What is HIV-1–Associated Toxoplasmosis?
Toxoplasmosis is the most common brain infection in patients with HIV/AIDS who are not taking the right preventive treatment. This infection usually shows up as one or more masses (also referred to as lesions) in the brain. There are also other health conditions related to AIDS that may result in similar masses or growths. These include primary brain lymphoma, which is typically linked with the Epstein-Barr virus, and progressive multifocal leukoencephalopathy (PML), a disease caused by the JC polyomavirus.
What Causes HIV-1–Associated Toxoplasmosis?
Toxoplasma gondii, a type of parasite that lives inside cells, causes the infection. It’s commonly found all over the world. You can get infected if you eat food, drink water, or touch something (like cat litter or soil) that’s contaminated with infectious bits of the parasite called oocysts. Interestingly, cats are the only animals where this parasite can reproduce.
After you swallow the parasite, it manages to get inside your body cells and can stay there, doing nothing, for a very long time. This is called a latent infection.
Usually, the infection only causes problems if your immune system can’t control it anymore. This can happen in people with advanced HIV, after organ or stem cell transplants, with prolonged steroid use, the use of certain medications called monoclonal antibodies, or chemotherapy. These situations all weaken your immune system, which might allow the dormant parasite to wake up and cause disease.
Risk Factors and Frequency for HIV-1–Associated Toxoplasmosis
Toxoplasmosis is an infection that is more common in areas where a higher percentage of the population has the disease. About 10% of adults in the United States have been exposed to the parasite that causes toxoplasmosis. This percentage, also known as seropositivity, is even higher in Africa and Europe, with some places having up to 80% seropositivity. In people who are prone to the disease, such as those with a weakened immune system, up to half can develop a severe form of toxoplasmosis that affects the brain.
While it’s traditionally been thought that cats and similar animals play a big role in the transmission of toxoplasmosis, owning a cat does not necessarily increase the risk of infection. However, for people with a severely weakened immune system, like those with HIV and a low CD4 count, the risk of the inactive infection becoming active again can be as high as 30% if no preventive measures are taken. Toxoplasmosis can also be passed on from a pregnant mother to her unborn child or through the transplant of an infected organ.
- 10% of adults in the United States have been exposed to toxoplasmosis.
- In Africa and Europe, this figure can go up to 80%.
- Half of people prone to the disease can develop severe toxoplasmosis affecting the brain.
- Owning a cat does not necessarily increase the risk of infection.
- People with a severely weakened immune system, like those with HIV and low CD4 counts, have a risk of up to 30% of the infection becoming active again if not properly prevented.
- Toxoplasmosis can also be transmitted from a pregnant mother to her fetus or through the transplantation of an infected organ.
Signs and Symptoms of HIV-1–Associated Toxoplasmosis
Cerebral toxoplasmosis, also known as toxoplasmic encephalitis, often shows up in patients with HIV. It usually presents itself as one or more ring-enhancing spots in the brain. Typically, symptoms develop gradually over a few days up to a month. Some noticeable symptoms include headaches, confusion and tiredness, while fever may or may not be present. It’s worth noting that long-term infection with toxoplasma may not be entirely symptom-free. Some patients may experience behavioral changes or develop mental health disorders. It’s also common, affecting up to 30% and 70% of patients, to experience seizures or specific problems with neurological function. Changes in mental state can also vary widely – from dull affect (decreased emotional response) to falling into a stupor or even a coma, often due to widespread inflammation in the brain or increased pressure within the skull. There may also be a phase where the toxoplasma is dormant and doesn’t cause any symptoms.
Though less common, toxoplasma can infect parts of the body other than the brain. It can potentially cause inflammation in the lungs and the inside layer of the eye (chorioretinitis), and in rarer cases, the intestines, liver, heart, bladder, spinal cord, bone marrow, and testes. In some extreme cases, toxoplasmosis may spread throughout the body.
Typical Symptoms of Cerebral Toxoplasmosis:
- Headaches
- Confusion
- Fatigue
- Fever (may not always be present)
- Behavioral changes
- Mental health disorders
- Seizures
- Neurological complications
- Varying degrees of altered mental status
Possible Other Body Parts Affected by Toxoplasmosis:
- Lungs
- Eyes (chorioretinitis)
- Intestines
- Liver
- Heart
- Bladder
- Spinal cord
- Bone marrow
- Testes
Testing for HIV-1–Associated Toxoplasmosis
Generally, there are no standard lab test results that can confirm toxoplasmosis, which is an infection caused by a parasite. However, a big increase in an enzyme called Lactate dehydrogenase (LDH) in your system could suggest toxoplasmosis has spread throughout your body or reached your lungs.
For HIV patients, doctors can use a combination of factors to suggest if cerebral toxoplasmosis (toxoplasmosis that has infected the brain) is likely. These factors include: having a CD4 count less than 100 cells/microliter which signifies a weak immune system; symptoms that align with cerebral toxoplasmosis; a positive T. gondii immunoglobulin (Ig) G antibody test, which shows your body has been exposed to the parasite causing toxoplasmosis; and brain imaging (like an MRI) that shows signs typically associated with cerebral toxoplasmosis.
If all these factors are present, then there’s at least a 90% chance you have cerebral toxoplasmosis. However, keep in mind that a positive antibody test alone does not confirm the diagnosis, just as a negative antibody test doesn’t necessarily rule the disease out.
In these brain scans, doctors often find multiple or single brain abnormalities that can be linked to swelling. These abnormalities usually appear in specific parts of the brain such as the basal ganglia, corticomedullary junction, or brain white matter.
If a more certain diagnosis is needed, doctors can perform a procedure called lumbar puncture or spinal tap. This can identify certain characteristics in your cerebrospinal fluid, which supports and cushions the brain and spinal cord, that are associated with toxoplasmosis, such as an increased level of white blood cells, elevated protein, and possibly decreased sugar. They can also do a specific test with this fluid, known as Polymerase chain reaction (PCR) test, which checks for the presence of T. gondii. This test is very specific, but not overly sensitive- meaning a positive result confirms cerebral toxoplasmosis, but a negative result doesn’t necessarily exclude it.
As a last resort, if there is uncertainty about the diagnosis and other disease possibilities are being considered, a brain biopsy could be performed. This is a medical procedure where a small piece of brain tissue is taken out and examined under a microscope. It can reveal specific changes in the brain tissue associated with toxoplasmosis. However, in most cases, this procedure isn’t necessary for a diagnosis.
Treatment Options for HIV-1–Associated Toxoplasmosis
Patients with HIV who are infected with toxoplasmosis, a parasite-related disease, are typically treated with two main types of therapy: antimicrobial therapy, which fights T. gondii – the parasite causing toxoplasmosis – and antiretroviral therapy for building their immune systems back up.
Pyrimethamine and sulfadiazine are frequently used to treat toxoplasmosis. The two drugs work together to block the process that the parasite needs to grow. Doctors often add folinic acid (also called leucovorin) to compensate for the depletion of folate, a type of B vitamin that’s important for cellular function and growth, which the first two drugs can nonselectively deplete. The initial treatment typically lasts for 6 weeks.
This initial treatment is followed by maintenance therapy, which goes on until the patient’s CD4 T-lymphocyte count, a type of white blood cell central to immune system function, is over 200 cells/microliters for more than 3 months. Maintenance therapy helps keep the patient’s immune system strong while also fighting against any remaining dormant forms of the parasite that could potentially come back to life and restart the infection. This process helps prevent a relapse.
For patients who are allergic to sulfonamides (a type of antibiotic), alternative treatment options include drugs like clindamycin, trimethoprim/sulfamethoxazole, pyrimethamine in combination with atovaquone and folinic acid, pyrimethamine combined with azithromycin and folinic acid or atovaquone alone if they can’t tolerate sulfur drugs or pyrimethamine. If a patient is in their first trimester of pregnancy, the preferred drug would be spiramycin since pyrimethamine might harm the fetus.
Some clinicians often use steroids when there is swelling in the body, but studies have shown this to be neither beneficial nor harmful. The most likely time steroids should be used with cerebral toxoplasmosis is when the brain seems to be severely affected and a diagnosis is urgently required.
Patient recovery from this therapy can be dramatic, with half of the patients showing neurological improvement by the third day and most by the seventh day after starting the treatment. If there isn’t significant improvement or if symptoms get worse by days 10 to 14, doctors might consider repeating imaging exams and possibly a brain biopsy. After treatment, 37% of survivors can have permanent neurologic effects and the death rate after one year could be anywhere from 10% to 60%.
In addition to the above, antiretroviral drugs (drugs that combat viruses) should be started as soon as possible, usually within two weeks of starting the therapy for toxoplasmosis. This type of therapy boosts the immune system, but it sometimes leads to a paradoxical worsening of symptoms as immunity recovers. This is a rare but known occurrence with toxoplasmosis as well as with mycobacterial and cryptococcal infections. In spite of this, starting early antiretroviral therapy has clear benefits and shouldn’t necessarily be delayed beyond two weeks.
What else can HIV-1–Associated Toxoplasmosis be?
When dealing with HIV-1 related toxoplasmosis, doctors would consider examining for the following related health conditions:
- CNS Lymphoma
- CNS Tuberculosis
- Cryptococcus
- Neurosyphilis
- Cardioembolic stroke
- Cytomegalovirus infection
Possible Complications When Diagnosed with HIV-1–Associated Toxoplasmosis
People with HIV-1 and toxoplasmosis can experience various complications, including:
- Changes in personality
- Seizures
- Nerve damage in the skull
- Weakness on one side of the body
- Loss of vision in half of the visual field
- Loss of coordination
- Difficulty with speech
Recovery from HIV-1–Associated Toxoplasmosis
After starting antibiotic treatment, getting better is a slow process and it might take a few weeks. It is important to have imaging tests done again after 4 to 6 weeks to check if the lesion (abnormal growth or wound) is reducing in size. Treatment is typically continued over a long term, but at lower doses. Once the therapy improves the CD4 count (a type of protein that plays a crucial role in the immune system) and the lesion is healed, it might be possible to stop the therapy.
Preventing HIV-1–Associated Toxoplasmosis
People living with HIV-1 linked to toxoplasmosis should be informed that it’s crucial to avoid consuming raw or undercooked meat. They should also rigorously wash their hands after touching cat litter or soil. HIV-1 is a type of HIV virus and toxoplasmosis is a disease that comes from a parasite, often found in raw meat and cat feces. By following these instructions, they can mitigate any further health risks or complications.
