Toxoplasmosis

Life cycle of T. gondii: After ingestion boy a host, oocysts (found in feces) and tissue cysts (found in muscle/CNS) transform into tachyzoites which localize in muscle and CNS. Tachzoites develop into tissue cyst bradyzoites which can survive indefinitely in muscle/brain. Cysts are typical `0-70 microns across and do not show up on imaging.

Signs and symptoms of acute infection:

In healthy adults: no symptoms or mild, flulike symptoms + swollen lymph nodes (neck, chin, armpits, groin) – usually lymph node swollen in infants and immunocompromised individuals: encephalitis, necrotizing retinochorioditis.

Diagnosis:

Several tests based on seropositivity are available.

  • IgG is a maker of lifetime exposure/chronic (encysted) infection
  • IgM is a maker of acute infection/reactivation

Why is this interesting?

  • According to some authors, T. gondii is the single pathogen most strongly suspected of causing psychiatric morbidity
  • T. gondii – 23% of US population is seropositive for chronic latent infection. Worldwide prevalence is about 50% (higher in some areas, including Latin America and Middle East)
  • Seropositivity indicating latent infection with T gondii (positive lgG titer) correlates with a broad variety of psychiatric illness including schizophrenia, bipolar disorder, OCD. The odds ratio for schizophrenia for individuals with latent infection: 2.73 cs. toxo-negative (2.1-3.6 Cl)[Yolker]. Postivie lgG titer also correlated with suicide attempts in a large sample of pregnant Danish women (n=45, 271) [Postolache 2013]
  • Acute infection (positive lgM titer) is an independent risk factor for acute exacerbation of schizophrenia in some studies [Monroe 2015]
  • T. gondii infection (even when latent) causes the “fatal attraction” phenomenon in rodents, whereby they lose their aversion to cat urine.
  • Reduced aversion to cat urine has also been observed experimentally in humans with latent T. gondii infection – but only among males [Flegr 2011]
  • T. gondii seropositivity correlates with a remarkable number of psychological findings – prolonged reaction times, greater risk of traffic accidents, changes in personality characteristics such as suspiciousness or novelty-seeking (often with different results in women vs. men). Also may be associated with changes in testosterone and dopamine levels.

The route of infection is contact with fecal oocysts or tissue cysts.

  • Contact with cat/mouse/bird feces
  • Contact with soil (especially garden soil)
  • Foodborne
    – Undercooked meat esp. pork, lamb, venison
    – Unwashed vegetables (contaminated with soil)
    – raw/undercooked seafood
    – unpasteurized milk, especially goat’s milk
  • Congenital infection (tachyzoites spread through placenta)
  • Organ transplant (esp. heart transplant)

If the mother is infected with T. gondii, treatment reduces the risk of transmission to fetus.

Treatment:

  • Effective anti-toxo agents include TMP/SMX (for prophylaxis) or pyrimethamine (for acute infection)
  • Once encysted T. gondii becomes very antibiotic-resistant. Nothing is proven to eliminate cysts in humans, although some regimens have been successful in mice and partly effective in humans (e.g. atovaquone).
  • Certain psychotropic medications are known to inhibit T. gondii growth. Ford [2015] provides a list of psychotropic with known anti-toxoplasmic activity (TATA+) vs. those without (TATA-).

TATA+: Fluphenazine, haloperidol, loxapine, paliperidone, risperidone, thioridazine, valproate (also: cyamemazine, levompromazine, zuclopenthixol)
TATA-: amisulpride, aripiprazole, carbamazepine, clozapine, lamotrigine, lithium, olanzapine, quetiapine, tiapride

Implications for treatment of psychiatric disorders:

  • 4 different RCTs have been conducted using anti-toxo agents as an adjunctive treatment for seropositive schizophrenics. All four were negative studies. It has been speculated that this is because the treatments given were not effective against cysts. [Chorlton 2017]
  • One study indicated that in bipolar individuals who are seropositive for toxoplasmosis TATA+ agents led to slightly better outcomes than TATA- agents. This was not true for schizophrenics, however. [Fond 2015]

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