Toxoplasmosis and HIV

BACKGROUND

Toxoplasmosis (toxo) is a parasitic infection that is caused by a single-celled parasite called Toxoplasma gondii.

Toxoplasma gondii is one of the most common parasites, and it is found all over the world. Individuals may be exposed to the parasite in soil, cat feces, or in raw or undercooked meat (especially lamb, pork, or venison). There have been rare reports of toxoplasmosis infection as a result of organ transplantation or blood transfusion. While the parasite can be found around the world, the disease occurs less frequently in areas where the environment is unfavorable for the oocysts, such as at the extremes of temperatures and at higher altitudes.

Toxoplasmosis is considered an opportunistic infection because it occurs in individuals who have weakened immune systems. It is estimated that more than 60 million Americans carry the parasite. However, 80-90% of infected patients experience no symptoms because their immune systems prevent the parasite from causing the illness.

Patients who have the human immunodeficiency virus (HIV) have a high risk of developing the infection because HIV primarily targets immune cells called CD4 T-cells. Patients progress to AIDS (acquired immune deficiency syndrome) when their CD4 cell counts drop to lower than 200 cells per microliter of blood. Healthy individuals have a CD4 cell count between 600 and 1,200 per microliter of blood. As the virus continues to weaken the immune system, patients become increasingly vulnerable to opportunistic infections.

According to the U.S. Centers for Disease Control and Prevention (CDC), toxoplasmosis is an AIDS-defining illness. This means that when HIV-infected patients develop the toxoplasmosis, their condition has progressed to AIDS.

Although the parasites are present in about 40% of the general population, few people actually develop an infection, unless they are severely immunocompromised. Researchers estimate that about 10-40% of HIV patients have antibodies against toxoplasmosis.

Pregnant women who are carriers of T. gondii may transmit the infection to their babies, even if the mothers experience no symptoms. During the first month after birth, infected babies may experience severe complications, such as mental retardation, convulsions, spasticity (muscle stiffness), cerebral palsy, deafness, and severely impaired vision. The baby's immune system is still developing during infancy and fetal infection with T. gondii may result in stillbirth or abortion.

CAUSES

Toxoplasma gondii is a single-celled parasitic organism that can infect most animals. However, sexual reproduction of the parasite only occurs in cats (both wild and domestic), which are the organism's definitive host. T. gondii's life cycle begins when a cat eats infected prey, which is typically a mouse or bird. Cats can also become infected if they eat raw, contaminated meat or accidentally ingest a small amount of infected soil.

Once ingested, T. gondii burrows into the walls of the cat's small intestine. The parasite forms early-stage cells called oocysts, which the cat excretes in its feces, usually for about two to three weeks. A single stool may contain millions of oocysts. Most healthy cats will not shed oocysts after this initial stage, which typically lasts about two to three weeks.

Within a few days, the excreted oocysts develop into mature, highly infectious cells that can survive in warm, moist soil for up to one year.

If another animal ingests the parasite, they multiply rapidly inside the host and eventually form cysts (inactive eggs) that lodge in the brain or muscles. Cysts form as early as seven days after infection and remain inside the host for the rest of its life. They produce little or no inflammatory response. The new host animal usually experiences no symptoms and will not excrete oocysts in its feces. At this stage, the parasite can only be transmitted if a predator eats the host.

When humans become infected with T. gondii, the parasite forms cysts that may affect almost any organ, but they are most likely to lodge in the brain, bones and heart. Healthy individuals typically do not show symptoms because the immune system keeps the parasite infiltration under control. In such instances, the parasites remain in an inactive state in the body for life.

When the parasite enters an immunocompromised patient, the parasite is active causing symptoms such as headache, confusion, and seizures that may lead to serious complications.

When a woman is exposed to the parasite during pregnancy, the organism may spread to the placenta. When this occurs, the infection may be transmitted to the fetus through the placenta or during vaginal delivery. According to secondary sources, if the mother becomes infected during the first trimester, there is about a 15% risk that the fetus will also become infected. This risk is estimated to increase to 30% during the second trimester and to 60% during the third trimester. The different rates of transmission are most likely related to placental blood flow, the virulence and amount of T. gondii acquired, and the overall health of the mother's immune system.

AVOIDING EXPOSURE

Cat feces: Infected cats excrete oocysts in their feces. Oocysts are extremely small. In fact, one million may be present in a single stool. Individuals should wash their hands thoroughly after gardening, working with soil, cleaning a cat's litter box, or touching anything that may have come into contact with cat feces.

Contaminated water: While uncommon in the United States, the drinking water in many areas of the world may be contaminated with Toxoplasma gondii. The world's largest outbreak occurred in the western Canadian province of British Columbia. Individuals who are traveling overseas should be aware of the possibility of contaminated drinking water.

Contaminated soil: Contaminated soil contains highly infectious cells that can survive longer than one year. Individuals who are exposed to soil during gardening or other outdoor activities should wear gloves and thoroughly wash their hands with soap and water.

Fruits and vegetables: Produce items may contain traces of the parasite because they grow in areas where the organism lives. Therefore, all fruits and vegetables should be thoroughly washed, especially when they are eaten raw, to avoid infection.

Infected organ transplant or transfused blood: There have been rare reports of toxoplasmosis infection as a result of organ transplantation or blood transfusion.

Knives, cutting boards or other utensils: Kitchen utensils should be washed thoroughly with antibacterial soap because they often come into contact with raw meat.

Undercooked, infected meat: Undercooked meat, especially venison, lamb, and pork, may be contaminated with Toxoplasma gondii. Thoroughly cooking meat may help prevent infection because the parasites are killed in high heat. Occasionally, unpasteurized goat's milk may also contain the cysts.

SYMPTOMS

Healthy individuals typically experience no symptoms. In such instances, the parasites remain in an inactive state in the body for life. If the patient develops an immunocompromised condition in the future, symptoms of toxoplasmosis may arise.

Mild symptoms include flu-like symptoms, swollen lymph nodes, and muscle aches and pains.

HIV patients typically develop severe symptoms of toxoplasmosis, including headache, confusion, poor coordination, seizures, ocular toxoplasmosis (severe inflammation of the retina), as well as lung problems that are similar to tuberculosis or pneumocystis pneumonia (lung infections).

Infected babies may experience severe complications, including mental retardation, convulsions, spasticity (muscle tightness), cerebral palsy, deafness, and severely impaired vision. In addition, the infant's head may be abnormally small (microcephaly) or abnormally large (hydrocephalus) due to increased pressure on the brain. Fetal infection with Toxoplasma gondii may result in stillbirth or abortion.

DIAGNOSIS

General: If toxoplasmosis is suspected, blood tests may be conducted to check for antibodies to the parasite. Most pregnant women in the United States are not routinely screened for toxoplasmosis. Only New Hampshire and Connecticut regularly screen infants for the infection. If a pregnant mother tests positive for the disease, the fetus may be tested with a prenatal test called amniocentesis. Imaging studies may be used to determine whether a patient with severe toxoplasmosis has lesions or cysts in the brain.

Blood tests: If toxoplasmosis is suspected, several blood tests may be conducted to check for antibodies to the parasite. Antibodies are proteins produced by the immune system that detect and bind to foreign substances that enter the body, including parasites like T. gondii. Because these antibody tests may be difficult to interpret, the U.S. Centers for Disease Control and Prevention (CDC) recommends that all positive results are confirmed by a laboratory that specializes in diagnosing toxoplasmosis. Initial test results usually take about a week, although expert confirmation may take longer.

Patients who are tested soon after exposure may have not yet developed antibodies to the parasite. Such patients may have a false negative test result. This means that the patient has toxoplasmosis, but tests negative for the infection. If it is suspected that the patient has toxoplasmosis, but the test results are negative, the patient will be retested in two to three weeks.

Amniocentesis: Prenatal testing for toxoplasmosis is possible with amniocentesis, which may be conducted at 15-18 weeks of gestation. During the procedure, a long, thin needle is inserted into the abdominal wall and into the uterus. A small amount of fluid is then removed from the sac surrounding the fetus. The sample is tested in a laboratory for evidence of toxoplasmosis. There is a risk of miscarriage, ranging from one out 200-400 patients. Some patients may experience minor complications, such as cramping, leaking fluid, or irritation where the needle was inserted.

Ultrasound scan: An ultrasound scan uses sound waves to produce images of the fetus inside the womb. Although an ultrasound scan cannot diagnose toxoplasmosis, it may help a healthcare provider detect signs of hydrocephalus (swelling of the head due to an accumulation of cerebrospinal fluid in the scull). Since most infants do not show signs of toxoplasmosis at birth, a negative ultrasound scan does not rule out infection.

Magnetic resonance imaging (MRI): A magnetic resonance imaging (MRI) test may be conducted to detect cysts or lesions in the brain. This test uses a magnetic field and radio waves to create images of the head and brain.

Brain biopsy: In rare cases, especially if patients do not respond to treatment, a neurosurgeon may take a small sample of tissue from the brain. The sample is then analyzed in a laboratory to check for the presence of toxoplasmic cysts. A brain biopsy is an invasive procedure that is associated with serious health risks, and therefore, should only be performed in extreme cases.

TREATMENT

General: In otherwise healthy individuals who are not pregnant, no treatment is necessary. Combination therapy of pyrimethamine, sulfadiazine, and folate supplements is the standard method of treatment for toxoplasmosis patients who are immunocompromised or pregnant. Toxoplasmosis patients who have cats should take their pets to their veterinarians to determine whether they carry the parasite.

Pyrimethamine (Daraprim©): Pyrimethamine (Daraprim©) is an antiparasitic medication that is effective against toxoplasmosis. This medication is a folic acid antagonist, which means it may prevent the body from absorbing vitamin B-9 (folic acid), especially when high doses are taken over a long period of time. Therefore, folic acid supplements are also recommended in patients who are taking pyrimethamine. Other potential side effects of pyrimethamine include bone marrow suppression and liver toxicity.

Sulfadiazine (Microsulfon©): Sulfadiazine (Microsulfon©) is an antibiotic that is commonly used in combination with pyrimethamine to treat toxoplasmosis. Possible side effects include nausea, vomiting, and diarrhea.

HIV patients who have toxoplasmosis typically receive pyrimethamine and sulfadiazine, along with folic acid supplements. An alternative treatment is pyrimethamine in addition to the antibiotic clindamycin (Cleocin©). However, clindamycin may cause severe diarrhea. Side effects of most drugs may be more severe in people with HIV. Most patients will need to take these medications for life. In some cases, toxoplasmosis treatment may be discontinued if the patient's CD4 count remains high for at least three to six months.

If a pregnant mother's child is infected with toxoplasmosis, patients may be treated with pyrimethamine and sulfadiazine. However, these are only used in extreme circumstances because they can cause serious side effects in both the mother and baby. While the drugs may lessen the severity of the infection, they cannot repair any damage that has already been done.

Infected pregnant women who have healthy babies may be treated with the antibiotic spiramycin. Use of this drug may reduce the chance that the baby will become infected. Unlike sulfadiazine, spiramycin is not likely to cause serious side effects in the mother or child. While this spiramycin is commonly used to treat toxoplasmosis in Europe, it is still considered an experimental drug in the United States. Healthcare providers may obtain the drug from the U.S. Food and Drug Administration (FDA).

INTEGRATIVE THERAPIES

Note : Currently, there is a lack of scientific data on the use of integrative therapies for the treatment or prevention of toxoplasmosis in patients with HIV. The integrative therapies listed below should be used only under the supervision of a qualified healthcare provider and should not be used in replacement of other proven therapies or preventive measures.

Unclear or conflicting scientific evidence :

Oregano : Early study shows that taking oregano by mouth may help treat parasites. Further research is needed to confirm these results.

Research suggests that oregano is well tolerated in recommended doses. Avoid if allergic or hypersensitive to oregano. Use caution if allergic or hypersensitive to other herbs from the Lamiaceae family including hyssop, basil, marjoram, mint, sage and lavender. Use caution with diabetes and bleeding disorders. Pregnant or breastfeeding women should not consume oregano at doses above those normally found in food.

Zinc : In a few studies, patients with cutaneous leishmaniasis were injected with zinc sulfate under the skin. Zinc may decrease the severity of infection and re-infection of S. mansoni, but does not seem to prevent initial infection. More research is necessary. The effects of zinc on the rate of parasitic re-infestation has been examined in children. No significant effect of zinc treatment was found. Recent data suggest that supplementation with zinc and vitamin A may favorably alter infection rate and duration among children. Due to conflicting results in this area, more research is needed before zinc can be recommended for the treatment of parasites.

Zinc (zinc sulfate, zinc acetate, zinc glycine, zinc oxide, zinc chelate, and zinc gluconate) is generally considered safe when taken in the recommended dosages. Avoid zinc chloride since studies have not been done on its safety or effectiveness. While zinc appears safe during pregnancy in amounts lower than the established upper intake level, caution should be used since studies cannot rule out the possibility of harm to the fetus.

Traditional or theoretical uses lacking sufficient evidence :

Black seed : Black seed (Nigella sativa) is an annual flowering plant native to southwest Asia. Although black seed has been suggested as a potential treatment for parasitic infections, human research is currently lacking.

Avoid in patients with known allergy to black seed or any of its constituents. Use cautiously in patients with immune disorders. Avoid if pregnant or trying to become pregnant.

Garlic : Garlic is used both medicinally and as a spice in food. It has been suggested that garlic may have antiparasitic effects. However, human research is needed before a conclusion can be made.

Avoid if allergic or hypersensitive to garlic or other members of the Lilaceae (lily) family (like hyacinth, tulip, onion, leek, chive). Avoid with a history of bleeding problems, asthma, diabetes, low blood pressure, or thyroid disorders. Stop using supplemental garlic two weeks before and immediately after dental/surgical/diagnostic procedures with bleeding risks. Avoid supplemental doses if pregnant or breastfeeding.

Iodine : Iodine is an element that the human body needs to make thyroid hormones. Although iodine has been suggested as a potential treatment for parasitic infections, human research in this area is currently lacking.

Reactions to iodine can be severe, and deaths have occurred. Avoid iodine-based products if allergic or hypersensitive to iodine. Do no use for longer than 14 days. Avoid Lugol solution and saturated solution of potassium iodide (SSKI, PIMA) with high amounts of potassium in the blood, pulmonary edema (fluid in the lungs), bronchitis, or tuberculosis. Avoid sodium iodide with gastrointestinal obstruction. Use cautiously when applying to the skin because it may irritate/burn tissues. Use sodium iodide cautiously with kidney failure. Iodine is considered safe in recommended doses for pregnant or breastfeeding women. Avoid povidone-iodine for perianal preparation during delivery or postpartum antisepsis.

PREVENTION

Wear gloves when gardening or handling soil. Wash hands thoroughly with soap and water after coming into contact with soil.

Do not eat raw or undercooked meat, especially pork, venison, or lamb.

Wash kitchen utensils thoroughly with soap and water.

Thoroughly wash all fruits and vegetables.

Avoid unpasteurized goat's milk.

Avoid feeding cats raw meat. Indoor cats are less likely to develop toxoplasmosis.

If possible, immunocompromised or pregnant women should not clean litter boxes. Wear gloves when cleaning a cat's litter box. Wash hands thoroughly with soap and water after handling anything that may have come into contact with cat feces.

AUTHOR INFORMATION

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

• AIDSinfo. http://aidsinfo.nih.gov. Accessed May 19, 2009.
• Centers for Disease Control and Prevention (CDC). www.cdc.gov. Accessed May 19, 2009.
• HIV InSite. http://hivinsite.ucsf.edu. Accessed May 19, 2009.
• National Toxicology Program. http://cerhr.niehs.nih.gov. Accessed May 19, 2009.
• Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com. Copyright © 2009. Accessed May 19, 2009.