Diseases: The winners are... A Johns Hopkins expert looks at achievements and challenges

THE BALTIMORE SUN

INFECTIOUS DISEASES, caused by microbes such as bacteria, viruses, parasites and fungi, result in illnesses such as pneumonia, influenza, tuberculosis and AIDS. The field has witnessed remarkable accomplishments in both the recent and remote past.

From a historical perspective, the most substantial progress has come in the categories of antibiotics, vaccines and public health. Of these, the most important is probably antibiotics, introduced during the 1940s with penicillin, which revolutionized medicine and is sometimes viewed as the greatest curative revolution in medical history. To paraphrase the late physician and educator Walsh McDermott, penicillin gave more curative power to a barefoot, itinerant care provider in the farthest reaches of Africa than all the collective talent of physicians in New York City.

With vaccines, the record is equally impressive: Diphtheria, mumps, whooping cough, measles, polio and tetanus have been reduced by 98 percent or more. Perhaps the most spectacular achievement was the elimination of smallpox in 1977. (Despite the magnitude of their effort, the architects of the smallpox eradication program have never been awarded a Nobel Prize).

In public health - food inspection, water purification, rodent control - progress is best illustrated by the remarkable difference between developed countries, where infectious diseases are the major cause of death in 5 percent, and underdeveloped countries, where they are the major cause of death in 35 percent.

With this rich heritage, I submit the following as the most substantial accomplishments and challenges in this field during the past ten years, a sort of Academy Awards of Infectious Diseases.

Diseases facing elimination

The nominees, identified by the Centers for Disease Control and Prevention and the World Health Organization, are mumps, rubella, cysticercosis, filariasis, guinea worm and polio. All are considered ""potentially eradicable," but polio is the most likely winner for the near future. Because about 88 percent of the population has been vaccinated, not enough vulnerable patients remain to sustain the virus. The last isolation of poliovirus occurred in 1990, and its eradication in the Western Hemisphere became ""official" about a year ago. A few focal points of polio cases remain in other parts of the world, but most authorities consider elimination to be simply a matter of time. For those who lived through the 1950s, polio eradication is a stunning victory.

Vaccine

Nominees, developed or newly promoted during the last decade, are vaccines against chicken pox, hepatitis B, pneumonia (Pneumovax), hepatitis A and Haemophilus influenzae.

The winner is hepatitis B vaccine, for several reasons. A devastating disease, hepatitis B is responsible for about 5,000 deaths a year in the United States because of cirrhosis or liver cancer. Its toll is much heavier in other parts of the world, where it is the most common cause of cancer. Another reason hepatitis B vaccine wins is that the virus, never having been grown successfully in the test tube, is a special pharmacologic challenge. The original vaccine was made by taking parts of the virus from blood donations, but in 1986, ""recombinant" techniques allowed the vaccine to be produced by microbes, making it a pure product. The U.S. Public Health Service introduced it as a component of routine vaccinations in children in 1991. Although hepatitis B is on the way out, it will take a vigorous vaccination campaign and a few generations to achieve eradication.

My second-place winner, the vaccine for Haemophilus influenzae, is worth noting. Severe infections with this bacterium, formerly a devastating problem in children and the most common cause of pediatric meningitis, now virtually have disappeared in the United States.

New virus

Nominees that have dominated medicine in the last decade include hepatitis C virus (now recognized as the most common cause of cirrhosis, even more common than alcoholism), herpes virus 6 (a common pediatric virus and the most common cause of seizures in children), Sin Nombre virus (the cause of the lethal infections originally discovered in the four corner states in 1993), and HIV (the cause of AIDS). This is a no-brainer: The award must go to HIV.

It is estimated that about one in 200 young adults in the United States is infected; for Baltimore residents, the estimate is about 7 percent of young adult men. About 90 percent of new cases are in the developing world, and the estimated total number currently infected is 21 million - the great majority in sub-Saharan Africa and Southeast Asia. For perspective, the largest temporally defined epidemic in the history of medicine - bubonic plague in the 14th century - caused 25 million deaths. HIV clearly will exceed that record.

New bacterium

The winner is Helicobacter pylori, now identified as the major cause of stomach ulcers, stomach cancer and a whole lot more. The possibility that a microbe might cause ulcers has been debated periodically in medicine since 1877, but few took it seriously.

More recently, an Australian gastroenterologist, Barry Marshall, reintroduced the concept in 1983. His colleagues viewed it as pretty outrageous, but they began to take it seriously when multiple studies showed that people with ulcers almost invariably had Helicobacterium infections and, perhaps even more importantly, antibiotics turned out to be better than Tums, Maalox, Zantac, Tagamet and other standard treatments. One reason the discovery is exciting is that it dramatically illustrates the potential role of infectious diseases in causing medical conditions that do not fit traditional concepts of the way microbes cause disease.

Old microbe

Among microbes that have plagued civilization for centuries and remain problematic, the nominees are tuberculosis, malaria, measles and hepatitis B. Each is responsible for more than one million deaths annually.

The winner is tuberculosis, the single most common cause of death on earth.

About one-third of the world's population is infected, and each year there are about 10 million new cases and about 3.1 million deaths. The tragedy of this situation is the consensus among health officials that tuberculosis is easily controlled with ""gumshoe" public health policies at a cost of about $1 per case. The potential use of good public health practices is well illustrated by the experience in Baltimore, which, since 1978, has witnessed the largest decrease in tuberculosis rates of any metropolitan area in the history of medicine.

Antiviral drugs

Compared with drugs against bacteria, drugs against viruses have a rather brief and meek history, with almost all developments occurring during the last decade.

The winner here is AZT. Initially tested in patients with HIV infection in 1986, it produced results so impressive that the study was stopped after only nine months and the drug was approved 103 days later, a new record at the Food and Drug Administration.

AZT's subsequent history, however, was somewhat painful; it was soon learned that its benefit is temporary because of resistance, and subsequent work has shown it must be combined with other drugs. Protease inhibitors, the most recent development in the field, appear capable of revolutionizing HIV care. Within nine months of introduction, they already have made a substantial impact. AZT wins the category, however, because it provided the rationale for designing a large national strategy for drug development and testing that, after 10 years, is now a finely tuned machine making substantial progress.

Resistant bacterium

Drugs designed to eradicate bacteria have a cherished place in the history of medicine. The ""antibiotic mill" includes 3,000 penicillins, 2,000 cephalosporins, 1,000 tetracyclines and many more.

The pharmaceutical industry's ability to develop new antibiotics is impressive, but the award goes to the enemy that has become even more impressive by developing resistance, the bacterium called Streptococcus pneumoniae or ""pneumococcus." This bacterium is responsible for at least 10 million infections per year in the United States, including most cases of pneumonia, ear infections in children, meningitis in adults and sinusitis. Always treated with penicillin in the past, in recent years the pneumococcus has developed resistance to this drug. Today, 25 percent of strains in the United States (including Baltimore) are resistant. Furthermore, the penicillin-resistant strains often are resistant to other antibiotics as well, introducing enormous complexities into the treatment of many common diseases. The cause appears to be antibiotic abuse, the widespread use of antibiotics for colds, bronchitis and many other conditions that do not merit this treatment.

Epidemic

In this category are multiple nominees, including two already cited, HIV and tuberculosis. Others include cholera (three major epidemics since 1991 and the first in the Western Hemisphere that included more than one million cases and about 10,000 deaths), plague in India in 1994, Ebola virus in Zaire in 1995, diphtheria in Russia in 1995 with more than 1,000 deaths; dengue in Central America in 1994 with 8,000 deaths and, more recently, mad cow disease in England and a newly recognized, potentially fatal form of diarrhea in Japan with about 9,000 cases.

The winner is the Ebola virus epidemic. Although relatively modest (316 cases and 245 deaths) compared to the others, its impact was profound because of the high fatality rate (80 percent), the mystery about its mechanism of transmission, and the fear engendered by the thought that people with incubating infection could travel throughout the world. As ""The Coming Plague" author Laurie Garrett pointed out, our total national budget to deal with this type of potential international epidemic was substantially lower than Dustin Hoffman's salary for his role in ""Outbreak." Ebola virus was the wake-up call largely responsible for both attention and funding at the federal level.

When antibiotics were introduced, many concluded that infectious diseases largely were conquered. A recent review, however, showed that during the last decade, death due to infectious diseases in the United States in fact has risen 58 percent. The biggest jump is among young adults, with a 630 percent increase largely ascribed to AIDS, but there also has been a 25 percent increase in the non-AIDS category.

In the developing world, infections account for about one-third of all deaths, most of which are preventable. Also remarkable is that since 1980, more than 20 microbes that cause major diseases have been discovered, including some that are quite unconventional in terms of their clinical expression (cancer, stomach ulcers and, possibly, coronary artery disease).

Perhaps the most profound message, however, is the unpredictability of infectious diseases. Given the opportunity in 1980 to foretell the future of infectious diseases, no one would have guessed the AIDS epidemic, that cholera would come to this hemisphere, that polio largely would be eradicated, that a bacterium would cause stomach ulcers, that a virus would become the major cause of liver disease, that the most common cause of pneumonia would become resistant to penicillin after remaining highly sensitive for four decades of exposure, or that a vaccine could prevent one of the most common causes of cancer (hepatitis B).

Unpredictability is a trademark of the discipline. Nevertheless, rTC relatively safe predictions are that old microbes will continue to cause problems, new microbes will be discovered, and heretofore unrecognized microbes will be found to cause many enigmatic conditions.

One last prediction

Despite the progress, the microbes ultimately may win.

John G. Bartlett, M.D., is chief of the infectious diseases division of Johns Hopkins University's School of Medicine.

Pub Date: 11/10/96

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