Toxoplasma gondii: Difference between revisions

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Toxoplasma gondii
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βˆ’
* Protozoan parasite associated with cats and raw beef mostly known for causing opportunistic infections and congenital infections
 +
*Protozoan parasite associated with cats and raw beef mostly known for causing opportunistic infections and congenital infections
   
βˆ’
== Microbiology ==
 +
==Background==
  +
===Microbiology===
   
βˆ’
* Protozoan parasite
 +
*Protozoan parasite
βˆ’
* Organized into twelve haplotypes
 +
*Organized into twelve haplotypes
   
βˆ’
== Epidemiology ==
 +
===Epidemiology===
   
βˆ’
* Zoonotic disease with worldwide distribution
 +
*Zoonotic disease with worldwide distribution
βˆ’
* Modes of transmission
 +
*Modes of transmission
βˆ’
** Ingesting tissue cysts in meat, or oocytes in food or water
 +
**Ingesting tissue cysts in meat, or oocytes in food or water
βˆ’
** Solid-organ transplantation, especially heart
 +
**Solid organ transplantation, especially heart
βˆ’
** Vertical or transplacental transmission
 +
**Vertical or transplacental transmission
βˆ’
** Case reports of lab-acquired needlestick transmission
 +
**Case reports of lab-acquired needlestick transmission
βˆ’
** Theoretical risk with blood transfusion
 +
**Theoretical risk with blood transfusion
βˆ’
* Seroprevalence around 10-18% in Canada [[CiteRef::shuhaiber2003se]][[CiteRef::ford-jones1996se]]
 +
*Seroprevalence around 10-18% in Canada [[CiteRef::shuhaiber2003se]][[CiteRef::ford-jones1996se]]
βˆ’
** As high as 60% in Nunavut, however [[CiteRef::messier2009se]]
 +
**As high as 60% in Nunavut, however [[CiteRef::messier2009se]]
βˆ’
* There are large parts of South and Central America, as well as Pacific Islands, that have very high seroprevalence [[CiteRef::pappas2009to]]
 +
*There are large parts of South and Central America, as well as Pacific Islands, that have very high seroprevalence [[CiteRef::pappas2009to]]
   
βˆ’
== Life Cycle ==
 +
===Life Cycle===
   
βˆ’
* The only definitive hosts are in the Felidae family, essentially housecats and their relatives
 +
*The only definitive hosts are in the Felidae family, essentially housecats and their relatives
βˆ’
* Intermediate hosts are many, and include birds and rodents
 +
*Intermediate hosts are many, and include birds and rodents
βˆ’
* An infected cat sheds oocytes into the environment (for 1 to 3 weeks), where they spend 1 to 5 days sporulating
 +
*An infected cat sheds oocytes into the environment (for 1 to 3 weeks), where they spend 1 to 5 days sporulating
βˆ’
** Each sporulated oocyst contains two sporocysts, and each sporocyst contains four sporozoites
 +
**Each sporulated oocyst contains two sporocysts, and each sporocyst contains four sporozoites
βˆ’
* Intermediate hosts ingest the sporozoites, where they mature into tachyzoites
 +
*Intermediate hosts ingest the sporozoites, where they mature into tachyzoites
βˆ’
* Tachyzoites migrate to brain and muscle, where they encyst and become bradyzoites
 +
*Tachyzoites migrate to brain and muscle, where they encyst and become bradyzoites
βˆ’
* Bradyzoites are ingested by a cat, completing the life cycle
 +
*Bradyzoites are ingested by a cat, completing the life cycle
   
βˆ’
== Pathophysiology ==
 +
===Pathophysiology===
   
βˆ’
* Following ingestion, bradyzoites and sporozoites invade the small intestinal mucosa and develop into tachyzoites within the gut epithelium
 +
*Following ingestion, bradyzoites and sporozoites invade the small intestinal mucosa and develop into tachyzoites within the gut epithelium
βˆ’
* There, they insert themselves into monocytes and other nucleated cells
 +
*There, they insert themselves into monocytes and other nucleated cells
βˆ’
* Infected cells travel throughout the body, carrying the tachyzoite with them
 +
*Infected cells travel throughout the body, carrying the tachyzoite with them
βˆ’
* Infection triggers a Th-1 response
 +
*Infection triggers a Th-1 response
   
βˆ’
== Clinical Presentation ==
 +
==Clinical Manifestations==
  +
===Immunocompetent===
   
  +
*Asymptomatic in 80% of primary infections
βˆ’
=== Immunocompetent ===
  
  +
*Symptoms, when they occur, can involve fever, cervical lymphadenopathy (painless and rubbery), myalgias, and weakness/fatigue
  +
**May mimic [[infectious mononucleosis]]
  +
*Can also cause [[chorioretinitis]]
  +
*Severity of illness depends in part on genotype, with strain II in North America and Europe being less severe
  +
**Rarely, unusual strains may cause pneumonitis, myocarditis, meningoencephalitis, or polymyositis, and can lead to death
   
  +
===Immunocompromised===
βˆ’
* Asymptomatic in 80% of primary infections
  
βˆ’
* Symptoms, when they occur, can involve fever, cervical lymphadenopathy, myalgias, and weakness/fatigue
  
βˆ’
** May mimic [[infectious mononucleosis]]
  
βˆ’
* Can also cause [[chorioretinitis]]
  
βˆ’
* Severity of illness depends in part on genotype, with strain II in North America and Europe being less severe
  
βˆ’
** Rarely, unusual strains may cause pneumonitis, myocarditis, meningoencephalitis, or polymyositis, and can lead to death
  
   
  +
*May be from primary infection or, more commonly, reactivation
βˆ’
=== Immunocompromised ===
  
  +
*Unlike in immunocompetent people, it is always a serious infection in the immunocompromised
  +
*Major risk factor is cellular immunodeficiency, as in HIV and some immunosuppressive medications
  +
**In HIV, beware with CD4 < 100
  +
*Typically presents with CNS involvement as '''encephalitis'''
  +
**Symptoms include fever, headache, lethargy, incoordination, ataxia, hemiparesis, loss of memory, dementia, or seizures
  +
*Can also present with pneumonitis (especially with bone marrow transplant), chorioretinitis, or myocarditis, and rarely involves essentially any other organ
   
  +
===Pregnancy===
βˆ’
* May be from primary infection or, more commonly, reactivation
  
βˆ’
* Unlike in immunocompetent people, it is always a serious infection in the immunocompromised
  
βˆ’
* Major risk factor is cellular immunodeficiency, as in HIV and some immunosuppressive medications
  
βˆ’
** In HIV, beware with CD4 < 100
  
βˆ’
* Typically presents with CNS involvement as '''encephalitis'''
  
βˆ’
** Symptoms include fever, headache, lethargy, incoordination, ataxia, hemiparesis, loss of memory, dementia, or seizures
  
βˆ’
* Can also present with pneumonitis, chorioretinitis, or myocarditis, and rarely involves essentially any other organ
  
   
  +
*As with other immunocompetent people, it is largely asymptomatic
βˆ’
=== Pregnancy ===
  
  +
*Refer to [[Toxoplasmosis in pregnancy]]
   
βˆ’
=== Congenital ===
 +
===Congenital===
   
  +
*Refer to [[Congenital toxoplasmosis]]
βˆ’
* 85% are asymptomatic at birth; 15% symptomatic
  
βˆ’
* Classic triad of chorioretinitis, intraparenchymal cerebral calcifications, and hydrocephalus
  
βˆ’
* Others: thrombocytopenia, hepatitis, hepatosplenomegaly
  
   
βˆ’
== Diagnosis ==
 +
==Diagnosis==
   
  +
*Immunocompetent or pregnant women with primary infection: IgG/IgM serology, possibly with avidity testing for pregnant women
βˆ’
== Management ==
  
  +
*Fetus, to rule out congenital infection following maternal primary infection: PCR of amniotic fluid
  +
*Newborn, to rule out congenital infection: PCR of placenta or cord, or serology
  +
*Immunocompromised patient, to diagnose cerebral or disseminated disease: PCR of blood, CSF, BAL, or tissue
  +
*Patient with chorioretinitis: Parallel serologies from aqueous humour and serum, or PCR of aqueous humour
   
  +
===Serology===
βˆ’
== Further Reading ==
  
   
  +
*Serology is the mainstay of diagnosis[[CiteRef::gangneux2012ep]]
βˆ’
* Epidemiology of and Diagnostic Strategies for Toxoplasmosis. ''Clin Microbiol Rev''. 2012;25(2):264. doi: [[https://doi.org/10.1128/CMR.05013-11 10.1128/CMR.05013-11]]
  
  +
*IgM antibodies
  +
**Detectable within 1 week, and titres plateau within 1 month and start decreasing after 1 to 6 months
  +
**IgM is still detectable for months or years after infection
  +
***Rarely, lost within 3 months
  +
***25% lost within 7 months
  +
***Often detectable for more than a year
  +
*IgG antibodies
  +
**Detectable 2 to 4 weeks after infection, and plateaus within 2 to 3 months
  +
**Declines but persists lifelong
  +
*IgG avidity testing can help to assess how recently the infection was acquired
  +
**Provides a measure of how tightly the antibodies bind, which is highest in early infection
  +
**A high avidity ratio (weak binding) suggests that the infection was acquired at least 4 months prior
  +
**Treatment delays avidity
  +
**Most useful during the first trimester of pregnancy, when high avidity effectively rules out acquisition during pregnancy
  +
  +
===PCR===
  +
  +
*Not routinely done
  +
*May be helpful from CSF, vitreous humour, or amniotic fluid
  +
*Not helpful on brain biopsy tissue
  +
  +
==Management==
  +
  +
=== Toxoplasmosis Encephalitis ===
  +
*In general, in the setting of known HIV and one or more suspicious lesions, treat empirically for CNS toxoplasmosis and reassess with repeat imaging at around 10 days, at which time there should be some response
  +
*First-line is a combination of [[Is treated by::pyrimethamine]] and [[Is treated by::sulfadiazine]], though that may be changing (see TMP-SMX, below)
  +
**[[Is treated by::Pyrimethamine]] (with folinic acid) is the backbone
  +
***[[Pyrimethamine]] 200 mg PO once followed by 50 mg PO daily if ≀60 kg or 75 mg PO daily if >60 kg
  +
***[[Leucovorin]] 10-25 mg PO daily
  +
**The second agent is typically [[Is treated by::sulfadiazine]], which can be replaced with [[Is treated by::clindamycin]] if needed
  +
***[[Sulfadiazine]] 1000 mg PO q6h if ≀60 kg or 1500 mg PO q6h if >60 kg
  +
***[[Clindamycin]] 600 mg PO/IV qid
  +
*Alternatives
  +
**[[Is treated by::TMP-SMX]]
  +
***Dose unclear; 40-120 mg/kg/day or 5 mg/kg (TMP component) p.o./IV every 8 hours
  +
***Likely safer than and as effective as the pyramethamine-based regimens<ref>Prosty C, Hanula R, Levin Y, Bogoch II, McDonald EG, Lee TC. Revisiting the Evidence Base for Modern Day Practice of the Treatment of Toxoplasmic Encephalitis: A Systematic Review and Meta-Analysis. Clin Infect Dis. 2022 Aug 9:ciac645. doi: 10.1093/cid/ciac645. Epub ahead of print. PMID: 35944134.</ref>
  +
***Given these new data, in the context of the difficulty and expense of obtainined pyramethamine, TMP-SMX may be considered first-line
  +
**[[Is treated by::Atovaquone]] 1500 mg PO bid + [[pyrimethamine]]
  +
**[[Atovaquone]] 1500 mg PO bid Β± [[sulfadiazine]]
  +
**[[Azithromycin]] 900-1200 mg PO daily + [[pyrimethamine]]
  +
  +
==== Patients with HIV ====
  +
*[[Is treated by::Pyrimethamine]] 200 mg PO once, followed by dose based on body weight:
  +
**Body weight ≀60 kg: [[Is treated by::pyrimethamine]] 50 mg PO daily + [[Is treated by::sulfadiazine]] 1000 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
  +
**Body weight >60 kg: [[Is treated by::pyrimethamine]] 75 mg PO daily + [[Is treated by::sulfadiazine]] 1500 mg PO q6h + leucovorin 10–25 mg PO daily (can increase to 50 mg daily or BID)
  +
*Alternatives
  +
**[[Is treated by::Pyrimethamine]] (with leucovorin) plus [[Is treated by::clindamycin]] 600 mg IV or PO q6h
  +
**[[Is treated by::TMP-SMX]] (TMP 5 mg/kg and SMX 25 mg/kg) (IV or PO) BID
  +
**[[Is treated by::Atovaquone]] 1500 mg PO BID + [[Is treated by::pyrimethamine]] (leucovorin)
  +
**[[Is treated by::Atovaquone]] 1500 mg PO BID + [[Is treated by::sulfadiazine]]
  +
**[[Is treated by::Atovaquone]] 1500 mg PO BID
  +
  +
===Pregnancy===
  +
  +
*Refer to [[Toxoplasmosis in pregnancy#Management|Toxoplasmosis in pregnancy]]
  +
  +
==Prevention==
  +
  +
*Cats: hand hygiene after handling cat, use gloves and wash hands when handling litter, wash litter tray with hot >60ΒΊC water, keep litter out of kitchen
  +
*Soil: use gloves for gardening, wash hands after soil contact
  +
*Water: avoid tap water in highly endemic countries, avoid ingestion of lake and river water
  +
*Food: avoid raw oysters/clams/mussels, wash all vegetables/fruits/herbs, cook meat well down
  +
  +
==Further Reading==
  +
  +
*Epidemiology of and Diagnostic Strategies for Toxoplasmosis. ''Clin Microbiol Rev''. 2012;25(2):264. doi: [[https://doi.org/10.1128/CMR.05013-11 10.1128/CMR.05013-11]]
   
 
{{DISPLAYTITLE:''Toxoplasma gondii''}}
  
{{DISPLAYTITLE:''Toxoplasma gondii''}}
βˆ’
[[Category:Prozotoa]]
 +
[[Category:Protozoa]]

Latest revision as of 11:16, 17 August 2022

  • Protozoan parasite associated with cats and raw beef mostly known for causing opportunistic infections and congenital infections

Background

Microbiology

  • Protozoan parasite
  • Organized into twelve haplotypes

Epidemiology

  • Zoonotic disease with worldwide distribution
  • Modes of transmission
    • Ingesting tissue cysts in meat, or oocytes in food or water
    • Solid organ transplantation, especially heart
    • Vertical or transplacental transmission
    • Case reports of lab-acquired needlestick transmission
    • Theoretical risk with blood transfusion
  • Seroprevalence around 10-18% in Canada 12
    • As high as 60% in Nunavut, however 3
  • There are large parts of South and Central America, as well as Pacific Islands, that have very high seroprevalence 4

Life Cycle

  • The only definitive hosts are in the Felidae family, essentially housecats and their relatives
  • Intermediate hosts are many, and include birds and rodents
  • An infected cat sheds oocytes into the environment (for 1 to 3 weeks), where they spend 1 to 5 days sporulating
    • Each sporulated oocyst contains two sporocysts, and each sporocyst contains four sporozoites
  • Intermediate hosts ingest the sporozoites, where they mature into tachyzoites
  • Tachyzoites migrate to brain and muscle, where they encyst and become bradyzoites
  • Bradyzoites are ingested by a cat, completing the life cycle

Pathophysiology

  • Following ingestion, bradyzoites and sporozoites invade the small intestinal mucosa and develop into tachyzoites within the gut epithelium
  • There, they insert themselves into monocytes and other nucleated cells
  • Infected cells travel throughout the body, carrying the tachyzoite with them
  • Infection triggers a Th-1 response

Clinical Manifestations

Immunocompetent

  • Asymptomatic in 80% of primary infections
  • Symptoms, when they occur, can involve fever, cervical lymphadenopathy (painless and rubbery), myalgias, and weakness/fatigue
  • Can also cause chorioretinitis
  • Severity of illness depends in part on genotype, with strain II in North America and Europe being less severe
    • Rarely, unusual strains may cause pneumonitis, myocarditis, meningoencephalitis, or polymyositis, and can lead to death

Immunocompromised

  • May be from primary infection or, more commonly, reactivation
  • Unlike in immunocompetent people, it is always a serious infection in the immunocompromised
  • Major risk factor is cellular immunodeficiency, as in HIV and some immunosuppressive medications
    • In HIV, beware with CD4 < 100
  • Typically presents with CNS involvement as encephalitis
    • Symptoms include fever, headache, lethargy, incoordination, ataxia, hemiparesis, loss of memory, dementia, or seizures
  • Can also present with pneumonitis (especially with bone marrow transplant), chorioretinitis, or myocarditis, and rarely involves essentially any other organ

Pregnancy

Congenital

Diagnosis

  • Immunocompetent or pregnant women with primary infection: IgG/IgM serology, possibly with avidity testing for pregnant women
  • Fetus, to rule out congenital infection following maternal primary infection: PCR of amniotic fluid
  • Newborn, to rule out congenital infection: PCR of placenta or cord, or serology
  • Immunocompromised patient, to diagnose cerebral or disseminated disease: PCR of blood, CSF, BAL, or tissue
  • Patient with chorioretinitis: Parallel serologies from aqueous humour and serum, or PCR of aqueous humour

Serology

  • Serology is the mainstay of diagnosis5
  • IgM antibodies
    • Detectable within 1 week, and titres plateau within 1 month and start decreasing after 1 to 6 months
    • IgM is still detectable for months or years after infection
      • Rarely, lost within 3 months
      • 25% lost within 7 months
      • Often detectable for more than a year
  • IgG antibodies
    • Detectable 2 to 4 weeks after infection, and plateaus within 2 to 3 months
    • Declines but persists lifelong
  • IgG avidity testing can help to assess how recently the infection was acquired
    • Provides a measure of how tightly the antibodies bind, which is highest in early infection
    • A high avidity ratio (weak binding) suggests that the infection was acquired at least 4 months prior
    • Treatment delays avidity
    • Most useful during the first trimester of pregnancy, when high avidity effectively rules out acquisition during pregnancy

PCR

  • Not routinely done
  • May be helpful from CSF, vitreous humour, or amniotic fluid
  • Not helpful on brain biopsy tissue

Management

Toxoplasmosis Encephalitis

  • In general, in the setting of known HIV and one or more suspicious lesions, treat empirically for CNS toxoplasmosis and reassess with repeat imaging at around 10 days, at which time there should be some response
  • First-line is a combination of pyrimethamine and sulfadiazine, though that may be changing (see TMP-SMX, below)
  • Alternatives
    • TMP-SMX
      • Dose unclear; 40-120 mg/kg/day or 5 mg/kg (TMP component) p.o./IV every 8 hours
      • Likely safer than and as effective as the pyramethamine-based regimens[1]
      • Given these new data, in the context of the difficulty and expense of obtainined pyramethamine, TMP-SMX may be considered first-line
    • Atovaquone 1500 mg PO bid + pyrimethamine
    • Atovaquone 1500 mg PO bid Β± sulfadiazine
    • Azithromycin 900-1200 mg PO daily + pyrimethamine

Patients with HIV

Pregnancy

Prevention

  • Cats: hand hygiene after handling cat, use gloves and wash hands when handling litter, wash litter tray with hot >60ΒΊC water, keep litter out of kitchen
  • Soil: use gloves for gardening, wash hands after soil contact
  • Water: avoid tap water in highly endemic countries, avoid ingestion of lake and river water
  • Food: avoid raw oysters/clams/mussels, wash all vegetables/fruits/herbs, cook meat well down

Further Reading

  • Epidemiology of and Diagnostic Strategies for Toxoplasmosis. Clin Microbiol Rev. 2012;25(2):264. doi: [10.1128/CMR.05013-11]
  1. ↑ Prosty C, Hanula R, Levin Y, Bogoch II, McDonald EG, Lee TC. Revisiting the Evidence Base for Modern Day Practice of the Treatment of Toxoplasmic Encephalitis: A Systematic Review and Meta-Analysis. Clin Infect Dis. 2022 Aug 9:ciac645. doi: 10.1093/cid/ciac645. Epub ahead of print. PMID: 35944134.

References

  1. ^  Samar Shuhaiber, Gideon Koren, Rada Boskovic, Thomas R Einarson, Offie Porat Soldin, Adrienne Einarson. Seroprevalence of Toxoplasma gondiiinfection among veterinary staff in Ontario, Canada (2002): Implications for teratogenic risk. BMC Infectious Diseases. 2003;3(1). doi:10.1186/1471-2334-3-8.
  2. ^  EL Ford-Jones, I Kitai, M Corey, R Notenboom, N Hollander, E Kelly, H Akoury, G Ryan, I Kyle, R Gold. Seroprevalence of Toxoplasma Antibody in a Toronto Population. Canadian Journal of Infectious Diseases. 1996;7(5):326-328. doi:10.1155/1996/172651.
  3. ^  V. Messier, B. LΓ©vesque, J.-F. Proulx, L. Rochette, M. D. Libman, B. J. Ward, B. Serhir, M. Couillard, N. H. Ogden, Γ‰. Dewailly, B. Hubert, S. DΓ©ry, C. Barthe, D. Murphy, B. Dixon. Seroprevalence of Toxoplasma gondii Among Nunavik Inuit (Canada). Zoonoses and Public Health. 2009;56(4):188-197. doi:10.1111/j.1863-2378.2008.01177.x.
  4. ^  Georgios Pappas, Nikos Roussos, Matthew E. Falagas. Toxoplasmosis snapshots: Global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis. International Journal for Parasitology. 2009;39(12):1385-1394. doi:10.1016/j.ijpara.2009.04.003.
  5. ^  K. Boyer, D. Hill, E. Mui, K. Wroblewski, T. Karrison, J. P. Dubey, M. Sautter, A. G. Noble, S. Withers, C. Swisher, P. Heydemann, T. Hosten, J. Babiarz, D. Lee, P. Meier, R. McLeod. Unrecognized Ingestion of Toxoplasma gondii Oocysts Leads to Congenital Toxoplasmosis and Causes Epidemics in North America. Clinical Infectious Diseases. 2011;53(11):1081-1089. doi:10.1093/cid/cir667.

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