The Power of Plagues. Irwin W. Sherman

infectious only after symptoms appear, and the infection requires that the victim be hospitalized.

Infectiousness, however, may persist even after disease symptoms have disappeared; such infectious but asymptomatic individuals are called carriers. The most famous of these carriers was the woman called “Typhoid Mary,” an Irish immigrant to the United States whose real name was Mary Mallon. In 1883 she began working as a cook for a wealthy New York banker, Charles Henry Warren, and his family. The Warren family rented their large house in Oyster Bay, Long Island, from a George Thompson. That summer, six of eleven people in the house came down with typhoid fever (caused by the “germ” Salmonella typhi), including Mrs. Warren, two daughters, two maids, and a gardener. Mr. Thompson, fearing he would be unable to rent his “diseased house” to others, hired George Soper, a sanitary engineer, to find the source of the epidemic. Soper’s investigation soon led him to Mary Mallon, who had been hired as a cook just 3 weeks before the outbreak of typhoid in the Warren household. Mary had remained with the Warrens for only a month and had already taken another position when Soper found her. On June 15, 1907, Soper published his findings in the Journal of the American Medical Association: Mary was a healthy carrier of typhoid germs. Although she was unaffected by the disease (which causes headache, loss of energy, diarrhea, high fever, and, in a tenth of cases, death), she still could spread it. When Soper confronted Mary and told her she was spreading death and disease through her cooking, she responded by seizing a carving fork, rushing at him, and driving Soper off. Soper, however, was undaunted and convinced the New York City Health Department that Mary was a threat to the public’s health. She was forcibly carried off to an isolation cottage at Riverside Hospital on Rikers Island in the Bronx. There, her feces were examined and found to contain the typhoid bacteria. Mary remained at the hospital, without her consent, for 3 years and then was allowed to go free as long as she remained in contact with the Health Department and did not engage in food preparation. She disappeared from the Health Department’s view for a time but then took employment as a cook at the Sloane Maternity Hospital under an assumed name, Mrs. Brown.

      During this time she spread typhoid to 25 doctors, nurses, and staff, 2 of whom died. She was sent again to Rikers Island, where she lived the rest of her life, 23 years, alone in a one-room cottage. During her career as a cook, “Typhoid Mary” probably infected many more than the 50 documented cases, and she surely caused more than 3 deaths. Mary Mallon was not the only human carrier of typhoid. In 1938 when she died, the New York City Health Department noted that there were 237 others living under their observation. She was the only one kept isolated for years, however, and one historian has ascribed this to prejudice toward the Irish and a non-compliant woman who could not accept that unseen and unfelt “bugs” could infect others. Mary Mallon told a newspaper: “I have never had typhoid in my life and have always been healthy. Why should I be banished like a leper and compelled to live in solitary confinement … ?”

      Predicting Plagues

      Recognizing the elements required for a parasite to spread in a population allows for better forecasting of the course a disease may take. Three factors are required for a parasite to spread from host to host: there must be infectious individuals, there must be susceptible individuals, and there must be a means for transmission between the two. Transmission may be by indirect contact involving vectors such as mosquitoes (in malaria and yellow fever) or flies (in sleeping sickness and river blindness) or ticks (in Lyme disease), or it may be by direct contact as it is with measles, influenza, SARS, and tuberculosis, where it is influenced by population density.

In the past, the sudden increase in the number of individuals in a population affected by a disease was called a plague. Today we frequently refer to such a disease outbreak as an epidemic, a word that comes from the Greek epi, meaning “among,” and demos, “the people.” Epidemiologists are disease forecasters who study the occurrence, spread, and control of a disease in a population, using statistical data and mathematical modeling to identify the causes and modes of disease transmission and to predict the likelihood of an epidemic, to identify the risk factors, and to help plan control programs such as quarantine and vaccination. When TSS broke out, epidemiologic studies linked the syndrome to the use of tampons, principally Rely tampons, and the recommendation was that the illness could be controlled in menstruating women by the removal of such tampons from the market. Acting on this advice, Procter & Gamble stopped marketing Rely tampons and the number of cases virtually disappeared.

      For an infection to persist in a population, each infected individual on average must transmit the infection to at least one other individual. The number of individuals each infected person infects at the beginning of an epidemic is given by the notation R₀; this is the basic reproductive ratio of the disease, or, more simply, the multiplier of the disease. The multiplier helps to predict how fast a disease will spread through the population.

      The value for R₀ can be visualized by considering the children’s playground game of touch tag. In this game one person is chosen to be “it,” and the objective of the game is for that player to touch another, who in turn also becomes ”it.” From then on each person touched helps to tag others. If no other player is tagged, the game is over, but if more than one other player becomes “it,” then the number of touch taggers multiplies. Thus, if the infected individual (it) successfully transmits the disease (touches another), then the number of diseased individuals (touch taggers) multiplies. In this example the value for R₀ is the number of touch taggers that result from being in contact with “it.”

      The longer a person is infectious and the greater the number of contacts that the infectious individual has with those who are uninfected, the greater the value of R₀ and the faster the disease will spread. An increase in the population size or in the rate of transmission increases R₀, whereas an increase in parasite mortality or a decrease in transmission will reduce the spread of disease in a population. Thus, a change that increases the value of R₀ tends to increase the proportion of hosts infected (prevalence) as well as the burden (incidence) of a disease. Usually, as the size of the host population increases, so do disease prevalence and incidence.

      If the value for R₀ is >1, then the “seeds” of the infection (i.e., the transmission stages) will lead to an ever-expanding spread of the disease—an epidemic or a plague—but in time, as the pool of susceptible individuals is consumed (like fuel in a fire), the epidemic may eventually burn itself out, leaving the population to await a slow replenishment of new susceptible hosts (providing additional fuel) through birth or immigration. Then a new epidemic may be triggered by the introduction of a new parasite or mutation, or there may be a slow oscillation in the number of infections, eventually leading to a persistent low level of disease. If R₀ is <1, though, then each infection produces <1 transmission stage and the parasite cannot establish itself.

The economic costs of the outbreak of SARS in 2003 were nearly $100 billion as a result of decreased travel and decreased investment in Southeast Asia. The University of California at Berkeley was so concerned about this epidemic that it put a ban on Asian students planning to enroll for the summer session. The question raised at the outset was: How long will the SARS outbreak last? Calculating the value of R₀ provided an answer. Analysis of ~200 cases during the first 10 weeks of the epidemic gave an R₀ value of 3.0, meaning that a single infectious case of SARS would infect about three others if control measures were not instituted. This value suggested a low to moderate rate of transmissibility and that hospitalization would block the spread of SARS. The prediction was borne out: transmission rates fell as a result of reductions in population contact rates and improved hospital infection control as well as more rapid hospitalization of suspected (but asymptomatic) individuals. By July of 2003 the R₀ value was much smaller than 1, and the ban on Asian students enrolling at the Berkeley campus of the University of California was lifted.

      Epidemiologists know that host population density is critical in determining whether a parasite can become established and persist. The threshold value for disease establishment can be obtained by finding the population density for which R₀