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Invaders and the Reluctant Human Host by Marian Segal Thousands of Milwaukee area residents got an unwanted crash course last April in cryptosporidiosis, a disease most had never heard of until they--or friends or family--contracted it. The culprit was a parasite, Cryptosporidium, that had invaded the city's drinking water supply, causing people to become sick with diarrhea and other intestinal symptoms; several died. Cryptosporidium lives in the intestines of cattle and other animals and is excreted in feces. Health officials suspect the water supply became contaminated from a high level of runoff into Lake Michigan from area dairy farms or slaughterhouses near the water plant's intake pipe. An inadequate filtration system allowed the parasites entry into the water supply. Cryptosporidiosis is just one of several diseases caused by parasites, which are largely unfamiliar to Americans. But in much of the rest of the world, they are all too well-known. These tiny ravagers--many no larger than a single cell--claim the health and lives of millions of people around the globe. Parasites live in or on another organism, known as the host, from which they receive nourishment and protection. Some pass successive stages of maturity in hosts of different species, including humans. Parasites are of different types, including protozoa (one-celled animals) and helminths (worms) ranging in size from microscopic eggs to adults up to several feet long. The illnesses they cause range from mild discomfort of short duration to chronic, debilitating disease and death. People who live in areas where the disease is endemic (constantly present) suffer the devastation most keenly. Hardest hit are developing countries in the tropics, where poor sanitation fosters the parasites and the insects that transfer many of them from one host to another. A major killer among the parasitic diseases, and perhaps the one best known to Americans, is malaria. It is caused by the protozoa Plasmodium, transferred to humans by the bite of the Anopheles mosquito. Although malaria is not a significant health problem in the United States, more than 1 billion people worldwide live in areas where the disease is endemic, and between 125 million and 200 million people are infected at any given time. Each year in Africa alone, malaria claims the lives of 1 million children. Millions more adults and children in Africa, South and Central America, Asia, and parts of Europe suffer from other devastating parasitic diseases as well. For example, African sleeping sickness, caused by the protozoan Trypanosoma brucei, is one of the most lethal of all human diseases. It produces fever, enlarged lymph glands, skin lesions, and painful swelling. Neurological symptoms, including tremors, headache, apathy, and convulsions, predominate later in the disease, which can end in coma and death. Schistosomiasis, a helminthic disease affecting approximately 200 million people between the tropics of Cancer and Capricorn, can produce bladder, intestinal or liver disease that may lead to death. Onchocerciasis (river blindness), found in Mexico, South and Central America, and Africa, results from infection with larvae of the Onchocerca volvulus worm, transmitted by flies that breed along fast-moving streams. It causes a skin rash, often with severe and constant itching. Eye lesions lead to blindness in about 5 percent of people infected. "It is true that parasitic diseases are a much greater problem in other parts of the world," says George Jackson, Ph.D., a microbiologist in FDA's Center for Food Safety and Applied Nutrition, "but they seem to be on the increase in industrialized temperate zone countries, and there are even certain parasitic infections among Native Alaskans." Travelers Play Host The rising incidence of parasitic diseases in the United States is due in part to increasing international travel. Approximately 8 million Americans travel to the developing world annually, according to the national Centers for Disease Control and Prevention, and the speed of jet transport permits travelers to return home within the incubation period of every infectious disease. As a result, the agency says, an increasing number of parasitic infections are being diagnosed in business travelers and tourists and are causing considerable disease and occasional death. One of these diseases is malaria. Plasmodium parasites infect red blood cells, causing a spiking fever, possible immune problems, damage to internal organs, and, potentially, death. Certain species of the parasite may lie dormant in the organs for years, until something--perhaps another infection--triggers the disease. Although once endemic in the U.S. Southeast, malaria was declared eradicated in this country in the 1940s; the last case originating here was reported to CDC in 1957. Yet from 1969 to 1980, the number of cases in civilians reported to that agency rose from 151 to 1,864, and since 1980, the number of cases in travelers has averaged 1,000 annually. Compounding the problem is the fact that malaria has become resistant to the drugs taken to prevent contracting the disease. Once brought in, local transmission is rare, but does occur, since the Anopheles mosquito does exist in this country. Other previously rare and potentially fatal parasitic infections, such as leishmaniasis (which may affect the skin, mucous membranes, or internal organs), schistosomiasis, and onchocerciasis, are also increasing among returning U.S. travelers. While those particular parasitic diseases are still uncommon in the United States, others are seen here much more often, especially in specific groups of people. Parasitic Disease and Weakened Immunity "There are certain parasites we're all exposed to that don't cause us much trouble unless we're particularly vulnerable to them," explains Randolph Wykoff, M.D. "The protozoa that cause pneumocystis pneumonia and toxoplasmosis can be fairly common in the population. Most people have been exposed to them with limited illness, if any." Wykoff, who is a specialist in tropical medicine and heads FDA's Office of AIDS Coordination, explains that little more than a decade ago these two diseases were seen infrequently-- almost exclusively in people with immune systems weakened by cancer chemotherapy, or in malnourished, chronically ill, and pre-term infants. That changed with the appearance and spread of HIV (human immune deficiency virus) infection. Immune suppression is the hallmark of this infection, which leads to AIDS. HIV-infected patients are vulnerable to many opportunistic infections (infections that would not cause illness in someone with a healthy immune system), including those caused by parasites. Pneumocystis pneumonia, toxoplasmosis, and cryptosporidiosis are responsible for much of the illness and death suffered by people with AIDS. Parasite Provides First Clue to AIDS "In fact, it was because of unexplained cases of pneumocystis- -an airborne respiratory infection caused by Pneumocystis carinii--that AIDS was first recognized in 1981," Wykoff says. "Pentamidine, the drug used to treat the disease, was available only through CDC. When the agency noticed an increase in the number of requests for pentamidine, it began an investigation that eventually led to identification of AIDS as a new disease." As HIV infections have increased, so has the incidence of pneumocystis pneumonia. According to CDC's HIV/AIDS Surveillance, 19,503 new cases of pneumocystis pneumonia were diagnosed in HIV-infected patients in 1992. Early symptoms are fever, cough, and shallow, rapid breathing. Chest x-ray shows parasitic infiltration of the lungs. As the disease progresses, cyanosis may develop--a bluish discoloration of the skin resulting from insufficient blood oxygen. Pneumocystis is the leading cause of death in people with AIDS, Wykoff says, but adds that control of the disease has improved since the introduction of preventive treatment with aerosolized pentamidine isethionate (NebuPent), approved by FDA in 1989. In 1992, Mepron (atovaquone) was approved to treat the pneumonia, joining Bactrim and Septra (combination products containing trimethoprim and sulfamethoxazole), both approved in 1976. Injectable pentamidine was approved to treat pneumocystis pneumonia in 1984. "Cryptosporidiosis is another parasitic infection of major concern in HIV-infected and other immune-suppressed patients," says Wykoff, "although it was unknown until relatively recently--the last decade or so--and people are still not sure how common it is." The parasite infects cells in the intestinal wall and releases a toxin that causes a profuse, watery diarrhea and abdominal cramping. In healthy people, the disease is self-limiting; symptoms usually last a week or two, and then rapidly abate. Immune-suppressed patients, however, are unable to clear the infection, and endure unremitting diarrhea. In these individuals, cryptosporidiosis becomes a debilitating wasting disease. According to the American Public Health Association's Control of Communicable Diseases in Man, 10 to 20 percent of AIDS patients develop cryptosporidiosis sometime during their illness. No drug is available to effectively combat the parasite, although several are under study. Current treatment is limited to rehydration therapy (replacing and maintaining fluids and electrolytes). Besides drinking plenty of fluids, patients may be given a liquid formula such as Pedialyte (for children) or Rehydralyte (for children and adults), which contains water, dextrose, potassium citrate, sodium chloride, and sodium citrate. Cryptosporidium is transmitted through the fecal-oral route. Careful hand washing and good sanitation practices are essential in preventing disease spread. Adequate water filtration should prevent waterborne transmission such as occurred in Milwaukee. Besides immune-suppressed patients, others at increased risk include children, foreign travelers, homosexual men, and close contacts of infected patients, such as family members, health-care workers, and day-care workers. A third parasitic infection associated with HIV is toxoplasmosis, caused by Toxoplasma gondii. As with Pneumocystis carinii, T. gondii is common in the U.S. population. An estimated 40 percent of Americans are or have been infected, but most either don't get sick or they develop a relatively harmless illness--slight fever, muscle pain, sore throat, headache, and inflammation of the lymph nodes lasting days or weeks. But again, infection in immune-suppressed people is much graver. According to CDC, toxoplasmosis is the most common opportunistic infection of the central nervous system in HIV-infected patients, and causes encephalitis (inflammation of the brain) or brain lesions in as many as 30 percent of AIDS patients. Symptoms include paralysis, mental deterioration, severe headache, seizures, and coma, usually ending in death. Toxoplasmosis is acquired by eating raw or undercooked meat contaminated with the parasite, or by exposure to contaminated cat feces. (See accompanying articles, "For Safe Food, Handle with Care" and "Toxo- Tabby.") Toxoplasmosis and Pregnancy Toxoplasmosis can also be transmitted to a fetus through the placenta. The fetus is presumed to be at risk only if the mother has a primary, active infection during the pregnancy; a former infection is believed not to be dangerous. CDC estimates there are between one and three congenital Toxoplasma infections per 1,000 live births in the United States each year. Only 10 percent of those infants develop symptoms, but of them, 85 percent develop severe neurologic and developmental problems, and approximately 12 percent die. Of those who have no symptoms at birth, up to 85 percent may develop chronic recurring eye disease and learning disabilities. Toxoplasmosis can also cause miscarriage, stillbirth, and pre-term birth. Acute toxoplasmosis is usually treated with Daraprim (pyrimethamine) together with sulfadiazine for three to four weeks. Immune-suppressed patients should continue treatment for up to six months or longer, however, and may need reduced dosages throughout their lifetimes to try to prevent recurrence. More Food-Borne Foes "There are more than 80 food-borne parasites," says FDA's George Jackson, "but, fortunately, not all are of great significance in this country at this time. However, the food market is becoming international--we're getting not only preserved foods, but fresh foods flown in from all parts of the world." Jackson says parasites are important not only because of the direct infections they cause, but because of their secretions and excretions. This is particularly true of the helminths. Even if the worms are pulled out of the food, their waste products--biologically active materials--are left behind in the flesh. Studies are getting started to discover what long-term effects they may have on humans. "Our own habits are also a big factor," Jackson says. "We like to eat raw vegetables in salads and we're eating more raw fish. While most parasites are easily killed by proper cooking, right now we're not doing that well enough." Probably the best-known--and most serious--food-borne parasitic disease in this country is trichinosis. Larvae of the Trichinella roundworm infect pigs and some game animals whose meat ends up on our dinner tables. The incidence of trichinosis has declined, however, with an average of only 44 cases per year from 1984 through 1988 reported to CDC. This is due partly to legislation requiring that garbage fed to pigs be cooked, killing any larvae. The sporadic outbreaks that occur are primarily among new immigrants from Asia. "There is very little Trichinella in pork in Asia," Jackson explains. "Therefore, Asian immigrants do not cook pork as thoroughly as we do." Trichinosis symptoms vary with individual immunity and the intensity of the infection. The adult worms develop and reproduce in the human digestive tract, where they may cause mild diarrhea. They then die and leave the body in feces. The new generation of larvae may then invade cells of the diaphragm, skeletal muscles or heart, causing serious damage, if present in large numbers. "If you get a very few worms, you probably will not know it, but if you get a large dose, you will," Jackson says. "The problem is that if it's a subclinical infection, you probably don't need to treat it, and if it's severe, you're in trouble. Once symptoms develop, it's already in the muscles where it causes so much damage." Treatment is aimed at helping the patient survive the acute infection. Effectiveness of the anthelmintic drug Mintezol (thiabendazole) varies among patients. Those who develop heart or central nervous system problems or who have allergic reactions such as hives and swelling are also given corticosteroids. New Recipes, New Risks While trichinosis is on the decline, fish-borne parasitic illnesses are on the rise, corresponding with the growing popularity in this country of raw fish dishes. Japanese sushi and sashimi, Latin American ceviche, Scandinavian gravlax, lomi-lomi salmon, and other raw fish recipes may tempt our taste buds, but if they're not carefully prepared, our stomachs may revolt. Seals, dolphins, porpoises, and other large sea mammals are host to a group of parasitic worms called anisakids. The parasites' eggs pass out of the mammal's body in feces. In the water, they hatch into larvae, which are then eaten by fish, such as cod, salmon or herring. When these infected fish reach our mouths raw or undercooked, trouble may ensue. "Fortunately, the most common symptoms of anisakiasis are more annoying than life-threatening," says Jackson. He explains that the larvae burrow into the mucosa of the stomach or intestine, producing sometimes painful 'attachment ulcers,' and sometimes nausea and vomiting. "Usually the worms don't last long--we're not their usual hosts--and they die or try to get out of us. They may be coughed or vomited up," he says. "Many people feel a tickling at the back of the throat. They reach back there and pull out this spaghetti-like worm." In the normal course, the disease usually subsides spontaneously. Sometimes gastroscopy (inserting a tube through the mouth to the stomach) is used to remove the larvae. If chronic illness develops, surgery may be required to remove lesions that have developed. Jackson says that on rare occasions the larvae penetrate the intestinal wall and go wandering in the body or settling in and affecting other organ systems. After the larvae begin to die, the body responds to their presence with a cellular reaction, which may be misdiagnosed as cancer. FDA is working on a new policy to minimize the public's exposure to fish-borne parasites. "We've decided to try to implement good manufacturing practice levels of allowable parasites on a species group basis," says Jeffrey Bier, Ph.D., research microbiologist in FDA's Office of Seafood. "The policy will be based on species groups because parasites are more visible and more easily detected in the flesh of certain species than in others." Bier explains that the cods, flounders and sea basses, for example, are similar in the incidence of parasites and in the ease with which the parasites can be detected visually. The process to detect them is candling, in which light is used to look through the flesh of the fish. Bier says the agency is collecting data on which to base proposed rules for good manufacturing practice levels of parasites for the cod and flounder families. Day-Care Dilemma Another parasite gaining ground in this country is Giardia lamblia, a protozoan also spread through the fecal-oral route, either directly through person-to-person contact or through contaminated food or water. It infects the small intestine and may cause gas, diarrhea, abdominal cramps, bloating, and, in severe cases, malabsorption and weight loss. Children are infected more frequently than adults, and the parasite is finding a wealth of young hosts in day-care centers. In random surveys, giardiasis has been identified in 10 to 15 percent of diaper-aged children attending day-care centers, compared with 2 percent of same-age children not attending centers, CDC reports. In addition, approximately 20 to 25 percent of day-care staff and family contacts of infected children also become infected. The agency attributes the spread to poor personal hygiene, closer interpersonal contact, and the children's frequent hand-to-mouth and object-to- mouth behavior. The simplest and most effective way to prevent the spread of giardiasis is hand washing. Experts advise day-care staff to wash their hands when they start work, before preparing or serving food, after diapering a child, and after going to the bathroom. Similarly, children's hands should be washed when they arrive at the center, before they eat or drink, and after they use the toilet or have their diapers changed. Other common-sense measures--such as cleaning and disinfecting diaper-changing areas after each use, keeping food preparation and diaper-changing areas separate, and keeping children with diarrhea at home--should also be followed. Giardiasis is not unique to day-care settings. According to CDC, Giardia is the most common cause of waterborne outbreaks of intestinal disease in the United States, and the number of such outbreaks has increased significantly in recent years. They occur most often in mountain communities and those that get drinking water from streams or rivers without a water filtration system. Hikers and campers who drink from contaminated lakes, rivers and streams are also frequently affected. Swimming pools have also become contaminated. Giardiasis seldom causes severe disability, but it is one of the leading causes of diarrheal illness in the United States. FDA has approved Furoxone (furazolidone) and Atabrine hydrochloride (quinacrine hydrochloride) for treatment. Flagyl (metronidazole) is also used. Though parasitic diseases appear to be increasing in the United States, with proper common-sense sanitation practices and careful food preparation, many of these creatures can be kept at bay. n Marian Segal is a member of FDA's public affairs staff. For Safe Food, Handle with Care Cook it thoroughly. Cook it thoroughly. Cook it thoroughly! That's the most important thing to know about preventing food-borne illness. FDA advises consumers to cook pork until it reaches an internal temperature of 71 degrees Celsius (160 degrees Fahrenheit). Fish should be cooked to an internal temperature of 60 C (140 F), flake easily, and be firm and opaque, or dull. If it's translucent, or shiny, it's not done. "Proper cooking should kill most parasites," says George Jackson, Ph.D., of FDA's Center for Food Safety and Applied Nutrition, "but you've got to be careful that it's not just the outside that's getting all the heat. Trichinella, for instance, is on the inside of the meat. Anisakids in fish might be on the outside of the fillet, but they could also be in the fillet." This is especially important to remember with microwaving, because the food often does not heat evenly. Rotate the dish once or twice during cooking, observe the standing time called for in the recipe or package directions, and check for doneness with a thermometer after removing it from the microwave oven. Insert the thermometer at several different spots. Raw fish dishes, such as sushi and ceviche, can be safe for most people to eat if they are made with very fresh fish that is commercially frozen and then thawed. In 1990, FDA issued an advisory to state and local regulatory agencies recommending that fish served raw, marinated, or partially cooked be blast-frozen to minus 35 C (minus 31 F) or below for 15 hours or frozen by regular means to minus 23 C (minus 10 F) or below for seven days. People with immune disorders should not eat raw fin fish or shellfish because, although freezing kills most parasites, it does not kill bacteria. People with immune disorders need to take extra precautions to thoroughly cook all meat, fish and poultry. Fruits and vegetables should be scrubbed and washed well to loosen any contaminants on the surface of the produce. For more detailed information on safe food handling and cooking, call the FDA Seafood Safety Hotline at (1-800) FDA-4010. You may request single copies of the following free publications from the Food and Drug Administration, HFI-40, Rockville, MD 20857: The Unwelcome Dinner Guest--Preventing Food-Borne Illness (91-2244) (Spanish 91-2244S) Food Safety and the Microwave (OM91-3007) Keep Your Food Safe (91-2234) (Spanish 92-2234S) Eating Defensively: Food Safety Advice for Persons with AIDS (92-2232) (Spanish 92-2232S) Get Hooked on Seafood Safety: Important Health Information for People with Immune Disorders (92-2261) Get Hooked on Seafood Safety: Important Health Information for People with Diabetes Mellitus (92-2258) Get Hooked on Seafood Safety: Important Health Information for People with Gastrointestinal Disorders (92- 2259) Get Hooked on Seafood Safety: Important Health Information for People with Liver Disease (92-2260) For a free copy of the U.S. Department of Agriculture publication "A Quick Consumer Guide to Safe Food Handling," write to Consumer Information Center, Item 528Z, Pueblo, CO 81009. More information on food handling is available from USDA's toll-free Meat and Poultry Hotline. Call (1-800) 535-4555 from 10 a.m. to 4 p.m. weekdays, Eastern time. n --M.S. Toxo-Tabby In addition to cooking meats thoroughly, cat owners need to take additional precautions against toxoplasmosis, because cats are a host for Toxoplasma gondii. Cats acquire the parasites from eating rodents, birds, or raw beef. "Recent studies show that cat ownership is not necessarily a problem," says Randolph Wykoff, M.D., director of FDA's Office of AIDS Coordination, "but people should handle their cat litter boxes appropriately and clean the boxes regularly." Pregnant women and immune-suppressed individuals should have someone else change litter boxes, if possible. If not, they should wear disposable gloves and wash their hands thoroughly afterward. They should also wear gloves when gardening or doing other activities involving contact with possibly contaminated soil. Cat owners should follow these recommended precautions: Feed cats dry, canned or boiled food--never undercooked meat or poultry--and discourage hunting; that is, keep cats as indoor pets only. Use disposable plastic liners in cat litter boxes and change the litter daily. (The parasite in the feces is not infectious until two or three days after excretion.) Seal the liner with a twist tie and dispose of it in a plastic garbage bag. After emptying, disinfect the litter box with scalding water left in the pan for five minutes. (If a plastic liner is used, disinfecting is not necessary.) Wash hands thoroughly after cleaning the litter box. Wash hands thoroughly after contact with soil possibly contaminated with cat feces, and especially before eating. Cover sandboxes when not in use to prevent stray cats from getting into them. --M.S. ####<