Title: Toxoplasma gondii

{{Short description|Species of protozoan parasite}}
{{Use dmy dates|date=September 2023}}
{{Speciesbox
 |image=Toxoplasma gondii tachy.jpg
 |image_caption=[[Giemsa]] stained ''T. gondii'' [[tachyzoite]]s, 1000× magnification
 |display_parents=2
 |genus=Toxoplasma
 |parent_authority=[[Charles Nicolle|Nicolle]] &amp; [[Louis Manceaux|Manceaux]], 1909&lt;ref&gt;{{cite journal |last1=Nicolle |first1=C. |last2=Manceaux |first2=L. |date=1909 |title=Sur un Protozoaire nouveau du Gondi |language=fr |journal=Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences |volume=148 |issue=1 |pages=[https://archive.org/details/comptesrendusheb148acad/page/369 369]–72 |url= https://archive.org/details/comptesrendusheb148acad}}&lt;/ref&gt;
 |species=gondii
 |authority=(Nicolle &amp; Manceaux, 1908)&lt;ref&gt;{{cite journal |last1=Nicolle |first1=C. |last2=Manceaux |first2=L. |date=1908 |title=Sur une infection à corps de Leishman (ou organismes voisins) du Gondi |language=fr |journal=Comptes Rendus Hebdomadaires des Séances de l'Académie des Sciences |volume=147 |issue=2 |pages=[https://archive.org/details/comptesrendusheb147acad/page/763 763]–66 |url= https://archive.org/details/comptesrendusheb147acad}}&lt;/ref&gt;
}}
[[File:Toxoplasma gondii.jpg|thumb|Dividing ''T.&amp;nbsp;gondii'' parasites]]

'''''Toxoplasma gondii''''' ({{IPAc-en|ˈ|t|ɒ|k|s|ə|ˌ|p|l|æ|z|m|ə|_|ˈ|ɡ|ɒ|n|d|i|.|aɪ|,_|-|iː}}) is a species of parasitic [[alveolate]] that causes [[toxoplasmosis]].&lt;ref&gt;{{cite book |last1=Dardé |first1=M. L. |last2=Ajzenberg |first2=D. |last3=Smith |first3=J. |chapter=Population structure and epidemiology of ''Toxoplasma gondii'' |editor1-last=Weiss |editor1-first=L. M. |editor2-last=Kim |editor2-first=K. |title=Toxoplasma Gondii: The Model Apicomplexan. Perspectives and Methods |date=2011 |publisher=[[Elsevier]] |location=Amsterdam, Boston, Heidelberg, London, New York |pages=49–80 |isbn=978-0-12-369542-0 |doi=10.1016/B978-012369542-0/50005-2 |chapter-url= https://books.google.com/books?id=yTUkJEphM_IC&amp;pg=PA49}}&lt;/ref&gt; Found worldwide, ''T.&amp;nbsp;gondii'' is capable of infecting virtually all [[warm-blooded]] [[animal]]s,&lt;ref name=&quot;Dubey_2010&quot;&gt;{{cite book |last1=Dubey |first1=J. P. |title=Toxoplasmosis of Animals and Humans |date=2010 |edition=2nd |pages=1–20 |chapter=General Biology |chapter-url= https://books.google.com/books?id=5Nm7t5p9APAC&amp;pg=PA1 |access-date=1 February 2019 |publisher=Taylor and Francis Group |location=Boca Raton / London / New York |isbn=978-1-4200-9237-0}}&lt;/ref&gt;{{rp|1}} but members of the cat family ([[felidae]]) are the only known [[definitive host#Hosts to parasites|definitive host]]s in which the parasite may undergo sexual reproduction.&lt;ref&gt;{{cite web |title=CDC - Toxoplasmosis - Biology |url= https://www.cdc.gov/parasites/toxoplasmosis/biology.html |date=17 March 2015 |access-date=14 June 2015}}&lt;/ref&gt;&lt;ref name=&quot;Knoll 688580&quot;&gt;{{Cite journal |last1=Knoll |first1=Laura J. |last2=Dubey |first2=J. P. |last3=Wilson |first3=Sarah K. |last4=Genova |first4=Bruno Martorelli Di |date=1 July 2019 |title=Intestinal delta-6-desaturase activity determines host range for ''Toxoplasma'' sexual reproduction |journal=bioRxiv |doi=10.1101/688580 |doi-access=free}}&lt;/ref&gt;

In [[rodent]]s, ''T.&amp;nbsp;gondii'' [[Behavior-altering parasites and parasitoids|alters behavior]] in ways that increase the rodents' chances of being [[Predation|preyed]] upon by felids.&lt;ref name=&quot;Berdoy2000&quot;&gt;{{cite journal |last1=Berdoy |first1=M. |last2=Webster |first2=J. P. |last3=Macdonald |first3=D. W. |title=Fatal attraction in rats infected with ''Toxoplasma gondii'' |journal=Proceedings of the Royal Society of London B: Biological Sciences| volume=267 |issue=1452 |pages=1591–94 |date=August 2000 |pmid=11007336 |pmc=1690701 |doi=10.1098/rspb.2000.1182}}&lt;/ref&gt;&lt;ref name=&quot;Webster2007&quot;&gt;{{cite journal |last=Webster |first=J. P. |title=The effect of ''Toxoplasma gondii'' on animal behavior: playing cat and mouse |journal=Schizophrenia Bulletin |volume=33 |issue=3 |pages=752–756 |date=May 2007 |pmid=17218613 |pmc=2526137 |doi=10.1093/schbul/sbl073}}&lt;/ref&gt;&lt;ref name=&quot;Webster2013&quot;&gt;{{cite journal |last1=Webster |first1=J. P. |last2=Kaushik |first2=M. |last3=Bristow |first3=G. C. |last4=McConkey |first4=G. A. |title=Toxoplasma gondii infection, from predation to schizophrenia: can animal behaviour help us understand human behaviour? |journal=The Journal of Experimental Biology |volume=216 |issue=Pt 1 |pages=99–112 |date=January 2013 |pmid=23225872 |pmc=3515034 |doi=10.1242/jeb.074716|bibcode=2013JExpB.216...99W }}&lt;/ref&gt;  Support for this &quot;manipulation hypothesis&quot; stems from studies showing that ''T.&amp;nbsp;gondii''-infected rats have a decreased aversion to cat [[urine]] while infection in [[mice]] lowers general [[anxiety]], increases explorative [[behavior]]s and increases a loss of aversion to predators in general.&lt;ref name=&quot;Berdoy2000&quot; /&gt;&lt;ref name=&quot;doi.org&quot;&gt;{{cite journal |last1=Boillat |first1=M. |last2=Hammoudi |first2=P. M. |last3=Dogga |first3=S. K. |last4=Pagès |first4=S. |last5=Goubran |first5=M. |last6=Rodriguez |first6=I. |last7=Soldati-Favre |first7=D. |date=2020 |title=Neuroinflammation-associated Aspecific Manipulation of Mouse Predator Fear by ''Toxoplasma gondii'' |journal=Cell Reports |volume=30 |issue=2 |at=pp. 320–334.e6 |doi=10.1016/j.celrep.2019.12.019|doi-access=free |pmid=31940479 |pmc=6963786 }}&lt;/ref&gt; Because cats are one of the only hosts within which ''T.&amp;nbsp;gondii'' can sexually reproduce, such behavioral manipulations are thought to be [[Adaptation|evolutionary adaptations]] that increase the parasite's [[Fitness (biology)|reproductive success]] since rodents that do not avoid cat habitations will more likely become cat prey.&lt;ref name=&quot;Berdoy2000&quot; /&gt; The primary mechanisms of ''T.&amp;nbsp;gondii''–induced behavioral changes in rodents occur through [[epigenetic remodeling]] in neurons that govern the relevant behaviors.&lt;ref name=&quot;TG Masterpiece review&quot;&gt;{{cite journal |last1=Hari Dass |first1=S. A. |last2=Vyas |first2=A. |title=''Toxoplasma gondii'' infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala |journal=Molecular Ecology |volume=23 |issue=24 |pages=6114–22 |date=December 2014 |pmid=25142402 |doi=10.1111/mec.12888 |bibcode=2014MolEc..23.6114H |s2cid=45290208}}&lt;/ref&gt;&lt;ref name=&quot;Masterpiece of epigenetic engineering&quot;&gt;{{cite journal |last1=Flegr |first1=J. |last2=Markoš |first2=A. |title=Masterpiece of epigenetic engineering – how ''Toxoplasma gondii'' reprogrammes host brains to change fear to sexual attraction |journal=Molecular Ecology |volume=23 |issue=24 |pages=5934–5936 |date=December 2014 |pmid=25532868 |doi=10.1111/mec.13006 |s2cid=17253786 |doi-access=free|bibcode=2014MolEc..23.5934F }}&lt;/ref&gt;

In humans infection is generally asymptomatic, but particularly in infants and those with [[Immunocompromised|weakened immunity]], ''T.&amp;nbsp;gondii'' may lead to a serious case of [[toxoplasmosis]].&lt;ref name=&quot;CDCdisease&quot; /&gt;&lt;ref name=&quot;Dubey_2010&quot; /&gt; ''T.&amp;nbsp;gondii'' can initially cause mild, flu-like symptoms in the first few weeks following exposure, but otherwise, healthy human adults are asymptomatic.&lt;ref name=&quot;Global threat&quot; /&gt;&lt;ref name=&quot;CDCdisease&quot;&gt;{{cite web|title=CDC Parasites – Toxoplasmosis (Toxoplasma infection) Disease|url= https://www.cdc.gov/parasites/toxoplasmosis/disease.html|access-date=12 March 2013}}&lt;/ref&gt;&lt;ref name=&quot;Dubey_2010&quot; /&gt; This asymptomatic state of infection is referred to as a [[latent infection]], and it has been associated with numerous subtle behavioral, psychiatric, and personality alterations in humans.&lt;ref name=&quot;Global threat&quot; /&gt;&lt;ref&gt;{{cite journal |last1=Cook |first1=T. B. |last2=Brenner |first2=L. A. |last3=Cloninger |first3=C. R. |last4=Langenberg |first4=P. |last5=Igbide |first5=A. |last6=Giegling |first6=I. |last7=Hartmann |first7=A. M. |last8=Konte |first8=B. |last9=Friedl |first9=M. |last10=Brundin |first10=L. |last11=Groer |first11=M. W. |last12=Can |first12=A. |last13=Rujescu |first13=D. |last14=Postolache |first14=T. T. |title=&quot;Latent&quot; infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults |journal=Journal of Psychiatric Research |volume=60 |pages=87–94 |date=January 2015 |pmid=25306262 |doi=10.1016/j.jpsychires.2014.09.019}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Flegr |first1=J. |title=Influence of latent Toxoplasma infection on human personality, physiology and morphology: pros and cons of the Toxoplasma-human model in studying the manipulation hypothesis |journal=The Journal of Experimental Biology |volume=216 |issue=Pt 1 |pages=127–33 |date=January 2013 |pmid=23225875 |doi=10.1242/jeb.073635 |doi-access=free|bibcode=2013JExpB.216..127F }}&lt;/ref&gt; Behavioral changes observed between infected and non-infected humans include a decreased aversion to cat urine (but with divergent trajectories by gender) and an increased risk of [[schizophrenia]] and suicidal ideation.&lt;ref&gt;{{cite journal|title=Evolutionary puzzle of Toxoplasma gondii with suicidal ideation and suicide attempts: An updated systematic review and meta-analysis|date=9 April 2020|pmid=32198980 |last1=Amouei |first1=A. |last2=Moosazadeh |first2=M. |last3=Nayeri Chegeni |first3=T. |last4=Sarvi |first4=S. |last5=Mizani |first5=A. |last6=Pourasghar |first6=M. |last7=Hosseini Teshnizi |first7=S. |last8=Hosseininejad |first8=Z. |last9=Dodangeh |first9=S. |last10=Pagheh |first10=A. |last11=Pourmand |first11=A. H. |last12=Daryani |first12=A. |journal=Transboundary and Emerging Diseases |volume=67 |issue=5 |pages=1847–1860 |doi=10.1111/tbed.13550 |doi-access=free }}&lt;/ref&gt;&lt;ref name=&quot;pmid30685531&quot;&gt;{{cite journal |last1=Burgdorf |first1=K. S. |last2=Trabjerg |first2=B. B. |last3=Pedersen |first3=M. G. |last4=Nissen |first4=J. |last5=Banasik |first5=K. |last6=Pedersen |first6=O. B. |display-authors=etal |title=Large-scale study of Toxoplasma and Cytomegalovirus shows an association between infection and serious psychiatric disorders |journal=Brain, Behavior, and Immunity |date=2019 |volume=79 |pages=152–158 |pmid=30685531 |doi=10.1016/j.bbi.2019.01.026 |doi-access=free }}&lt;/ref&gt; Preliminary evidence has suggested that ''T.&amp;nbsp;gondii'' infection may induce some of the same alterations in the [[human brain]] as those observed in rodents.&lt;ref name=&quot;TG Neuronal&quot;&gt;{{cite journal |last1=Parlog |first1=A. |last2=Schlüter |first2=D. |last3=Dunay |first3=I. R. |title=Toxoplasma gondii-induced neuronal alterations |journal=Parasite Immunology |volume=37 |issue=3 |pages=159–70 |date=March 2015 |pmid=25376390 |doi=10.1111/pim.12157 |hdl=10033/346575 |s2cid=17132378}}&lt;/ref&gt;&lt;ref name=&quot;TG CNS&quot;&gt;{{cite journal |last1=Blanchard |first1=N. |last2=Dunay |first2=I. R. |last3=Schlüter |first3=D. |title=Persistence of Toxoplasma gondii in the central nervous system: a fine-tuned balance between the parasite, the brain and the immune system |journal=Parasite Immunology |volume=37 |issue=3 |pages=150–58 |date=March 2015 |pmid=25573476 |doi=10.1111/pim.12173 |hdl=10033/346515 |s2cid=1711188 |doi-access=free}}&lt;/ref&gt;&lt;ref name=&quot;Webster2013&quot; /&gt;&lt;ref&gt;{{cite journal |last1=Pearce |first1=B. D. |last2=Kruszon-Moran |first2=D. |last3=Jones |first3=J. L. |date=2012 |title=The Relationship Between Toxoplasma Gondii Infection and Mood Disorders in the Third National Health and Nutrition Survey |journal=Biological Psychiatry |volume=72 |issue=4| pages=290–95 |doi=10.1016/j.biopsych.2012.01.003 |pmid=22325983 |pmc=4750371}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=de Barros |first1=J. L. |last2=Barbosa |first2=I. G. |last3=Salem |first3=H. |last4=Rocha |first4=N. P. |last5=Kummer |first5=A. |last6=Okusaga |first6=O. O. |last7=Soares |first7=J. C. |last8=Teixeira |last9=A. L. |title=Is there any association between Toxoplasma gondii infection and bipolar disorder? A systematic review and meta-analysis |journal=Journal of Affective Disorders |volume=209 |pages=59–65 |date=February 2017 |pmid=27889597 |doi=10.1016/j.jad.2016.11.016}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Flegr |first1=J. |last2=Lenochová |first2=P. |last3=Hodný |first3=Z. |last4=Vondrová |first4=M |title=Fatal attraction phenomenon in humans: cat odour attractiveness increased for toxoplasma-infected men, but decreased for infected women |journal=PLOS Neglected Tropical Diseases |volume=5 |issue=11 |article-number=e1389 |date=November 2011 |pmid=22087345 |pmc=3210761 |doi=10.1371/journal.pntd.0001389 |doi-access=free}}&lt;/ref&gt;{{Excessive citations inline|date=February 2025}} Many of these associations have been strongly debated and newer studies have found them to be weak, concluding:&lt;ref&gt;{{cite journal |first1=Karen |last1=Sugden |first2=Terrie E. |last2=Moffitt |first3=Lauriane |last3=Pinto |first4=Richie |last4=Poulton |first5=Benjamin S. |last5=Williams |first6=Avshalom |last6=Caspi |title=Is Toxoplasma Gondii Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-Representative Birth Cohort |journal=PLOS ONE |volume=11 |issue=2 |article-number=e0148435 |date=17 February 2016 |doi=10.1371/journal.pone.0148435| pmid=26886853 |pmc=4757034 |bibcode=2016PLoSO..1148435S |doi-access=free}}&lt;/ref&gt;

{{Blockquote|On the whole, there was little evidence that ''T.{{nbsp}}gondii'' was related to increased risk of psychiatric disorder, poor impulse control, personality aberrations, or neurocognitive impairment.}}

''T. gondii'' is one of the most common parasites in developed countries;&lt;ref&gt;{{cite web|title=Cat parasite linked to mental illness, schizophrenia|date=5 June 2015 |url= http://www.cbsnews.com/news/cat-parasite-toxoplasma-gondii-linked-to-mental-illness-schizophrenia/|publisher=CBS|access-date=23 September 2015}}&lt;/ref&gt;&lt;ref&gt;{{cite web|title=CDC – About Parasites|url= https://www.cdc.gov/parasites/about.html|access-date=12 March 2013}}&lt;/ref&gt; [[Serology|serological]] studies estimate that up to 50% of the global population has been exposed to, and may be chronically infected with, ''T.&amp;nbsp;gondii''; although infection rates differ significantly from country to country.&lt;ref name=&quot;Global threat&quot;&gt;{{cite journal |last1=Flegr |first1=J. |last2=Prandota |first2=J. |last3=Sovičková |first3=M. |last4=Israili |first4=Z. H. |title=Toxoplasmosis – a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries |journal=PLOS ONE |volume=9 |issue=3 |article-number=e90203 |date=March 2014 |pmid=24662942 |pmc=3963851 |doi=10.1371/journal.pone.0090203 |quote=Toxoplasmosis is becoming a global health hazard as it infects 30–50% of the world human population. Clinically, the life-long presence of the parasite in tissues of a majority of infected individuals is usually considered asymptomatic. However, a number of studies show that this 'asymptomatic infection' may also lead to development of other human pathologies. ... The seroprevalence of toxoplasmosis correlated with various disease burden. Statistical associations does not necessarily mean causality. The precautionary principle suggests, however, that possible role of toxoplasmosis as a triggering factor responsible for development of several clinical entities deserves much more attention and financial support both in everyday medical practice and future clinical research. |bibcode=2014PLoSO...990203F |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Pappas |first1=G. |last2=Roussos |first2=N. |last3=Falagas |first3=M. E. |title=Toxoplasmosis snapshots: global status of Toxoplasma gondii seroprevalence and implications for pregnancy and congenital toxoplasmosis |journal=International Journal for Parasitology |volume=39 |issue=12 |pages=1385–94 |date=October 2009 |pmid=19433092 |doi=10.1016/j.ijpara.2009.04.003}}&lt;/ref&gt; Estimates have shown the highest IgG seroprevalence to be in [[Ethiopia]], at 64.2%, as of 2018.&lt;ref&gt;{{Cite journal |last1=Bigna |first1=Jean Joel |last2=Tochie |first2=Joel Noutakdie |last3=Tounouga |first3=Dahlia Noelle |last4=Bekolo |first4=Anne Olive |last5=Ymele |first5=Nadia S. |last6=Youda |first6=Emilie Lettitia |last7=Sime |first7=Paule Sandra |last8=Nansseu |first8=Jobert Richie |date=21 July 2020 |title=Global, regional, and country seroprevalence of ''Toxoplasma gondii'' in pregnant women: a systematic review, modelling and meta-analysis |journal=Scientific Reports |volume=10 |issue=1 |page=12102 |doi=10.1038/s41598-020-69078-9 |pmid=32694844 |pmc=7374101 |bibcode=2020NatSR..1012102B |issn=2045-2322}}&lt;/ref&gt;

== Structure ==

[[File:Toxplasma.png|thumb|right|Diagram of ''T.&amp;nbsp;gondii'' structure]]
''T. gondii'' contains organelles called [[rhoptry|rhoptries]] and [[microneme]]s. They contain proteins for invasion and effectors for manipulating the hosts immune response. To inject them into host cells, ''T. gondii'' uses the apical complex located in the tip of the cell to puncture the host membrane and discharge the contents of these organelles. The two microtubulins and their associated proteins inside the conoid of the apical complex facilitate this by organizing and docking the rhoptries to the complex. The mechanism underlying this is yet to be discovered fully but the roles of the microtubulins and the four associated proteins have been identified.&lt;ref name=&quot;Sustained rhoptry docking and disch&quot;&gt;{{cite journal |last1=Dos Santos Pacheco |first1=Nicolas |last2=Tell i Puig |first2=Albert |last3=Guérin |first3=Amandine |last4=Martinez |first4=Matthew |last5=Maco |first5=Bohumil |last6=Tosetti |first6=Nicolò |last7=Delgado-Betancourt |first7=Estefanía |last8=Lunghi |first8=Matteo |last9=Striepen |first9=Boris |last10=Chang |first10=Yi-Wei |last11=Soldati-Favre |first11=Dominique |title=Sustained rhoptry docking and discharge requires Toxoplasma gondii intraconoidal microtubule-associated proteins |journal=Nature Communications |date=2024 |volume=15 |issue=1 |page=379 |doi=10.1038/s41467-023-44631-y|pmid=38191574 |pmc=10774369 |bibcode=2024NatCo..15..379D }}&lt;/ref&gt;

== Life cycle ==

[[File:Toxoplasma gondii Life cycle PHIL 3421 lores.png|thumb|210px|Life cycle of ''Toxoplasma gondii'']]
[[File:Toxoplasmosis life cycle en.svg|thumb|210px|More detailed diagram. The feces of infected cats infects rodents hunted by cats, which rodents are more likely to be eaten by cats; it also infects animals bred for meat, which is a vector depending on how the meat is treated.]]
The [[Biological life cycle|life cycle]] of ''T.&amp;nbsp;gondii'' may be broadly summarized into two components: a sexual component that occurs only within cats (felids, wild or domestic), and an asexual component that can occur within virtually all warm-blooded animals, including humans, cats, and birds.&lt;ref name=&quot;Weiss_2011&quot;&gt;{{cite book |first1=Louis M |last1=Weiss |first2=Kami |last2=Kim |name-list-style=vanc |title=''Toxoplasma Gondii'': The Model Apicomplexan: Perspectives and Methods |url= https://books.google.com/books?id=yTUkJEphM_IC |access-date=12 March 2013 |date=2011 |publisher=Academic Press |isbn=978-0-08-047501-1 |edition=2nd}}&lt;/ref&gt;{{rp|2}} Because ''T.&amp;nbsp;gondii'' can sexually reproduce only within cats, cats are therefore the definitive host of ''T.&amp;nbsp;gondii''. All other hosts – in which only asexual reproduction can occur – are [[intermediate host]]s.

=== Sexual reproduction in the feline definitive host ===
When a feline is infected with ''T.&amp;nbsp;gondii'' (e.g. by consuming an infected mouse carrying the parasite's tissue cysts), the parasite survives passage through the [[stomach]], eventually infecting [[epithelial cell]]s of the cat's small intestine.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|39}} Inside these intestinal cells, the parasites undergo sexual development and reproduction, producing millions of thick-walled, [[zygote]]-containing cysts known as oocysts. Felines are the only definitive host because they lack expression of the enzyme [[delta-6-desaturase]] (D6D) in their intestine. This enzyme converts [[linoleic acid]]; the absence of expression allows systemic linoleic acid accumulation. Recent findings showed that this excess of linoleic acid is essential for ''T.&amp;nbsp;gondii'' sexual reproduction.&lt;ref name=&quot;Knoll 688580&quot; /&gt;

[[File:ToxoOocystFecalFlotation.jpg|thumb|''T. gondii'' [[oocysts]] in a [[fecal flotation]]|180px]]

=== Feline shedding of oocysts ===

Infected epithelial cells eventually rupture and release oocysts into the [[intestinal lumen]], whereupon they are shed in the cat's feces.&lt;ref name=&quot;Dubey_2010&quot; /&gt;{{rp|22}}  Oocysts can then spread to soil, water, food, or anything potentially contaminated with the feces. Highly resilient, oocysts can survive and remain infective for many months in cold and dry climates.&lt;ref&gt;{{cite journal |last1=Dubey |first1=J. P. |last2=Ferreira |first2=L. R. |last3=Martins |first3=J. |last4=Jones |first4=J. L. |s2cid=41292680 |title=Sporulation and survival of ''Toxoplasma gondii'' oocysts in different types of commercial cat litter |journal=The Journal of Parasitology |volume=97 |issue=5 |pages=751–54 |date=October 2011 |pmid=21539466 |doi=10.1645/GE-2774.1 |url= https://zenodo.org/record/1236371}}&lt;/ref&gt;

Ingestion of oocysts by humans or other warm-blooded animals is one of the common routes of infection.&lt;ref name=&quot;Dubey2009History&quot; /&gt;  Humans can be exposed to oocysts by, for example, consuming unwashed vegetables or contaminated water, or by handling the feces (litter) of an infected cat.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|2}}&lt;ref name=&quot;Kapperud1996&quot;&gt;{{cite journal |last1=Kapperud |first1=G. |last2=Jenum |first2=P. A. |last3=Stray-Pedersen |first3=B. |last4=Melby |first4=K. K. |last5=Eskild |first5=A. |last6=Eng |first6=J. |title=Risk factors for Toxoplasma gondii infection in pregnancy. Results of a prospective case-control study in Norway |journal=American Journal of Epidemiology |volume=144 |issue=4 |pages=405–12 |date=August 1996 |pmid=8712198 |doi=10.1093/oxfordjournals.aje.a008942 |doi-access=free}}&lt;/ref&gt;  Although cats can also be infected by ingesting oocysts, they are much less sensitive to oocyst infection than are intermediate hosts.&lt;ref&gt;{{cite journal |last=Dubey |first=J. P. |title=Advances in the life cycle of ''Toxoplasma gondii'' |journal=International Journal for Parasitology |volume=28 |issue=7 |pages=1019–24 |date=July 1998 |pmid=9724872 |doi=10.1016/S0020-7519(98)00023-X |url= https://zenodo.org/record/1259613}}&lt;/ref&gt;&lt;ref name=&quot;Dubey_2010&quot; /&gt;{{rp|107}}

=== Initial infection of the intermediate host ===

[[Intermediate host]]s found include pigs, chickens, goats, sheep&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|2}} and ''[[Macropus rufus]]'' by Moré et al. 2010.&lt;ref name=&quot;More-et-al-2017&quot;&gt;{{cite book |last1=Moré |first1=Gastón |last2=Venturini |first2=Maria Cecilia |last3=Pardini |first3=Lais |last4=Unzaga |first4=Juan Manuel |title=Parasitic Protozoa of Farm Animals and Pets |publisher=[[Springer International Publishing|Springer]] |publication-place=[[Cham, Switzerland]] |date=8 November 2017 |isbn=978-3-319-70131-8}}&lt;/ref&gt;{{rp|162}} [[Cattle]] and [[horse]]s are [[disease resistance|resistant]] and thought to be incapable of significant infection.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|11}} ''T.&amp;nbsp;gondii'' is considered to have three stages of infection; the tachyzoite stage of rapid division, the bradyzoite stage of slow division within tissue cysts, and the oocyst environmental stage.&lt;ref name=&quot;Robert-Gangneux2012&quot; /&gt; Tachyzoites are also known as &quot;tachyzoic merozoites&quot; and bradyzoites as &quot;bradyzoic merozoites&quot;.&lt;ref&gt;{{cite journal|last1=Markus |first1=M. B. |title=Terms for coccidian merozoites |journal=Annals of Tropical Medicine &amp; Parasitology |date=1987 |volume=81 |issue=4 |page=463 |doi=10.1080/00034983.1987.11812147 |pmid=3446034}}&lt;/ref&gt; When an oocyst or tissue cyst is ingested by a human or other warm-blooded animal, the resilient cyst wall is dissolved by [[Protease|proteolytic enzymes]] in the stomach and small intestine, freeing sporozoites from within the oocyst.&lt;ref name=&quot;Dubey2009History&quot; /&gt;&lt;ref name=&quot;Robert-Gangneux2012&quot; /&gt;  The parasites first invade cells in and surrounding the intestinal epithelium, and inside these cells, the parasites differentiate into tachyzoites, the motile and quickly multiplying cellular stage of ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|39}}  Tissue cysts in tissues such as brain and muscle tissue, form about 7–10 days after initial infection.&lt;ref name=&quot;Robert-Gangneux2012&quot; /&gt; Although severe infection of ''M. rufus'' has been observed it is unknown whether this is common.&lt;ref name=&quot;More-et-al-2017&quot; /&gt;

=== Asexual reproduction in the intermediate host ===

Inside host cells, the [[tachyzoites]] replicate inside specialized [[vacuole]]s (called the [[parasitophorous vacuole]]s) created from host cell membrane during invasion into the cell.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|23–39}}  Tachyzoites multiply inside this vacuole until the host cell dies and ruptures, releasing and spreading the tachyzoites via the bloodstream to all [[Organ (anatomy)|organs]] and tissues of the body, including the [[brain]].&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|39–40}}

=== Growth in tissue culture ===

The parasite can be easily grown in monolayers of mammalian cells maintained in vitro in [[tissue culture]]. It readily invades and multiplies in a wide variety of [[fibroblast]] and [[monocyte]] [[cell line]]s. In infected cultures, the parasite rapidly multiplies and thousands of tachyzoites break out of infected cells and enter adjacent cells, destroying the monolayer in due course. New monolayers can then be infected using a drop of this infected culture fluid and the parasite indefinitely maintained without the need of animals.

[[File:Toxoplasma gondii tissue cyst in mouse brain.jpg|thumb|''T. gondii'' tissue cyst in a mouse brain. Individual [[bradyzoite]]s can be seen within.]]

=== Formation of tissue cysts ===

Following the initial period of infection characterized by tachyzoite proliferation throughout the body, pressure from the host's [[immune system]] causes ''T.&amp;nbsp;gondii'' tachyzoites to convert into bradyzoites, the semi-[[Dormancy|dormant]], slowly [[Cellular division|dividing]] cellular stage of the parasite.&lt;ref name=&quot;Miller2009&quot;&gt;{{cite journal |last1=Miller |first1=C. M. |last2=Boulter |first2=N. R. |last3=Ikin |first3=R. J. |last4=Smith |first4=N. C. |title=The immunobiology of the innate response to ''Toxoplasma gondii'' |journal=International Journal for Parasitology |volume=39 |issue=1 |pages=23–39 |date=January 2009 |pmid=18775432 |doi=10.1016/j.ijpara.2008.08.002}}&lt;/ref&gt; Inside host cells, clusters of these bradyzoites are known as tissue cysts. The cyst wall is formed by the parasitophorous vacuole membrane.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|343}}  Although bradyzoite-containing tissue cysts can form in virtually any organ, tissue cysts predominantly form and persist in the brain, the [[eye]]s, and [[striated muscle]] (including the heart).&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|343}}  However, specific tissue tropisms can vary between intermediate host species; in pigs, the majority of tissue cysts are found in muscle tissue, whereas in mice, the majority of cysts are found in the brain.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|41}}

Cysts usually range in size between five and 50''&amp;nbsp;''[[micrometre|μm]] in diameter,&lt;ref&gt;{{cite web |title=CDC Toxoplasmosis – Microscopy Findings |url=http://www.dpd.cdc.gov/dpdx/HTML/Frames/S-Z/Toxoplasmosis/body_Toxoplasmosis_mic1.htm |access-date=13 March 2013 |archive-date=6 November 2013 |archive-url=https://web.archive.org/web/20131106080413/http://www.dpd.cdc.gov/dpdx/HTML/Frames/S-Z/Toxoplasmosis/body_Toxoplasmosis_mic1.htm }}&lt;/ref&gt; (with 50&amp;nbsp;μm being about two-thirds the width of the average human hair).&lt;ref name=&quot;Robbins2012&quot;&gt;{{cite book |first=Clarence R. |last=Robbins |title=Chemical and Physical Behavior of Human Hair |url= https://books.google.com/books?id=q3MGMTYAfu4C&amp;pg=PR7 |access-date=12 March 2013 |date=2012 |publisher=Springer |isbn=978-3-642-25610-3 |page=585}}&lt;/ref&gt;

Consumption of tissue cysts in meat is one of the primary means of ''T.&amp;nbsp;gondii'' infection, both for humans and for meat-eating, warm-blooded animals.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|3}}  Humans consume tissue cysts when eating raw or undercooked meat (particularly pork and lamb).&lt;ref&gt;{{cite journal |last1=Jones |first1=J. L. |last2=Dubey |first2=J. P. |title=Foodborne toxoplasmosis |journal=Clinical Infectious Diseases |volume=55 |issue=6 |pages=845–51 |date=September 2012 |pmid=22618566 |doi=10.1093/cid/cis508 |doi-access=free}}&lt;/ref&gt; Tissue cyst consumption is also the primary means by which cats are infected.&lt;ref name=&quot;Dubey_2010&quot; /&gt;{{rp|46}}

An exhibit at the [[San Diego Natural History Museum]] states [[urban runoff]] with cat feces transports ''Toxoplasma gondii'' into the ocean, which can kill sea otters.&lt;ref&gt;{{cite web|url=http://www-csgc.ucsd.edu/RESEARCH/PROJPROF_PDF/Conrad_CZ169.pdf|title=Parasite Shed in Cat Feces Kills Sea Otters – California Sea Grant|website=www-csgc.ucsd.edu|access-date=14 March 2018|archive-date=1 July 2010|archive-url=https://web.archive.org/web/20100701141220/http://www-csgc.ucsd.edu/RESEARCH/PROJPROF_PDF/Conrad_CZ169.pdf}}&lt;/ref&gt;

=== Chronic infection ===

Tissue cysts can be maintained in host tissue for the lifetime of the animal.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|580}}  However, the perpetual presence of cysts appears to be due to a periodic process of cyst rupturing and re-encysting, rather than a perpetual lifespan of individual cysts or bradyzoites.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|580}}  At any given time in a chronically infected host, a very small percentage of cysts are rupturing,&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|45}} although the exact cause of this tissue cyst rupture is, as of 2010, not yet known.&lt;ref name=&quot;Dubey_2010&quot; /&gt;{{rp|47}}

Theoretically, ''T.&amp;nbsp;gondii'' can be passed between intermediate hosts indefinitely via a cycle of consumption of tissue cysts in meat. However, the parasite's life cycle begins and completes only when the parasite is passed to a feline host, the only host within which the parasite can again undergo sexual development and reproduction.&lt;ref name=&quot;Dubey2009History&quot; /&gt;

=== Population structure in the wild ===
In 2006, researchers reviewed evidence that ''T.&amp;nbsp;gondii'' has an unusual population structure dominated by three clonal lineages called Types I, II and III that occur in North America and Europe, despite the occurrence of a sexual phase in its life cycle. They estimated that a common ancestor existed about 10,000 years ago.&lt;ref name=&quot;pmid16902086&quot;&gt;{{cite journal |last1=Khan |first1=A. |last2=Böhme |first2=U. |last3=Kelly |first3=K. A. |last4=Adlem |first4=E. |last5=Brooks |first5=K. |last6=Simmonds |first6=M. |last7=Mungall |first7=K. |last8=Quail |first8=M. A. |last9=Arrowsmith |first9=C. |last10=Chillingworth |first10=T. |last11=Churcher |first11=C. |last12=Harris |first12=D. |last13=Collins |first13=M. |last14=Fosker |first14=N. |last15=Fraser |first15=A. |last16=Hance |first16=Z. |last17=Jagels |first17=K. |last18=Moule |first18=S. |last19=Murphy |first19=L. |last20=O'Neil |first20=S. |last21=Rajandream |first21=M. A. |last22=Saunders |first22=D. |last23=Seeger |first23=K. |last24=Whitehead |first24=S. |last25=Mayr |first25=T. |last26=Xuan |first26=X. |last27=Watanabe |first27=J. |last28=Suzuki |first28=Y. |last29=Wakaguri |first29=H. |last30=Sugano |first30=S. |last31=Sugimoto |first31=C. |last32=Paulsen |first32=I. |last33=Mackey |first33=A. J. |last34=Roos |first34=D. S. |last35=Hall |first35=N. |last36=Berriman |first36=M. |last37=Barrell |first37=B. |last38=Sibley |first38=L. D. |last39=Ajioka |first39=J. W. |title=Common inheritance of chromosome Ia associated with clonal expansion of ''Toxoplasma gondii'' |journal=Genome Research |volume=16 |issue=9 |pages=1119–1125 |date=2006 |pmid=16902086 |pmc=1557770 |doi=10.1101/gr.5318106}}&lt;/ref&gt; Authors of a subsequent and larger study on 196 isolates from diverse sources including ''T.&amp;nbsp;gondii'' in the bald eagle, gray wolf, Arctic fox and sea otter, also found that ''T.&amp;nbsp;gondii'' strains infecting North American wildlife have limited genetic diversity with the occurrence of only a few major clonal types. They found that 85% of strains in North America were of one of three widespread genotypes II, III and Type 12. Thus ''T.&amp;nbsp;gondii'' has retained the capability for sex in North America over many generations, producing largely clonal populations, and matings have generated little genetic diversity.&lt;ref name=&quot;pmid21802422&quot;&gt;{{cite journal |last1=Dubey |first1=J. P. |last2=Velmurugan |first2=G. V. |last3=Rajendran |first3=C. |last4=Yabsley |first4=M. J. |last5=Thomas |first5=N. J. |last6=Beckmen |first6=K. B. |last7=Sinnett |first7=D. |last8=Ruid |first8=D. |last9=Hart |first9=J. |last10=Fair |first10=P. A. |last11=McFee |first11=W. E. |last12=Shearn-Bochsler |first12=V. |last13=Kwok |first13=O. C. |last14=Ferreira |first14=L. R. |last15=Choudhary |first15=S. |last16=Faria |first16=E. B. |last17=Zhou |first17=H. |last18=Felix |first18=T. A. |last19=Su |first19=C. |title=Genetic characterisation of ''Toxoplasma gondii'' in wildlife from North America revealed widespread and high prevalence of the fourth clonal type |journal=International Journal for Parasitology |volume=41 |issue=11 |pages=1139–1147 |date=2011 |pmid=21802422 |doi=10.1016/j.ijpara.2011.06.005 |bibcode=2011IJPar..41.1139D |s2cid=16654819 |url= https://zenodo.org/record/1259063}}&lt;/ref&gt;

== Cellular stages ==

During different periods of its life cycle, individual parasites convert into various cellular stages, with each stage characterized by a distinct cellular [[Morphology (biology)|morphology]], [[biochemistry]], and behavior. These stages include the tachyzoites, merozoites, bradyzoites (found in tissue cysts), and sporozoites (found in oocysts).

Some stages are [[motility|motile]] and some [[calcium-dependent protein kinase]]s ({{visible anchor|TgCDPK}}s) are involved in this parasite's motility.&lt;ref name=&quot;Frenal-et-al-2017&quot;&gt;{{cite journal |last1=Frénal |first1=Karine |last2=Dubremetz |first2=Jean-François |last3=Lebrun |first3=Maryse |last4=Soldati-Favre |first4=Dominique |title=Gliding motility powers invasion and egress in Apicomplexa |journal=[[Nature Reviews Microbiology]] |publisher=[[Nature Portfolio]] |volume=15 |issue=11 |date=4 September 2017 |issn=1740-1526 |doi=10.1038/nrmicro.2017.86 |pages=645–660 |pmid=28867819| s2cid=23129560 |url= https://archive-ouverte.unige.ch/unige:96648}}&lt;/ref&gt;&lt;ref name=&quot;Brochet-Billker-2016&quot;&gt;{{cite journal |last1=Brochet |first1=Mathieu |last2=Billker |first2=Oliver |title=Calcium signalling in malaria parasites |journal=[[Molecular Microbiology (journal)|Molecular Microbiology]] |publisher=[[Wiley (publisher)|Wiley]] |volume=100 |issue=3 |date=12 February 2016 |issn=0950-382X |doi=10.1111/mmi.13324 |pages=397–408| pmid=26748879 |s2cid=28504228 |doi-access=free}}&lt;/ref&gt; Gaji et al. 2015 find {{visible anchor|TgCDPK3}} is required to begin the action of motility because it [[phosphorylation|phosphorylates]] ''T.&amp;nbsp;gondii''{{'}}s [[myosin A|myosin''&amp;nbsp;''A]] ({{visible anchor|TgMYOA}}).&lt;ref name=&quot;Frenal-et-al-2017&quot; /&gt;&lt;ref name=&quot;Brochet-Billker-2016&quot; /&gt; TgCDPK3 is the functional orthologue of [[CDPK1]] in this parasite.&lt;ref name=&quot;Brochet-Billker-2016&quot; /&gt;

=== Tachyzoites ===
[[File:Parasite140105-fig3 Toxoplasmosis in a bar-shouldered dove - TEM of 2 tachyzoites.tif|thumb|Two tachyzoites, transmission electron microscopy&lt;ref name=&quot;RigouletHennache2014&quot; /&gt;]]

[[Motile]], and quickly multiplying, tachyzoites are responsible for expanding the population of the parasite in the host.&lt;ref name=&quot;RigouletHennache2014&quot;&gt;{{cite journal |last1=Rigoulet |first1=J. |last2=Hennache |first2=A. |last3=Lagourette |first3=P. |last4=George |first4=C. |last5=Longeart |first5=L. |last6=Le Net |first6=J. L. |last7=Dubey |first7=J. P. |title=Toxoplasmosis in a bar-shouldered dove (Geopelia humeralis) from the Zoo of Clères, France |journal=Parasite |volume=21 |page=62 |date=2014 |pmid=25407506 |pmc=4236686 |doi=10.1051/parasite/2014062}} {{open access}}&lt;/ref&gt;&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|19}}  When a host consumes a tissue cyst (containing bradyzoites) or an oocyst (containing sporozoites), the bradyzoites or sporozoites stage-convert into tachyzoites upon infecting the intestinal epithelium of the host.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|359}} During the initial acute period of infection, tachyzoites spread throughout the body via the blood stream.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|39–40}} During the later, latent (chronic) stages of infection, tachyzoites stage-convert to bradyzoites to form tissue cysts. To survive in the host, tachyzoites manipulate the immune response by injecting the contents of rhoptries into host cells. This seems to be vital for their survival, as knock-out strains of ''T. gondii'' which are unable to inject hosts with rhoptries have been shown to be avirulent ''in vivo''.&lt;ref name=&quot;Sustained rhoptry docking and disch&quot;/&gt;

=== Merozoites ===

[[File:ToxoCystUnstained.jpg|thumb|An unstained ''T.&amp;nbsp;gondii'' tissue cyst. [[Bradyzoite]]s can be seen within.|200px]]
Like tachyzoites, merozoites divide quickly and are responsible for expanding the population of the parasite inside the cat's intestine before sexual reproduction.&lt;ref name=&quot;Weiss_2011&quot; /&gt; When a feline definitive host consumes a tissue cyst (containing bradyzoites), bradyzoites convert into merozoites inside intestinal epithelial cells. Following a brief period of rapid population growth in the intestinal epithelium, merozoites convert into the noninfectious sexual stages of the parasite to undergo sexual reproduction, eventually resulting in zygote-containing oocysts.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|306}}

Studying the sexual phases of the ''T.&amp;nbsp;gondii'' life cycle remains challenging and determining the precise triggers and molecular mechanisms governing this developmental program remains an ongoing area of research. Major challenges associated with the ability to cultivate presexual and sexual stages of ''T.&amp;nbsp;gondii'' ''in vitro'' have limited our understanding of this developmental program and how it is triggered by the parasite in response to the infection of the cat. Multiple studies &lt;ref&gt;{{cite journal |last1=Hehl |first1=Adrian B. |last2=Basso |first2=Walter U. |last3=Lippuner |first3=Christoph |last4=Ramakrishnan |first4=Chandra |last5=Okoniewski |first5=Michal |last6=Walker |first6=Robert A. |last7=Grigg |first7=Michael E. |last8=Smith |first8=Nicholas C. |last9=Deplazes |first9=Peter |title=Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-overlapping gene families to attach, invade, and replicate within feline enterocytes |journal=BMC Genomics |date=13 February 2015 |volume=16 |issue=1 |page=66 |doi=10.1186/s12864-015-1225-x |doi-access=free |pmid=25757795 |pmc=4340605 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Behnke |first1=Michael S. |last2=Zhang |first2=Tiange P. |last3=Dubey |first3=Jitender P. |last4=Sibley |first4=L. David |title=Toxoplasma gondii merozoite gene expression analysis with comparison to the life cycle discloses a unique expression state during enteric development |journal=BMC Genomics |date=8 May 2014 |volume=15 |issue=1 |page=350 |doi=10.1186/1471-2164-15-350 |doi-access=free |pmid=24885521 |pmc=4035076 }}&lt;/ref&gt; revealed distinct differences in the [[transcriptome]]s of the asexual and sexual stages of ''T.&amp;nbsp;gondii''. Additionally, metabolic disparities within the feline host have been identified as key factors influencing the transition to sexual stages.&lt;ref&gt;{{cite journal |last1=Genova |first1=Bruno Martorelli Di |last2=Wilson |first2=Sarah K. |last3=Dubey |first3=J. P. |last4=Knoll |first4=Laura J. |title=Intestinal delta-6-desaturase activity determines host range for Toxoplasma sexual reproduction |journal=PLOS Biology |date=20 August 2019 |volume=17 |issue=8 |article-number=e3000364 |doi=10.1371/journal.pbio.3000364 |doi-access=free |pmid=31430281 |pmc=6701743 }}&lt;/ref&gt; However, linking gene expression patterns to stage transitions and deciphering the genetic triggers driving the switch from asexual to sexual development remain unresolved.

Important recent advancements in the field have shed new light on the regulatory mechanisms governing sexual development in ''T.&amp;nbsp;gondii''. Farhat and colleagues &lt;ref&gt;{{cite journal |last1=Farhat |first1=Dayana C. |last2=Swale |first2=Christopher |last3=Dard |first3=Céline |last4=Cannella |first4=Dominique |last5=Ortet |first5=Philippe |last6=Barakat |first6=Mohamed |last7=Sindikubwabo |first7=Fabien |last8=Belmudes |first8=Lucid |last9=De Bock |first9=Pieter-Jan |last10=Couté |first10=Yohann |last11=Bougdour |first11=Alexandre |last12=Hakimi |first12=Mohamed-Ali |title=A MORC-driven transcriptional switch controls Toxoplasma developmental trajectories and sexual commitment |journal=Nature Microbiology |date=April 2020 |volume=5 |issue=4 |pages=570–583 |doi=10.1038/s41564-020-0674-4 |pmid=32094587 |pmc=7104380 }}&lt;/ref&gt; showed that chromatin modifiers MORC and HDAC3 play critical roles in silencing sexual development-specific genes. In MORC-depleted parasites, a broad activation of sexual gene expression was observed. In a later study, it was suggested that MORC-depleted parasites have disrupted sub-telomeric gene silencing. The disorganization in telomeres may have led to the misregulation of sexual development.

Moreover, the discovery of specific transcription factors essential for sexual commitment has provided invaluable insights into the intricate regulatory network orchestrating stage specificity in ''T.&amp;nbsp;gondii''. Multiple parasite transcription factors have been identified as critical suppressors of presexual development,&lt;ref&gt;{{cite journal |last1=Antunes |first1=Ana Vera |last2=Shahinas |first2=Martina |last3=Swale |first3=Christopher |last4=Farhat |first4=Dayana C. |last5=Ramakrishnan |first5=Chandra |last6=Bruley |first6=Christophe |last7=Cannella |first7=Dominique |last8=Robert |first8=Marie G. |last9=Corrao |first9=Charlotte |last10=Couté |first10=Yohann |last11=Hehl |first11=Adrian B. |last12=Bougdour |first12=Alexandre |last13=Coppens |first13=Isabelle |last14=Hakimi |first14=Mohamed-Ali |date=11 January 2024 |title=In vitro production of cat-restricted Toxoplasma pre-sexual stages |journal=Nature |volume=625 |issue=7994 |pages=366–376 |doi=10.1038/s41586-023-06821-y|pmid=38093015 |pmc=10781626 |bibcode=2024Natur.625..366A }}&lt;/ref&gt; permitting the study of presexual stages and opening new avenues for using genetics to drive the full sexual cycle ''in vitro''. Specifically, the depletion of AP2XI-2 and AP2XII-1 in ''T.&amp;nbsp;gondii'' induces merozoite-specific gene expression, raising the possibility for cultivating ''T.&amp;nbsp;gondii'' sexual development in laboratory settings.

Crucial questions still persist regarding the genetic determinants that dictate whether parasites develop into macrogametes or microgametes. The development of new molecular and genomic approaches, such as single-cell transcriptomics and [[proteomics]], should be useful to those in the field working towards unraveling the molecular intricacies of this process.

=== Bradyzoites ===

Bradyzoites are the slowly dividing stage of the parasite that make up tissue cysts. When an uninfected host consumes a tissue cyst, bradyzoites released from the cyst infect intestinal epithelial cells before converting to the proliferative tachyzoite stage.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|359}} Following the initial period of proliferation throughout the host body, tachyzoites then convert back to bradyzoites, which reproduce inside host cells to form tissue cysts in the new host.

=== Sporozoites ===

Sporozoites are the stage of the parasite residing within oocysts. When a human or other warm-blooded host consumes an oocyst, sporozoites are released from it, infecting epithelial cells before converting to the proliferative tachyzoite stage.&lt;ref name=&quot;Weiss_2011&quot; /&gt;{{rp|359}}

== Immune response ==
Initially, a ''T.&amp;nbsp;gondii'' infection stimulates production of IL-2 and IFN-γ by the innate immune system.&lt;ref name=&quot;Miller2009&quot; /&gt; Continuous IFN-γ production is necessary for control of both acute and chronic ''T.&amp;nbsp;gondii'' infection.&lt;ref name=&quot;Miller2009&quot; /&gt; These two cytokines elicit a CD4+ and CD8+ T-cell mediated immune response.&lt;ref name=&quot;Miller2009&quot; /&gt; Thus, T-cells play a central role in immunity against ''Toxoplasma'' infection. T-cells recognize ''Toxoplasma'' antigens that are presented to them by the body's own Major Histocompatibility Complex (MHC) molecules. The specific genetic sequence of a given MHC molecule differs dramatically between individuals, which is why these molecules are involved in transplant rejection. Individuals carrying certain genetic sequences of MHC molecules are much more likely to be infected with ''Toxoplasma''. One study of &amp;gt;1600 individuals found that Toxoplasma infection was especially common among people who expressed certain MHC alleles (HLA-B*08:01, HLA-C*04:01, HLA-DRB 03:01, HLA-DQA*05:01 and HLA-DQB*02:01).&lt;ref&gt;{{cite journal |last1=Parks |first1=S. |last2=Avramopoulos |first2=D. |last3=Mulle |first3=J. |last4=McGrath |first4=J. |last5=Wang |first5=R. |last6=Goes |first6=F. S. |last7=Conneely |first7=K. |last8=Ruczinski |first8=I. |last9=Yolken |first9=R. |last10=Pulver |first10=A. E. |title=HLA typing using genome wide data reveals susceptibility types for infections in a psychiatric disease enriched sample |journal=Brain, Behavior, and Immunity |volume=70 |date=May 2018 |pages=203–213 |doi=10.1016/j.bbi.2018.03.001|pmid=29574260 |s2cid=4482168 }}&lt;/ref&gt;

IL-12 is produced during ''T.&amp;nbsp;gondii'' infection to activate [[Natural killer cell|natural killer (NK) cells]].&lt;ref name=&quot;Miller2009&quot; /&gt; [[Tryptophan]] is an essential amino acid for ''T.&amp;nbsp;gondii,'' which it scavenges from host cells. IFN-γ induces the activation of [[indole-amine-2,3-dioxygenase]] (IDO) and [[tryptophan-2,3-dioxygenase]] (TDO), two enzymes that are responsible for the degradation of tryptophan.&lt;ref name=&quot;Henriquez 2009&quot;&gt;{{cite journal |last1=Henriquez |first1=S. A. |last2=Brett |first2=R. |last3=Alexander |first3=J. |last4=Pratt |first4=J. |last5=Roberts |first5=C. W. |title=Neuropsychiatric disease and Toxoplasma gondii infection |journal=Neuroimmunomodulation |volume=16 |issue=2 |pages=122–133 |date=2009 |pmid=19212132 |doi=10.1159/000180267 |s2cid=7382051}}&lt;/ref&gt; Immune pressure eventually leads the parasite to form cysts that normally are deposited in the muscles and in the brain of the hosts.&lt;ref name=&quot;Miller2009&quot; /&gt;

=== Immune response and behavior alterations ===
The IFN-γ-mediated activation of IDO and TDO is an evolutionary mechanism that serves to starve the parasite, but it can result in depletion of tryptophan in the brain of the host. IDO and TDO degrade tryptophan to [[N'-Formylkynurenine|N-formylkynurenine]]. Administration of L-kynurenine is capable of inducing depressive-like behavior in mice.&lt;ref name=&quot;Henriquez 2009&quot; /&gt;  ''T.&amp;nbsp;gondii'' infection has been demonstrated to increase the levels of [[kynurenic acid]] (KYNA) in the brains of infected mice and in the brain of schizophrenic persons.&lt;ref name=&quot;Henriquez 2009&quot; /&gt; Low levels of tryptophan and [[serotonin]] in the brain were already associated with depression.&lt;ref&gt;{{cite journal |last1=Konsman |first1=J. P. |last2=Parnet |first2=P. |last3=Dantzer |first3=R. |title=Cytokine-induced sickness behaviour: mechanisms and implications |journal=Trends in Neurosciences |volume=25 |issue=3 |pages=154–59 |date=March 2002 |pmid=11852148 |doi=10.1016/s0166-2236(00)02088-9 |s2cid=29779184}}&lt;/ref&gt;

== Risk factors for human infection ==

The following have been identified as being [[Risk factor (epidemiology)|risk factor]]s for ''T.&amp;nbsp;gondii'' infection in humans and warm-blooded animals:
* by consuming raw or undercooked meat containing ''T.&amp;nbsp;gondii'' [[#Formation of tissue cysts|tissue cysts]].&lt;ref name=&quot;Kapperud1996&quot; /&gt;&lt;ref name=&quot;Tenter2000&quot;&gt;{{cite journal |last1=Tenter |first1=A. M. |last2=Heckeroth |first2=A. R. |last3=Weiss |first3=L. M. |title=''Toxoplasma gondii'': from animals to humans |journal=International Journal for Parasitology |volume=30 |issue=12–13 |pages=1217–58 |date=November 2000 |pmid=11113252 |pmc=3109627 |doi=10.1016/S0020-7519(00)00124-7}}&lt;/ref&gt;&lt;ref name=&quot;Jones2009risk&quot;&gt;{{cite journal |last1=Jones |first1=J. L. |last2=Dargelas |first2=V. |last3=Roberts |first3=J. |last4=Press |first4=C. |last5=Remington |first5=J. S. |last6=Montoya |first6=J. G. |title=Risk factors for Toxoplasma gondii infection in the United States |journal=Clinical Infectious Diseases |volume=49 |issue=6 |pages=878–84 |date=September 2009 |pmid=19663709 |doi=10.1086/605433 |doi-access=free}}&lt;/ref&gt;&lt;ref name=&quot;Cook2000&quot;&gt;{{cite journal |last1=Cook |first1=A. J. |last2=Gilbert |first2=R. E. |last3=Buffolano |first3=W. |last4=Zufferey |first4=J. |last5=Petersen |first5=E. |last6=Jenum |first6=P. A. |last7=Foulon |first7=W. |last8=Semprini |first8=A. E. |last9=Dunn |first9=D. T. |title=Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis |journal=BMJ |volume=321 |issue=7254 |pages=142–47 |date=July 2000 |pmid=10894691 |pmc=27431 |doi=10.1136/bmj.321.7254.142}}&lt;/ref&gt;&lt;ref name=Sakikawa2012&gt;{{cite journal |last1=Sakikawa |first1=M. |last2=Noda |first2=S. |last3=Hanaoka |first3=M. |last4=Nakayama |first4=H. |last5=Hojo |first5=S. |last6=Kakinoki |first6=S. |last7=Nakata |first7=M. |last8=Yasuda |first8=T. |last9=Ikenoue |first9=T. |last10=Kojima |first10=T. |title=Anti-Toxoplasma antibody prevalence, primary infection rate, and risk factors in a study of toxoplasmosis in 4,466 pregnant women in Japan |journal=Clinical and Vaccine Immunology |volume=19 |issue=3 |pages=365–67 |date=March 2012 |pmid=22205659 |pmc=3294603 |doi=10.1128/CVI.05486-11}}&lt;/ref&gt; The most common threat to citizens in the [[United States]] is from eating raw or undercooked pork.&lt;ref name=&quot;Dubey, J. P. 2005&quot;&gt;{{cite journal |last1=Dubey |first1=J. P. |last2=Hill |first2=D. E. |last3=Jones |first3=J. L. |last4=Hightower |first4=A. W. |last5=Kirkland |first5=E. |last6=Roberts |first6=J. M. |last7=Marcet |first7=P. L. |last8=Lehmann |first8=T. |last9=Vianna |first9=M. C. |last10=Miska |first10=K. |last11=Sreekumar |first11=C. |last12=Kwok |first12=O. C. |last13=Shen |first13=S. K. |last14=Gamble |first14=H. R. |title=Prevalence of viable Toxoplasma gondii in beef, chicken, and pork from retail meat stores in the United States: risk assessment to consumers |journal=The Journal of Parasitology |volume=91 |issue=5 |pages=1082–93 |date=October 2005 |pmid=16419752 |doi=10.1645/ge-683.1 |s2cid=26649961}}&lt;/ref&gt;
* by ingesting water, soil, vegetables, or anything contaminated with [[#Sexual reproduction in the feline definitive host|oocysts]] shed in the [[feces]] of an infected animal.&lt;ref name=&quot;Tenter2000&quot; /&gt; Cat fecal matter is particularly dangerous: Just one cyst consumed by a cat can result in thousands of oocysts. This is why physicians recommend pregnant or ill persons do not clean the cat's litter box at home.&lt;ref name=&quot;Dubey, J. P. 2005&quot; /&gt;  These oocysts are resilient to harsh environmental conditions and can survive over a year in contaminated soil.&lt;ref name=&quot;Robert-Gangneux2012&quot;&gt;{{cite journal |last1=Robert-Gangneux |first1=F. |last2=Dardé |first2=M. L. |title=Epidemiology of and diagnostic strategies for toxoplasmosis |journal=Clinical Microbiology Reviews |volume=25 |issue=2 |pages=264–96 |date=April 2012 |pmid=22491772 |pmc=3346298 |doi=10.1128/CMR.05013-11 |bibcode=2012CliMR..25..264R }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Mai |first1=K. |last2=Sharman |first2=P. A. |last3=Walker |first3=R. A. |last4=Katrib |first4=M. |last5=De Souza |first5=D. |last6=McConville |first6=M. J. |last7=Wallach |first7=M. G. |last8=Belli |first8=S. I. |last9=Ferguson |first9=D. J. |last10=Smith |first10=N. C. |title=Oocyst wall formation and composition in coccidian parasites |journal=Memórias do Instituto Oswaldo Cruz |volume=104 |issue=2 |pages=281–89 |date=March 2009 |pmid=19430654 |doi=10.1590/S0074-02762009000200022 |doi-access=free|hdl=1807/57649 |hdl-access=free }}&lt;/ref&gt;
* from a [[blood transfusion]] or [[organ transplant]]&lt;ref&gt;{{cite journal |last1=Siegel |first1=S. E. |last2=Lunde |first2=M. N. |last3=Gelderman |first3=A. H. |last4=Halterman |first4=R. H. |last5=Brown |first5=J. A. |last6=Levine |first6=A. S. |last7=Graw |first7=R. G. |title=Transmission of toxoplasmosis by leukocyte transfusion |journal=Blood |volume=37 |issue=4 |pages=388–94 |date=April 1971 |pmid=4927414 |doi=10.1182/blood.V37.4.388.388 |doi-access=free}}&lt;/ref&gt;
* from [[vertically transmitted infection|transplacental transmission]] from mother to fetus, particularly when ''T.&amp;nbsp;gondii'' is contracted during [[pregnancy]]&lt;ref name=&quot;Tenter2000&quot; /&gt;
* from drinking [[unpasteurized]] goat milk&lt;ref name=&quot;Jones2009risk&quot; /&gt;
* from raw and treated sewage and bivalve shellfish contaminated by treated sewage&lt;ref&gt;{{cite journal |last1=Gallas-Lindemann |first1=C. |last2=Sotiriadou |first2=I. |last3=Mahmoodi |first3=M. R. |last4=Karanis |first4=P. |title=Detection of Toxoplasma gondii oocysts in different water resources by Loop Mediated Isothermal Amplification (LAMP) |journal=Acta Tropica |volume=125 |issue=2 |pages=231–36 |date=February 2013 |pmid=23088835 |doi=10.1016/j.actatropica.2012.10.007}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Alvarado-Esquivel |first1=C. |last2=Liesenfeld |first2=O. |last3=Márquez-Conde |first3=J. A. |last4=Estrada-Martínez |first4=S. |last5=Dubey |first5=J. P. |s2cid=23241017 |title=Seroepidemiology of infection with Toxoplasma gondii in workers occupationally exposed to water, sewage, and soil in Durango, Mexico |journal=The Journal of Parasitology |volume=96 |issue=5 |pages=847–50 |date=October 2010 |pmid=20950091 |doi=10.1645/GE-2453.1}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Esmerini |first1=P. O. |last2=Gennari |first2=S. M. |last3=Pena |first3=H. F. |title=Analysis of marine bivalve shellfish from the fish market in Santos city, São Paulo state, Brazil, for Toxoplasma gondii |journal=Veterinary Parasitology |volume=170 |issue=1–2 |pages=8–13 |date=May 2010 |pmid=20197214 |doi=10.1016/j.vetpar.2010.01.036 |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Dattoli |first1=V. C. |last2=Veiga |first2=R. V. |last3=Cunha |first3=S. S. |last4=Pontes-de-Carvalho |first4=L. |last5=Barreto |first5=M. L. |last6=Alcantara-Neves |first6=N. M. |title=Oocyst ingestion as an important transmission route of Toxoplasma gondii in Brazilian urban children |journal=The Journal of Parasitology |volume=97 |issue=6 |pages=1080–84 |date=December 2011 |pmid=21740247 |doi=10.1645/GE-2836.1 |pmc=7612830 |s2cid=7170467 |url= https://www.arca.fiocruz.br/handle/icict/8292}}&lt;/ref&gt;

A common argument in the debate about whether cat ownership is ethical involves the question of ''T.&amp;nbsp;gondii'' transmission to humans.&lt;ref&gt;{{cite web |url= https://www.smithsonianmag.com/science-nature/moral-cost-of-cats-180960505/ |title=The Moral Cost of Cats |last=Gross |first=Rachel |date=20 September 2016 |website=Smithsonian Magazine |publisher=Smithsonian Institution |access-date=23 October 2020}}&lt;/ref&gt; Even though &quot;living in a household with a cat that used a [[litter box]] was strongly associated with infection,&quot;&lt;ref name=&quot;Kapperud1996&quot; /&gt; and that living with several kittens or any cat under one year of age has some significance,&lt;ref name=&quot;Jones2009risk&quot; /&gt; several other studies claim to have shown that living in a household with a cat is not a significant risk factor for ''T.&amp;nbsp;gondii'' infection.&lt;ref name=&quot;Cook2000&quot; /&gt;&lt;ref&gt;{{cite journal |last1=Bobić |first1=B. |last2=Jevremović |first2=I. |last3=Marinković |first3=J. |last4=Sibalić |first4=D. |last5=Djurković-Djaković |first5=O. |s2cid=9423818 |title=Risk factors for Toxoplasma infection in a reproductive age female population in the area of Belgrade, Yugoslavia |journal=European Journal of Epidemiology |volume=14 |issue=6 |pages=605–10 |date=September 1998 |pmid=9794128 |doi=10.1023/A:1007461225944}}&lt;/ref&gt;

Specific vectors for transmission may also differ based on geographic location. &quot;The seawater in California is thought to be contaminated by ''T.&amp;nbsp;gondii'' oocysts that originate from cat feces, survive or bypass sewage treatment, and travel to the coast through river systems. ''T.&amp;nbsp;gondii'' has been identified in a California mussel by polymerase chain reaction and DNA sequencing. In light of the potential presence of ''T.&amp;nbsp;gondii'', pregnant women and immunosuppressed persons should be aware of this potential risk associated with eating raw oysters, mussels, and clams.&quot;&lt;ref name=&quot;Jones2009risk&quot; /&gt;

In warm-blooded animals, such as [[brown rat]]s, sheep, and dogs, ''T.&amp;nbsp;gondii'' has also been shown to be sexually transmitted.&lt;ref&gt;{{cite journal |last1=Dass |first1=S. A. |last2=Vasudevan |first2=A. |last3=Dutta |first3=D. |last4=Soh |first4=L. J. |last5=Sapolsky |first5=R. M. |last6=Vyas |first6=A. |title=Protozoan parasite ''Toxoplasma gondii'' manipulates mate choice in rats by enhancing attractiveness of males |journal=PLOS ONE |volume=6 |issue=11 |article-number=e27229 |date=2011 |pmid=22073295 |pmc=3206931 |doi=10.1371/journal.pone.0027229 |bibcode=2011PLoSO...627229D |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Arantes |first1=T. P. |last2=Lopes |first2=W. D. |last3=Ferreira |first3=R. M. |last4=Pieroni |first4=J. S. |last5=Pinto |first5=V. M. |last6=Sakamoto |first6=C. A. |last7=Costa |first7=A. J. |title=''Toxoplasma gondii'': Evidence for the transmission by semen in dogs |journal=Experimental Parasitology |volume=123 |issue=2 |pages=190–94 |date=October 2009 |pmid=19622353 |doi=10.1016/j.exppara.2009.07.003}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |first1=Gutierrez |last1=J. |last2=O'Donovan |first2=J. |last3=Williams |first3=E. |last4=Proctor |first4=A. |last5=Brady |first5=C. |last6=Marques |first6=P. X. |last7=Worrall |first7=S. |last8=Nally |first8=J. E. |last9=McElroy |first9=M. |last10=Bassett |first10=H. |last11=Sammin |first11=D. |last12=Buxton |first12=D. |last13=Maley |first13=S. |last14=Markey |first14=B. K. |title=Detection and quantification of ''Toxoplasma gondii'' in ovine maternal and foetal tissues from experimentally infected pregnant ewes using real-time PCR |journal=Veterinary Parasitology |volume=172 |issue=1–2 |pages=8–15 |date=August 2010 |pmid=20510517 |doi=10.1016/j.vetpar.2010.04.035}}&lt;/ref&gt; Although ''T.&amp;nbsp;gondii'' can infect, be transmitted by, and [[Asexual reproduction|asexually reproduce]] within humans and virtually all other warm-blooded animals, the parasite can [[Sexual reproduction|sexually reproduce]] only within the [[intestine]]s of members of the [[Felidae|cat family (felids)]].&lt;ref name=&quot;Dubey2009History&quot;&gt;{{cite journal |last=Dubey |first=J. P. |title=History of the discovery of the life cycle of ''Toxoplasma gondii'' |journal=International Journal for Parasitology |volume=39 |issue=8 |pages=877–82 |date=July 2009 |pmid=19630138 |doi=10.1016/j.ijpara.2009.01.005}}&lt;/ref&gt;  Felids are therefore the [[Host (biology)|definitive hosts]] of ''T.&amp;nbsp;gondii''; all other hosts (such as human or other mammals) are [[intermediate host]]s.

== Preventing infection ==

The following precautions are recommended to prevent or greatly reduce the chances of becoming infected with ''T.&amp;nbsp;gondii''. This information has been adapted from the websites of United States [[Centers for Disease Control and Prevention]]&lt;ref name=&quot;CDCPrevention&quot;&gt;{{cite web|title=CDC: Parasites – Toxoplasmosis (Toxoplasma infection) – Prevention &amp; Control|url= https://www.cdc.gov/parasites/toxoplasmosis/prevent.html|access-date=13 March 2013}}&lt;/ref&gt; and the [[Mayo Clinic]].&lt;ref name=MayoClinicPrevention&gt;{{cite web|title=Mayo Clinic – Toxoplasmosis – Prevention|url= http://www.mayoclinic.com/health/toxoplasmosis/DS00510/DSECTION=prevention|access-date=13 March 2013}}&lt;/ref&gt;

=== From food ===
Basic [[food-handling safety]] practices can prevent or reduce the chances of becoming infected with ''T.&amp;nbsp;gondii'', such as washing unwashed fruits and vegetables, and avoiding raw or undercooked meat, poultry, and seafood. Other unsafe practices such as drinking unpasteurized milk or untreated water can increase odds of infection.&lt;ref name=&quot;CDCPrevention&quot; /&gt; As ''T.&amp;nbsp;gondii'' is commonly transmitted through ingesting microscopic cysts in the tissues of infected animals, meat that is not prepared to destroy these presents a risk of infection. Freezing meat for several days at subzero temperatures (0&amp;nbsp;°F or −18&amp;nbsp;°C) before cooking may break down all cysts, as they rarely survive these temperatures.&lt;ref name=&quot;Dubey_2010&quot; /&gt;{{rp|45}} During cooking, whole cuts of red meat should be cooked to an internal temperature of at least {{convert|145|°F|°C|abbr=on}}.  [[Doneness|Medium rare]] meat is generally cooked between {{convert|130|and|140|F|C}},&lt;ref name=&quot;fieldguide&quot;&gt;{{cite book |first=Aliza |last=Green |date=2005 |title=Field Guide to Meat |url= https://archive.org/details/fieldguidetomeat0000gree |url-access=registration |publisher=Quirk Books| location=Philadelphia, PA |pages=[https://archive.org/details/fieldguidetomeat0000gree/page/294 294–95] |isbn=978-1-59474-017-6}}&lt;/ref&gt; so cooking meat to at least [[Doneness|medium]] is recommended. After cooking, a rest period of 3 min should be allowed before consumption. However, ground meat should be cooked to an internal temperature of at least {{convert|160|°F|°C|abbr=on}} with no rest period. All poultry should be cooked to an internal temperature of at least {{convert|165|°F|°C|abbr=on}}. After cooking, a rest period of 3 min should be allowed before consumption.

=== From environment ===
{{More citations needed section|date=February 2023}}
Oocysts in cat feces take at least a day to [[sporulate]] (to become infectious after they are shed), so disposing of cat litter daily greatly reduces the chance of infectious oocysts developing. As these can spread and survive in the environment for months, humans should wear gloves when gardening or working with soil, and should wash their hands promptly after disposing of cat litter. These precautions apply to outdoor sandboxes/play sand pits, which should be covered when not in use. Cat feces should never be flushed down a toilet.

Pregnant women are at higher risk of transmitting the parasite to their unborn child and [[immunocompromised]] people of acquiring a lingering infection. Because of this, they should not change or handle cat litter boxes. Ideally, cats should be kept indoors and fed only food that has low to no risk of carrying oocysts, such as commercial cat food or well-cooked table food.

=== Vaccination ===
No approved human vaccine exists against ''Toxoplasma gondii''.&lt;ref name=&quot;pmid36310233&quot;&gt;{{cite journal |vauthors=Zhang Y, Li D, Lu S, Zheng B |title=Toxoplasmosis vaccines: what we have and where to go? |journal=npj Vaccines |volume=7 |issue=1 |article-number=131 |date=October 2022 |pmid=36310233 |pmc=9618413 |doi=10.1038/s41541-022-00563-0}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Verma |first1=R. |last2=Khanna |first2=P. |title=Development of Toxoplasma gondii vaccine: A global challenge |journal=Human Vaccines &amp; Immunotherapeutics |volume=9 |issue=2 |pages=291–93 |date=February 2013 |pmid=23111123 |pmc=3859749 |doi=10.4161/hv.22474}}&lt;/ref&gt; Research on human vaccines is ongoing.&lt;ref name=&quot;pmid36310233&quot;/&gt;&lt;ref&gt;{{cite web |url=http://cordis.europa.eu/result/rcn/151498_en.html |title=TOXPOX Result In Brief – Vaccine against Toxoplasmosis |publisher=CORDIS, European Commission |date=14 January 2015 |access-date=11 December 2015 |archive-date=22 December 2015 |archive-url=https://web.archive.org/web/20151222142502/http://cordis.europa.eu/result/rcn/151498_en.html }}&lt;/ref&gt;

For [[sheep]], an approved live vaccine sold as Toxovax (from [[Merck &amp; Co.|MSD Animal Health]]) provides lifetime protection.&lt;ref name=&quot;pmid36310233&quot;/&gt;&lt;ref&gt;{{cite web |url=http://www.sheepvax.co.nz/risk-factors/risk-factors-for-toxoplasmosis/ |title=TOXOVAX® |publisher=MSD Animal Health |access-date=10 November 2015 |archive-date=22 January 2016 |archive-url=https://web.archive.org/web/20160122230713/http://www.sheepvax.co.nz/risk-factors/risk-factors-for-toxoplasmosis/ }}&lt;/ref&gt;&lt;ref name=&quot;pmid36090161&quot;&gt;{{cite journal |vauthors=Hasan T, Nishikawa Y |title=Advances in vaccine development and the immune response against toxoplasmosis in sheep and goats |journal=Frontiers in Veterinary Science |volume=9 |issue= |article-number=951584 |date=2022 |pmid=36090161 |pmc=9453163 |doi=10.3389/fvets.2022.951584|doi-access=free}}&lt;/ref&gt;

There is currently no commercially available vaccine to prevent ''T.&amp;nbsp;gondii'' infection in cats. However, research into feline vaccines for toxoplasmosis is ongoing, with several candidates showing positive results in clinical trials.&lt;ref name=&quot;pmid36310233&quot;/&gt;&lt;ref name=&quot;pmid31926434&quot;&gt;{{cite journal |vauthors=Bonačić Marinović AA, Opsteegh M, Deng H, Suijkerbuijk AW, van Gils PF, van der Giessen J |title=Prospects of toxoplasmosis control by cat vaccination |journal=Epidemics |volume=30 |article-number=100380 |date=December 2019 |pmid=31926434 |doi=10.1016/j.epidem.2019.100380|doi-access=free }}&lt;/ref&gt;

== Treatment ==
{{Main|Toxoplasmosis#Treatment}}
In humans, active toxoplasmosis can be treated with a combination of drugs such as [[pyrimethamine]] and [[sulfadiazine]], plus [[folinic acid]]. Immune-compromised patients may need continuous treatment until/unless their immune system is restored. There is no known human treatment for chronic infections.&lt;ref&gt;{{cite web|url= https://www.cdc.gov/parasites/toxoplasmosis/treatment.html |title=CDC - Toxoplasmosis - Treatment |date=28 February 2019 |publisher=U.S. Centers for Disease Control |access-date=13 July 2021}}&lt;/ref&gt;

The most significant limitation of current clinical treatments is their inability to eliminate the dormant bradyzoite tissue cysts established during chronic infection. These cysts persist in the brain and muscle tissues, making the infection lifelong and prone to reactivation in immunocompromised hosts, such as those with HIV/AIDS or undergoing immunosuppressive therapy.&lt;ref&gt;Toxoplasmosis: Current and Emerging Parasite Druggable Targets - MDPI. [https://www.mdpi.com/2076-2607/9/12/2531 Link to Source]&lt;/ref&gt; 

While not approved for these uses, a large amount of [[antipsychotic]] medications are known to kill ''T.&amp;nbsp;gondii'' tachyzoites in [[In vitro|in-vitro]] cultures of human brain tissue. Examples include [[fluphenazine]], [[Valproate|valproic acid]],&lt;ref name=&quot;Fond 179–183&quot;&gt;{{Cite journal |last1=Fond |first1=Guillaume |last2=Macgregor |first2=Alexandra |last3=Tamouza |first3=Ryad |last4=Hamdani |first4=Nora |last5=Meary |first5=Alexandre |last6=Leboyer |first6=Marion |last7=Dubremetz |first7=Jean-Francois |date=2014-03-01 |title=Comparative analysis of anti-toxoplasmic activity of antipsychotic drugs and valproate |journal=European Archives of Psychiatry and Clinical Neuroscience |language=en |volume=264 |issue=2 |pages=179–183 |doi=10.1007/s00406-013-0413-4 |pmid=23771405 |issn=1433-8491 |url=https://inserm.hal.science/inserm-00844714 }}&lt;/ref&gt; [[haloperidol]],&lt;ref&gt;{{Cite journal |last1=Jones-Brando |first1=Lorraine |last2=Torrey |first2=E. Fuller |last3=Yolken |first3=Robert |date=2003-08-01 |title=Drugs used in the treatment of schizophrenia and bipolar disorder inhibit the replication of Toxoplasma gondii |url=https://www.sciencedirect.com/science/article/pii/S0920996402003572 |journal=Schizophrenia Research |volume=62 |issue=3 |pages=237–244 |doi=10.1016/S0920-9964(02)00357-2 |pmid=12837520 |issn=0920-9964|url-access=subscription }}&lt;/ref&gt; and [[zuclopenthixol]].&lt;ref name=&quot;Fond 179–183&quot;/&gt; It is unclear if tissue cysts are killed by these.

Some experimental and established [[antiparasitic]] medication is known to kill tissue cysts in in-vitro mice cells, with an example of an established drug being [[azithromycin]].&lt;ref&gt;{{Cite journal |last1=Montazeri |first1=Mahbobeh |last2=Mehrzadi |first2=Saeed |last3=Sharif |first3=Mehdi |last4=Sarvi |first4=Shahabeddin |last5=Shahdin |first5=Shayesteh |last6=Daryani |first6=Ahmad |date=2018-10-01 |title=Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review |journal=Parasitology Research |language=en |volume=117 |issue=10 |pages=3045–3057 |doi=10.1007/s00436-018-6027-z |issn=1432-1955}}&lt;/ref&gt;

There is no evidence that the administration of antiparasitics, including [[azithromycin]], helps those diagnosed with schizophrenia (see [[Toxoplasma gondii#Behavioral differences of infected hosts|Behavioral differences of infected hosts]]).&lt;ref&gt;{{Cite journal |last=Chorlton |first=Sam D. |date=2017-07-01 |title=Toxoplasma gondii and schizophrenia: a review of published RCTs |journal=Parasitology Research |language=en |volume=116 |issue=7 |pages=1793–1799 |doi=10.1007/s00436-017-5478-y |issn=1432-1955}}&lt;/ref&gt;

== Environmental effects ==
In many parts of the world, where there are high populations of feral cats, there is an increased risk to the native wildlife due to increased infection of ''Toxoplasma gondii''. It has been found that the serum concentrations of ''T.&amp;nbsp;gondii'' in the wildlife population were increased where there are high amounts of cat populations. This creates a dangerous environment for organisms that have not evolved in cohabitation with felines and their contributing parasites.&lt;ref&gt;{{cite journal |last1=Hollings |first1=T. |last2=Jones |first2=M. |last3=Mooney |first3=N. |last4=McCallum |first4=H. |date=2013 |title=Wildlife disease ecology in changing landscapes: Mesopredator release and toxoplasmosis |journal=International Journal for Parasitology: Parasites and Wildlife |volume=2 |pages=110–118|doi=10.1016/j.ijppaw.2013.02.002 |pmid=24533323 |pmc=3862529 |bibcode=2013IJPPW...2..110H }}&lt;/ref&gt;

=== Impact on marine species ===
==== Cetaceans ====
Toxoplasmosis has been implicated in the deaths of various cetacean species, such as the critically endangered [[Māui dolphin]] and [[Hector's dolphin]] found in New Zealand.&lt;ref&gt;{{cite news |last1=Clark-Dow |first1=Emma |title=Dolphin found on Auckland beach died of disease often spread by cats |url=https://www.stuff.co.nz/environment/300856491/dolphin-found-on-auckland-beach-died-of-disease-often-spread-by-cats#:~:text=M%C4%81ui%20dolphins%20are%20one%20of,and%20oil%20exploration%20and%20toxoplasmosis.&amp;text=The%20Government%20committed%20$4.88%20million,and%20reduce%20storm%20water%20runoff. |publisher=Stuff NZ |date=April 18, 2023}}&lt;/ref&gt;&lt;ref name=&quot;Solomon_2013&quot;&gt;{{cite news |last1=Solomon |first1=Christopher |title=How Kitty Is Killing the Dolphins |url=https://www.scientificamerican.com/article/pathogens-from-humans-cats-kill-seals-dolphins/ |publisher=Scientific American |date=May 1, 2013}}&lt;/ref&gt; With only 54 Māui dolphins over the age of one remaining, ''T. gondii'' is considered a significant human-caused threat to the dolphins' populations.&lt;ref&gt;{{cite web |title=Toxoplasmosis and Hector's and Māui dolphin |url=https://www.doc.govt.nz/nature/pests-and-threats/diseases/toxoplasmosis-and-hectors-and-maui-dolphin/ |website=New Zealand Department of Conservation/Te Papa Atawhai}}&lt;/ref&gt; Fatal cases of ''T. gondii'' have also been confirmed among [[spinner dolphin]]s off the coast of Hawaii, among [[bottlenose dolphin]]s, [[Risso's dolphin]]s, and [[striped dolphin]]s along the Mediterranean coast, among [[Indo-Pacific humpback dolphin]]s in Australia, and again among free-ranging bottlenose dolphins in Brazil.&lt;ref&gt;{{cite journal |last1=Landrau-Giovannetti |first1=Nelmarie |title=Prevalence and genotype of Toxoplasma gondii in stranded Hawaiian cetaceans |journal=Diseases of Aquatic Organisms |date=2022 |volume=152 |pages=27–36|doi=10.3354/dao03699 |pmid=36394138 |doi-access=free }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Di Guardo |first1=Giovanni |title=Toxoplasma gondii: Clues From Stranded Dolphins |journal=Veterinary Pathology |date=2013 |volume=50 |issue=5 |page=737|doi=10.1177/0300985813486816 |pmid=24014612 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Resendes |first1=A. R |title=Disseminated toxoplasmosis in a Mediterranean pregnant Risso's dolphin (Grampus griseus) with transplacental fetal infection |journal=The Journal of Parasitology |date=2002 |volume=88 |issue=5 |pages=1029–1032|doi=10.1645/0022-3395(2002)088[1029:DTIAMP]2.0.CO;2 |pmid=12435153 }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Bowater |first1=R. O |title=Toxoplasmosis in Indo-Pacific humpbacked dolphins (Sousa chinensis), from Queensland |journal=Australian Veterinary Journal |date=2003 |volume=81 |issue=10 |pages=627–632|doi=10.1111/j.1751-0813.2003.tb12509.x |pmid=15080475 |url=http://era.daf.qld.gov.au/id/eprint/470/ }}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Costa-Silva |first1=Samira |title=Toxoplasma gondii in cetaceans of Brazil: a histopathological and immunohistochemical survey |journal=Brazilian Journal of Veterinary Parasitology |date=2019 |volume=28 |issue=3 |pages=395–402|doi=10.1590/S1984-29612019051 |pmid=31411314 |doi-access=free |hdl=11449/183823 |hdl-access=free }}&lt;/ref&gt;

A 2011 study of 161 Pacific Northwest marine mammals ranging from a [[sperm whale]] to [[harbor porpoise]]s that had either become stranded or died found that 42 percent tested positive for both ''T. gondii'' and ''S. neurona''.&lt;ref name=&quot;Solomon_2013&quot; /&gt; Approximately 14 per cent of the western Arctic [[beluga whale]] population is believed to asymptomatically carry ''T. gondii'' with a few deaths attributed to the infection.&lt;ref&gt;{{cite news |last1=Gosnell |first1=Jennifer |title=Arctic belugas infected by kitty litter disease |url=https://canadiangeographic.ca/articles/arctic-belugas-infected-by-kitty-litter-disease/ |publisher=Canadian Geographic |date=March 25, 2014}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Iqbal |first1=Asma |title=Toxoplasma gondii infection in stranded St. Lawrence Estuary beluga Delphinapterus leucas in Quebec, Canada |journal=Diseases of Aquatic Organisms |date=September 2018 |volume=130 |issue=3 |pages=165–175|doi=10.3354/dao03262 |pmid=30259869 }}&lt;/ref&gt;

==== Minks and otters ====
Toxoplasmosis is one of the contributing factors toward mortality in southern [[sea otter]]s, especially in areas where there is large urban run-off.&lt;ref name=&quot;Conrad, P. 2005&quot;&gt;{{cite journal |last1=Conrad |first1=P. A. |last2=Miller |first2=M. A. |last3=Kreuder |first3=C. |last4=James |first4=E. R. |last5=Mazet |first5=J. |last6=Dabritz |first6=H. |last7=Jessup |first7=D. A. |last8=Gulland |first8=Frances |last9=Grigg |first9=M. E. |date=October 2005 |title=Transmission of ''Toxoplasma'': Clues from the study of sea otters as sentinels of ''Toxoplasma gondii'' flow into the marine environment |journal=International Journal for Parasitology |volume=35 |issue=11–12 |pages=1155–1168 |doi=10.1016/j.ijpara.2005.07.002|pmid=16157341 }}&lt;/ref&gt; In their natural habitats, sea otters control sea urchin populations and, thus indirectly, control sea kelp forests. By enabling the growth of sea kelp, other marine populations are protected as well as CO&lt;sub&gt;2&lt;/sub&gt; emissions are reduced due to the kelp's ability to absorb atmospheric carbon.&lt;ref&gt;{{cite web |work=Defenders of Wildlife |date=2020 |title=Sea Otter |url= https://defenders.org/wildlife/sea-otter}}&lt;/ref&gt; An examination on 105 beachcast otters revealed that 38.1% had parasitic infections, and 28% of said infections had resulted in protozoal meningoencephalitis deaths.&lt;ref name=&quot;Conrad, P. 2005&quot; /&gt; ''Toxoplasma gondii'' was found to be the root cause in 16.2% of these deaths, while 6.7% of the deaths were due to a closely related protozoan parasite known as ''[[Sarcocystis neurona]]''.&lt;ref name=&quot;Conrad, P. 2005&quot; /&gt;

Minks, being semiaquatic, are also susceptible to infection and being antibody-positive toward ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Ahlers, A. A. 2015&quot;&gt;{{cite journal |last1=Ahlers |first1=Adam A. |last2=Mitchell |first2=Mark A. |last3=Dubey |first3=Jitender P. |last4=Schooley |first4=Robert L. |last5=Heske |first5=Edward J. |date=1 April 2015 |title=Risk Factors for ''Toxoplasma gondii'' Exposure in Semiaquatic Mammals in a Freshwater Ecosystem |journal=Wildlife Diseases |volume=51 |issue=2 |pages=488–492|doi=10.7589/2014-03-071 |pmid=25574808 }}&lt;/ref&gt; Minks can follow a similar diet as otters and feasts on crustaceans, fish, and invertebrates, thus the transmission route follows a similar pattern to otters. Because of the mink's ability to transverse land more frequently, and often seen as an invasive species itself, minks are a bigger threat in transporting ''T.&amp;nbsp;gondii'' to other mammalian species, rather than otters who have a more restrictive breadth.&lt;ref name=&quot;Ahlers, A. A. 2015&quot; /&gt;

==== Other marine mammals ====
''T. gondii'' has killed at least twelve endangered [[Hawaiian monk seal]]s.&lt;ref name=&quot;Solomon_2013&quot; /&gt;&lt;ref&gt;{{cite web |title=The Toll of Toxoplasmosis: Protozoal Disease Has Now Claimed the Lives of 12 Monk Seals and Left Another Fighting to Survive |url=https://www.fisheries.noaa.gov/feature-story/toll-toxoplasmosis-protozoal-disease-has-now-claimed-lives-12-monk-seals-and-left |website=NOAA Fisheries |date=29 August 2024 |publisher=National Marine Fisheries Service}}&lt;/ref&gt; There has been a documented fatal case in a [[West Indian manatee]].&lt;ref&gt;{{cite journal |last1=Bonde |first1=Robert |title=Toxoplasmic meningoencephalitis in a West Indian manatee |journal=Journal of the American Veterinary Medical Association |date=1984 |volume=183 |issue=11 |pages=1294–6|pmid=6643252 }}&lt;/ref&gt;

==== Black-footed penguins ====
Although under-studied, penguin populations, especially those that share an environment with the human population, are at-risk due to parasite infections, mainly ''Toxoplasma gondii''. The main subspecies of penguins found to be infected by ''T.&amp;nbsp;gondii'' include wild Magellanic and Galapagos penguins, as well as blue and African penguins in captivity.&lt;ref name=&quot;Acosta et al. 2019&quot;&gt;{{cite journal |last1=Acosta |first1=I. C. L. |last2=Souza-Filho |first2=A. F. |last3=Muñoz-Leal |first3=S. |last4=Soares |first4=H. S. |last5=Heinemann |first5=M. B. |last6=Moreno |first6=L. |last7=González-Acuña |first7=D. |last8=Gennari |first8=S. M. |date=April 2019 |title=Evaluation of antibodies against ''Toxoplasma gondii'' and ''Leptospira'' spp. in Magellanic penguins (''Speniscus magellanicus'') on Magdalena Island, Chile |journal=Veterinary Parasitology: Regional Studies and Reports |volume=16 |pages=1–4|article-number=100282 |doi=10.1016/j.vprsr.2019.100282 |pmid=31027597 |s2cid=91996679 }}&lt;/ref&gt; In one study, 57 (43.2%) of 132 serum samples of Magellanic penguins were found to have ''T.&amp;nbsp;gondii''. The island that the penguin is located, Magdalena Island, is known to have no cat populations, but a very frequent human population, indicating the possibility of transmission.&lt;ref name=&quot;Acosta et al. 2019&quot; /&gt;

==== Histopathology ====
Examination of black-footed penguins with toxoplasmosis reveals hepatomegaly, splenomegaly, cranial hemorrhage, and necrotic kidneys.&lt;ref name=&quot;Ploeg, M. 2011&quot; /&gt; Alveolar and hepatic tissue presents a high number of immune cells such as macrophages containing tachyzoites of ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Ploeg, M. 2011&quot;&gt;{{cite journal |last1=Ploeg |first1=M. |last2=Ultee |first2=T. |last3=Kik |first3=M. |date=2011 |title=Disseminated Toxoplasmosis in Black-footed Penguins (''Spheniscus demersus'') |journal=Avian Diseases |volume=55 |issue=4 |pages=701–703 |doi=10.1637/9700-030411-Case.1|pmid=22312996 |s2cid=31105636 }}&lt;/ref&gt;  Histopathological features in other animals affected with toxoplasmosis had tachyzoites in eye structures such as the retina which lead to blindness.&lt;ref name=&quot;Ploeg, M. 2011&quot; /&gt;

== Water transmission ==
The transmission of oocysts has been unknown, even though there have many documented cases of infection in marine species. Researchers have found that the oocytes of ''T.&amp;nbsp;gondii'' can survive in seawater for at least six months, with the amount of salt concentration not affecting its life cycle. There have been no studies on the ability of ''T.&amp;nbsp;gondii'' oocysts life cycle within freshwater environments, although infections are still present. One possible hypothesis of transmission is via amoeba species, particularly ''Acanthamoeba'' spp., a species that is found in all water environments (fresh, brackish, and full-strength seawater). Normally, amoebas function as a natural filter, phagocytizing nutrients and bacteria found within the water. Some pathogens have used this to their advantage, however, and evolved to be able to avoid being broken down and, thus, survive encased in the amoeba – this includes Holosporaceae, Pseudomonaceae, Burkholderiacceae, among others.&lt;ref&gt;{{cite journal |last1=Greub |first1=Gilbert |last2=Raoult |first2=Didier |date=April 2004 |title=Microorganisms Resistant to Free-living Amoebae |journal=Clinical Microbiology Reviews |volume=17 |issue=2 |pages=413–433 |doi=10.1128/CMR.17.2.413-433.2004|pmid=15084508 |pmc=387402 }}&lt;/ref&gt; Overall, this aids the pathogen in transportation but, also, protection from drugs and sterilizers that would, otherwise, cause death in the pathogen.&lt;ref&gt;{{cite journal |last1=Cirillo |first1=Jeffrey D. |last2=Falkow |first2=Stanley |last3=Tompkins |first3=Lucy S. |last4=Bermundez |first4=Luiz E. |date=September 1997 |title=Interaction of ''Mycobacterium avium'' with environmental amoebae enhances virulence |journal=Infection and Immunity |volume=65 |issue=9 |pages=3759–3767 |doi=10.1128/iai.65.9.3759-3767.1997|doi-access=free |pmid=9284149 |pmc=175536 }}&lt;/ref&gt; Studies have shown that ''T.&amp;nbsp;gondii'' oocysts can live within amoebas after being engulfed for at least 14 days without significant obliteration of the parasite.&lt;ref name=&quot;Winiecka-Krusnell, J. 2009&quot;&gt;{{cite journal |last1=Winiecka-Krusnell |first1=Jadwiga |last2=Dellacasa-Lindberg |first2=Isabel |last3=Dubey |first3=J. P. |last4=Barragan |first4=Antonio |date=February 2009 |title=''Toxoplasma gondii'': Uptake and survival of oocysts in free-living amoebae |journal=Experimental Parasitology |volume=121 |issue=2 |pages=124–131 |doi=10.1016/j.exppara.2008.09.022|pmid=18992742 }}&lt;/ref&gt; The ability of the microorganism to survive in vitro is dependent on the microorganism itself, but there are a few overarching mechanisms present. ''T.&amp;nbsp;gondii'' oocysts have been found to resist an acidic pH and, thus, are protected by the acidification found in endocytic vacuoles and lysosomes.&lt;ref name=&quot;Winiecka-Krusnell, J. 2009&quot; /&gt; Phagocytosis further increases with the carbohydrate-rich surface membrane located on the amoebae.&lt;ref&gt;{{cite journal |last1=Elloway |first1=E. A. G. |last2=Armstrong |first2=R. A. |last3=Bird |first3=R. A. |last4=Kelly |first4=S. L. |last5=Smith |first5=S. N. |date=1 December 2004 |title=Analysis of ''Acanthamoeba polyphaga'' surface carbohydrate exposure by FITC-lectin binding and fluorescence evaluation |journal=Journal of Applied Microbiology |volume=97 |issue=6 |pages=1319–1325 |doi=10.1111/j.1365-2672.2004.02430.x|pmid=15546423 |s2cid=23877072 }}&lt;/ref&gt; The pathogen can be released either by lysis of the amoebae or by exocytosis, but this is understudied &lt;ref&gt;{{cite journal |last1=Paquet |first1=Valérie E. |last2=Charette |first2=Steve J. |date=8 February 2016 |title=Amoeba-resisting bacteria found in multilamellar bodies secreted by ''Dictyostelium discoideum'': Social amoebae can also package bacteria |journal=FEMS Microbiology Ecology |volume=92 |issue=3 |article-number=fiw025 |doi=10.1093/femsec/fiw025|doi-access=free |pmid=26862140 |hdl=20.500.11794/313 |hdl-access=free }}&lt;/ref&gt;

== Impact on wild birds ==
Almost all species of birds that have been tested for ''Toxoplasma gondii'' have shown to be positive. The only bird species not reported with clinical symptoms of toxoplasmosis would be wild ducks, and there has only been one report found on domesticated ducks occurring in 1962.&lt;ref&gt;{{cite journal |last1=Boehringer |first1=Emilio Geronimo |last2=Fornari |first2=Oscar Elias |last3=Boehringer |first3=Irene K. |date=November 1962 |title=The first case of ''T. gondii'' in domestic ducks in Argentina |journal=Avian Diseases |volume=6 |issue=4 |pages=391–396 |doi=10.2307/1587913|jstor=1587913 }}&lt;/ref&gt; Species with resistance toward ''T.&amp;nbsp;gondii'' include domestic turkeys,&lt;ref&gt;{{cite journal |last1=Drobeck |first1=Hans Peter |last2=Manwell |first2=Reginald D. |last3=Bernstein |first3=Emil |last4=Dillon |first4=Raymond D. |date=November 1953 |title=Further studies of toxoplasmosis in birds |journal=American Journal of Epidemiology |volume=59 |issue=3 |pages=329–339 |doi=10.1016/S0304-4017(02)00034-1|pmid=12031816 }}&lt;/ref&gt; owls, red tail hawks, and sparrows, depending on the strain of ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Dubey, J. 2002&quot;&gt;{{cite journal |last=Dubey |first=J. P. |date=June 2002 |title=A review of toxoplasmosis in wild birds |journal=Veterinary Parasitology |volume=106 |issue=2 |pages=121–153 |doi=10.1016/S0304-4017(02)00034-1|pmid=12031816 }}&lt;/ref&gt; ''T.&amp;nbsp;gondii'' is considerably more severe in pigeons, particularly crown pigeons, ornamental pigeons, and pigeons originating from Australia and New Zealand. Typical onset is quick and usually results in death. Those that do survive often have chronic conditions of encephalitis and neuritis.&lt;ref name=&quot;Dubey, J. 2002&quot; /&gt; Similarly, canaries are observed to be just as severe as pigeons, but the clinical symptoms are more abnormal when compared to other species. Most of the infection affects the eye, causing blindness, choroidal lesions, conjunctivitis, atrophy of the eye, blepharitis, and chorioretinitis &lt;ref name=&quot;Dubey, J. 2002&quot; /&gt; Most of the time, the infection leads to death. Research by Michael Grigg, chief of the molecular parasitology unit at the [[National Institute of Allergy and Infectious Diseases]], found that more than one half of dead raptors and more than one third of dead seabirds examined had the ''T. gondii'' parasite.&lt;ref name=&quot;Solomon_2013&quot; /&gt;

== Current environmental efforts ==
Urbanization and global warming are extremely influential in the transmission of ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Yan, C. 2016&quot;&gt;{{cite journal |last1=Yan |first1=Chao |last2=Liang |first2=Li-Jun |last3=Zheng |first3=Kui-Yang |last4=Zhu |first4=Xing-Quan |date=10 March 2016 |title=Impact of environmental factors on the emergence, transmission and distribution of ''Toxoplasma gondii'' |journal=Parasites &amp; Vectors |volume=9 |issue=1 |article-number=137 |doi=10.1186/s13071-016-1432-6 |doi-access=free |pmid=26965989 |pmc=4785633 |bibcode=2016PVec....9..137Y }}&lt;/ref&gt; Temperature and humidity are huge factors in the sporulation stage: low humidity is always fatal to the oocysts, and they are also vulnerable to extreme temperatures.&lt;ref name=&quot;Yan, C. 2016&quot; /&gt; Rainfall is also an important factor for survival of waterborne pathogens. Because increased rainfall directly increases the flow rate in rivers, the amount of flow into coastal areas is increased as well. This can spread waterborne pathogens over wide areas.
  
There is no effective vaccine for ''T.&amp;nbsp;gondii'', and research on a live vaccine is ongoing. Feeding cats commercially available food, rather than raw, undercooked meat, prevents felines from becoming a host for oocysts, as higher prevalence is in areas where raw meat is fed.&lt;ref&gt;{{cite journal |last1=Elmore |first1=Stacey A. |last2=Jones |first2=Jeffrey L. |last3=Conrad |first3=Patricia A. |last4=Patton |first4=Sharon |last5=Lindsay |first5=David S. |last6=Dubey |first6=J. P. |date=April 2010 |title=''Toxoplasma gondii'': Epidemiology, feline clinical aspects, and prevention |journal=Trends in Parasitology |volume=26 |issue=4 |pages=190–196 |doi=10.1016/j.pt.2010.01.009|pmid=20202907 |url=https://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1529&amp;context=publichealthresources |url-access=subscription }}&lt;/ref&gt; Researchers also suggest that owners restrict cats to live indoors and to be neutered or spayed to decrease stray cat populations and to reduce intermediate host interactions. It is suggested that fecal matter from litter boxes be collected daily, placed in a sealable bag, and disposed of in the trash rather than flushed in the toilet, so that water contamination is limited.&lt;ref name=&quot;Shapiro-et-al-2019&quot;&gt;{{cite journal |last1=Shapiro |first1=Karen |last2=Bahia-Oliveira |first2=Lillian |last3=Dixon |first3=Brent |last4=Dumètre |first4=Aurélien |last5=de Wit |first5=Luiz A. |last6=VanWormer |first6=Elizabeth |last7=Villena |first7=Isabelle |date=April 2019 |title=Environmental transmission of ''Toxoplasma gondii'': Oocysts in water, soil and food |journal=Food and Waterborne Parasitology |volume=12 |article-number=e00049 |doi=10.1016/j.fawpar.2019.e00049 |doi-access=free|pmid=32095620 |pmc=7033973 }}&lt;/ref&gt;
  
Studies have found that wetlands with a high density of vegetation decrease the concentration of oocysts in water through two possible mechanisms. Firstly, vegetation decreases flow velocities, which enables more settling because of increased transport time.&lt;ref name=&quot;Shapiro-et-al-2019&quot; /&gt; Secondly, the vegetation can remove oocysts through its ability to mechanically strain the water, as well as through the process of adhesion (i.e. attachment to biofilms). Areas of erosion and destruction of coastal wetlands have been found to harbour increased concentrations of ''T.&amp;nbsp;gondii'' oocysts, which then flow into open coastal waters. Current physical and chemical treatments typically utilized in water treatment facilities have been proven to be ineffective against ''T.&amp;nbsp;gondii''. Research has shown that UV-C disinfection of water containing oocysts results in inactivation and possible sterilization.&lt;ref&gt;{{cite journal |last1=Dumètre |first1=Aurélien |last2=Le Bras |first2=Caroline |last3=Baffet |first3=Maxime |last4=Meneceur |first4=Pascale |last5=Dubey |first5=J. P. |last6=Derouin |first6=Francis |last7=Duguet |first7=Jean-Pierre |last8=Joveux |first8=Michel |last9=Moulin |first9=Laurent |date=May 2008 |title=Effects of ozone and ultraviolet radiation treatments on the infectivity of ''Toxoplasma gondii'' oocysts |journal=Veterinary Parasitology |volume=153 |issue=3–4 |pages=209–213 |doi=10.1016/j.vetpar.2008.02.004|pmid=18355965 }}&lt;/ref&gt;

== Genome ==
The [[genome]]s of more than 60 [[Genome|strains]] of ''T.&amp;nbsp;gondii'' have been sequenced. Most are 60–80''&amp;nbsp;''Mb in size and consist of 11–14 [[chromosome]]s.&lt;ref name=&quot;Lau 2016&quot;&gt;{{cite journal |last1=Lau |first1=Y. L. |last2=Lee |first2=W. C. |last3=Gudimella |first3=R. |last4=Zhang |first4=G. |last5=Ching |first5=X. T. |last6=Razali |first6=R. |last7=Aziz |first7=F. |last8=Anwar |first8=A. |last9=Fong |first9=M. Y. |title=Deciphering the Draft Genome of ''Toxoplasma gondii'' RH Strain |journal=PLOS ONE |volume=11 |issue=6 |article-number=e0157901 |date=29 June 2016 |pmid=27355363 |pmc=4927122 |doi=10.1371/journal.pone.0157901 |bibcode=2016PLoSO..1157901L |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Bontell |first1=I. L. |last2=Hall |first2=N. |last3=Ashelford |first3=K. E. |last4=Dubey |first4=J. P. |last5=Boyle |first5=J. P. |last6=Lindh |first6=J. |last7=Smith |first7=J. E. |title=Whole genome sequencing of a natural recombinant ''Toxoplasma gondii'' strain reveals chromosome sorting and local allelic variants |journal=Genome Biology |volume=10 |issue=5 |pages=R53 |date=20 May 2009 |pmid=19457243 |pmc=2718519 |doi=10.1186/gb-2009-10-5-r53 |doi-access=free}}&lt;/ref&gt; The major strains encode 7,800–10,000 [[protein]]s, of which about 5,200 are conserved across RH, GT1, ME49, VEG.&lt;ref name=&quot;Lau 2016&quot; /&gt; A database, ToxoDB, has been established to document genomic information on ''Toxoplasma''.&lt;ref&gt;{{cite journal |last1=Kissinger |first1=J. C. |last2=Gajria |first2=B. |last3=Li |first3=L. |last4=Paulsen |first4=I. T. |last5=Roos |first5=D. S. |title=ToxoDB: accessing the ''Toxoplasma gondii'' genome |journal=Nucleic Acids Research |volume=31 |issue=1 |pages=234–36 |date=January 2003 |pmid=12519989 |pmc=165519 |doi=10.1093/nar/gkg072}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Gajria |first1=B. |last2=Bahl |first2=A. |last3=Brestelli |first3=J. |last4=Dommer |first4=J. |last5=Fischer |first5=S. |last6=Gao |first6=X. |last7=Heiges |first7=M. |last8=Iodice |first8=J. |last9=Kissinger |first9=J. C. |last10=Mackey |first10=A. J. |last11=Pinney |first11=D. F. |last12=Roos |first12=D. S. |last13=Stoeckert |first13=C. J. |last14=Wang |first14=H. |last15=Brunk |first15=B. P. |title=ToxoDB: An integrated ''Toxoplasma gondii'' database resource |journal=Nucleic Acids Research |volume=36 |issue=Database issue |pages=D553–56 |date=January 2008 |pmid=18003657 |pmc=2238934 |doi=10.1093/nar/gkm981}}&lt;/ref&gt;&lt;ref&gt;{{Cite web|url= http://toxodb.org/toxo/|title=ToxoDB: The ''Toxoplasma'' Genomics Resource|website=toxodb.org |access-date=1 March 2018}}&lt;/ref&gt;

== History ==
In 1908, while working at the [[Pasteur Institute of Tunis|Pasteur Institute]] in [[Tunis]], [[Charles Nicolle]] and [[Louis Manceaux]] discovered a protozoan organism in the tissues of a hamster-like rodent known as the [[gundi]], ''[[Ctenodactylus gundi]]''.&lt;ref name=&quot;Dubey2009History&quot; /&gt;  Although Nicolle and Manceaux initially believed the organism to be a member of the [[genus (biology)|genus]] ''[[Leishmania]]'' that they described as ''&quot;Leishmania gondii&quot;'', they soon realized they had discovered a new organism entirely; they renamed it ''Toxoplasma gondii''. The new genus name ''Toxoplasma'' is a reference to its morphology: ''Toxo'', from Greek {{lang|grc|{{linktext|τόξον}}}} (''{{transliteration|grc|toxon}}'', 'arc, bow'), and {{lang|grc|{{linktext|πλάσμα}}}} (''{{transliteration|grc|plasma}}'', 'shape, form') and the host in which it was discovered, the gundi (gondii).&lt;ref&gt;{{Cite journal |last1=Flegr |first1=Jaroslav |last2=Prandota |first2=Joseph |last3=Sovičková |first3=Michaela |last4=Israili |first4=Zafar H. |date=24 March 2014 |title=Toxoplasmosis – A Global Threat. Correlation of Latent Toxoplasmosis with Specific Disease Burden in a Set of 88 Countries |journal=PLOS ONE |volume=9 |issue=3 |article-number=e90203 |doi=10.1371/journal.pone.0090203 |issn=1932-6203 |pmc=3963851 |pmid=24662942|bibcode=2014PLoSO...990203F |doi-access=free}}&lt;/ref&gt; The same year Nicolle and Mancaeux discovered ''T.&amp;nbsp;gondii'', Alfonso Splendore identified the same organism in a [[rabbit]] in [[Brazil]]. However, he did not give it a name.&lt;ref name=&quot;Dubey2009History&quot; /&gt; In 1914, Italian tropicalist [[Aldo Castellani]] &quot;was first to suspect that toxoplasmosis could affect humans&quot;.&lt;ref&gt;{{cite book |editor-first=Jeremy M. |editor-last=Norman |title=Morton's Medical Bibliography: An Annotated Check-list of Texts Illustrating the History of Medicine |edition=5th |publisher=Garrison and Morton / Scolar Press |location=Aldershot |date=1991 |at=p. 860 (§ 5535.1)}}&lt;/ref&gt;

The first conclusive identification of ''T.&amp;nbsp;gondii'' in humans was in an infant girl delivered full term by [[Caesarean section]] on May 23, 1938, at [[Babies' Hospital]] in [[New York City]].&lt;ref name=&quot;Dubey2009History&quot; /&gt;  The girl began having [[seizure]]s at three days of age, and doctors identified [[lesion]]s in the [[Macula of retina|maculae]] of both of her eyes. When she died at one month of age, an [[autopsy]] was performed. [[Lesion]]s discovered in her brain and eye tissue were found to have both free and intracellular ''T.&amp;nbsp;gondii''.&lt;ref name=&quot;Dubey2009History&quot; /&gt; Infected tissue from the girl was [[Homogenization (biology)|homogenized]] and [[inoculate]]d intracerebrally into rabbits and mice; they then developed [[encephalitis]]. Later, [[congenital]] transmission was confirmed in many other species, particularly infected sheep and rodents.

The possibility of ''T.&amp;nbsp;gondii'' transmission via consumption of undercooked meat was first proposed by D. Weinman and A.H. Chandler in 1954.&lt;ref name=&quot;Dubey2009History&quot; /&gt; In 1960, the relevant cyst wall were shown to dissolve in the proteolytic enzymes found in the stomach, releasing infectious bradyzoites into the stomach (which pass into the intestine). The hypothesis of transmission via consumption of undercooked meat was tested on children hospitalized in a [[sanatorium]] in [[Paris]] in 1965 by Georges Desmonts et al.; incidence of ''T.&amp;nbsp;gondii'' rose from 10% to 50% after a year of adding two portions of cooked-rare beef or horse meat to many children's daily diets, and to 100% among those fed cooked-rare lamb chops.&lt;ref&gt;{{Cite journal |last1=Desmonts |first1=G. |last2=Couvreur |first2=J. |last3=Alison |first3=F. |last4=Baudelot |first4=J. |last5=Gerbeaux |first5=J. |last6=Lelong |first6=M. |date=November 1965 |title=[Epidemiological study on toxoplasmosis: the influence of cooking slaughter-animal meat on the incidence of human infection] |journal=Revue Française d'Études Cliniques et Biologiques |volume=10 |issue=9 |pages=952–958 |issn=0370-4793 |pmid=5853186}}&lt;/ref&gt;&lt;ref name=&quot;Dubey2009History&quot; /&gt;

A 1959 [[Mumbai]]-based study found their prevalence in strict [[vegetarians]] was similar to that of non-vegetarians. This raised the possibility of a third major route of infection, beyond congenital and non well-cooked meat carnivorous transmission.&lt;ref name=&quot;Dubey2009History&quot; /&gt;

In 1970, oocysts were found in (cat) feces. The [[fecal–oral route]] of infection via oocysts was demonstrated.&lt;ref name=&quot;Dubey2009History&quot; /&gt; In the 1970s and 1980s feces of a vast range of infected animal species was tested to see if it contained oocysts—at least 17 species of [[felid]]s shed oocysts, but no non-felid has been shown to allow ''T.&amp;nbsp;gondii'' sexual reproduction (leading to oocyst shedding).&lt;ref name=&quot;Dubey2009History&quot; /&gt;

In 1984 Elmer R. Pfefferkorn published his discovery that treatment of human [[fibroblast]]s with human recombinant [[interferon gamma]] blocks the growth of ''T.&amp;nbsp;gondii''.&lt;ref&gt;{{cite journal |doi=10.1073/pnas.81.3.908 |title=Interferon gamma blocks the growth of Toxoplasma gondii in human fibroblasts by inducing the host cells to degrade tryptophan |date=1984 |last1=Pfefferkorn |first1=E. R. |journal=Proceedings of the National Academy of Sciences |volume=81 |issue=3 |pages=908–912 |pmid=6422465 |pmc=344948 |bibcode=1984PNAS...81..908P |doi-access=free}}&lt;/ref&gt;

== Behavioral differences of infected hosts ==
There are many instances where behavioural changes were reported in rodents with ''T.&amp;nbsp;gondii''. The changes seen were a reduction in their innate dislike of cats, which made it easier for cats to prey on the rodents. In an experiment conducted by Berdoy and colleagues, the infected rats showed preference for the cat odour area versus the area with the rabbit scent, therefore making it easier for the parasite to take its final step in its definitive feline host.&lt;ref name=&quot;Berdoy2000&quot; /&gt; This is an example of the [[extended phenotype]] concept, that is, the idea that the behaviour of the infected animal changes in order to maximize survival of the genes that increase predation of the intermediate rodent host.&lt;ref name=&quot;McConkey2012&quot;&gt;{{cite journal |last1=McConkey |first1=G. A. |last2=Martin |first2=H. L. |last3=Bristow |first3=G. C. |last4=Webster |first4=J. P. |title=''Toxoplasma gondii'' infection and behaviour – location, location, location? |journal=The Journal of Experimental Biology |volume=216 |issue=Pt 1 |pages=113–19 |date=January 2013 |pmid=23225873 |pmc=3515035 |doi=10.1242/jeb.074153|bibcode=2013JExpB.216..113M }}&lt;/ref&gt;

* Differences in sex-dependent behavior observed in infected hosts compared to non-infected individuals can be attributed to differences in testosterone. Infected males had higher levels of testosterone while infected females had significantly lower levels, compared to their non-infected equivalents.&lt;ref name=&quot;Flegr2008Parasitology&quot;&gt;{{cite journal |last1=Flegr |first1=J. |last2=Lindová |first2=J. |last3=Kodym |first3=P. |title=Sex-dependent toxoplasmosis-associated differences in testosterone concentration in humans |journal=Parasitology |volume=135 |issue=4 |pages=427–31 |date=April 2008 |pmid=18205984 |doi=10.1017/S0031182007004064 |s2cid=18829116}}&lt;/ref&gt;
* Looking at humans, studies using the [[16PF Questionnaire|Cattell's 16 Personality Factor questionnaire]] found that infected men scored lower on Factor G (superego strength/rule consciousness) and higher on Factor''&amp;nbsp;''L (vigilance) while the opposite pattern was observed for infected women.&lt;ref name=&quot;Flegr2007SchizoBull&quot;&gt;{{cite journal |last=Flegr |first=J. |title=Effects of toxoplasma on human behavior |journal=Schizophrenia Bulletin |volume=33 |issue=3 |pages=757–60 |date=May 2007 |pmid=17218612 |pmc=2526142 |doi=10.1093/schbul/sbl074}}&lt;/ref&gt; Such men were more likely to disregard rules and were more expedient, suspicious, and jealous. On the other hand, women were more warm-hearted, outgoing, conscientious, and moralistic.&lt;ref name=&quot;Flegr2007SchizoBull&quot; /&gt; 
* Published research has also indicated that ''T.&amp;nbsp;gondii'' infection could potentially promote changes in a person's political beliefs and values. Those who are infected with the parasite tend to exhibit a higher degree of &quot;us versus them&quot; thinking.&lt;ref name=&quot;T gondii – politics&quot;&gt;{{cite journal |last1=Kopecky |first1=R. |last2=Příplatová |first2=L. |last3=Boschetti |first3=S. |last4=Talmont-Kaminski |first4=K. |last5=Flegr |first5=J. |date=2022 |title=Le Petit Machiavellian Prince: Effects of Latent Toxoplasmosis on Political Beliefs and Values |journal=Evolutionary Psychology |volume=20 |issue=3 |pages=1–13 |article-number=14747049221112657 |doi=10.1177/14747049221112657 |pmc=10303488 |pmid=35903902 |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{Cite web |last=Singh |first=Ananya |date=10 October 2022 |title=A Common Parasite Could Be Altering People's Political Beliefs, Suggests Study |url=https://theswaddle.com/a-common-parasite-could-be-altering-peoples-political-beliefs-suggests-study/ |access-date=30 November 2022 |website=The Swaddle}}&lt;/ref&gt;
* Mice infected with ''T.&amp;nbsp;gondii'' have a worse motor performance than non-infected mice.&lt;ref&gt;{{cite journal |last1=Hrdá |first1=S. |last2=Votýpka |first2=J. |last3=Kodym |first3=P. |last4=Flegr |first4=J. |title=Transient nature of ''Toxoplasma gondii''-induced behavioral changes in mice |journal=The Journal of Parasitology |volume=86 |issue=4 |pages=657–63 |date=August 2000 |pmid=10958436 |doi=10.1645/0022-3395(2000)086[0657:TNOTGI]2.0.CO;2 |s2cid=2004169}}&lt;/ref&gt;&lt;ref&gt;{{cite journal |last1=Hutchison |first1=W. M. |last2=Aitken |first2=P. P. |last3=Wells |first3=B. W. |title=Chronic ''Toxoplasma'' infections and motor performance in the mouse |journal=Annals of Tropical Medicine and Parasitology |volume=74 |issue=5 |pages=507–10 |date=October 1980 |pmid=7469564 |doi=10.1080/00034983.1980.11687376}}&lt;/ref&gt; Thus, a computerized simple reaction test was given to both infected and non-infected adults. It was found that the infected adults performed much more poorly and lost their concentration more quickly than the [[control group]]. But, the effect of the infection only explains less than 10% of the variability in performance&lt;ref name=&quot;Flegr2007SchizoBull&quot; /&gt; (i.e., there could be other confounding factors).
* Correlation has also been observed between [[seroprevalence]] of ''T.&amp;nbsp;gondii'' in humans and increased risk of traffic accidents. Infected subjects have a 2.65 times higher risk of getting into a traffic accident.&lt;ref&gt;{{cite journal |last1=Flegr |first1=J. |last2=Havlícek |first2=J. |last3=Kodym |first3=P. |last4=Malý |first4=M. |last5=Smahel |first5=Z. |title=Increased risk of traffic accidents in subjects with latent toxoplasmosis: a retrospective case-control study |journal=BMC Infectious Diseases |volume=2 |article-number=11 |date=July 2002 |pmid=12095427 |pmc=117239 |doi=10.1186/1471-2334-2-11 |doi-access=free}}&lt;/ref&gt; A Turkish study confirmed this holds true among drivers.&lt;ref&gt;{{cite journal |last1=Kocazeybek |first1=B. |last2=Oner |first2=Y. A. |last3=Turksoy |first3=R. |last4=Babur |first4=C. |last5=Cakan |first5=H. |last6=Sahip |first6=N. |last7=Unal |first7=A. |last8=Ozaslan |first8=A. |last9=Kilic |first9=S. |last10=Saribas |first10=S. |last11=Aslan |first11=M. |last12=Taylan |first12=A. |last13=Koc |first13=S. |last14=Dirican |first14=A. |last15=Uner |first15=H. B. |last16=Oz |first16=V. |last17=Ertekin |first17=C. |last18=Kucukbasmaci |first18=O. |last19=Torun |first19=M. M. |title=Higher prevalence of toxoplasmosis in victims of traffic accidents suggest increased risk of traffic accident in Toxoplasma-infected inhabitants of Istanbul and its suburbs |journal=Forensic Science International |volume=187 |issue=1–3 |pages=103–08 |date=May 2009 |pmid=19356869 |doi=10.1016/j.forsciint.2009.03.007}}&lt;/ref&gt;
* This parasite has been associated with many neurological disorders such as [[schizophrenia]]. In a meta-analysis of 23 studies that met inclusion criteria, the seroprevalence of antibodies to ''T.&amp;nbsp;gondii'' in people with schizophrenia is significantly higher than in control populations (OR=2.73, P&lt;0.000001).&lt;ref&gt;{{cite journal |last1=Torrey |first1=E. F. |last2=Bartko |first2=J. J. |last3=Lun |first3=Z. R. |last4=Yolken |first4=R. H. |title=Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis |journal=Schizophrenia Bulletin |volume=33 |issue=3 |pages=729–36 |date=May 2007 |pmid=17085743 |pmc=2526143 |doi=10.1093/schbul/sbl050}}&lt;/ref&gt;
* A 2009 summary of studies found that suicide attempters had far more indicative (IgG) antibodies than mental health inpatients without a suicide attempt.&lt;ref&gt;{{cite journal |last1=Arling |first1=T. A. |last2=Yolken |first2=R. H. |last3=Lapidus |first3=M. |last4=Langenberg |first4=P. |last5=Dickerson |first5=F. B. |last6=Zimmerman |first6=S. A. |last7=Balis |first7=T. |last8=Cabassa |first8=J. A. |last9=Scrandis |first9=D. A. |last10=Tonelli |first10=L. H. |last11=Postolache |first11=T. T. |s2cid=33395780 |title=Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders |journal=The Journal of Nervous and Mental Disease |volume=197 |issue=12 |pages=905–08 |date=December 2009 |pmid=20010026 |doi=10.1097/nmd.0b013e3181c29a23 }}&lt;/ref&gt; Infection was also shown to be associated with suicide in women over the age of 60. (P&lt;0.005) &lt;ref&gt;{{cite journal |last1=Ling |first1=V. J. |last2=Lester |first2=D. |last3=Mortensen |first3=P. B. |last4=Langenberg |first4=P. W. |last5=Postolache |first5=T. T. |title=''Toxoplasma gondii'' seropositivity and suicide rates in women |journal=The Journal of Nervous and Mental Disease |volume=199 |issue=7 |pages=440–44 |date=July 2011 |pmid=21716055 |pmc=3128543 |doi=10.1097/nmd.0b013e318221416e}}&lt;/ref&gt;
* Research on the linkage between ''T.&amp;nbsp;gondii'' infection and entrepreneurial behavior showed that students who tested positive for ''T.&amp;nbsp;gondii'' exposure were 1.4 times more likely to major in business and 1.7 times more likely to have an emphasis in &quot;management and entrepreneurship&quot;. Among 197 participants of entrepreneurship events, ''T.&amp;nbsp;gondii'' exposure was correlated with being 1.8 times more likely to have started their own business.&lt;ref&gt;{{cite journal |last1=Johnson |first1=S. K. |last2=Fitza |first2=M. A. |last3=Lerner |first3=D. A. |last4=Calhoun |first4=D. M. |last5=Beldon |first5=M. A. |last6=Chan |first6=E. T. |last7=Johnson |first7=P. T. |date=2018 |title=Risky business: linking ''Toxoplasma gondii'' infection and entrepreneurship behaviours across individuals and countries |journal=Proceedings of the Royal Society B: Biological Sciences |volume=285 |issue=1883 |article-number=20180822 |doi=10.1098/rspb.2018.0822 |pmc=6083268 |pmid=30051870}}&lt;/ref&gt;
* Another population-representative study with 7440 people in the United States found that ''Toxoplasma'' infection was 2.4 fold more common in people who had a history of manic and depression symptoms (bipolar disorder Type 1) compared to the general population.&lt;ref&gt;{{cite journal |last1=Pearce |first1=B. D. |last2=Kruszon-Moran |first2=D. |last3=Jones |first3=J. L. |date=2012 |title=The Relationship Between ''Toxoplasma gondii'' Infection and Mood Disorders in the Third National Health and Nutrition Survey |journal=Biological Psychiatry |volume=72 |issue=4 |pages=290–95 |doi=10.1016/j.biopsych.2012.01.003 |pmc=4750371 |pmid=22325983}}&lt;/ref&gt;

As mentioned before, these results of increased proportions of people seropositive for the parasite in cases of these neurological disorders do not necessarily indicate a causal relationship between the infection and disorder. It is also important to mention that in 2016 a population-representative birth cohort study which was done, to test a hypothesis that [[toxoplasmosis]] is related to impairment in brain and behaviour measured by a range of phenotypes including neuropsychiatric disorders, poor impulse control, personality and neurocognitive deficits. The results of this study did not support the results in the previously mentioned studies, more than marginally. None of the P-values showed significance for any outcome measure. Thus, according to this study, the presence of ''T.&amp;nbsp;gondii'' antibodies is not correlated to increase susceptibility to any of the behaviour phenotypes (except possibly to a higher rate of unsuccessful attempted suicide). This team did not observe any significant association between ''T.&amp;nbsp;gondii'' seropositivity and [[schizophrenia]]. The team notes that the null findings might be a false negative due to low statistical power because of small sample sizes but against this weights that their setup should avoid some possibilities for errors in the about 40 studies that did show a positive correlation. They concluded that further studies should be performed.&lt;ref&gt;{{cite journal |last1=Sugden |first1=K. |last2=Moffitt |first2=T. E. |last3=Pinto |first3=L. |last4=Poulton |first4=R. |last5=Williams |first5=B. S. |last6=Caspi |first6=A. |title=Is ''Toxoplasma gondii'' Infection Related to Brain and Behavior Impairments in Humans? Evidence from a Population-representative Birth Cohort |journal=PLOS ONE |volume=11 |issue=2 |article-number=e0148435 |date=2016 |pmid=26886853 |pmc=4757034 |doi=10.1371/journal.pone.0148435 |bibcode=2016PLoSO..1148435S |doi-access=free}}&lt;/ref&gt;

The mechanism behind behavioral changes is partially attributed to increased dopamine metabolism,&lt;ref&gt;{{cite journal |last1=Prandovszky |first1=E. |last2=Gaskell |first2=E. |last3=Martin |first3=H. |last4=Dubey |first4=J. P. |last5=Webster |first5=J. P. |last6=McConkey |first6=G. A. |title=The neurotropic parasite Toxoplasma gondii increases dopamine metabolism. |journal=PLOS ONE |date=2011 |volume=6 |issue=9 |article-number=e23866 |doi=10.1371/journal.pone.0023866 |pmid=21957440|pmc=3177840 |bibcode=2011PLoSO...623866P |doi-access=free}}&lt;/ref&gt; which can be neutralized by dopamine antagonist medications.&lt;ref&gt;{{cite journal |last1=Webster |first1=J. P. |last2=Lamberton |first2=P. H. |last3=Donnelly |first3=C. A. |last4=Torrey |first4=E. F. |title=Parasites as causative agents of human affective disorders? The impact of anti-psychotic, mood-stabilizer and anti-parasite medication on Toxoplasma gondii's ability to alter host behaviour. |journal=Proceedings. Biological Sciences |date=22 April 2006 |volume=273 |issue=1589 |pages=1023–30 |doi=10.1098/rspb.2005.3413 |pmid=16627289|pmc=1560245}}&lt;/ref&gt; ''T.&amp;nbsp;gondii'' has two genes that code for a bifunctional [[phenylalanine hydroxylase|phenylalanine]] and [[tyrosine hydroxylase]], two important and rate-limiting steps of dopamine biosynthesis. One of the genes is constitutively expressed, while the other is only produced during cyst development.&lt;ref&gt;{{cite journal |last1=Gaskell |first1=E. A. |last2=Smith |first2=J. E. |last3=Pinney |first3=J. W. |last4=Westhead |first4=D. R. |last5=McConkey |first5=G. A. |title=A unique dual activity amino acid hydroxylase in Toxoplasma gondii. |journal=PLOS ONE |date=2009 |volume=4 |issue=3 |article-number=e4801 |doi=10.1371/journal.pone.0004801 |pmid=19277211|pmc=2653193 |bibcode=2009PLoSO...4.4801G |doi-access=free}}&lt;/ref&gt;&lt;ref&gt;{{cite web |last2=Mitchell |first2=Alex |last1=Sangrador |first1=Amaia |title=Protein focus: Don't blame the cat – the toxoplasmosis effect |url= http://interprodb.blogspot.com/2014/11/protein-focus-dont-blame-cat.html |archive-url= https://web.archive.org/web/20160922213903/http://interprodb.blogspot.com/2014/11/protein-focus-dont-blame-cat.html |url-status=live |archive-date=22 September 2016 |website=InterPro database blog |access-date=27 May 2019 |date=6 November 2014}}&lt;/ref&gt; In addition to additional dopamine production, ''T.&amp;nbsp;gondii'' infection also produces long-lasting epigenetic changes in animals that increase the expression of [[vasopressin]], a probable cause of alterations that persist after the clearance of the infection.&lt;ref&gt;{{cite journal |last1=Hari Dass |first1=S. A. |last2=Vyas |first2=A. |title=Toxoplasma gondii infection reduces predator aversion in rats through epigenetic modulation in the host medial amygdala |journal=Molecular Ecology |date=December 2014 |volume=23 |issue=24 |pages=6114–22 |doi=10.1111/mec.12888 |pmid=25142402|bibcode=2014MolEc..23.6114H |s2cid=45290208}}&lt;/ref&gt;

In 2022, a study published in ''Communications Biology'' of a well-documented population of wolves studied throughout their lives, suggested that ''T.&amp;nbsp;gondii'' also may have a significant effect on their behavior.&lt;ref&gt;{{Cite journal |last1=Meyer |first1=Connor J. |last2=Cassidy |first2=Kira A. |last3=Stahler |first3=Erin E. |last4=Brandell |first4=Ellen E. |last5=Anton |first5=Colby B. |last6=Stahler |first6=Daniel R. |last7=Smith |first7=Douglas W. |date=2022-11-24 |title=Parasitic infection increases risk-taking in a social, intermediate host carnivore |journal=Communications Biology |language=en |volume=5 |issue=1 |page=1180 |doi=10.1038/s42003-022-04122-0 |pmid=36424436 |issn=2399-3642|pmc=9691632 }}&lt;/ref&gt; It suggested that infection with this parasite emboldened infected wolves into behavior that determined leadership roles and influenced risk-taking behavior, perhaps even motivating establishment of new independent packs that they would establish and lead in behavior patterns differing from that of the packs into which they were born. The study determined that at times, an infected wolf would become the only breeding male in a pack, leading to a significant effect on another species by ''T.&amp;nbsp;gondii''.

==Potential medical use==
In July 2024, a study published in ''[[Nature Microbiology]]'' showed that ''T.&amp;nbsp;gondii'' can be engineered to deliver the [[MECP2]] protein, a therapeutic target of [[Rett syndrome]], to the brain of infected mice.&lt;ref&gt;{{cite journal |last=Bracha |first=Shahar |display-authors=etal |title=Engineering Toxoplasma gondii secretion systems for intracellular delivery of multiple large therapeutic proteins to neurons |journal=Nature Microbiology |date=July 29, 2024|volume=9 |issue=8 |pages=2051–2072 |doi=10.1038/s41564-024-01750-6|pmid=39075233 |pmc=11306108 }}&lt;/ref&gt;&lt;ref&gt;{{cite web |url=https://theconversation.com/a-common-parasite-could-one-day-deliver-drugs-to-the-brain-how-scientists-are-turning-toxoplasma-gondii-from-foe-into-friend-235928
 |last1=Sullivan |first1=Bill |title=A common parasite could one day deliver drugs to the brain − how scientists are turning Toxoplasma gondii from foe into friend |website=The Conversation |archive-url=https://web.archive.org/web/20240811192519/https://theconversation.com/a-common-parasite-could-one-day-deliver-drugs-to-the-brain-how-scientists-are-turning-toxoplasma-gondii-from-foe-into-friend-235928 |archive-date=August 11, 2024 |date=August 7, 2024 |access-date=August 11, 2024}}&lt;/ref&gt;

== See also ==
* [[Toxoplasma lactate dehydrogenase 1 regulatory UTR]]

== References ==
{{Reflist|32em}}

== External links ==
{{Scholia|topic}}
* [https://www.toxodb.org ToxoDB: The ''Toxoplasma gondii'' genome resource] at the VEuPathDB [[Bioinformatics Resource Centers|Bioinformatics Resource Center]] 
* [https://www.cdc.gov/parasites/toxoplasmosis/ Parasites - Toxoplasmosis (Toxoplasma infection)] by the [[Centers for Disease Control and Prevention]]
* [https://www.takingouttoxo.org/ Taking out Toxo and the Toxoplasmosis Research Institute and Center] at the [[University of Chicago]]
* [https://toxoplasmaparasite.blogspot.com/ Anti-Toxo: A ''Toxoplasma'' news blog and list of research laboratories] by [https://medicine.iu.edu/faculty/13502/sullivan-william Bill Sullivan] of the School of Medicine at the [[Indiana University]]

{{Alveolata}}
{{Chromalveolate diseases}}
{{Taxonbar|from=Q131003}}
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[[Category:Conoidasida]]
[[Category:Protists described in 1908]]
[[Category:Suicide-inducing parasitism]]
[[Category:Parasites of cats]]
[[Category:Cat diseases]]
[[Category:Parasites of rodents]]
[[Category:Rodent-carried diseases]]
[[Category:Cats as pets]]
[[Category:Apicomplexa species]]