1. Bioterrorism: What We’ve Seen and What We haven’t Part II: Smallpox Presented at Dean’s Forum: UIC School of Public Health January 23, 2002 Ronald C. Hershow, M.D. Douglas Passaro, M.D.

2. 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 Photo: National Archives

3. Mummy: Ramses V

5. Death Rides A Pale Horse

6. Smallpox History

7. Edward Jenner Notion of cowpox vaccine implanted by a milkmaid’s remark Jenner studied protective effect of naturally acquired cowpox during ensuing years 1796, first “vaccination” performed using material taken from a milkmaid’s lesion

8. Edward Jenner Gives Small Pox Vaccine (1802)

9. Smallpox Eradication 1960’s -Restricted to India, Pakistan, Bangladesh, Indonesia, Africa, South America 1967 WHO - 10 year plan to eradicate smallpox Pessimism: –Developing World Huge population Limited resources Scarcity of trained personnel Competing health problems

10. Smallpox Eradication Optimism: –Only human to human transmission –No animal reservoir –Vaccination simple, highly protective –Disease easily recognized –Invariably pathogenic, little subclinic illness –Not highly communicable in most endemic areas (little closed ventilation) –Health structures in endemic countries growing

11. Initial Plan mass vaccination - 80% coverage outbreak control  good surveillance  rapid response  “ring vaccination” William Foege, in Nigeria, demonstrated that effective reporting and intensive ring vaccination could interrupt transmission even if less than half of the population was vaccinated

12. India 1963 –India, started its own eradication efforts Soviet vaccine most adults vaccinated Problems : (1) Rapid population growth, steady pool of susceptibles (2) Frequent travel back and forth from urban to rural areas, religious festival attracted and “mixed” millions of people (3) Religious beliefs (Shitala Mata) led to hostility towards vaccinators (4) Poor surveillance –rainy season –outbreak reporting would be perceived as “failure”

13. India (cont’d) Solutions: (1) Mobile search teams (2) Markets, school (3) Mobilizing 100,000 health workers for monthly “Search Week” (4) Firefighters trained as surveillance-containment teams (5) Financial rewards (6) “Dawn Raids” to vaccinate in the state of Bihar

14. Terminal Phase Outbreak containment March 1975- Last indigenous case reported from state of Bihar 1976 - Last case in Ethiopia

16. The Ultimate Betrayal 1980 the Soviet Union starts Smallpox weapons program producing tons of virus at a time when virus stocks housed in other countries were being systematically destroyed and vaccine was thought to exist in only 2 labs. In 1986 WHO recommends destruction of existing virus stocks after genetic sequencing could be performed 1994, Alibek, former deputy director of Soviet bioweapons program defects

17. Revelations of Alibek Successful weaponization of smallpox accomplished Virus transferred to a facility in Siberia Occurred concurrent with serious economic problems in Russia Raised the question of whether other countries might acquire the technology and weapons

18. Smallpox Vaccination Who is protected? –No one born after 1972 - 40% of U.S. population is < 29 y.o. –Waning immunity of those vaccinated < 1972? How much vaccine is there? –U.S. - 15 million doses (Fauci) –WHO - 0.5 million doses –Other countries - ?? Will diluted virus “work?” –Undiluted - 95% take –1:5 dilution - 90% take –1:10 dilution - 70% take (estimates )

19. Smallpox: Contagious In 1972, a single case of small pox transferred multiple times before the diagnosis was made infected 11 others, who in turn infected 138 more people, led to the isolation of 10,000 people and vaccination of 20,000,000 people in Yugoslavia.

20. Smallpox Vaccination Complications (a live virus vaccine) Disseminated vaccinia Eczema vaccinatum Points: For each 1 million vaccinated, there were > 250 complications Vaccine immune globulin (VIG) Rx is needed - short supply Pre-AIDS!

21. Smallpox: Vaccination Complications Most common –Inadvertent inoculation (skin, eye) Less Common –Generalized vaccinia (242/million) † –Post-vaccination encephalitis (2.9/million)* * Lane, et al., NEJM, 1969;281:1201 † Lane, et al., J Infect Dis., 1970; 122:303

22. Smallpox: Vaccination Complications (continued) Less common (continued) –Fetal vaccinia –Eczema vaccinatum (38/million) † –Vaccinia necrosum (0.9/million) † Primary vaccination - 1 death/million* Revaccination - 0.1 deaths/million*

23. Smallpox: Vaccination Complications WHO: Inadvertent inoculation below eye WHO: Eczema vaccinatum WHO: Vaccinia necrosum

24. Post-exposure use of Vaccine In the event of attack, vaccine administered quickly (1 st four days) to contacts may prevent or lessen the severity of subsequent infection. Post-exposure prophylaxis –Pregnant patients (VIG + Vaccinia vaccine) –Eczema (VIG + Vaccina vaccine) –Immunocompromised patients, No consensus (VIG alone vs. VIG + Vaccinia vaccine?) Ström J., Zetterberg B., ed. (1966) Smallpox outbreak and vaccination problems in Stockholm, Sweden, 1963.Acta Medica Scandinavica, supplementum, 464:1-171