### Microbiology *[[Toxoplasma]]* *gondii*, a parasite found in almost all animals. Cats are the definitive host. There are several lineages, Type II is in Europe. In North America, there are atypical genotypes that have been > "associated with severe ocular and systemic disease and unusual presentations of toxoplasmosis in immunocompetent patients." [^1] ### Epidemiologic Risks Eating undercooked meat, especially pork, lamb, and wild game (there was an outbreak in hunters who ate undercooked deer in Illinois), [^2] and soil contaminated with cat poo. It can be on raw fruits and vegetables. > "We evaluated 148 case patients with recent T. gondii infection and 413 control patients. In multivariate analysis, an elevated risk of recent T. gondii infection was associated with the following factors: eating raw ground beef; eating rare lamb; eating locally produced cured, dried, or smoked meat; working with meat; drinking unpasteurized goat's milk (ick), and having 3 or more kittens (owning, not giving birth to). Eating raw oysters, clams, or mussels was significant in a separate model among persons asked this question." [^4] and > "In the 1960s and 1990s, toxoplasmosis outbreaks mainly occurred through ingestion of cysts in meat and meat derivatives; in the 1980s, through milk contaminated with tachyzoites; in 2000, due to the presence of oocysts in water, sand, and soil; and in 2010, due to oocysts in raw fruits and vegetables." [^5] And drinking camel's milk in herders in Butana area. Eating undercooked food is a much greater risk than cat excrement; cats are an overrated risk. Except, I suppose, eating raw cat. Occasionally passed on in transplanted organs. There were cases in France linked to imported horse meat; "Wilbur, I am so sorry." It also occurs in families; when one has toxoplasmosis, the family should be screened. [^3] There was a presumed waterborne outbreak. [^6] ### Syndromes Acute disease: usually asymptomatic, it can febrile, malaise, night sweats, myalgias, sore throat, maculopapular rash, hepatosplenomegaly disease with lots of lymphadenopathy. Sort of mono without the exudative [[Pharyngitis]] and monospot. Patients on biologics can get severe disseminated disease with [[encephalitis]]. [^7] Reactivation Disease: CNS mass lesions in [[HIV]] patients with CD4 < 200 and transplant patients. myocarditis, [[pneumonia]] and eye involvement can also occur in these patients as well. It can reactivate in patients who receive myeloablative conditioning and with high-dose total body irradiation for stem cell transplant. [^8] Reactivation can happen in transplant patients (who benefit from prevention) [^9] and as a manifestation of thymoma. [^10] Disseminated disease in the immunoincompetent has a bad outcome. [^11] Bad Driving: People who are *[[Toxoplasma]]* seropositive have more car accidents than those who are not, except for those who have RhD positive blood. Really. [^12] I wonder if I can use that to get out of a speeding ticket. Your honor, it's not my fault, it's the *[[Toxoplasma]]*. And seropositives are more aggressive and impulsive, so no wonder they are bad drivers. [^13] [^14] The higher the IgG levels in latent disease, the more neurocognitive issues in [[HIV]] patients. [^15] And perhaps a reason for seizures. [^16] And truck drivers? Often seropositive. [^17] Great. Huge trucks driven at excess speeds by seizing aggressive bad drivers. And seropositive kids may not be as good at math [^18] and may have more mental illness [^19], including anxiety disorder. [^20] Parasites in the brain may be a bad thing if they are in a useful place. Good thing we only use 10% of our brain. Not. [^21] Mental illness? Maybe. Association is not causation, but the associations are curious, especially in light of the other associations and neuro-affinity. [^22] ### Treatment In [[HIV]] patients who are seropositive for [[Toxoplasma]], the disease can be prevented with daily, [[Trimethoprim-Sulfamethoxazole]] or macrolides (not [[erythromycin]] or [[Atovaquone]]. CNS disease. [[Pyrimethamine]] PLUS either [[sulfadiazine]] OR [[clindamycin]] AND Folinic acid. OR [[Trimethoprim-Sulfamethoxazole]] po or IV OR [[Pyrimethamine]] AND folinic acid PLUS either [[clarithromycin]] po OR [[Atovaquone]] po OR [[Azithromycin]] po OR [[dapsone]] po 100 mg qd. From a systematic review: > "One well-designed trial showed that [[trimethoprim]]-sulphamethoxazole was more effective than a placebo for clinical recovery of [[Toxoplasma]] lymphadenopathy in immunocompetent hosts. For [[Toxoplasma]] encephalopathy, the efficacy of [[Pyrimethamine]]+sulphadiazine and [[trimethoprim]]+sulphamethoxazole were similar, whereas [[Pyrimethamine]]+sulphadiazine versus [[Pyrimethamine]]+[[clindamycin]] showed no difference, irrespective of the outcome. Intravitreal [[clindamycin]]+dexamethasone and conventional treatment with oral [[Pyrimethamine]]+sulphadiazine had similar efficacy with regard to all outcome measures in ocular toxoplasmosis, and intravitreal therapy was found to be safe. Adverse effects seemed more common with [[Pyrimethamine]]+sulphadiazine. Most trials for [[encephalitis]] and ocular manifestations had a high risk of bias and were of poor methodological quality. There were no trials evaluating drugs for toxoplasmosis in pregnancy, or for congenital toxoplasmosis. [[Pyrimethamine]]+sulphadiazine is an effective therapy for the treatment of toxoplasmic [[encephalitis]]; [[trimethoprim]]+sulphamethoxazole and [[Pyrimethamine]]+[[clindamycin]] are possible alternatives. Treatment with either oral or intravitreal antibiotics seems reasonable for ocular toxoplasmosis." [^23] Once therapy is complete, secondary prophylaxis should be continued indefinitely. In [[HIV]] patients on HAART, if CD4 > 200 and viral load <50 for a year can stop prophylaxis. I am not going to give advice for treatment in pregnancy. ### Notes In [[HIV]], CNS mass lesions are usually between *[[Toxoplasma]]* and CNS lymphoma, [[Toxoplasma]] tends to be multiple and seropositive; lymphoma tends to be single and seronegative. If single lesion and seropositive, patients should improve clinically in 10 days or so on therapy. If they do not, or worsen, strongly consider biopsy. There is also an interesting literature showing an association between toxoplasmosis and schizophrenia. Really. Or so the voices tell me. In mice, *[[Toxoplasma]]* makes the animals less fearful and more likely to be et, thus completing the parasite's lifecycle. ### Puswhisperers [Don't Change The Litter Box Before Driving](http://www.pusware.com/PW1/LitterBox.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop630.mp3) [Hiccups](http://www.pusware.com/PW2/Hiccups.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop235.mp3) [A Return to the bad old days](http://www.pusware.com/PW3/BadOldDays.html). [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop490.mp3) [The Attic is Full](http://www.pusware.com/PW9/AtticFull.html) [Audio. The Gobbet 'o Pus Podcast](http://www.pusware.com/gobbet/gop1061.mp3) ### Rationalizations [^1]: Pomares C, Devillard S, Holmes TH, Olariu TR, Press CJ, Ramirez R, Talucod J, Estran R, Su C, Dubey JP, Ajzenberg D, Montoya JG. Genetic Characterization of [[Toxoplasma]] gondii DNA Samples Isolated From Humans Living in North America: An Unexpected High Prevalence of Atypical Genotypes. J Infect Dis. 2018 Oct 20;218(11):1783-1791. doi: 10.1093/infdis/jiy375. PMID: 29982713. [^2]: Jones JL, Dubey JP. Foodborne toxoplasmosis. Clin Infect Dis. 2012 Sep;55(6):845-51. doi: 10.1093/cid/cis508. Epub 2012 May 22. PMID: 22618566. [^3]: Contopoulos-Ioannidis DG, Maldonado Y, Montoya JG. Acute [[Toxoplasma]] gondii Infection among Family Members in the United States. _Emerging Infectious Diseases_. 2013;19(12):1981-1984. doi:10.3201/eid1912.121892. [^4]: Jones JL, Dargelas V, Roberts J, Press C, Remington JS, Montoya JG. Risk factors for [[Toxoplasma]] gondii infection in the United States. Clin Infect Dis. 2009 Sep 15;49(6):878-84. doi: 10.1086/605433. PMID: 19663709. [^5]: Pinto-Ferreira F, Caldart E, Pasquali A, et al. Patterns of Transmission and Sources of Infection in Outbreaks of Human Toxoplasmosis. _Emerging Infectious Diseases_. 2019;25(12):2177-2182. doi:10.3201/eid2512.181565. [^6]: Brandão-de-Resende C, Santos H, Rojas Lagos A, et al. Clinical and Multimodal Imaging Findings and Risk Factors for Ocular Involvement in a Presumed Waterborne Toxoplasmosis Outbreak, Brazil. _Emerging Infectious Diseases_. 2020;26(12):2922-2932. doi:10.3201/eid2612.200227. [^7]: Gharamti AA, Rao A, Pecen PE, Henao-Martínez AF, Franco-Paredes C, Montoya JG. Acute _Toxoplasma_ Dissemination With [[Encephalitis]] in the Era of Biological Therapies. Open Forum Infect Dis. 2018 Oct 17;5(11):ofy259. doi: 10.1093/ofid/ofy259. PMID: 30460322; PMCID: PMC6237240. [^8]: Meers S, Lagrou K, Theunissen K, Dierickx D, Delforge M, Devos T, Janssens A, Meersseman W, Verhoef G, Van Eldere J, Maertens J. Myeloablative conditioning predisposes patients for [[Toxoplasma]] gondii reactivation after allogeneic stem cell transplantation. Clin Infect Dis. 2010 Apr 15;50(8):1127-34. doi: 10.1086/651266. PMID: 20218875. [^9]: Robert-Gangneux F, Meroni V, Dupont D, et al. Toxoplasmosis in Transplant Recipients, Europe, 2010–2014. _Emerging Infectious Diseases_. 2018;24(8):1497-1504. doi:10.3201/eid2408.180045. [^10]: Daniel B Chastain, Joeanna I Sams, Gregory M Steele, Lindsey O Lowder, Carlos Franco-Paredes, Expanding Spectrum of _Toxoplasma gondii_: Thymoma and Toxoplasmic [[Encephalitis]], _Open Forum Infectious Diseases_, Volume 5, Issue 7, July 2018, ofy163, [https://doi.org/10.1093/ofid/ofy163](https://doi.org/10.1093/ofid/ofy163) [^11]: Schmidt M, Sonneville R, Schnell D, Bigé N, Hamidfar R, Mongardon N, Castelain V, Razazi K, Marty A, Vincent F, Dres M, Gaudry S, Luyt CE, Das V, Micol JB, Demoule A, Mayaux J. Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: a multicenter study. Clin Infect Dis. 2013 Dec;57(11):1535-41. doi: 10.1093/cid/cit557. Epub 2013 Aug 30. PMID: 23994819. [^12]: Flegr, J., Klose, J., Novotná, M. _et al.* Increased incidence of traffic accidents in _Toxoplasma_-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. _BMC Infect Dis_ **9**, 72 (2009). https://doi.org/10.1186/1471-2334-9-72 [^13]: Cook tuberculosis, Brenner LA, Cloninger CR, Langenberg P, Igbide A, Giegling I, Hartmann AM, Konte B, Friedl M, Brundin L, Groer MW, Can A, Rujescu D, Postolache TT. "Latent" infection with [[Toxoplasma]] gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res. 2015 Jan;60:87-94. doi: 10.1016/j.jpsychires.2014.09.019. Epub 2014 Sep 28. PMID: 25306262. [^14]: Peng X, Brenner LA, Mathai AJ, Cook tuberculosis, Fuchs D, Postolache N, Groer MW, Pandey JP, Mohyuddin F, Giegling I, Wadhawan A, Hartmann AM, Konte B, Brundin L, Friedl M, Stiller JW, Lowry CA, Rujescu D, Postolache TT. Moderation of the relationship between [[Toxoplasma]] gondii seropositivity and trait impulsivity in younger men by the phenylalanine-tyrosine ratio. Psychiatry Res. 2018 Dec;270:992-1000. doi: 10.1016/j.psychres.2018.03.045. Epub 2018 Mar 22. PMID: 30057257; PMCID: PMC6371810. [^15]: Bharti AR, McCutchan A, Deutsch R, Smith DM, Ellis RJ, Cherner M, Woods SP, Heaton RK, Grant I, Letendre SL. Latent [[Toxoplasma]] Infection and Higher [[Toxoplasma]] gondii Immunoglobulin G Levels Are Associated With Worse Neurocognitive Functioning in [[HIV]]-Infected Adults. Clin Infect Dis. 2016 Dec 15;63(12):1655-1660. doi: 10.1093/cid/ciw655. Epub 2016 Oct 28. PMID: 27794019; PMCID: PMC5146725. [^16]: Ngoungou EB, Bhalla D, Nzoghe A, Dardé ML, Preux PM. Toxoplasmosis and epilepsy--systematic review and meta analysis. PLoS Negl Trop Dis. 2015 Feb 19;9(2):e0003525. doi: 10.1371/journal.pntd.0003525. PMID: 25695802; PMCID: PMC4335039. [^17]: Alvarado-Esquivel C, Pacheco-Vega SJ, Hernández-Tinoco J, Salcedo-Jáquez M, Sánchez-Anguiano LF, Berumen-Segovia LO, Rábago-Sánchez E, Liesenfeld O. [[Toxoplasma]] gondii infection in interstate truck drivers: a case-control seroprevalence study. Parasit Vectors. 2015 Feb 5;8:77. doi: 10.1186/s13071-015-0690-z. PMID: 25651797; PMCID: PMC4322546. [^18]: Ferreira EC, Marchioro AA, Guedes TA, Mota DC, Guilherme AL, de Araújo SM. Association between seropositivity for [[Toxoplasma]] gondii, scholastic development of children and risk factors for T. gondii infection. Trans R Soc Trop Med Hyg. 2013 Jun;107(6):390-6. doi: 10.1093/trstmh/trt026. Epub 2013 Apr 18. PMID: 23598948. [^19]: Flegr J, Horáček J. Negative Effects of Latent Toxoplasmosis on Mental Health. Front Psychiatry. 2020 Feb 18;10:1012. doi: 10.3389/fpsyt.2019.01012. PMID: 32132937; PMCID: PMC7040223. [^20]: Markovitz AA, Simanek AM, Yolken RH, et al. [[Toxoplasma]] gondii and anxiety disorders in a community-based sample. Brain, Behavior, and Immunity. 2015 Jan;43:192-197. DOI: 10.1016/j.bbi.2014.08.001. PMID: 25124709 [^21]: https://en.wikipedia.org/wiki/Ten_percent_of_the_brain_myth [^22]: Suvisaari J, Torniainen-Holm M, Lindgren M, Härkänen T, Yolken RH. [[Toxoplasma]] gondii infection and common mental disorders in the Finnish general population. J Affect Disord. 2017 Dec 1;223:20-25. doi: 10.1016/j.jad.2017.07.020. Epub 2017 Jul 10. PMID: 28715724; PMCID: PMC5588865. [^23]: Rajapakse S, Chrishan Shivanthan M, Samaranayake N, Rodrigo C, Deepika Fernando S. Antibiotics for human toxoplasmosis: a systematic review of randomized trials. Pathog Glob Health. 2013 Jun;107(4):162-9. doi: 10.1179/2047773213Y.0000000094. PMID: 23816507; PMCID: PMC4001466.