Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection

Tedford, Ellen; McConkey, Glenn A.

doi:10.3390/pathogens6020019

Cited by 60 publications

(33 citation statements)

References 102 publications

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“…These cysts can reactivate when the host's immunity is compromised; intermittent subclinical reactivation of these cysts may also occur. A growing number of studies of animals and epidemiological studies of humans suggest a possible link between latent Toxoplasma infection and changes in behavior via altered or subverted host neuronal activity (33,34). A "loss of fear" phenotype has been described for rodents (35), providing strong support for the behavioral manipulation hypothesis.…”

Section: Treatment Of Toxoplasmosis In Humans Nonpregnant Immunocompementioning

confidence: 95%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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SUMMARYPrimary infection is usually subclinical, but cervical lymphadenopathy or ocular disease can be present in some patients. Active infection is characterized by tachyzoites, while tissue cysts characterize latent disease. Infection in the fetus and in immunocompromised patients can cause devastating disease. The combination of pyrimethamine and sulfadiazine (pyr-sulf), targeting the active stage of the infection, is the current gold standard for treating toxoplasmosis, but failure rates remain significant. Although other regimens are available, including pyrimethamine in combination with clindamycin, atovaquone, clarithromycin, or azithromycin or monotherapy with trimethoprim-sulfamethoxazole (TMP-SMX) or atovaquone, none have been found to be superior to pyr-sulf, and no regimen is active against the latent stage of the infection. Furthermore, the efficacy of these regimens against ocular disease remains uncertain. In multiple studies, systematic screening for infection during gestation, followed by treatment with spiramycin for acute maternal infections and with pyr-sulf for those with established fetal infection, has been shown to be effective at preventing vertical transmission and minimizing the severity of congenital toxoplasmosis (CT). Despite significant progress in treating human disease, there is a strong impetus to develop novel therapeutics for both the acute and latent forms of the infection. Here we present an overview of toxoplasmosis treatment in humans and in animal models. Additional research is needed to identify novel drugs by use of innovative high-throughput screening technologies and to improve experimental models to reflect human disease. Such advances will pave the way for lead candidates to be tested in thoroughly designed clinical trials in defined patient populations.

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Section: Treatment Of Toxoplasmosis In Humans Nonpregnant Immunocompementioning

confidence: 95%

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

et al. 2018

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“…During latent infection, T. gondii is located within neurons, inducing changes to the host cells and altering signature neurological signaling pathways [ 46 , 47 ]. Experiments in mice showed an increase in levels of dopamine metabolites in the brain cortex and a decrease in serotonin levels in the amygdala and norepinephrine levels in the cortex and amygdala of T. gondii -infected mice; however, these data are under discussion [ 48 , 49 ].…”

Section: Discussionmentioning

confidence: 99%

Toxoplasma gondii exposure and neurological disorders: An age- and gender-matched case-control pilot study

Alvarado‐Esquivel

Rico-Almochantaf

Hernández‐Tinoco

et al. 2017

EuJMI

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Little is known about the association of Toxoplasma gondii infection and neurological disorders. We performed a case-control study with 344 patients with neurological diseases and 344 neurologically healthy age- and gender-matched subjects. Sera of participants were analyzed for anti-T. gondii IgG and IgM antibodies using commercially available immunoassays. Anti-T. gondii IgG antibodies were detected in 25 (7.3%) cases and in 35 (10.2%) controls (odds ratio [OR] = 0.69; 95% confidence interval [CI]: 0.40–1.18; P = 0.17). Anti-T. gondii IgM antibodies were found in 5 (14.3%) of the 25 IgG seropositive cases and in 13 (37.1°%) of the 35 IgG seropositive controls (P = 0.15). Anti-T. gondii IgG antibodies were found in 8 (3.8%) of 213 female cases and in 23 (10.8%) of 213 female controls (OR = 0.32; 95% CI: 0.14–0.73; P = 0.005); and in 17 (13.0%) of 131 male cases and in 12 (9.2%) of 131 male controls (P = 0.32). No direct association between IgG seropositivity and specific neurological disorders was detected. We found no support for a role of latent T. gondii infection in the risk for neurological disorders in this setting. With respect to specific neurological disorders, further studies using larger patient cohorts will be required.

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“…Though the extent to which T. gondii infection universally influences rodent behavior is unclear, several mechanisms have been proposed to account for the observed behavioral changes. Possible mechanisms include variations in secreted neurotransmitters, the neuroanatomic location of T. gondii cysts, or modulation of the CNS by the neuroinflammatory response (34,45).…”

Section: Mechanisms By Which T Gondii Might Affect Rodent Behaviormentioning

confidence: 99%

Latent Toxoplasmosis Effects on Rodents and Humans: How Much is Real and How Much is Media Hype?

Johnson

Koshy

2020

mBio

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Toxoplasma gondii is a ubiquitous, intracellular protozoan parasite with a broad range of intermediate hosts, including humans and rodents. In many hosts, T. gondii establishes a latent long-term infection by converting from its rapidly dividing or lytic form to its slowly replicating and encysting form. In humans and rodents, the major organ for encystment is the central nervous system (CNS), which has led many to investigate how this persistent CNS infection might influence rodent and human behavior and, more recently, neurodegenerative diseases. Given the interest in this topic, here we seek to take a global approach to the data for and against the effects of latent T. gondii on behavior and neurodegeneration and the proposed mechanisms that might underlie behavior modifications.

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Neurophysiological Changes Induced by Chronic Toxoplasma gondii Infection

Cited by 60 publications

References 102 publications

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Treatment of Toxoplasmosis: Historical Perspective, Animal Models, and Current Clinical Practice

Toxoplasma gondii exposure and neurological disorders: An age- and gender-matched case-control pilot study

Latent Toxoplasmosis Effects on Rodents and Humans: How Much is Real and How Much is Media Hype?

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