Santayana's dictum that "those who cannot remember the past are doomed to repeat it" has a biological corollary: The belief that we've vanquished our ancient microbial enemies leaves us alarmingly vulnerable to them

Re-emerging diseases:
gone today, here tomorrow?

Steve Mirsky

We have two choices. Follow Choice 1, and the headlines in 10 years will probably report the latest internecine squabbles in Congress, or which athlete signed for how many millions. Choice 2, on the other hand, could lead to headlines such as "New Flu Strain Spreads: Death Toll Reaches Half Million."

In 1969, Surgeon General William Stewart, testifying before Congress, said that we could "close the book on infectious disease." Antibiotics and vaccines had left the medical community flush with a string of impressive victories, from penicillin to polio. The war, they thought, was almost over.

Today, confronted with what have become known as emerging and re-emerging diseases, we know better. "'Emergence' is in fact regression, a return to the standard that prevailed universally in the previous century,"1 Nobel Laureate and Columbia biologist Joshua Lederberg wrote in a special infectious disease issue of the Journal of the American Medical Association. A report in the same issue quantified the growing threat: In the United States between 1980 and 1992, the death rate due to infectious diseases increased 58 percent.2 AIDS accounts for slightly more than half of that jump, but other conditions, especially respiratory infections, also contributed significantly.

Since the heady days of victory declarations, new diseases such as AIDS and Ebola have suddenly appeared, and old afflictions, thought conquered, have flared. Diphtheria is making a comeback in the former Soviet Union. Tuberculosis -- which never really went away, though upscale opera buffs might have thought it was confined to productions of "La Boheme" -- is once again a threat in urban centers, including New York City. Group A streptococcal conditions are on the rise, which means that scarlet fever could become familiar again. And everyone in the infectious-disease field fears the day when a powerful new strain of flu sweeps the world. "The war has been won," one scientist recently quipped. "By the other side."

Keeping our eyes on moving targets

In fact, that sentiment may reflect as much hyperbole as the former surgeon general's. Perhaps a better snapshot of the current situation is that the battle has been joined. The World Health Organization and the Centers for Disease Control and Prevention have revved up their efforts to check infectious diseases, including re-emergent ones. In October 1995, WHO established a new division devoted to worldwide surveillance and control of emerging diseases. The CDC came up with a prevention strategy in 1994. Although Congress funded CDC's efforts to the tune of only $6.7 million in 1995-less than Dustin Hoffman's salary for starring as an infection fighter in "Outbreak" -- they have raised the figure to $26 million for 1997. Public awareness of infectious disease, perhaps due in part to such movies, may have influenced Congress' outlook.

WHO has identified six diseases whose worldwide re-emergence should be monitored: diphtheria, cholera, dengue fever, yellow fever, and -- believe it or not -- bubonic plague. A list of diseases for the United States might differ, but, as Lederberg also put it, "We arrive at the realization that world health is indivisible, that we cannot satisfy our most parochial needs without attending to the health conditions of the globe." With a crowded marketplace in Kikwit, Zaire, site of the last Ebola flare-up, less than 24 hours away from a New York City subway, borders are meaningless to pathogenic microbes.

Lists may help public health authorities focus their attention, but their value is limited. "Ask anyone 15 years ago about what diseases should be on such a list and no one would have said AIDS," notes Stephen Morse of the epidemiology division in Columbia's School of Public Health. "We didn't even know it existed. Now it's at the top of every list. The reality is that any list I give you will be deeply flawed. That said, there are re-emerging conditions that are hardy perennials, and they have not been eliminated."

Every returning condition marches to the beat of a different drum. "These re-emerging infections each have a little wrinkle to them that is important," says Dr. Glenda Garvey, Columbia clinical professor of medicine and interim chief of infectious disease at Columbia-Presbyterian Medical Center. "TB is the result of socioeconomic conditions and human behavior." Prisons and homeless shelters are ideal venues for TB spread, with confined populations in close quarters. With our help, strains of TB have also developed drug resistance; incomplete courses of antibiotic therapy allow the hardiest bugs to survive and develop new, more powerful lineages. "It is possible," Morse says, "that the multi-drug-resistant strain of TB that has spread throughout the East Coast originated in a homeless shelter across the street from Columbia-Presbyterian." TB also hitched a ride on the HIV wagon by attacking the immunocompromised-an emerging disease thus helping re-ignite an old one.

"The return of Group A strep may be due to a change in virulence," Garvey says, reflecting mutation in the exterior of the bacterium. The misnamed "flesh-eating bacteria" of 1994 were a type of Group A strep infection, as are rheumatic and scarlet fevers. "Scarlet fever was a problem for my mother's generation," says Morse. "It essentially disappeared, and for no good reason. We don't understand why [diseases] flare from time to time, and until we do I'm uncomfortable ignoring them."

Flu likewise changes its coat and in turn its level of virulence. "If there is anything in this business you can safely put on a list of diseases that are coming, it's flu," Morse says. Rather than the flus that lay everybody up for a weekend every winter, the strain Morse dreads is the kind that killed 22 million in the pandemic of 1918-19. "Those processes in nature that have given us the pandemic influenzas are not finished.

"We're going to see it. Now, it won't be this year. It may not be next year. And I would not want to predict when that is going to happen. Nobody has ever succeeded in predicting the next flu pandemic. But that I think it will happen is a virtual certainty. We will live to see it. Is the next flu pandemic going to be as bad as 1918? None of them yet has been, but someday it's going to have to happen."

The flu virus is a trickster, constantly changing its surface antigens, so that our immune systems need to relearn how to fight it every time it adopts a new costume. "To our bodies, it's a new virus," Morse says. "Old wine in new bottles, if you will." A larger-scale genetic shift could also make the virus something like new wine in new bottles. Researchers will have to characterize the new flu early enough for vaccinations to be created and delivered to enough people for prevention to be successful. If a powerful new flu arises and those public health measures are not in place quickly enough, myriad people may become very sick, with the elderly and infirm fighting for their lives.

Eternal vigilance or infernal results

Vaccination practices are also at the heart of the pertussis and diphtheria threats. "There was only one vaccine for pertussis in many countries, and it was thought to have neurological complications," Garvey notes. "In England, they did the experiment: They simply stopped vaccinating for pertussis. And they wound up with a lot of sick kids. In this country, we are now seeing the waning of immunity."

The diphtheria situation in the former Soviet Union involves a more serious disease combined with a crumbling public health infrastructure; organized vaccination efforts are in shambles. Amazingly, conditions in some American cities have deteriorated to comparable levels. "In some inner cities," Morse says, "vaccination rates are one-third of what they should be. New York City is better but still no better than about one-half. We're missing a lot of people. If those rates dropped considerably, we could see a lot more diphtheria and whooping cough." A slightly warmer climate combined with deteriorating cities could also enable various diseases that seem exotic today (yellow fever made it as far north as Philadelphia in the past century) to come back. Dengue fever could likewise become familiar.

Even malaria has the potential to become familiar again domestically, especially if warmer weather combined with urban blight brings mosquitoes and malaria carriers together. The CDC documents 11 cases of homegrown malaria in the past 11 years. The latest, reported in March, involves a migrant worker from Georgia, living in a trailer park with stagnant water serving as mosquito breeding pools. His companions included workers from tropical climes, from whom local mosquitoes probably picked up the infectious agent and then passed it along. In their report on this malaria case, CDC researchers advise that "malaria should be considered by all physicians who provide care for persons with unexplained fever-regardless of travel history and particularly during summer months."

That kind of readiness can keep future headlines free of news of worldwide pandemics. The price of liberty from infectious disease, as for most freedoms, is eternal vigilance. In his previous position at the Rockefeller University, Morse was one of the earliest voices raising awareness about these conditions; his objective at Columbia is to establish a center for emerging and re-emerging diseases, bringing together all appropriate disciplines and coordinating with other centers internationally. This will no doubt mean close cooperation with the CDC, which has four areas of focus.

"First, you need surveillance," says Bob Howard of the CDC's National Center for Infectious Diseases. Worldwide systems for tracking blips on the disease radar screen are already being established. "You also have to have science that is up-to-date and capable of dealing with what you discover in the field," Howard continues. "Once you do, you want to have appropriate prevention and control in place, and that includes communication to let people know what the threats are and how to control or prevent the spread of that disease threat.

"Finally," Howard adds, "there's got to be that strong public health infrastructure in place. If you don't have a system in place, the three previous things will not work." The CDC estimates that a fully functional prevention strategy would cost about $125 million annually-slightly more than it cost to produce "Outbreak."

TB or not TB?
TB rates in New York City are dropping once again, thanks to the labor-intensive, low-tech technique of directly observed therapy (DOT). "Dr. Thomas Frieden, director of the Bureau of TB in New York, set up this elaborate, highly organized system of getting unskilled workers to go door to door to make sure people take the medications," says Randi Hutter Epstein, the 1996 Reuter Fellow in Medical Journalism at Columbia's Graduate School of Journalism. Dr. Hutter Epstein observed the DOT system up close: by becoming part of it.

"A great problem is that a lot of the people who are sick and transmit the disease don't want to be helped," she explains. "Some of them are dying of AIDS, some of them are illegal immigrants, and they're not going to show up at a government-run health clinic. It's a lot of detective work, and it's a lot of interpersonal skills, because these people don't want to tell you who their contacts were, especially if they're illegal immigrants or some of their contacts are involved in drugs. They don't really want to give out their names and numbers to anyone who might have anything to do with the government."

Through incredible perseverance, DOT workers make sure that more than 90 percent of TB patients finish their entire course of medication. "The epidemic has slowed dramatically in New York," Hutter Epstein says. "So much so that there was a fear that the city would cut the money that goes into the program. But if we do that, we're going to see TB rise again." -- Steve Mirsky

Related links...

  • Outbreak emerging-disease page

  • New, Reemerging, and Drug-Resistant Infections, National Center for Infectious Diseases

  • Stephen A. Berger, MD, "Electronic Media and Emerging Zoonoses," Emerging Infectious Diseases 3(2):239, 1997, republished on Medscape (requires free registration)

  • Alison Jacobson, MD, "Emerging and Re-Emerging Viruses," (University of Cape Town, South Africa, Dept. of Microbiology)

    1 Lederberg J. Infection emergent (editorial). JAMA 1996;275 (3): 243-245.

    2 Pinner RW, Teutsch SM, Simonsen L, et al. Trends in infectious diseases mortality in the United States. JAMA 1 996;275: 1 89- 1 93.

    STEVE MIRSKY writes the "Anti-Gravity" column for Scientific American and is the 1997 Reuter Fellow in Medical Journalism at Columbia's Graduate School of Journalism.

    Photo Credits: Miami Photo Copyright 1993 Gil T Photography, Mosquito Photo John Vandyk, Iowa State University Department of Entomology image altered by Howard Roberts