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--> 4 Epidemiology The earliest writers on smallpox—Ko Hung in China, Vagbhata in India, and al-Razi in Asia Minor—describe it primarily as a disease of children. This is a mark of well-established endemic prevalence, and argues that smallpox had been present in those areas for centuries. At the beginning of the 20th century—a hundred years after the introduction of vaccination—smallpox was endemic in almost every country of the world. In 1920, the only countries with large enough populations to support endemic smallpox where it was absent were Australia and New Zealand, which were protected by distance and effective seaport quarantines. A population with at least 200,000 susceptible individuals is required to support endemic smallpox. Characteristics Of Historical Outbreaks All histories of smallpox record periods punctuated by major epidemics, which can be distinguished by two epidemiologically distinct situations. The first was when smallpox was introduced into a location where it had not occurred previously, or at least not for many years, so that a large portion of the population was susceptible. This led to epidemics affecting all age groups and producing considerable social disruption since most breadwinners were afflicted. The second situation was one in which, for a variety of demographic, climatic, and other reasons, optimum conditions for transmission fluctuated so that epidemics occurred every few years against a background of endemicity. This situation was much less socially disruptive than the first because there were always many smallpox-immune adults. The size and density of the population at risk affect the chances of contact between susceptible and infectious persons, and thus the rapidity with which
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--> 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 . 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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--> nonendemic areas was principally to close family members, even when a high proportion of the population had not been vaccinated [13, 14]. Although the human-to-human transmission rate of the disease can be high, an individual infected patient did not have numerous close contacts unless he or she was in a large household, a hospital, or some other institution (homes for elderly, for example, suffered in recorded outbreaks). This experience suggests that a future outbreak of smallpox would infect people of all ages, but that the epidemic would not become explosive, as would be the case with a disease transmitted prior to the onset of illness. Control Strategies Herd immunity (a large number of immune individuals in the exposed population) limits the spread of diseases transmitted by subclinically infected persons or patients who are fully mobile. It is less important for smallpox, since once infectious, patients are typically confined to bed. Hindsight reveals that the vast majority of vaccinations during the panics associated with smallpox outbreaks in the past were unnecessary since transmission was limited mainly to close contacts within the household or hospital. Prompt diagnosis, isolation, and vaccination of close contacts is of much greater importance. This was essentially the strategy employed in the global eradication program. Given that the disease would probably be transmitted to the second generation of patients before being diagnosed, however, suitable antiviral therapies would be of great value. Yet, as discussed in Chapter 6, no currently available antiviral agent is effective against variola virus infection, development of such an agent would be time-consuming and costly, and its therapeutic effectiveness would remain unproven until an outbreak occurred. A smallpox outbreak would be a medical emergency. Criteria for contraindications to vaccination and for the type of vaccine to be used would need to be less strict than in the absence of the disease. Rapidity of response would probably be of greater immediate concern than safety. Nevertheless, the considerable number of individuals immunocompromised as a result of the AIDS epidemic and increased organ transplant and chemotherapy procedures constitute a special risk since inoculating these individuals with the traditional live vaccinia vaccine is not acceptable (see also Chapter 7). The lessons of the past can help us prepare for future smallpox outbreaks. At the same time, however, the techniques of the past need to be augmented by the best contemporary knowledge available.
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