Toxoplasmosis

Toxplasmosis is caused by Toxoplasma gondii, an intracellular obligate parasite (i.e. it can only feed on the living tissues of the host). It is one of the commonest human parasites and has features in common with the pathogen that causes malaria. Cats are the main source of infection. Infectious oocysts are excreted by the cat for up to two weeks after the initial infection, and can survive in warm, moist soil for more than 1 year. The active proliferating forms of the organism is called tachyzoites. They can be found in any organ but occur most commonly in the brain, skeletal muscle, and heart muscle.
Humans acquire infection from domestic cats or from eating raw or undercooked meat from another intermediate host^1,2. Human to human transfer only occurs via the maternal-foetal route but is being seen with increasing frequency in patients whose immunity is compromised by HIV³.

T gondii is worldwide in distribution, but the disease occurs less frequently in areas where the environment is unfavorable for the oocysts, such as higher altitudes and extremes of temperature⁴. Seropositivity does not guarantee that an individual will exhibit signs of the disease. In the United States, as many as 40% of adults have serologic evidence of subclinical infection with T gondii². One UK study found the overall seroprevalence in pregnant women in Kent was 9.1%².

Toxoplasma infections may present in four main ways:

1. Acquired infection in non-compromised patients
   • These are usually mild, and commonly present as asymptomatic lymphadenopathy, often localised to the neck, but sometimes more generalised. The condition usually resolves within one to three months, but can last up to a year.⁵
   • A generalised non-pruritic skin rash may occur; usually transient and most pronounced on the trunk and proximal extremities⁵. Systemic manifestations in the uncompromised host is uncommon but can include dermatomyositis⁶, pericarditis⁷, pneumonia⁸, hepatitis⁹ and rarely encephalitis.¹⁰
2. Congenital infection in non-compromised patients
   • Transmission to a fetus from an immunocompetent mother is more severe if infection takes place close to conception, and can lead to natural abortion¹¹.
   • The chance of infection increases as the pregnancy proceeds, but the consequences become less severe¹².
   • Severe congenital toxoplasmosis is marked by the classic triad of chorioretinitis (see below), intracranial calcifications, and hydrocephalus.¹³
3. Acquired infection in immunocompromised patients
   This occurs in AIDS patients, patients with lymphoreticular malignancies (particularly Hodgkin's), collagen vascular disease, organ transplantation, and a wide variety of other immunocompromising conditions^{5 2}. Necrotising encephalitis¹⁴, pneumonitis², and myocarditis¹⁵ are the commonest autopsy findings. Severe disseminated toxoplasmosis can occur in AIDS patients and may lead to multi-organ failure¹⁶.
4. Ocular manifestations
   Ocular damage can occur in immunocompetent and immunocompromised patients. Cysts deposited in or near the retina cause focal necrotising retinitis. Symptoms include a painful red eye, blurred vision, floaters, photophobia, and metamorphopsia (image distortion)¹⁷.
   When the optic nerve becomes involved , the typical manifestation is optic neuritis or papillitis associated with oedema, often called Jensen disease¹⁷.
   Antigens to toxoplasma may cause a hypersensitivity reaction resulting in retinal vasculitis and granulomatous or nongranulomatous anterior uveitis¹⁸.
   The most common finding in congenital toxoplasmosis is retinochoroiditis that has a predilection for the posterior pole. It is seen in 75-80% of cases and is bilateral in 85% of cases¹⁷.
   Ocular toxoplasmosis was thought to be a rare feature of acquired infection (only 1-3% of patients)
   but it is now considered that some cases previously classified as congenital were in fact acquired postnatally¹⁹.

Depending on presenting features, the list of differential diagnosis might include encephalitis, mononucleosis, pneumonia in the immunocompromised, sarcoidosis, tuberculosis, and causes of abdominal pain in the elderly².

• Lab Studies - The immunoglobulin M (IgM) immunofluorescent antibody test (IgM-IFA) is used as standard for the diagnosis of acute toxoplasmosis. An IgM-IFA titer of 1:160 or greater or an IgM-enzyme-linked immunosorbent assay (IgM-ELISA) titer of 1:256 or greater is considered diagnostic of recently acquired T gondii infection². In cases of diagnostic difficulty, T. gondii-specific IgG²⁰ and polymerase chain reaction (PCR)²¹ tests have been used.
• Imaging Studies - MRI is considered the best diagnostic imaging technique for toxoplasmic encephalitis, and may detect lesions not visualised on CT scan²².
• Other Tests - Cerebrospinal fluid may show elevated protein, normal glucose, and mononuclear pleocytosis. The presence of tissue cysts is diagnostic for toxoplasmosis but does not distinguish between acute and chronic infection². Indirect latex agglutination test and enzyme-linked immunosorbent assays may be helpful²³.
  The presence of tachyzoites or toxoplasmal antigens in tissue or smears may be contributory in confirming acute infection².
  Brain biopsy may reveal the presence of tachyzoites, and may be required for patients with suspected toxoplasmic encephalitis who have negative serology or who fail to respond to two week's empirical treatment. This investigation is being supplanted by less invasive methods in many cases²⁴.

• Immunocompromised patients may be seriously ill with encephalitis, pneumonitis, or myocarditis and may require stabilisation, and treatment of acute symptoms such as seizures, respiratory failure and cardiovascular compromise².
• Pyrimethamine and a sulfonamide (eg, sulfadiazine) is the first-line treatment for acute toxoplasmosis.². Growing concerns about resistance has stimulated the search for new drugs²⁵.
  Clindamycin may be used as an alternative to sulfonamides. Folinic acid 5 mg/d PO reduces incidence of pyrimethamine-induced bone marrow suppression²⁶.
  • Immunocompetent patients - treat for 3-4 weeks.
  • Immunocompromised patients are treated for as long as 6 weeks, followed by lifelong suppressive therapy with low doses of all three drugs². Thrice-weekly rather than daily therapy has been used with no increase in complications²⁷.
• First trimester of pregnancy - treatment is difficult because the safety data of pyrimethamine is limited²⁵, and it is important to confirm that serology is showing an acute and not a latent infection²⁸.
• Ocular toxoplasmosis is usually treated with pyrimethamine and sulfadiazine, although trimethoprim/sulfamethoxazole can be used as an alternative²⁹. The duration and type of treatment needs to be tailored to the individual patient, taking into account immunocompetency and the severity of the disease³⁰.
• Congenital toxoplasmosis, current research favours the use of pyrimethamine plus sulfadiazine; initiated shortly after birth and continued for 12 months³¹.

Ongoing research is evaluating the risks and benefits of prenatal treatment to reduce the clinical manifestations of congenital toxoplasmosis³², but the results so far suggest that treatment early in pregnancy may reduce the development of intracranial lesions in the baby³³.

• Nervous system involvement can lead to seizures³⁴, mental retardation³⁵ and deafness.³⁶
• The commonest congenital complication seen in surviving children is delay in neuropsychomotor development.³⁷
• Ocular disease can lead to partial or complete blindness.³⁸
• Dementia³⁹, gastrointestinal involvement⁴⁰, and fulminant dissemination into lungs and heart⁴¹ have been described in AIDS patients.

• Most cases in immunocompetent healthy individuals remain subclinical or resolve spontaneously.
• The prognosis in AIDS patients was poor but has improved considerably⁴² since the advent of highly active antiretroviral therapy (HAART).⁴³
• Prenatal screening and treatment has reduced the incidence of congenital cerebral lesions, but not of ocular complications.³³
• Developments in diagnosis and management have improved the prognosis for ocular disease in immunocompetent patients.⁴⁴Prognosis in immunocompromised patients must be more guarded, but improves if therapy is continued lifelong.⁴⁵

• Evidence-based preventive measures focussing on hygiene measures when preparing food available and should be adhered to in localities where prevalence is high⁴⁶.
• Pregnant women should avoid contact with cat litter and wear gloves when gardening and during any contact with soil or sand.
• The issue of screening is a controversial one. Although techniques are now available to differentiate active from latent infection, governments in countries where prevalence is low (such as the UK) have taken the decision to invest more in primary prevention than screening⁴⁷. However, the development of effective prenatal testing and treatment may make focussed screening a more cost-effective option in areas of high prevalence.³²