New Study Associates Parasite With Various Neuropsychiatric and Behavioral Conditions
Hannah C.Oct 01, 2020
At the beginning of summer, health authorities in several states announced warnings against amoeba in freshwater lakes that cause a severe brain infection. A recent study highlights a parasite called Toxoplasma gondii, or T. gondii, and its association with neuropsychiatric and behavioral conditions.
Scientists from Imperial College London’s London Centre for Neglected Tropical Disease Research published their study in the cell journal Trends in Parasitology. Evidence suggests that T. gondii may be an underestimated threat to the world. (See link for article)
congenital toxoplasmosis (babies suffer with developmental issues and other abnormalities)
Regarding treatment the article states parasites notoriously evolve and resist drugs over time.
Researchers state that treatment and prevention need to expand beyond acute diseases and congenital transmission.
They also report that early trials of JAG21, a tetrahydroquinolone (a semi-hydrogenated derivative of quinoline),removed 100% of active T. gondii and that they hope to develop it into a nasal spray.
Excerpt from study:
Further, JAG21 is efficacious against drug-resistant Plasmodium falciparum in vitro (Malaria). Causal prophylaxis and radical cure are achieved after P. berghei sporozoite infection with oral administration of a single dose (2.5 mg/kg) or 3 days treatment at reduced dose (0.625 mg/kg/day), eliminating parasitemia, and leading to 100% survival. Enzymatic, binding, and co-crystallography/pharmacophore studies demonstrate selectivity for apicomplexan relative to mammalian enzymes. JAG21 has significant promise as a pre-clinical candidate for prevention, treatment, and cure of toxoplasmosis and malaria. https://www.frontiersin.org/articles/10.3389/fcimb.2020.00203/full
How T. gondii infection causes seizures, and psychiatric illness for some
Summary: Study shows how Toxoplasma parasitic infections promote the loss of inhibitory signaling in the brain by altering the behavior of microglia.
Source: Virginia Tech
Think about traffic flow in a city – there are stop signs, one-way streets, and traffic lights to organize movement across a widespread network. Now, imagine what would happen if you removed some of the traffic signals.
Among your brain’s 86 billion neurons are the brain’s own version of stop signals: inhibitory neurons that emit chemicals to help regulate the flow of ions traveling down one cell’s axon to the next neuron. Just as a city without traffic signals would experience a spike in vehicle accidents, when the brain’s inhibitory signals are weakened, activity can become unchecked, leading to a variety of disorders.
In a new study published in GLIA on March 11, Virginia Tech neuroscientists at the Fralin Biomedical Research Institute at VTC describe how the common Toxoplasma gondii parasite prompts the loss of inhibitory signaling in the brain by altering the behavior of nearby cells called microglia.
The Centers for Disease Control and Prevention estimates that 40 million Americans have varying levels of Toxoplasma infection, although most cases are asymptomatic. Commonly passed to humans via exposure to farm animals, infected cat litter, or undercooked meat, the parasitic infection causes unnoticeable or mild, to flu-like symptoms in most healthy people. But for a small number of patients, these microscopic parasites hunker down inside of neurons, causing signaling errors that can result in seizures, personality and mood disorders, vision changes, and even schizophrenia.
“After the initial infection, humans will enter a phase of chronic infection. We wanted to examine how the brain circuitry changes in these later stages of parasitic cyst infection,” said Michael Fox, a professor at the Fralin Biomedical Research Institute and the study’s lead author.
The parasite forms microscopic cysts tucked inside of individual neurons.
“The theory is that neurons are a great place to hide because they fail to produce some molecules that could attract cells of the immune system,” said Fox, who is also director of the research institute’s Center for Neurobiology Research.
Fox and his collaborator, Ira Blader, recently reported that long-term Toxoplasma infections redistribute levels of a key enzyme needed in inhibitory neurons to generate GABA, a neurotransmitter released at the specialized connection between two neurons, called a synapse.
Building on that discovery, the scientists revealed that persistent parasitic infection causes a loss of inhibitory synapses, and they also observed that cell bodies of neurons became ensheathed by other brain cells, microglia. These microglia appear to prevent inhibitory interneurons from signaling to the ensheathed neurons.
“In neuropsychiatric disorders, similar patterns of inhibitory synapse loss have been reported, therefore these results could explain why some people develop these disorders post-infection,” Fox said.
Fox said the inspiration for this study started years ago when he met Blader, a collaborating author and professor of microbiology and immunology at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, after he delivered a seminar at Virginia Tech. Blader studied Toxoplasma gondii and wanted to understand how specific strands of the parasite impacted the retina in mouse models.
Working together, the two labs found that while the retina showed no remarkable changes, inhibitory interneurons in the brain were clearly impacted by the infection. Mice – similar to humans – exhibit unusual behavioral changes after Toxoplasma infection. One hallmark symptom in infected mice is their tendency to approach known predators, such as cats, displaying a lack of fear, survival instincts, or situational processing.
“Even though a lot of neuroscientists study Toxoplasma infection as a model for immune response in the brain, we want to understand what this parasite does to rewire the brain, leading to these dramatic shifts in behavior,” Fox said.
Future studies will focus on further describing how microglia are involved in the brain’s response to the parasite.
Among the research collaborators is Gabriela Carrillo, the study’s first author and a graduate student in the Translational Biology, Medicine, and Health Program. Previously trained as an architect before pursuing a career in science, Carrillo chose this topic for her doctorate dissertation because it involves an interdisciplinary approach.
“By combining multiple tools to study infectious disease and neuroscience, we’re able to approach this complex mechanistic response from multiple perspectives to ask entirely new questions,” Carrillo said. “This research is fascinating to me because we are exposing activated microglial response and fundamental aspects of brain biology through a microbiological lens.”
The study’s other contributing authors include Valerie Ballard, a Roanoke Valley Governor’s School high school student; Taylor Glausen, a graduate student working in Blader’s laboratory at the University at Buffalo; Zack Boone, a Virginia Tech undergraduate student; Cyrus Hinkson, a fourth-year Virginia Tech Carilion School of Medicine student; and Elizabeth Wohlfert, an assistant professor of microbiology and immunology at the University at Buffalo.
Source: Virginia Tech Media Contacts:
Whitney Slightham – Virginia Tech Image Source:
The image is in the public domain.
Toxoplasma infection induces microglia‐neuron contact and the loss of perisomatic inhibitory synapses
Infection and inflammation within the brain induces changes in neuronal connectivity and function. The intracellular protozoan parasite, Toxoplasma gondii, is one pathogen that infects the brain and can cause encephalitis and seizures. Persistent infection by this parasite is also associated with behavioral alterations and an increased risk for developing psychiatric illness, including schizophrenia. Current evidence from studies in humans and mouse models suggest that both seizures and schizophrenia result from a loss or dysfunction of inhibitory synapses. In line with this, we recently reported that persistent T. gondii infection alters the distribution of glutamic acid decarboxylase 67 (GAD67), an enzyme that catalyzes GABA synthesis in inhibitory synapses. These changes could reflect a redistribution of presynaptic machinery in inhibitory neurons or a loss of inhibitory nerve terminals. To directly assess the latter possibility, we employed serial block face scanning electron microscopy (SBFSEM) and quantified inhibitory perisomatic synapses in neocortex and hippocampus following parasitic infection. Not only did persistent infection lead to a significant loss of perisomatic synapses, it induced the ensheathment of neuronal somata by myeloid‐derived cells. Immunohistochemical, genetic, and ultrastructural analyses revealed that these myeloid‐derived cells included activated microglia. Finally, ultrastructural analysis identified myeloid‐derived cells enveloping perisomatic nerve terminals, suggesting they may actively displace or phagocytose synaptic elements. Thus, these results suggest that activated microglia contribute to perisomatic inhibitory synapse loss following parasitic infection and offer a novel mechanism as to how persistent T. gondii infection may contribute to both seizures and psychiatric illness.
Felids (domestic and wild cats) are important in the epidemiology of the parasite Toxoplasma gondii because they are the only hosts that can excrete the environmentally resistant oocysts. We conducted a systematic review and meta-analysis to estimate the global prevalence of T. gondii in species of the family Felidae.
We searched seven databases (PubMed, Embase, Google Scholar, ScienceDirect, Scopus, Proquest and Web of Science) for studies reporting seroprevalence of T. gondii in felids from 1967 to 31 December 2017. A total of 217 published papers, containing 223 datasets were eligible for inclusion in the meta-analysis, comprised 59,517 domestic and 2733 wild cats from 1967 to 2017.
The pooled global T. gondii seroprevalence was estimated to be 35% (95% CI: 32–38%) and 59% (95% CI: 56–63%) in domestic cats and wild felids, respectively, using random effects model. The seroprevalence was higher in Australia and Africa where the T. gondii seropositivity in domestic cats was 52% (95% CI: 15–89%) and 51% (95% CI: 20–81%), respectively. The lowest seroprevalence was estimated in Asia 27% (95% CI: 24–30%). The seroprevalence values for T. gondii in wild felids were 74% (95% CI: 62–83%) in Africa, 67% (95% CI: 23–111%) in Asia, 67% (95% CI: 58–75%) in Europe and 66% (95% CI: 41–91%) in South America.
Our study provides the global prevalence of T. gondii in species of the family Felidae and is a source of information to aid public health workers in developing prevention plans.
The following excerpt from the study is important:
Based on formal reports, over one billion people in the world are estimated to be infected with T. gondii, which is transmitted mainly by ingestion of food, water, vegetables and fruits contaminated with sporulated oocysts shed from cats or ingesting tissue cysts from raw or undercooked meat ….The Centers for Disease Control and Prevention (CDC) reported that toxoplasmosis is the second most common cause of death due to food-borne diseases.
Nymphs of Ixodes ricinus are most susceptible to infection with T. gondii and they reported that the role of ticks in transmitting of toxoplasmosis should be considered in further investigations. They also added that Toxoplasma artificially (intracoelomatically) introduced into the organism of I. ricinus females can penetrate and multiply in hypoderma, salivary glands, peritracheal connective tissue and muscular tissue. Moreover, Jagow and Hoffmann (1970) found that Toxoplasma lived in Nymphs and adults of Ornithodoros moubata up till 10 and 2 days, respectively. They also found transmission was unsuccessful either through sucking or with the next stage of the same ticks or through the F1-generation of the ticks infected with Toxoplasma. Whereas, Gidel and Provost (1965)isolated Toxoplasma gondiifrom to the genus Amblyomma parasiting a bovine in Centre African Republic by inoculation into rabbits and guinea pigs and proved pathogenic for mice.
Prudence would err on the side of caution and transmission of T. gondii by ticks should be highly suspected.
Parasite patients often express the psyche of the parasites – sticky, clingy, impossible to tolerate – but a wonderful human being is behind all of that.
We are all a composite of many personalities. Chronic infections outnumber our own cells by 10:1. We are 90% “other” and 10% “us”. Our consciousness is a composite of 90% microbes and 10% us.
Our thinking, feeling, creativity, and expression are 90% from the microbes within us. Patients often think, crave, and behave as if they are the parasite.
Our thinking is shaded by the microbes thinking through us. The food choices, behavioral choices, and who we like is the thinking of the microbes within us expressing themselves.
Patients will reject all treatments that affect the issue that requires treating.
Patients will not guide themselves to health when the microbes have taken over.
With this information in mind, it’s quite clear how Lyme/MSIDS is such a complex disease as many are dealing not only with Lyme but other coinfections including parasites which are either directly transmitted by a tick or activated due to a trigger and a dysfunctional immune system.
The association between infection and psychiatric disorders was one of the milestones of early 20th century medicine. The identification of Treponema pallidum in the brains of individuals with “general paresis of the insane” by Noguchi and Moore in 1913 established the role of tertiary syphilis and showed that bacterial infections can cause long-term changes in both neurological and psychiatric functioning. The eventual development of treatments for syphilis and the subsequent curing of individuals with general paresis also showed that the discovery of an infectious cause of a neuropsychiatric disorder could be followed by effective treatment. The association between infection and some cases of psychiatric disorders was further solidified by the identification of an increased rate of encephalitis lethargica following the influenza epidemic of 1918-1919. Influenza control measures might be partially credited for the rarity of encephalitis lethargica in the modern era…..
Microorganisms capable of his latency include a diverse range of taxa including viruses such as the herpesviruses herpes simplex virus types 1 and 2, cytomegalovirus, and Epstein Barr virus as well as retroviruses such as human immunodeficiency virus, measles virus, bacteria such as Chlamydiae and Borreliae, and protozoa such as Toxoplasma gondii…(See link for article)
Quebec health officials reported an outbreak of the parasitic infection, toxoplasmosis, in a at least six hunters who consumed the deer meat they killed during a hunting trip to the United States last November-December.
This hunter had left with nine other hunters, including five others who have also presented with symptoms. The similarity of symptoms and clinical signs of the six sick hunters exhibited a common etiology.
The source of the contamination was identified to be undercooked meat from white-tailed deer harvested in Illinois.
Testing was performed for leptospirosis, hepatitis E, brucellosis, tularemia and toxoplasmosis. The results of the serologies were compatible with an acute Toxoplasma gondii infection in all cases (presence of IgM antibodies or seroconversion of antibodies IgG negative to positive; the avidity of IgG, when tested, was low, indicating a recent infection).
This is the first case of toxoplasmosis outbreak in Quebec associated with the consumption of deer meat.
So this is frightening for Wisconsinites as infection can be obtained by eating undercooked deer meat as well as it’s been found in Castor bean ticks which can potentially be spread here by migrating birds.
Furthermore, this study on the castor bean tick found “Borrelia lusitaniae, Borrelia spielmanii, Borrelia garinii, Anaplasma phagocytophilum,and Rickettsia helvetica in both midgut and salivary glands with Rickettsia felis only detected in salivary glands suggesting that the migration of these pathogens between these two organs might not be triggered by the blood meal. https://parasitesandvectors.biomedcentral.com/articles/10.1186/s13071-019-3418-7.
Plain English – transmission could happen much more quickly.
I. ricinus can also transmit a number of pathogens including Babesia divergens (babesiosis), louping ill virus, tick-borne encephalitis virus, Borrelia burgdorferi (Lyme disease) and Anaplasma phagocytophila (tick-borne fever of ruminants, human granulocytic anaplasmosis).