department of internal medicine. bioterrorism jim czarnecki, d.o. resident lecture series
TRANSCRIPT
Department of Internal Medicine
Department of Internal Medicine
Bioterrorism
Jim Czarnecki, D.O.
Resident Lecture Series
Department of Internal Medicine
Introduction
Department of Internal Medicine
Introduction
Among weapons of mass destruction, biological ones are more destructive and cheaper than chemical weapons, and in certain cases, are as devastating as nuclear devices.
Lethal amounts of biological agents are relatively easy to conceal, transport, and disperse.
Example – Aerosolized release of 100 kg of anthrax spores would result in between 130,000 and 3,000,000 deaths.
Department of Internal Medicine
Introduction
The financial consequence of biological attack are also extreme.
A current economic model developed by the CDC estimated a cost of $26.2 billion per 100,000 persons exposed to aerosolized Bacillus anthracis.
Primary health-care providers throughout the US will probably be the first to observe (and report) unusual illnesses or injuries in the event of a covert attack.
Department of Internal Medicine
History
Department of Internal Medicine
History
Development parallels the history of human conflict although the greatest advances in weaponry has occurred in the last 100 years.
First documented attacks were against animals in World War I.
The offensive efforts of the US began at Camp Detrick in 1942.
The British have only field-test anthrax based weapons. The Japanese have actually utilized biological weapons
– plague in World War II.
Department of Internal Medicine
History
In 1969, President Nixon declared the end of the US offensive biological weapons program.
In 1972 the Biological and Toxin Weapons Convention formed a unilateral agreement, and was signed by 140 countries.
Biological weapons developed continued within the Soviet Union.
Department of Internal Medicine
History
Today terrorist groups employ biological agents and pose an ongoing risk.
In 1984, 751 people in The Dalles, Oregon, contracted salmonellosis after a religious cult spread the bacteria on restaurant salad bars in an attempt to disrupt elections.
A Japanese doomsday cult used Sarin nerve gas for its attack on the Tokyo subway, resulting in 6000 casualties and 12 deaths.
A case of anthrax was confirmed in South Florida in 2001. A container of ricin was found in South Carolina in October
2003.
Department of Internal Medicine
Organisms
Department of Internal Medicine
Organisms
The list of potential biologic agents or toxins is substantial.
High-priority agents include organisms that: Can be easily disseminated or transmitted person-to-
person Cause high mortality Might cause public panic and social disruption Require special action for public health preparedness
Department of Internal Medicine
Organisms
The CDC has identified a number of high priority organisms as category A agents.
Of particular concern, smallpox and anthrax can be grown easily in large quantities and are sturdy organisms that are resistant to destruction.
They are well suited to aerosol dissemination to reach large areas and numbers of people.
Department of Internal Medicine
Organisms – Category A Agents
Variola major (smallpox) Bacillus anthracis (anthrax) Yersinia pestis (plague) Clostridium botulinum (botulism) Francisella tularensis (tularemia) Filoviruses (Ebola, Marburg) Arenaviruses (Lassa, Junin and related viruses)
Department of Internal Medicine
Organisms
Second highest priority agents include those that: Moderately easy to disseminate Cause moderate morbidity and low mortality Require specific enhancements of diagnostic capacity
and enhanced disease surveillance
Department of Internal Medicine
Organisms – Category B Agents
Coxiella burnetii (Q fever) Brucella spp. (brucellosis) Burkholderia mallei (glanders) B. pseudomallei (melioidosis) Chlamydia psittaci (psittacosis) Rickettsia prowazekii (typus fever) Alpha viruses (eastern equine encephalitis, western
equine encephalitis, Venezuelan equine encephalitis) Ricin toxin
Department of Internal Medicine
Organisms – Category B Agents
Epsilon toxin of Clostridium perfringens Staphylococcus enterotoxin B Salmonella spp. Shigella dysenteriae Escherichia coli O157:H7 Vibrio cholerae Cryptosporidium parvum
Department of Internal Medicine
Organisms
Third highest priority agents include emerging pathogens that could be engineered for mass dissemination in the future because of: Availability Ease of production and dissemination Potential for high morbidity and mortality and major
health impact
Department of Internal Medicine
Organisms – Category C Agents
Nipah virus Hanta viruses Tickborne hemorrhagic fever viruses Tickborne encephalitis viruses Yellow fever Multidrug resistant tuberculosis
Department of Internal Medicine
Anthrax
An Overview
Department of Internal Medicine
Anthrax
Background
Department of Internal Medicine
Anthrax - Background
Described in the early literature of the Greeks, Romans, and Hindus. The fifth plague described in the book of Genesis may be among the earliest descriptions of anthrax.
Most of the terms associated with anthrax relate to cutaneous or respiratory anthrax.
Department of Internal Medicine
Anthrax
Pathophysiology
Department of Internal Medicine
Anthrax - Pathophysiology
Primarily a disease of herbivores, although pigs, dogs, and cats are not immune, they are more resistant to the disease.
Birds usually are naturally resistant to anthrax. Humans are relatively resistant to cutaneous
invasion of anthrax, but succumb to infection by microscopic or gross breaks in the skin.
Bacteremic anthrax with hematogenous spread most commonly follows inhalational anthrax.
Department of Internal Medicine
Anthrax - Pathophysiology
B. anthracis remains in the capillaries of invaded organs, and the local and fatal effects of the infection result, in large part, to the toxins released.
Anthrax in the spore stage can exist indefinitely in the environment.
Inhalation anthrax occurs after inhaling spores into the lungs.
Spores are ingested by alveolar macrophages and are then carried to the mediastinal lymph nodes.
Department of Internal Medicine
Anthrax - Pathophysiology
Anthrax in the lungs does not cause pneumonia, but does cause hemorrhagic mediastinitis and pulmonary edema.
Hemorrhagic pleural effusions frequently accompany inhalational anthrax.
Death from anthrax occurs as a result of the effects of lethal toxins.
Near death or just after death, victims bleed from all body orifices.
Department of Internal Medicine
Anthrax
MMWR
Department of Internal Medicine
Anthrax - MMWR
Frequency Natural incidence is rare in the US – an occupational hazard for
veterinaries, farmers, etc.
Mortality/Morbidity Most cases are cutaneous anthrax are mild, and resolve with or
without treatment. Septecemic antrax and inhalational anthrax have the highest
mortality. Inhalational is a rapidly fulminating disease that is nearly always fatal (mortality > 90%).
Cutaneous antrax is readily curable if treated properly (mortality is < 1%).
Department of Internal Medicine
Anthrax - MMWR
Intestinal anthrax is difficult to diagnose and is associated with a higher mortality (20-60%).
Race No racial predilection for, or protection from, anthrax exists
Sex No sex predilection exists.
Age No age predilection exists – persons of any age can be affected
if anthrax is used as a bioterrorist weapon.
Department of Internal Medicine
Anthrax
Clinical Overview
Department of Internal Medicine
Anthrax - History
Cutaneous Occurs 1-7 days after skin exposure and penetration
of B. anthrasis. Form most commonly affects the exposed areas of
the upper extremities, and to a lesser extent, the head and neck.
Hematogenous dissemination occurs in 5-10% of untreated cases.
Department of Internal Medicine
Anthrax - History
Inhalational Begins abruptly, 1-60 days after inhaling large
concentration (8000-10,000) of anthrax spores. Evidence points out fewer weapons-grade anthrax
spores may be required to to cause inhalational anthrax.
Presents initially with nonspecific symptoms, including low-grade fever and a nonproductive cough.
Patients may complain of substernal discomfort early in the illness.
Department of Internal Medicine
Anthrax - History
Inhalational (continued) After initial improvement, the disease progresses
rapidly with: High fever Severe shortness of breath Tachypnea Cyanosis Profuse diaphoresis Hematemesis Chest pain (may mimic acute myocardial infarction)
Department of Internal Medicine
Anthrax - Physical
Cutaneous Begins as a pruritic papule that enlarges in 24-48
hours to form an ulcer surrounded by a satellite halo. Regional lymphadenopathy of the nodes draining the
infected area my occur. Characteristically is pruritic but not painful.
Adenopathy associated with cutaneous anthrax may be painful.
The ulcer evolve into a black eschar in 7-10 days and last for 7-14 days before separating and leaving a permanent scar.
Department of Internal Medicine
Anthrax - Physical
Cutaneous (continued) Lymphadenopathy associated with cutaneous anthrax
may persist long after disappearance of the ulcer/eschar.
Department of Internal Medicine
Anthrax - Physical
Inhalational Chest percussion or radiographs reveal a widened
mediastinum. Pulmonary infiltrates are not present because
inhalational anthrax presents as a hemorrhagic mediastinitis, not pneumonia, which may be associated with bloody pleural effusions.
Inhalational anthrax usually is fatal; the patient succumbs to shock and to the effects of lethal toxin.
Department of Internal Medicine
Anthrax
Workup
Department of Internal Medicine
Anthrax – Lab Studies
The preferred diagnostic procedure for cutaneous anthrax is staining the ulcer exudate with methylene blue or Giemsa stain.
B. anthracis readily grows on blood agar. In patients with cutaneous anthrax who have
fever and systemic symptoms that suggest spread, blood culture may be indicated; treat the cultures as biohazard II specimens.
Department of Internal Medicine
Anthrax – Imaging Studies
If inhalational anthrax is suspected, obtain a chest radiograph or CT scan.
The appearance of chest x-ray / CT scan may suggest the diagnosis, especially if other predisposing disorders that might result in a widening mediastinum (eg, dissecting aortic aneurysm), are absent.
Department of Internal Medicine
Anthrax
Treatment
Department of Internal Medicine
Anthrax - Treatment
Preferred agent used to treat anthrax is penicillin.
It is also the preferred agent to treat inhalational anthrax / anthrax meningitis. Use meningeal doses for inhalational anthrax because meningitis often is present as well.
Doxycycline also is a preferred agent. No previous clinical experience exists with using
quinolones in human anthrax.
Department of Internal Medicine
Anthrax - Treatment
Use any quinolone for patients unable to take penicillin or doxycycline.
Treatment ordinarily continues for 1-2 weeks. Post exposure prophylaxis to prevent inhalation
anthrax should be continued for 60 days. No reason exists for instituting double-drug
coverage against B. anthracis, which is a very sensitive organism.
Department of Internal Medicine
Anthrax
Polychrome methylene blue stain of Bacillus anthracis
Department of Internal Medicine
Anthrax
Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain.
Department of Internal Medicine
Anthrax
Cutaneous anthrax
Department of Internal Medicine
Anthrax
Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa
Department of Internal Medicine
Anthrax
Histopathology of the large intestine showing submucosal thrombosis and edema.
Department of Internal Medicine
Anthrax
Chest radiograph
showing widened
mediastinum
resulting from
inhalation
Anthrax.
Department of Internal Medicine
Anthrax
Hemorrhagic meningitis resulting from inhalation anthrax
Department of Internal Medicine
Plague
An Overview
Department of Internal Medicine
Plague
Background
Department of Internal Medicine
Plague - Background
First described in the Old Testament. First pandemic was believed to have started in
Africa and killed 100 million people over a span of 60 years.
In the Middle Ages, it killed approximately one fourth of Europe’s population.
In the early twentieth century plague epidemics accounted for roughly 10 million deaths in India.
Department of Internal Medicine
Plague - Background
Has worldwide distribution It is an acute, contagious, febrile illness transmitted by
an infected rat flea. Human to human transmission is rare except during
epidemics of pneumonic plague. Cause is plague bacillus, a rod-shaped bacteria referred
to as Yersinia pestis. Named in honor of Alexander Yersin, who first isolated
the bacteria in 1894 during the pandemic that began in China in the 1860s.
Department of Internal Medicine
Plague
Pathophysiology
Department of Internal Medicine
Plague - Pathophysiology
Domestic and urban rats are the most important reservoirs for the plague.
The most important vector for transmission of plague is the rat flea, Xenopsylla cheopis.
Once introduced into a host, the bacilli migrate to the regional lymph nodes, and are phagocytosed by polymorphonuclear cells, and multiply intracellularly.
Department of Internal Medicine
Plague - Pathophysiology
Involved lymph nodes show dense concentrations of plague bacilli, destruction of the normal architecture, and medullary necrosis.
The bacteria is a nonmotible, non-spore-forming, pleomorphic, gram-negative coccobacillus.
Department of Internal Medicine
Plague
MMWR
Department of Internal Medicine
Plague - MMWR
Frequency In the US – causes approximately 10 cases of plague
are reported yearly in AZ, CA, CO, NM, and Utah. In recent years, the CDC has specified Y pestis as a
prime candidate for use in bioterrorism. Mortality / Morbidity
Untreated, the mortality rate from plague can be as much as 50%.
With appropriate antibiotics and supportive therapy, the mortality rate is reduced to 5%.
Department of Internal Medicine
Plague - MMWR
Race Most cases occur in whites
Sex Males and females have been equally affected.
Age Most cases occur in persons younger than 20 years.
Department of Internal Medicine
Plague
Clinical Overview
Department of Internal Medicine
Plague - History
Travel to endemic areas within and outside the US.
History of a flea bite. Close contact with a potential host. Exposure to dead rodents or rabbits should
heighten consideration of a plague diagnosis.
Department of Internal Medicine
Plague - History
Bubonic Plague Patients most commonly present with this form Incubation period varies (2-6 days) Have sudden onset of high fever, chills, & headache Experience body aches, extreme exhaustion,
weakness, abdominal pain, and/or diarrhea Painful, swollen lymph glands (buboes) arise, usually
in the groin, axilla, or neck.
Department of Internal Medicine
Plague - History
Meningeal plague Fever, headache, and nuchal rigidity occur Buboes are common with meningeal plague Axillary buboes are associated with an increased
incidence of the meningeal form Pharyngeal plague
Results from ingestion of plague bacilli Experience sore throat, fever, and painful cervical
lymph nodes
Department of Internal Medicine
Plague - History
Pneumonic plague Highly contagious and transmitted by aerosol droplets Abrupt onset of fever and chills, accompanied by
cough, chest pain, dyspnea, purulent sputum, or hemoptysis
Buboes may or may not appear in pneumonic plague
Department of Internal Medicine
Plague - Physical
Bubonic plague Vesicles may be observed at the site of the infected
flea bite A generalized papular rash of the hands and feet may
be observed Buboes are unilateral, oval, extremely tender lymph
nodes and can vary from 2-10 cm in size Femoral lymph nodes are most commonly involved Hepatomegaly and splenomegaly often occur,
causing tenderness
Department of Internal Medicine
Plague - Physical
Pharyngeal plague causes pharyngeal erythema and painful and tender anterior cervical nodes
Pneumonic plague causes fever, lymphadenopathy, productive sputum, or hemoptysis
Generalized purpura may be observed and can progress to necrosis and gangrene of the distal extremities
Patients may die from a high level of bacteremia
Department of Internal Medicine
Plague
Differentials
Department of Internal Medicine
Plague - Differentials
Acute Renal Failure Anthrax Brucellosis Catscratch Disease Cellulitis Chancroid Dengue Fever DIC Lymphoma, B-Cell
Malaria Pharyngitis Pneumonia Rocky Mountain Spotted
Fever Sepsis, Bacterial Septic Shock Syphillis Tularemia
Department of Internal Medicine
Plague
Workup
Department of Internal Medicine
Plague – Lab Studies
Expertise testing for plague bacilli is limited to reference laboratories in plague-endemic states and the CDC.
Leukocytosis with a predominance of neutrophils is observed, and the degree of leukocytosis is proportional to the severity of the illness.
Leukemoid reactions may be observed, more common in children.
Department of Internal Medicine
Plague – Lab Studies
Peripheral blood smear shows toxic granulations and Dohle bodies
Thrombocytopenia is common, and levels of fibrin degradation products may be elevated
Serum transaminase and bilirubin levels may be elevated
Proteinuria may be present and renal function tests may be abnormal
Hypoglycemia may be observed
Department of Internal Medicine
Plague – Lab Studies
Direct immunofluorescence testing of fluid or cultures may aid in rapid diagnosis
A passive hemagglutination test with a 4-fold or greater increase in titer suggests plague infection
Department of Internal Medicine
Plague – Imaging Studies
Chest films demonstrate patchy infiltrates, consolidation, or a persistent cavity in those patients with pneumonic plague
EKG reveals sinus tachycardia and ST-T changes
Obtain CT scan of the head in a patient with altered mental status
Nuclear imaging may help in localizing areas of lymphadenitis and meningeal inflammation.
Department of Internal Medicine
Plague
Treatment
Department of Internal Medicine
Plague – Medical Care
Place in strict respiratory isolation for 48-72 hours after starting antibiotic therapy.
Report all patients thought to have plague to the local health department and the WHO.
Alert laboratory personnel to the possibility of the diagnosis of plague.
Hemodynamic monitoring and ventilatory support are performed as appropriate.
Department of Internal Medicine
Plague – Medical Care
IV fluids, epinephrine, and dopamine are implemented as necessary for correction of dehydration and hypotension.
Department of Internal Medicine
Plague – Surgical Care
Enlarging or fluctuant buboes require incision and drainage.
Department of Internal Medicine
Plague - Medication
Streptomycin is the preferred drug of choice to treat plague.
In patients who are allergic to streptomycin or who cannot tolerate streptomycin, doxycycline is a reasonable alternative.
Chloramphenicol is the preferred drug of choice in meningeal plague or for patients with hypotension.
Department of Internal Medicine
Plague
1998 world distribution of Plague.
Department of Internal Medicine
Plague
Oriental rat flea (Xenopsylla cheopis), the primary vector of plague, engorged with blood.
Department of Internal Medicine
Plague
Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague.
Department of Internal Medicine
Plague
Wayson stain showing the characteristic “safety pin” appearance of Yersinia pestis.
Department of Internal Medicine
Plague
Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis.
Department of Internal Medicine
Plague
Histopathology of lung in fatal human plague – fibrinopurulent pneumonia.
Department of Internal Medicine
Plague
Histopathology of lung showing pneumonia with many Yersinia pestis organisms on Giemsa stain.
Department of Internal Medicine
Plague
Histopathology of spleen in fatal human plague.
Department of Internal Medicine
Plague
Histopathology of lymph node showing medullary necrosis and Yersinia pestis.
Department of Internal Medicine
Plague
Hospitalized patient
demonstrating necrosis
of plague manifestation.
Department of Internal Medicine
Competency Exam
Department of Internal Medicine
Competency Exam - Question 1
A key role for public health in a bioterrorism event is epidemiological investigation.
A) True
B) False
Department of Internal Medicine
Competency Exam - Question 1
A key role for public health in a bioterrorism event is epidemiological investigation.
A) True
B) False
Department of Internal Medicine
Competency Exam - Question 2
Depending on the virus, fatality rates from hemorrhagic fever may approach 90%.
A) True
B) False
Department of Internal Medicine
Competency Exam - Question 2
Depending on the virus, fatality rates from hemorrhagic fever may approach 90%.
A) True
B) False
Department of Internal Medicine
Competency Exam - Question 3
Botulinum antitoxin must be given early because it can reverse paralysis that has already occurred.
A) True
B) False
Department of Internal Medicine
Competency Exam - Question 3
Botulinum antitoxin must be given early because it can reverse paralysis that has already occurred.
A) True
B) False
Department of Internal Medicine
End of Lecture
Thank you for your attendance.