DECEMBER 26, 2002


     As we enter a new century, the ancient scourge of smallpox, a disease that had been almost eradicated by vaccination, is emerging again as a threat – as a weapon of bioterrorism.  In the past, smallpox (variola) surpassed cholera, yellow fever, and even bubonic plague in its contagion, virulence, and mortality rate.  The decimation of many Native Americans on our western frontier by European settlers during the 18th and 19th centuries is a shameful episode in our history.  Sometimes, blankets that had been used to cover afflicted immigrants were sold, traded, or even smuggled into their camps in order to spread the disease.  Its terrible effects were seen even in the early 19th century; there were 2500 smallpox deaths in Kentucky 1898-1901.

     In 1796, after observing that milkmaids and others who had developed the benign cowpox did not get smallpox, the English surgeon, Edward Jenner, made a vaccine from cowpox serum that led to the widespread, highly effective vaccination of whole populations.  As a result, the last epidemic of smallpox in the USA was a small one in New York City in 1947.  In 1967, the World Health Organization mounted a highly successful international vaccination program and smallpox was considered to be a disease that had been conquered.  The last vaccination in the USA was in 1972.

     As a disease, smallpox spreads by droplets expelled from an ill person’s oropharynx or by direct personal contact or contact with contaminated bedding or clothing.  It is most infectious from the onset of the rash through the next 7-10 days.  Transmission is greatest when the victim’s rash is ending and infectivity declines as the scabs form.  Smallpox has a seasonal occurrence; large outbreaks usually occur in winter and are rare in summer.  It has no host or reservoir except humans and no subclinical carriers.

     The inhalation of the droplets infects the lungs; the virus multiplies in the eptithelial cells and mononuclear cells and the first viremia is cleared by the RES, but there is extensive multiplication of the virus in the RES and a second massive viremia.  Major symptoms are fever, myalgia, malaise and involvement of the skin and internal organs, with high fever, abdominal pain, and delirium.  It is 12 days from the initial infection to the second viremia and in 2 more days a maculopapular rash with lesions of the oral mucosa, pharynx, face, forearms, trunk and legs.  In one to two days it becomes vesicular and then pustular.  Crusts that cause scarring form in 8-9 days.  The viral load is large and death occurs in the second week from widespread focal cell death.  Death of the organism results from the massive inflammatory response and its complications.  The most lethal forms of smallpox are: 1) The uniformly fatal early hemorrhagic smallpox in which the toxemia of the prodrome continues until the victim dies on the 5th or 6th day of the rash or less and 2) The malignant with its terrible confluent lesions in which the reddened skin feels like crepe paper and peels away in large amounts.

     The clinical diagnosis is made by noting the rash with its centrifugal distribution and by such signs as the appearance of the lesions within one to two days, the lesions being at the same stage, and present even on the palms and soles.  The laboratory diagnosis is made by growing the virus in tissue culture or eggs and identifying it.  Specimens need to be collected by a vaccinated person wearing gloves and a mask.

     The discovery of just a single case is an international health emergency.  The aerosol release of the smallpox virus even in a small amount can infect 15-20 persons.  The time period from release to diagnosis is 12-14 incubation days plus 2-5 days to make a definitive diagnosis.  Therefore, all suspected persons need to be isolated and vaccinated within 4 days of exposure.  It is imperative that they should not be hospitalized because the widespread dissemination of the virus, especially by aerosol, can produce a serious health threat.  Instead, the person needs to be isolated for 17 days at home or in a special nonhospital facility.  If at home, the patient must be quarantined – forcibly when necessary.  The home care is primarily supportive inasmuch as there is no definitive treatment.

     Although there has been a long history of biological warfare, it was not a prominent feature of modern warfare and there was relatively little concern about it until the post WWII years.  Then, the rapid technological developments during the 1940s and the “cold war” era made it apparent that biological weapons were becoming available and could be used over long distances when placed on bombs or carried by missiles.  Consequently, in 1972, at the Biological and Toxic Weapons Convention, a proposal to discontinue biologic weapons was developed that was ratified by 140 nations, including the USSR and Iraq.  Although there was no mechanism for verification of compliance with the proposal, the USA Research Program was dismantled.  In fact, the success of vaccination programs was so great that in 1980 the WHO recommended that routine vaccinations should cease; in as much as their complications threatened to become more of a problem than smallpox.  As a precaution, and in accord with principles of preventive medicine, some of the Variole virus used for vaccinations was stored by the USA and the USSR.

     In the past few years, however, the bioterrorism threat has emerged again.  In 1999, the Director of the Russian bioterrorism program announced that they had had an active program since 1980 to develop more virulent, contagious recombinant strains of the virus.  In the USA, fears of bioterrorism have mounted since “9/11” and have almost skyrocketed with the Iraq crisis.  USSR defectors have disclosed that 10 nations have the capability to launch a bioterrorist attack.  In particular, the Iraqi capability to do so is intact; it is known that they have at least 20,000 botulinum and 8,000 anthrax spores.  Along with smallpox, plague, anthrax, and botulism spores are suitable for aerolization and for delivery on missile warheads.  In addition to Iraq, Libya, Iran, Syria, and North Korea have been recruiting Russian scientists.  It is estimated that between 10% and 50% of the vaccinated and unvaccinated persons in the USA, especially those between ages 5 and 40, are at risk for infection if we are attacked with bioterrorist weapons including the smallpox virus.  Other microbial agents likely to be used are plague, anthrax, and botulism.

     In summary, smallpox has been eliminated as a disease, but modern science has created the opportunity for bioterrorism and the population of the USA is immunologically naïve for the Variola virus.  The smallpox case fatality rate is about 30% but vaccination reduces the risk of disease; however, smallpox vaccination has not been free of adverse complications.  Therefore, in view of the risk of bioterrorism, the selection of defined populations for smallpox vaccination is necessary.  The current CDC recommendations include: 1) No general vaccination of the population; 2) The vaccination of smallpox response teams; and 3) The vaccination of health care workers.