The New Plagues
Modern medicine has made awesome progress on man fronts. And for many years one of its major achievements seemed to be in the war on infectious diseases. But now that tide has turned in an ominous and alarming reversal.In 1930, the antibiotic penicillin was teased out of a common fuzzy blue-green mold. This single discovery revolutionized the way bacterial diseases were treated. In addition, vaccines for measles, mumps, German measles, diphtheria, whooping cough and tetanus were developed. Sabin and Salk tamed the polio virus with an oral vaccine served on a sugar cube. The smallpox vaccine officially eradicated the viral disease from the globe.More than 25 years ago, as a result of all these medical breakthroughs, the U.S. Surgeon General declared proudly and broadly that it was time to close the book on infectious diseases. Medicine in the mid-20th century assumed an attitude of complacency, almost arrogance, regarding infectious disease. Antibiotics were used as a matter of course to treat previously life-threatening bacterial infections. Improved hygiene and sanitation in the industrial world seemed to decrease the incidence of epidemic diseases associated with poor living conditions and overcrowding. Childhood vaccinations virtually eliminated dreaded illnesses that were scourges of the past. And life was good.However, for the past quarter century, we've been living in an era of dramatic change. Worldwide, populations are growing, accompanied by expanding poverty, urban decay, immigration and homelessness. International travel and commerce are increasing, and technology is improving. But along with these human changes, microorganisms have adapted and changed as well, in order to survive. They have developed changes in the way they overcome our immune defenses and have started to produce new toxins. They are developing antibiotic resistance and have become co-factors in several chronic diseases like peptic ulcers, cervical cancer, coronary artery disease and hypertensive kidney disease. We are now, but too slowly, realizing that humans may be face-to-face with a potential apocalypse of infectious disease in at least four forms: 1) The emergence of new diseases, 2) the re-emergence of diseases previously thought to be under control, 3) the emergence of antibiotic resistant strains of bacteria, and 4) the re-emergence of vaccine-preventable diseases.Here are just a few of the new emerging diseases that have appeared over the past generation:Ebola and Marburg viruses. These viruses were the nonfictional basis for the recent popular science fiction movie Outbreak. In 1967, the Marburg virus was associated with a small epidemic in Germany among laboratory workers who had been exposed to sick African Green monkeys. The Ebola viruses caused several epidemics in 1976, 1979 and 1996 in Zaire and Sudan, Africa. These epidemics resulted in very high mortality rates, ranging from 89-100 percent for the Zaire strain. Victims died grotesquely of massive hemorrhage throughout their entire bodies. The use of dirty needles by local hospital workers greatly aided transmission of the disease, but the initial source, probably some kind of animal, has not been identified.The Ebola virus also was the subject of the best selling book, The Hot Zone by Richard Preston, which described a true and terrifying 1989 incident. Shortly after a shipment of macaque monkeys had been transported from the Philippines to a research facility in Reston, Va., some of the monkeys began to die in their cages. Blood and tissue examinations revealed the presence of the characteristic thread-like Ebola virus. Fortunately this strain of virus did not affect humans, since no precautions were taken in handling these monkeys, and there were many opportunities for exposure. But this incident shows dramatically that animals with which humans have limited contact can harbor organisms about which we know nothing and which can be fatal. Human activities like dam-building, clearing of the rainforests, and intensive farming not only disrupt and destroy the biosystems of the planet, but also may set the stage for potentially deadly contact between humans and previously untapped virus reservoirs.Hantavirus. In May and June of 1993, there was a mysterious outbreak of respiratory illness in 30 healthy young people living in the rural Four Corners region of the American Southwest (where New Mexico, Colorado, Utah and Arizona meet). What began with flu-like symptoms with muscles aches, fever and fluid build-up in the lungs rapidly became fatal in 55 percent of the confirmed cases. By late July 1994, the Center for Disease Control (CDC) in Atlanta had reported 83 confirmed cases with 45 deaths in 14 states. The disease is now called Hantavirus Pulmonary Syndrome (HPS) and is caused by the rodent-borne Muerto Canyon virus.In the original 1993 outbreak, unusually heavy spring rains in the Southwest helped produce a bountiful crop of pion nuts, which in turn sustained an explosive increase in the population of deer mice, an animal reservoir of the virus. Medical scientists now know that infected mice shed the virus in their urines, feces and saliva, and the hapless and accidental human host gets infected by breathing in aerosols from these materials. This illness is another example of contact between the susceptible host and an animal-borne virus, resulting from a relatively minor shift in local weather patterns. There have been recent reports of an outbreak of the hantavirus in Argentina, where the virus was transmitted directly from person to person.AIDS. This is the disease that has been most widely publicized and studied since the late 1970s when physicians began to notice unusual occurrences of Pneumocystis carinii pneumonias and Kaposi's sarcomas in previously healthy young men in the United States. In 1983 the HIV virus was isolated and identified. While AIDS originally was limited primarily to homosexuals and needle sharers, it is now spread throughout the population. Since the late 1970s, the HIV virus has spread around the globe, infecting an estimated 17 million people and killing maybe a million of its victims.Legionnaires' disease. Though the earliest documented case was in 1947, with at least five earlier outbreaks that were previously undefined, it wasn't until 1976 that this disease was identified. A multisystem illness characterized by pneumonia-like symptoms and a high fatality rate appeared among Legionnaires attending a bicentennial convention in Philadelphia. Hotel air conditioning ducts contaminated with the bacteria Legionella pneumophila was determined to be the cause of the outbreak.In 1994 aboard the ocean liner Horizon, 1,200 disgruntled passengers had to be evacuated in Bermuda because of the threat of Legionnaires' disease on the ship. During that summer's previous voyages, there had been 11 confirmed cases, 24 suspected cases, and one death on the Horizon.Lyme disease. First described in 1975 after an outbreak among children in Lyme, Conn., this tick-borne disease is associated in its early stages with a rash, headache, stiff neck, muscle and joint pain, malaise, fatigue and lymph-node swelling. Weeks to months later, symptoms may include inflammation of the brain, spinal cord or heart, and migrating musculoskeletal pain, followed by chronic arthritis.In 1982 the causative agent of the disease, the spiral-shaped bacterium Borrelia burghdorferi, was described. This is an example of an emerging disease transmitted by an insect carrier (black-legged or deer ticks) in wooded areas, especially in the Northeast United States. There have been a total of 14 cases of Lyme disease reported in New Mexico through 1996, although all of these cases appear to have occurred from exposure in endemic areas outside the state.E coli 0157:H7. First identified and recognized as a disease-producing agent (pathogen) in 1982, this bacteria causes bloody diarrhea, abdominal cramps and hemolytic uremic syndrome, the most common cause of kidney failure in children. This illness can be acquired primarily by eating undercooked ground beef, but also by ingesting raw milk, apple cider and roast beef.It's easy to see how contaminated food products and mass food processing can expose large segments of the population to this emerging disease. Children and the elderly are the most vulnerable to this infection, and the organism can spread easily from person to person, especially in institutional settings like day-care and nursing home facilities, where handling dirty diapers or linens and not washing hands are common practices.In 1993 at a Jack-In-The-Box fast-food restaurant, ingestion of contaminated undercooked hamburgers resulted in a multi-state outbreak of E coli 0157 with the death of at least four children. There are now about 20,000 cases a year in the United States, and just last month there was a small outbreak focused in the South Valley of Albuquerque.Cryptosporidium. According to the Environmental Protection Agency, most U.S. surface water is contaminated with this chlorine-resistant intestinal parasite. The infection is transmitted by drinking contaminated water and causes watery diarrhea. Although the diarrhea goes away without treatment, it can be much more severe in children and immuno-compromised people, with weight loss and fever accompanying the diarrhea.In the spring of 1993, the water supply in Milwaukee, Wis., was contaminated with cryptosporidia, resulting in the largest documented outbreak of water-borne disease in U.S. history. More than 403,000 people had prolonged diarrhea, with 4,400 hospitalizations and 100 deaths. This outbreak illustrates how contaminated water supplies can put entire communities at risk for emerging infections.UNDER CONTROL NO LONGERThe primary factor in the re-emergence of diseases previously thought to be under control is global travel. Germs once confined to limited areas can now hitchhike to other corners of the globe within hours. Changes in the organisms themselves are also a problem in these illnesses. These bacteria are developing new ways to evade our immune defenses, and they are producing more toxic substances, as well as becoming resistant to ordinary antibiotic drugs. The following diseases illustrate these points.Cholera. This classic illness is one of the most devastating bacterial diseases known to mankind. Onset is rapid, with vomiting and copius amounts of odorless "rice paper" diarrhea. A victim may lose as much as 15-20 liters of fluid a day, and the untreated mortality rate is greater than 60 percent. The disease has long been endemic in India and Bangladesh, but within the past 25 years, global travel has facilitated its emergence in other parts of the world. Between 1991 and 1993 there were more than 900,000 cases worldwide, not counting the tragic deaths of 50,000 people in Rwandan refugee camps who were infected with a new antibiotic-resistant strain of the bacterium.Since 1991, South America has been suffering a cholera epidemic that is thought to have originated from a Chinese boat that dumped tainted water into a Peruvian harbor. Local fishermen then spread contaminated shellfish to consumers. In 1994 there were more than 850 cholera victims in Southern Russia, stemming from the decaying health services and deteriorating sanitary conditions after the collapse of the Soviet Union. Officials feared that where outbreaks used to be rare, full epidemics may erupt. Again in 1994, a cholera epidemic started sweeping Latin America, presumably as a result of a ship arriving from Asia with its ballast tanks full of contaminated water. From Latin America, public health officers are concerned that the plague may expand to the Caribbean Islands. Within the past three years there has been at least one death due to cholera aboard an international airliner arriving in California from Asia.Group A Streptococcus. The cause of the common "strep throat," these bacteria may lead to rheumatic heart and inflammation of the kidneys if left untreated. Two recent events brought the more invasive form of Group A Strep infections into public awareness. The first was the stunning and untimely death of Muppeteer Jim Henson in 1990. The second was the outbreak in Gloustershire, England, which prompted the media to dub this bug the "flesh-eating bacterium" because of its association with a condition known as necrotizing faciitis. What appears to make this variant of the Group A Strep such a gruesome and rapid killer is that the bacterial cell itself is infected with a virus that helps produce an especially powerful toxin that devours red blood cells and tissues. The past seven years has witnessed not only an apparent increase in the incidence of this severe and invasive form of Group A Strep, but also clusters of rheumatic fever cases and the emergence of a new condition called "toxic shock-like syndrome," which has a mortality rate of 30 percent.Dengue. This mosquito-borne viral disease is not called "breakbone fever" for nothing. Sufferers have an abrupt onset of severe generalized aches, excruciating muscle pains, agonizingly severe headaches, blinding pain behind the eyes, and a fever of up to 104 degrees. In 1981 Cuba experienced a major epidemic of this disease; in the 1990s there have been outbreaks in the Caribbean and Central America as a result of hurricane damage with standing pools of stagnant water and a lack of mosquito control. The Asian tiger mosquito, which carries the dengue virus, became established in the United States when an air shipment of used tires containing mosquito eggs arrived from Asia. Now our country also plays host to the insect carrier capable of transmitting this disease.Tuberculosis (TB). This scourge of the past conjures up visions of frail, coughing patients isolated in sanitariums. Because of an improving standard of living and good sanitation in developed countries, the disease was in decline until 1984. Then a complex combination of factors led to a dramatic increase, complicated by the nightmare appearance of a multiple drug-resistant strain of TB. These factors included the AIDS epidemic, overcrowded and dirty conditions in prisons and homeless shelters, and immigration, both illegal and legal. In 1993 there was a well-publicized and shocking story of a 16-year-old Vietnamese immigrant who had contracted TB in her native land and had introduced the infection into her new Westminster, Calif., high school. Almost 400 students, or 30 percent of the population of the school, ended up testing positive for the infection, and 12 of those young people came down with the drug-resistant strain.THE ROOTS OF DRUG RESISTANCESome public awareness, though perhaps not enough, has been drawn recently to outbreaks of antibiotic-resistant organisms in hospitals and communities. There are several factors contributing to this phenomenon, including prescription practices on the part of physicians, treatment compliance on the part of patients, and agricultural drug use.Unfortunately, both misuse and overuse by doctors prescribing antibiotic drugs is all too common worldwide. Physicians may inappropriately, but with good intentions, prescribe antibiotics for viral infections when they are generally only effective against bacterial infections. Sometimes they order an antibiotic just to get certain patients "off their backs" because some patients aggressively demand something to make them feel better, even though their illness may not be bacterial in origin. Sometimes doctors prescribe an antibiotic for a true bacterial infection when neither the causative organism nor its antibiotic susceptibilities have been determined by microbiologists in the laboratory. Often they order the newer, more expensive drug alternatives, when an old, cheap, tried and true generic one would be every bit as effective.Broad spectrum antibiotics are being used indiscriminately when a more narrowly focused specific drug would be more appropriate. Universal adoption of antibiotic treatment has made the problem of overuse even worse. While other medical resources are scarce in developing countries, the relative cheapness and availability of antibiotic drugs encourage their over-prescription at a worldwide level. Then, when outbreaks of resistant organisms appear, global air travel assures that these outbreaks are no longer limited by location. When human hosts board an airplane, resistant microbes can hitch a ride to any corner of the planet in a matter of hours.The blame doesn't totally lie with doctors, however. The attitude and approach that patients take toward taking their antibiotic treatments is another problem area contributing to the rise of resistant bacteria. As mentioned earlier, there are patients who adamantly demand unnecessary antibiotics from their physicians for themselves or their children. There are also patients who save past prescriptions for future illnesses.In many countries, antibiotic drugs are available over the counter, which allows patients not only to diagnose but to treat themselves, often inappropriately. In the United States there has been a shift in patterns of health care, from an emphasis on hospital inpatient treatment to outpatient care. This change promotes the use of prescribed antibiotic regimens without medical supervision, and this in turn allows more people to quit the regimen before the full course is complete. Patients commonly quit taking their medicine as soon as they begin to feel better, thinking that they don't want to take any more drugs than are necessary. Or they quit because they may have unpleasant but common side effects like nausea or diarrhea associated with the treatment.Whatever the reasons for not completing the full round of antibiotics, this compliance failure not only prolongs bacterial infections, but also gives newly resistant microbes a chance to multiply before the antibiotic is inevitably re-prescribed to kill off their unresisting bacterial relatives. Also, outpatients who don't take their antibiotic treatment properly may then spread their antibiotic-resistant germs beyond the wall of the home or hospital and into the community at large.A third contributor to the rise of resistant bacteria is through agricultural use of antibiotics. Farmers put antibiotics and hormones in animal feed so livestock will get fatter and have fewer infections. This has resulted in resistant bacteria entering the meat-eating community through antibiotic-containing animal flesh. The bovine growth hormone given to dairy cows to increase milk production also causes more udder infections and dosing with antibiotics. Milk can legally contain up to 80 different antibiotics, as long as the amount is under a certain limit!All of this antibiotic usage, some unnecessary overkill, inadvertently has increased the prevalence of resistant organisms. Here are some examples of emerging antibiotic resistant microbes that are of the most concern to medical and public health personnel.Methicillin-Resistant Staphaureus (MRSA). Staphylococcus aureus can be a nasty enough bug without being antibiotic resistant. It can cause boils on the skin, pus-filled wounds, infections of the bloodstream and bones, and fatal toxic shock. When penicillin was introduced in 1930 as a medical miracle, these bacteria were universally sensitive. However, by 1944 there already were strains capable of resisting the action of the drug, and now 95 percent of isolates worldwide are penicillin-resistant. The chemical modification of penicillin to create semi-synthetic variations of the drug, such as Methicillin that could kill the penicillin-resistant strains, put a bandaid on the problem for a few years, but eventually led to the emergence of the MRSA in 1961.By 1992, almost 15 percent of all Staph aureus found and nearly 40 percent of it in large city hospitals were resistant to methicillin. This left only one reliably effective antibiotic of last resort against Staph aureus -- the expensive "silver bullet" called vancomycin. However, even now the potential nightmare of vancomycin-resistant Staph aureus is becoming terrifyingly true. In May, Japan reported a new strain of the vancomycin-resistant organism; in June, England reported its first case; and currently there are at least two cases in the University of Southern California hospital.Vancomycin-Resistant Enterococci (VRE). These bacteria are a major cause of hospital-acquired infections. Traditionally, they could be treated with a combination of penicillin and an anitibiotic called aminoglycoside. However, starting in 1979, reports began to surface of a high-level aminoglycoside resistance. Then by 1986 many enterococci had developed penicillin resistance as well. Organisms with this pattern of resistance no longer responded to traditional treatment, leading to increasing use once again of the expensive silver bullet.The result? By 1993, 7.9 percent of all hospital incidents and 13.6 percent of those found in Intensive Care Unit patients were resistant to vancomycin. Scientists fear that enterococci may be a reservoir for vancomycin-resistant genes and that maybe, just maybe, these genes can be accidentally transferred to Staph aureus, creating a "superbug" resistant to all antibiotics known to man. Indeed, this is what may have happened already.Penicillin-Resistant Strep pneumonia (PRSP). Streptococcus pneumonia is one of the leading causes of blood infections, pneumonia, meningitis and ear infections in the United States, especially in young children and babies, people with severely weakened immune systems, and the elderly. This organism was universally zapped by penicillin until the late 1960s. From 1974 to 1984 penicillin resistance spread worldwide. Unlike the MRSA and VRE, which initially emerged as hospital-acquired infections, PRSP infections are primarily community acquired, particularly through day-care and nursing home facilities. Now among pediatric populations in the United States, up to 30 percent of Strep pneumonia strains may be penicillin resistant.Tuberculosis (TB). Alluded to earlier, this organism also has learned how to outwit antibiotic treatments. TB is an extraordinarily tough bug to treat, so the standard regimen is a combination of several drugs over a period of six months. This complexity and length of treatment, even for nonresistant TB, have precluded progress against the disease in developing countries. Now, the emergence of multiple-drug-resistant strains, resistant to as many as two to seven drugs, is outright cause for alarm. Many of these organisms appeared in New York and New Jersey and are thought to be due to the failure of patients to take their complete treatment regimen. These multiple-resistant bugs have found a large population of highly susceptible hosts in AIDS patients and people in prisons and homeless shelters. Current treatment options consisting of less conventional drugs and even longer courses of therapy are out of the question for many of these disease victims.WHY SHOTS DON'T WORKThird world countries continue to be chronically plagued by infectious diseases that are preventable by vaccines. In general, especially in the United States and other developed countries, vaccination programs implemented over the past 50 years have dramatically reduced the incidence of many of the dreaded so-called "childhood diseases." Vaccine failure, which occurs when the vaccine itself is less than 100 percent effective, and failure to comply with Department of Health vaccination schedules and recommendations, especially in pre-school-age children, account for most of the sporadic outbreaks of vaccine-preventable diseases in this country.However, it is troublesome that a number of small epidemics of these diseases are occurring among people who have been properly vaccinated, suggesting that there may be reason to believe there are re-emerging vaccine-preventable illnesses. For example:Measles. This is a highly communicable viral rash, primarily in babies 12-15 months old. It also can be a severe illness in adults, with pneumonia and ear infections common complications. There was a national resurgence of this disease from 1989 to 1991. Adults born before 1957 are generally considered naturally immune, although an outbreak in New Mexico in 1995 involved several persons of this age group. Another outbreak in June and July of 1996 affected half a dozen people in Santa Fe. The Department of Health recommends the vaccine in babies at 12 months of age, with a second dose at 4 to 6 years of age before starting school.Mumps. This viral disease causes fever and swelling and tenderness of the salivary glands. In adolescent males, it can cause inflammation and swelling of the testicles. Complications may include aseptic meningitis or encephalitis. In 1993 in New Mexico there was an outbreak of mumps in which all of the victims had had their complete vaccination series. This may represent an example of less-than-100 percent effectiveness of the vaccine.Whooping cough. This is one of the most contagious infectious diseases and can affect people of any age. A single cough in the face of a newborn may be enough to infect the infant. Since the advent of the DPT vaccine, the incidence has dropped from 200,000 cases a year in the United States in the 1940s to about 5,000 cases a year in the 1990s. However, in 1993 the New England Journal of Medicine reported an epidemic among children in Cincinnati. And in 1994 and 1995 there were separate outbreaks in Hobbs and Carlsbad. Once again, most of these children had been properly vaccinated. The Department of Health currently recommends a series of five DPT shots at two, four and six months of age, and a booster at 12-15 months and 4-7 years.SO WHAT ARE WE DOING ABOUT IT?The Center for Disease Control (CDC) has defined a four-goal plan for preventing illness from emerging infectious disease. These goals are surveillance, applied research, prevention and control, and strengthening of the public health infrastructure. Surveillance involves detection, prompt investigation and monitoring of emerging pathogens, along with the diseases they cause and the factors influencing their emergence. Applied research includes integrating laboratory science and epidemiology to optimize public health care, that is, making sure those who study these diseases are up to date on what is being detected in the labs. Prevention and control are designed to enhance the communication of critical public health information about emerging diseases and to ensure prompt implementation of preventive measures. The last goal is to improve the poorly funded and deteriorated public health infrastructure at local, state and federal levels in order to be able to support the first three goals.Nevertheless, no quick fixes to solve the problem of antibiotic resistance are on the horizon. The wonder drugs of the 20th century have been modified and improved, but no new class of antibiotic has been developed in the past 20 years. Pharmaceutical companies have found that genuinely new drugs are not profitable, and the FDA has made regulatory obstacles dauntingly expensive and time-consuming. The current cost of putting a new antibiotic on the market in this country ranges from $100-350 million dollars.The battle against infectious disease that humans thought they had won by the early 1970s has only just begun. Cutbacks in both private and government research into new "ammunition" to fight the battle has given the "bugs" a real chance to win the war. Although the objectives of the CDC plan are conceptually sound and constructive, it may prove to be a more difficult task to find the money, manpower and public interest and demand required to actually accomplish the goals.Katherine Henderson, a microbioligist, has a masters degree in Biomedical Science and for the past 15 years has been a medical technologist at the Lovelace Medical Center in Albuquerque.