Daraprim

Definition

Toxoplasmosis is an infectious disease caused by the one-celled protozoan parasite Toxoplasma gondii. Although most individuals do not experience any symptoms, the disease can be very serious, and even fatal, in individuals with weakened immune systems.

Description

Toxoplasmosis is caused by a one-celled protozoan parasite known as Toxoplasm gondii. Cats, the primary carriers of the organism, become infected by eating rodents and birds infected with the organism. Once ingested, the organism reproduces in the intestines of cats, producing millions of eggs, known as oocysts, which are excreted in cat feces daily for approximately two weeks. In the United States, it is estimated that approximately 30% of cats have been infected by T. gondii. Oocysts are not capable of producing infection until approximately 24 hours after being excreted, but they remain infective in water or moist soil for approximately one year. When cattle, sheep, or other livestock forage through areas with contaminated cat feces, these animals become carriers of the disease. Fruits and vegetables can also become contaminated when irrigated with untreated water that has been contaminated with cat feces. In humans and other animals, the organisms produce thick-walled, dormant structures, called cysts, in the muscle and other tissues of the body.

Most humans contract toxoplasmosis by eating cyst-contaminated raw or undercooked meat, vegetables, or milk products. Humans can also become infected when they come into contact with the T. gondii eggs while cleaning a cat's litterbox, gardening, or playing in a sandbox, for instance. Once infected, an individual is immune to reinfection. The incubation period or period between infection and the start of the disease ranges from several days to months.

Anyone can be infected by T. gondii, but usually only those individuals with weakened immune systems (immunocompromised) develop symptoms of the disease. For them, toxoplasmosis can be severe, debilitating, and fatal. Immunocompromised individuals at-risk include those with AIDS, cancer, or other chronic illnesses.

There is no person-to-person transmission, except from an infected mother to her child in the womb. Approximately six out of 1,000 women contract toxoplasmosis during pregnancy. Nearly half of these maternal infections are passed on to the fetus. Known as congenital toxoplasmosis, this form of the disease is acquired at birth by approximately 3,300 infants in the United States every year. The risk of fetal infection is estimated to be between one in 1,000 to one in 10,000. In children born with toxoplasmosis, symptoms may be severe and quickly fatal, or may not appear until several months, or even years, after birth.

Causes and symptoms

Healthy individuals do not usually display symptoms. When symptoms do occur, they are usually mild, resembling infectious mononucleosis, and include the following:

• Enlarged lymph nodes
• Muscle pains
• Fever that comes and goes
• General ill feeling.

The distinction is made between acquired toxoplasmosis, where an individual becomes infected, and neonatal congenital toxoplasmosis, where a fetus is born with the infection because the mother became infected during pregnancy. If a fetus becomes infected early in pregnancy, it can cause the fetus to spontaneously abort, be stillborn. If full-term, the infant may die in infancy or suffer from central nervous system lesions. If the mother becomes infected in the last three months of pregnancy, however, the prognosis is good and the baby may not even display any symptoms.

In adults, if the infection continues for an extended period of time, chronic toxoplasmosis can cause an inflammation of the eyes, called retinochoroiditis, that can lead to blindness, severe yellowing of the skin and whites of the eyes (jaundice), easy bruising, and convulsions.

Adults with weakened immune systems have a high risk of developing cerebral toxoplasmosis, including inflammation of the brain (encephalitis), one-sided weakness or numbness, mood and personality changes, vision disturbances, muscle spasms, and severe headaches. If untreated, cerebral toxoplasmosis can lead to coma and death. This form of encephalitis is the second most common AIDS-related nervous system infection that takes advantage of a person's weakened immune system (opportunistic infection).

Diagnosis

A diagnosis of toxoplasmosis is made based on clinical signs and supporting laboratory results, including visualization of the protozoa in body tissue or isolation in animals and blood tests. Laboratory tests for toxoplasmosis are designed to detect increased amounts of a protein or antibody produced in response to infection with the toxoplasmosis organism. Antibody levels can be elevated for years, however, without active disease.

Treatment

Most individuals who contract toxoplasmosis do not require treatment, because their immune systems are able to control the disease. Symptoms are not usually present. Mild symptoms may be relieved by taking over-the-counter medications, such as acetaminophen (Tylenol) and ibuprofen (Motrin, Advil). Sore throat lozenges and rest may also ease the symptoms.

Although the treatment of women infected with toxoplasmosis during pregnancy is controversial, most physicians feel that treatment is justified. Transmission of toxoplasmosis from the mother to the fetus may be prevented if the mother takes the antibiotic spiramycin. Later in a pregnancy, if the fetus has contracted the disease, treatment with the antibiotic pyrimethamine (Daraprim, Fansidar) or sulfonamides may be effective. Babies born with toxoplasmosis who show symptoms of the disease may be treated with pyrimethamine, the sulfa drug sulfadiazine (Microsulfon), and folinic acid (an active form of folic acid).

AIDS patients who have not been infected may be given a drug called TMP/SMX (Bactrim or Septra) to prevent toxoplasmosis infection. To treat cases of toxoplasmosis in immunocompromised AIDS patients, a combination of pyrimethamine and a sulfa-based drug, either sulfadiazine or clindamycin (Cleocin), have been used together and can be effective in treating this disease. Other antibiotic combinations and dosing schedules are still being investigated. Physicians have reported success in alleviating symptoms by using trimethoprim-sulfamethoxazole (Proloprim or Trimpex) or dapsone (DDS) plus pyrimethamine. These drugs can produce side effects, such as allergic reaction, itching, rashes, and nausea, and patients must be monitored closely.

Prognosis

The prognosis is poor when congenital toxoplasmosis is acquired during the first three months of pregnancy. Afflicted children die in infancy or suffer damage to their central nervous systems that can result in physical and mental retardation. Infection later in pregnancy usually results in only mild symptoms, if any. The prognosis for acquired toxoplasmosis in adults with strong immune systems is excellent. The disease often disappears by itself after several weeks. However, the prognosis for immuniodeficient patients is not as positive. These patients often relapse when treatment is stopped. The disease can be fatal to all immunocompromised patients, especially AIDS patients, and particularly if not treated. As a result, immunocompromised patients are typically placed on anti-toxoplasmosis drugs for the rest of their lives.

Prevention

There are no drugs that can eliminate T. gondii cysts in animal or human tissues. Humans can reduce their risks of developing toxoplasmosis by practicing the following:

• Freezing (to 10.4°F/-12°C) and cooking foods to an internal temperature of 152°F/67°C will kill the cysts
• Practicing sanitary kitchen techniques, such as washing utensils and cutting boards that come into contact with raw meat
• Keeping pregnant women and children away from household cats and cat litter
• Disposing of cat feces daily, because the oocysts do not become infective until after 24 hours
• Helping cats to remain free of infection by feeding them dry, canned, or boiled food and by discouraging hunting and scavenging
• Washing hands after outdoor activities involving soil contact and wearing gloves when gardening.

Key Terms

Cyst

The thick-walled dormant form of many organisms.

Immunocompromised

A state in which the immune system is suppressed or not functioning properly.

Oocyst

The egg form of the toxoplasmosis organism.

Protozoan

A single-celled, usually microscopic, organism.

Further Reading

For Your Information

Books

• Conn's Current Therapy, edited by Robert E. Rakel. Philadelphia: W.B. Saunders Company, 1997, 160-167.
• The Merck Manual of Diagnosis and Therapy. Rahway, NJ: Merck & Co., Inc., 1997.
• Shulman, Stanford T., et al. The Biologic and Clinical Basis of Infectious Diseases, 5th edition. Philadelphia: W.B. Saunders Company, 1997, 378-81 and 449.
• Tierney, Lawrence M., Stephen J. McPhee, and Maxine A. Papadakis. Current Medical Diagnosis & Treatment. Stamford, CT: Appleton & Lange, 1997, 322-25.

  Periodicals

• Alger, L.S. "Toxoplasmosis and Parvovirus B19." Infectious Disease Clinics of North America, 11 (March 1997): 55-75.
• Campagna, A.C. "Pulmonary Toxoplasmosis." Seminars in Respiratory Infections, 12 (June 1997):98-105.
• Rose, I. "Morphology and Diagnostics of Human Toxoplasmosis." General & Diagnostic Pathology, 142 (June 1997): 257-70.

Gale Encyclopedia of Medicine. Gale Research, 1999.