Combating Infectious Diseases

Introduction

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Overview

It is over in a matter of days. The victim staggers, disoriented and exhausted, and collapses in a fever. His eyes turn bright red, and he starts vomiting blood. Within a matter of hours, he “crashes” and “bleeds out,” succumbing to an agonizing death with blood seeping from his eyes, ears and other orifices. At autopsy, pathologists discover, aghast, that the patient's internal organs have disintegrated into an indistinguishable mass of tissue. The killer: A “hot” virus, a highly contagious and deadly microbe that has never been seen before and that has no known cure.

But the threat of hot viruses is less far-fetched than many moviegoers once thought. In the past two months, more than 160 people have died during an outbreak of the deadly Ebola virus in southwestern Zaire. Most of the deaths occurred in the city of Kikwit, 300 miles east of the capital of Kinshasa. The epidemic's acute phase now appears to be over, but more deaths are expected.

The Ebola outbreak served as an unwelcome reminder that, for all its advances, modern medicine has yet to win the war against infectious diseases. Americans worry more about chronic maladies such as heart disease and cancer, but infectious and parasitic diseases continue to be the leading cause of death on the planet. Nearly a third of the 51 million deaths worldwide in 1993 were caused by infections and parasites, according to the Geneva-based World Health Organization (WHO). Tuberculosis and malaria, diseases of little concern to most Americans, killed 2.7 million and 2 million, respectively. 1

But it is the rare and nearly always fatal illnesses like Ebola, Lassa and Rift Valley fevers that attract the most attention. For now, these diseases are as exotic as the places for which they were named, * erupting in remote areas of the world where they kill most infected individuals and then disappear as quickly as they emerged. With expanding international trade and air travel, however, infectious diseases that once were confined to isolated regions now pose potential threats virtually anywhere in the world.

“What is frightening to us all is the fact that the potential for spread of deadly organisms is greater than ever,” says Donald A. Henderson, a senior science adviser to the U.S. Public Health Service who led the successful international effort to eradicate smallpox beginning in 1967. “With the speed of travel today and the large numbers of people traveling among countries, the spread of virulent organisms into industrial countries such as the United States is becoming more likely.”

Hot viruses are but the most dramatic expression of what public health specialists call emerging infectious diseases. Officially defined as infectious diseases whose incidence in humans has increased within the past two decades or threatens to increase in the near future, these microbes include a host of bacteria and parasitic organisms as well as viruses. 2

“These are viruses that had not previously been recognized that appeared suddenly,” says Stephen S. Morse, a virologist at the Rockefeller University in New York City who coined the term “emerging infections.” “It's a way of describing something that comes out of nowhere and suddenly seems to be rapidly going everywhere.”

Some emerging pathogens, such as Ebola and equine morbillivirus, which erupted last fall in Australia, infecting both horses and humans, had never been seen before. The most devastating of all such infectious diseases is AIDS, caused by the human immunodeficiency virus (HIV). Other infections that had been around for centuries but were controlled by modern drugs now are re-emerging in drug-resistant forms. These include tuberculosis (TB), meningitis and infections caused by certain common bacteria such as staphylococcus and enterococcus.

Most worrisome to U.S. public health experts, emerging pathogens are on the increase in the United States as well as overseas. One of the newest threats is the hantavirus, which causes flu-like symptoms followed rapidly by respiratory failure. It first erupted in this country in June 1993 in the desert Southwest. The virus has since been identified in 21 states, striking 106 people and killing 55.

Of course, modern technology explains some of the increase in traceable cases of emerging infections. “We are better able to detect things today than we were in the past and therefore are able to detect cases of disease that would in the past have gone unnoticed and unrecognized,” Morse says.

But that does not fully account for the extent of the phenomenon, as AIDS so tragically shows. “In whatever exotic or perhaps prosaic place AIDS may have originated, it's now worldwide,” Morse says. “So there is nothing that is too exotic to some day be a threat to our health if conditions are right.”

Ebola, perhaps the most feared of the emerging pathogens, is a case in point. The first reported cases of this deadly hemorrhagic fever occurred in 1976 in Zaire, where 276 of 300 people infected with the virus died. Another limited outbreak occurred later that year in neighboring Sudan. In both instances, the disease erupted and disappeared so quickly that investigators from the World Health Organization and the U.S. Centers for Disease Control and Prevention (CDC) were unable to trace Ebola to its source.

Ebola emerged again in 1989, this time much closer to home, among a shipment of laboratory monkeys from the Philippines that were being held in the Washington suburb of Reston, Va. Although that outbreak was contained and did not spread to humans, it showed just how easily deadly microbes could make their way from remote rural areas to major urban centers.

Air travel may eventually expose Americans to exotic viruses like Ebola, but home-grown infections are already taking a rising toll. Tick-borne Lyme disease, first reported in the United States in 1975, now strikes about 10,000 persons a year. A deadly form of the E. coli bacterium, Escherichia coli O157:H7, first reported in the early 1980s, has become a common contaminant of meat and poultry. Even tap water has been suspect since 1993, when the parasite Cryptosporidium caused the largest recognized outbreak of waterborne illness in the country's history. More than 400,000 people in Milwaukee got sick after drinking from a contaminated municipal water supply. 3

Public health experts admit that emerging infections have caught them off guard. “In the United States we did such a good job developing antibiotics that by the early 1960s scientists were abandoning the field of infectious diseases because it was felt that there was nothing more to be done,” Henderson says. “Entire departments of microbiology folded up, there were very few specialists left, and people were moving on to chronic diseases. . . . By the 1980s, we were left with very little in the way of basic infrastructure.”

Specialists in this shrinking field worry that the United States lacks the incentives to stage an offensive against emerging infections before they cause a major catastrophe. For one thing, they say, disease prevention is not as profitable to the pharmaceutical or medical industries as treatment. “Money in this country for health care is used for after people get sick,” says Barry R. Bloom, a professor of microbiology and immunology at the Howard Hughes Medical Center at the Albert Einstein College of Medicine in the Bronx. “Who makes money when you prevent disease?”

Brian Mahy, director of the CDC's viral and rickettsial disease division, says inadequate funding for drug research has worsened the plight of victims of emerging infections such as Ebola. “I think it's a shame that we have absolutely nothing we can offer - a serum or a vaccine or a drug - for what everyone agrees is probably the most horrible infectious disease that we know about,” he says.

As public health specialists worry about how best to confront the threat of infectious diseases, these are some of the questions they are asking:

Is the U.S. public health system up to the task of protecting Americans from infectious diseases?

Twenty-five years ago such a question would have been dismissed with a confident “yes.” The preceding three decades had seen the development of antibiotics able to cure tuberculosis and myriad other bacterial infections, as well as vaccines that prevented polio and other life-threatening childhood diseases. Responding to these advances, then-U.S. Surgeon General William H. Stewart declared in 1967 that it was time for the scientific community to close the book on infectious diseases and turn its attention to fighting chronic problems like heart disease and cancer. 4

For all the recent concern about the public health system's deterioration, it has responded ably to recent outbreaks of emerging infections. Within a month of the first mysterious deaths from acute respiratory failure in the Southwestern United States in June 1993, the CDC managed to identify the disease's cause - a strain of hantavirus never before seen in the U.S. - as well as its source and mode of transmission. Once they discovered that the virus was spread by inhaling airborne particles of deer mouse droppings, health officials warned area residents to avoid unventilated, rodent-infested buildings, thus preventing further spread of the deadly disease.

But the CDC's success in stopping the hantavirus epidemic in its tracks is not a true barometer of the public health system's preparedness, most experts agree. Budget constraints have forced the agency to reduce its payroll and delay modernization of its 40-year- old lab facilities at a time when emerging infections demand additional expertise and state-of-the-art lab equipment. 5

“Staffing is the biggest problem,” says the CDC's Mahy. “But we also have had to fight to get Congress to restore money to build a virology laboratory to replace a building that's collapsing around us and that houses our world influenza center and many other critical activities.”

“Every expert who has looked into this problem agrees that our public health system needs considerable upgrading and that worldwide needs are even more pressing,” says Morse at the Rockefeller University. “Here in the United States, our public health system has what the people at CDC refer to as a crumbling foundation. Well, if our foundation is crumbling, you can imagine what it must be like in parts of Asia, Africa and elsewhere, where there never really was a foundation in the first place.”

The disparity is most troubling, Morse says, because it is those underserved parts of the world that are most vulnerable to emerging infections. “These areas have a great deal of biodiversity and a great deal of ecological and demographic change, and therefore all the conditions that we would expect could precipitate the emergence of human infections.”

Most experts agree that surveillance - the ability to quickly detect an outbreak of infection - is the component of the public health system most in need of improvement. “We need to have a far more alert system around the world to detect outbreaks and investigate them,” says Public Health Service adviser Henderson. “Both are very weak around the world. We're all concerned that something may emerge and begin to spread and we won't pick it up in due time, so it causes serious problems.”

Surveillance systems usually are created to track specific diseases, such as TB or malaria. As those diseases have been brought under control through drugs and vaccines, the systems designed to oversee them have eroded, becoming what Morse terms “victims of their own success.”

In his view, what remains of the surveillance systems is inadequate to deal with emergent diseases like Ebola. “These diseases are seen as bigger problems for other countries than for industrial countries,” Morse says. “That's a level of complacency that is pernicious because we have resources here and we're very much at risk.”

Are vaccines and antibiotics the best weapons against infectious diseases?

For almost 200 years, vaccines have provided a critical first line of defense against several devastating infectious diseases.

Thanks to vaccines, which confer immunity against infection, six diseases that once were the leading causes of death among infants and children - diphtheria, whooping cough (pertussis), tetanus, measles, polio and TB - have been brought under control in much of the world. Polio, which struck more than 21,000 American children in 1952, has been virtually wiped out in the Western Hemisphere, thanks to vaccines developed in the 1950s and early 1960s. Measles, mumps, diphtheria and whooping cough - all of which struck hundreds of thousands of children in the U.S. every year in earlier decades - have been greatly reduced by preventive vaccines.

In addition to saving lives and preventing permanent disability, vaccines are among the most cost-effective weapons against infectious diseases. “Vaccines are cheap as dirt,” says Bloom. When the cost of administering vaccines is compared with the cost of treating patients after they come down with a disease, the cost-effectiveness becomes even more apparent. 6 “Prevention is always likely to be more cost- effective than waiting for people to get sick,” Bloom says. “Vaccines are among the best tools we have and they pay back seven dollars for every dollar spent in giving them.”

One problem with vaccines as tools in the fight against infectious diseases is their spotty availability. Most vaccines require refrigeration, which is unavailable in many remote areas where vaccines are most needed. “There are still hundreds of deaths from time to time during outbreaks of yellow fever in Africa, even though we have had an effective vaccine against the disease since the 1930s,” Morse says. “Another problem is that many people in Africa can't afford immunizations.”

Countries that emphasize immunizations as a key ingredient of public health efforts have made great strides toward eradicating childhood diseases. After a 12-year vaccination program, Finland last year became the first country ever to eradicate measles, German measles and mumps. 7 In the United States, meanwhile, almost 28,000 Americans came down with measles in 1990, at the peak of an epidemic that killed 130. 8

Successful immunization programs require parents to take their children to the doctor periodically for booster shots, a responsibility that many fail to meet. As a result, even in the United States, many children are not receiving their full complement of vaccinations. 9

“Vaccines are wonderful, except our kids aren't getting vaccinated,” Bloom says. He cites a CDC survey that showed fewer than 55 percent of American children received their inoculations in 1992. In some cities the inoculation rates were even lower. Only 38 percent of children in the Bronx, where Bloom's institute is located, received their vaccinations that year, while Houston recorded a dismal 11 percent inoculation rate. “It's even more appalling when you consider that more than 80 percent of children in [developing] countries were getting their vaccinations under WHO programs,” Bloom says.

Normally, an antibiotic must be taken consistently over a period of days or even weeks to completely eliminate a bacterial infection. But patients often feel better after only a few days of treatment and may stop taking the drug before it has had time to have the full effect. As a result, the stronger bacteria survive and go on to infect other people. Over time, this process can lead to the emergence of an entire new strain of drug-resistant bacteria.

“What's amazing to me is that we've been able to use some of these antibiotics as long as we have,” says Morse. “We need to educate the public as well as physicians because as soon as a new drug is introduced, someone who gets an infection thinks this drug would be good for them. Sooner or later, they'll find a doctor who'll prescribe it for them. We're dumping antibiotics into the environment, and sooner or later you can expect to see antibiotic resistance appearing.”

For many years, science kept up with this trend by developing new antibiotics that were able to kill the new bacteria. But researchers are running out of drugs. Drug-resistant TB is much harder to cure than earlier strains of the disease. Even more alarming are increasingly frequent outbreaks of drug-resistant staphylococcal and enterococcal infections in hospitals. Particularly worrisome are infections resistant to vancomycin, the most powerful antibiotic in use, as well as the antibiotic of last resort against bacteria that have developed resistance to other drugs.

“We started with staph infections, which were very susceptible to penicillin,” Bloom explains. “Very shortly thereafter, however, it ceased to be effective, and methicillin was developed to deal with staph infections, and it was good for four or five years. Now there is a category of methicillin-resistant staph, and we treat them with vancomycin. If this fails to work, we'll have to shut down the surgery wards.”

Do humans have only themselves to blame for the recent spate of emerging infections?

Like other organisms, microbes that exist today are the product of millennia of adaptation to the surrounding environment. When organisms mutate - or change their biological characteristics - the changes that make them more successful in their environment are likely to be perpetuated in succeeding generations. This principle, embodied in Charles Darwin's theory of evolution, holds true for infectious microorganisms as well as for higher life forms.

Mutation is apparent in many infectious diseases. HIV, for example, mutates rapidly even after it invades human tissues, developing a succession of different patterns on its external protein coat that make it impossible for the human immune system to recognize, attack and kill the virus before it causes AIDS. Similarly, it is mutations from one generation to the next that enable influenza to develop new strains from year to year or for bacteria to develop resistance to antibiotics over time.

Human behavior has long been recognized as a contributor to the incidence of disease. Poor sanitary conditions resulting from war or economic collapse still are directly linked to outbreaks of infections. This is the case in Russia, where a recent epidemic of diphtheria is attributed to the near-collapse of the country's health- care system since the breakup of the Soviet Union. Similarly, civil war in Rwanda is blamed for last summer's outbreak of cholera in overcrowded and squalid refugee camps.

But in their quest to understand infectious diseases, scientists also are looking at subtler patterns of human development. This is especially true of emerging pathogens, whose appearance is coinciding with the most radical environmental changes ever produced by human behavior. “What's new today,” Bloom says, “is the apparent recognition of infectious disease as a response to environmental change.”

In some instances, the link between emerging infections and human development may stretch over many years. Lyme disease, a tick-borne ailment first observed in Connecticut in 1975, appears to be the result of a chain of environmental changes that began with the clearing of vast tracts of forests in the Northeast 200 years ago. As European settlers cleared the land for farming, they pushed the native deer population out of the region. After farmers moved on to more fertile land to the west, the Northeast was allowed to revert to woodland. With the forests came the deer, only in much greater numbers than before because of hunting restrictions and the disappearance of natural predators. By now, however, the region was heavily developed, and the deer shared most of their habitat with humans.

“When you have a forest and you don't go into the forest, you may never come in contact with the denizens of that forest,” Morse explains. “When you build your house in the forest, as we like to do, then you are at risk for whatever the denizens of that forest might carry, such as Lyme disease.”

The same logic holds for regions of the world where exploding human populations are pushing people into previously uninhabited territory. “When you clear the land for agriculture, you change the environment in a way that may suddenly allow a rodent species or some insect species, such as a mosquito, that might carry a previously [rare] disease to suddenly increase in number,” Morse says.

Infectious agents such as HIV, Ebola and Lassa fever are suspected of arising under just such conditions in central and west Africa. Similarly, outbreaks of lethal new and re-emerging infections in South America have coincided with the rapid deforestation of the Amazon basin. “With the hacking apart of the Amazon,” says Bloom, “malaria has gone bonkers because people are living where they haven't lived before.”

Some analysts see the appearance of AIDS and other emerging infections as a harbinger of a host of lethal microbes likely to be unleashed by a natural order determined to protect the ecosystem from further human encroachment. “In a sense, the Earth is mounting an immune response against the human species,” Preston writes in The Hot Zone. “It is beginning to react to the human parasite, the flooding infection of people, the dead spots of concrete all over the planet, the cancerous rot-outs in Europe, Japan and the United States, thick with replicating primates, the colonies enlarging and spreading and threatening to shock the biosphere with mass extinctions. Perhaps the biosphere does not 'like' the idea of 5 billion humans.” 10

Critics of this apocalyptic view say that hot viruses like Ebola are too deadly to have much of an impact on the growing human population. “Ebola, for example, kills its victims in two weeks, which doesn't give them much time to infect anyone else,” reporter Malcolm Gladwell writes in a review of Preston's book. “Ebola kills too quickly to sustain a serious epidemic.” 11

Not all new diseases emerge because humans invade the natural territories of lethal pathogens. Climate changes also play a role. “This is particularly true for diseases caused by mosquito-borne viruses,” write the authors of a landmark study of emerging infectious diseases, “since temperature increases in cooler climates may enlarge areas suitable for mosquito breeding.” Increased precipitation, they add, might lead some mosquito species to “alter their range and thus come into contact with new viruses or hosts; other species might become extinct in certain areas.” 12

Climate changes “can also affect the survival of infectious agents, particularly viruses, outside their hosts,” the researchers note. “Humidity can favor or hinder the transmission of pathogenic agents. The seasonality of some human viral diseases (such as influenza A) may be due to climatic factors that exert an influence on the organism, its host or both; sudden alterations in the climate could dramatically affect disease incidence.” 13

Morse at the Rockefeller University points to the sudden appearance of hantavirus in the desert Southwest as a case in point. The hantavirus lives naturally in the deer mouse, normally a reclusive rodent, without harming its host. The 1993-94 outbreak of hantavirus pulmonary syndrome occurred after an unusually wet season, which produced a bumper crop of the vegetation that supports the deer mouse.

As the mouse population boomed, the animals were forced to expand their territory, bringing them into closer contact with humans. Hantavirus, released into the environment in the urine and feces of deer mice, infected humans who inhaled contaminated dust particles. Unlike the deer mouse, people cannot harbor the hantavirus without becoming gravely ill. “That led to an outbreak, a cluster of cases of disease that would not otherwise have happened,” Morse says.

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* Ebola was named for a river in northern Zaire near the site of the first reported outbreak in 1976. Lassa fever is named for the town in Nigeria where it was first reported in 1969. Kenya's Rift Valley was the site of the first reported case of another viral fever, which caused a major outbreak in Egypt in 1977.

Background

Global outbreaks, or pandemics, of infectious diseases have occurred throughout recorded history, occasionally shaping events far beyond the borders of the affected regions. 14

The Greek poet Homer wrote in the Iliad of a deadly illness common during the Trojan War (1193-1184 B.C.) that he associated with the appearance of rats in urban areas. Homer was referring to plague, one of the oldest and most devastating global scourges. Caused by a bacterium, Yersinia pestis, plague usually is transmitted to humans when they are bitten by infected fleas whose primary hosts are rats and other rodents. Bubonic plague - named for the buboes, or swollen lymph nodes, that appear in the groin and neck areas of infected individuals - is the most common form of the disease.

Like later pandemics, bubonic plague is believed to have spread by human travel and commerce. From central Asia, plague traveled to European seaports in flea-infested furs or in live rats that made their way aboard ships. During the Middle Ages, bubonic plague was the cause of the Black Death, the pandemic that began in Europe in 1346 and killed 20 million people - about a quarter of the European population - over the next four years.

Plague pandemics would continue to afflict Europe, hastening the breakdown of the feudal order, as well as other parts of the world. The last major epidemic of bubonic plague occurred in India in the early 1900s, when more than 10 million people died from the disease.

India may have been the source of another major infectious disease, smallpox, which was endemic there and in Egypt for centuries before spreading throughout the world aboard the ships of European explorers. Caused by a virus, smallpox produced fever and the multiple skin lesions for which it was known. Smallpox is believed to have caused more human deaths than any other infectious disease in history.

More than superior weaponry, it was smallpox that enabled the Spanish conquistadors to gain control of much of the Americas. While smallpox was deadly among European populations, it was even more virulent among Native Americans, who had never been exposed to the virus.

First introduced by the Spanish army into Mexico in 1520, smallpox killed 3.5 million Aztec Indians - more than half the population - over two years before spreading throughout South America. European settlers also brought smallpox to North America. From the first outbreak in Massachusetts in 1617, the disease spread rapidly, in some cases killing more than half the Native Americans exposed to the pathogen.

Modern Medicine

It was against smallpox that modern medicine achieved its greatest victory in the war against infectious diseases. As early as the 10th century, Chinese physicians discovered that scratching material from the pustule of an infected smallpox patient into the skin of a healthy person offered some protection against death from the disease. A more effective vaccination against smallpox came in 1796, when Edward Jenner, an English physician, successfully prevented the disease from affecting a boy he had inoculated with material from a patient with cowpox, a genetically similar but far less virulent disease.

Jenner's vaccine was to drastically reduce the incidence of smallpox. In the United States alone, the number of cases fell from more than 110,000 in 1920 to fewer than 3,000 in 1940. The last case of smallpox in the U.S. was reported in 1949. Smallpox continued to take a large toll worldwide, however, especially in less developed countries that lacked the means to transport the vaccine to remote areas and refrigerate it. As recently as the late 1960s, some 2 million people died from the disease each year.

Unlike most microorganisms, the smallpox virus was unique to humans. Without human hosts, the virus could not survive. With this in mind, the World Health Organization in 1967 launched a global program to eradicate smallpox forever.

Scientists focused their efforts on areas where smallpox was common, immunizing residents and conducting exhaustive surveillance in an effort to halt outbreaks of the disease before they could reach epidemic proportions. The program paid off. In 1977, the last case of smallpox erupted. Two years later, the WHO declared its program a success and announced that for the first time modern medicine had succeeded in actually eradicating an infectious disease.

Vaccines have proved invaluable in fighting other infectious diseases as well. Before the early 1960s, anxious parents kept their children away from public swimming pools as soon as the summer's first cases of poliomyelitis struck their communities. Polio, also called infantile paralysis, is a crippling and sometimes fatal viral disease that most often strikes children. President Franklin D. Roosevelt was among the rare adult victims of polio, and the lasting image of the disease is that of children in steel leg braces. Because there is no cure, the only defense against polio was to avoid contagion.

Unlike most childhood infectious diseases, which were retreating as a result of newly discovered antibiotics and vaccines, polio became more virulent in the United States, reaching about 60,000 cases a year by the early 1950s. 15 The annual epidemic slowed dramatically after 1954, when Jonas Salk introduced his polio vaccine, and 1961, when an oral vaccine developed by Albert Sabin became available for distribution at schools across the country.

The polio vaccine was highly effective: The last outbreak of the disease in the United States occurred in 1979, and no cases have been reported in the Western Hemisphere since a single case in Peru in 1991. The WHO announced last October that polio had been conquered in the Western Hemisphere.

Because polio, like smallpox, occurs only in humans, it should be possible to eradicate the disease altogether. An initial target to do so by 1990 failed; more than 100,000 cases of polio occurred that year, mostly in Africa, China and India. Impediments to the polio eradication program include lack of availability of the vaccine in some affected areas and storage problems due to lack of refrigeration.

The Age of AIDS

A little-noticed item in the CDC weekly report of June 5, 1981, heralded the arrival of a new scourge that would shake public confidence in modern medicine's power over microbes: acquired immune deficiency syndrome, or AIDS.

After identifying the human immunodeficiency virus (HIV) that causes AIDS, scientists gradually found ways to combat some of the deadly infections associated with the condition, such as Kapsosi's sarcoma and Pneumocystis carinii pneumonia. But 14 years after AIDS emerged in the United States, millions of dollars of research efforts have produced only a handful of drugs to combat the virus itself, while an effective vaccine still remains out of reach. 16 As AIDS continues to spread, it has become the leading cause of death among Americans ages 22-45.

AIDS has brought in its wake a host of other infectious diseases that prey on the HIV-weakened immune system. Most alarming for its potential to spread far beyond the growing community of HIV-positive individuals is a drug-resistant form of tuberculosis.

TB is highly contagious: Anyone can contract the disease by inhaling the bacteria contained in droplets from the cough or sneeze of an infected person. The number of cases in the United States rose 14 percent between 1985 and 1993. 17 Even though the incidence of new cases has leveled off, * a growing number of them are resistant to antibiotics, making them all but impossible to treat.

Other diseases not commonly considered threats to U.S. residents also are making a comeback in this country, as well as overseas. Malaria, once endemic throughout much of the South, was largely eradicated in this country with the development of anti-malarial drugs and pesticides that killed disease-carrying mosquitoes. But some 1,200 cases of malaria have been reported each year in the United States in the 1990s. Many patients became infected in other countries, where malaria is on the rise, but some cases have been reported in people who had not traveled abroad, suggesting the return of malarial mosquitoes to some parts of the country.

Outside the United States, the reemergence of lethal infectious diseases is more pronounced, raising concern about the rapid international transmission of deadly infections. An outbreak of pneumonic plague, a highly contagious form of the disease, killed 54 people in India last fall. As thousands fled the town of Surat on the western coast, many countries interrupted air travel with Bombay and New Delhi, fearing the disease's spread.

Cholera, which broke out in Peru in January 1991, has spread throughout much of South America, where it had not been seen for more than a century. Similarly, the first-ever outbreak of yellow fever in Kenya has spawned an epidemic in that country over the past few years.

New Pathogens Hit U.S.

Even before the outbreak of the AIDS epidemic, there were signs that it was too soon to declare victory in the war against infectious diseases in the United States. In 1976, 182 people attending a convention of the American Legion in Philadelphia fell ill with a mysterious disease. Twenty-nine people died before the culprit was identified - a previously unknown bacterium that thrived and was spread through air-conditioning systems. Although it can be treated, Legionnaires' disease has recurred ever since.

The 1970s also saw the emergence of a new tick-borne pathogen. Named for the Connecticut town where it was first observed, Lyme disease is believed to have arrived with the explosion of the deer population in the Eastern United States, and with it the deer tick, a tiny cousin of the more familiar summertime pest. Characterized by reddening of the skin around the bite, fever, headache and joint pain, Lyme disease has continued to spread, causing several thousand cases each year.

Until recently, Americans gave little thought to the safety of the food and water they consumed. Cholera and other foodborne and waterborne diseases were considered to be scourges of the Third World. But in 1993, a lethal strain of E. coli, normally a harmless bacterium found throughout the environment, cropped up in hamburgers served in fast-food restaurants in four states of the Pacific Northwest, striking nearly 600 people with bloody diarrhea. Four children died of the disease.

Worried about the E. coli outbreak and increasing incidents of Salmonella poisoning, the Agriculture Department issued rules in 1993 requiring labels on packages of fresh, uncooked meat and poultry warning consumers to carefully wash hands, utensils and surfaces that come in contact with these products. Rare hamburgers and raw eggs are no longer considered safe to consume, and consumers are warned to cook these products thoroughly to reduce the chance of illness.

In 1993, a parasitic disease, cryptosporidiosis, struck Milwaukee. Like cholera, the disease is contracted by consuming contaminated water. In this case, the contamination was traced to agricultural runoff that reached the urban water supply. Before it was identified and contained, more than 400,000 people suffered prolonged diarrhea and about 4,400 were hospitalized. The number of deaths caused by the outbreak is still being investigated.

Like other strep infections, the new strain can be killed with penicillin, though massive doses are required. But Group A strep is especially pernicious because early symptoms of infection are easily confused with those of flu, which is not treated with antibiotics. By the time the correct diagnosis is made, it often is too late for antibiotic treatment. Group A strep kills about 20 percent of its victims, commonly by releasing toxins that cause pneumonia and kidney and liver damage.

Group A strep can cause toxic shock syndrome, a life-threatening condition similar to a staph infection of the same name that first appeared in the 1980s among women using superabsorbent tampons. Group A strep also can cause septicemia, a blood infection, and necrotizing fasciitis, a condition involving the rapid destruction of muscle and fat tissue - dubbed the “flesh-eating bacteria” in Britain during an outbreak last year. In December and January alone, nine people in Virginia fell ill with group A strep infections and five of them died. 18 Quebec opposition leader Lucien Bouchard narrowly survived a bout with Group A strep last December after doctors amputated his left leg to prevent progression of the disease.

The June 1993 outbreak of a mysterious respiratory disease on a Navajo reservation in New Mexico and Arizona marked the emergence of hantavirus, a microbe known to parts of Asia and Scandinavia but never before seen in the United States. In contrast with AIDS, which took years to identify and isolate, the hantavirus was identified by CDC scientists within a month and its source traced to rodent droppings. Despite the agency's fast work, 18 people would die by June 21, 1993, from what would be called hantavirus pulmonary syndrome.

Hantavirus has since been linked to 106 people in 21 states. More than half of them died of the disease, making hantavirus one of the most lethal viruses currently found in the United States.

Hot Viruses

Amid the host of new and resurgent pathogens, none awakens the fear of the rare but deadly group of microbes known as “hot” viruses. Distinguished from other infectious agents by the speed with which they dispatch their victims and the grisly symptoms of disease they cause, hot viruses have emerged with increasing frequency in recent years. All cause hemorrhagic fever, end frequently in death and often are transmitted by bites of infected insects or contact with infected rodents or monkeys.

Like HIV, hot viruses are believed to have existed harmlessly for many years, perhaps centuries, in remote parts of the world in host populations of insects, rodents or other animals. They've stricken humans only in recent years as population growth and the search for new agricultural land have driven people into areas of infection. Examples include Argentine, Bolivian and Venezuelan hemorrhagic fevers, which have broken out since the 1960s, and mosquitoborne Rift Valley fever, the first major outbreak of which occurred in Egypt in 1977.

But no emerging virus has raised greater fear than Ebola, the microbe responsible for the current outbreak of hemorrhagic fever in Zaire. Ebola is one of a group of microbes called filoviruses because of their thread-like shape. 19 The first filovirus was observed in 1967 in Marburg, Germany, where an outbreak of hemorrhagic fever among a shipment of laboratory monkeys from Uganda killed several people who had come in contact with the animals. Marburg disease, as the condition was called, struck again in South Africa in 1975. In neither outbreak were scientists able to identify the source of contagion.

Ebola, the only other known filovirus, was first seen in 1976, in separate outbreaks in Zaire and neighboring Sudan. Named for the Ebola River, which runs through the outbreak region, the new pathogen killed more than 200 people, between 50 percent and 90 percent of the people who fell ill. Ebola Zaire and Ebola Sudan also subsided and disappeared before scientists could pin down their origins. The virus re-emerged in 1989 in a shipment of lab monkeys imported from the Philippines while they were quarantined in the Washington suburb of Reston, Va. 20

Fortunately, the outbreak of Ebola Reston, as the strain involved was named, did not extend beyond the monkeys. Technicians of the U.S. Army Medical Research Institute of Infectious Disease, based in Fort Detrick, Md., staged a top-secret operation to contain the outbreak, killing all 450 monkeys. The Army facility and a lab run by the CDC in Atlanta are the only two labs in the country adequately equipped to store and study hot viruses such as Ebola.

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** The CDC counted 24,361 new cases of TB in 1994, almost 4 percent fewer than in 1993.

Current Situation

With the exception of a single case last November, Ebola was not again confirmed in humans until April 1995, when the current outbreak began in Kikwit, Zaire. 21 By the end of May, the death toll had reached 164 out of a total 211 confirmed cases, a fatality rate of about 78 percent. 22

The disease virtually wiped out Kikwit's hospital personnel, leaving a team of 22 specialists from the WHO, the CDC, the Pasteur Institute in Paris and Doctors Without Borders in Belgium to handle the crisis with 11 local doctors. They traced the outbreak to a hospital lab worker who fell ill April 14, but have been unable to find the source of the disease itself. 23

While scientists have yet to trace the source of Ebola, they are looking for a potential animal carrier of the virus. But even if an animal vector is identified, the search may not end there. Henderson recalls an earlier disease, monkey pox, seen for the first time in humans in the early 1970s. “Although the disease spread from monkeys to humans, it turned out that monkeys were not the primary source,” he says, “but that they in turn contracted it from ground squirrels.”

Ebola, like HIV, is not easily transmitted, requiring contact with blood or bodily fluids. Nevertheless, Henderson worries that mutations might enable the virus to change its mode of transmission.

“It's a curious disease,” he says. “It occurs primarily in hospital settings, but so far you don't see it spreading widely out to the community except through people who have been discharged from hospital.” His main concern is the potential for Ebola to become airborne or spread through a vector such as a mosquito. “I find that frightening as all get out,” Henderson says.

Need for Surveillance

The ability of lethal viruses to suddenly “jump” species, spreading from animals to humans, sparked another outbreak of a previously unseen virus last fall in Australia. There, a new type of morbillivirus - a group that also includes measles and canine distemper - spread from horses to two men. Before the infection was contained, 14 horses and a horse trainer died. Extremely virulent, equine morbillivirus, as the new virus is called, killed 70 percent of the horses it infected. 24

The Australian team investigating the morbillivirus managed to identify and contain the outbreak in a week. But most experts warn that the international system currently in place to trace outbreaks of infectious diseases cannot be counted on to intervene so quickly. As the medical community has shifted its attention to treating and preventing chronic diseases, resources and personnel once dedicated to tracking and fighting infections have disappeared.

“We're all worried about the state of our surveillance system,” says Morse at the Rockefeller University. “We know what surveillance is, we know how to carry it out, we have much better tools than we did 10 years ago, and yet our surveillance systems are not improving. If anything, they are getting worse.”

The flaws are most glaring, experts say, in some of the very places where emerging pathogens are most likely to occur. “Places where we would expect new agents to emerge are those with dense crowding, with the best chance of contagion, poor hygiene, near tropical rain forests or where people are invading territory that hasn't been invaded before,” Henderson says. “These conditions are especially apparent in tropical areas with large insect populations - that is, a large pool of potential vectors. These are areas that by definition have very little in the way of surveillance and very few sentinel places to look at problems as they arise.”

Experts at the WHO and the CDC agree with this view and have presented proposals to improve surveillance. Sadly, they say, any improvements that may come in response to concern over hot viruses will come too late for victims of the most serious emerging disease of our time, AIDS. “We might have detected HIV in the early 1960s had we had better methods of surveillance,” Henderson says.

While the need for improved surveillance is most evident in less developed nations, there also is cause for concern in the United States. “The public health infrastructure of this country is poorly prepared for the emerging disease problems of a rapidly changing world,” the CDC asserted in a recent study. “Current systems that monitor infectious diseases domestically and internationally are inadequate to confront the present and future challenges of emerging infections.” 25

Reporting of outbreaks in the United States is incomplete, the agency found, because physicians are required to report only a limited number of diseases and because surveillance depends too heavily on voluntary collaboration between the CDC and state and local health departments.

The CDC has called for improvements in four areas to improve surveillance: faster detection and response to emerging and re- emerging diseases; more research into diagnosis and prevention; better coordination of prevention efforts; and a stronger network for reporting a broader range of emerging diseases. 26

“We need a new weapons system for fighting infectious diseases,” Morse says. “If we think of this as a new weapons system, which is really what it is, one that can protect us against an all-pervasive enemy that is always there to trouble us, it's a very cheap weapons system. The importance of this to our future has got to be as great as Star Wars or any other defense program, and the cost is minuscule in comparison to what we would get out of it.”

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Outlook

While experts agree that surveillance needs to be improved to thwart the resurgence of infectious diseases, research into prevention and treatment also needs funding.

“Surveillance is key,” says the CDC's Mahy, “but still at the end of the day, you also need some sort of treatment for these diseases. But we are sadly lacking in research capacity. For the last 19 years, since Ebola was first reported, when we might have been able to fund some research on developing a drug or a vaccine, nothing has been done. There has been no money essentially to work on these viruses.”

Mahy cites the shutdown three years ago of an Army research effort to develop drugs against Lassa fever as an example of shortsighted budgetary action. “Due to government cuts, the Army axed their entire antiviral research program, so it no longer exists,” he says. “All that work, which might have gone on to produce some sort of a drug for Ebola, just stopped. As a result, all the doctors on the ground are able to do is give the patients a glucose drip. That's not of much use to them.”

Barring a wider catastrophe that threatens the United States, the current mood in Congress bodes ill for the new funds Mahy is calling for. The president's budget proposal for fiscal 1996 requests $8.8 million for research and surveillance of emerging infections, Mahy says. But Republican lawmakers, he says, have proposed $3.9 million for 1996, cutting $2.8 million from the current year's appropriation of $6.7 million for emerging infections. 27

“We're fighting hard to get it back,” Mahy says, “but it's very difficult at this point.”

Ebola's Future

HIV is so lethal because it does not kill its host for a decade or more. Indeed, HIV-positive individuals, often unaware of their infection for several years, can spread the virus long before being incapacitated by AIDS. In contrast, most scientists think that Ebola and other hot viruses, by killing their hosts so quickly, do not pose an especially grave threat of widespread contagion. “By killing their hosts faster than they can get themselves transmitted, they burn themselves out,” says Morse.

“Scientists have been saying for 100 years that infections have nothing to gain by sinking the ship they're on,” says Paul Ewald, a biologist at Amherst College, describing the traditional view that hot viruses are doomed to rapid extinction by their very tendency to kill their human hosts so quickly. “My argument is, if you've got a helicopter to take you from one ship to another, you may benefit by using up everything on board until the ship starts sinking and then get in your helicopter and move on.”

If there is a vector, such as a mosquito, that can spread it from host to host, the virus has nothing to gain from keeping its host healthy enough to be able to move around and infect other people. “Ebola, if it kills a high percentage of its hosts, but requires the host to move around to transmit it, is not going to be able to perpetuate itself for long,” Ewald says. “But if the virus can last for years outside its host, then it could become a bigger problem.”

Even without the emergence of a vector to make Ebola highly transmissible, most scientists predict that we have not seen the last of this lethal microbe. When Ebola made its only documented appearance to date in the United States six years ago, it did not strike humans. “In retrospect, it all worked out,” says Henderson. “But the big issue is this: What do we do in an outbreak? We simply haven't worked this through.”

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Pro/Con

Is the new Vaccines for Children program improving immunization rates in the United States?

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Short Features

Tuberculosis Returns to the United States

Until only a few decades ago, tuberculosis (TB) was one of the most dreaded diseases in the United States and around the world. Its victims suffered slow, painful deaths from respiratory failure or from an infection their weakened immune systems could no longer resist. The only recognized treatment was rest in “sanitariums,” special hospitals set up in rural areas where TB patients could breathe clean air and be isolated from the uninfected population.

The introduction of penicillin, the first modern antibiotic, in the 1940s was a major victory in the war against TB. This was the first drug that could actually kill Mycobacterium tuberculosis and restore TB patients to health. Since then, the disease has been successfully treated with a combination of four newer antibiotics - isoniazid, rifampicin, pyrazinamide and ethambutol - taken over two months, followed by a four-month treatment with isoniazid and rifampicin alone.

Drug treatment initially was very successful. The death rate from TB in New York City, once a hotbed of TB infection, plummeted from 197 deaths per 100,000 people at the turn of the century to only two deaths per 100,000 people in 1980. The number of newly reported cases of TB nationwide fell from 135,000 in 1947 to 22,000 in 1985. 1

But just when TB seemed to be heading the way of smallpox and polio into mankind's distant memory, the disease began to resurface with a vengeance. By 1992, the number of new cases in the United States had climbed to 30,000.

The World Health Organization (WHO), which in 1993 declared a global TB emergency, estimates that the disease claims nearly 3 million lives each year, more than any other infectious disease.

The forms of TB seen today, from the poorest developing countries to New York and other U.S. cities, are far more virulent than the forms treated so readily with penicillin a half-century ago. Even the newer, stronger antibiotics are proving to be no match for the disease. Multidrug-resistant TB is spreading throughout the world and accounts for nearly half the new cases and most of the relapses seen in the United States.

Multidrug-resistant TB is the product of incomplete treatment of infected individuals. Because patients usually feel better soon after beginning treatment, they may be tempted to stop taking their drugs before they have killed all the bacteria, often selling the expensive medications or giving them to sick family members. Patients who interrupt their treatment enable the most drug-resistant TB bacteria to survive and grow in their bodies, and go on to infect other people.

Ironically, it was the earlier victory against TB that fueled the disease's return in the 1980s and '90s. After the introduction of modern antibiotics, attention shifted to chronic diseases such as heart disease and cancer, and resources to fight TB dried up. By 1988, New York City's TB control budget stood at only $4 million, a tenth of the 1968 level.

“There are basically three reasons for TB's return to New York and other cities,” says Barry R. Bloom, an expert in TB research at the Howard Hughes Medical Institute at Albert Einstein College of Medicine in the Bronx. “The first is AIDS, which causes immunosuppression, making it far more likely that people infected with TB will develop active disease. The second is the disintegration of social structures and the resulting homelessness and overcrowded conditions in shelters, which are as good a way as any to make TB happen. The third is the crumbling of our public health system, especially the cessation of federal funding of state TB control programs in the early 1970s.”

Although there are other ways to combat TB, the most effective is directly observed treatment of individuals who already are infected with the disease. This approach, first used in Tanzania in 1977 and recommended by the WHO, requires health workers to watch their patients swallow each dose of medicine every day for at least the first two months, and preferably all six months, of treatment.

Widely publicized outbreaks of multidrug-resistant TB in New York hospitals and prisons in the late 1980s prompted the CDC and other agencies to renew funding for TB control in 1989. New York's TB program hired additional outreach workers to follow up each case for the duration of treatment and offered incentives such as subway tokens and food vouchers to encourage patients to participate. Today, nearly 40 percent of New York's TB patients are undergoing directly controlled treatment, compared with a national average of only 17 percent, and the incidence of TB in the city has already started to decline, falling by 15 percent from 1992 to 1993. 2

The CDC counted 24,361 new cases of TB nationwide in 1994, almost 4 percent fewer than in 1993. But public health experts worry that recent progress against TB may hold the seeds of its resurgence unless the renewed attention to the disease is permanent.

“Every so often there's a disaster that makes people take notice,” says Stephen S. Morse, a virologist at the Rockefeller University in New York City. “Suddenly we're back there doing surveillance of TB again, but we're always behind the need. The crisis appears, and then we respond to the crisis, which is not really a proactive response, nor is it efficient. Like everything else we do in infectious diseases, once the immediate crisis is over the system becomes a victim of its own success.”

[1] Office of Technology Assessment, Impacts of Antibiotic Resistant Bacteria, summer 1995 (forthcoming).

[2] See World Health Organization, WHO Report on the Tuberculosis Epidemic, 1995.

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Public Health System Is Key to Fighting Infectious Diseases

The key to preventing outbreaks of infectious diseases from becoming epidemics is a strong public health system. To be successful, health professionals must quickly detect an outbreak of infection and immediately notify a central authority that is responsible for coordinating efforts to isolate and control the contagion.

In the United States, that central authority is the Centers for Disease Control and Prevention (CDC). Established in 1946 and headquartered in Atlanta, Ga., the CDC maintains a list of about 50 infectious diseases - ranging from acquired immune deficiency syndrome (AIDS) to yellow fever - that health professionals are expected to report.

Reporting is voluntary for most infections on the list. The exceptions are diseases requiring quarantine - cholera, diphtheria, plague, suspected smallpox, 1''

Even more critical, the system is slow to respond to previously unreported diseases. “Outbreaks of any disease that is not on the CDC's current list of notifiable illnesses may go undetected altogether or may be detected only after an outbreak is well under way,” concluded a landmark study by the Institute of Medicine. 2

Once outbreaks are detected and reported, it is up to the CDC to coordinate efforts to stop them. The CDC's National Center for Infectious Diseases (NCID) maintains samples of the world's known microbes in a vast facility that also houses one of the country's two biocontainment labs, where samples of Ebola and other deadly germs are kept. The other is at the Army Medical Research Institute of Infectious Diseases at Fort Detrick, Md. Keeping samples of microbes alive in labs may enable scientists to develop vaccines to prevent the spread of infections or drugs to treat patients once they have fallen ill.

In addition to surveillance and research, the NCID helps foreign governments and international agencies such as the Geneva-based World Health Organization (WHO) control outbreaks of infectious diseases when they occur. NCID recently sent experts to Kikwit, Zaire, to help stop the spread of the Ebola virus.

One obstacle to improving the public health system's line of defense against new and recurrent infectious diseases is funding. “NCID, along with the rest of the CDC, has an almost diminishing budget to work with, and much of that is being directed to AIDS,” says Donald A. Henderson, a senior science adviser to the U.S. Public Health Service.

The funding problem is especially grave for the labs that house and conduct research on lethal emerging viruses. “Over the past three or four years, Fort Detrick has had budget cutbacks, and many of the top people have left, so the program is greatly weakened,” Henderson says.

The CDC recently issued recommendations to strengthen the public health system's ability to respond to infectious diseases. In addition to strengthening surveillance at the state and local levels, the agency proposed creating two new U.S. surveillance networks to detect emerging diseases and improving coordination at four existing centers to promote faster international response once outbreaks occur.

Brian Mahy, director of the CDC's viral and rickettsial diseases division, says the proper diagnosis of Ebola during the recent outbreak in Zaire was delayed when the viral samples were sent erroneously to an institute in Antwerp, Belgium, that no longer has the capacity to diagnose hemmorhagic fevers. “The public health response to infectious diseases is a worldwide problem, not just a U.S. problem,” Mahy says.

At a time of reduced funding worldwide, scientists are struggling to improve the understaffed and poorly coordinated international reporting system on their own. In September 1993, a group of scientists meeting in Geneva created ProMED, the Program for Monitoring Emerging Diseases. Co-sponsored by the WHO and the Federation of American Scientists, ProMED maintains an electronic forum to which scientists and health-care providers can report any unusual infections and share information on treatment and prevention strategies. The new reporting system already has helped identify several emerging infection outbreaks, including last fall's equine morbillivirus outbreak in Australia.

“Worldwide, we need networks for surveillance, and there's a lot that can be done just by improving, streamlining and better coordinating systems that already exist so that they can share data,” says Stephen Morse, a virologist at the Rockefeller University in New York City and one of the founders of ProMED. “But there's no point in providing surveillance data if there isn't going to be some use made of the information, and that's often the problem. The data often are collected and disappear into a black hole. The CDC and WHO are working very hard on excellent plans to improve this. What's needed now is money.”

[1] Smallpox was officially eradicated in 1979, but remains on the CDC's list.

[2] Joshua Lederberg, Robert E. Shope and Stanley C. Oaks Jr., eds., Emerging Infections (1992), p. 120.

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Recent Outbreaks of Infectious Diseases

A number of lethal infectious diseases have been discovered and identified in the past two decades. They include AIDS, Ebola hemorrhagic fever, Lyme disease and hantavirus pulmonary syndrome. During the same period, virulent forms of previously known pathogens caused major disease outbreaks as well. Some of the most recent outbreaks are shown on the map below.

Dengue, 1993:

This mosquitoborne tropical virus causes hemorrhagic fever and shock. It ranks only behind malaria in the number of worldwide cases of insectborne diseases. The 1993 outbreak occurred in Costa Rica.

Hantavirus, 1993:

Hantavirus pulmonary syndrome has struck 106 people in 21 states since it first appeared in the Southwestern U.S. More than half of those infected with the mouseborne microbe have died of acute respiratory failure.

Ebola, 1995:

First reported in 1976, this is one of the most lethal viruses ever seen. At least 164 of 211 people infected during the recent outbreak in Zaire had died by the end of May.

Diphtheria, 1993:

This childhood disease, easily controlled by vaccination, has made a comeback in Russia in recent years. The out-break is attributed to the near-collapse of the nation's health-care system following the breakup of the Soviet Union.

Yellow Fever, 1993:

An outbreak of this ancient, mosquitoborne viral disease occurred in western Kenya in 1993; it is spreading to fast-growing cities in central Africa.

Rift Valley Fever, 1993:

This new, mosquito-borne viral disease has cropped up near dams and irrigation sites in Africa. The first major outbreak was reported in Egypt in 1993.

Lassa Fever, 1992:

Urbanization and poor sanitation contributed to the appearance of this new viral disease in West Africa. It spreads through contact with rodent urine or feces.

Pandemic Cholera, 1991:

First reported in Peru, this virulent strain of an ancient waterborne bacterium has spread to much of Central and South America, as well as Mexico.

Cryptosporidiosis, 1993:

Contamination of Milwaukee's water supply sickened 400,000 people, marking the worst outbreak of waterborne disease in U.S. history.

Escherichia coli O157:H7, 1993:

A virulent strain of a common bacteria, unknown before 1988, killed four children and sickened at least 500 people who consumed tainted hamburger meat in the Pacific Northwest.

Pneumonic Plague, 1994:

A highly contagious form of the age-old disease broke out in Surat, India.

Equine morbillivirus, 1994:

The first new morbilli-form virus to emerge since the 10th century killed a man and 14 horses in an apparently isolated outbreak in Queensland, Australia.

Malaria, 1995:

More than 700 people have died in an out-break in Bangladesh, attributed to a sudden influx of mosquitoes from India, which had carried out an aggressive pesticide campaign. The malaria outbreak follows a diarrhea epidemic that has claimed more than 400 lives in Bangladesh.

Source: Centers for Disease Control and Prevention

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The Leading Causes of Death

Nearly a third of the 51 million deaths worldwide in 1993 were caused by infections and parasites, according to the Geneva-based World Health Organization (WHO). Cause: Infectious and parasitic diseases 32% 16,445,000 Diseases of the circulatory system 19% 9,767,000 Malignant neoplasms 12% 6,013,000 External causes 8% 3,996,300 Perionatal and neonatal causes 6% 3,180,000 Chronic lower-respiratory diseases 6% 2,888,000 Maternal causes 1% 508,000 Other causes 0.3% 170,000 Unknown causes 16% 8,123,700

Note: Total does not add to 100 percent because of rounding.

Source: World Health Organization, The World Health Report 1995.

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The Threat of Emerging Infections

Outbreaks of infectious diseases are on the upswing. Emerging infections, which include newly discovered pathogens as well as new forms of older infectious agents, have a variety of causes, some still shrouded in mystery. Most produce the typical symptoms of acute infection - fever, headache, malaise, vomiting and diarrhea. Some have no known treatment or cure. The following list includes some of the better-known emerging infections: -------------------------------------------------------- VIRAL -------------------------------------------------------- Disease Agent: Filoviruses (Ebola, Marburg) Factors Facilitating Emergence: Unknown Symptoms and Treatment: Sudden fever, diarrhea, vomiting, massive hemorrhaging. Support treatment only, no cure. -------------------------------------------------------- Disease Agent: Hantaviruses Factors Facilitating Emergence: Environmental changes increasing exposure to rodent hosts. Symptoms and Treatment: Hemorrhagic fever, kidney failure. Support treatment, ribavirin (an antiviral drug) may help. -------------------------------------------------------- Disease Agent: Human Immunodeficiency Virus (HIV) Factors Facilitating Emergence: Travel, migration to cities. Sexual transmission, use of contaminated needles, transfusions. Symptoms and Treatment: AIDS. Several antiviral drugs can slow progression; other drugs are used to treat opportunistic infections from immunosuppression. -------------------------------------------------------- Disease Agent: Influenza Factors Facilitating Emergence: Raising pigs and ducks, some flu viruses' natural hosts, may facilitate rapid genetic changes, causing periodic epidemics. Symptoms and Treatment: Sore throat, fever, malaise. Immunization; some drugs can shorten illness.. -------------------------------------------------------- Disease Agent: Lassa fever Factors Facilitating Emergence: Rapid urbanization in squalid conditions bringing humans in contact with rodent hosts. Symptoms and Treatment: Fever, malaise, headache, sometimes shock, seizures. Ribavarin, ventilation and dialysis sometimes needed. -------------------------------------------------------- Disease Agent: Rift Valley fever Factors Facilitating Emergence: Dam construction, irrigation, facilitating spread of mosquito vector (carrier). Symptoms and Treatment: Abrupt onset of fever, severe fever complications in survivors, with visual and nerve damage. --------------------------------------------------------- BACTERIAL --------------------------------------------------------- Disease Agent: Cholera Factors Facilitating Emergence: Recent epidemic in South America introduced from Asia by ship; spread by travel and inadequate water chlorination. Symptoms and Treatment: Acute intestinal symptoms. Recent strains resistant to several antibiotics. -------------------------------------------------------- Disease Agent: Escherichia coli O157:H7 Factors Facilitating Emergence: Contamination of meat during butchering process; spread by poor handling and inadequate cooking. Symptoms and Treatment: Hemolytic uremic syndrome, hemorrhagic colitis. Oral or intravenous replacement of fluids. -------------------------------------------------------- Disease Agent: Legionnaires' disease (Legionella) Factors Facilitating Emergence: Plumbing and air-conditioning systems. Symptoms and Treatment: Fever, confusion, pneumonia. Erythromycin and rifampicin. -------------------------------------------------------- Disease Agent: Lyme disease Factors Facilitating Emergence: Proliferation of deer and deer tick vector in heavily wooded inhabited areas. Symptoms and Treatment: Fatigue, headache, sometimes persistent arthritis. Oral or intravenous antibiotics. -------------------------------------------------------- Disease Agent: Tuberculosis Factors Facilitating Emergence; Increase in immunosuppressed population, improper treatment exposing more people to disease. Symptoms and Treatment; Cough, weight loss, can spread beyond lungs to other organs. Combination of antibiotics for at least six months. -------------------------------------------------------- Disease Agent: Group A Streptococcus infections Factors Facilitating Emergence: Uncertain. Symptoms and Treatment: Necrotizing fasciitis, streptococcal toxic shock. Antibiotics. -------------------------------------------------------- Disease Agent Toxic shock syndrome (Staphylococcus) Factors Facilitating Emergence Super-absorbency tampons, post-surgical infection Symptoms and Treatment High fever, vomiting, severe diarrhea, rash, shock. Fluid/electrolyte replacement, intravenous antibiotics. -------------------------------------------------------- PARASITIC -------------------------------------------------------- Disease Agent: Cryptosporidium and other waterborne pathogens Factors Facilitating Emergence: Protozoan-contaminated surface water. Symptoms and Treatment: Diarrhea, vomiting, usually lasts less than 30 days. Fluid/electrolyte replacement. -------------------------------------------------------- Disease Agent: Malaria (in new areas) Factors Facilitating Emergence: Migration and travel to mosquito-infested areas. Symptoms and Treatment: Fever, headache, can cause respiratory and renal failure. Chloroquine, but some forms may be resistant to most drugs.

Source: Stephen S. Morse, “Factors in the Emergence of Infectious Diseases,” Emerging Infectious Diseases, January-March 1995, p. 8.

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Bibliography

Books

Garrett, Laurie , The Coming Plague: Newly Emerging Diseases in a World Out of Balance, Farrar, Straus and Giroux, 1994. The author, a journalist with a graduate education in immunology, provides a detailed analysis of a broad spectrum of diseases that have emerged or re-emerged in recent years. She discusses efforts to trace their origins, control outbreaks and develop treatments.

Karlen, Arno , Man and Microbes: Disease and Plagues in History and Modern Times, G.P. Putnam's Sons, 1995. Emerging infections can be traced to human development, Karlan writes in this natural history of infectious disease. He places the current outbreaks in the context of past epidemics of plague, smallpox and other diseases that helped shape the course of history.

Stanley C. Oaks, Jr. , Emerging Infections: Microbial Threats to Health in the United States, National Academy Press, 1992. This Institute of Medicine study examines the risk factors involved in emerging infections and proposes a strategy for strengthening the international surveillance system to detect these often lethal diseases.

Preston, Richard , The Hot Zone, Random House, 1994. Preston recounts the outbreak of Ebola virus among a shipment of laboratory monkeys housed in Reston, Va., in 1989. He describes the microbe's previous appearances and the problems faced by public health authorities in dealing with such a lethal pathogen.

Articles

Greenburg, Dan , “Germ Warfare,” New York, Oct. 3, 1993. Hospitals in New York and other cities are experiencing a worrisome increase in patient bacterial infections that are resistant to antibiotics, including the drug of last resort, vancomycin.

Morse, Stephen S. , “Factors in the Emergence of Infectious Diseases,” Emerging Infectious Diseases, January-March 1995, pp. 7-15. Morse, who coined the term “emerging infections,” summarizes the state of current knowledge about these diseases in the first issue of a new medical journal devoted to the study of new and re-emerging infections.

“Outbreak of Fear,” Newsweek, May 22, 1995, pp. 48-55. The recent outbreak of deadly Ebola hemorrhagic fever in Zaire has heightened concern over the ability of the United States to ward off epidemics of new infectious diseases. The article also describes outbreaks of other emerging diseases.

Ross, Philip E. , “A New Black Death?”, Forbes, Sept. 12, 1994, pp. 240-250. Lulled into complacency by the development of potent infection-fighting drugs, the United States and other countries have allowed their surveillance systems to lapse even as new diseases continue to emerge, Ross writes.

Siebert, Charles , “Smallpox Is Dead. Long Live Smallpox,” The New York Times Magazine, Aug. 21, 1994, pp. 30-37, 44, 52, 55. Following the global eradication of smallpox in 1979, samples of the deadly virus survive in only two locations, Moscow and the Centers for Disease Control and Prevention in Atlanta, Ga. A decision to destroy these samples has been delayed repeatedly as scientists argue over the merits of that decision.

Reports and Studies

Control and Prevention, Centers for Disease , Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States, 1994. The CDC proposes four goals for preventing the spread of new and resurgent infections, including a better surveillance system to detect and respond to outbreaks and more research aimed at improving diagnosis and prevention.

Assessment, Office of Technology , Impacts of Antibiotic Resistant Bacteria, summer 1995 (forthcoming). The rising incidence of bacterial infections that do not respond to treatment with common antibiotics requires the development of ways to prevent infection as well as new drugs to fight these pervasive microbes, OTA concludes.

Organization, World Health , The World Health Report 1995: Bridging the Gaps, May 2, 1995. This first annual survey of global health by the Geneva-based U.N. agency emphasizes the role of poverty in deaths from infectious diseases. Although a WHO inoculation program has helped reduce the incidence of six major childhood infections, some 2.4 million children in developing countries die each year from these preventable diseases.

Organization, World Health , WHO Report on the Tuberculosis Epidemic, 1995, March 1995. The spreading global TB epidemic can be stopped quickly, according to the U.N. agency, but only if governments will systematically oversee the treatment of all infected individuals to ensure they complete therapy until they are cured.

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The Next Step

Periodical Abstracts database

Ebola

“Avoiding a Biological Meltdown,” The Los Angeles Times, May 17, 1995, p. B6. An editorial states that global cooperation is needed in the fight against contagious viruses, such as the Ebola virus that has stricken Zaire in May 1995.

Cimons, Marlene , “Researchers Puzzled Over Virus' Continuity, Host,” The Los Angeles Times, May 13, 1995, p. A5. Initial studies using DNA sequencing indicate that the virus causing the outbreak of Ebola in Zaire in May 1995 is the same one found in that region in 1976 and 1979.

Rochell, Anne , “Ebola the Culprit in Zaire Deaths,” Atlanta Constitution, May 12, 1995, p. A3. Scientists at the CDC in Atlanta said that the strain of Ebola responsible for dozens of deaths in Zaire resembles the most dangerous known strain of the virus. The CDC has received reports that the current outbreak has spread out of Kikwit.

SoRelle, Ruth , “Killer Outbreak in Zaire,” Houston Chronicle, May 12, 1995, p. A1. Ebola virus outbreaks have been identified in Africa three times before the current epidemic in Zaire. But because of the recent attention given exotic diseases in the popular media, what was once far away now seems terrifyingly immediate.

“Zaire Battles Virus, Panic,” Boston Globe, May 14, 1995, p. 2. With rumors and lurid headlines fanning fears, health specialists in Zaire trying to prevent the spread of the Ebola virus concentrated on containing panic that could cause people to try to get out of the quarantined city of Kikwit.

Hantavirus Outbreak

Bales, Fred , “Hantavirus and the Media: Double Jeopardy for Native Americans,” American Indian Culture & Research Journal, 1994, pp. 251- 263. The outbreak of the Hantavirus illness during the summer of 1993 brought not only death to the Navajos of the Southwest but sterotypical reporting and invasions of privacy. The media's coverage of the disease is discussed.

Devaughn, Melissa , “Hantavirus Hits the Trail,” Backpacker, May 1995, p. 19. Hantavirus, a viral disease spread by airborne particles of dried rodent urine, droppings or saliva, has been found on the Appalachian Trail. Hikers face little risk, but a few simple precautions are recommended.

Holden, Constance , “Public Health Threats,” Science, March 10, 1995, p. 1427. Three new diseases discovered in 1993 - cryptosporidosis, hantavirus disease and hemolytic uremic syndrome - along with four others have been added to the list of some 50 communicable diseases that are reported by states to the CDC.

Hurt, Harry, III , “A Deadly New Virus,” Self, April 1995, pp. 88- 93. Strains of the hantavirus are carried by rodents, and there is no cure or treatment. Although the lethal virus is rare at present, public health scientists are scrambling to stay ahead of it because it is widespread in rodent populations throughout the US.

“Indians Reject Name Linking Illness to Tribe,” The New York Times, April 24, 1994, p. 21. The Navajo Nation Council says that the hantavirus that has killed 40 people, including many Navajo Indians, should not be named after a canyon on its reservation. The council voted 52 to 0 on April 21 to ask the Centers for Disease Control and Prevention not to recommend naming the virus Muerto Canyon Hantavirus.

Infectious Diseases

Conradi, Peter , “Russia Hit by Infectious Diseases,” British Medical Journal, 1995, p. 821. Countries of the former Soviet Union are seeing a sharp increase in the incidence of infectious diseases. Poverty and the breakdown of the communist health care system seem to be to blame.

Kellerman, Vivien , “Can Science Conquer the Scourge of Infectious Diseases?,” The New York Times, Jan. 29, 1995, p. L2. Bruce Farber, a specialist in infectious diseases, is interviewed.

McConnell, John , “Emerging and New Infectious Diseases,” Lancet, June 4, 1994, p. 1423. Diseases caused by previously unrecognized or re-emergent infectious agents have become so prevalent that the World Health Organization and the CDC are setting up special programs to combat them. Tuberculosis has re-emerged, and several strains found only in HIV-infected patients have been found.

Ringel, Marcia , “Fighting to Control Infectious Diseases,” The New York Times, July 17, 1994, p. N3. Sindy M. Paul, a senior public health physician of the New Jersey Health Department, is interviewed about infection control and public health issues.

Gordon R. Douglas, Jr. , “Infectious Diseases,” JAMA: The Journal of the American Medical Association, June 1, 1994. Infectious diseases, such as Haemophilus influenzae type b and Streptococcus pneumoniae, and their treatments are discussed. HIV vaccine trials and the outbreak of a unique hantavirus in the southwestern U.S. are also highlighted.

Wade, Nicholas , “Microbes Into Infinity,” The New York Times, May 14, 1995, p. 4. Terrifying as the spread of the deadly Ebola virus in Zaire is, the real cause of alarm lies in a broader issue that the Ebola epidemic raises: an unrelenting stream of new or newly awakened disease organisms has emerged in recent years, and it shows no sign of ending. In the last two decades the U.S. has been struck by Lyme disease, Legionnaires' disease, toxic shock syndrome, HIV and hantavirus, and a crop of spectacularly violent pathogens has been recorded from Africa and South America, such as the Ebola, Lassa fever, Marburg and Sabia viruses.

Lassa/Rift Valley Viruses

“International Notes: Rift Valley Fever - Egypt, 1993,” Morbidity & Mortality Weekly Report, Sept. 30, 1994, p. 693. Rift Valley fever (RFV) is caused by an RNA-containing virus of the Bunyaviridae family, and RVF epizootics are characteristically associated with domesticated ruminants (e.g., sheep, cattle, buffalo, goats and camels) and humans living in close proximity. A report of serosurveys of RVF in Answan Egypt in 1993 is presented.

Malaria

Bishop, Jerry E. , “Tobacco, Used to Make Malaria Vaccine, Might Prove a Source of Cheap Therapies,” The Wall Street Journal, Jan. 3, 1995, p. A13. A biotechnology experiment indicates that a tobacco plant, which produced a malaria vaccine through genetic engineering, showed that the much-disparaged weed holds promise for low-cost, high-volume production of a variety of vaccines.

Kumar, Sanjay , “Malaria Epidemic in Rajasthan,” Lancet, Oct. 29, 1994, p. 1217. The official government figure for deaths due to Plasmodium falciparum malaria in Rajasthan India in 1994 is 248, but non-governmental organizations contend that the number is much higher. An irrigation project in Rajasthan is being blamed for the outbreak.

Maurice, John , “Malaria Vaccine Raises a Dilemma,” Science, Jan. 20, 1995, pp. 320-323. Colombian scientist Manuel Patarroyo has developed what could be the first effective malaria vaccine and is trying to distribute it world wide. The vaccine, SPf66, has met with some controversy in scientific circles.

Parasitic Diseases

Brown, David , “Infection Is World's No. 1 Cause of Death,” The Washington Post, May 2, 1995, p. A3. Infectious and parasitic diseases are the leading cause of mortality on the Earth, but heart disease, stroke and cancer, disorders associated with longevity, smoking and an affluent lifestyle, now kill almost as many people worldwide, the World Health Organization reported.

Brown, Phyllida , “Two Cheers for a New Vaccine,” World Press Review, February 1995, p. 44. Colombian biochemist Manuel Patarroyo has developed a malaria vaccine that has passed a tough trial in Tanzania. The SPf66 vaccine is the first vaccine against any parasitic disease of humans.

Norm Brewer , “Before Gulf War, Pentagon Knew Vaccine for Disease Was Available,” Detroit News, Dec. 12, 1994, p. E1. For years before the 1991 Persian Gulf War, the Pentagon knew a vaccine existed for leishmaniasis, a rare parasitic disease some doctors think may be causing the mysterious symptoms of many American desert war veterans.

Mestel, Rosie , “Killer Parasite Urges Cells to Destroy Themselves,” New Scientist, Feb. 4, 1995, p. 18.

Tuberculosis

J. Moore-Gillon; , “Increasing Incidence of Tuberculosis in England and Wales: A Study of the Likely Causes,” British Medical Journal, April 15, 1995, pp. 967-969. A study of the incidence of TB in England and Wales was conducted to examine factors responsible for the recent increase in TB rates. The national rise in TB affected only the poorest areas, indicating a major role for socioeconomic factors.

Darbyshire, Janet H. , “Tuberculosis: Old Reasons for a New Increase?”, British Medical Journal, April 15, 1995, pp. 954-955. Notifications of TB have increased in England, Wales, other European countries and the U.S. over the past few years. The increase in the number of reported cases is discussed in an editorial.

DeCock, Kevin M. , “Screening for tuberculosis and HIV in resource-poor countries,” Lancet, April 8, 1995, pp. 873-874. A study that assessed TB screening of persons attending a center for voluntary HIV testing and counseling in the Dominican Republic is described. Third World countries should make identification and treatment of smear-positive cases of TB a priority for TB control programs.

“Fighting Drug-Resistant TB,” Times-Picayune, March 8, 1994, p. B6. An editorial says disturbing evidence of tuberculosis's growing strength, compiled by the Centers for Disease Control and Prevention, shows that one in seven cases of TB in the U.S. is resistant to drugs that previously offered a cure.

“Four Airplane Passengers Infected With Tuberculosis by Dying Woman,” San Francisco Chronicle, March 3, 1995, p. A3. Federal investigators said on March 2, 1995, that a woman with severe tuberculosis who took airline flights between Baltimore and Honolulu in May 1994 infected four other people sitting nearby - the first recorded case of TB transmission between airplane passengers.

Jeffewy Starke , “Immigrants and Tuberculosis Control,” New England Journal of Medicine, April 20, 1995, p. p.6. An editorial discusses two articles that assessed the impact that immigration has had on TB in the U.S. Among foreign-born persons, there is a relatively high risk of TB that is drug-resistant, and steps must be taken to prevent a further resurgence of TB in the United States.

Platt, Anne E. , “The 10 Most Underreported Stories of 1994: Why Haven't We Stopped Tuberculosis?”, St. Louis Journalism Review, April 1995, p. 15. The growing epidemic of tuberculosis is one of the 10 most underreported news stories of 1994. Tuberculosis kills more people than any other infectious or communicable disease in the world, despite the fact that it is curable.

“World-Wide: Tuberculosis Has Risen,” The Wall Street Journal, April 20, 1995, p. A1. The CDC said tuberculosis has risen sharply among foreigners in the U.S., and the trend should continue unless there is a greater effort to control the disease among immigrants.

for Disease Control, U.S. Centers , “The Centers for Disease Control and Prevention on Emerging Infectious Disease Threats,” Population & Development Review, September 1994, pp. 687-690. Excerpts from a 1994 CDC publication entitled “Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States” are presented. The publication focuses on the situation in the U.S. but with full recognition of the global nature of the problem.

Schrader, Ann , “Immunizations Cost-Effective,” Denver Post, Sept. 9, 1994, p. A9. The director of the Centers for Disease Control and Prevention spoke to several hundred people on Sept. 8, 1994, at a regional childhood immunization conference in Denver, and stressed that immunizations are cost-effective. In Colorado, about 63 percent of 2-year-olds are fully immunized, compared with a national average of 72 percent.

Washington, Shelia , “CDC Head Looks to Champion Immunization,” Chicago Defender, Sept. 27, 1994, p. 6. David Satcher, the first African American to head the Centers for Disease Control and Prevention, is implementing the Childhood Immunization Initiative to immunize children in the U.S. against 15 “vaccine preventable” diseases by age 2.

Vaccine Development

Fackelmann, Kathy A. , “AIDS Research: From Vaccines to Safer Sex,” Science News, August 13, 1994, pp. 102-103. A report on the Tenth International AIDS Conference in Yokohama Japan is presented. Topics discussed at the conference ranged from vaccine development to long-term survivors of HIV infection.

Marwick, Charles , “Exciting Potential of DNA Vaccines Explored,” JAMA: The Journal of the American Medical Association, May 10, 1995. A new approach in vaccine development involves delivering the gene sequences of the desired antigen into the host by inserting the gene for the antigen via a nonreplicating plasmid vector. This new approach is discussed.

Russell, Philip K. , “Heading Off a Crisis in Vaccine Development,” Issues in Science & Technology, spring 1995, pp. 26-32. Despite its vast scientific resources and great expenditures on health care, the U.S. is doing a poor job in developing new vaccines. An R&D partnership between industry and government is the best way to develop vaccines.

World Health Organization

The World Health Organization has grown into a complex bureaucracy with an outdated organizational structure in the last 45 years the author says. The structure, culture and mission of the World Health Organization are examined.

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Contacts

National Center for Infectious Diseases
Centers for Disease Control and Prevention, 1600 Clifton Rd. N.E., MS C-14, Atlanta, Ga. 30333,
(404) 639-3311.
Health care providers are required to report to this U.S. government unit all cases of listed infectious diseases. The CDC is then responsible for responding to outbreaks.

National Foundation for Infectious Diseases
4733 Bethesda Ave., #750, Bethesda, Md. 20814,
(301) 656-0003.
In addition to raising funds for research, the foundation provides information on infectious diseases and sponsors annual immunization awareness campaigns.

Pan American Health Organization
525 23rd St. N.W., Washington, D.C. 20037,
861-3200.
This division of the World Health Organization oversees the WHO's activities in the Western Hemisphere, such as a tuberculosis program aimed at convincing governments to institute direct-observation treatment plans to combat the current spread of TB.

World Health Organization
20, Avenue Appia, CH-1211 Geneva 27, Switzerland, 41-22-
791-2969.
This agency of the United Nations is the leading international repository of information on infectious disease outbreaks anywhere in the world and coordinates international teams to control epidemics.

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Footnotes

[1] World Health Organization, The World Health Report 1995, May 2, 1995.

[2] See Joshua Lederberg, Robert E. Shope and Stanley C. Oaks, Jr., eds., Emerging Infections (1992). Lederberg, a professor at the Rockefeller University, received the Nobel Prize in 1958 for his work in the genetic structure and function of microorganisms. Shope, director of the Yale University Arbovirus Unit, has discovered and identified a number of emerging microbes. Oaks, a microbiologist, was study director of the Institute of Medicine's Division of Health Sciences Policy at the time of publication.

[3] For background, see “Food Safety,” The CQ Researcher, June 4, 1993, pp. 481-504, and “Water Quality,” The CQ Researcher, Feb. 11, 1994, pp. 121-144.

[4] William H. Stewart, “A Mandate for State Action,” presented at the Association of State and Territorial Health Officers, Dec. 4, 1967, cited in Laurie Garrett, The Coming Plague (1994), p. 33.

[5] See Lawrence K. Altman, “U.S. Agency on Front Line of Disease War: Crowded, Understaffed and Overwhelmed,” The New York Times, May 20, 1995, p. A9.

[6] See The World Bank, World Development Report 1993, pp. 213-225.

[7] See Heikki Peltola et al., “The Elimination of Indigenous Measles, Mumps, and Rubella from Finland by a 12-Year, Two-Dose Vaccination Program,” The New England Journal of Medicine, Nov. 24, 1994, pp. 1397-1402.

[8] Michael B. Heisler and Julius B. Richmond, “Lessons from Finland's Successful Immunization Program,” The New England Journal of Medicine, Nov. 24, 1994, pp. 1446-1447.

[9] For background, see “Childhood Immunizations,” The CQ Researcher, June 18, 1993, pp. 529-552.

[10] Richard Preston, The Hot Zone (1994), p. 287.

[11] Malcolm Gladwell, “Killer Monkeys of Reston,” The Washington Post Book World, Oct. 16, 1994. Gladwell is a Post reporter based in New York City.

[12] Lederberg et al., op, cit., pp. 76, 77.

[13] Ibid. p. 77.

[14] Unless otherwise noted, information in this section is based on Lederberg et al.

[15] See Arno Karlen, Man and Microbes (1995), pp. 149-154.

[16] See “Combating AIDS,” The CQ Researcher, April 21, 1995, pp. 345- 368.

[17] See Mario C. Raviglione, Dixie E. Snider Jr. and Arata Kochi, “Global Epidemiology of Tuberculosis: Morbidity and Mortality of a Worldwide Epidemic,” Journal of the American Medical Association, Jan. 18, 1995, pp. 220-226.

[18] See “Group A Streptococcus Outbreak in Virginia,” CDC/NCID Focus, March 1995, p. 3.

[19] The Latin word for thread is filum.

[20] For a report of the Ebola outbreak in Reston, see Preston, op. cit.

[21] See “Return of a Killer Virus,” U.S. News & World Report, April 17, 1995, p. 20.

[22] Reuters, June 1, 1995. For background, see “Outbreak of Fear,” Newsweek, May 22, 1995, pp. 48-55, and “In Search of the Dying,” Time, May 29, 1995, pp. 44-47.

[23] See Bob Drogin, “Ebola Appears Even Stronger Than in 1976,” Los Angeles Times, Washington edition, May 15, 1996.

[24] See Keith Murray et al., “A Morbillivirus That Caused Fatal Disease in Horses and Humans,” Science, April 7, 1995, pp. 94-97.

[25] Centers for Disease Control and Prevention, Addressing Emerging Infectious Disease Threats: A Prevention Strategy for the United States, 1994, p. 3.

[26] Ibid.

[27] The cutbacks are provided in a bill (HR 1158) that would rescind spending authority previously appropriated for fiscal 1995. The Senate approved the conference report on the bill May 25. President Clinton has said he would veto the bill. See Andrew Taylor, “Senate Clears Rescissions Bill After Talks With Clinton Fail,” CQ Weekly Report, May 27, 1995, pp. 1494-1495.

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