TOXOPLASMOSIS (Toxoplasma gondii)
Life cycle of T. gondii: After ingestion by a host, oocysts (found in feces) and tissue cysts (found in muscle/CNS) transform into tachyzoites which localize in muscle and CNS. Tachyzoites develop into tissue cyst bradyzoites which can survive indefinitely in muscle/brain. Cysts are typically 10-70 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 only one lymph node swollen In infants and immunocompromised individuals: encephalitis, necrotizing retinochorioditis)
Diagnosis: Several tests based on seropositivity are available.
• IgG is a marker of lifetime exposure/chronic (encysted) infetion
• IgM is a marker 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 is common-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 IgG titer) correlates with a broad variety of psychiatric illnesses including schizophrenia, bipolar disorder, OCD. Odds ratio for schizophrenia for individuals with latent infection : 2.73 vs. toxo-negative (2.1-3.6 CI)[Yolker). Positive IgG titer also correlated with suicide attempts in a large sample of pregnant Danish women (n=45,271) (Postolache 2013] Acute infection (positive IgM 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.
cat urine has also been observed experimentally in humans with latent T. gondii infection – but only among males [Flegr 2011] ondii 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.
• Route of infection is by contact with fecal oocysts or tissue cysts.
• Contact with cat/mouse/bird feces
• Contact with soil (especially garden soil)
• Food borne
– 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 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. Certain psychotropic medications are known to inhibit T. gondii growth. Ford [2015] provides a list of psychotropics with known anti-toxoplas (TATA+) vs. those without (TATA-).
TATA+: fluphenazine, haloperidol, loxapine, paliperidone, risperidone, thioridazine, valproate (also: cyamemazine, levomepromazine, zucloptnhixol)
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 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]