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Toxoplasmosis

What is toxoplasmosis?

Toxoplasmosis is an infection caused by the parasite Toxoplasma gondii (T. gondii). The parasite is transmitted to people through eating undercooked meat, especially pork, lamb, beef, wild meat (deer and so on), or raw shellfish such as oysters, clams and mussels, contaminated with the parasite. Cats are natural hosts of this parasite, and it may be transmitted to people through inadvertent contact with cat feces.

Toxoplasmosis infection most often causes disease in the brain and spinal cord, although other parts of the body, including the eyes, heart, lungs, skin, liver, and gastrointestinal (GI) tract, can be infected. In North America, toxoplasmosis in HIV-positive people is usually a reactivation of an old infection that did not initially cause disease. When someone is first infected with the parasite, there are usually no symptoms, and the immune system is able to control and contain the infection. However, in untreated HIV infection the immune system degrades and loses the ability to control the parasite. As your CD4 count falls below the 200 cell/mm3 mark, your risk for developing symptoms of toxoplasmosis and other AIDS-related infections increases. Taking HIV treatment (commonly called ART) exactly as prescribed to maintain a high CD4 count helps prevent toxoplasmosis from (re)occurring.

Symptoms

Symptoms of toxoplasmosis can include the following:

  • dull, constant headache
  • intermittent fever
  • confusion

Symptoms may also include focal neurological deficits, such as:

  • weakness, or even paralysis, of one side of the body
  • speech disorder, especially slurred words
  • weakness or loss of sensation in any limb
  • loss of an area of vision

Focal neurological deficits are problems caused by disturbances (lesions, tumours, infections, stroke) in a particular area of the brain. They cause a specific loss of sensory or motor function. For example, a toxoplasmosis lesion on the brainstem may cause difficulty swallowing or speaking; a lesion near the area of the brain that controls sight can cause the loss of an area of vision.

Diagnosis

The symptoms of toxoplasmosis are similar to those of many other conditions that can affect the brain and spinal cord. Physical examinations, lab tests, and scans (CT scans and MRI) are necessary to confirm the diagnosis.

A person who has any of the symptoms described above will receive a physical examination, including some general tests of the nervous system. If there seem to be neurological problems, you will be referred to a neurologist (a doctor whose specialty is the brain and nervous system).

Blood samples will be taken and tested to find out if you have been exposed to the toxoplasmosis parasite or to other germs that could cause similar symptoms. Most physicians rely on assessing a combination of symptoms and results of laboratory tests and CT or MRI scans in order to make a diagnosis of toxoplasmosis. However, initially the symptoms of toxoplasmosis may be mild or mimic other conditions and so a consultation with a neurologist may be necessary to help your doctors understand the cause of your symptoms. The neurologist will conduct an extensive physical examination which will assess cognition (ability to think and reason); motor function (including size, strength, and tone of muscles); sensory nerve function (ability to tell the difference between light and firm touch, etc.); coordination (ability to perform certain movements, balance, walk, etc.); and reflexes. This series of tests can allow the neurologist to pinpoint the location of the lesion in the brain. These tests will not confirm the diagnosis of toxoplasmosis, but they can eliminate some other possible diagnoses.

A lumbar puncture (spinal tap) may be done to remove a sample of cerebrospinal fluid (CSF). This fluid will be tested to find out if the patient has been exposed to the parasite or to other germs that could cause similar symptoms. Although antibodies to toxoplasmosis may be found in the CSF, this test cannot confirm the diagnosis of toxoplasmosis, but can eliminate other possible diagnoses.

Images of the inside of the brain and spinal cord can be produced with a CT scan. In a patient with toxoplasmosis, the scan can reveal multiple lesions in the cortex and deep grey-matter structures such as the basal ganglia. However, the CT images can vary widely: there may be single lesions, lesions with diffuse enhancement, as well as non-enhancing lesions.

The only definitive way to diagnose toxoplasmosis is through a brain biopsy. This involves cutting open the skull and removing a small piece of brain for analysis in the lab. This procedure is so invasive and potentially so dangerous that it is almost never performed.

Treatment

Treatment for toxoplasmosis may be taken at home or in hospital depending on the size, number, and location of the lesions, the symptoms experienced, and the person's ability to tolerate the medications.

The most effective treatment is a combination of the oral antibiotic drugs pyrimethamine (50 to 100 mg per day) and sulfadiazine (4 to 8 grams per day), plus the B vitamin folinic acid (10 mg per day). Although improvement in symptoms is usually seen within seven days and on CT scans after 14 days, treatment should continue for at least six weeks.

Pyrimethamine is fairly well tolerated by most people, but its side effects can include nausea, vomiting, and diarrhea in the first few days of treatment. Sulfadiazine can cause skin rashes, itching, sensitivity to light, joint pain, fever, and chills. Both drugs can cause allergic reactions; "sulfa" reactions are common among HIV-positive people. Folinic acid is taken to help protect the bone marrow from the suppressive effects of both drugs.

Pyrimethamine may not always be available or there may be a delay in accessing this drug. As a result, some infectious disease specialists may prescribe other treatments for toxoplasmosis including a combination of two antibiotics: co-trimoxazole. This is the name given to the combination of trimethoprim-sulfamethoxazole (sold as Bactrim, Septra and in generic formulations). After all symptoms and signs have cleared up, and the infection has been controlled, daily treatment to suppress the parasite is required. Suppressive therapy usually consists of lower doses of the same drugs that successfully treated the active infection. Eventually, as the immune system improves because of ART, doctors discontinue prescribing suppressive therapy (see the section on preventing toxoplasmosis for details).

ART and toxoplasmosis

U.S. treatment guidelines state that most physicians would likely encourage patients with toxoplasmosis to initiate ART within “two to three weeks after the diagnosis of toxoplasmosis.” ART helps to strengthen the immune system’s ability to control toxoplasmosis and many other germs.

Preventing toxoplasmosis

Taking reduced doses of medicines to prevent another occurrence of toxoplasmosis is called secondary prophylaxis. Once a person has recovered from toxoplasmosis, doctors prescribe suppressive therapy to prevent recurrence. U.S. guidelines state the following: “the combination of pyrimethamine plus sulfadiazine plus leucovorin is highly effective as suppressive therapy for patients with [toxoplasmosis] and provides protection against PCP [pneumocystis pneumonia; another life-threatening complication of AIDS]." However, the guidelines list other combinations of medicines that may be considered for preventing a recurrence of toxoplasmosis.

The same guidelines make this statement about discontinuing prophylaxis against toxoplasmosis:

“Adult and adolescent patients receiving chronic maintenance therapy for toxoplasmosis [of the brain, this is called encephalitis (TE)] are at low risk for recurrence of TE if they have successfully completed initial therapy for TE, remain asymptomatic with regard to signs and symptoms of TE, and have an increase in their CD4 counts to more than 200 cells/mL after ART that is sustained for more than 6 months. Discontinuing chronic maintenance therapy in such patients is a reasonable consideration, although occasional recurrences have been reported. The recommendation is based on results in a limited number of patients from observational studies and one randomized clinical trial and inference from more extensive cumulative data indicating the safety of discontinuing secondary prophylaxis for other opportunistic infections during advanced disease. As part of the evaluation to determine whether discontinuation of therapy is appropriate, some specialists recommend obtaining an MRI of the brain to assess for resolution of brain lesions.”

Cat care

Pets are an important source of companionship and emotional support for people. HIV-positive cat owners may help reduce the risk of developing toxoplasmosis with the following steps:

  • using dust-free cat litter
  • wearing gloves and a mask to remove feces from the litter box daily
  • dust-free litter may help prevent the toxoplasmosis parasite from being inhaled with the dust
  • always wash your hands thoroughly after cleaning cat litter
  • keep cats indoors and avoid handling stray cats
  • feed cats canned or dried commercial food or well-cooked table food

Food safety

Other ways to reduce your risk of exposure to the parasite that causes toxoplasmosis and other germs include the following:

  • wash hands after contact with raw meat and after contact with soil
  • wash raw fruit and vegetables before eating them
  • avoid eating raw or undercooked meats (including beef, chicken, pork, lamb and wild meat) and shellfish

References

  1. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 25 July, 2017. Available at: https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-opportun...
  2. Hernandez AV, Thota P, Pellegrino D, et al. A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: is trimethoprim-sulfamethoxazole a real option? HIV Medicine. 2017 Feb;18(2):115-124.
  3. Lejeune M, Miró JM, De Lazzari E, et al. Restoration of T cell responses to Toxoplasma gondii after successful combined antiretroviral therapy in patients with AIDS with previous toxoplasmic encephalitis. Clinical Infectious Diseases. 2011 Mar 1;52(5):662-70.
  4. Jacobson JM, Hafner R, Remington J, et al. Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS. AIDS. 2001 Mar 30;15(5):583-9.
  5. Podzamczer D, Salazar A, Jiménez J, et al. Intermittent trimethoprim-sulfamethoxazole compared with dapsone-pyrimethamine for the simultaneous primary prophylaxis of Pneumocystis pneumonia and toxoplasmosis in patients infected with HIV. Annals of Internal Medicine. 1995 May 15;122(10):755-61.
  6. Gallien S, Bigé N, Kitzis MD, et al. Drug-to-drug interaction between dapsone and minocycline: an unusual cause of relapse of toxoplasmic encephalitis in an HIV-infected patient. Scandinavian Journal of Infectious Diseases.  2009;41(9):700-2.
  7. Furco A, Carmagnat M, Chevret S, et al. Restoration of Toxoplasma gondii-specific immune responses in patients with AIDS starting HAART. AIDS. 2008 Oct 18;22(16):2087-96.
  8. Dubey JP, Ferreira LR, Martins J, et al. Sporulation and survival of Toxoplasma gondii oocysts in different types of commercial cat litter. Journal of Parasitology. 2011 Oct;97(5):751-4.
  9. Lindsay DS, Dubey JP. Long-term survival of Toxoplasma gondii sporulated oocysts in seawater. Journal of Parasitology. 2009 Aug;95(4):1019-20.
  10. Hill DE, Dubey JP. Toxoplasma gondii prevalence in farm animals in the United States. International Journal of Parasitology. 2013 Feb;43(2):107-13.
  11. Jones JL, Dargelas V, Roberts J, et al. Risk factors for Toxoplasma gondii infection in the United States. Clinical Infectious Diseases. 2009 Sep 15;49(6):878-84.

Author(s): Maclean D, Foley R, Hosein SR

Published: 2021