Bioterrorism: Getting the Big Picture Texas Society of Infection Control Practitioners

This program has been created and made possible through a grant from the Texas Department of Health.

Goal At the end of this workshop Infection Control Practitioners will be able to describe various components necessary to develop and implement a successful bioterrorism preparedness program

Objectives Name the 6 Category A Biological Agents, treatment and prophylaxis Discuss appropriate laboratory support systems for dealing with bioterrorism events Describe key concepts of Mental Health in Disasters/Bioterrorism

Objectives List appropriate infection control precautions for Category A biological agents Identify security, transportation and communication needs in your facility Identify roles of external agencies in a disaster event

Saint Louis Unversity School of Public Health Definition of Bioterrorism The unlawful use, or threatened use, of microorganisms or toxins derived from living organisms to produce death or disease in humans, animals, or plants. The act is intended to create fear and/or intimidate governments or societies in the pursuit of political,religious, or ideological goals.

Saint Louis Unversity School of Public Health Bioterrorism Agents Potentially hundreds Features of most likely agents Availability Ease of production Lethality Stability Infectivity

Saint Louis Unversity School of Public Health Bioterrorism: A Legitimate Threat Most agents relatively easy to produce Availability of information on the Internet Access to dual use equipment Relatively inexpensive 1970 study–cost of 50% casualty rate per km 2 conventional - $2,000 nuclear - $800 anthrax - $1

Saint Louis Unversity School of Public Health Bioterrorism: A Legitimate Threat Dissemination may cover large area Difficult to detect release Symptoms occur days or weeks later Some have secondary spread

Saint Louis Unversity School of Public Health Bioterrorism: A Legitimate Threat Use can cause panic Users able to protect selves Users can escape before effect

Saint Louis Unversity School of Public Health Bioterrorism: A Legitimate Threat Former Soviet scientists successfully weaponized many agents Active research was undertaken to engineer more virulent strains

Saint Louis Unversity School of Public Health Bioterrorism: A Legitimate Threat With the collapse of the Soviet Union, microbe stock & technology has possibly landed in hands of terrorists State sponsorship of terrorism At least 17 nations are known to have offensive biological weapons programs

Saint Louis Unversity School of Public Health Delivery Mechanisms Aerosol likely route for most agents Easiest to disperse Highest number of people exposed Most contagious route of infection Food / Waterborne less likely Only effective for some agents

Saint Louis Unversity School of Public Health Epidemiology Clues suggesting a bioweapon release Large numbers present at once (epidemic) Previously healthy persons affected High morbidity and mortality Unusual syndrome or pathogen for region Recent terrorist claims or activity Unexplained epizootic of dead, sick animals

Saint Louis Unversity School of Public Health Role of Primary Care Physician Have a high level of suspicion Keep BT agents in differential diagnosis Recognize typical BT disease syndromes Be aware of unusual epidemiologic trends Know treatment/prophylaxis of BT agents Know how to report suspected BT cases

Bioterrorism-Diseases Risk Category A

Centers for Disease Control Category A Biological Agents Can be easily disseminated or transmitted from person to person Result in high mortality rates and have the potential for major public health impact Might cause public panic and social disruption Require special action for public health preparedness

Centers for Disease Control Category A Biological Agents Anthrax Botulism Plague Smallpox Tularemia Viral Hemorrhagic Fever

Centers for Disease Control Category B Biological Agents Are moderately easy to disseminate Result in moderate morbidity rates and low mortality rates Require specific enhancements of CDC's diagnostic capacity and enhanced disease surveillance

Centers for Disease Control Category B Biological Agents Brucellosis Epsilon toxin of Clostridium perfringens Food safety threats Salmonella E. coli O157:h7 Shigella

Centers for Disease Control Category B Biological Agents Glanders Melioidosis Psittacosis Q Fever Ricin toxin Staphylococcal enterotoxin B

Centers for Disease Control Category B Biological Agents Typhus fever Viral encephalitis Water safety threats Vibrio cholerae Cryptosporidium

Centers for Disease Control Category C Biological Agents 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 and potential for high morbidity and mortality rates and major health impact

Centers for Disease Control Category C Biological Agents Emerging infectious diseases Nipah virus Hantavirus

Common Clinical Manifestations of Bioterrorism Agents Skin lesions w/fever Acute respiratory distress w/fever Influenza-like illness Neurologic syndromes

Skin Lesions w/Fever Smallpox Cutaneous Anthrax

Acute Respiratory Distress w/Fever Inhalation Anthrax Pneumonic Plague

Flu-like Illnesses Tularemia Inhalational Anthrax Viral Hemorrhagic Fever Smallpox (Pretty much everything except the kitchen sink!)

Neurologic Illnesses Ricin VX Sarin gas Mustard gas Botulism

Smallpox

Saint Louis Unversity School of Public Health Smallpox: History Caused by variola virus Most deaths of any infectious disease ~500 million deaths in 20 th Century ~2 million deaths in 1967 Known in ancient times Described by Ramses Natural disease eradicated Last U.S. case – 1949 (imported) Last international case – 1978 Declared eradicated in 1979 Photo: National Archives

Saint Louis Unversity School of Public Health Smallpox: Bioweapon Potential Features making smallpox a likely agent Can be produced in large quantities Stable for storage and transportation Known to produce stable aerosol High mortality Highly infectious Person-to-person spread Most of the world has little or no immunity

Saint Louis Unversity School of Public Health Smallpox: Bioweapon Potential Current concerns Former Soviet Union scientists have confirmed that smallpox was successfully weaponized for use in bombs and missiles Active research was undertaken to engineer more virulent strains Possibility of former Soviet Union virus stock in unauthorized hands

Saint Louis Unversity School of Public Health Smallpox: Bioweapon Potential Nonimmune population <20% of U.S. with substantial immunity Availability of virus Officially only 2 stocks (CDC and Russia) Potential for more potent attack Combined with other agent (e.g. VHF) Engineered resistance to vaccine

Saint Louis Unversity School of Public Health Smallpox: Bioweapon Potential Delivery mechanisms Aerosol Easiest to disperse Highest number of people exposed Most contagious route of infection Most likely to be used in bioterrorist attack Fomites Theoretically possible but inefficient

Saint Louis Unversity School of Public Health Smallpox: Epidemiology All ages and genders affected Incubation period From infection to onset of prodrome Range 7-17 days Typical days

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Transmission Airborne route known effective mode Initially via aerosol in BT attack Then person-to-person Hospital outbreaks from coughing patients Highly infectious <10 virions sufficient to cause infection Aerosol exposure <15 minutes sufficient

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Person-to-person transmission Secondary Attack Rate (SAR) 25-40% in unvaccinated contacts Relatively slow spread in populations (compared to measles, etc.) Higher during cool, dry conditions Historically 3-4 contacts infected May be in unvaccinated population Very high potential for nosocomial spread Usually requires face-to-face contact

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Transmission via fomites Contaminated hospital linens/laundry May have been successfully used as weapon in French-Indian War

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Infectiousness – Rash is marker Onset approx one day before rash Peaks during first week of rash ? Carrier state possible Some data show virus detectable in saliva of contacts who never become infected Unclear if they can transmit infection, but theoretically possible

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Infectious Materials Saliva Vesicular fluid Scabs Urine Conjunctival fluid Possibly blood

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Role of index case severity Does not predict transmissibility Does not predict severity of 2° cases Role of prior vaccination Immunity wanes with time Maintain partial immunity for many years Partial immunity reduces disease severity Reduces transmissibility (less virus shed)

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Mortality 25-30% overall in unvaccinated population Infants, elderly greatest risk (>40%) Higher in immunocompromised May be dependent on ICU facilities Dependent on virus strain Dependent on disease variant

Saint Louis Unversity School of Public Health Smallpox: Epidemiology Factors that allowed smallpox eradication Slow spread Effective, relatively safe vaccine No animal/insect vectors No sig. carrier state (infected die or recover) Infectious only with symptoms Prior infection gives lifelong immunity International cooperation

Saint Louis Unversity School of Public Health Smallpox: Microbiology Variola virus – the agent of smallpox Orthopoxviridae family 2 strains of variola –Variola major –Variola minor Vaccinia –Used for current vaccine –Namesake of “vaccine” Cowpox – used by Jenner in first vaccine Monkeypox – rare but serious disease from monkeys in Africa

Saint Louis Unversity School of Public Health Smallpox: Microbiology Variola major Classic smallpox Predominant form in Asian epidemics Highest mortality (~30%)

Saint Louis Unversity School of Public Health Smallpox: Microbiology Variola minor Same incubation period, mode of transmission, clinical presentation Causes milder disease Less severe prodrome and rash Mortality ~1% Discovered in 20 th century Started in S. Africa Was most predominant form in N. America

Saint Louis Unversity School of Public Health Smallpox: Microbiology Environmental survival Longest (>24hr) in low temp/low humidity Inactive within few hours in high temp/humidity Dispersed aerosol completely inactivated within 2 days of release

Saint Louis Unversity School of Public Health Smallpox: Pathogenesis Virus lands on respiratory/oral mucosa Macrophages carry to regional nodes Primary viremia on Day 3 Invades reticuloendothelial organs Secondary viremia on Day 8

Saint Louis Unversity School of Public Health Smallpox: Pathogenesis White Blood Cells infected WBCs migrate capillaries, invade dermis Infects dermal cells Influx of WBCs, mediators cause vesicle Systemic inflammatory response Triggered by viremia Sepsis, multiorgan failure, often DIC

Saint Louis Unversity School of Public Health Smallpox: Pathogenesis Severity of disease Not influenced by severity of source case Probably related to degree of viremia Inoculation dose –Longer exposure, higher concentration at release Virulence of variola –strain, engineered resistance Host immune status Type of rash predictive of outcome More severe rashes = poorer outcomes

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Three stages of disease Incubation Asymptomatic Prodromal Nonspecific febrile illness, flu-like Eruptive Characteristic rash

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Incubation Stage From time of infection to onset of symptoms Average days (range 7-17) Important for epidemiologic investigation Considered non-infectious during this stage Virus sometimes culturable

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Prodromal Stage Common symptoms High fever, prostration, low back myalgias, HA Occasional symptoms Vomiting, abdominal pain, delirium Duration typically 3-5 days End of stage heralded by mucosal lesions Mucosal lesions onset of infectiousness

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Eruptive Stage (Rash) May start with transient defervescence Characteristic rash Centrifugal (in order of appearance & severity) Initially oral mucosa– borders pre-eruptive stage Head, face Forearms, hands, palms Legs, soles, +/- trunk

Saint Louis Unversity School of Public Health Classic Centrifugal Rash of Smallpox Involving Face and Extremities, Including the Soles. Photo: National Archives

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Rash stages of development All lesions in one region at same stage Starts macular, then papular Deep, tense vesicles by Day 2 of rash Turns to round, tense, deep pustules Pustules dry to scabs by Day 9 Scabs separate

Classic Smallpox Rash, Demonstrating Same Development Stage (Pustular) of All Lesions in a Region Photo: National Archives

Smallpox

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Scarring From separated scabs Fibrosis, granulation in sebaceous glands Pink, depressed pock marks Prominent on face, usually >5 lesions Permanent

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Rash variations Sine eruptione variant Prodrome without rash Clinically less severe

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Modified variant Previously vaccinated with partial immunity Milder rash, better outcome, faster resolution Photo: National Archives

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Rash variations Ordinary (Classic presentation) variant >90% all cases Subdivided based on confluence of lesions –Discrete (<10% mortality) –Semi-confluent (25-50% mortality), most common –Confluent (50-75% mortality)

Saint Louis Unversity School of Public Health Photo: National Archives

Saint Louis Unversity School of Public Health Photo: National Archives

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Rash variations Flat (Malignant) variant Uncommon Prodrome more sudden, severe More likely severe abdominal pain Rash never forms pustules/scabs Leathery in appearance Sometimes hemorrhagic or exfoliating DDX – acute abdomen, hemorrhagic varicella >90% mortality

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Rash variations Hemorrhagic Rare Prodrome more acute and severe Bleeding diathesis before onset of rash Rash is also hemorrhagic Pregnant women at highest risk (?immune state) Higher risk of transmission (more fluid shedding) DDX – meningococcemia, DIC Mortality 100%

Saint Louis Unversity School of Public Health Smallpox: Clinical Features In an outbreak setting atypical or variant rashes must be considered smallpox until proven otherwise

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Complications Sepsis/toxemia Usual cause of death Associated with multiorgan failure Usually occurs during 2 nd week of illness Encephalitis Occasional Similar to demyelination of measles, varicella

Saint Louis Unversity School of Public Health Smallpox: Clinical Features Complications Secondary bacterial infections uncommon Staphylococcus aureus cellulitis –Responds to appropriate antibiotics Corneal ulcers –A leading cause of blindness before 20 th Century Conjunctivitis rare During 1 st week of illness

Saint Louis Unversity School of Public Health Smallpox: Diagnosis Clinical diagnosis Sufficient in outbreak setting >90% have classical syndrome Prodrome followed by rash Rarely, variants can be difficult to recognize Hemorrhagic – mimics meningococcemia Malignant – more rapidly fatal Sine eruptione – prodrome without rash Partially immune – milder, often atypical

Saint Louis Unversity School of Public Health Smallpox: Diagnosis Traditional confirmatory methods Electron microscopy of vesicle fluid Rapidly confirms if orthopoxvirus Culture on chick membrane or cell culture Slow, specific for variola Newer rapid tests Available only at reference labs (e.g. CDC) PCR, RFLP

Saint Louis Unversity School of Public Health Smallpox: Diagnosis Differential Diagnosis Chickenpox (varicella) Vesicles shallow, in crops, varied stages Centripetal, spares palms/soles Other orthopox viruses Monkeypox – only in Africa, monkey contact Vaccinia – after exposure to vaccine Cowpox – rare, only in UK

Smallpox Chickenpox Physical exam Centrifugal distribution Peaks at 7 to 10 days Lesions in same stage of evolution 4-6 mm diameter Round shape Desquamation in days Lesions on palms and sole Physical exam Central distribution Peaks at 3-5 days Lesions in different stages of evolution 2-4 mm diameter Oval shape Desquamation in 6-14 days Uncommon to have lesions on palms and sole

Smallpox Chickenpox

Saint Louis Unversity School of Public Health Smallpox: Treatment Management of cases Supportive Post-exposure prophylaxis Vaccine Vaccinia immunoglobulin Primary prophylaxis Vaccine

Saint Louis Unversity School of Public Health Smallpox: Treatment Managing confirmed or suspected cases No specific effective antiviral treatment Supportive care is critical Electrolytes / Volume / Ventilation / Pressors Antibiotics only for secondary infections e.g. S. aureus cellulitis Isolation Vaccinate (in case diagnosis is wrong)

Saint Louis Unversity School of Public Health Smallpox: Post-Exposure Prophylaxis Vaccine Protective if given within 3-4 days exposure Reduces incidence 2-3 fold Decreases mortality by ~50% Vaccinia immune globulin (VIG) 3 fold decrease in incidence and mortality Passive immunity for 2 weeks Very limited supply (at CDC)

Saint Louis Unversity School of Public Health Smallpox: Infection Control Vital component of outbreak management Transmission is key No animal/arthropod vectors No known asymptomatic reservoirs carrier state hypothetical but not confirmed Higher rate in cool, dry conditions

Saint Louis Unversity School of Public Health Smallpox: Infection Control Transmission Overall secondary attack rate 25-40% Historically 3-4 cases per index patient Outbreak in mostly nonimmune population Anticipate cases per contact All body fluids infectious Respiratory secretions main culprit Cough dramatically increases transmission

Saint Louis Unversity School of Public Health Smallpox: Infection Control Period of infectiousness Onset usually 1 day before rash associated with mucosal lesions sometimes transient defervescense at end of prodromal stage Lasts until all lesions scabbed over Longer duration with more severe cases

Saint Louis Unversity School of Public Health Smallpox: Infection Control Isolation of Cases Home isolation is preferable Avoids nosocomial spread Droplet and inoculation protection Contact precautions – glove, gown, face shield Aerosol protection Negative pressure room, HEPA filter Assign immune persons for care

Saint Louis Unversity School of Public Health Smallpox: Infection Control Management of Case Contacts Carefully identify true contacts Exposure to a case patient after fever onset Contact with secretions OR Face-to-face contact OR In nosocomial setting with a case –Includes ALL hospital patients and staff Except for nosocomial, large group exposure unlikely – usually bedridden by fever onset

Saint Louis Unversity School of Public Health Smallpox: Infection Control Management of Case Contacts Vaccination Proven benefit given within 3-4 days of exposure Observation for 17 days Twice daily temperature check Isolation if fever > 38.0º C

Saint Louis Unversity School of Public Health Smallpox: Infection Control Handling of specimens BSL4 laboratory containment only Handling of linens/laundry Place in leak-proof containers Autoclave before laundering Launder in hot water & bleach Cremation recommended for corpses

Saint Louis Unversity School of Public Health Smallpox: Infection Control Surveillance and containment critical Correct identification of those at risk Conservation of vaccine Target only those with true risk Limited national supply Components Aggressive case-seeking Aggressive contact-seeking & observation

Saint Louis Unversity School of Public Health Smallpox: Decontamination Original aerosol release setting Likely no decontamination applicable Rapid dispersion of virus –<6 hours in higher heat, humidity –Most gone by 24 hours even under ideal conditions –Completely dissipated by 2 days Delayed onset of symptoms (at least 1 week) Virus long gone by time of index case recognition in covert release

Saint Louis Unversity School of Public Health Smallpox: Decontamination If known recent release HEPA filtration Sterilization of surfaces Standard disinfectants such as bleach

Saint Louis Unversity School of Public Health Smallpox Essential Pearls Smallpox has been weaponized Case fatality will likely approach 30% Clinical diagnosis Asymptomatic incubation period 7-17 days Prodrome with high fever 3-5 days Eruptive phase with typical rash Centrifugal (head, face, hands/palms, feet/soles) Vesicles all same stage of development

Saint Louis Unversity School of Public Health Smallpox Essential Pearls Highly infectious Not infectious prior to fever onset Infectiousness starts one day before rash Lasts until all lesions scabbed over Secondary attack rate 25-40% Expect º cases per index case No specific treatment, only supportive

Saint Louis Unversity School of Public Health Smallpox Essential Pearls Case identification & isolation essential Droplets / secretions (contact isolation) Aerosols (negative pressure isolation) Isolate at home if possible (quarantine) Post-exposure prophylaxis for contacts Vaccine (with VIG for hi-risk groups) Fever observation x 17days, isolate if >38.0

Saint Louis Unversity School of Public Health Smallpox Essential Pearls Report any suspected smallpox cases to your State and Local Health Departments