BioterrorismDr Rikin Hasnani

Introduction History CDC classification Potential agents of bioterrorism Role of Public Health system in bioterrorism attack

Introduction

Bioterrorism involves the deliberate release of viruses, bacteria, or their by-products (e.g., toxin) to cause morbidity and mortality in humans, animals, or plants.

All bioterrorism agents are naturally occurring organisms or toxins that can cause sporadic disease under natural circumstances, but on occasion, medical manipulation has been attempted to increase resistance to antibiotics or increase organism virulence.

Bioterrorism is an attractive weapon because biological agents are relatively easy and inexpensive to obtain, can be easily disseminated, and can cause widespread fear and panic beyond the actual physical damage.

Key Features of Biologic Agents Used as Bioweapons High morbidity and mortality Potential for person-to-person spread Low infective dose and highly infectious by aerosol Lack of rapid diagnostic capability Lack of universally available effective vaccine Potential to cause anxiety Availability of pathogen and feasibility of production Environmental stability Database of prior research and development Potential to be “weaponized”

History

Classification

Centers for Disease Control and Prevention (CDC) classifies potential biologic threats into three categories: A, B, and C

Category A agents are the highest-priority pathogens: can be easily disseminated or transmitted from person to person result in high mortality rates have the potential for major public health impact might cause public panic and social disruption require special action for public health preparedness

Category A agents

Anthrax (Bacillus anthracis) Botulism (Clostridium botulinum toxin) Plague (Yersinia pestis) Smallpox (Variola major) Tularemia (Francisella tularensis)Viral hemorrhagic fevers:     Arenaviruses: Lassa, New World (Machupo, Junin, Guanarito, and

Sabia) Bunyaviridae: Crimean Congo, Rift Valley     Filoviridae: Ebola, Marburg     Flaviviridae: Yellow fever; Omsk fever; Kyasanur Forest

Category B agents include those that are moderately easy to disseminate, result in moderate morbidity rates and low mortality rates, and require specifically enhanced diagnostic capacity

Category B Agents

PULMONARY AGENTS Glanders (Burkholderia mallei) Melioidosis (Burkholderia pseudomallei) Psittacosis (Chlamydophila psittaci) Q fever (Coxiella burnetii) Ricin toxin from Ricinus communis (castor beans) NONPULMONARY AGENTS Brucellosis (Brucella species) Epsilon toxin of Clostridium perfringens Food safety threats (e.g., Salmonella species, Escherichia coli O157 : H7, Shigella) Staphylococcal enterotoxin B

Category C Agents

These agents have the future potential for engineering for easy dissemination or high mortality.

Influenza (novel strain) Nipah virus Typhus disease (Rickettsia prowazekii) Viral encephalitis (alphaviruses [e.g., Venezuelan equine encephalitis, eastern equine encephalitis, western equine encephalitis]) Water safety threats (e.g., Vibrio cholerae, Cryptosporidium parvum)

Anthrax

Anthrax is caused by a sporulating gram-positive rod, Bacillus anthracis Human disease largely occurs through contact with animal products,

such as animal skins, where the bacillus form converts back to the spore form.

In 2001, however, 22 cases of anthrax occurred in the United States as an act of bioterrorism through the postal system, placing anthrax on the forefront of bioterrorism.

Disease occurs when the spore form is introduced subcutaneously or via inhalation, becomes the vegetative (bacillus) form, and starts replication. Endotoxin secretion, along with a thick capsule that avoids phagocytosis, leads to local spread, edema, hemorrhage, and tissue necrosis.

The anthrax capsule, edema factor toxin, and lethal factor toxin act in concert to drive disease.

Clinical features

1) Inhalational anthrax : Incubation period 1-7days Within 24 hours, disease rapidly progresses with the development of

respiratory failure, hemorrhagic mediastinitis, necrotizing pneumonia, shock, multiorgan failure and death.

The development of shock and multiorgan failure can occur rapidly, and along with the hemorrhagic mediastinitis, is the clinical hallmark of anthrax.

Cutaneous anthrax has an incubation period of 7 to 14 days after inoculation of spores into the subcutaneous space.

Initially a small, painless papule develops that can be pruritic. The papule enlarges and develops a central vesicle, followed by erosion

into a painless black eschar. Edema of surrounding tissues, and regional lymphadenopathy is seen

along with systemic symptoms of fever and malaise. The hands, arms, face, and neck are the most common areas affected.

Gastrointestinal anthrax occurs after consumption of undercooked meats of infected animals.

Bowel edema occurs, followed by mesenteric lymphadenitis and necrosis, with rapid progression to shock and death.

Management

Diagnosis is made by culture of the blood, sputum, pleural fluid, cerebrospinal fluid, or skin.

Treatment : Ciprofloxacin Doxycyclin

Small pox

Variola virus is the causative agent of smallpox and is a member of the Poxviridae family.

Smallpox was eradicated worldwide in 1977 but now has regained interest as a potential bioterrorism agent.

Due to an increasing unvaccinated population along with its contagiousness and ability to be transmitted by aerosol, smallpox is a CDC category A bioterrorism agent.

Only two stockpiles of the virus remain (at the CDC and the Russian State Research Center) for continued research.

Five main clinical categories: ordinary, - macule , papule, vesicle, pustule modified, more rapid but less severe flat, hemorrhagic,more common in pregnant female Variola sine eruptione

Variola: first and second day of rash (4th-5th day of fever)

Variola: 4th day of rash

•For the first time-on the fourth day of the rash and the fifth day of infectiousness, a typical vesicular appearance is seen

Variola major: drying rash (7-9 days)

•The rash is becoming less infectious•Conjunctival lesions are usually benign and heal completely

Variola major: confluent on day 7 of rash

Variola major: scabbing of rash: day 11

Diagnosis is primarily clinical. RT PCR is awailable only at Centre for disease control. Treatment is supportive, with some evidence that cidofivir has activity in

animal model.

Plague

Yersinia pestis is the etiologic agent of plague and has caused a number of pandemics throughout human history.

Transmission to humans occurs by rodent-infected flea bites, infected animal scratches or bites, exposure to infected humans, and bioterrorism.

Clinical features

In bubonic plague, a sudden onset of fevers, chills, and headache is followed by pain and swelling in the regional lymph nodes proximal to the site of the bite or scratch.

This lymph node (bubo) is characterized by intense tenderness with erythema and edema. Fluctuation test is negative.

Septicemic plague occurs with acute fever followed by sepsis without the presence of a bubo.

Pneumonic plague , has short incubation period and rapidly develops ARDS

Management

Diagnosis : clinical diagnosis is difficult Laboratory diagnosis is primarily by culture of the sputum or blood as Y.

pestis grows well on most laboratory media. Serology and rapid diagnostic testing by ELISA or PCR is also available

but is used primarily in field testing. Treatment : Streptomycin is drug of choice Gentamycin or doxycycline can also be used.

Tularemia

Tularemia is caused by the gram-negative bacterium Francisella tularensis and is a zoonotic disease, with humans as accidental hosts.

Human infections occur by contact with ticks and flies, handling infected animals, improperly prepared animal meat, animal scratches and bites, drinking contaminated water, or aerosolization of the organism from the environment or in bioterrorism.

Human-to-human transmission does not occur.

Clinical features

Six patterns of disease Ulceroglandular, Glandular, Pneumonic, Oropharyneal, Oculoglandular

Management

Diagnosis : Bacteria is very difficult to grow on culture media. Diagnosis is made by ELISA or histologic examination showing gram-

negative intracellular organisms. X ray shows patchy opacities bilaterally,and hilar adenopathy. Pleural effusions and a miliary pattern can alsooccur, although this is

less common. Mediastinal adenopathy is seen rarely. Treatment : Genatamycin is drug of choice Doxycyclin and ciprofloaxacin are 2nd choice

Glanders

It is caused by Burkholderia mallei It is primary a disease of horses. Human is infected due to contact or

droplet infection. Clinical features : usually acute or chronic skin infection Droplet infection can cause pneumonia and sepsis rapidly Usually misclassified on culture as it is a rare disease. Treatment : Imipenem is the drug of choice 3rd generation cephalosporin, ciorofloxacin are alternative

Melioidosis

Caused by Burkholderia pseudomallei. Soil and water are natural reservoir Spread to human by direct contact or inhalation In bioterrorism aerosolisation will lead to pneumonia. Most patients develop sepsis and MODS rapidly. Diagnosis is by culture Treatment : imipenem or 3rd gen cephalsoprin in acute condition

followed by 20day treatment with doxycycline or cotrimoxazole.

Psittacosis

Psittacosis is caused by Chlamydophila psittaci, an intracellular bacterium routinely associated with birds such as parrots, cockatiels, and canaries.

Intentional aerosolization would lead to multiple cases of nonspecific “atypical pneumonia” with cough, fever, and headache.

Diagnosis is by ELISA , difficult to grow on cultures Treatment is macrolide or doxycycline or ciprofloxacin

Q Fever

Q fever is a zoonotic disease caused by Coxiella burnetii. Cattle, sheep, and goats are the primary reservoirs It does not cause clinical disease in animals, bacteria is found in milk,

urine, feces, amniotic fluids, and placenta. Infection by droplet spread. Clinical features : high fevers (> 104° F), severe headache, myalgia, sore

throat, nonproductive cough, nausea, vomiting, diarrhea, abdominal pain, and chest pain.

Fever usually lasts for 1 to 2 weeks. Thirty percent to 50% of patients with symptomatic infection will develop

pneumonia

Endocarditis, chronic Q fever(>6 months) are rare complications. Diagnosis is made by indirect immunoflouroscence assay. Doxycycline 100 mg twice daily for 15 to 21 days is the treatment of

choice for Q fever.

Role of physician

The recognition of a bioterrorism event versus a naturally occurring infection relies on a high suspicion on behalf of the clinician.

However it is difficult in initial stages of disease when symptoms are non specific.

a systematic approach is advocated initially in all febrile respiratory illnesses, with suspicion and should contact public health when specific clinical findings or epidemiologic features are detected that lead the clinician to suspect a bioterrorism or emerging infectious disease event

Role Of Public Health System

Being Prepared Education of medical community Education of public Training of special response teams Participation in exercises for different scenarios Development of communication systems Development of interagency protocols

Initial Response to BT Induced Disease Early detection through surveillance/ rapid assessment of reports Mobilize laboratory Rapid confirmation of agent, site, initial at-risk population,

prophylaxis and/or treatment Alert medical community, ERs, labs Implement disease specific plans (e.g. Smallpox) Determine resource needs and possible quarantine Coordinate with partner agencies (local/state/national

Continued Response to BT Induced Diseases Closely monitor communication network for new information Provide, accurate, timely information to public Continue epidemiologic investigation to refine at risk population Assess environmental contamination Provide or coordinate testing/ prophylaxis/ treatment to at-risk

population Access biological stockpiles as necessary

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