia. Many scholars think that Moses’ time, during the 10 plagues of Egypt, anthrax may have caused what was known as the fifth plague, described as a sickness affecting horses, cattle, sheep, camels and oxen” (p.1).

1700s- In fact, the CDC (2013) reports that, the first clinically descriptive anthrax were actually reported in 1752 by “Maret in 1752… and Fournier in 1769” (p.2). It was reported that before this, anthrax had only been described through historical accounts.

1800s-During the 1800s, doctors started to see the disease of Anthrax but had not yet identified the pathogen. Their patients mainly involved the workers of the clothing mills at the time and so the disease was named “ wool sorters disease” (CDC 2013 pg.4). Then in the late 1800s, a man named Robert Koch developed a set of postulates based upon Bacillus anthracis, which is the bacterium that causes anthrax. He was able to study the rod shaped bacteria and found that part of the reason it was so resilient was that the bacteria produces spores. Spores are a protein coat that the bacteria produce when it is put under certain stress. Because of this extra protein coat, the bacteria were able to survive long periods in very extreme conditions. His work lead him to be able to culture the disease and monitor the effects that it had on animals. The CDC explains that, “ [The] Koch’s postulates… demonstrate a causal relationship between a specific microorganism and a disease” (p.3). These postulates are an important part of immunology today and helped to form the basis of today’s study of disease. Then, in 1881, along came the father of modern immunology Louis Pasteur. Louis Pasteur was able to take Koch’s work further by actually looking at the pathology of the disease, or how the disease affected humans. He did this with the intent of creating a Vaccine and so he did. He was able to create the first Animal Anthrax vaccine in 1881 (CDC 2013). While this was shown to be a great step in the cure for Anthrax, his vaccine only worked on animals. It wasn’t until the 1950s that the first human anthrax vaccine was created (CDC 2013). The vaccine was given as a test to a group of goat hair mill workers. They were tracked over a case of two years and it was determined that the vaccine was 92.5% effective in preventing cutaneous anthrax (CDC 2013). The form of vaccine we use today is based on an updated version from 1970.

Anthrax and Bioterrorism

Anthrax has been getting attention in recent years due to its deadly onset and use as a bioweapon. The CDC has a full report estimating Anthrax to be the most likely agent used in a bioterror operation. According to the CDC (2014), “ If a bioterrorist attack were to happen, Bacillus anthracis, the bacteria that causes anthrax, would be one of the biological agents most likely to be used. Biological agents are germs that can sicken or kill people, livestock, or crops. Anthrax is one of the most likely agents to be used because,

·      Anthrax spores are easily found in nature, can be produced in a lab, and can last for a long time in the environment.

·      Anthrax makes a good weapon because it can be released quietly and without anyone knowing. The microscopic spores could be put into powders, sprays, food and water. Because they are so small you may not be able to see, smell, or taste them.

·      Anthrax has been used as a weapon before.

Anthrax has been used as a weapon around the world for nearly a century. In 2001, powdered anthrax spores were deliberately put into letters that were mailed through the U.S. postal system. Twenty-two people, including 12 mail handler, got anthrax, and five of these 22 people died” (p.1).

Pathogenisis:

Anthrax is caused by a bacteria called Bacillus anthracis. The disease is found in three main forms; Inhalation Anthrax, Gastrointestinal Anthrax, and Cutaneous Anthrax.  Some important pathogenic factors of Bacillus anthracis include the fact that it is a large (relatively 1.0 to 1.5 mcm x 3.0 to 5.0 mcm), gram-positive bacillus (rod shaped) bacterium that is able to produce an endospore (Center for Infectious Disease Research and Policy 2013). The bacterium is able to form long chains of the vegetative form (non spore form) and also it is aerobic (needs oxygen to survive).  According to the Center for Infectious Disease Research and Policy at the University of Minnesota (2013), the bacteria is non-motile. This means that it is not able to move on its own. This is a good thing since they are more confined to a location and rest upon dependency of a vehicle or possibly a vector to transmit them to a new host. The CIDRAP at the University of Minnesota (2013) lists some of the most common virulence factors associated with the bacteria. First on its list is LF or Lethal Factor.

Lethal factor (LF) is a zinc metalloprotease. LF combines with PA to form lethal toxin. The PA is a Protective antigen and is a binding protein that permits the entry of toxin into host cells through a process called endocytosis. The PA forms the hole in the membrane of the host that allows the LF to penetrate into the cytoplasm of the cell. The combination of the two is called Lethal Toxin (CIDRAP 2013).  LT is thought to stimulate the over production of cytokines. Cytokines are immunological components that help fight infection and cellular regulation from macrophages. This factor will actually cause a lysis of the macrophages (CIDRAP 2013). The CIDRAP (2013) also illustrates the effectiveness of Lethal Toxin by stating, “Lethal toxin has been shown to cause endothelial cell apoptosis and endothelial barrier dysfunction, which may contribute to vascular destruction (Kirby 2004, Warfel 2005). It has also been shown to reduce myocardial function (Moayeri 2009, Sweeney 2010).” As if that wasn’t bad enough we also have an additional toxin called the Edema toxin. The Edema toxin converts ATP to cAMP in the intercellular compartment. This will lead to a hypotonic environment as high levels of cAMP lead to impaired water homeostasis maintenance (CIDRAP 2013). 

As stated earlier there are 3 main types of Anthrax; Cutaneous Inhalational and Gastrointestinal. 

Inhalational Anthrax:

As it maybe presumed, Inhalational Anthrax is considered the most deadly. Inhalational Anthrax occurs in the following steps (CIDRAP 2013). Firstly, the endospores are introduced into the body through the pathway of inhalation. Because of their size they are able to reach the alveoli. Within the alveoli the endospores are inactive, meaning that they are not able to multiple or perform complex metabolic functions. At this stage they are then phagocytized by macrophages as they body tries to quell the unknown invaders. The spores are then taken to a regional lymph node in order to be destroyed and processed. It is at this location that they are reanimated and take on their vegetative form. It is at this point that they begin to multiply within the lymphatic system. After the infection grows, pressure is placed on the mediastinum due to inflammation and regional hemorrhagic lymphadenitis (Abramova 1993).  This widening of the mediastinum is noted on chest radiograph or enlarged lymph nodes can also be directly visualized on a chest CT scan. If the lymphatic system becomes blocked then pulmonary edema may occur. Pulmonary edema is a very dangerous condition in which there is a build up fluid within the lungs. After some time, the bacteria may be able to enter the bloodstream and cause septic shock and bacteremia. The stress placed on the lungs and septic shock are the most common causes of death within this class. The infectious dose of an organism refers to the amount of cells that is takes to cause an infection within a person. According to the CIDRAP (2013), “ The median infective dose… for inhalational anthrax is estimated at 8,000 to 50,000 spores (Franz 1997), although the minimum infective dose may be considerably lower” (p.1). 

Cutaneous Anthrax:

Cutaneous Anthrax occurs in the following stages. The initial presentation is similar to that of inhalational Anthrax. The endospores are introduced through the skin from a preexisting lesion or abrasion. In this case they are somewhat opportunistic. Once the bacteria is present in the subcutaneous layer of the skin the return to their vegetative form. Initial, early infections are characterized by a localized necrosis with a soft-tissue or mucosal edema (Bischof 2007). Because the wound will be easily visible quick antibiotic is enough to eradicate the infection (CIDRAP 2013).

Gastro-Intestinal Anthrax:

This form of Anthrax is relatively rare and is caused by the ingestion of Anthrax spores. Because it is so rare not as much information is available about this form as the other forms of the disease. It is thought that not only is the disease caused by ingestion of the spore form of the disease but also the vegetative form (Inglesby 2002). There are two forms of gastrointestinal anthrax: oropharyngeal and abdominal. According to the CIDRAP (2013), “In oropharyngeal anthrax, the portal of entry is the oral or pharyngeal mucosa. A mucosal ulcer occurs initially, followed by regional lymphadenopathy and localized edema. In abdominal anthrax, the portal of entry often is the terminal ileum or cecum. Intestinal lesions occur and are followed by regional lymphadenopathy. Edema of the bowel wall and ascites (sometimes massive) may be present. Hematogenous spread with resultant toxemia can occur”  (p.1).

Signs and Symptoms:

Inhalation anthrax presents with Flu-like symptoms. These include mild fever, fatigue and muscle aches, which may last a few hours or days. As mentioned previously the pathophysiology of the disease places a great pressure on the mediastinum in the body, so it is to be expected that you should have mild chest discomfort, shortness of breath, coughing up blood, painful swallowing and even nausea. In the later stages you may have trouble breathing, present signs of shock or even meningitis (Mayo clinic).  It is important to note that those most susceptible to the disease are those who work with animal hides that come from the middle east and Africa. This is the most common naturally occurring transmission of the disease.

Gastrointestinal anthrax presents in some similar ways as inhalational anthrax, such are; nausea, vomiting fever, sore throat and difficulty swallowing. Some additional symptoms are; abdominal pain, headache, loss of appetite severe, bloody diarrhea in the late stage and a swollen neck (Mayo Clinic).

Subcutaneous anthrax will present as a raised, itchy red bump that appears to be an insect bite and develops into a painless sore black centered lesion. The black center is a specific sign of the anthrax disease as it is very distinct (Mayo Clinic).

Treatment Options:

According to the CDC (2014), “Doctors have several options for treating patients with anthrax, including antibiotics and antitoxin. Patients with serious cases of anthrax will need to be hospitalized. They may require aggressive treatment, such as continuous fluid drainage and help breathing through mechanical ventilation.” (p.1). This is called a thoracocentesis and is used for the treatment of pleural effusions and pulmonary edema. 

Antibiotics:

Any of the different types of anthrax can be treated with different antibiotics. The use of certain antibiotics depends on patient allergy but it is not uncommon to still see penicillin used as an antibiotic to treat anthrax (CDC 2014).

Antitoxin:

As we went over earlier the main virulence factor for the disease is its combined bacteriotoxins. To combat this the CDC replies that there are different antitoxin treatments available. This treatment needs to be done as soon as possible if an individual is suspected of having anthrax especially inhalation anthrax (CDC 2014).

It is important to know that there is a vaccine available for both inhalation anthrax and cutaneous anthrax (CDC n.d). However, it is common to give this vaccine only to those individuals who are associated with high risk areas. The military is a wonderful example of a populous who is deployable to high risk areas. They will not even give it to the military members until they are about to breech a high risk area. The CDC reports that, "Currently, FDA has not approved the vaccine for use after exposure for anyone. However, if there were ever an anthrax emergency, people who are exposed might be given anthrax vaccine to help prevent disease. This would be allowed under a special protocol for use of the vaccine in emergencies" (p.1). The vaccine consists of 5 shots over 18 months and an annual booster. The CDC seems to lean towards not giving the vaccine to everyone because it may carry a higher risk of allergic reactions though, they are not clear on exactly why this is. Allergic reactions can happen to any treatment and they had said previously that the vaccine did not contain an active form of B. anthracis. I could only see the effective treatment plan being increased with additional public knowledge available about why regular population can not get vaccinated. And if  after that data does become available that they be able to disperse these vaccinations to those who are not subject to the contraindications. 

References

Bischof, T., Hahn, B., & Sohnle, P. (2007). Characteristics of Spore Germination in a Mouse Model of Cutaneous Anthrax. Journal of Infectious Diseases, 195(6), 888-894. doi:10.1086/511824

Center for Disease Control and Prevention (2014, November). Who Is At Risk | Anthrax | CDC. Retrieved June 15, 2014, from http://www.cdc.gov/anthrax/risk/index.html

Davison, S., Couture-Tosi, E., Candela, T., Mock, M., & Fouet, A. (2005). Identification of the Bacillus anthracis Phage Receptor. Journal of Bacteriology, 187(19), 6742-6749. doi:10.1128/JB.187.19.6742-6749.2005

Klee, S. R., Brzuszkiewicz, E. B., Nattermann, H., Brüggemann, H., Dupke, S., Wollherr, A., . . . Liesegang, H. (2010). The Genome of a Bacillus Isolate Causing Anthrax in Chimpanzees Combines Chromosomal Properties of B. cereus with B. anthracis Virulence Plasmids. PLOS One, 5(7). doi:10.1371/journal.pone.0010986.t002

New York State, Dept of Health (2011, October 11). Anthrax (malignant edema, woolsorters' disease). Retrieved June 15, 2014, from http://www.health.ny.gov/diseases/communicable/anthrax/fact_sheet.htm

Mayo Clinic (2014, June 10). Anthrax Symptoms - Diseases and Conditions - Mayo Clinic. Retrieved June 15, 2014, from http://www.mayoclinic.org/diseases-conditions/anthrax/basics/symptoms/con-20022705

University of Minnesota (2013, May 1). Anthrax | CIDRAP. Retrieved June 15, 2014, from http://www.cidrap.umn.edu/infectious-disease-topics/anthrax

References for Media

(In order of appearance)

http://www.cdc.gov/anthrax/history/index.html 

http://www.cdc.gov/anthrax/bioterrorism/threat.html

http://giphy.com/gifs/A30hVv6SbTNFm

http://giphy.com/gifs/growth-bacteria-bacillus-kwSe0Dw7rIXFS

http://en.wikipedia.org/wiki/Anthrax