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Microorganisms Sep 2023Blood and tissue protozoan infections are responsible for an enormous burden in tropical and subtropical regions, even though they can also affect people living in... (Review)
Review
Blood and tissue protozoan infections are responsible for an enormous burden in tropical and subtropical regions, even though they can also affect people living in high-income countries, mainly as a consequence of migration and travel. These pathologies are responsible for heavy socio-economic issues in endemic countries, where the lack of proper therapeutic interventions and effective vaccine strategies is still hampering their control. Moreover, the pathophysiological mechanisms associated with the establishment, progression and outcome of these infectious diseases are yet to be fully described. Among all the players, extracellular vesicles (EVs) have raised significant interest during the last decades due to their capacity to modulate inter-parasite and host-parasite interactions. In the present manuscript, we will review the state of the art of circulating host-derived EVs in clinical samples or in experimental models of human blood and tissue protozoan diseases (i.e., malaria, leishmaniasis, Chagas disease, human African trypanosomiasis and toxoplasmosis) to gain novel insights into the mechanisms of pathology underlying these conditions and to identify novel potential diagnostic markers.
PubMed: 37764162
DOI: 10.3390/microorganisms11092318 -
Redox Biology Nov 2023Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is...
Toxoplasmosis is a major infectious disease, affecting approximately one-third of the world's population; its main clinical manifestation, ocular toxoplasmosis (OT), is a severe sight-threatening disease. Nevertheless, the diagnosis of OT is based on clinical findings, which needs improvement, even with biochemical tests, such as polymerase chain reaction and antibody detections. Furthermore, the efficacy of OT-targeted treatment is limited; thus, additional measures for diagnosis and treatments are needed. Here, we for the first time report a significantly reduced iron concentration in the vitreous humor (VH) of human patients infected with OT. To obtain further insights into molecular mechanisms, we established a mouse model of T. gondii infection, in which intravitreally injected tracer Fe, was accumulated in the neurosensory retina. T. gondii-infected eyes showed increased lipid peroxidation, reduction of glutathione peroxidase-4 expression and mitochondrial deformity in the photoreceptor as cristae loss. These findings strongly suggest the involvement of ferroptotic process in the photoreceptor of OT. In addition, deferiprone, an FDA-approved iron chelator, reduced the iron uptake but also ameliorated toxoplasma-induced retinochoroiditis by reducing retinal inflammation. In conclusion, the iron levels in the VH could serve as diagnostic markers and iron chelators as potential treatments for OT.
Topics: Animals; Mice; Humans; Toxoplasmosis, Ocular; Ferroptosis; Toxoplasma; Chorioretinitis; Retina; Iron
PubMed: 37738924
DOI: 10.1016/j.redox.2023.102890 -
BMC Veterinary Research Sep 2023Q fever and toxoplasmosis are economically important zoonoses as they cause considerable losses in livestock (cattle, sheep and goats) and wildlife (antelopes, giraffes,...
Q fever and toxoplasmosis in South African livestock and wildlife: a retrospective study on seropositivity, sporadic abortion, and stillbirth cases in livestock caused by Coxiella burnetii.
BACKGROUND
Q fever and toxoplasmosis are economically important zoonoses as they cause considerable losses in livestock (cattle, sheep and goats) and wildlife (antelopes, giraffes, lions, and cheetahs) through reproductive disorders such as abortions and stillbirths. Q fever and toxoplasmosis testing in South Africa is conducted by the Agricultural Research Council-Onderstepoort Veterinary Research (ARC-OVR). However, both zoonoses are understudied and not monitored in South Africa as they are not considered controlled or notifiable diseases in the Animal Disease Act 35 of 1984. A retrospective study was conducted on Q fever (2007-2009) and toxoplasmosis (2007-2017) using diagnostic laboratory data at the ARC-OVR. Also, we report on sporadic abortion and stillbirth cases in livestock from diagnostic tissue samples submitted for Coxiella burnetii polymerase chain reaction (PCR) detection at the ARC-OVR.
RESULTS
During 2007 to 2009, 766 animal samples were tested for C. burnetii antibodies and seropositivity was 0.9% (95%CI: 0.3-1.7) with sheep (1.9%; 95%CI: 0.6-4.4) having the highest seropositivity followed by cattle (0.7%; 95%CI: 0.09-2.6), while all goats (0.0%; 95%CI: 0.0-4.2) and wildlife (0.0%; 95%CI: 0.0-2.5) tested were negative. From 2007 to 2017, 567 sera were tested for T. gondii antibodies; overall seropositivity was 12.2% (95%CI: 9.6-15). Wildlife had highest seropositivity to T. gondii antibodies (13.9%; 95%CI: 9.0-19.7) followed by goats (12.9%; 95%CI: 9.2-17.4) and sheep (12.3%; 95%CI: 5.1-23.8) while seropositivity in cattle was 2.4% (95%CI: 0.06-12.9). Of 11 animals tested by C. burnetii PCR detection (2021-2022), 10 (91.0%) were positive. The amplicon sequences showed similarity to Coxiella burnetii strain 54T1 transposase gene partial coding sequence.
CONCLUSIONS
We have confirmed the occurrence of the causative agents of Q fever and toxoplasmosis in livestock and wildlife in South Africa, with data limitations. These zoonoses remain of importance with limited information about them in South Africa. This study provides baseline information for future studies on Q fever and toxoplasmosis in South African livestock and wildlife, as well other African countries. Due to limited data collection experienced in this study, it is recommended that improvements in data collection samples tested should include associated factors such as sex, age, and breed of the animals.
Topics: Female; Pregnancy; Animals; Cattle; Sheep; Coxiella burnetii; Stillbirth; Animals, Wild; Q Fever; Retrospective Studies; Livestock; South Africa; Zoonoses; Acinonyx; Antelopes; Antibodies; Blood Group Antigens; Giraffes; Goats; Cattle Diseases; Goat Diseases; Sheep Diseases
PubMed: 37735412
DOI: 10.1186/s12917-023-03645-w -
SAGE Open Medicine 2023The study determined the rate of recent and past infections, associated factors, and awareness among expectant mothers assessing antenatal care in a tertiary hospital...
OBJECTIVES
The study determined the rate of recent and past infections, associated factors, and awareness among expectant mothers assessing antenatal care in a tertiary hospital in Nigeria.
METHODS
This prospective cohort study was conducted among pregnant women. A questionnaire was used to gather information on socio-demographics, infection risk factors, and awareness of the infection. Using an ELISA kit, the IgG and IgM antibodies were assessed in blood samples from these women. For samples that tested positive for IgM, a real-time polymerase chain reaction was used to amplify the DNA. SPSS version 23 was used for data entry and analysis. The -value < 0.05 was adjudged to be significant.
RESULTS
A total of 250 pregnant women participated in the study. The rate of recent infection (IgM antibody positivity) was 3.6% (9/250), while past infection (IgG antibody positivity) was 68.4% (171/250). Polymerase chain reaction confirmed 5/9 recent infections as positive. Factors significantly associated with toxoplasmosis were gardening ( = 0.037) and undercooked meat ( = 0.023). Only 27 out of 250 pregnant women in this research had heard of toxoplasmosis, which translates to a low awareness rate of 10.8%.
CONCLUSIONS
The recent infection among pregnant women in this study indicates the possibility of mother-to-child transmission with attendant sequelae. There was a significant association between past infections and stillbirth. Routine screening for toxoplasmosis should be incorporated into the antenatal program since none of the symptoms could significantly predict illness. In addition, regular antennal care instruction should cover toxoplasmosis education.
PubMed: 37915843
DOI: 10.1177/20503121231202230 -
Frontiers in Immunology 2024Ocular toxoplasmosis (OT) is an intraocular infection caused by the parasite OT is manifested as retinal choroiditis and is the most common infectious cause of... (Review)
Review
Ocular toxoplasmosis (OT) is an intraocular infection caused by the parasite OT is manifested as retinal choroiditis and is the most common infectious cause of posterior uveitis. Invasion of the retina by leads to disruption of the blood-ocular barrier and promotes the migration of immune cells to the ocular tissues. Cytokines such as IFN-γ and IL-1β are effective for controlling parasite growth, but excessive inflammatory responses can cause damage to the host. In this review, we will discuss in detail the latest advances in the immunopathology and treatment of OT.
Topics: Humans; Toxoplasmosis, Ocular; Toxoplasma; Animals; Cytokines
PubMed: 38799473
DOI: 10.3389/fimmu.2024.1403025 -
Contact (Thousand Oaks (Ventura County,... 2023Apicomplexan parasites are a group of protists that cause disease in humans and include pathogens like ., the causative agent of malaria, and , the etiological agent of... (Review)
Review
Apicomplexan parasites are a group of protists that cause disease in humans and include pathogens like ., the causative agent of malaria, and , the etiological agent of toxoplasmosis and one of the most ubiquitous human parasites in the world. Membrane contact sites (MCSs) are widespread structures within eukaryotic cells but their characterization in apicomplexan parasites is only in its very beginnings. Basic biological features of the parasitic cycle support numerous organellar interactions, including the transfer of Ca and metabolites between different compartments. In , Ca signals precede a series of interrelated molecular processes occurring in a coordinated manner that culminate in the stimulation of key steps of the parasite life cycle. Calcium transfer from the endoplasmic reticulum to other organelles via MCSs would explain the precision, speed, and efficiency that is needed during the lytic cycle of . In this short review, we discuss the implications of these structures in cellular signaling, with an emphasis on their potential role in Ca signaling.
PubMed: 37560622
DOI: 10.1177/25152564231189064 -
Molecular and Biochemical Parasitology May 2024Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens... (Review)
Review
Apicomplexan parasites are the primary causative agents of many human diseases, including malaria, toxoplasmosis, and cryptosporidiosis. These opportunistic pathogens undergo complex life cycles with multiple developmental stages, wherein many key steps are regulated by phosphorylation mechanisms. The genomes of apicomplexan pathogens contain protein kinases from different groups including tyrosine kinase-like (TKL) family proteins. Although information on the role of TKL kinases in apicomplexans is quite limited, recent studies have revealed the important role of this family of proteins in apicomplexan biology. TKL kinases in these protozoan pathogens show unique organization with many novel domains thus making them attractive candidates for drug development. In this mini review, we summarize the current understanding of the role of TKL kinases in human apicomplexan pathogens' (Toxoplasma gondii, Plasmodium falciparum and Cryptosporidium parvum) biology and pathogenesis.
PubMed: 38719028
DOI: 10.1016/j.molbiopara.2024.111628 -
Heliyon Nov 2023It is estimated that 30 % of the world's population harbours the parasite Toxoplasma gondii, particularly in the brain. Beyond its implication in potentially severe... (Review)
Review
It is estimated that 30 % of the world's population harbours the parasite Toxoplasma gondii, particularly in the brain. Beyond its implication in potentially severe opportunistic or congenital infections, this persistence has long been considered as without consequence. However, certain data in animals and humans suggest that this carriage may be linked to various neuropsychiatric or neurodegenerative disorders. The hypothesis of a potential cerebral oncogenicity of the parasite is also emerging. In this personal view, we will present the epidemiological arguments in favour of an association between toxoplasmosis and cerebral malignancy, before considering the points that could underlie a potential causal link. More specifically, we will focus on the brain as the preferred location for T. gondii persistence and the propensity of this parasite to interfere with the apoptosis and cell cycle signalling pathways of their host cell.
PubMed: 38034818
DOI: 10.1016/j.heliyon.2023.e22147 -
Nature Jan 2024Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms....
Sexual reproduction of Toxoplasma gondii, confined to the felid gut, remains largely uncharted owing to ethical concerns regarding the use of cats as model organisms. Chromatin modifiers dictate the developmental fate of the parasite during its multistage life cycle, but their targeting to stage-specific cistromes is poorly described. Here we found that the transcription factors AP2XII-1 and AP2XI-2 operate during the tachyzoite stage, a hallmark of acute toxoplasmosis, to silence genes necessary for merozoites, a developmental stage critical for subsequent sexual commitment and transmission to the next host, including humans. Their conditional and simultaneous depletion leads to a marked change in the transcriptional program, promoting a full transition from tachyzoites to merozoites. These in vitro-cultured pre-gametes have unique protein markers and undergo typical asexual endopolygenic division cycles. In tachyzoites, AP2XII-1 and AP2XI-2 bind DNA as heterodimers at merozoite promoters and recruit MORC and HDAC3 (ref. ), thereby limiting chromatin accessibility and transcription. Consequently, the commitment to merogony stems from a profound epigenetic rewiring orchestrated by AP2XII-1 and AP2XI-2. Successful production of merozoites in vitro paves the way for future studies on Toxoplasma sexual development without the need for cat infections and holds promise for the development of therapies to prevent parasite transmission.
Topics: Animals; Cats; Humans; Chromatin; Disease Models, Animal; Epigenesis, Genetic; In Vitro Techniques; Life Cycle Stages; Merozoites; Nuclear Proteins; Promoter Regions, Genetic; Protozoan Proteins; Toxoplasma; Toxoplasmosis; Transcription, Genetic
PubMed: 38093015
DOI: 10.1038/s41586-023-06821-y -
EFSA Journal. European Food Safety... Dec 2023This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and...
This report by the European Food Safety Authority and the European Centre for Disease Prevention and Control presents the results of the zoonoses monitoring and surveillance activities carried out in 2022 in 27 Member States (MSs), the United Kingdom (Northern Ireland) and 11 non-MSs. Key statistics on zoonoses and zoonotic agents in humans, food, animals and feed are provided and interpreted historically. In 2022, the first and second most reported zoonoses in humans were campylobacteriosis and salmonellosis, respectively. The number of cases of campylobacteriosis and salmonellosis remained stable in comparison with 2021. Nineteen MSs and the United Kingdom (Northern Ireland) achieved all the established targets in poultry populations for the reduction of prevalence for the relevant serovars. samples from carcases of various animal species, and samples for quantification from broiler carcases, were more frequently positive when performed by the competent authorities than when own checks were conducted. Yersiniosis was the third most reported zoonosis in humans, followed by Shiga toxin-producing (STEC) and infections. and West Nile virus infections were the most severe zoonotic diseases, with the most hospitalisations and highest case fatality rates. In 2022, reporting showed an increase of more than 600% compared with 2021 in locally acquired cases of human West Nile virus infection, which is a mosquito-borne disease. In the EU, the number of reported foodborne outbreaks and cases, hospitalisations and deaths was higher in 2022 than in 2021. The number of deaths from outbreaks was the highest ever reported in the EU in the last 10 years, mainly caused by and to a lesser degree by . and in particular Enteritidis remained the most frequently reported causative agent for foodborne outbreaks. Norovirus (and other calicivirus) was the agent associated with the highest number of outbreak human cases. This report also provides updates on brucellosis, (Q fever), echinococcosis, rabies, toxoplasmosis, trichinellosis, infection with complex (focusing on and ) and tularaemia.
PubMed: 38089471
DOI: 10.2903/j.efsa.2023.8442