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:
œThe Unwelcome Dinner Guest--Preventing Food-Borne
Illness (91-2244) (Spanish 91-2244S)
œFood Safety and the Microwave (OM91-3007)
œKeep Your Food Safe (91-2234) (Spanish 92-2234S)
œEating Defensively: Food Safety Advice for Persons with
AIDS (92-2232) (Spanish 92-2232S)
œGet Hooked on Seafood Safety: Important Health
Information for People with Immune Disorders (92-2261)
œGet Hooked on Seafood Safety: Important Health
Information for People with Diabetes Mellitus (92-2258)
œGet Hooked on Seafood Safety: Important Health
Information for People with Gastrointestinal Disorders (92-
2259)
œGet 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:
œFeed cats dry, canned or boiled food--never undercooked
meat or poultry--and discourage hunting; that is, keep cats as
indoor pets only.
œUse 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.
œAfter 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.)
œWash hands thoroughly after cleaning the litter box.
œWash hands thoroughly after contact with soil possibly
contaminated with cat feces, and especially before eating.
œCover sandboxes when not in use to prevent stray cats from
getting into them. 
--M.S.
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