smallpox spreads. While very brief exposures of susceptible persons could occasionally lead to infection, epidemiologists engaged in the global smallpox eradication program concluded that the disease spreads rather slowly. Because of the importance of face-to-face contact, the household constituted by far the most frequently affected group. However, hospitals, schools, and public events also contributed significantly to the spread of smallpox. Because of the long incubation period of the infection (see Chapter 3), infected travelers could cover long distances while apparently healthy and could thus introduce smallpox into areas far removed from the source of their infection. In the past, fellow travelers were sometimes infected when ambulant patients, probably infected with vaccine modified smallpox, traveled in close contact with others. If an outbreak were to occur today, however, most infected travelers would become infectious after arriving at their destinations, some of which would likely be far from their point of infection.

Subclinical infections with variola virus seldom occurred, except when individuals who had been vaccinated were in close contact with infectious cases. These individuals rarely transmitted smallpox to others and were of little epidemiological importance. An attack of smallpox is followed by death or recovery. Persistent, latent, or recurrent infection does not occur, and cases are not infectious after the rash disappears. Survivors generally have immunity for life. Smallpox spread slowly, with an interval of 2 to 3 weeks between each generation of cases. Even during winter and spring, when smallpox appeared to be more easily transmitted, an infectious patient seldom infected as many as five other persons.

Likely Characteristics of Future Smallpox Outbreaks

Only three smallpox outbreaks that occurred during and following the eradication program were clearly identified as attributable to accidents at laboratories handling live variola virus. Regulations governing the handling of live variola virus and related clinical material subsequently became much more stringent, so the most likely source of a future outbreak would be deliberate release by terrorists or rogue nations.

In an accidental release, those infected could range from a single individual to a moderate number of individuals. Deliberate release, however, would probably result in essentially simultaneous infection of many individuals. If the release exposed persons who were highly mobile, the relatively lengthy incubation period of the infection could enable the infection to spread widely before being identified. Thereafter the outbreak would probably resemble those that occurred historically in places where smallpox was not endemic and that came to light only after the infection had been passed to the second generation of patients [13].

Individuals infected with variola virus become sick before they are fully infectious to others. For this reason, the spread of smallpox historically in



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