An Eclectic Look at Infectious Diseases

Graphic: Cathleen Heard A week after the controversial XIII International AIDS Conference in Durban, South Africa, a much smaller gathering in Atlanta took a broader view of the current emergence and reemergence of many infectious diseases. The International Conference on Emerging Infectious Diseases 2000, held July 16-19, attracted more than 2,000 attendees representing 35 nations. The Centers for Disease Control and Prevention (CDC), the American Society for Microbiology, the Council of State and Territorial Epidemiologists, and the Association of Public Health Laboratories, supported by several pharmaceutical companies, organized the meeting, the second such event, and proceedings will be published in the CDC's journal Emerging Infectious Diseases. "The first meeting, also held in Atlanta two years ago, was in response to an Institute of Medicine report in 1992, headed by Joshua Lederberg [president emeritus and Raymond and Beverly Sackler Foundation Scholar, Rockefeller University, and chairman of The Scientist's Editorial Advisory Board], that highlighted the complacency in the developed world that infectious diseases had largely been controlled. The report identified factors for the emergence and reemergence of infectious disease," said James Hughes, director of the National Center for Infectious Diseases, at the opening session. "CDC set up a plan in 1994, recognizing that we need to be prepared to confront the unexpected--hantavirus, AIDS, and West Nile virus are examples," he added. This year's meeting was wide ranging and multidisciplinary. Plenary sessions, invited panels, slide shows, and posters examined the roots of disease outbreaks, from the nuances of viral nucleic acid sequences; to the effects of human behavior, politics, and economics on epidemics; to influences of global weather patterns. Talks considered old foes such as malaria, polio, and tuberculosis; current challenges such as AIDS and foodborne diseases; and new infectious diseases such as Nipah and Hendra virus encephalitis. Attendees reflected the eclectic nature of the conference. "These are groups that don't often come together--entomologists, public health workers, physicians, veterinarians, molecular biologists, and epidemiologists," Hughes remarked. Ironically, considering the international flavor of the meeting, the major story to receive media play was a talk early in the schedule by Stuart B. Levy, a professor of medicine at Tufts University, about the dangers of antibacterial compounds in household products that are hardly characteristic of the developing world. Because epidemiology traces disease incidence over time, the discussions had a distinct temporal feel. Following is a look at conference highlights that focused on the past, present, and future of infectious disease. © 2000 Corbis eyewireViruses in humans have originated in such sources as chimpanzees, fruit bats, and pigs. A Secret Past: Bioterrorism The intentional use of microbes as weapons is newsworthy in light of recent increases in defense expenditures--the U.S. Department of Health and Human Services spent $175 million on bioterrorism preparedness in 1999, with $270 million slated for this year.1,2 But current heightened awareness springs from a shocking recent history revealed in the 1990s. That is, despite signing the Biological Weapons Convention in 1972, the former Soviet Union continued a massive bioweapons buildup, while a much less ambitious U.S. offensive effort ended immediately. "Boris Yeltsin admitted that their program continued until March 1992. We knew very little about their program over those 20 years. The quality of the U.S. and U.S.S.R. bioweapons programs was similar; the quantities were very different," said David Franz, vice president of the chemical and viral defense division of the Southern Research Institute in Frederick, Md., who recently investigated the Iraqi bioweapons arsenal. Donald A. Henderson, director of the Johns Hopkins University Center for Civilian Biodefense, described the evolution of U.S. defensive bioweapons policy. (See also Commentary, page 6.) "From 1990 until 1993, there was concern about bioterrorism and bioweapons, but it was regarded as a very unlikely event that was not high on anyone's agenda," he explained. But three incidents in 1995 changed all that--the defection of Saddam Hussein's son-in-law and information he provided on Iraqi bioweapons; the release of the nerve gas sarin by the AUM Shinrikyo sect in a Japanese subway; and reports from Ken Alibek,3,4 first deputy director of the Soviet bioweapons effort, Biopreparat, who worked with anthrax, smallpox, tularemia, plague, and other pathogens before defecting to the United States. "It was a real shock," Henderson recalled, "to learn that smallpox was eradicated by 1980, but that 80 to 100 tons of smallpox virus per year were being stockpiled in a Moscow facility." The 1995 wake-up call prompted the U.S. government to fund training of "first responders." But it has only been over the past year that epidemiologists have been able to persuade government offcials to change their approach. "This is a public health problem. Police and fire workers are almost irrelevant. People need to understand that a gas explosion is different from the release of a bioweapon. An epidemic is not like that; it doesn't affect many people so suddenly," Henderson said. Taking bioweapons seriously could have other benefits. "Investment in bioterrorism will pay off in dealing with emerging infectious diseases," maintained Hughes. © 2000 Corbis Corporation The Present: Nipah Virus Nipah virus lacks the familiarity factor of HIV or West Nile virus, but an outbreak in Malaysia and Singapore from October 1998 through March 1999, and another ongoing now, underscore the epidemiological significance of movements of animals from their natural habitats--and the fact that eradication one season may not continue through the next. Nipah virus takes its name from a village in peninsular Malaysia. The virus persists in low numbers in the island flying fox Pteropus hypomelanus, a type of fruit bat, which does not become ill. When passed to a pig, the virus explosively replicates. The pig develops a peculiar, loud cough, by which the virus passes to humans, where it causes severe encephalitis. Of the 269 human cases in 1999, 108 were fatal.5,6 At first, investigators thought the disease was Japanese encephalitis. But when vaccination programs didn't prevent further cases and studies revealed that the victims had in common contact with coughing pigs, the idea emerged that a new viral disease had jumped species--a zoonose traveling from pigs to people. But that wasn't all. As large numbers of pigs moved south, so too did the human disease. "The 11 cases in Singapore were traced to abattoir workers, and the import of pigs from Malaysia," said Yee-Sin Leo, clinical director and consultant in the infectious diseases department at Tan Tock Seng Hospital in Singapore. Then in the summer of 2000, routine surveillance of pig blood in Singapore revealed infection again, and four of 160 workers were found to harbor the virus. Removing the porcine source reportedly ended the 1999 Nipah virus outbreak. "Piggeries were destroyed, and 1.1 million pigs culled, at great cost. Many people lost their jobs and had to move," according to Hume Field, an investigator with the Animal Research Institute in Queensland, Australia. Then the disease seemed to disappear. In Singapore, a follow-up screening of abattoir workers between March and September 1999 found only three infected people among 635 tested, and all recovered, reported Leo. But the disease--or at least signs of infection--is back. Nipah virus is a single-stranded RNA virus, a member of the paramyxovirus family and most closely related to Hendra virus. In 1994, Hendra jumped from horses to humans in two Australian outbreaks, and in fact previous to that was known as equine morbillivirus. Fruit bats also pass Hendra virus. Field is concerned that changing geographic distribution of fruit bats is spreading new human diseases. In addition to Hendra, Australia is experiencing outbreaks of rabieslike lyssavirus infection and a febrile illness from Menangle virus passed from pigs and fruit bats. John S. MacKenzie, professor and head of the department of microbiology and parasitology at the University of Queensland, added to the list: Ross River virus, Barmah Forest virus, and Chikungunya virus. "We are truly seeing emergence of these agents. Retrospective studies of sera and tissues show no evidence of past infection. Hendra and Nipah viruses are ancient. They were probably sitting in their natural hosts minding their own business, and some series of events prompted a spillover into other species," MacKenzie commented. For the Nipah outbreak in Malaysia, the trigger was probably moving pigs; for Hendra in Australia, it was an influx of fruit bats into urban areas. Another scare factor is that each of these viruses can infect not-so-exotic species too, including dogs and cats. © 2000 Corbis Corporation The Future--HIV and More The magnitude of the AIDS epidemic is appalling: 50 million infected and six million new cases a year, 16 million dead, and 40 million AIDS orphans by 2010. What will the future bring? Bruce Levin, a professor of biology at Emory University, is using mathematical models to predict what might happen. He varies such parameters as age at the time of infection, virulence of HIV substrains, and the effectiveness of treatments in extending the symptom-free period to foresee the course of the epidemic. Several such simulations indicate that it will take a treatment that delays symptoms and slows the rate of transmission to ultimately decrease the number of infected individuals. The study of HIV in particular, and emerging infectious diseases in general, touches on ecology, epidemiology, and evolution. But it also touches on the human heart. Ten thousand years is a mere flicker of evolutionary time, hardly significant, yet it is also far too many human lifetimes when considered in the context of the AIDS pandemic. Even Levin's rosiest outlook is gloomy: "We can't count on evolution to reduce the incidence or rate of mortality of HIV/AIDS in our lifetime, or that of many generations to come. If the primary frequency of CCR5 mutation (which confers HIV resistance) is 10 percent, and 1 percent of the population is infected, it will take 10,000 or so years before 50 percent of the population will be resistant." Before "emerging infectious diseases" became a field worthy of its own acronym, the phenomenal success of antibiotics had led to a false sense of security that humans had the medical means to vanquish any microbial foe. Then came Legionnaire's disease, AIDS, Lyme disease, hantavirus, and a host of other new or seemingly new disorders, as once-defeated foes quietly returned, or found themselves preserved in bioweapons. Researchers, public health workers, and unfortunately many sick people, are realizing that juxtaposing species in ways not found in nature can set the stage for zoonoses, with unpredictable, and perhaps unimaginable, consequences. AIDS most likely arose from a man exposed to chimpanzee blood in 1959--yet today, eating chimp and other primate meat is widespread. "In Africa, 'bushmeat' is available in markets. The potential human exposure to a wide variety of SIVs [simian immunodeficiency viruses] has increased substantially, as have conditions to facilitate widespread infection," explained Beatrice Hahn, a professor of medicine and microbiology at the University of Alabama in Birmingham who led the team that traced HIV to chimpanzees.7 Hughes and others at the meeting called HIV "the revenge of the rain forest." And although a zoonotic epidemic is hardly intentional, the overall message is sobering: Not only do scientists not yet know precisely how AIDS arose and where the pandemic is headed, but such a scourge could easily happen again. S Ricki Lewis (rickilewis@nasw.org) is a contributing editor for The Scientist. References 1. E. Russo, "Bioterrorism concerns heightened," The Scientist, 13[6]:1, March 15, 1999. 2. D.A. Henderson, "The looming threat of bioterrorism," Science, 283:1279-82, 1999. 3. T. Hollon, "Ken Alibek: for the biodefense," The Scientist, 14[8]:18, April 17, 2000. 4. K. Alibek, Biohazard, New York, Random House, 1999. 5. K.B. Chua et al., "Nipah virus: a recently emergent deadly paramyxovirus," Science, 288:1432-5, May 26, 2000. 6. K. Ahmad, "Malaysia culls pigs as Nipah virus strikes again," Lancet, 356:230, July 15, 2000. 7. F. Gao et al. "Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes," Nature, 397:436-41, 1999.

An Eclectic Look at Infectious Diseases

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