The Power of Plagues. Irwin W. Sherman

the Russian authorities, but he was released after Metchnikoff intervened. Upon the completion of his degree, Haffkine attempted to find a post at the university, but it was denied him because of his refusal to be baptized. In 1889 he emigrated to Paris, where he joined Metchnikoff at the Pasteur Institute to work on a vaccine for cholera. When plague broke out in India in 1896, Haffkine moved to Bombay, where in 1897 he prepared an effective vaccine using dead bacilli. In 1902, however, 19 people out of the thousands who had received the vaccine died; this created a distrust of Haffkine’s vaccine for plague. It was later discovered that the deaths had been due to another doctor’s mistake in contaminating the vaccine with tetanus bacilli; Haffkine was blamed, however, and his career never recovered. He worked at other posts in India and retired to France in 1914. Although he visited Odessa in 1927, he found he could not adapt to the anti-Semitism that had been wrought by the Russian Revolution, and so he returned to France until his death.

      Currently, there is no licensed vaccine available against plague. A formalin-killed whole-cell vaccine against Y. pestis was in use in the United States until 1999, when it was discontinued. This vaccine provided protection against bubonic plague, but there was good evidence that the vaccine provided little protection against primary pneumonic plague, and adverse side effects were known to occur. A live attenuated strain of Y. pestis (EV76) has also been used. It protected against bubonic plague efficiently and induced high titers of antibodies, but it did not confer long-lasting immunity and there were mild to severe side reactions. The immunogenicity and virulence of the EV76 vaccine preparations used in different countries were found to be highly variable, most likely because of the genetic drift of the bacteria used. Indeed, high genomic plasticity is observed in Y. pestis, which results from frequent chromosomal rearrangements between the numerous copies of insertion sequences present in its genome.

      Recently, recombinant protein-based vaccine candidates have been developed. Two of these vaccines, RypVax and rF1V, have been shown to be superior in clinical trials. These vaccines rely mainly on a combination of two protein antigens, F1 and LcrV, and are strong inducers of an antibody response. These vaccines, however, provide poor and inconsistent protection in African green monkeys, probably due to a weak cellular immune response that is essential for good protection against plague.

      Coda

      Plague cannot be eradicated since it is present in wildlife rodent reservoirs. It has been shown that warmer springs and wetter summers in Kazakhstan increase the prevalence of plague in its main host, the great gerbil. Such conditions were present during the first and second pandemics—conditions that might become more common in the future with global warming. A plague outbreak may cause widespread panic, as occurred in India in 1994 when a relatively small outbreak, with 50 deaths, was reported in the city of Surat. This led to a nationwide collapse in tourism and trade, with an estimated loss of $600 million.

      It should not be overlooked that plague has been weaponized throughout history, from the catapulting of plague-infected corpses over city walls in the Crimean port city of Kaffa in 1346-1347, to the Russians hurling cadavers of plague victims into the ranks of the enemy in 1710 during the battle against Swedish forces in Reval, to the Japanese dropping infected fleas from airplanes during World War II, to a refined aerosol formulation developed by the Soviet Union. The use of an aerosol released by terrorists in a confined space could result in significant mortality and widespread panic. Although plague cannot match the so-called “big three” diseases (malaria, HIV/AIDS, and tuberculosis) in the numbers of current cases, it far exceeds them in pathogenicity and rapid spread under the right conditions. Plague should not be seen as an historical curiosity. It is an infectious disease we cannot afford to ignore.