toxoplasmosis

see also:

• parasites
• https://www.cdc.gov/toxoplasmosis/about/

• Toxoplasma gondii was discovered in 1908 and is one of the most successful global parasites which appears to be primarily spread by oocytes shed in cat faeces
• cats appear to be the definitive host and the only host capable of shedding oocytes
• congenital infection was discovered in 1938
• there is only one species but there appears to be genomic variability
• it infects approx. one third of humans but infection over the age of 5 yrs in immunocompetent humans is thought to be asymptomatic although there are recent concerns it may have a role in various neurologic conditions such as:
  • dementia
  • gliomas - possibly a 2-3x increased risk
  • schizophrenia - may double the risk
  • lowered cognition
  • behavioural changes such as more risk taking and aggression
• the main concerns in humans are:
  • congenital infection
  • infection in immunocompromised patients such as those with AIDS
• CD8+ T cells have a potent weapon against T. gondii: an enzyme called caspase-8 which is an important regulator of our immune systems and induces apoptosis of infected T cells ¹⁾

• cats ingest a bradyzoite which then undergo sexual phase in the small intestine and then shed millions of oocytes in feaces as a product of schizogony and gametogony
• unlike other forms of the parasites, the oocytes can survive for long periods in water
• the oocytes are ingested by other mammalian hosts (including marine) which then excyst and invade the host as tachyzoites which may become tissue cysts in the form of bradyzoites which are very resistant to antimicrobial medications
  • on finding a potential host cell, three Toxoplasma proteins, collectively known as the MIC1/4/6 complex, that recognize particular glycans on the host-cell surface and appear to gather glycosylated host proteins together, while cholesterol helps make that reorganization possible and creates the right conditions to allow Toxoplasma to release specialized organelles called rhoptries into the host cell which contain proteins that manipulate the host cell and help establish receptors to allow the Toxoplasma to enter the host cell²⁾
    • the sugars recognized by the MIC1/4/6 complex are widely distributed across mammalian tissues, and the complex can recognize more than one glycan type
  • the protein TgPRO produced by Toxoplasma, allows Toxoplasma packed into a tissue cysts to manage oxidative stress that can damage cells by controlling genes involved in energy production and iron use - it appears TgPRO supports parasite growth in the naturally dense environment of a chronic-stage cyst³⁾
• oocytes also excyst in tissues after parenteral innoculation
• tachyzoites and bradyzoites are killed by water
• cattle and horses are resistant to clinical T. gondii, although a similar organism, Neospora caninum is a common cause of cattle abortions, while a similar organism, Sarcocystis neurona may cause fatal encephalomyelitis in horses

• mammalian hosts can acquire infection by either:
  • ingestion of oocytes from cats feaces or contaminated soil (only 1 oocyte may be required for humans, pigs and mice!)
  • ingestion of under-cooked or raw meat - especially lamb, but also beef, horse meat or raw shellfish (although unlike cats, mice and presumably humans may need to ingest > 100 bradyzoites to become infected)
    • it is easily killed by prior freezing for a few days or cooking meat to inner temp of 66degC (or medium cooked meat)
    • a study in 2020 showed that Australian lamb mince meat had over 40% chance of being infected⁴⁾
  • drinking unpasteurized goat's milk
  • congenital vertical transmission during pregnancy
    • only if newly acquired maternal infection, and highest risk of transmission is in 1st and 2nd TM
• cats are relatively immune to infection via ingestion of oocytes, but very sensitive to infection after eating raw meat with only one bradyzoite which then can result in the shedding of millions of oocytes in faeces

• babies most at risk are those born to mothers who acquired RECENT infection just before or during pregnancy
• may be asymptomatic at birth but present later in life
• hydrocephalus
• microcephalus
• seizures
• intracerebral calcification
• chorioretinitis

• 80-90% are asymptomatic
• however:
  • CNS infection may play a role in dementia, Parkinsons, etc.
    • Toxoplasma gondii infection of neurons alters the production and content of extracellular vesicles directing astrocyte phenotype and contributing to the loss of GLT-1 in the infected brain.⁵⁾

• cervical lymphadenopathy - usually nontender and < 3cm
• may have sore throat, fevers, myalgias
• may have retroperitoneal and mesenteric lymphadenopathy with abdominal pain
• splenomegaly
• may infect heart tissue, eyes
  • ocular infection may cause recurrent, usually unilateral (3/4 are unilateral) retinal inflammation (toxoplasmic retinochoroiditis) whether as a primary or reactivation of infection, resulting in characteristic retinal scars, and may complain of seeing floaters
    • prevalence in an Australian study was 1 in 149 people ⁶⁾
    • 60% may develop visual impairment and 25% become permanently blind
    • on resolution of any attack of inflammation, the individual is left with a pigmented retinal scar that has a highly typical clinical appearance, these may occur at any location across the retina although there is a tendency for the lesions (perhaps around 24% of lesions) to occur in the central retina, i.e., in the region of the macula and optic disc.
    • Pregnancy and cataract surgery have both been associated with an increased risk of reactivation
• neurologic symptomatic disease is rare in immunompetent adults and became evident in those with AIDS

• 50% develop CNS involvement which may cause seizure, vertigo, cranial nerve deficits, headache, focal neurology and altered mental state due to either encephalitis, meningoencephalitis or mass lesions
• may develop:
  • myocarditis
  • pneumonitis similar to P. carinii / jiroveci - dry cough, SOB, fever
  • organ specific reactivation toxoplasmosis esp. ocular

• usually subacute onset with focal neurology
• up to 25% have an acute onset with seizures or cerebral haemorrhage
• less common presentations include parkinsonian symptoms, neuropsychiatric, spinal cord
• untreated, late stage AIDS may develop pneumonitis +/- extrapulmonary toxoplasmosis

• ocular toxoplasmosis is one of the most common types (30-50%) of infectious uveitis, affecting the posterior pole in those countries of high endemicity of T. gondii infection, among 30-80% of human population ⁷⁾
• causes a progressive and recurring necrotizing retinitis although most cases with only peripheral lesions are self-limiting and regarded as not needing Rx
• if parasites reach an eye (usually via bloodstream) and they yield a focus of inflammation, the lesion is progressed to retinitis and involves the choroid secondarily
• the hallmark of the ocular lesion is retinitis, adjacent to an inactive retinochoroidal scar presumably due to rupture of a cyst in the scar
• complications include chronic iridocyclitis, cataract formation, secondary glaucoma, band keratopathy, cystoid macular oedema, retinal detachment, and optic atrophy secondary to optic nerve involvement
• diagnosis is largely clinical
  • suggestive fundoscopic appearances include:
    • headlights in fog appearance if severe vitiritis is present
    • white retinal reflex
    • retinal lesions
      • active lesions are seen as whitish foci of retinochoroiditis, frequently adjacent to a pigmented and/or atrophic scar
      • whitish inflammatory lesions located on the disc with associated vitritis is suggestive
  • serology is generally unhelpful as many are seropositive and asymptomatic
• Mx:
  • aim of the treatment is to arrest parasite multiplication during the active period of retinochoroiditis and to minimize damage to the retina and optic disc
  • usual Rx is pyrimethamine and sulfadiazine with corticosteroids