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Toxoplasmosis

Toxoplasmosis is a protozoan disease that rarely develops among healthy people but can be a serious problem for those with malignant tumors, recipients of organ transplantation, people with HIV disease, and the unborn child.

Symptoms

The disease presents itself differently in the three main categories of patients: (1) the immunologically normal, (2) unborn children, and (3) those with immunodeficiency.

Table 29.7 Pneumocystosis

Symptoms

Gradual onset, shortness of breath, rapid breathing, non-productive cough, slight or absent fever, dusky color of skin and mucous membranes

Incubation period

4 to 8 weeks

Causative agent

Pneumocystis carinii, a tiny fungus related to the ascomycetes

Pathogenesis

Pneumocystosis can result from reactivation of latent infection or be newly acquired. Spores of P. carinii escape body defenses, enter the lungs with inspired air, attach to alveolar walls, multiply. Alveoli fill with fluid, macrophages, and P. carinii. The walls thicken, impairing oxygen exchange

Epidemiology

Pneumocystis carinii widespread in domestic and wild animals as a latent lung infection, but the source of animal and human infections is unknown. Most humans become infected in early childhood. Disease arises in individuals with immunodeficiency; epidemics can occur in hospitalized premature infants and elderly nursing home residents

Prevention and treatment

Formerly leading cause of death in those with AIDS, now usually prevented by medication, e.g., trimethoprim-sulfamethoxazole, as soon as the CD4+ lymphocyte count drops to 200 cells per ml. Same medication is used for treatment; alternatives available. Medication is continued for life, or until the CD4+ cell count rises and remains above 200 as a result of HAART or other treatment of the underlying immunodeficiency

756 Chapter 29 HIV Disease and Complications of Immunodeficiency

Toxoplasmosis can be acquired by immunocompetent individuals who eat raw or undercooked meat or who are exposed to cat feces. Most infections are asymptomatic, but 10% to 20% develop symptoms similar to those of infectious mononucleosis. They usually consist of sore throat, fever, enlarged lymph nodes and spleen, and sometimes a rash. These symptoms subside over weeks or months and do not require treatment. Rarely, a severe, even life-threatening illness develops, due to involvement of the heart or central nervous system. ■ infectious mononucleosis, p. 726

Toxoplasmosis of the unborn results from almost half of maternal infections that occur during pregnancy. Fetal toxoplasmosis during the first trimester of pregnancy is the least common but most severe, often resulting in miscarriage or stillbirth. Babies born live may have severe birth defects including small or enlarged heads, and their lungs and liver may also be damaged by the disease. Later, these babies may develop seizures or manifest mental retardation. Almost two-thirds of fetal toxoplasmosis cases occur during the last trimester of pregnancy, however, and the effects on the fetus are usually less severe. Most of these infants appear normal at birth, although later in life, retinitis, infection of the retina, the light-sensitive part of the eye, can be a big problem for them. This manifests itself as recurrent episodes of pain, sensitivity to light, and blurred vision, usually involving only one eye. Less common late consequences of congenital toxoplasmosis include mental retardation and epilepsy.

Toxoplasmosis that complicates immunodeficiency is commonly life threatening. Brain involvement in the form of encephalitis occurs in more than half the cases, manifest by confusion, weakness, impaired coordination, seizures, stiff neck, paralysis, and coma. Involvement of the brain, heart, and other organs often results in death.

Causative Agent

Toxoplasmosis is caused by Toxoplasma gondii, a tiny (3 by 7 mm) banana-shaped protozoan (figure 29.14a) that has a worldwide distribution and infects most warm-blooded animals, including household pets, pigs, sheep, cows, rodents, and birds. Its species name derives from the fact that the protozoan was first discovered in the gondi, an African desert rodent. The life cycle of T.gondii is shown in figure 29.14b. The definitive host, the one in which sexual reproduction occurs, is the cat or other feline (ocelot, puma, bobcat, Bengal tigers, and so on). The organism reproduces in the cat's intestinal lining, resulting in numerous offspring, some of which spread throughout the body and others that differentiate into male and female gametes (sexual forms). Union of gametes results in the formation of a thick-walled oval structure (oocyst) about 12 mm in diameter that is shed in the cat's feces. Millions of the oocysts are shed each day generally over a period of 1 to 3 weeks. In the soil, the oocysts undergo further development over 1 to 5

Sporocysts

Sporozoite

Congenital infection

Sporocysts

Sporozoite

T. gondii

Congenital infection

Cyst wall

T. gondii

Cyst wall

Figure 29.14 Toxoplasma gondii (a) Invasive forms. (b) Life cycle. Oocysts from cat feces and cysts from raw or inadequately cooked meat can infect humans and many other animals. (c) Cyst in tissue.

days into an infectious form containing two sporocysts, each with four sporozoites. These may remain viable for up to a year, contaminating soil and water and, secondarily, hands and food. In general, the cats recover from the acute infection and do not shed oocysts again. The oocysts are infectious for cats and other animals, including humans.

When non-feline animals ingest the oocysts, usually from contaminated food or water, the sporozoites emerge from the oocysts and invade the cells of the small intestine, especially its lower part, the ileum, but there is no sexual cycle. The intestinal infection spreads by the lymphatics and blood vessels throughout the tissues of the host, infecting cells of the heart, brain, and muscles. As host immunity develops, multiplication slows, and a tough fibrous capsule forms, surrounding large numbers of a smaller form of T. gondii. These capsules packed with organisms are called cysts (figure 29.14c), and they remain viable for months or years. The life cycle is completed when a cat becomes infected by eating an animal with cysts in its tissues.

Pathogenesis

The organisms enter the body by ingestion of oocysts or inadequately cooked meat containing tissue cysts. Toxoplasma gondii is infectious for any kind of warm-blooded animal cell except non-nucleated red blood cells. Entry into the host cell is aided by an enzyme produced by the organism, which alters the host cell membrane. Proliferation of T. gondii in cells of the host causes destruction of the cells. Unless the infecting dose of the organism is very high, this process is normally brought under control by the immune response of the host, tissue cysts develop, and infected humans usually show few if any symptoms. In patients with immunodeficiency, however, infection can be widespread and uncontrolled, producing many areas of tissue necrosis. The disease process can result from a newly acquired infection, or declining immunity can allow reactivation of latent infection with escape of T.gondii from a person's tissue cysts.

Epidemiology

Toxoplasma gondii is distributed worldwide, but it is less common in cold and in hot, dry climates. Human infection is widespread. Serological surveys show the infection rate increases with age, ranging from 10% to 67% among those over 50. Most infections are acquired from ingesting oocysts that contaminate fingers, food, or drink, and probably from inhaling contaminated dust in an enclosed space such as a barn. Young, homeless cats that commonly eat rodents and birds are likely sources of the organism. Small epidemics have occurred from drinking water contaminated with oocysts. Gardening in areas frequented by cats can result in T.gondii contamination of hands or vegetables. Eating rare meat poses a definite risk. Tissue cysts are present in about 25% ofpork, in 10% of lamb, and less commonly in beef and chicken.

Prevention and Treatment

General measures for preventing T. gondii infection include washing hands after handling raw meat, coming in contact with soil, or changing cat litter. Meat, especially lamb, pork, and venison, should be cooked until the pink color is lost from its interior. Fruits and vegetables should be washed before eating. Cats should not be allowed to hunt birds and rodents, nor should they be fed undercooked or raw meat. Children's sandboxes should be kept tightly covered when not in use. These measures are especially important for pregnant women and persons with immunodeficiency.

29.3 Infectious Complications of Acquired Immunodeficiency 757

HIV-infected patients and those about to receive immuno-suppressant medications are tested for antibody to T. gondii. A positive test indicates they have latent infection. Therefore, those with positive tests are given prophylactic trimethoprim-sulfamethoxazole if they have fewer than 100 CD4+ T cells per microliter. Treatment of toxoplasmosis employs related medications, pyrimethamine with sulfadiazine. Alternatives are available. The main features of toxoplasmosis are presented in table

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