Kill Toxoplasmosis for good

[Karmeleon]

Apparently t gondii is a part of a diverse group of parasites called apicomplexans. Here is their theorized evolutionary tree: Apicomplexa - Wikipedia

Apicomplexa - Wikipedia

en.wikipedia.org

Diseases caused by Apicomplexa include:

• Babesiosis (Babesia)
• Malaria (Plasmodium)
• Cryptosporidiosis (Cryptosporidium parvum)
• Cyclosporiasis (Cyclospora cayetanensis)
• Cystoisosporiasis (Cystoisospora belli (formerly known as "Isospora Belli"))
• Toxoplasmosis (Toxoplasma gondii)

I would not wonder if an underlying weak spot of them or the way they hijack tissue would create a nice anti apicomplexa framework of substances, and or treatments (methylene blue + red light)....
Maybe they also share a common path for their abilities in immune suppression which could be reversed and so any problems with 'em fixed.

 

[Karmeleon]

Thyme extract is also potent by it's carvacrol content:

Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model​

Effects of Thymus vulgaris ethanolic extract on chronic toxoplasmosis in a mouse model - Parasitology Research

The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by...

link.springer.com

The current work was undertaken to investigate the potential effectiveness of Thymus vulgaris ethanolic extract (TVE) against Toxoplasma gondii infection in chronic experimental toxoplasmosis. To evaluate prophylactic effects, mice received 500 mg/kg TVE for 5 days before they were infected by an avirulent Me49 T. gondii strain. To investigate the therapeutic effects of the extract postinfection, daily treatment with TVE was initiated at 6 weeks postinfection and continued for 10 days. The following groups of animals were used as controls: uninfected/non-treated, infected/non-treated, and infected/treated with a combination of pyrimethamine and sulfadiazine. Brain cyst count and histopathological changes using H&E and Feulgen stains were used to evaluate the efficacy of TVE. The mean number of brain cysts was significantly decreased by 24 % in mice treated prophylactically with TVE. TVE also significantly reduced the mean number of brain cysts when administered to animals already chronically infected with T. gondii. The effect of TVE was comparable to that of treatment with a mixture of sulfadiazine and pyrimethamine (46 and 51 % reduction, respectively). Moreover, considerable amelioration of the pathological lesions in the brain and retina was observed. The results demonstrate the potential efficacy of T. vulgaris as a new natural therapeutic and prophylactic agent for use in the treatment of chronic toxoplasmosis.

Choi W, Jiang M, Chu J (2013) Antiparasitic effects of Zingiber officinale (Ginger) extract against Toxoplasma gondii. J Appl Biomed 11(1):15–26.​

Journal of APPLIED BIOMEDICINE: Antiparasitic effects of Zingiber officinale (Ginger) extract against Toxoplasma gondii

Gharadaghi Y, Bahavarnia SR (2014) Repairing effect of Allium cepa on testis degeneration caused by Toxoplasma gondii in the rat​

An extra-point++ for Onion, worthwhile to find out if juice alone works, or you have to ingest all the gassy fodmaps...

 

[FoodForeal]

I would not wonder if an underlying weak spot of them or the way they hijack tissue would create a nice anti apicomplexa framework of substances, and or treatments (methylene blue + red light)....
Maybe they also share a common path for their abilities in immune suppression which could be reversed and so any problems with 'em fixed.

Yes they apparently have a circular ring organelle called an apicoplast (Apicoplast - Wikipedia) which is required for penetrating the host. This plasmid is derived from secondary endobiosis which means that it comes from algae that was absorbed by a protozoan and remained when the protozoans continued reproducing. Since mammal cells don't have anything resembling that it could be targeted somehow. Maybe if there's some folk remedy for algae or something like that which could target apicomplexans. I would think if there was a cure for malaria and toxoplasmosis as easy as that it would've been discovered already though.

 

[Karmeleon]

In context of one bug invites another -> immune supression already established...
Another lovely member of cat derived inhabitants (not limited to cats):

Bartonella henselae, formerly Rochalimæa henselae, is a proteobacterium that is the causative agent of cat-scratch disease[1] (bartonellosis).
There are multiple subspecies each a little bit different to diagnose and treat, but not less dangerous. It's not the same family as toxoplasma but shares
hosts often times.
It is also seemingly hard to kill with high chance of relapse and mis-diagnosis as crohn's or other serious degenerative disease, which we know by now
form follows function, so infection sort of creates the degenerative disease after function being destroyed.

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Bartonella henselae and inflammatory bowel disease​

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohn's disease in an adolescent boy. Bartonella henselae infection was diagnosed by specific serology and the patient recovered. Ileitis could be related to B. henselae infection.

Bartonella henselae and inflammatory bowel disease - PubMed

Sustained fever and increased thickness of the distal ileum on ultrasound suggested Crohn's disease in an adolescent boy. Bartonella henselae infection was diagnosed by specific serology and the patient recovered. Ileitis could be related to B. henselae infection.

pubmed.ncbi.nlm.nih.gov

Essential Oils with High Activity against Stationary Phase Bartonella henselae​

Bartonella henselae is a fastidious Gram-negative intracellular bacterium that can cause cat scratch disease, endocarditis in humans and animals, as well as other complications, leading to acute or chronic infections. The current treatment for Bartonella infections is not very effective presumably due to bacterial persistence. To develop better therapies for persistent and chronic Bartonella infections, in this study, with the help of SYBR Green I/PI viability assay, we performed a high-throughput screening of an essential oil library against the stationary phase B. henselae. We successfully identified 32 essential oils that had high activity, including four essential oils extracted from Citrus plants, three from Origanum, three from Cinnamomum, two from Pelargonium, and two from Melaleuca, as well as frankincense, ylang-ylang, fir needle, mountain savory (winter), citronella, spearmint, elemi, vetiver, clove bud, allspice, and cedarwood essential oils. The minimal inhibitory concentration (MIC) determination of these 32 top hits indicated they were not only active against stationary phase non-growing B. henselae but also had good activity against log-phase growing B. henselae. The time-kill assay showed 13 active hits, including essential oils of oregano, cinnamon bark, mountain savory (winter), cinnamon leaf, geranium, clove bud, allspice, geranium bourbon, ylang-ylang, citronella, elemi, and vetiver, could eradicate all stationary phase B. henselae cells within seven days at the concentration of 0.032% (v/v). Two active ingredients, carvacrol and cinnamaldehyde, of oregano and cinnamon bark essential oils, respectively, were shown to be very active against the stationary phase B. henselae such that they were able to eradicate all the bacterial cells even at the concentration ≤ 0.01% (v/v). More studies are needed to identify the active components of some potent essential oils, decode their antimicrobial mechanisms, and evaluate their activity against Bartonella infections in animal models. View Full-Text

Essential Oils with High Activity against Stationary Phase Bartonella henselae

Bartonella henselae is a fastidious Gram-negative intracellular bacterium that can cause cat scratch disease, endocarditis in humans and animals, as well as other complications, leading to acute or chronic infections. The current treatment for Bartonella infections is not very effective...

www.mdpi.com

Recommendations for Treatment of Human Infections Caused by Bartonella Species​

Various antibiotic regimens have been used to treat patients with complicated CSD (retinitis, encephalopathy, and visceral forms) (56, 108). The combination of doxycycline (100 mg p.o. or i.v. twice daily) with rifampin (300 mg p.o. twice daily) has been successful in treating patients with retinitis (Table 6, recommendation AII) (56, 84, 108). If treatment is chosen for patients with central nervous system (CNS) disease, the combination of doxycycline and rifampin is preferred. The optimum duration of antibiotic therapy for immunocompetent patients with complicated CSD has not been determined. Of note, there is a marked difference between the dramatic clinical response to antibiotics observed in immunocompromised patients with CSD and the minimal response observed in immunocompetent patients.

Aspirin was the most effective drug for the pain; and during World War II, soldiers with trench fever were “maintained in hospital no longer than necessary, then sent to convalescent depot where fresh air, good food and progressive exercise quickly restored them to full capacity so that they were able to return to duty” (44). During World War I, soldiers with trench fever cleared the infection in the absence of antibiotic treatment. However, successful treatment of some trench fever patients with tetracycline or chloramphenicol was reported after World War II, although these data remain anecdotal (10). Thus, it seems reasonable to prescribe doxycycline for such patients. In addition, we recommend that patients with the acute form of B. quintana bacteremia be treated with gentamicin (3 mg/kg of body weight i.v. once daily for 14 days), in combination with doxycycline (200 mg p.o. daily) for 28 days (Table 6, recommendation AI). Treatment of paucisymptomatic, persistent B. quintana bacteremia may be of importance for the prevention of endocarditis in these patients (35). A retrospective review of the treatment histories for patients with chronic bacteremia found that only those who were treated with doxycycline for 4 weeks and gentamicin for 14 days were cured, whereas those treated with beta-lactams or doxycycline alone were not (35).

https://journals.asm.org/doi/full/10.1128/AAC.48.6.1921-1933.2004

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Interesting that two compounds stick out and are also very effective for Toxoplasma infection:
Two active ingredients, carvacrol and cinnamaldehyde, of oregano and cinnamon bark essential oils, respectively, were shown to be very active against the stationary
phase B. henselae such that they were able to eradicate all the bacterial cells even at the concentration ≤ 0.01% (v/v).

In Vitro Anti-Toxoplasma gondii and Antimicrobial Activity of Amides Derived from Cinnamic Acid​

Most cinnamic acids, their esters, amides, aldehydes, and alcohols present several therapeutic actions through anti-inflammatory, antitumor, and inhibitory activity against a great variety of microorganisms. In this work, eight amines derived from cinnamic acid were synthesized and tested against host cells infected with Toxoplasma gondii and the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, and three strains of Staphylococcus aureus. Compounds 3 and 4 showed the best result against intracellular T. gondii, presenting antiparasitic activity at low concentrations (0.38 and 0.77 mM). The antibacterial activity of these compounds was also evaluated by the agar microdilution method, and amides 2 and 5 had a minimum inhibitory concentration of 250 µg mL−1 against two strains of S. aureus (ATCC 25923 and bovine strain LSA 88). These also showed synergistic action along with a variety of antibiotics, demonstrating that amines derived from cinnamic acid have potential as pharmacological agents. View Full-Text

In Vitro Anti-Toxoplasma gondii and Antimicrobial Activity of Amides Derived from Cinnamic Acid

Most cinnamic acids, their esters, amides, aldehydes, and alcohols present several therapeutic actions through anti-inflammatory, antitumor, and inhibitory activity against a great variety of microorganisms. In this work, eight amines derived from cinnamic acid were synthesized and tested...

www.mdpi.com

Evaluation of Origanum vulgare Essential Oil and Its Active Ingredients as Potential Drugs for the Treatment of Toxoplasmosis​

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was firstly studied, and then, carvanol (Ca), the main ingredient of Ov EO was evaluated using the MTT assay on human foreskin fibroblast (HFF) cells in vitro. The cytotoxicity was evaluated using the MTT assay on HFF cells. The CC50 of Ov EO and Ca was 134.9 and 43.93 μg/ml, respectively. Both of them exhibited anti-parasitic activity, and inhibited the growth of T. gondii in a dose-dependent manner. For the inhibition effect, Ca was better than Ov EO at the same concentration, the IC50 of Ov EO and Ca was 16.08 and 7.688 μg/ml, respectively. In addition, treatment with Ca, was found to change the morphology of T. gondii tachyzoites and made their shapes curl up. These results showed that Ca was able to inhibit the proliferation of T. gondii by reducing invasion, which may be due to its detrimental effect on the mobility of tachyzoites. Our results indicated that Ca could be a potential new and effective drug for treating toxoplasmosis.

Evaluation of Origanum vulgare Essential Oil and Its Active Ingredients as Potential Drugs for the Treatment of Toxoplasmosis

Toxoplasma gondii is a serious hazard to public health and animal husbandry. Due to the current dilemma of treatment of toxoplasmosis, it is urgent to find new anti-T. gondii drugs to treat toxoplasmosis. In this study, the anti-T. gondii activity of Origanum vulgare essential oil (Ov EO) was...

www.frontiersin.org

 

[Karmeleon]

Yes they apparently have a circular ring organelle called an apicoplast (Apicoplast - Wikipedia) which is required for penetrating the host. This plasmid is derived from secondary endobiosis which means that it comes from algae that was absorbed by a protozoan and remained when the protozoans continued reproducing. Since mammal cells don't have anything resembling that it could be targeted somehow. Maybe if there's some folk remedy for algae or something like that which could target apicomplexans. I would think if there was a cure for malaria and toxoplasmosis as easy as that it would've been discovered already though.

Interesting didn't know that. So maybe plant compounds working against those maybe originated to decimate other algae...
To reduce Algae growth in aquariums it's common to limit phosphate content. That would explain an increase in those infection types by environmental use of super phosphate fertilizers and phosphate use in meats. Very much in line with peats view of excess phosphate. It's also very likely that people on vegetarian or vegan diets are helped by a drop in total phosphor consumption, if phosphor is a needed growth factor in these type of micro organisms.

Tetracycline was mentioned before as a anti candida compound too.

Toxic effects of tetracycline and its degradation products on freshwater green algae​

Tetracycline antibiotics are the most widely used antibiotics in the world and the most common veterinary drugs and feed additives used in livestock, poultry and aquaculture operations. Because antibiotics cannot be completely removed by currently existing sewage treatment facilities, these materials enter the environment directly via sewage treatment plant discharge, where they degrade. Accordingly, the metabolism and the ecological toxicity of tetracycline degradation products are worthy of attention. Herein, we investigated the effects of tetracycline and its degradation products (anhydrotetracycline and epitetracycline hydrochloride) on the growth, cell structure and algal cell oxidative stress of common Chlorella vulgaris. The results showed that the 96h-EC50 values of tetracycline (TC), anhydrotetracycline (ATC) and epitetracycline (ETC) on algal cells were 7.73, 5.96 and 8.42 mg/L, respectively. Moreover, the permeability of algal cells exposed to high concentrations of these three drugs was significantly enhanced. In addition, there were structural changes in the cells such as plasmolysis and starch granule deposition appeared, the thylakoid lamellae in the chloroplasts became blurred and deformed, and the vacuoles became larger. Exposure to higher concentrations (>5 mg/L) of TC and its degradation products ATC and ETC significantly upregulated the activity of ROS, as well as the antioxidants SOD and CAT. The levels of the lipid peroxidation product MDA also showed the same trend. Finally, ATC had the strongest toxicity toward algal cells, followed by TC and then ETC.

Toxic effects of tetracycline and its degradation products on freshwater green algae - PubMed

Tetracycline antibiotics are the most widely used antibiotics in the world and the most common veterinary drugs and feed additives used in livestock, poultry and aquaculture operations. Because antibiotics cannot be completely removed by currently existing sewage treatment facilities, these...

pubmed.ncbi.nlm.nih.gov

Aquarium Medications Part 2 | Antibiotic & Antimicrobial Treatments​

Aquarium Medications Part 2 | Antibiotic & Antimicrobial Treatments

Aquarium & Pond medications Part 2, antibiotics and antimicrobials such as Kanamycin, Triple Sulfa, Tetracycline, Metronidazole, Nitrofurazone, Neomycin, & more. Based on research from aquarium keeping guru Carl Strohmeyer

www.americanaquariumproducts.com

 

[Karmeleon]

Babesia a Microbe of similar genus family like malaria and toxoplasmosis might be treated with the same approaches but susceptibility varies.
And the connection to cancer and Crohn's (misdiagnosed IBS/IBD anyone?) becomes intriguing, it's very possible that those critters are implicated way more than one would expect . Also treatment for blood parasites sometimes includes isoniacid, so niacin / niacinamide could help a lot.

​

babesiosis: clinical cases in the european part of the Russian Federation​

(PDF) Бабезиозы человека: клинические случаи в европейской части Российской Федерации Human babesiosis: clinical cases in the european part of the Russian Federation

PDF | The article describes four clinical observations of patients with babesiosis detected in the European part of the Russian Federation, two of whom... | Find, read and cite all the research you need on ResearchGate

www.researchgate.net

In a patient with imported babesiosis, we successfully used quinine monotherapy followed by a course of therapy with clarithromycin. A patient infected on the territory of the Russian Federation was treated with a combination of quinine and clindamycin, which also showed a parasitological effect with complete elimination of the pathogen. The development of a severe course of babesiosis, complicated by multiple organ failure, was influenced by such factors as the late admission of the patient (day 12 of illness), advanced age, the presence of a burdened premorbid background (history of malignant disease, autoimmune thyroiditis), high parasitemia in the blood ( 1B636 240 parasites per 1 µl of blood or 904 parasites per 1000B erythrocytes). Since 2007 in the ICU of ICH No. 2 with a complicated course of infectious diseases, such as malaria, meningococcal infection, successfully use extracorporeal methods of hemocorrection using CVVHD and plasmapheresis. Carrying out CVVHD leads to the removal of a wide range of toxic and biologically active substances (IL, TNF, other cytokines, etc.). In turn, plasmapheresis removes not only toxic substances, but also the removal of an excess amount of “free hemoglobin” that accumulates during the destruction of erythrocytes, which makes it possible to reduce or even prevent severe kidney damage [33]. The removal of the "toxic pressure" contributes to a more rapid restoration of an adequate immune response of the body. We believe that it was the use of a complex of these intensive care methods that made it possible to avoid a lethal outcome in this case, an extremely severe course of babesiosis. Carrying out CVVHD leads to the removal of a wide range of toxic and biologically active substances (IL, TNF, other cytokines, etc.). In turn, plasmapheresis removes not only toxic substances, but also the removal of an excess amount of “free hemoglobin” that accumulates during the destruction of erythrocytes, which makes it possible to reduce or even prevent severe kidney damage [33]. The removal of the "toxic pressure" contributes to a more rapid restoration of an adequate immune response of the body. We believe that it was the use of a complex of these intensive care methods that made it possible to avoid a lethal outcome in this case, an extremely severe course of babesiosis. Carrying out CVVHD leads to the removal of a wide range of toxic and biologically active substances (IL, TNF, other cytokines, etc.). In turn, plasmapheresis removes not only toxic substances, but also the removal of an excess amount of “free hemoglobin” that accumulates during the destruction of erythrocytes, which makes it possible to reduce or even prevent severe kidney damage [33]. The removal of the "toxic pressure" contributes to a more rapid restoration of an adequate immune response of the body. We believe that it was the use of a complex of these intensive care methods that made it possible to avoid a lethal outcome in this case, an extremely severe course of babesiosis. In turn, plasmapheresis removes not only toxic substances, but also the removal of an excess amount of “free hemoglobin” that accumulates during the destruction of erythrocytes, which makes it possible to reduce or even prevent severe kidney damage [33]. The removal of the "toxic pressure" contributes to a more rapid restoration of an adequate immune response of the body. We believe that it was the use of a complex of these intensive care methods that made it possible to avoid a lethal outcome in this case, an extremely severe course of babesiosis. In turn, plasmapheresis removes not only toxic substances, but also the removal of an excess amount of “free hemoglobin”

JAMES SCHALLER, MD DISCOVERS BABESIA AS A CANCER PRIMER​

Introduction: In 2001 we reported the first case of use of imatinib mesylate (Gleevec) for treatment of idiopathic hypereosinophilia syndrome (HES). These findings have been replicated in some patients with HES. After 1 year of taking imatinib, the patient stopped this medication, and during the last 5 years the patient has not experienced a relapse. He has, however, recently been diagnosed with babesiosis. This new diagnosis might relate to his HES. Methods: After 6 years we decided to follow up on this patient's treatment. We interviewed the patient, his son, his aunt, and 2 consulting physicians and also reviewed relevant laboratory results to determine whether his HES had returned and whether his residual morbidity had changed. Results: The patient has had no relapse of HES and his eosinophil counts have remained low-normal. He was recently diagnosed with babesiosis, and was prescribed atovaquone and azithromycin with a significant decrease in morbidity. His eosinophil cationic protein levels have also fallen to low-normal since starting atovaquone and azithromycin.

Discussion: New Babesia species are emerging as human infections. Most do not have available antibody or polymerase chain reaction diagnostic testing at this time. Manual differential examinations are of variable utility due to low numbers of infected red blood cells, suboptimal technique, and limited experience. Therefore, a diagnosis might need to be empirical at times, and should be based on signs and symptoms. Conclusion: The patient has not relapsed in the 5 years that he has not been taking imatinib. Babesiosis should be added to the many possible causes of HES. It is unknown how often babesiosis causes HES as well as what percentage of HES patients have babesiosis.

Inhibitory effects of Uncaria tomentosa bark, Myrtus communis roots, Origanum vulgare leaves and Cuminum cyminum seeds extracts against the growth of Babesia and Theileria in vitro​

Catʼs claw （Uncaria tomentosa）, myrtle （Myrtus communis）, oregano （Origanum vulgare）, and cumin （Cuminum cyminum） have diverse medicinal properties. The current study evaluated the growth-inhibitory effects of these herbal extracts against Babesia and Theileria parasites in vitro and examined their cytotoxic properties. The half maximal inhibitory concentration （IC50） values against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi for acetonic U. tomentosa extract were 16.1 ± 0.7, 12.8 ± 2.8, 29.5 ± 1.5, 41.7 ± 14.5, and 69.5 ± 4.7 µg/ml, and those for acetonic M. communis extract were 88 ± 35.1, 115.6 ± 9.5, 33.8 ± 1.9, 28.3 ± 8.5, and 58.1 ± 0.4 µg/ml, respectively. The half maximal effective concentration （EC50） values for acetonic U. tomentosa and M. communis extracts on Madin-Darby bovine kidney （MDBK） cell lines were 50.7 ± 3.7 and 470 ± 42.4 µg/ml, and those on human foreskin fibroblast （HFF） cell lines were 337.3 ± 22.5 and 856 ± 32.9 µg/ml, respectively. The ethanolic O. vulgare extract and methanolic C. cyminum extract exhibited IC50 values of 240.4 ± 9.7, 135.9 ± 2.9, 116.6 ± 1.6, 101.2 ± 52.6, and 173.5 ± 78.5 µg/ml and 293.3 ± 3.1, 289.9 ± 2.4, 243.2 ± 6.8, 282.2 ± 5.3, and 273.1 ± 26.9 µg/ml against B. bovis, B. bigemina, B. divergens, B. caballi, and T. equi, respectively, with EC50 values on MDBK and HFF cell lines at 1000 ± 44.6 and ＞ 1000 µg/ml, respectively. In conclusion, these extracts are effective against Babesia and Theileria in vitro without cytotoxic properties. Further research is necessary to identify the bioactive component of the herbal extracts and to evaluate the chemotherapeutic efficacy of the identified bioactive component against Babesia and Theileria in cattle and horses in the future.

Inhibitory effects of methanolic Olea europaea and acetonic Acacia laeta on growth of Babesia and Theileria​

Objective: To evaluate the antipiroplasmic activities of methanolic extract of Olea europaea (MOE) and acetonic extract of Acacia laeta (AAL) against Babesia and Theileria parasites in vitro and evaluate the chemotherapeutic effects of these extracts against Babesia (B.) microti in vivo.
Methods: Fluorescence assay using SYBR Green 1 nucleic acid stain was used to detect inhibitory effects of the two extracts as well as the combination effects of the two extracts with diminazene aceturate and atovaquone on four Babesia species and Theileria equi in vitro while for in vivo experiments, 8-weekold female BALB/c mice were injected intraperitoneally with 1 × 107B. microti-iRBCs and treated orally at a dose of 150 mg/kg of both extracts.
Results: The half maximal inhibitory concentration (IC50) values of AAL against B. bovis, B. bigemina, B. divergens, B. caballi, and Theileria equi were lower than those of MOE extracts. Toxicity assay on Madin–Darby bovine kidney, mouse embryonic fibroblast (MH/3T3), and human foreskin fibroblast cell lines showed that MOE and AAL affected only the viability of Madin–Darby bovine kidney cell line with half maximal effective concentrations (EC50) of (794.7±41.9) and (873.9±17.5) μg/mL, respectively. The oral treatments of MOE and AAL at 150 mg/kg inhibited the growth of B. microti in mice by 80.4% and 64.4%, respectively. The MOE and diminazene aceturate combination showed a higher chemotherapeutic effect than that of monotherapy.
Conclusions: MOE and AAL have the potential to be an alternative remedy for treating piroplasmosis. Furthermore, the combination therapy of MOE + DA was more potent against B. microti infection in mice than their monotherapies.

Inhibitory effects of methanolic Olea europaea and acetonic Acacia laeta on growth of Babesia and Theileria Beshbishy AM, El-Saber Batiha G, Adeyemi OS, Yokoyama N, Igarashi I - Asian Pac J Trop Med

Asian Pacific Journal of Tropical Medicine, Editorial office of Hainan Medical University

www.apjtm.org

A Case of Severe Babesiosis in a Patient with Crohn's Colitis on Adalimumab​

A 56-year-old male with Crohn's ileocolitis complicated by fistula on maintenance treatment with adalimumab, presented to the emergency department with 10 days of spiking fevers, chills, fatigue, abdominal pain, and anorexia after a trip to Connecticut. Physical exam revealed fever, tachycardia, hypotension and hepatosplenomegaly. At presentation, he was mildly anemic and thrombocytopenic, with leukocytes at 5400/uL, alkaline phosphatase at 140 U/L, an elevated LDH and low haptoglobin. Thick peripheral blood smear suggested babesia microti infection, which was confirmed by DNA PCR. His parasitemia level was 5.7%. He was started on oral atovaquone 750mg every 12 hours and oral azithromycin 1g every 24 hours with improvement in his parasitemia level to 1.24% by day 6, 1% by day 10, and 0% by day 14. Babesiosis is a tick-borne illness caused by intraerythrocytic protozoa. While most cases are asymptomatic, a more severe clinical disease can be seen in patients with advanced age (greater than 40 years), asplenia and depressed cellular immunity. As seen in our patient, who was immunocompromised from treatment with a TNF-alpha inhibitor (adalimumab), impaired immunity resulted in a more severe infection and prolonged hospital course. His parasitemia level did not clear until after day 10 of treatment and he had to remain on the higher dose azithromycin/atovaquone combination therapy for 3 more weeks to avoid relapsing illness. In addition, among the inflammatory bowel disease (IBD) population, the often-vague presentation of severe babesiosis can mimic a Crohn's flare - potentially delaying initiation of antimicrobial therapy and increasing risk for morbidity and mortality in these already vulnerable patients. Given the dramatic rise in cases of babesiosis in the Northeast and upper Midwest over the last decade, early consideration of babesiosis among immunocompromised IBD patients presenting with fever and poorly localized symptoms is essential. Ultimately, this case report illustrates how the severity and clinical course of a babesiosis infection varies with the immune status of a patient and highlights the importance of early consideration of babesiosis in immunocompromised IBD patients presenting with fever and non-specific symptoms.

A Case of Severe Babesiosis in a Patient with Crohn's... : Official journal of the American College of Gastroenterology | ACG

An abstract is unavailable.

journals.lww.com

 

[Karmeleon]

Discovery of New Antimalarial Compounds by use of Molecular Connectivity Techniques​

Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity functions were used to select several potentially suitable drugs which were tested for antimalarial properties by use of an in-vitro micro test which estimates parasite growth by measurement of incorporation of [3H]hypoxanthine. Hexetidine stands out among the compounds selected. Activity assays were performed with Plasmodium falciparum passou and 3CD7 strains, for which the IC50 values (doses resulting in 50% inhibition) were 320 and 400 ng mL−1 respectively. These results are comparable with those obtained for quinine chlorhydrate (IC50 = 60 and 107.8 ng mL−1) and chloroquine sulphate (IC50 = 231 and 415 ng mL−1), the drugs used for reference. These results demonstrate the usefulness of our topological approach for the selection and design of new lead drugs active against Plasmodium falciparum.

Activity results obtained with hydroxyzine and Plasmodium falciparum: d, passou strain; s, 3CD7 strain.​

(PDF) Discovery of New Antimalarial Compounds by use of Molecular Connectivity Techniques

PDF | Molecular connectivity has been applied to the search for new compounds with antimalarial activity. Linear discriminant analysis and connectivity... | Find, read and cite all the research you need on ResearchGate

www.researchgate.net

Using Machine Learning to Predict Synergistic Antimalarial Compound Combinations With Novel Structures​

Using Machine Learning to Predict Synergistic Antimalarial Compound Combinations With Novel Structures

The parasite Plasmodium falciparum is the most lethal species of Plasmodium to cause serious malaria infection in humans, and with resistance developing rapidly novel treatment modalities are currently being sought, one of which being combinations of ...

www.ncbi.nlm.nih.gov

The parasite Plasmodium falciparum is the most lethal species of Plasmodium to cause serious malaria infection in humans, and with resistance developing rapidly novel treatment modalities are currently being sought, one of which being combinations of existing compounds. The discovery of combinations of antimalarial drugs that act synergistically with one another is hence of great importance; however an exhaustive experimental screen of large drug space in a pairwise manner is not an option. In this study we apply our machine learning approach, Combination Synergy Estimation (CoSynE), which can predict novel synergistic drug interactions using only prior experimental combination screening data and knowledge of compound molecular structures, to a dataset of 1,540 antimalarial drug combinations in which 22.2% were synergistic. Cross validation of our model showed that synergistic CoSynE predictions are enriched 2.74 × compared to random selection when both compounds in a predicted combination are known from other combinations among the training data, 2.36 × when only one compound is known from the training data, and 1.5 × for entirely novel combinations. We prospectively validated our model by making predictions for 185 combinations of 23 entirely novel compounds. CoSynE predicted 20 combinations to be synergistic, which was experimentally validated for nine of them (45%), corresponding to an enrichment of 1.70 × compared to random selection from this prospective data set. Such enrichment corresponds to a 41% reduction in experimental effort. Interestingly, we found that pairwise screening of the compounds CoSynE individually predicted to be synergistic would result in an enrichment of 1.36 × compared to random selection, indicating that synergy among compound combinations is not a random event. The nine novel and correctly predicted synergistic compound combinations mainly (where sufficient bioactivity information is available) consist of efflux or transporter inhibitors (such as hydroxyzine), combined with compounds exhibiting antimalarial activity alone (such as sorafenib, apicidin, or dihydroergotamine). However, not all compound synergies could be rationalized easily in this way. Overall, this study highlights the potential for predictive modeling to expedite the discovery of novel drug combinations in fight against antimalarial resistance, while the underlying approach is also generally applicable.

Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani​

Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although Babesia duncani was first described almost 30 years ago, further research is needed to elucidate its pathogenesis and clarify optimal treatment regimens. Here, we screened a panel of herbal medicines and identified Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Alchornea cordifolia, and Polygonum cuspidatum to have good in vitro inhibitory activity against B. duncani in the hamster erythrocyte model. Furthermore, we found their potential bioactive compounds, cryptolepine, artemisinin, artesunate, artemether, and baicalein, to have good activity against B. duncani, with IC50 values of 3.4 μM, 14 μM, 7.4 μM, 7.8 μM, and 12 μM, respectively, which are comparable or lower than that of the currently used drugs quinine (10 μM) and clindamycin (37 μM). B. duncani treated with cryptolepine and quinine at their respective 1×, 2×, 4× and 8× IC50 values, and by artemether at 8× IC50 for three days could not regrow in subculture. Additionally, Cryptolepis sanguinolenta 90% ethanol extract also exhibited no regrowth after 6 days of subculture at doses of 2×, 4×, and 8× IC50 values. Our results indicate that some botanical medicines and their active constituents have potent activity against B. duncani in vitro and may be further explored for more effective treatment of babesiosis.

Botanical Medicines Cryptolepis sanguinolenta, Artemisia annua, Scutellaria baicalensis, Polygonum cuspidatum, and Alchornea cordifolia Demonstrate Inhibitory Activity Against Babesia duncani - PubMed

Human babesiosis is a CDC reportable disease in the United States and is recognized as an emerging health risk in multiple parts of the world. The current treatment for human babesiosis is suboptimal due to treatment failures and unwanted side effects. Although <i>Babesia duncani</i> was first...

pubmed.ncbi.nlm.nih.gov

efflux or transporter inhibitors (such as hydroxyzine) -> disables antibiotic resistance!​

antimalarial activity alone (such as sorafenib, apicidin, or dihydroergotamine) -> ergot class has antibiotic activity​

 

[FoodForeal]

@Karmeleon just want to say you're finding some insightful studies, Great work! Potentially we can help treat or cure toxoplasmosis, malaria, and lyme disease since at least parts of all these diseases are often caused by apicomplexans.

 

[Karmeleon]

@Karmeleon just want to say you're finding some insightful studies, Great work! Potentially we can help treat or cure toxoplasmosis, malaria, and lyme disease since at least parts of all these diseases are often caused by apicomplexans.

Thank you, exactly! That's my intention behind posting all that stuff, if i do it just for myself it would be less work, but the benefit for everyone and participation of you-others are way more valuable. The forums about tick-born stuff people are trying to catch their tales without much success, i think a greater picture is needed for these complex creatures and what they do to us. A peaty-metabolic approach feels the best shot with every aspect we've got (terrain, nutrients, stress, hormones, infections, developmental....). I was thinking about splitting the thread into different parasite species, treatment approaches, maybe we have to later. Now its more convenient to have it in one place.

:some personal note
I was able to source some Hydroxyzine and stick to a dose about half a tablet-12.5mg split in 2 doses per day.
Also i got the scutellaria baicalensis extract, astralagus extract, also do a split in 2-3 doses a day (scutellaria 80%: 300mgx2, astralagus 5% 500mgx2).
Not overdoing in terms of Dopamin Agent withdrawal (DAWS) i stick to 50mcg Lisuride (ergot drugs also have activity) and 0.5mg Cypro at night.
In my foods a added enough Thyme, Oregano, Cumin (1/2-1tsp), Ceylon Cinnamon (1/2 tsp) to count as middle eastern cuisine :).
The stash of Tonic water is depleted atm, maybe i add some gin-tonic as night time tread, I've found some cinchona tincture at an online pharmacy i'll check this one out too. I got some high endo-toxin symptoms with sinus migraine and anhedonia for about 2 days after doing this cocktail, i increased my doses of pregnenolone and progest-e to counter the endo-toxin, by now gut is settling down and my mood and energy levels are improving vastly. Key component were the hydroxyzine and the herbals. Feels like something very inflammatory and serotonergic always in the background is now (nearly) gone.
I had a history of tick bite too, but all anti-gen test came back negative. The only clue i had something is very wrong was a collapsed IGG3 in an immune panel.
Dr. google says IGG3 is nearly zero if you got some kind of bacteremia / sepsis going on.

I also wonder about the typical cuisine of middle east -> india, they all rely heavily on mentioned cooking herbs, and for india at least total cancer rates and alzheimers are WAY below the Western rates. If babesia have a multitude of species also bartonella, possibly toxoplasma i bet they are simply not detected by tests and are an underlying disease driver for a lot of people. I've read that chronic infection - super infection of salmonella type of bacteria is common and dangerous in babesia infections.... Also chicken farmers utilize Cinnamon and Oregano oils in their feed, since antibiotics are out of fashion, to increase yield. Chicken/poultry are a major source of salmonella, besides pigs are too.

 

[FoodForeal]

Maybe a potential lead would be why cows seem to be more immune to T. gondii than other animals.

Toxoplasma gondii infection in sheep and cattle - PubMed

Toxoplasma gondii is a protozoan parasite that can infect all warm-blooded animals. Sheep and cattle show different susceptibilities to T. gondii infection. Primary infection in pregnant sheep can result in abortion or the birth of weak lambs but they are then protected against further challenge...

pubmed.ncbi.nlm.nih.gov

"Cattle on the other hand can be readily infected, but abortion or perinatal mortality have not been recorded. The evidence suggests that cattle develop a more effective immune response to T. gondii infection than sheep. Potential mechanisms to explain these differences are discussed in this paper."

Seroprevalence of Toxoplasma gondii in Dairy Cattle with Reproductive Problems in Sudan

Toxoplasmosis, caused by Toxoplasma gondii, is one of the most common parasitic infections of humans and other warm-blooded animals in most parts of the world. The disease is common among sheep and goats and it is recognized as one of the major causes ...

www.ncbi.nlm.nih.gov

"The disease is common among sheep and goats and it is recognized as one of the major causes of reproductive failure in these animals. Cattle, on the other hand, can be infected, but abortion or perinatal mortality has not been recorded."
"Cattle are generally described as insensitive to T. gondii infection. Cattle would harbour few parasite tissue cysts, which may not persist for the lifetime of the host [23–25].
The prevalence was also observed to be significantly (P ≤ 0.05) higher in males (30.8%) than females."


I think viruses don't exist and vaccination against them is therefore unnecessary, but a "vaccine" or purposeful infection with a milder version of a parasite as described here may be interesting to look into.

Cattle parasite study points to possible way to fight malaria

Herds of African cattle may hold the secret to new ways of fighting parasitic diseases like malaria, which kills some 600,000 people a year, scientists said on Friday.

www.reuters.com

"
The researchers from the University of Edinburgh found that cows are protected from a parasite that causes a deadly disease called East Coast Fever if they have previously been infected with a closely-related but milder species of the parasite.

This discovery, they said, suggests that “fighting fire with fire” is a strategy that might work against a range of parasitic diseases, including severe malarial infection in people.

“Our results suggest seeking a simple vaccine that could protect cows from East Coast fever by inoculating them with a related but far less harmful parasite,” said Mark Woolhouse, who led the study with a team from several other universities and the International Livestock Research Institute.
"

Go to page 120: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/sp.efsa.2016.EN-995

Discovering How Toxoplasma Hijacks Host Cells to Ride to the Brain

In a paper out today in Cell Host & Microbe, a collaborative team led by UC Davis School of Veterinary Medicine researcher Jeroen Saeij identified one of the T. gondii genes responsible for how well the parasite survives in a host.

www.vetmed.ucdavis.edu

"
Researchers found zero brain cysts in the infected mice, showing that the deletion of TgWIP had a huge effect on the parasite’s ability to reach the brain.
This looks like it could be the master regulator of Toxoplasma’s ability to hijack immune cells for its own benefit,” Saeij said. “We’re really excited about this. This gene is clearly important for the lifecycle of Toxoplasma and this discovery could be the building block for other researchers to develop novel treatments against Toxoplasma infection.”
"

 

[Karmeleon]

Sounds like the story of cow pox vs small pox. Weren't cow pox the first vaccine ever? Use cow pustule infectious material (maybe with immune modifying compounds included) and inject those into people. Definitive a pufa and hormonal involvement too, or to speak progesterone, female cows were more protected than male ones.
But why cows? It should not be the rumen, all herbivores cited, goat, sheep, have 4 stomachs. And goat need a lot more copper than those others, copper is also anti planctonic, destroys cyanobacteria, protobacteria. Intersting find was:

Team of scientists uncover copper poisoning as ancient mechanism in bacterial predation by protozoa​

Protozoans were the first eukaryotes to interact with bacteria and their evolutionary success was directly attributed to their ability to effectively engulf (through phagocytosis), kill and then digest their prey. Eventually, predatory protozoa that acquired the most effective mechanisms to kill bacteria became dominant, but the same evolutional pressure forced bacteria to develop resistance mechanisms to minimize damage. In the recent study published in Molecular Microbiology “A role for copper in protozoan predation-selecting bacterial copper resistance for 2 billion years” (DOI 10.1111/mmi.13483), a novel concept of protozoan predation as a major selection factor for maintenance and acquisition of copper resistance determinants was developed. The driving force behind the outlining of this hypothesis was our desire to explain the widespread presence of copper resistance determinants in environments where copper concentrations are very low, such as in a deep ocean. The effect of anthropological factors on copper resistance development in those environments is also minimal. Therefore, we have looked for a naturally occurring selective pressure that could result in the increased occurrence of copper resistance determinants in bacteria. Our experiments showed that protozoa use copper to poison and kill bacterial prey and, in our opinion, preselect for bacteria that possess mechanisms counteracting the toxicity of copper. This hypothesis was tested by examining survival of bacteria differing in their copper resistance determinants in two distinct unicellular eukaryote models, Dictyostelium discoideum and Paracercomanas. We could conclusively show the role of Cu(I) in protozoan predation of bacteria, confirming our original hypothesis. This study was led by Professors Christopher Rensing and Yong-Guan Zhu, Institute of Urban Environment, Chinese Academy of Sciences in Xiamen. Both professors have been collaborating on environmental microbiology and biogeochemistry over the last 10 years.​

Team of scientists uncover copper poisoning as ancient mechanism in bacterial predation by protozoa----Institute,xiamen,Urban,Environment,Academy,health,Sciences

Team of scientists uncover copper poisoning as ancient mechanism in bacterial predation by protozoa

english.iue.cas.cn

The Impact of Protozoan Predation on the Pathogenicity of Vibrio cholerae​

In the aquatic environment, Vibrio spp. interact with many living organisms that can serve as a replication niche, including heterotrophic protists, or protozoa. Protozoa engulf bacteria and package them into phagosomes where the cells are exposed to low pH, antimicrobial peptides, reactive oxygen/nitrogen species, proteolytic enzymes, and low concentrations of essential metal ions such as iron. However, some bacteria can resist these digestive processes. For example, Vibrio cholerae and Vibrio harveyi can resist intracellular digestion. In order to survive intracellularly, bacteria have acquired and/or developed specific factors that help them to resist the unfavorable conditions encountered inside of the phagosomes. Many of these intra-phagosomal factors used to kill and digest bacteria are highly conserved between eukaryotic cells and thus are also expressed by the innate immune system in the gastrointestinal tract as the first line of defense against bacterial pathogens. Since pathogenic bacteria have been shown to be hypervirulent after they have passed through protozoa, the resistance to digestion by protist hosts in their natural environment plays a key role in enhancing the infectious potential of pathogenic Vibrio spp. This review will investigate the current knowledge in interactions of bacteria with protozoa and human host to better understand the mechanisms used by both protozoa and human hosts to kill bacteria and the bacterial response to them.

The Impact of Protozoan Predation on the Pathogenicity of Vibrio cholerae

In the aquatic environment, Vibrio spp. interact with many living organisms that can serve as a replication niche, including heterotrophic protists, or protozoa. Protozoa engulf bacteria and package them into phagosomes where the cells are exposed to low pH, antimicrobial peptides, reactive...

www.frontiersin.org

The Rumen Protozoa​

The Rumen Protozoa

All ruminants are dependent on the microorganisms that live in their forestomach - the rumen - to break down ingested feed constituents into a form that the host animal can utilize. Protozoa are part of this complex ruminal population and are essential for the nutritional well-being and...

books.google.at

I

It start to feel more like a whole eco-system.... Maybe we never were a prefered target for protozoa - apicomplexans. If protozoa are more after their primary food source - bacteria - and use copper as a weapon to kill prey.
Isn't cow liver one of the top source of copper? They create a lot of bacteria in their rumen and at least in sheep if protozoa are decimated copper accumulates in their livers - for sheep a deadly disease. So copper kills bacteria and kind of feeds? protozoa. The underlying principle may be protozoa are feeding off bacteria if they have enough dietary copper and if their primary prey isn't available they go for secondary mitochondria?
Doesn't explain why cows are special in that regard but it gives a clue.

 

[FoodForeal]

Something to keep in mind with these parasites is that they have become highly specialized over the eons and they discard genes that make up dead weight. For example, myxozoans:
"While the evolutionary history of myxozoans is still an active area of research, it is currently taught that myxozoans are highly derived cnidarians that have undergone dramatic evolution from a free swimming, self-sufficient jellyfish-like creature into their current form of obligate parasites composed of very few cells, and sometimes only a single cell.[6] As myxozoans evolved into microscopic parasites, they lost many genes responsible for multicellular development, coordination, cell-cell communication, and even, in some cases, aerobic respiration.[7] The genomes of some myxozoans are now among the smallest genomes of any known animal species.[8]" Myxozoa - Wikipedia
If apicomplexans have lost their bacterial hunting weaponry than copper may be a dead end, but like you said it could be a clue to something at least.


On the "vaccine" idea from the paper I linked earlier: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/sp.efsa.2016.EN-995
"Vaccination with S48 strain T. gondii was shown to reduce tissue cyst formation in vaccination and challenge studies in sheep and pigs. "

Haven't read it fully yet but this study seems to have an interesting look into how the immune system begins to tolerate the disease as time goes on: Disease Tolerance in Toxoplasma Infection
"Toxoplasma must evade sterilizing immunity, but still rely on the host's immune response for survival and transmission. To do this, Toxoplasma exploits a central cost-benefit tradeoff in immunity: the need to escalate inflammation for pathogen clearance vs. the need to limit inflammation-induced bystander damage."

So our body wants to kill toxoplasma but it doesn't want to hurt healthy cells and toxoplasma also plays on that to help suppress the immune system while still keeping it active enough to ride on dendritic immune cells to desired tissue.
If we could turn off our immune system temporarily without causing other infections and before toxoplasmosis can spread too much and then turn it back on when t gondii is trying to amplify immune response, the immune system may be wrenched from under its control.

Maybe the immune system could be modulated to change its response so that it can be cleared completely in one fell swoop although its probably impossible for all to be eliminated completely and any lessening in immune response would mean that it could proliferate and replace the damaged population. Plus it would cause lots of damage to the body. But the main problem seems to be that t. gondii convinces the immune system that there will be too much collateral damage if it attacks. If we can override that we may be able to elicit a sterilizing response.

It seems that a strong immune system helps a lot with preventing infection initially, pretty common sense. Obviously a good reminder that the first step to recovery is ensuring maximal health through controlling your diet, healthy vs unhealthy activities, and environment. Wifi even is a consideration because it acts on cell function even though it is non-ionizing radiation.

Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection

The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining ...

www.ncbi.nlm.nih.gov

"Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen."
"During chronic infection, parasite-specific T lymphocytes release high levels of IFN-γ, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production."

Another study on immune system but with focus on t gondii manipulation of it. T gondii needs the immune system to react in order to spread, but not enough that it kills it off completely. The abstract mentions that t gondii can suppress apoptosis even by inhibiting caspase, but maybe things that increase autophagy like fasting can overcome this. So from what I can see so far toxoplasmosis benefits from downregulated immunity but will stop suppression if immune response becomes too suppressed. Perhaps at a time when you feel most sick (immune suppressed? Or would you feel more sick when fighting it harder? I suppose symptoms differ depending on whether the parasite is damaging the body or inflammatory immune response is causing damage, something to look into) it would actually be best to use a treatment that increases immune response to surprise toxoplasmosis at a time when it thinks it can spread.
The abstract mentions an "unusual" parasite specific pro inflammatory pathway which is key for toxoplasmosis to counter along with a common toll receptor pathway. Maybe things that promote antiparasitic effects in general could enhance the response to t. gondii and reduce inflammatory collateral damage.

From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii

Abstract. The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-γ induction

academic.oup.com

The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-γ induction is vital in resistance to the parasite. Dendritic cells, neutrophils and macrophages are important sources of IL-12 during infection. T. gondii possesses two mechanisms for triggering IL-12. One is dependent upon the common adaptor protein MyD88, and is likely to involve Toll-like receptors. The other is a more unusual pathway that involves triggering through CCR5 by a parasite cyclophilin molecule. Countering these potent pro-inflammatory activities, T. gondii has several mechanisms to down-regulate immunity. Intracellular infection causes a blockade in the NFκB macrophage signaling pathway, correlating with reduced capacity for IL-12 and TNF-α production. The parasite also prevents STAT1 activity, resulting in decreased levels of IFN-γ-stimulated MHC surface antigen expression. Furthermore, infection also induces resistance to apoptosis through inhibition of caspase activity. Extracellular pathways of suppression involve soluble mediators such as IL-10 and lipoxins that have potent IL-12 down-regulatory effects. The balance of pro-inflammatory and anti-inflammatory signaling which T. gondii engages is likely dictated by requirements for a stable host–parasite interaction. First, there is a need for Toxoplasma to induce an immune response robust enough to allow host survival and establish long-term chronic infection. Second, the parasite must avoid immune-elimination and induction of pro-inflammatory pathology that can cause lethality if unchecked. The widespread distribution of T. gondii and the normally innocuous nature of infection indicate the skill with which the parasite achieves the two seemingly contrary goals.

Hello PUFA my old friend. Maybe eating pufa as prophylactic could make it think it is in cat gut and have sex instead of trying to infect the brain of what it thinks is cat but is actually human. Jk but interesting to think about.

JCI - The molecular biology and immune control of chronic Toxoplasma gondii infection

www.jci.org

"T. gondii invades the small intestine of its host (4, 5). Recent work from Laura Knoll’s laboratory suggests that the parasite may sense linoleic acid in the feline gut as a critical signal for sexual stage differentiation in these species (6). "

Immune response to t gondii diagram. Click "back to article" to see the paper Human immunity to Toxoplasma gondii

 

[Karmeleon]

Maybe a potential lead would be why cows seem to be more immune to T. gondii than other animals. View attachment 35097

Toxoplasma gondii infection in sheep and cattle - PubMed

Toxoplasma gondii is a protozoan parasite that can infect all warm-blooded animals. Sheep and cattle show different susceptibilities to T. gondii infection. Primary infection in pregnant sheep can result in abortion or the birth of weak lambs but they are then protected against further challenge...

pubmed.ncbi.nlm.nih.gov

"Cattle on the other hand can be readily infected, but abortion or perinatal mortality have not been recorded. The evidence suggests that cattle develop a more effective immune response to T. gondii infection than sheep. Potential mechanisms to explain these differences are discussed in this paper."

Seroprevalence of Toxoplasma gondii in Dairy Cattle with Reproductive Problems in Sudan

Toxoplasmosis, caused by Toxoplasma gondii, is one of the most common parasitic infections of humans and other warm-blooded animals in most parts of the world. The disease is common among sheep and goats and it is recognized as one of the major causes ...

www.ncbi.nlm.nih.gov

"The disease is common among sheep and goats and it is recognized as one of the major causes of reproductive failure in these animals. Cattle, on the other hand, can be infected, but abortion or perinatal mortality has not been recorded."
"Cattle are generally described as insensitive to T. gondii infection. Cattle would harbour few parasite tissue cysts, which may not persist for the lifetime of the host [23–25].
The prevalence was also observed to be significantly (P ≤ 0.05) higher in males (30.8%) than females."


I think viruses don't exist and vaccination against them is therefore unnecessary, but a "vaccine" or purposeful infection with a milder version of a parasite as described here may be interesting to look into.

Cattle parasite study points to possible way to fight malaria

Herds of African cattle may hold the secret to new ways of fighting parasitic diseases like malaria, which kills some 600,000 people a year, scientists said on Friday.

www.reuters.com

"
The researchers from the University of Edinburgh found that cows are protected from a parasite that causes a deadly disease called East Coast Fever if they have previously been infected with a closely-related but milder species of the parasite.

This discovery, they said, suggests that “fighting fire with fire” is a strategy that might work against a range of parasitic diseases, including severe malarial infection in people.

“Our results suggest seeking a simple vaccine that could protect cows from East Coast fever by inoculating them with a related but far less harmful parasite,” said Mark Woolhouse, who led the study with a team from several other universities and the International Livestock Research Institute.
"

Go to page 120: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/sp.efsa.2016.EN-995
View attachment 35099

Discovering How Toxoplasma Hijacks Host Cells to Ride to the Brain

In a paper out today in Cell Host & Microbe, a collaborative team led by UC Davis School of Veterinary Medicine researcher Jeroen Saeij identified one of the T. gondii genes responsible for how well the parasite survives in a host.

www.vetmed.ucdavis.edu

"
Researchers found zero brain cysts in the infected mice, showing that the deletion of TgWIP had a huge effect on the parasite’s ability to reach the brain.
This looks like it could be the master regulator of Toxoplasma’s ability to hijack immune cells for its own benefit,” Saeij said. “We’re really excited about this. This gene is clearly important for the lifecycle of Toxoplasma and this discovery could be the building block for other researchers to develop novel treatments against Toxoplasma infection.”
"

In Vitro Activity of Riboflavin against the Human Malaria Parasite Plasmodium falciparum​

The human malaria parasite Plasmodium falciparum digests hemoglobin and polymerizes the released free heme into hemozoin. This activity occurs in an acidic organelle called the food vacuole and is essential for survival of the parasite in erythrocytes. Since acidic conditions are known to enhance the auto-oxidation of hemoglobin, we investigated whether hemoglobin ingested by the parasite was oxidized and whether the oxidation process could be a target for chemotherapy against malaria. We released parasites from their host cells and separately analyzed hemoglobin ingested by the parasites from that remaining in the erythrocytes. Isolated parasites contained elevated amounts (38.5% ± 3.5%) of oxidized hemoglobin (methemoglobin) compared to levels (0.8% ± 0.2%) found in normal, uninfected erythrocytes. Further, treatment of infected cells with the reducing agent riboflavin for 24 h decreased the parasite methemoglobin level by 55%. It also inhibited hemozoin production by 50% and decreased the average size of the food vacuole by 47%. Administration of riboflavin for 48 h resulted in a 65% decrease in food vacuole size and inhibited asexual parasite growth in cultures. High doses of riboflavin are used clinically to treat congenital methemoglobinemia without any adverse side effects. This activity, in conjunction with its impressive antimalarial activity, makes riboflavin attractive as a safe and inexpensive drug for treating malaria caused by P. falciparum.

In Vitro Activity of Riboflavin against the Human Malaria Parasite Plasmodium falciparum

The human malaria parasite Plasmodium falciparum digests hemoglobin and polymerizes the released free heme into hemozoin. This activity occurs in an acidic organelle called the food vacuole and is essential for survival of the parasite in erythrocytes. ...

www.ncbi.nlm.nih.gov

Riboflavin deficiency and severity of malaria.​

The riboflavin status of 64 children suffering from malarial infection was assessed by measuring the activation coefficient of erythrocyte glutathione reductase. Thirty-five children were found to be deficient in riboflavin whereas in 29 children riboflavin status was within the normal range. The median parasite count and its range on admission in the deficient group (2.7 per cent, range 0.3-13.6) was lower than that in the non-deficient group (5.3 per cent, range 0.6-30.2). The correlation between activity coefficient and parasite count was significant (R = -0.49). The recovery process was slower in the deficient group even though they had a relatively lower parasite count. It is inferred that riboflavin deficiency leads to inhibition of growth and multiplication of plasmodia. Its beneficial effects in malaria infection needs further evaluation.

Riboflavin deficiency and severity of malaria. | Semantic Scholar

It is inferred that riboflavin deficiency leads to inhibition of growth and multiplication of plasmodia in children suffering from malarial infection and its beneficial effects in malaria infection needs further evaluation. The riboflavin status of 64 children suffering from malarial infection...

www.semanticscholar.org

Riboflavin metabolism​

Riboflavin, also known as vitamin B2 is an important component of the cofactors FAD and FMN. These cofactors form part of flavoproteins and essential for many metabolic pathways including fatty acid metabolism, citrate cycle and electron transport chain. FAD is a crucial electron acceptor in addition to NAD+ and NADP+ in these pathways. The apicomplexans Plasmodium falciparum and Toxoplasma gondii do not possess the metabolic ability to synthesise riboflavin de novo and therefore the enzymes involved in synthesis of riboflavin from GTP and ribulose 5-phosphate are absent in both genomes. These species salvage riboflavin from host and generate FMN and FAD de novo as these possess the enzymes riboflavin kinase and FAD synthase. Although depletion of riboflavin in growth medium has not resulted in any inhibition of growth of P. falciparum parasites cultured with erythrocytes, the in vivo studies showed the association of riboflavin deficiency with adverse effects in parasite growth. It may suggest that the stores of riboflavin in erythrocytes is sufficient to supplement the parasites [1]. A clinical study of malaria-infected children with riboflavin deficiency pointed out that the parasite count is lower in these children compared to children with riboflavin in normal range, although the riboflavin-deficient children recovered slower [2]. In contrast, a recent study by Akompong et al demonstrated that the treatment of infected erythrocyte cells with riboflavin for 24 hours resulting in reduction in parasite levels of oxidised haemoglobin by 55%, hemozoin by 50% and size of food vacuole by 47%. In addition, treating for 48 hours has resulted in further reduction in food vacuole size and inhibition of asexual Plasmodium growth [3]. This may suggest the toxicity of higher concentrations of flavins in P. falciparum and further studies need to be conducted in order to understand the role of riboflavin in apicomplexan metabolism and growth. The transporters which are involved in the transport of riboflavin through parasite membranes are not yet identified in both P. falciparum and T. gondii.

Riboflavin metabolism | LAMP

www.llamp.net

Protective effects of camel milk on acute and chronic infection of toxoplasma gondii in mice​

Yan Xinlei1,3,*, Han Wenying1,3, Yang Zhili2, Wang Hejing1, Li Ruifeng2,*
1Uood Science and Engineering College of Inner Mongolia Agricultural University, Hohhot010018, China
2Department of Pediatrics, Inner Mongolia Maternal and Child Health Hospital, Hohhot010020, China
3These authors contributed equally to this work
ABSTRACT
In this study, the effects of camel milk in mice infected with T. gondii was evaluated. We established acute and chronic infection mouse models, as well as a dexamethasone-based immunocompromised model. All mice were treated with camel milk, milk, or phosphate-buffered saline (PBS), followed by analyses of survival rate, cyst count, serum cytokine levels and brain inflammation in mice. There were significant differences in linear trend (P < 0.05) in the survival curve of treating by camel milk, milk and PBS. And serum levels of IL-2 (P < 0.05) of camel milk-treated mice were lower compared with milk group, while serum levels of IL-4 and IFN-y (P < 0.05 for both, P < 0.01 for both) were higher of camel milk-treated mice than milk and PBS group. Additionally, camel milk reduced the extent of brain inflammation in mice with chronic T. gondii infection and immunocompromised mice. Importantly, camel milk alleviated the clinical symptoms of toxoplasmosis in mice. In conclusion, our findings suggest that camel milk exhibits promise for preventing or treating T. gondii infections.

Protective effects of camel milk on acute and chronic infection of toxoplasma gondii in mice-Indian Journals

In this study, the effects of camel milk in mice infected with T. gondii was evaluated. We established acute and chronic infection mouse models, as well as a dexamethasone-based immunocompromised model. All mice were treated with camel milk, milk, or phosphate-buffered saline (PBS), followed by...

www.indianjournals.com

I think those protozoa are after the Riboflavin in the red blood cells, so it's unintentional to hitch hike them.

 

[FoodForeal]

I think those protozoa are after the Riboflavin in the red blood cells, so it's unintentional to hitch hike them.

Interesting. It's not unintentional for malaria to target red blood cells though. For whatever reason (Could be nothing more than the riboflavin I suppose) they choose to reproduce asexually there.
"Plasmodium belongs to the phylum Apicomplexa, a taxonomic group of single-celled parasites with characteristic secretory organelles at one end of the cell.[14] Within Apicomplexa, Plasmodium is within the order Haemosporida, a group that includes all apicomplexans that live within blood cells.[15] Based on the presence of the pigment hemozoin and the method of asexual reproduction, the order is further split into four families, of which Plasmodium is in the family Plasmodiidae.[16]

The genus Plasmodium consists of over 200 species, generally described on the basis of their appearance in blood smears of infected vertebrates.[17] These species have been categorized on the basis of their morphology and host range into 14 subgenera:[16]" Plasmodium - Wikipedia

T. gondii reproduces elsewhere but still gets the riboflavin it needs.

These species salvage riboflavin from host

Notice it is plural specie(s), although malaria definitely specializes.

 

[Karmeleon]

Something to keep in mind with these parasites is that they have become highly specialized over the eons and they discard genes that make up dead weight. For example, myxozoans:
"While the evolutionary history of myxozoans is still an active area of research, it is currently taught that myxozoans are highly derived cnidarians that have undergone dramatic evolution from a free swimming, self-sufficient jellyfish-like creature into their current form of obligate parasites composed of very few cells, and sometimes only a single cell.[6] As myxozoans evolved into microscopic parasites, they lost many genes responsible for multicellular development, coordination, cell-cell communication, and even, in some cases, aerobic respiration.[7] The genomes of some myxozoans are now among the smallest genomes of any known animal species.[8]" Myxozoa - Wikipedia
If apicomplexans have lost their bacterial hunting weaponry than copper may be a dead end, but like you said it could be a clue to something at least.


On the "vaccine" idea from the paper I linked earlier: https://efsa.onlinelibrary.wiley.com/doi/pdf/10.2903/sp.efsa.2016.EN-995
"Vaccination with S48 strain T. gondii was shown to reduce tissue cyst formation in vaccination and challenge studies in sheep and pigs. "

Haven't read it fully yet but this study seems to have an interesting look into how the immune system begins to tolerate the disease as time goes on: Disease Tolerance in Toxoplasma Infection
"Toxoplasma must evade sterilizing immunity, but still rely on the host's immune response for survival and transmission. To do this, Toxoplasma exploits a central cost-benefit tradeoff in immunity: the need to escalate inflammation for pathogen clearance vs. the need to limit inflammation-induced bystander damage."
So our body wants to kill toxoplasma but it doesn't want to hurt healthy cells and toxoplasma also plays on that to help suppress the immune system while still keeping it active enough to ride on dendritic immune cells to desired tissue.
If we could turn off our immune system temporarily without causing other infections and before toxoplasmosis can spread too much and then turn it back on when t gondii is trying to amplify immune response, the immune system may be wrenched from under its control.

Maybe the immune system could be modulated to change its response so that it can be cleared completely in one fell swoop although its probably impossible for all to be eliminated completely and any lessening in immune response would mean that it could proliferate and replace the damaged population. Plus it would cause lots of damage to the body. But the main problem seems to be that t. gondii convinces the immune system that there will be too much collateral damage if it attacks. If we can override that we may be able to elicit a sterilizing response.

It seems that a strong immune system helps a lot with preventing infection initially, pretty common sense. Obviously a good reminder that the first step to recovery is ensuring maximal health through controlling your diet, healthy vs unhealthy activities, and environment. Wifi even is a consideration because it acts on cell function even though it is non-ionizing radiation.

Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection

The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining ...

www.ncbi.nlm.nih.gov

"Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen."
"During chronic infection, parasite-specific T lymphocytes release high levels of IFN-γ, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production."

Another study on immune system but with focus on t gondii manipulation of it. T gondii needs the immune system to react in order to spread, but not enough that it kills it off completely. The abstract mentions that t gondii can suppress apoptosis even by inhibiting caspase, but maybe things that increase autophagy like fasting can overcome this. So from what I can see so far toxoplasmosis benefits from downregulated immunity but will stop suppression if immune response becomes too suppressed. Perhaps at a time when you feel most sick (immune suppressed? Or would you feel more sick when fighting it harder? I suppose symptoms differ depending on whether the parasite is damaging the body or inflammatory immune response is causing damage, something to look into) it would actually be best to use a treatment that increases immune response to surprise toxoplasmosis at a time when it thinks it can spread.
The abstract mentions an "unusual" parasite specific pro inflammatory pathway which is key for toxoplasmosis to counter along with a common toll receptor pathway. Maybe things that promote antiparasitic effects in general could enhance the response to t. gondii and reduce inflammatory collateral damage.

From cells to signaling cascades: manipulation of innate immunity by Toxoplasma gondii

Abstract. The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-γ induction

academic.oup.com

The intracellular opportunistic protozoan Toxoplasma gondii is a potent stimulus for cell-mediated immunity, and IL-12-dependent IFN-γ induction is vital in resistance to the parasite. Dendritic cells, neutrophils and macrophages are important sources of IL-12 during infection. T. gondii possesses two mechanisms for triggering IL-12. One is dependent upon the common adaptor protein MyD88, and is likely to involve Toll-like receptors. The other is a more unusual pathway that involves triggering through CCR5 by a parasite cyclophilin molecule. Countering these potent pro-inflammatory activities, T. gondii has several mechanisms to down-regulate immunity. Intracellular infection causes a blockade in the NFκB macrophage signaling pathway, correlating with reduced capacity for IL-12 and TNF-α production. The parasite also prevents STAT1 activity, resulting in decreased levels of IFN-γ-stimulated MHC surface antigen expression. Furthermore, infection also induces resistance to apoptosis through inhibition of caspase activity. Extracellular pathways of suppression involve soluble mediators such as IL-10 and lipoxins that have potent IL-12 down-regulatory effects. The balance of pro-inflammatory and anti-inflammatory signaling which T. gondii engages is likely dictated by requirements for a stable host–parasite interaction. First, there is a need for Toxoplasma to induce an immune response robust enough to allow host survival and establish long-term chronic infection. Second, the parasite must avoid immune-elimination and induction of pro-inflammatory pathology that can cause lethality if unchecked. The widespread distribution of T. gondii and the normally innocuous nature of infection indicate the skill with which the parasite achieves the two seemingly contrary goals.

Hello PUFA my old friend. Maybe eating pufa as prophylactic could make it think it is in cat gut and have sex instead of trying to infect the brain of what it thinks is cat but is actually human. Jk but interesting to think about.

JCI - The molecular biology and immune control of chronic Toxoplasma gondii infection

www.jci.org

"T. gondii invades the small intestine of its host (4, 5). Recent work from Laura Knoll’s laboratory suggests that the parasite may sense linoleic acid in the feline gut as a critical signal for sexual stage differentiation in these species (6). "

Immune response to t gondii diagram. Click "back to article" to see the paper Human immunity to Toxoplasma gondii

I do also think immune modulation is key for eradication and achieving sterilizing immunity.

Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells​

Chronic infection with Toxoplasma gondii is one of the most common parasitic infections in humans. Formation of tissue cysts is the basis of persistence of the parasite in infected hosts, and this cyst stage has generally been regarded as untouchable. Here we provide the first evidence that the immune system can eliminate T. gondii cysts from the brains of infected hosts when immune T cells are transferred into infected immunodeficient animals that have already developed large numbers of cysts. This T cell-mediated immune process was associated with accumulation of microglia and macrophages around tissue cysts. CD8+ immune T cells possess a potent activity to remove the cysts. The initiation of this process by CD8+ T cells does not require their production of interferon-γ, the major mediator to prevent proliferation of tachyzoites during acute infection, but does require perforin. These results suggest that CD8+ T cells induce elimination of T. gondii cysts through their perforin-mediated cytotoxic activity. Our findings provide a new mechanism of the immune system to fight against chronic infection with T. gondii and suggest a possibility of developing a novel vaccine to eliminate cysts from patients with chronic infection and to prevent the establishment of chronic infection after a newly acquired infection.

Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells

Chronic infection with Toxoplasma gondii is one of the most common parasitic infections in humans. Formation of tissue cysts is the basis of persistence of the parasite in infected hosts, and this cyst stage has generally been regarded as untouchable. ...

www.ncbi.nlm.nih.gov

Propranolol efficacy as a novel adjuvant for immunization against Toxoplasma gondii tachyzoites​

Severe or lethal damages, caused by Toxoplasma gondii infection in congenital cases and immunocompromised patients implies the necessity for development of a vaccine and an appropriate adjuvant would be needed to elicit a protective Th1 biased-immune response. The adjuvant activity of propranolol was surveyed and compared with alum by immunization of BALB/c mice with protein components of T. gondii tachyzoites. Five groups of BALB/c mice were immunized with phosphate buffered saline (negative control), Toxoplasma lysate antigen (TLA), alum plus TLA, Propranolol plus TLA, and alum, propranolol and TLA. Immunization efficacy was evaluated by lymphocyte proliferation and DTH tests, challenge with live tachyzoites, IFN-γ production by spleen cells, serum TNF-α concentration and anti- Toxoplasma total IgG, IgG1 and IgG2a measurements. Mice of the PRP-TLA group induced significantly more IFN-γ and TNF-α production and lymphocyte proliferation than other groups. This group of mice also showed more anti-T. gondii IgG2a and DTH responses and showed a significantly increased survival time after challenge. These findings indicate that propranolol as an adjuvant in combination with TLA, may enhance cellular immunity against T. gondii.

Propranolol efficacy as a novel adjuvant for immunization against Toxoplasma gondii tachyzoites

Severe or lethal damages, caused by Toxoplasma gondii infection in congenital cases and immunocompromised patients implies the necessity for developme…

www.sciencedirect.com

Sex-dependent neurotransmitter level changes in brains of Toxoplasma gondii infected mice​

The protozoan parasite Toxoplasma gondii has the ability to alter intermediate host behavior, most impressively the natural aversion to cat scent, to favor the predation by the definitive host. However, the underlying mechanism of the observed phenomenon still remains unknown. Since changes in the neurotransmitter level are postulated as a possible contributing factor, the aim of this work was to assess the monoamine systems activity in specified brain regions involved in the natural defense behaviors, emotion evaluation, and motor and sensory stimuli integration in experimentally T. gondii infected mice compared to uninfected controls. Taking into account the natural differences between genders, the experiments were carried out on both male and female mice. Our results revealed statistically significant changes in all tested monoamine systems with regard to both gender and time after T. gondii invasion. Acute toxoplasmosis was accompanied by a decrease in noradrenergic system activity in females and its slight increase in some brain areas of males. Acute invasion also induced a rise in serotonin system activity, mostly in males. The most striking observation was an increase in the dopamine release noted in acutely infected males. We discuss our results in terms of their possible contribution to T. gondii-induced intermediate host behavior alterations and parasite transmission and with regard to postulated relationship between T. gondii seroprevalence and occurrence of certain disorders such as schizophrenia in humans.

► Toxoplasma gondii invasion induces neurotransmitters changes in both female and male mice. ► Acute invasion results in the decrease of the noradrenergic system activity in females. ► Acute toxoplasmosis is accompanied by a rise in serotonergic and dopaminergic activity in male mice.

Sex-dependent neurotransmitter level changes in brains of Toxoplasma gondii infected mice

The protozoan parasite Toxoplasma gondii has the ability to alter intermediate host behavior, most impressively the natural aversion to cat scent, to …

www.sciencedirect.com

Selective Disruption of Phosphatidylcholine Metabolism of the Intracellular Parasite Toxoplasma gondii Arrests Its Growth*​

Toxoplasma gondii is an intracellular protozoan parasite capable of causing devastating infections in immunocompromised and immunologically immature individuals. In this report, we demonstrate the relative independence of T. gondii from its host cell for aminoglycerophospholipid synthesis. The parasite can acquire the lipid precursors serine, ethanolamine, and choline from its environment and use them for the synthesis of its major lipids, phosphatidylserine (PtdSer), phosphatidylethanolamine (PtdEtn), and phosphatidylcholine (PtdCho), respectively. Dimethylethanolamine (Etn(Me)2), a choline analog, dramatically interfered with the PtdCho metabolism of T. gondii and caused a marked inhibition of its growth within human foreskin fibroblasts. In tissue culture medium supplemented with 2 mm Etn(Me)2, the parasite-induced lysis of the host cells was dramatically attenuated, and the production of parasites was inhibited by more than 99%. The disruption of parasite growth was paralleled by structural abnormalities in its membranes. In contrast, no negative effect on host cell growth and morphology was observed. The data also reveal that the Etn(Me)2-supplemented parasite had a time-dependent decrease in its PtdCho content and an equivalent increase in phosphatidyldimethylethanolamine, whereas other major lipids, PtdSer, PtdEtn, and PtdIns, remained largely unchanged. Relative to host cells, the parasites incorporated more than 7 times as much Etn(Me)2 into their phospholipid. These findings reveal that Etn(Me)2 selectively alters parasite lipid metabolism and demonstrate how selective inhibition of PtdCho synthesis is a powerful approach to arresting parasite growth.

Selective Disruption of Phosphatidylcholine Metabolism of the Intracellular Parasite Toxoplasma gondii Arrests Its Growth *

Toxoplasma gondii is an intracellular protozoan parasite capable of causing devastating infections in immunocompromised and immunologically immature individuals. In this report, we demonstrate the relative independence of T. gondii from its host cell for aminoglycerophospholipid synthesis. The...

www.jbc.org

Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma​

The obligate intracellular lifestyle of apicomplexan parasites necessitates an invasive phase underpinned by timely and spatially controlled secretion of apical organelles termed micronemes. In Toxoplasma gondii, extracellular potassium levels and other stimuli trigger a signaling cascade culminating in phosphoinositide-phospholipase C (PLC) activation, which generates the second messengers diacylglycerol (DAG) and IP3 and ultimately results in microneme secretion. Here we show that a delicate balance between DAG and its downstream product, phosphatidic acid (PA), is essential for controlling microneme release. Governing this balance is the apicomplexan-specific DAG-kinase-1, which interconverts PA and DAG, and whose depletion impairs egress and causes parasite death. Additionally, we identify an acylated pleckstrin-homology (PH) domain-containing protein (APH) on the microneme surface that senses PA during microneme secretion and is necessary for microneme exocytosis. As APH is conserved in Apicomplexa, these findings highlight a potentially widely used mechanism in which key lipid mediators regulate microneme exocytosis.

Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma

The obligate intracellular lifestyle of apicomplexan parasites necessitates an invasive phase underpinned by timely and spatially controlled secretion…

www.sciencedirect.com

Impairment of natural resistance to Toxoplasma gondii infection in rats treated with beta adrenergics, beta blockers, corticosteroids or total body irradiation.​

The data shows that Fisher rats treated with propranolol, betamethasone or exposed to cobalt60-treatment before challenge with T. gondii exhibit an impaired resistance to this opportunistic parasite infection. In fact, in rats propranolol-treatment induces an increase mortality rate up to 66.6% (P < 0.01, with respect to controls). Whereas betamethasone or cobalt60-treatment induces an increased of mortality rate about 33.3% (P < 0.05 respectively, with respect to unirradiated rats). In contrast to beta blocker, corticosteroid-treated or irradiated rats, beta adrenergic-treated rats do not significantly differ from untreated rats in their time of survival. These data lead the authors to hypothesise that in rats the natural resistance to T. gondii can be modulate beta adrenergics or corticosteroids.

Europe PMC

Europe PMC is an archive of life sciences journal literature.

europepmc.org

Radiation depletes Vitamin A, Riboflavin, Folates and increases Serotonin and Histamine.

 

[FoodForeal]

I do also think immune modulation is key for eradication and achieving sterilizing immunity.

Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells​

Phosphatidic Acid-Mediated Signaling Regulates Microneme Secretion in Toxoplasma​

Yeah our immune system can take care of it if we can stop t. gondii's suppression of it. It can regulate immune system and affect behavior through brain control. Pretty amazing parasite.

Interesting I just found a study on brain cysts and how immune cells remove them: Chitinase Dependent Control of Protozoan Cyst Burden in the Brain
This one discusses cysts (bradyzoites) in general: The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis

You were talking about reducing phosphate in aquariums earlier. So reducing phosphate makes it harder for t. gondii to signal?


More evidence the immune system is capable of sterilizing chronic toxoplasmosis but is suppressed by t. gondii's immunomodulatory capabilities:

New evidence shows cytotoxic T cells can identify, invade, and destroy targets of large mass like Toxoplasma gondii tissue cysts

CD8+ cytotoxic T lymphocytes can kill host cells infected with various microorganisms and single individual cancer cells through direct cell-to-cell contact, but their ability to destroy a target of large mass remains unexplored. A study provided novel evidence on the capability of the immune...

www.sciencedaily.com

"study provided novel evidence on the capability of the immune system to eliminate large parasite-filled cysts associated with chronic Toxoplasma gondii infection by utilizing the aggressive invader activity of cytotoxic T cells."

General parasite immune suppression related to t. gondii:

Revisiting the Mechanisms of Immune Evasion Employed by Human Parasites

For the establishment of a successful infection, i.e., long-term parasitism and a complete life cycle, parasites use various diverse mechanisms and factors, which they may be inherently bestowed with, or may acquire from the natural vector biting the host at the infection prelude, or may take...

www.frontiersin.org

 

[FoodForeal]

It seems that a strong immune system helps a lot with preventing infection initially, pretty common sense. Obviously a good reminder that the first step to recovery is ensuring maximal health through controlling your diet, healthy vs unhealthy activities, and environment. Wifi even is a consideration because it acts on cell function even though it is non-ionizing radiation.

Regulation and Function of T-Cell-Mediated Immunity during Toxoplasma gondii Infection

The intracellular protozoan Toxoplasma gondii is a widespread opportunistic parasite of humans and animals. Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining ...

www.ncbi.nlm.nih.gov

"Normally, T. gondii establishes itself within brain and skeletal muscle tissues, persisting for the life of the host. Initiating and sustaining strong T-cell-mediated immunity is crucial in preventing the emergence of T. gondii as a serious pathogen."
"During chronic infection, parasite-specific T lymphocytes release high levels of IFN-γ, which is required to prevent cyst reactivation. T-cell-mediated cytolytic activity against infected cells, while easily demonstrable, plays a secondary role to inflammatory cytokine production."

Continuing off of this, the wikipedia article on granulation says toxoplasmosis cysts are formed by granulation, but the quoted study says IFN-γ is required to prevent cyst reactivation, so this is something to look into.
"

Activity in granuloma formation​

A granuloma is the body's way of dealing with a substance it cannot remove or sterilize. Infectious causes of granulomas (infections are typically the most common cause of granulomas) include tuberculosis, leprosy, histoplasmosis, cryptococcosis, coccidioidomycosis, blastomycosis, and toxoplasmosis. Examples of non-infectious granulomatous diseases are sarcoidosis, Crohn's disease, berylliosis, giant-cell arteritis, granulomatosis with polyangiitis, eosinophilic granulomatosis with polyangiitis, pulmonary rheumatoid nodules, and aspiration of food and other particulate material into the lung.[26] The infectious pathophysiology of granulomas is discussed primarily here.

The key association between IFN-γ and granulomas is that IFN-γ activates macrophages so that they become more powerful in killing intracellular organisms.[27] Activation of macrophages by IFN-γ from Th1 helper cells in mycobacterial infections allows the macrophages to overcome the inhibition of phagolysosome maturation caused by mycobacteria (to stay alive inside macrophages).
"

IFN-γ seems to transform the terrain of the body into a killing floor for macrophages to slaughter invaders. All the cells retreat and signal friendly while hardening themselves against collateral damage from the rampage. But what if toxoplasma is inside the friendly cells? From the studies I have linked it seems that IFN-γ does lead to successful killing but toxoplasma can still inhibit other signalling that leads to the final kill signal. So figuring how to get conditions right for IFN-γ expression is important.

Like I said, somehow this IFN-γ is related both to creation of granulation and breaking of granulation toxoplasma cysts to kill them. Maybe it's somewhere in the chitinase study I linked earlier.

Interesting I just found a study on brain cysts and how immune cells remove them: Chitinase Dependent Control of Protozoan Cyst Burden in the Brain
This one discusses cysts (bradyzoites) in general: The Bradyzoite: A Key Developmental Stage for the Persistence and Pathogenesis of Toxoplasmosis

or your study link on cysts in the brain removal

Removal of Toxoplasma gondii Cysts from the Brain by Perforin-Mediated Activity of CD8+ T Cells​

Here's a good overview of toxoplasmosis: Tachyzoite - an overview | ScienceDirect Topics
"
Tachyzoites (tachos = fast) refer to the rapidly growing life stage of T. gondii that has also been called endozoites or trophozoites. Bradyzoites (brady = slow), also called cystozoites, are the life stage found in the tissue cyst and are believed to replicate slowly. Both stages replicate within a parasitophorous vacuole within the host cell, which is modified by the particular life stage into either a tachyzoite or a bradyzoite (tissue cyst)-specific vacuole. Tissue cysts are intracellular structures in which the bradyzoites divide by endodyogeny, the same replicative mechanism as tachyzoites.
"
So tachyzoites replicate until they reach the brain and form bradyzoite tissue cysts. The parasitophorus vacuole was confusing me on cyst vs host cell. Still it seems that immune cells can penetrate these cysts. I haven't found a spot where it says how the cysts are formed, but if it is by immune granulation how did the immune system not kill them instead of granulating them? The immune suppression of toxoplasma?

 

[FoodForeal]

I just realized they paywalled why cattle have better immune systems with that paper I linked earlier. Toxoplasma gondii infection in sheep and cattle

Now we may never know why cows defeat toxoplasmosis.

 

[Karmeleon]

Got arround that. I bet it's also around retinol self-self identification like you mentioned, cows somehow do a way better job to identify and exterminate foreign visitors. I was also able to find the connection of IFN-y to allow macrophages to sterilize the terrain so to speak and NK Cells do the job of injecting IFN-y.

Multiple roles for NK cells during T. gondii infection.
Natural killer (NK) cells function in different phases of immunity in response to parasite infection. Step 1: Innate. During the innate response, T. gondii infection stimulated production of inflammatory cytokines IL-1β, IFNα/β, IL-6, IL-12, IL-15, and IL-18, driving NK cell production of IFNγ. This results in early control of parasite infection by targeting intracellular parasites. IL-6 can stimulate NK cell IL-17 production. The importance of NK cell IL-17 is not well understood. Cytotoxic (CTL) response by NK cells is also induced; however, the importance of this function for control of acute parasite infection is not well known. Other factors important for NK cell responses include CD28, STAT4, Tbet, and NfκB family members (cRel, p50). Eomesodermin (Eomes) role is unclear. Step 2: Regulation. NK cells produce IL-10 and regulate innate responses by down-regulating IL-12 and possibly other cytokines. This is aryl hydrocarbon receptor (AHR)-dependent. Whether NK cell IL-10 can impact CD4 and CD8 T cell responses is not known. Step 3: Adaptive. NK cells can participate in adaptive immunity as memory-like cells. NK cells may be important for (2°) secondary T. gondii infections. Whether NK cells that experience T. gondii infection early live long-term or develop memory-like features and the mechanisms behind these cell-intrinsic fates are unknown.

The Diverse Role of NK Cells in Immunity to Toxoplasma gondii Infection​

The obligate intracellular parasite Toxoplasma gondii (T. gondii), found in ~30% of humans worldwide, is a significant health risk for people with HIV/AIDS, people undergoing chemotherapy treatment or organ transplantation, and for developing fetuses as a result of congenital infection [1]. Infection can cause death, blindness, spontaneous abortion, or mental retardation and is correlated with behavior and neurocognitive changes [2]. No therapies exist to prevent or clear parasite infection, which is lifelong. CD8 T cell interferon (IFN)γ is the major mechanism of protection [3,4]; however, many immune factors contribute to successful parasite control. One is the natural killer cell (NK cell) [5]. NK cells are considered group 1 innate lymphoid cells (ILCs) and provide defense against tumors and intracellular pathogens (viruses, bacteria, and parasites) [6]. They use surface receptors (activating, inhibitory, and cytokine) to survey host cells and tissues for damage or infection. Receptor engagement stimulates killing of diseased target cells (cytotoxicity) and initiating IFNγ production. Activating receptors recognize specific ligands expressed on target cell surfaces and activate via cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAM) or associated adapter molecules DAP10 and DAP12 [7]. Inhibitory receptors inhibit by assessing self through MHC Class I (MHCI) recognition and, when triggered, recruit ITAM-antagonizing phosphatases SHIP1 and SHP1 via cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIM) [8]. Inflammatory cytokines IFNα/β, Interleukin (IL)-2, IL-12, IL-15, and IL-18 synergize with activating receptor signals or stimulate NK cell activation alone [7]. Other functional surface proteins include FcγRs, Fas, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Ultimately, these surface proteins regulate NK cell function depending upon the stimulatory environment. Studies of NK cell responses to T. gondii have broadly impacted parasite immunology and NK cell fields. Thus, T. gondii is an excellent and relevant model to investigate NK cell biology. This model will be important in future studies, given newly emerging NK cell adaptive immune and regulatory roles and their therapeutic potential.

The Diverse Role of NK Cells in Immunity to Toxoplasma gondii Infection

www.ncbi.nlm.nih.gov

 

[FoodForeal]

Toxoplasma gondii - Wikipedia

en.wikipedia.org

"Tissue cysts can be maintained in host tissue for the lifetime of the animal.[30]: 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.[30]: 580  At any given time in a chronically infected host, a very small percentage of cysts are rupturing,[30]: 45  although the exact cause of this tissue cysts rupture is, as of 2010, not yet known.[4]: 47 "

Toxoplasma eats tryptophan

Toxoplasma gondii - Wikipedia

en.wikipedia.org

"Initially, a T. gondii infection stimulates production of IL-2 and IFN-γ by the innate immune system.[38] Continuous IFN-γ production is necessary for control of both acute and chronic T. gondii infection.[38] These two cytokines elicit a CD4+ and CD8+ T-cell mediated immune response.[38] 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 >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).[48]

IL-12 is produced during T. gondii infection to activate natural killer (NK) cells.[38] Tryptophan is an essential amino acid for T. 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.[49] Immune pressure eventually leads the parasite to form cysts that normally are deposited in the muscles and in the brain of the hosts.[38]

Immune response and behavior alterations[edit]​

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. Administration of L-kynurenine is capable of inducing depressive-like behavior in mice.[49] T. gondii infection has been demonstrated to increase the levels of kynurenic acid (KYNA) in the brains of infected mice and KYNA has also been demonstrated to be increased in the brain of schizophrenic persons.[49] Low levels of tryptophan and serotonin in the brain were already associated with depression.[50]"