Biological Terrorism Smallpox 5/9/01

History Caused by variola virus Most deaths of any infectious disease ~500 million deaths in 20th 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

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

Bioweapon Potential Prior attempted use as bioweapon French and Indian Wars (1754-1767) British gave Native Americans infected blankets Outbreaks ensued, some tribes lost 50% Allegations of use in U.S. Civil War Alleged use by Japanese in China in WWII

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

Bioweapon Potential Nonimmune population Availability of virus <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

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- any object or substance capable of carrying infectious organisms Theoretically possible but inefficient

Epidemiology All ages and genders affected Incubation period From infection to onset of prodrome Range 7-17 days Typical 12-14 days

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

Epidemiology Infectious Materials Saliva Scabs Urine Possibly blood

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

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

Clinical Features Three stages of disease Incubation- From time of infection to onset of symptoms Average 12-14 days (range 7-17) Asymptomatic Prodromal Nonspecific febrile illness, flu-like Eruptive Characteristic rash

PICS

Classic Centrifugal Rash of Smallpox Involving Face and Extremities, Including the Soles. Photo: National Archives

Classic Centrifugal Rash of Smallpox Involving Face and Extremities. Photo: National Archives

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

Discrete Type of Classical Smallpox Rash Photo: National Archives

Confluent Type of Classical Smallpox Rash Photo: National Archives

Diagnosis Traditional confirmatory methods Newer rapid tests 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

Prevention Vaccination policies Stability Last mandated in U.S. in 1972 World travelers until 1979 Laboratory workers Stability Freeze-dried lasts decades Current stock probably still potent

Prevention Supply Production 7-15 million doses in U.S. as of 1999 >20 years old Stock controlled by CDC Production No current active production the U.S. government has enough vaccine to vaccinate every person in the United States in the event of a smallpox emergency http://www.bt.cdc.gov/agent/smallpox/vaccination/facts.asp