Toxoplasmosis (sometimes called `toxo' for short) is illness caused by a protozoan called Toxoplasma gondii.

Transmission

T. gondii is transmitted by eating raw or undercooked meat, or from cat faeces. An American study found that nearly a quarter of pork samples, a tenth of mutton samples and 1% of beef samples bought in a market were infected. Previously frozen food appeared not to be infectious.

Pregnant women who become infected with the parasite during pregnancy can pass it on to their babies. There is no evidence that it can be passed from person to person by direct contact. In the UK about half the population have been exposed to the organism, but it is more common in other countries in Europe. About 8% of people with AIDS in Britain develop toxoplasmosis.

Symptoms

Toxoplasma can cause illness in people with perfectly healthy immune systems, such as birth defects in some babies in the uterus, and a glandular fever-like illness in adults.

In people with HIV with CD4 counts below 200, toxoplasmosis most commonly causes lesions in the brain (cerebral toxoplasmosis). By exerting pressure on normal brain tissue these at first cause headache, fever, lethargy and confusion, progressing to fits, vision distortions, strokes (a weakness on one side of the body), changes in thinking and personality and difficulty speaking. Without treatment, as the abscesses grow bigger they can cause coma and eventually death.

However, a number of other problems in HIV can produce similar symptoms; for more information on these, see the entries on CMV, lymphoma, HIV-associated dementia, progressive multifocal leukoencephalopathy and tuberculosis.

Rarely, T. gondii can cause problems in the eyes, lungs (toxoplasmic pneumonia), retina, heart, pancreas, liver, colon and/or testicles.

Diagnosis

After infection with T. gondii the body makes antibodies to it which can usually but not always be detected by a blood test. A positive test result means that you have been exposed to T. gondii at some point. It does not necessarily mean that you have toxoplasmosis now, but if you have suppressed immunity, then 'dormant' T. gondii could be re-activated in the future. A negative antibody test suggests that you have not previously been exposed to T.gondii. It may be especially worthwhile for you to take appropriate precautions to avoid infection in the future (see below).

PCR tests can also be used to look for T.gondii DNA. Like antibody tests, a negative result means you probably, but not definitively, have not been exposed. A positive test on a sample of cerebrospinal fluid suggests that you do have active toxoplasmosis. However, sometimes a PCR test can fail to detect the organisms' DNA even when you have active disease.

A CT or MRI scan will show the typical abscesses, but again this does not definitely confirm toxoplasmosis, since a lymphoma and some other conditions would look similar.

If tests and brain scans suggest that your symptoms may be due to toxoplasmosis, most doctors will start toxoplasmosis treatment. The symptoms should improve within 14 days and a brain scan should show that the lesions have improved within three weeks. If these improvements are not seen after 7-10 days, most doctors will consider doing a brain biopsy (taking a sample of brain tissue to test) to find out definitively if toxoplasmosis is present. This is a difficult decision, since the procedure involves a slight risk, and must be discussed carefully and fully with your doctor.

Prophylaxis

Tests for T. gondii can show whether you are latently infected with the parasite and therefore potentially at risk of developing active toxoplasmosis if your CD4 count falls below 200 before any active disease occurs.

If this test is negative, it may be worth taking precautions to avoid exposure to T. gondii. Although the parasite can be present in cat's faeces, owning a cat does not necessarily place an HIV-positive person at increased risk of toxoplasmosis. Changing cat litter on a daily basis removes the oocysts before they have a chance to mature and become infectious. Rinsing the box with boiling water will also kill the parasites. Ideally, the litter should be changed by an HIV-negative person, or if this is not possible, you should wear gloves, avoid creating dust that might be inhaled and wash your hands thoroughly afterwards. Cats that are kept indoors and fed on canned or well-cooked table foods only are unlikely to become infected. Stray cats are the most likely to be infected.

To minimise the risk of becoming infected through food, avoid undercooked meat.

For people who have been infected with the parasite, there is good evidence that it is possible to prevent a first occurrence of toxoplasmosis by routine prophylaxis. Co-trimoxazole, or dapsone (usually given in combination with pyrimethamine), appear to be effective. Since co-trimoxazole started to be widely used for PCP prophylaxis, toxoplasmosis has also become very much less common. As with PCP prophylaxis, the obvious benefits of prophylaxis against toxoplasmosis have to be weighed against the very real possibility of side-effects from the drugs.

Pyrimethamine on its own is not recommended for toxoplasmosis prophylaxis. One study showed that it does not prevent the disease, while another found that pyrimethamine recipients had increased mortality compared with those given an inactive placebo.

A large American study found that for people who cannot tolerate co-trimoxazole as PCP prophylaxis, atovaquone suspension was equally effective as dapsone at preventing PCP and toxoplasmosis.

Experimental regimens for toxoplasmosis prophylaxis include azithromycin (which like atovaquone can kill Toxoplasma cysts) and clarithromycin.

If your CD4 count rises above 200 while taking HAART it appears safe to stop taking prophylaxis treatment. This is because the immune system is able to control the toxoplasmosis organism and prevent it from causing illness. A randomised study carried out in Spain^[1] showed that after 30 months, no recurrences of toxoplasmosis occurred in the patients who stopped cotrimoxazole prophylaxis after their CD4 cell counts rose above 200 cells/mm³.

Treatment

Toxoplasmosis usually responds well to treatment. Good recovery is the general rule. A number of treatment options exist, which will depend on local experience, any adverse reactions to drugs and whether you're taking AZT or not.

The mainstay of initial treatment is a combination of pyrimethamine plus sulphadiazine. Pyrimethamine can cause blood abnormalities in some people, so folinic acid (also known as leucovorin) is usually given with it to reduce its effects on the bone marrow.

The sulphadiazine is often given intravenously in severe disease, although it is usually prescribed in its oral form. It is also this component that can cause allergic reactions and blood problems in 20%-40% of people with AIDS. In this case, it may be necessary to replace the sulphadiazine with clindamycin. Clindamycin is given at a dose of 600 mg every 6 hours, either as tablets or intravenously; it has fewer side-effects, but diarrhoea can sometimes be a problem.

Substituting clarithromycin or azithromycin for sulfadiazine in the treatment combination has an inferior clinical outcome (Derouin).

After a few weeks on this therapy, and once a brain scan has shown improvement, it is necessary to switch to maintenance therapy which could be a low dose of pyrimethamine plus sulphadiazine, or pyrimethamine plus clindamycin. These have the added advantage of providing some prophylaxis against PCP. Maintenance therapy on one of these options has to be continued for life because the relapse rate would be very high without it.

In cases of very severe toxoplasmosis or when there is a lot of swelling around the abscesses on the brain scan, steroids such as dexamethasone may be given by injection or tablets, together with prophylactic drugs against fits.

Atovaquone liquid suspension has shown promising results. In tests with rats it was actually able to kill the cysts and trophozoite forms of Toxoplasma, rather than merely suppressing them; this effect has not been seen in humans with the current formulation of atovaquone. The drug has been used successfully to treat toxoplasmosis in people who are unable to tolerate the standard treatments.

The macrolide antibiotic azithromycin has also been tested as a treatment for toxoplasmosis. Trial results to date have been conflicting. Azithromycin is available on a compassionate use basis in the USA and on a named patient basis in the UK for the treatment of toxoplasmosis, and is widely available for the treatment of bacterial infections. The related drug clarithromycin is also active against Toxoplasma and appears to be an effective treatment in combination with pyrimethamine in the short-term, but with frequent side-effects.

Other experimental approaches include the addition of the cytokine interferon gamma to anti-toxoplasmosis treatment, as in test tube studies it inhibits Toxoplasma and prevents death in animals with toxoplasmosis, as well as being synergistic with anti-microbial drugs. There have been a few case reports of the successful use of the antibiotic doxycycline to treat toxoplasmosis in people who had failed to respond to standard therapies. Interleukin-2 has also been shown to improve the survival of animals with toxoplasmosis.

Maintenance treatment and antiretroviral therapy

If your CD4 cell count remains below 200 cells/mm³ after you have been treated successfully for toxoplasmosis, you will need to keep taking maintenance treatment to prevent the toxoplasmosis from occurring again.

If your CD4 cell count rises above 200 cells/mm³ while taking antiretroviral therapy, it appears safe to stop taking maintenance treatment. This is because the immune system is able to control the toxoplasmosis organism and prevent it from causing illness.

Toxoplasmosis in the highly active antiretroviral therapy era

Although the opportunistic infection is much less common in the HAART era due to use of antiretroviral therapy, Italian researchers have shown that a significant number of cases have been diagnosed in individuals who had previously received some antiretroviral therapy. The study identified 205 new cases of toxoplasmosis in 805 HIV-positive individuals diagnosed with neurological disorders between 2000 in 2002 in Italy.

The median CD4 cell count at the time of diagnosis with toxoplasmosis encephalitis was 34 cells/mm³ and the median viral load was 100,000 copies/ml. Antiretroviral therapy had been used by 76 patients (36%) prior to the development of toxoplasmosis encephalitis, and 66 (87%) of these patients had received HAART for a median of 24 months prior to their neurological diagnosis. At the time of diagnosis with toxoplasmosis encephalitis 44 of these patients were still taking HAART. Of the patients who were taking HAART, at the time of neurological diagnosis 11% had a CD4 cell count above 200 cells/mm³ and 12% had an undetectable viral load.

When the investigators studied the data for the entire study population of 805 patients they found that male sex (p = 0.02), previous exposure to antiretroviral therapy (p = 0.02), the use of prophylaxis against toxoplasmosis encephalitis (p = 0.02), and a higher CD4 cell count at the time of neurological diagnosis decreased the risk of developing toxoplasmosis encephalitis.

Prophylaxis against toxoplasmosis was only being taken by 35 (17%) of the 205 patients diagnosed with the condition. Furthermore, the investigators note that 31 (66%) of the 47 patients taking antiretroviral therapy with a CD4 cell count below 100 cells/mm³ were not taking prophylaxis against toxoplasmosis encephalitis when the condition was diagnosed (Antinori 2004).