Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It is the etiologic agent of toxoplasmosis, a neglected disease in which incidence and symptoms differ between patients and regions. In immunocompetent patients, toxoplasmosis manifests as acute and chronic forms. Acute toxoplasmosis presents as mild or asymptomatic disease that evolves, under the host immune response, into a persistent chronic disease in healthy individuals. Chronic toxoplasmosis establishes as latent tissue cysts in the brain and skeletal muscles. In immunocompromised patients, chronic toxoplasmosis may reactivate, leading to a potentially life-threatening condition. Recently, the association between toxoplasmosis and various diseases has been shown. These span primary neuropathies, behavioral and psychiatric disorders, and different types of cancer. Currently, a direct pre-clinical or clinical molecular connotation between toxoplasmosis and most of its associated diseases remains poorly understood. In this review, we provide a comprehensive overview on Toxoplasma-induced and associated diseases with a focus on available knowledge of the molecular players dictating these associations. We will also abridge the existing therapeutic options of toxoplasmosis and highlight the current gaps to explore the implications of toxoplasmosis on its associated diseases to advance treatment modalities.

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Brain abscess due to Aggregatibacter aphrophilus and Bacteroides uniformis

Acta Medica Academica ◽

10.5644/ama2006-124.144 ◽

2015 ◽

Vol 44 (2) ◽

pp. 181

Author(s):

Maja Bogdan ◽

Vlasta Zujić Atalić ◽

Ivan Hećimović ◽

Dubravka Vuković

Keyword(s):

Magnetic Resonance Imaging ◽

Case Report ◽

Surgical Treatment ◽

Brain Abscess ◽

Neurological Deficit ◽

Resonance Imaging ◽

Aggregatibacter Aphrophilus ◽

Threatening Condition ◽

Life Threatening ◽

The Brain

Objective. The aim of this report was to describe the occurrence of a bacterial brain abscess in a healthy individual, without any predisposing condition. Case report. A thirteen-year old boy was admitted to the Department of Neurosurgery after the onset of vomiting, headache and dizziness. A neurological deficit was detected during the physical examination so urgent magnetic resonance imaging of the brain was performed, revealing an intrahemispheric, right positioned solitary expansive mass with ring enhancement. Purulent material was obtained during osteoplastic craniotomy with total extirpation of the brain abscess. Aggregatibacter aphrophilus and Bacteroides uniformis were isolated. The patient’s general condition improved and the neurological deficit subsided as a result of the prompt recognition and treatment of this life threatening condition. Conclusion. To achieve a favourable clinical outcome, prompt recognition and surgical treatment of a brain abscess are of primary importance,followed by administration of appropriate antimicrobial therapy. To our best knowledge, this is the first report of this combination of microorganisms as the cause of a brain abscess.

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Nanosilver Colloid Inhibits Toxoplasma gondii Tachyzoites and Bradyzoites in Vitro

Iranian Journal of Parasitology ◽

10.18502/ijpa.v14i3.1474 ◽

2019 ◽

Cited By ~ 1

Author(s):

Saeedeh SHOJAEE ◽

Nima FIROUZEH ◽

Hussein KESHAVARZ ◽

Sanaz JAFARPOUR AZAMI ◽

Mahboobeh SALIMI ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Structural Changes ◽

Protozoan Parasite ◽

Blue Dye ◽

Type I ◽

Worldwide Distribution ◽

Life Threatening ◽

Strain Type ◽

In Vitro Effects

Background: Toxoplasma gondii, the coccidian protozoan parasite with worldwide distribution, is the agent of toxoplasmosis. The disease is life threatening in congenital form and in immunocompromised patients. The present study was carried out in 2016 to evaluate the in vitro effects of nanosilver colloid on tachyzoites and bradyzoites of T. gondii, RH and Tehran strains. Methods: Different concentrations (5, 10 , 20 ppm) of nanosilver colloid were added to tachyzoites of T. gondii , RH strain (type I) and bradyzoites and tissue cysts of T. gondii , Tehran strain (type II) and incubated for 30, 60, 90 and 120 minutes. The mortality rates of tachyzoites and bradyzoites were evaluated by trypan blue dye and MTT assay. Then SEM carried out to show the changes between control and exposed parasites. Results: The greatest mortality rate was seen in 20 ppm concentration and after 120 minutes of exposure. By electron microscopy, the structural changes were seen in tachyzoites of RH and tissue cyst of Tehran strain in comparison with control groups. Conclusion: Nanosilver colloid was effective on both tachyzoites and bradyzoites of T. gondii, RH and Tehran strains.

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Toxoplasmosis

Oxford Textbook of Medicine ◽

10.1093/med/9780199204854.003.070804_update_005 ◽

2010 ◽

pp. 1090-1097

Author(s):

Oliver Liesenfeld ◽

Eskild Petersen

Keyword(s):

Polymerase Chain Reaction ◽

Toxoplasma Gondii ◽

Direct Detection ◽

Protozoan Parasite ◽

Human Infection ◽

Clinical Samples ◽

Worldwide Distribution ◽

Polymerase Chain ◽

The Brain ◽

Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection may be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction, PCR) or by serological techniques....

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Toxoplasmosis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0162 ◽

2020 ◽

pp. 1416-1424

Author(s):

Oliver Liesenfeld ◽

Eskild Petersen

Keyword(s):

Polymerase Chain Reaction ◽

Toxoplasma Gondii ◽

Direct Detection ◽

Protozoan Parasite ◽

Human Infection ◽

Clinical Samples ◽

Worldwide Distribution ◽

Polymerase Chain ◽

The Brain ◽

Undercooked Meat

Toxoplasma gondii is a protozoan parasite with worldwide distribution that infects up to one-third of the world’s population. Human infection is acquired through ingestion in water or food of oocysts shed by cats, or by ingestion of bradyzoites released from cysts contained in uncooked or undercooked meat (e.g. sheep, swine, cattle). Following invasion in the intestine, tachyzoites rapidly disseminate throughout the host. Immune mechanisms mediate the formation of cysts, primarily in the brain, eye, and skeletal and heart muscles, where they persist for the life of the host. Presence of infection can be established by direct detection of the parasite in clinical samples (often by polymerase chain reaction) or by serological techniques.

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Subglottic haemangioma in children: experience with open surgical excision

The Journal of Laryngology & Otology ◽

10.1017/s0022215106003586 ◽

2006 ◽

Vol 120 (12) ◽

pp. 1033-1037 ◽

Cited By ~ 18

Author(s):

Y Bajaj ◽

B E J Hartley ◽

M E Wyatt ◽

D M Albert ◽

C M Bailey

Keyword(s):

Surgical Excision ◽

Treatment Modalities ◽

Direct Result ◽

Tertiary Referral Centre ◽

Threatening Condition ◽

Life Threatening ◽

One Stop ◽

Open Excision ◽

Subglottic Haemangioma

Subglottic haemangioma is a potentially life-threatening condition for which various treatment modalities are available. The objective of this study was to evaluate our results for open excision of subglottic haemangioma. The study assessed 18 patients who had been treated at a paediatric tertiary referral centre. Most of these patients (83.3 per cent) had undergone open surgical excision without post-operative tracheostomy and had been intubated for several days post-operatively (single-stage procedure). In most of these patients (66.7 per cent), an anterior cartilage graft had been used for reconstruction. The average follow up in this study was 25 months. All the patients in this series had achieved an adequate airway after the procedure. One patient had developed a recurrence of haemangioma in the trachea at a later date. The results of open surgical excision in this study were very encouraging. Seventeen out of 18 (94.4 per cent) patients had avoided tracheostomy or had been decannulated as a direct result of surgery. One of these 18 patients (5.6 per cent) had required a temporary post-operative tracheostomy for 13 months as the subglottis cleared; this was classed as a partial success. Our experience is that open excision is a highly successful ‘one stop’ treatment for subglottic haemangioma, which avoids prolonged use of steroids and multiple endoscopic procedures. No patient in this series developed subglottic stenosis, which can be a significant complication of laser application.

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Guanabenz Repurposed as an Antiparasitic with Activity against Acute and Latent Toxoplasmosis

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01683-15 ◽

2015 ◽

Vol 59 (11) ◽

pp. 6939-6945 ◽

Cited By ~ 30

Author(s):

Imaan Benmerzouga ◽

Lisa A. Checkley ◽

Michael T. Ferdig ◽

Gustavo Arrizabalaga ◽

Ronald C. Wek ◽

...

Keyword(s):

Translational Control ◽

Protozoan Parasite ◽

Empty Space ◽

Antiparasitic Activity ◽

Content Type ◽

Life Threatening ◽

Brain Cysts ◽

The Brain

ABSTRACTToxoplasma gondiiis a protozoan parasite that persists as a chronic infection.Toxoplasmaevades immunity by forming tissue cysts, which reactivate to cause life-threatening disease during immune suppression. There is an urgent need to identify drugs capable of targeting these latent tissue cysts, which tend to form in the brain. We previously showed that translational control is critical during infections with both replicative and latent forms ofToxoplasma. Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages ofToxoplasmaand the related apicomplexan parasitePlasmodium falciparum(a malaria agent). We also found that inhibition of translational control interfered with tissue cyst biologyin vitro.Toxoplasmabradyzoites present in these abnormal cysts were diminished and misconfigured, surrounded by empty space not seen in normal cysts. These findings prompted analysis of the efficacy of guanabenzin vivoby using established mouse models of acute and chronic toxoplasmosis. In addition to protecting mice from lethal doses ofToxoplasma, guanabenz has a remarkable ability to reduce the number of brain cysts in chronically infected mice. Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain.

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CD11c- and CD11b-expressing mouse leukocytes transport single Toxoplasma gondii tachyzoites to the brain

Blood ◽

10.1182/blood-2005-02-0666 ◽

2006 ◽

Vol 107 (1) ◽

pp. 309-316 ◽

Cited By ~ 239

Author(s):

Nathalie Courret ◽

Sylvie Darche ◽

Pierre Sonigo ◽

Geneviève Milon ◽

Dominique Buzoni-Gâtel ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Fluorescent Protein ◽

Ex Vivo ◽

Protozoan Parasite ◽

Blood Parasites ◽

Cell Periphery ◽

Mesenteric Lymph Nodes ◽

Cell Plasma ◽

Green Fluorescent ◽

The Brain

AbstractThe protozoan parasite Toxoplasma gondii enters hosts through the intestinal mucosa and colonizes distant tissues such as the brain, where its progeny persists for a lifetime. We investigated the role of CD11c- and CD11b-expressing leukocytes in T gondii transport during the early step of parasitism from the mouse small intestine and during subsequent parasite localization in the brain. Following intragastric inoculation of cyst-containing parasites in mice, CD11c+ dendritic cells from the intestinal lamina propria, the Peyer patches, and the mesenteric lymph nodes were parasitized while in the blood, parasites were associated with the CD11c- CD11b+ monocytes. Using adoptive transfer experiments, we demonstrated that these parasitized cells triggered a parasitic process in the brain of naive recipient mice. Ex vivo analysis of parasitized leukocytes showed that single tachyzoites remained at the cell periphery, often surrounded by the host cell plasma membrane, but did not divide. Using either a dye that labels circulating leukocytes or an antibody known to prevent CD11b+ circulating leukocytes from leaving the microvascular bed lumen, and chimeric mice in which the hematopoietic cells expressed the green fluorescent protein, we established that T gondii zoites hijacked CD11b+ leukocytes to reach the brain extravascular space.

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TgTKL1 Is a Unique Plant-Like Nuclear Kinase That Plays an Essential Role in Acute Toxoplasmosis

mBio ◽

10.1128/mbio.00301-18 ◽

2018 ◽

Vol 9 (2) ◽

Cited By ~ 2

Author(s):

Joseph M. Varberg ◽

Isabelle Coppens ◽

Gustavo Arrizabalaga ◽

Rajshekhar Y. Gaji

Keyword(s):

Toxoplasma Gondii ◽

Tyrosine Kinase ◽

Host Cell ◽

Essential Role ◽

Cell Attachment ◽

Protozoan Parasite ◽

Lytic Cycle ◽

Host Cell Attachment ◽

Acute Toxoplasmosis ◽

Insight Into

ABSTRACT In the protozoan parasite Toxoplasma gondii , protein kinases have been shown to play key roles in regulating parasite motility, invasion, replication, egress, and survival within the host. The tyrosine kinase-like (TKL) family of proteins are an unexplored set of kinases in Toxoplasma . Of the eight annotated TKLs in the Toxoplasma genome, a recent genome-wide loss-of-function screen showed that six are important for tachyzoite fitness. By utilizing an endogenous tagging approach, we showed that these six T. gondii TKLs (TgTKLs) localize to various subcellular compartments, including the nucleus, the cytosol, the inner membrane complex, and the Golgi apparatus. To gain insight into the function of TKLs in Toxoplasma , we first characterized TgTKL1, which contains the plant-like enhanced disease resistance 1 (EDR1) domain and localizes to the nucleus. TgTKL1 knockout parasites displayed significant defects in progression through the lytic cycle; we show that the defects were due to specific impairment of host cell attachment. Transcriptomics analysis identified over 200 genes of diverse functions that were differentially expressed in TgTKL1 knockout parasites. Importantly, numerous genes implicated in host cell attachment and invasion were among those most significantly downregulated, resulting in defects in microneme secretion and processing. Significantly, all of the mice inoculated intraperitoneally with TgTKL1 knockout parasites survived the infection, suggesting that TgTKL1 plays an essential role in acute toxoplasmosis. Together, these findings suggest that TgTKL1 mediates a signaling pathway that regulates the expression of multiple factors required for parasite virulence, underscoring the potential of this kinase as a novel therapeutic target. IMPORTANCE Toxoplasma gondii is a protozoan parasite that can cause chronic and life-threatening disease in mammals; new drugs are greatly needed for treatment. One attractive group of drug targets consists of parasite kinases containing unique features that distinguish them from host proteins. In this report, we identify and characterize a previously unstudied kinase, TgTKL1, that localizes to the nucleus and contains a domain architecture unique to plants and protozoa. By disrupting TgTKL1, we showed that this kinase is required for the proper expression of hundreds of genes, including many that are required for the parasite to gain entry into the host cell. Specifically, parasites lacking TgTKL1 have defects in host cell attachment, resulting in impaired growth in vitro and a complete loss of virulence in mice. This report provides insight into the importance of the parasite tyrosine kinase-like kinases and establishes TgTKL1 as a novel and essential virulence factor in Toxoplasma .

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Effects of Malaysian strains of Toxoplasma gondii on behaviours and their possible risk in schizophrenia-like rat model

10.1101/2020.12.10.418301 ◽

2020 ◽

Author(s):

Mohammed Nasiru Wana ◽

Malaika Watanabe ◽

Samaila Musa Chiroma ◽

Ngah Zasmy Unyah ◽

Sharif Alhassan Abdullahi ◽

...

Keyword(s):

Toxoplasma Gondii ◽

Protozoan Parasite ◽

Spatial Learning And Memory ◽

Type I ◽

Memory Retention ◽

Male Wistar Rats ◽

Behavioural Tests ◽

Behaviour Changes ◽

Phosphate Buffered Saline ◽

The Brain

ABSTRACTToxoplasma gondii (T. gondii) is a protozoan parasite that reside majorly in the brain of its intermediate host. T. gondii infected rodent’s shows some degree of behaviour deficits, while T. gondii infection in humans is associated with psychiatric problems such as schizophrenia. The present study aimed to evaluate the effects of Malaysian strains of T. gondii on rats. Forty five, four weeks old, male Wistar rats were used. The rats were assigned into five groups: two control groups (CG1 and CG2) and three experimental groups (EG1, EG2, EG3). CG1 rats received phosphate buffered saline (PBS), CG2 received MK-801 (as a model for schizophrenia), EG1, EG2, EG3 received orally 5 × 103 single T. gondii oocysts strain of type I, type II and type III respectively. After infection, all the five groups of rats were tested for T. gondii antibodies at two weeks post-infection (PI). Behavioural tests of exploratory activity (open field) and spatial learning and memory retention (Morris water maze) were performed on the ninth and tenth weeks PI followed by histological staining of rat brain. T. gondii IgM antibodies were detected in EG1, EG2 and EG3, but not in CG1 and CG2. The behaviour results demonstrated that rats from CG2, EG1, EG2 and EG3 had increased in their locomotor activities and memory deficits compared to control, while learning remain intact. Moreover, tissue cysts were found widely distributed exclusively in the whole brain of EG1, EG2 and EG3 without tropism. These findings taken together, implies that Malaysian strains of T. gondii are implicated in some causes of behaviour changes that are responsible for schizophrenia-like conditions if humans were infected.

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Bradyzoite-Specific Surface Antigen SRS9 Plays a Role in Maintaining Toxoplasma gondii Persistence in the Brain and in Host Control of Parasite Replication in the Intestine

Infection and Immunity ◽

10.1128/iai.01862-06 ◽

2007 ◽

Vol 75 (4) ◽

pp. 1626-1634 ◽

Cited By ~ 89

Author(s):

Seon-Kyeong Kim ◽

Ariela Karasov ◽

John C. Boothroyd

Keyword(s):

Toxoplasma Gondii ◽

Chronic Infection ◽

Acute Infection ◽

Surface Proteins ◽

Mammalian Host ◽

Wild Type ◽

Life Threatening ◽

Parasite Replication ◽

The Brain ◽

Developmental Switch

ABSTRACT Toxoplasma gondii is a ubiquitous parasite that persists for the life of a healthy mammalian host. A latent, chronic infection can reactivate upon immunosuppression and cause life-threatening diseases, such as encephalitis. A key to the pathogenesis is the parasite's interconversion between the tachyzoite (in acute infection) and bradyzoite (in chronic infection) stages. This developmental switch is marked by differential expression of numerous, closely related surface proteins belonging to the SRS (SAG1-related sequence) superfamily. To probe the functions of bradyzoite-specific SRSs, we created a bioluminescent strain lacking the expression of SRS9, one of the most abundant SRSs of the bradyzoite stage. Imaging of mice intraperitoneally infected with tachyzoites revealed that during an acute infection, wild-type and Δsrs9 strains replicated at similar rates, disseminated systemically following similar kinetics, and initially yielded similar brain cyst numbers. However, during a chronic infection, Δsrs9 cyst loads substantially decreased compared to those of the wild type, suggesting that SRS9 plays a role in maintaining parasite persistence in the brain. In oral infection with bradyzoite cysts, the Δsrs9 strain showed oral infectivity and dissemination patterns indistinguishable from those of the wild type. When chronically infected mice were treated with the immunosuppressant dexamethasone, however, the Δsrs9 strain reactivated in the intestinal tissue after only 8 to 9 days, versus 2 weeks for the wild-type strain. Thus, SRS9 appears to play an important role in both persistence in the brain and reactivation in the intestine. Possible mechanisms for this are discussed.

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