Toxoplasmosis overview

# Overview
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii.The parasite infects most warm-blooded animals, including humans, but the primary host is the felid (cat) family.  Animals are infected by eating infected meat, by ingestion of faeces of a cat that has itself recently been infected, or by transmission from mother to fetus. Cats have been shown as a major reservoir of this infection, contact with infected undercooked meat seems to be a more important cause of human infection in many countries. Toxoplasmosis manifests as a painless lymphadenopathy in an immunocompetent individual.  In patients with AIDS and other immunocompromised conditions, it mainly involves brain and presents with fever and focal neurological symptoms.The major risk factors for acquiring the infection is consuming raw meat and ingestion of food contaminated with toxoplasma oocysts excreted in cat feces.   

# Historical Perspective
Toxoplasma gondi was first identified in 1908 by Nicolle and Manceaux. Sabin & Olitsky in 1937 described that toxoplasma was an obligate intracellular parasite and could be passed onto laboratory animals by intracranial,  subcutaneous, intraperitoneal inoculation of brain homogenates (The slurry of tissues and cells which result when cell structure has been mechanically disrupted). They have also suggested that ingestion of toxoplasma contaminated tissue can result in toxoplasmosis. In 1937 to 1940, Wolf and Cowen have described necrotic and granulomatous lesions on an autopsy of a 3-day old infant's brain infected with toxoplasma. They have also reported that the mothers were asymptomatic but carried antibodies against Toxoplasma and the possibility of congenital transmission was expressed. Sabin and Feldman developed a serological test to identify infected individuals by using antibodies specific to toxoplasma, called the Sabin Feldman Dye test. The serological test when used in large population studies showed a high proportion of humans and domestic animals carried antibodies against toxoplasma. Dubley described the life cycle of the parasite in 1970 and established that the cats are the definitive hosts and any warm-blooded animal can be an intermediate host.

# Pathophysiology
Toxoplasma gondii is a protozoan parasite that infects most species of warm-blooded animals, including humans, causing the disease toxoplasmosis. Members of the cat family (Felidae) are the only known definitive hosts for the sexual stages of T. gondii and thus are the main reservoirs of infection.  Cats become infected with T. gondii by carnivorism .  After tissue cysts or oocysts are ingested by the cat, viable organisms are released and invade epithelial cells of the small intestine where they undergo an asexual followed by a sexual cycle and then form oocysts, which are excreted.  The unsporulated oocyst takes 1 to 5 days after excretion to sporulate (become infective).  Although cats shed oocysts for only 1 to 2 weeks, large numbers may be shed.  Oocysts can survive in the environment for several months and are remarkably resistant to disinfectants, freezing, and drying, but are killed by heating to 70C for 10 minutes.

# Causes
Toxoplasma gondii is a species of parasitic protozoa in the genus Toxoplasma.

# Differentiating toxoplasmosis from other diseases
Toxoplasmosis manifests as a painless lymphadenopathy in an immunocompetent individual.  In patients with AIDS and other immunocompromised conditions, it mainly involves brain and presents with fever and focal neurological symptoms. The major differential diagnosis of focal CNS lesions in patients with AIDS is CNS lymphoma, which manifests as multiple enhancing lesions in 40% of cases. Other differentials in the diagnosis of toxoplasmosis include brain abscess, cytomegalovirus, herpes simplex, histoplasmosis, infectious mononucleosis, listeria monocytogenes infection (Listeriosis), lymphoblastic lymphoma, metastatic cancer with unknown primary site.

# Epidemiology and Demographics
Serologic prevalence data indicate that toxoplasmosis is one of the most common of humans infections throughout the world.  Infection is more common in warm climates and at lower altitudes than in cold climates and mountainous regions.  High prevalence of infection in France has been related to a preference for eating raw or undercooked meat, while high prevalence in Central America has been related to the frequency of stray cats in a climate favoring survival of oocysts. The overall seroprevalence in the United States as determined with specimens collected by the third National Health and Nutritional Assessment Survey (NHANES III) between 1988 and 1994 was found to be 22.5%, with seroprevalence among women of childbearing age (15 to 44 years) of 15%.

# Risk factors
The major risk factors for acquiring the infection is consuming raw meat and ingestion of food contaminated with toxoplasma oocysts excreted in cat feces.

# Screening
Majority of the countries do not follow standard screening for the detection of toxoplasma infection during the antenatal period. Women are tested for antibodies against toxoplasma on their first antenatal visit, and if they are seropositive they are followed up periodically in every trimester to examine the trends in IgG titer levels. All HIV-infected patients should be tested for prior exposure by measuring anti-Toxoplasma IgG. Patients with HIV and CD4+ T lymphocyte counts <100 cells/microliter with detectable anti-Toxoplasma IgG are at risk for reactivation of latent infection and should receive prophylactic treatment. Screening for Toxoplasma is routinely performed for cardiac donors.

# Natural History, Complications, and Prognosis
If left untreated in people with a weakened immune system, such as those infected with HIV, and fetuses, the disease can become seriously ill, and occasionally be fatal. The parasite can cause encephalitis (inflammation of the brain) and neurologic diseases and can affect the heart, liver, and eyes (chorioretinitis). Complications that can develop as a result of toxoplasmosis are mental retardation, seizures, motor difficulties, severe vision loss, hydrocephalus or microcephalus, hearing loss. Prognosis of infection in immunocompromised individual is dependent on the severity of the disease. Severe infection causes death at an early age, asymptomatic infection will present in the 1st or 2nd decade with progressive chorioretinitis with poor prognosis.

# Diagnosis

## History and symptoms
Acquired infection with Toxoplasma in immunocompetent persons is generally an asymptomatic infection. However, 10% to 20% of patients with acute infection may develop cervical lymphadenopathy and/or a flu-like illness. The clinical course is usually benign and self-limited; symptoms usually resolve within a few months to a year. Immunodeficient patients often have central nervous system (CNS) disease but may have retinochoroiditis, or pneumonitis. In patients with AIDS, toxoplasmic encephalitis is the most common cause of intracerebral mass lesions and is thought to be caused by reactivation of chronic infection. Toxoplasmosis in patients being treated with immunosuppressive drugs may be due to either newly acquired or reactivated latent infection.

## Physical examination
The most common physical examination findings of toxoplasmosis include painless lymphadenopathy in immunocompetent individuals. Other findings include fever, malaise, myalgias, and a maculopapular skin rash that spares the palms and the soles. In retinochoroiditis examination reveals multiple yellow-white cotton like patches with indistinct margins located in small clusters in the posterior pole.

## Laboratory findings
Toxoplasma infection is diagnosed by the presence of parasite in the fluids such as blood, body fluids, or tissue by DNA amplification, microscopy or by isolation of the organism. The most commonly used diagnostic test is the PCR of the amniotic fluid and a positive test is diagnostic of congenital toxoplasmosis. The most commonly used diagnostic investigation for early detection is the serological detection of antibodies (IgG, IgM and IgA) in the serum. A combination of all the antibodies (IgG, IgM, IgA) is usally employed.

## Chest X ray
There are no specific chest x ray findings associated with toxoplasmosis.

## CT brain
Toxoplasmic encephalitis is the most common cause of intracerebral mass lesions and is caused by reactivation of chronic infection. Typically cerebral toxoplasmosis manifest as multiple lesions, with a predilection for the basal ganglia, thalami, and corticomedullary junction. Intracerebral mass lesions can be diagnosed using CT  and MRI scan. Findings of CT brain include multiple hypodense regions predominantly in the basal ganglia and at the corticomedullary junction.

## MRI brain
On brain MRI, toxoplasmosis is characterized by isointense or hyperintense lesions with surrounding perilesional oedema. Lesions often demonstrate ring enhancement or nodular enhancement

# Treatment

## Medical therapy
Treatment of immunocompetent adults with lymphadenopathic toxoplasmosis is rarely indicated. Antimalarials and antibiotics are the mainstays of treatment. Treatment for ocular diseases should be based on a complete ophthalmologic evaluation.When a pregnant woman is diagnosed with acute toxoplasmosis, amniocentesis can be used to determine whether the fetus has been infected or not.If the parasite has not yet reached the fetus, spiramycin can help to prevent placental transmission. If the fetus has been infected, the pregnant woman can be treated with pyrimethamine and sulfadiazine, with folinic acid, after the first trimester. Persons with AIDS who develop active toxoplasmosis (usually toxoplasmic enchephalitis) need treatment that must be taken until a significant immunologic improvement is achieved as a result of antiretroviral therapy.

## Surgery
Surgical intervention is not recommended for the management for toxoplasmosis infection.

## Prevention
Effective measures for the primary prevention of toxoplasmosis include general sanitation and food safety steps such as hands should be washed well with soap and water after outdoor activities, especially before you eat or while handing preparation of food. A woman with no previous exposure should avoid handling raw meat, exposure to cat faeces, and gardening (cat faeces are common in garden soil).

## Secondary prevention
Secondary preventive measures are same as of primary preventive.