department of internal medicine. bioterrorism jim czarnecki, d.o. resident lecture series

Department of Internal Medicine


Bioterrorism

Jim Czarnecki, D.O.

Resident Lecture Series


Introduction


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.


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.


History


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.


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.


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.


Organisms


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


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.


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)


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


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


Organisms – Category B Agents

Epsilon toxin of Clostridium perfringens Staphylococcus enterotoxin B Salmonella spp. Shigella dysenteriae Escherichia coli O157:H7 Vibrio cholerae Cryptosporidium parvum


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


Organisms – Category C Agents

Nipah virus Hanta viruses Tickborne hemorrhagic fever viruses Tickborne encephalitis viruses Yellow fever Multidrug resistant tuberculosis


Anthrax

An Overview


Anthrax

Background


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.


Anthrax

Pathophysiology


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.



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.



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.


Anthrax

MMWR


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%).


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.


Anthrax

Clinical Overview


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.


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.


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)


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.


Anthrax - Physical

Cutaneous (continued) Lymphadenopathy associated with cutaneous anthrax

may persist long after disappearance of the ulcer/eschar.


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.


Anthrax

Workup


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.


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.


Anthrax

Treatment


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.


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.


Anthrax

Polychrome methylene blue stain of Bacillus anthracis


Anthrax

Histopathology of mediastinal lymph node showing a microcolony of Bacillus anthracis on Giemsa stain.


Anthrax

Cutaneous anthrax


Anthrax

Histopathology of large intestine showing marked hemorrhage in the mucosa and submucosa


Anthrax

Histopathology of the large intestine showing submucosal thrombosis and edema.


Anthrax

Chest radiograph

showing widened

mediastinum

resulting from

inhalation

Anthrax.


Anthrax

Hemorrhagic meningitis resulting from inhalation anthrax


Plague

An Overview


Plague

Background


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.


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.


Plague

Pathophysiology


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.


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.


Plague

MMWR


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%.


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.


Plague

Clinical Overview


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.


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.


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


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


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


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


Plague

Differentials


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


Plague

Workup


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.



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



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


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.


Plague

Treatment


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.


Plague – Medical Care

IV fluids, epinephrine, and dopamine are implemented as necessary for correction of dehydration and hypotension.


Plague – Surgical Care

Enlarging or fluctuant buboes require incision and drainage.


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.


Plague

1998 world distribution of Plague.


Plague

Oriental rat flea (Xenopsylla cheopis), the primary vector of plague, engorged with blood.


Plague

Swollen lymph glands, termed buboes, are a hallmark finding in bubonic plague.


Plague

Wayson stain showing the characteristic “safety pin” appearance of Yersinia pestis.


Plague

Fluorescence antibody positivity is observed as bright, intense green staining around the cell wall of Yersinia pestis.


Plague

Histopathology of lung in fatal human plague – fibrinopurulent pneumonia.


Plague

Histopathology of lung showing pneumonia with many Yersinia pestis organisms on Giemsa stain.


Plague

Histopathology of spleen in fatal human plague.


Plague

Histopathology of lymph node showing medullary necrosis and Yersinia pestis.


Plague

Hospitalized patient

demonstrating necrosis

of plague manifestation.


Competency Exam


Competency Exam - Question 1

A key role for public health in a bioterrorism event is epidemiological investigation.

A) True

B) False



Depending on the virus, fatality rates from hemorrhagic fever may approach 90%.

A) True

B) False



Botulinum antitoxin must be given early because it can reverse paralysis that has already occurred.

A) True

B) False


End of Lecture

Thank you for your attendance.

department of internal medicine. bioterrorism jim czarnecki, d.o. resident lecture series

Documents

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