Bioterrorism

Dr. Somy Thottathil did an awesome lecture on bioterrorism this past week. And although it is hopefully something we never have to see, as one of the major hospitals designated as a bioterrorism site in Chicago, it is something that we should be prepared to recognize and treat. It’s also good review for all the med school knowledge we haven’t needed (thankfully) for some time now. The main topics we’ll focus on are the Category A agents:  Botulism, Plague, Anthrax, Smallpox, and Viral Hemorrhagic Fevers (which includes Ebola, Marburg, Lassa Fever, and Crimean-Congo Hemorrhagic Fever). We are only going to discuss Ebola as current outbreaks are still occurring.

Background

Bioterrorism agents are divided into 3 categories based on the agent’s ability to infect, kill, and disrupt everyday life. The main distinction for category A agents is that they have been previously used as a bioterrorism weapon in the past.

• Each biological agent has specific guidelines for decontamination and healthcare precautions. However, at the same time, all biologic agents (especially in the ED) should prompt strict adherence to standard, airborne, droplet and contact precautions. Once the specific agent is identified, then the specific guidelines can be used.
  • Standard Decontamination:  an important process started in the ED. All clothing and personal effects are removed from patient and placed in plastic bags (bags are labeled and inventoried). Patient is then showered using copious amounts of soap and water
• It is important to note that these diseases do occur in nature with spontaneous infections occurring. However, they are often localized to a certain region with relatively few people infected each year. The presence of multiple people with the infection outside their endemic region should alert to the possibility of a bioterrorism attack.

Botulism (Clostridium botulinum)

• Botulism is a rare and potentially fatal disease caused by the Botulinum neurotoxin. Botulism comes from the Latin word botulus meaning sausage. The first case of botulism was described by sausage poisoning in Germany in the 1800s.
• There are 8 toxins produced by C. botulinum, but only 3 of the toxins cause disease in humans
  • Toxin A is what is used in BoTox
• There are many forms of botulism:  Infantile (honey), wound (IVDU associated with black tar heroin), gastrointestinal (canned food), iatrogenic (few case reports from injected BoTox), and inhalational (aerosolized for bioterrorism). The gastrointestinal and inhalation forms are the top concerns of bioterrorism experts.

Presentation

• Symptoms occur 6 hours to 5 days after toxin exposure starting with GI symptoms including nausea, vomiting, abdominal cramps, and either diarrhea or constipation–this is often mistaken for gastroenteritis
• This then leads to symptoms of muscle weakness and paralysis often described as a descending, symmetric paralysis. Patients will often present with bilateral cranial nerve neuropathies
  • Pupils are often dilated and non-reactive to light (important differentiation form myasthenia gravis, which does not affect the pupil)

Diagnosis and Treatment

• Dx:  Mouse Bioassay of serum or stool is gold standard.
• Tx
  • Supportive care:  often requiring intubation (ventilatory support can last 2-8 weeks).
  • trivalent equine antitoxin shows decreased vent days
  • human botulism immunoglobulin also shows decreased vent days
  • Standard Precautions:  There is no person-to-person transmission since transmitted via ingestion of spores, not the bacteria.

The Plague (Yersinia pestis)

Background:

The plague can come in 3 forms:  bubonic, septicemia, and pneumonic. The form we all remember from medieval times is the bubonic plague. This is caused by bites from fleas which can lead to eschar wounds on the skin. The bacteria travel to lymph nodes causing buboes (inflamed, tender lymph nodes). In ~50% of these cases, the bacteria then can enter the bloodstream leading to sepsis (the septic form of the disease) and death. Bubonic plague has mortality ~60% without treatment. The bacteria can then infect the lungs via hematogenous spread causing pneumonic plague. Once the lungs are infected, the individual becomes very contagious as bacteria can spread via cough.

If the natural form of the plague wasn’t already scary enough, humans created an aerosolized form in the 1970s that directly leads to the pneumonic form of the disease. This is very contagious with mortality rates nearing 100% without treatment. Antibiotics must be started within first 24 hours of symptoms to decrease mortality to 20-60%.

Plague Presentation:

Presents with sudden fever, chills, and headache. Then patient develops nausea/vomiting within a few hours of these symptoms. Buboes develop 1-8 days later. Femoral buboes are most common but can also be found in inguinal, axillary, and cervical LN as well. The buboes typically recede in 10-14 days spontaneously. Therefore, they do not require intervention, and should not be drained as lymph fluid is highly contagious. Septicemia can develop in 2-6 days if left untreated. This can also present with altered mental status and bladder distention.

Pneumonic presentation either from hematogenous spread or aerosolized bioterrorism attack has incubation period of 1-3 days (though can last up to 10 days). It will include symptoms of pneumonia including chest pain, SOB, localized necrosis/cavitation, and hemoptysis.

Diagnosis and Treatment

• Dx:  blood and sputum cultures with Gram Stain
  • Plague is a gram negative organism. Gram negative pneumonias are rare outside of at risk populations and differential includes:  Pseudomonas, Klebsiella, and Acinetobacter
• Tx:  Gentamicin, Ciprofloxacin, or doxycycline are all acceptable choices. Requires 10-14 days of treatment
• Post-exposure Prophylaxis:  doxycycline, ciprofloxacin, or chloramphenicol are acceptable choices. Done for 7 days
• Precautions
  • Bubonic plague:  Standard and contact precautions. Requires droplet precautions for 48 hours until pneumonic form can be ruled out
  • If pneumonic form is present, requires droplet precautions until 48 hours of completed antibiotic therapy.

Anthrax (Bacillus anthracis)

Presentation

There are two forms of anthrax disease:  cutaneous (sheepherders in Mongolia type) and inhalational (found in the mail type). Inhalational type has incubation period of 2-7 days (but can be up to 6 weeks). Days 1-3 includes flu-like symptoms including fever, dry cough, myalgia, malaise, and is marked by profound sweats. This is followed by a brief period of improvement, which then rapidly descends into the acute phase with respiratory distress including hypoxia, tachypnea, chest pain, shock, and mediastinitis. CXR often shows widened mediastinum with mediastinal lymphadenopathy. In ~50% of cases, the disease can progress to meningitis described as “Cardinals Cap” due to its ability to cause hemorrhaging.

Cutaneous Anthrax is caused by direct inoculation of skin by bacteria. This could be spread person-to-person by direct contact with patient’s wounds and person’s skin. Incubation period is often 1-5 days. It starts as a painless, pruritic, small papule that progresses to vesicle in 1-2 days. It then ruptures, leaving a necrotic ulcer with surrounding erythema and edema (has somewhat similar appearance to Brown Recluse Spider Bite). The ulcer turns black in 2-3 weeks, leaving an eschar (anthrax is actually Greek for “coal” based on this eschar), which eventually separates leaving a scar. Cutaneous anthrax is rarely fatal as often isolated to skin and rarely becomes septic. Mortality <1% if treated and ~20% if untreated.

Dx and Treatment

• Dx:  gram stain and culture of wound, blood, or sputum. May include LP based on presentation
• Tx:
  • ciprofloxacin 400 mg IV q12 (1st line) for 60 days
    • If allergy to above, then doxycycline 100 mg IV q12h+ clindamycin 90 mg IV q8h for 60 days
  • Raxibacumab (ABthrax):  targets anthrax toxin
• Postexposure prophylaxis:
  • Vaccinated at days #0, #14, #28
  • Ciprofloxacin 500 mg PO q12h or doxycycline 100 mg PO q12h for 60 days for 60 days. This was extended to 60 days due to case reports of incubation period up to 45 days.
• Person-to-person transmission is not possible of inhalational type. However, as often the exposure is through powder, the patient’s clothes and belongings should be removed and decontaminated with 10% bleach.

Smallpox (variola virus)

Background

Last known case was in 1977 in Somalia. Last known US case was in 1949. It is a very contagious disease. The highest viral shedding occurs during 1st week of symptoms, but remains infectious until the last pox scab falls off. There are only 2 known sites of virus:  Atlanta, Georgia with CDC and in Moscow, Russia. Several governments of the world including US have large stockpiles of vaccinia vaccine if an outbreak did occur (US has large enough stockpile for every US citizen).

Presentation

Incubation period is 7-19 days (most often 12 days). Initial phase begins as fever, fatigue/weakness, lumbar back pain, myalgia, and nausea/vomiting. 2-4 days after this initial presentation, the characteristic rash becomes present. The rash is worst on the face, arms, legs, and includes the palms and soles (one of only handful of rashes that involve palms and soles). Unlike chickenpox (different stages of lesions), smallpox lesions are generally all at the same stage. Also can help differentiate from chickenpox in that rash starts on legs and then involves chest (chickenpox starts on trunk and then extends into extremities). The lesions begin as clear fluid-filled vesicles, progress to pustules, and then harden and form a crust, ultimately falling off in 3-4 weeks.

 

Dx and Treatment

• Dx:  PCR DNA Test
• Tx:
  • Active Disease
    • Vaccinia Vaccine within 72 hrs can decrease total disease severity and can decrease symptoms within 7 days
    • Supportive care and wound management for open lesions
  • Postexposure Prophylaxis
    • Vaccinia Vaccine:  can administer up to 3 days post-exposure. Shown to prevent infection and lessen severity of disease if does occur
  • Precautions
    • Airborne and contact isolation with negative pressure room. Strict quarantine of pt and everyone exposed. Respiratory isolation is required for 17 days for everyone exposed.

Ebola (filovirus)

Background

Transmitted via direct contact and body fluids (including urine, saliva, semen, breastmilk, feces, and vomit) that come into contact with mucous membranes. Ebola should be considered in any patient with fever who has traveled from an endemic area within 21 days. Mortality rate can range as high as 90%. The 2014-2016 epidemic occurred in Guinea, Sierra Leone, and Liberia with 28,626 suspected, probable, and confirmed cases with 11,310 deaths. Patient zero was identified as a one-year-old child who died in 12/2013. People who attended the funeral contracted ebola. There is a new ongoing outbreak in the Congo with 608 confirmed cases and 368 death (20% of which occurred in last month).

Presentation

Incubation period can range from 2-21 days (though most commonly ~11 days). The symptoms can be widespread including:  fever (87%), fatigue (76%), loss of appetite (64.5%), vomiting (67%), diarrhea (65%), headache (53%), abdominal pain (44%), and hemorrhagic symptoms (<43%). Hemorrhagic symptoms are the last to occur and can lead to petechiae and bleeding from any site.

Dx and Treatment

• Dx:
  • PCR-DNA is gold-standard
    • WHO approved a rapid antigen finger stick test with 92% sensitivity in 2015
  • Should also investigate more common causes of fever in patient from endemic areas including malaria (blood smear, antigen testing), Typhoid, Influenza, and traveler’s diarrhea. Malaria (40%) and traveler’s diarrhea (12%) were most common cause of fever in travelers from these endemic areas.
• Tx
  • Supportive Care
  • Precautions
    • Contact, airborne, and droplet precautions
    • Semen has tested positive as late as 3 months after acute infection. It is recommended that men abstain from sex for 3 months after acute infection (or wear condoms). At 3 months, semen should be tested with PCR. If negative, again tested 1 week later. Can resume normal sexual activity if two negative PCR tests
    • Breastmilk has tested positive during acute infection. Breastfeeding should be avoided until symptoms resolve, and breastmilk is PCR negative twice at 48 hrs apart.
  • Vaccine:  there are 2 promising vaccine trials currently being researched. They have received special fast track approval processing. They are still in phase I testing, however, they have had very promising results thus far. They are not standard of care yet, although, they have been used on a “compassionate” level for healthcare workers with needle stick injury who have all remained healthy.

Summary

There are 6 category A bioterrorism agents. Three of them are bacterial (plague, anthrax, and tularemia). They can all be treated with IV ciprofloxacin in their active disease states. These diseases also require prophylactic antibiotics to any person exposed (often family members, healthcare workers, or government employees) which can be done with doxycycline (preferred as cheaper and US government has stockpiled) or ciprofloxacin (2nd line as more expensive and more side effects). Two of the diseases are viral (Smallpox and Ebola). These require supportive care. Smallpox requires vaccine within 72 hours. Ebola has vaccine research currently being performed. Botulism is the last disease state and is toxin mediated. It is treated with supportive care and Botulinum antitoxin.

In the ED, all bioterrorism suspected presentations should entail strict adherence to standard, contact, droplet, and airborne precautions. Patient should have all belongings removed and placed in bag for inventory. Patient should be decontaminated with copious soap and water. Once the agent is identified, the specific precautions for said agent can be practiced.