A Tour around Toxoplasmosis

(Date of publication 24 March 2005)

Has one of your male neighbours recently started driving recklessly, gambling wildly or become something of a delinquent? If so, one possible explanation is chronic infection with the parasitic protozoon Toxoplasma gondii. This condition is common all over the world and one effect in men is a personality change, so that the sufferer loses control, disregards rules and follows urges, whilst simultaneously becoming detached, critical and dogmatic. To find out why, we need to look at the organism's life cycle.

The definitive host for T. gondii is the cat, with rats and mice being common intermediate hosts. When rodents become infected, certain behavioural changes are induced: decreases in motor performance, learning capacity and fear, and increases in activity and reaction times. These are considered to be evolutionary adaptations of the parasite to facilitate transmission from intermediate to definitive host by increasing predation. When the intermediate host is man rather than a rodent, these effects are obviously redundant, but one documented consequence is a significantly higher risk of traffic accidents. There may also be an association with the development of psychoses.

T. gondii is an obligate intracellular parasite with similar properties to the pathogen causing malaria. The complete life cycle is shown in this diagram and photomicrographs of the various developmental stages can be found here. Humans are usually infected by accidentally ingesting traces of faeces from an infected cat that is shedding the organism, or by eating undercooked meat from another intermediate host that contains cysts. Ingestion of tissue cysts or oocysts is followed by the infection of intestinal epithelial cells. After becoming tachyzoites, the organisms are disseminated throughout the body via the blood or lymphatic system. Once the peripheral tissues are reached, they transform into tissue cysts which appear to persist for the life of the host.

Most people are unaware of becoming infected and remain asymptomatic, although a proportion develop 'flu-like' symptoms with swollen lymph glands and muscle pains that may last for a month or more. The disease then typically becomes latent when the cysts – which contain bradyzoites – develop, most frequently in the brain and skeletal and cardiac muscle. These typically cause little or no inflammatory response and treatment is not required. However, infection can be reactivated subsequently, particularly if the host becomes immunocompromised as a result of malignancy, AIDS or organ transplantation.

Toxoplasmosis can be particularly serious in HIV patients, where it is typically caused by reactivation of a chronic infection and manifests primarily as toxoplasmic encephalitis. This condition is an important cause of focal brain lesions in patients with HIV; here is a CT scan demonstrating multiple enhancing brainstem lesions, and here a photograph of a brain slice with multiple T. gondii abscesses. Toxoplasmic encephalitis characteristically has a subacute onset with focal neurologic abnormalities, and is frequently accompanied by headache, altered mental status and fever. The most common focal signs are motor weakness and speech disturbances, but patients may also present with seizures, visual field defects and sensory disturbances. Victims generally have CD4 T-cell counts <100/µL. If you are particularly interested in the diagnosis of toxoplasmosis, this site has a detailed section covering serology, CSF studies, DNA detection, isolation studies, neuroradiological studies and histopathology. Treatment usually consists of a combination of pyrimethamine and sulphadiazine, which exhibit synergistic activity against folic acid synthesis by the parasite. Around half the people who take sulphadiazine have an allergic reaction to it, but this can be overcome by using a desensitisation procedure.

The other group of people particularly at risk is pregnant women; their babies stand a 40% chance of being affected if the mothers contract toxoplasmosis during pregnancy. According to the Organization of Tetralogy Information Services, 'Congenital toxoplasmosis only occurs when the mother has an active infection during pregnancy. In general, there is no increased risk to the foetus when toxoplasmosis occurred more than 6 months prior to conception.' The sequellae of in utero infection can be blindness, epilepsy and impaired mental development.

An estimated 400 – 4,000 cases of foetal toxoplasmosis occur in the United States each year. While some affected babies exhibit the classic signs of chorioretinitis, hydrocephalus and intracranial calcifications, most have no obvious signs of toxoplasmosis. However, up to 80% develop visual or learning difficulties later in life. Although this site only recommends the screening of pregnant women who are at high risk, or those in whom routine ultrasound examinations have revealed foetal abnormalities, a very recent US study found that signs, symptoms and identifiable risk factors were absent in more than half the mothers of infants with congenital toxoplasmosis. Consequently, the authors recommend screening all pregnant women and all newborn infants.

Other research has focused on avidity testing, measuring the capacity of the toxoplasmosis antibody to bind to the corresponding antigen, and found that it is weak soon after infection but becomes very strong after 16 weeks. This technique can therefore pinpoint the time of infection and, critically, whether it occurred before or after conception. Perhaps even more importantly, a method has now been developed to deliver medication directly to T. gondii within cysts, providing a totally new target for anti-parasitic treatment.

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