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Background: Toxoplasmosis is a chronic protozoan parasitic infection that affects nearly one-third of the global population. During the COVID-19 pandemic, cases were observed in patients with COVID-19 and toxoplasmosis. Therefore, this systematic review and meta-analysis aimed to determine the frequency of Toxoplasma gondii exposure in patients with COVID-19. Methods: A literature search was conducted in six databases or search tools (PubMed, Scopus, Embase, Web of Science, ScienceDirect, and Google Scholar) until March 3, 2024. Study selection, quality assessment, and data extraction were performed independently by three investigators. Statistical analysis was performed using R version 4.3, applying a random-effects model. The quality of the included observational studies was assessed using the "JBI-MAStARI". Results: A total of 5,936 studies were retrieved, 13 of which were included in the final meta-analysis. The sample included a total of 2,947 patients with COVID-19 from four countries, of whom approximately 43.3% were men and 49.4% were women. Among the patients, 1,323 showed evidence of exposure to T. gondii through IgG detection, while 1,302 COVID-19 patients were explicitly examined for T. gondii by IgM detection, and 36 positive cases were identified. The frequency of exposure to T. gondii, determined by the presence of IgG in patients with COVID-19, reached 49% (95% CI: 34–63%; 2,947 participants; 13 studies; I2 = 98%, p < 0.01). In addition, the frequency of exposure to T. gondii, evaluated by IgM presence in patients with COVID-19, was 2% (95% CI: 0–6%; 1,302 participants; 6 studies; I2 = 94%, p < 0.01). Conclusion: It was shown that almost half of COVID-19 patients had previous exposure to T. gondii through the presence of IgG, and a small percentage, 2%, showed active infection through IgM detection. Although the results indicate a possible correlation between exposure to T. gondii and the presence of COVID-19, it is essential to note that this study is based on observational research, which precludes establishing a causal relationship. Consequently, further research is required to deepen understanding of the interaction between the two conditions. Terms used: The Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI), Prospective International Registry of Systematic Reviews (PROSPERO), and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). [ABSTRACT FROM AUTHOR]

Background: Malaria disease is one of the most dangerous protozoan parasitic infections with a high mortality rate in developing countries. Malaria is a public health issue, especially in Hormozgan province, and is highly affected by foreign immigrants (Pakistani and Afghani); thus, the present study aimed to evaluate the effect of an intervention based on the health belief model (HBM) on the promotion of malaria prevention behaviors in Afghani immigrants over the age of 18. The participants resided in Persian city in Hormozgan province. Methods: The present quasi-experimental study was conducted on 200 Afghans immigrants over 18 years of age who visited four comprehensive health service centers in Parsian city, south of Iran in June until December 2023. Sampling was by cluster method. In this way, the health centers were considered as clusters, and then 4 centers were randomly selected from among them (two centers of the control group and two centers of the intervention group) and participants were selected by a systematic random method by list of records in the National Integrated Health Record System (called SIB) (100participants control group, 100 participants intervention group). The data were collected using a researcher-made questionnaire based on the HBM before and after the educational intervention An educational program was designed and implemented to promote preventive behaviors against malaria in five sessions using different strategies and based on the HBM for the intervention group. The data were analyzed using independent-samples T-test, paired-samples T-test, Pearson's correlation coefficient, analysis of covariance and linear regression. All statistical analyses and hypothesis testing were done in IBM SPSS version 25, at a significance level of 0.05. Results: In the intervention group, there was a significant difference in the mean scores of knowledge (6.48, 95% CI: 5.9,7.05), perceived susceptibility (10.57, 95% CI: 10.03, 11.1), perceived severity (16.61, 95% CI: 15.83, 16.83), perceived self-efficacy (18.26, 95% CI: 17.55, 18.96), perceived benefits (15.43, 95% CI: 14.68, 16.17), perceived barriers (-22.49, 95% CI: -23.63, -21.30), cues to action (15.06, 95% CI: 14.36, 15.75), and preventive behaviors (20.05, 95% CI: 19.44, 20.65), before and after the educational intervention. P-value < 0.001. The regression analysis showed that the constructs of perceived susceptibility (T = 4.72, P < 0.001), cues to action (T = 5.30, P < 0.001)and perceived self-efficacy (T = 4.93, P < 0.001) led to the greatest change in malaria prevention behaviors(R-Square = 0.549). Conclusion: The present findings showed that the HBM -based intervention was effective in preventive behaviors against malaria in Afghans. It is recommended to design suitable educational interventions in order to increase the perceived susceptibility, cues to action and self-efficacy in order to improve preventive behaviors against malaria in Afghans. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoan parasites from different species of leishmania. The disease is transmitted by female sandflies that carry these parasites. In this study, datasets on leishmaniasis published in the GEO database were analyzed and summarized. The analysis in all three datasets (GSE43880, GSE55664, and GSE63931) used in this study has been performed on the skin wounds of patients infected with a clinical form of leishmania (Leishmania braziliensis), and biopsies have been taken from them. To identify differentially expressed genes (DEGs) between leishmaniasis patients and controls, the robust rank aggregation (RRA) procedure was applied. We performed gene functional annotation and protein-protein interaction (PPI) network analysis to demonstrate the putative functionalities of the DEGs. The study utilized Molecular Complex Detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to detect molecular complexes within the protein-protein interaction (PPI) network and conduct analyses on the identified functional modules. The CytoHubba plugin's results were paired with RRA analysis to determine the hub genes. Finally, the interaction between miRNAs and hub genes was predicted. Based on the RRA integrated analysis, 407 DEGs were identified (263 up-regulated genes and 144 down-regulated genes). The top three modules were listed after creating the PPI network via the MCODE plug. Seven hub genes were found using the CytoHubba app and RRA: CXCL10, GBP1, GNLY, GZMA, GZMB, NKG7, and UBD. According to our enrichment analysis, these functional modules were primarily associated with immune pathways, cytokine activity/signaling pathways, and inflammation pathways. However, a UBD hub gene is interestingly involved in the ubiquitination pathways of pathogenesis. The mirNet database predicted the hub gene's interaction with miRNAs, and results revealed that several miRNAs, including mir-146a-5p, crucial in fighting pathogenesis. The key hub genes discovered in this work may be considered as potential biomarkers in diagnosis, development of agonists/antagonist, novel vaccine design, and will greatly contribute to clinical studies in the future. [ABSTRACT FROM AUTHOR]

AbstractExposure to biosolids in human waste handling occupations is associated with a risk for illness due to microbial infections. Although several years of exposure to biosolids might be hypothesized to be a prophylaxis against infection, the risks associated with infections from antibiotic-resistant organisms can also be a potential concern. Therefore, this study aimed to conduct a screening level risk assessment by deriving occupational exposure limits (OELs) characterizing the risks of adverse health effects among workers in human waste handling occupations with a focus on exposure to two pharmaceuticals commonly found in biosolids: ciprofloxacin (CIP) and azithromycin (AZ). Epidemiological and exposure studies of workers exposed to biosolids were identified through searches of major scientific databases. Screening OELs (sOELs) for these antibiotics were derived using a standardized methodology. The airborne concentrations of CIP and AZ antibiotics were determined using an exposure factors approach. The health-based exposure limits (i.e., sOELs) and the acceptable daily exposure (ADE) values for both of these antibiotics were derived as 80 μg/m3 and 12 μg/kg-day, respectively. An exposure factor approach suggested that inhalation route exposures to CIP and AZ are well below the sOELs and ADE daily doses, and likely too low to cause direct adverse health effects through antibiotic inhalation. A critical review of epidemiological studies on different occupations handling biosolids showed that the workers in industries with potential biosolids exposure have experienced an increased incidence of microbial-exposure-related illness. The health effects seen in the workers have been attributed to bacterial, viral, and protozoan infections. To the extent that bacteria are the pathogen of concern, it is not clear whether these bacteria are resistant to antibiotics commonly found in biosolids. It is also unclear whether the presence of antibiotics or antibiotic-resistant bacteria increases the susceptibility of these workers. Additional studies will provide more definitive estimates of inhalation and dermal exposures to CIP and AZ and could verify the exposure estimates in this study based on the literature and common exposure factors. [ABSTRACT FROM AUTHOR]

Introduction: Hemophagocytic lymphohistiocytosis characterized by hemophagocytosis leading to uncontrolled inflammation; the most common etiology in secondary cases of hemophagocytic lymphohistiocytosis is viral infections, especially Epstein–Barr virus. Visceral leishmaniasis is a vectorborne protozoal disease caused by Leishmania donovani complex. It is common in tropical and subtropical regions, with 50,000–90,000 new cases annually. Case presentation: A 15-month-old Arab female was admitted to our hospital with 15 days of fever and decreased weight. On clinical examination, she had a markedly enlarged liver and spleen that were palpable 4 cm and 6 cm below the costal margin, respectively. The peripheral blood smear showed hypochromic microcytic anemia, poikilocytosis, reactive lymphocytosis, and mild thrombocytopenia. Bone marrow aspiration did not show malignancy or any other pathological findings. The patient was put on antibiotic therapy without improvement. Repeated bone marrow aspiration showed erythrophagocytosis; intracellular small round organisms looked like the amastigote form of Leishmania (Donovan bodies) with no evidence of malignancies. Her lab values showed ferritin greater than 500 ug/L, pancytopenia, and hypertriglyceridemia. The patient was diagnosed with hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis. Conclusion: Hemophagocytic lymphohistiocytosis secondary to visceral leishmaniasis is an extensively rare phenomenon in the medical literature that causes challenges in diagnosis and management. Steroids should be used wisely to not cover the symptoms of infections or malignancy, and amphotericin B resistance should be kept in mind in unresponsive Leishmania cases. [ABSTRACT FROM AUTHOR]

Aims Evaluate the in vitro efficacy of the essential oils derived from Aloysia citrodora (Verbenaceae), Cymbopogon winterianus (Poaceae), and Ocimum gratissimum (Lamiaceae) against Acanthamoeba polyphaga trophozoites. Additionally, microemulsions formulated with these essential oils, along with their major components, were analyzed. Methods and results The prepared microemulsions were characterized using polarized light microscopy and rheological techniques. The amoebicidal activity was determined by measuring the inhibitory concentration (IC50). Flow cytometry was employed to detect membrane damage and alterations in trophozoites size. The results revealed transparent and thermodynamically stable microemulsions. The essential oil from O. gratissimum exhibited a lower IC50, with values of 280.66 and 47.28 µg ml−1 after 24 and 48 h, respectively. When microemulsions containing essential oils were tested, the IC50 values exhibited a reduction of over 80% after 24 h. Particularly, eugenol, a constituent of the O. gratissimum essential oil, displayed higher amoebicidal activity. The essential oils also caused damage to the cell membrane, resulting in the subsequent death of the trophozoites. Conclusions The EOs of A. citrodora, C. winterianus , and O. gratissimum and their microemulsions showed antiparasitic effect against A. polyphaga trophozoites, representing promising alternatives for the treatment of diseases caused by this protozoan. [ABSTRACT FROM AUTHOR]

This article explores the synthesis and biological activities of curcumin pyrazole analogues. Curcumin, derived from the root of Curcuma longa, has been found to possess various beneficial properties. The study focuses on a new method for preparing curcumin pyrazole derivatives, which involves the addition of boric acid to improve yields and reaction times. The synthesized compounds were tested for their effectiveness against leishmaniasis and tuberculosis, with one analogue showing promising results against leishmaniasis. Molecular docking studies were also conducted to evaluate the binding of the analogues to a key binding site in leishmania. The authors acknowledge the support of Taif University in Saudi Arabia for this research. [Extracted from the article]

Background: Malaria is one of the most public health and life-threatening parasitic infections caused by the protozoan parasite. Since children are immunologically naive to the malaria parasite, they are the main vulnerable groups to be affected by malaria. Aim: This study aimed at determining the prevalence of malaria among children in urban area at Byahi Health Center, Rubavu district. Methods: Cross-sectional study was used to achieve the objectives. To obtain the information regarding social demographic characteristics, written questionnaires in native language were distributed to caregivers. Blood smears were collected and sent to laboratory department for analysis. Data were analyzed using Statistical package for the social sciences (SPSS). Results: Among 50 children who participated in the study, the majority were males over females with 58% and 42% respectively. The prevalence of malaria among children in urban area was higher with 30%. Among the participants, children of age range 1-5 years shown a high prevalence of malaria than those of 5-8 months with 13 and 2 positive cases respectively and children of 1-5 years old was statistically significant with a p-value (p 0.027). Conclusion: After getting the results above, we have seen that children from urban area are affected by malaria with the overall prevalence of 30%. There is a need of improving and rechecking the existing malaria in children, prevention and control measures of the country. Byahi health center should create awareness about the importance early malaria checkup recommended reducing malaria infection. The parents are recommended to protect their children and district leaders should make researcher in others school. It must be reported to Ministry of Health that malaria infection mostly affects children. [ABSTRACT FROM AUTHOR]

Human zoonotic visceral leishmaniasis (ZVL) and canine leishmaniasis (CanL) constitute a major public and veterinary health concern and are both caused by the infection with the protozoan parasite Leishmania infantum. One of the main target organs in CanL is the liver. This complex organ, composed of various highly specialized cell types, has garnered significant attention from the scientific community as a crucial player in innate immune functions. In the context of CanL, liver infection by parasites and the host immune response generated strongly influence the disease outcome. Thus, taking advantage of a co-culture system involving canine hepatocytes and L. infantum-infected autologous Kupffer cells (KCs), allowing cell-to-cell interaction, the current report aims to shed light on the hepatocyte-KCs immune interaction. The co-culture of infected KCs with hepatocytes revealed a vital role of these cells in the activation of a local immune response against L. infantum parasites. Although KCs alone can be immunologically silenced by L. infantum infection, the cell-to-cell interaction with hepatocytes in co-culture can lead to local immune activation. In co-culture it was observed gene expression increased the number of innate immune receptors, specifically cell membrane TLR2 and cytoplasmatic NOD1 along with high TNF-α generation. Altogether, these results suggest that the immune response generated in co-culture could induce the recruitment of other circulating cells to contain and contribute to the resolution of the infection in the liver. This work also enhances our understanding of the liver as a vital organ in innate immunity within the context of CanL. [ABSTRACT FROM AUTHOR]

The development of rapid, accurate, and efficient detection methods for protozoan parasites can substantially control the outbreak of protozoan parasites infection, which poses a threat to global public health. Idealistically, electrochemical biosensors would be able to overcome the limitations of current detection methods due to their simplified detection procedure, on-site quantitative analysis, rapid detection time, high sensitivity, and portability. The objective of this scoping review is to evaluate the current state of electrochemical biosensors for detecting protozoan parasites. This review followed the most recent Preferred Reporting Items for Systematic Review and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) recommendations. Using electrochemical biosensor and protozoan parasite keywords, a literature search was conducted in PubMed, Scopus, Web of Science, and ScienceDirect on journals published between January 2014 and January 2022. Of the 52 studies, 19 were evaluated for eligibility, and 11 met the review's inclusion criteria to evaluate the effectiveness and limitations of the developed electrochemical biosensor platforms for detecting protozoan parasite including information about the samples, biomarkers, bioreceptors, detection system platform, nanomaterials used in fabrication, and limit of detection (LoD). Most electrochemical biosensors were fabricated using conventional electrodes rather than screen-printed electrodes (SPE). The range of the linear calibration curves for the developed electrochemical biosensors was between 200 ng/ml and 0.77 pM. The encouraging detection performance of the electrochemical biosensors demonstrate their potential as a superior alternative to existing detection techniques. On the other hand, more study is needed to determine the sensitivity and specificity of the electrochemical sensing platform for protozoan parasite detection. [ABSTRACT FROM AUTHOR]

Autoimmune pancreatitis type 2 is a relatively novel entity with some still controversial issues. The current diagnostic algorithm relies on imaging studies and histology. Therapy includes corticosteroids with consequently low risk of relapse in the following year. However, the pathogenesis remains unclear, and data are insufficient for long-term prognosis. We have treated a 17-year-old boy whose autoimmune pancreatitis type 2 was revealed during surgery for a pre-existing biliary tract anomaly with concurrent protozoal infection. We discuss the co-occurrence of these conditions in terms of eventual pathogenesis correlation and combined effect on long-term prognosis. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a deadly protozoan parasitic disease and a significant health problem in underdeveloped and developing countries. The global spread of the parasite, coupled with the emergence of drug resistance and severe side effects associated with existing treatments, has necessitated the identification of new and potential drugs. Objective: This study aimed to identify promising compounds for the treatment of leishmaniasis by targeting two essential enzymes of Leishmania donovani: trypanothione reductase (Try-R) and trypanothione synthetase (Try-S). Methods: High-throughput virtual and in vitro screening of in-house and commercial databases was conducted. A pharmacophore model with seven features was developed and validated using the Guner-Henery method. The pharmacophore-based virtual screening yielded 690 hits, which were further filtered through Lipinski's rule, ADMET analysis, and molecular docking against Try-R and Try-S. Molecular dynamics studies were performed on selected compounds, and in vitro experiments were conducted to evaluate their activity against the promastigote and amastigote forms of L. donovani. Results: The virtual screening and subsequent analysis identified 33 promising compounds. Molecular dynamics studies of two compounds (comp-1 and comp-2) demonstrated stable binding interactions with the target enzymes and high affinity. In vitro experiments revealed that 13 compounds exhibited moderate activity against both the promastigote (IC50, 41 µM–76 µM) and the amastigote (IC50, 44 µM–72 µM) forms of L. donovani. Compounds 1 and 2 showed the highest percent inhibition and the lowest IC50 values. Conclusion: The identified compounds demonstrated significant inhibitory activity against Leishmania donovani and stable interactions with target enzymes. These findings suggest that the compounds could serve as promising leads for developing new treatments for leishmaniasis. [ABSTRACT FROM AUTHOR]

Background: miRNAs are known as non-coding RNAs that can regulate gene expression. They are reported in many microorganisms and their host cells. Parasite infection can change or shift host miRNAs expression, which can aim at both parasite eradication and infection. Purpose: This study dealt with examination of miRNA expressed in intestinal protozoan, coccidia , as well as profile changes in host cell miRNA after parasitic infection and their role in protozoan clearance/ survival. Methods: The authors searched ISI Web of Sciences, Pubmed, Scholar, Scopus, another databases and articles published up to 2024 were included. The keywords of miRNA, intestinal protozoa, toxoplasma and some words associated with topics were used in this search. Results: Transfection of miRNA mimics or inhibitors can control parasitic diseases, and be introduced as a new therapeutic option in parasitology. Conclusion: This review can be used to provide up-to date knowledge for future research on these issues. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the clinical burden, spatial dynamics, and associated risk factors of Plasmodium infection among the natives of Chakwal, Punjab Pakistan from 2019 to 2023 to guide targeted screening and treatment interventions. Method: A community-based cross-sectional study was conducted using primary and secondary data sources. Participants were recruited using a multi-stage cluster sampling by taking informed consent for the primary data sources. Whereas a secondary dataset of Plasmodium infection was obtained from the database of surveyed hospitals after ethical consideration. All the participants living in the study area for at least 3 months were included, while patients with chronic illness were excluded. Sociodemographic and environmental data were collected using a structured questionnaire. Plasmodium infection was diagnosed using microscopy, rapid diagnostic tests (RDTs), and nested polymerase chain reaction (PCR) as the reference standard. A Zero-inflated negative binomial logistic regression model and interpolation of malaria distribution to environmental variables were employed to determine the association and spatiotemporal patterns of malaria in Chakwal. Results: Among the 2457 participants, the prevalence of Plasmodium vivax infection (99%) was significantly higher than P. falciparum (0.8%) and mixed infection (0.2%). Females had a higher infection rate than males and the infection rate was higher in adults (21–40 years) and children (0–20 years). Age category (61–100), P. vivax species, temperature, rainfall, monsoon season, and mixed infection factors were significantly associated (p < 0.05) with increased Plasmodium infection risk. Geospatial mapping indicated potential malaria hotspots in Sarkal Kasar, Chak Baili, Mulkwal, Chohan, and other close areas of the Potohar region. Conclusion: The clinical burden of P. vivax was the highest during monsoon season in Chakwal. Age, gender, climatic factors, and mixed infection were significant risk factors for malaria transmission in this region. Targeted screening and treatment strategies should prioritize identified hotspots and high-risk groups to effectively control malaria in Potohar region of Pakistan. [ABSTRACT FROM AUTHOR]

Efficient cattle production and provision of animal-sourced foods in much of Africa is constrained by vector-borne bacterial and protozoal diseases. Effective vaccines are not currently available for most of these infections resulting in a continuous disease burden that limits genetic improvement. We tested whether stimulation of innate immunity using the Toll-like Receptor (TLR) 7 agonist imiquimod, formulated with saponin and water-in-oil emulsion, would protect against morbidity and mortality due to Anaplasma marginale, a tick-borne pathogen of cattle highly endemic in west Africa. In Trial 1, haplotype matched Friesian x Sanga (F1) A. marginale negative calves were allocated to either the experimental group (n = 10) and injected with the synthetic TLR 7 agonist/saponin formulation or to an untreated control group (n = 10). TLR7 agonist/saponin injected calves responded with significantly elevated rectal temperature, enlarged regional lymph nodes, and elevated levels of IL-6 post-injection as compared to control group calves. All calves were then allowed to graze in pasture for natural exposure to tick transmission. All calves in both groups acquired A. marginale, consistent with the high transmission rate in the endemic region. The need for antibiotic treatment, using pre-existing criteria, was significantly lower in the experimental group (odds ratio for not requiring treatment was 9.3, p = 0.03) as compared to the control group. Despite treatment, 6/10 calves in the control group died, reflecting treatment failures that are typical of anaplasmosis in the acute phase, while mortality in the experimental group was 1/10 (odds ratio for survival was 13.5, p = 0.03). The trial was then repeated using 45 Friesian x Sanga calves per group. In Trial 2, the odds ratios for preventing the need for treatment and for mortality in the TLR7 agonist/saponin experimental group versus the control group were 5.6 (p = 0.0002) and 7.0 (p = 0.004), respectively, reproducing the findings of the initial trial. Together these findings demonstrate that innate immune stimulation using a TLR7 agonist formulated with saponin and water-in-oil emulsion provides significant protection against disease caused by tick borne A. marginale in highly susceptible cross-bred cattle, critically important for their potential to increase productivity for smallholder farmers in Africa. [ABSTRACT FROM AUTHOR]

Malaria, a protozoal infection caused by the six species of the genus Plasmodium, is one of the most important diseases known to humankind, with most infections caused by either of the two species - Plasmodium vivax and Plasmodium falciparum. Previously, it was held that falciparum malaria was responsible for causing severe, life-threatening disease, with vivax malaria causing mild or uncomplicated infections. In this case series, the clinical, hematological, and biochemical profiles of eight patients with features of complications due to P. vivax malaria, along with their clinical course, response to treatment, and clinical outcomes have been described. Among these, the most common clinical features were fever, headache, and myalgias. Five patients had altered mental status, two were prostrated, two were hypotensive, and one had recurrent generalized seizures. Three patients had pancytopenia, two had both anemia and thrombocytopenia, and one had evidence of disseminated intravascular coagulation. Six patients had clinical jaundice, four had elevated transaminases, and four had acute kidney injury. All cases showed excellent response to anti-malarial therapy. Hence, this case series revealed that P. vivax is capable of causing severe, life-threatening organ dysfunction akin to those seen in P. falciparum malaria and that early diagnosis and treatment initiation are associated with positive patient end outcomes. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a spectrum of conditions caused by infection with the protozoan Leishmania spp. parasites. Leishmaniasis is endemic in 98 countries around the world, and resistance to current anti-leishmanial drugs is rising. Our work has identified and characterised a previously unstudied galactokinase-like protein (GalK) in Leishmania donovani , which catalyses the MgATP-dependent phosphorylation of the C-1 hydroxyl group of d -galactose to galactose-1-phosphate. Here, we report the production of the catalytically active recombinant protein in E. coli , determination of its substrate specificity and kinetic constants, as well as analysis of its molecular envelope using in solution X-ray scattering. Our results reveal kinetic parameters in range with other galactokinases with an average apparent Km value of 76 μM for galactose, V max and apparent K cat values with 4.46376 × 10−9 M/s and 0.021 s−1, respectively. Substantial substrate promiscuity was observed, with galactose being the preferred substrate, followed by mannose, fructose and GalNAc. Ld GalK has a highly flexible protein structure suggestive of multiple conformational states in solution, which may be the key to its substrate promiscuity. Our data presents novel insights into the galactose salvaging pathway in Leishmania and positions this protein as a potential target for the development of pharmaceuticals seeking to interfere with parasite substrate metabolism. • Galactose, mannose, fructose and GalNAc are substrates for Ld GalK. • Kinetic parameters are in range with other galactokinases. • Structural flexibility indicates conformational changes upon ligand binding. • Development of anti-leishmanial therapeutics exploiting galactose metabolism. [ABSTRACT FROM AUTHOR]

Malaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug‐resistant Plasmodium falciparum have hampered the efficacy of current anti‐malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood‐stage anti‐plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti‐malarial, anti‐fungal, anti‐inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood‐stage inhibitory activity of 26 hybrid compounds was evaluated against mixed‐stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC50 values determined after 48 h of treatment based on the drug‐response curves. Two potent compounds (11 and 10), with 2‐Br and 2,6‐diCl substitutions, showed pronounced activity with IC50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature‐stage trophozoites than ring‐stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human‐derived Mo7e cells, and murine‐derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum‐dihydrofolate reductase, where 11 and 10 showed a binding affinity of −10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4‐nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti‐plasmodial agent. [ABSTRACT FROM AUTHOR]

Diseases caused by insect-borne protozoan parasites, namely malaria, leishmaniasis, and trypanosomiasis, range from subclinical infections to severe illnesses in various hosts, including immunocompetent humans, with a profound impact on public health and economies worldwide. In addition to their usual hemolymphatic invasion and dissemination within the mammalian host, insect-borne protozoan parasites can colonize noncanonical tissues. Cumulative research has shed light on the diverse and complex effects of these pathogens on the respiratory system, which have been largely overlooked. These findings provide valuable insights into the pathophysiology of insect-borne protozoan infections and have the potential to impact the development of innovative approaches for the prevention, diagnosis, treatment, and interruption of the chain of transmission of these devastating diseases. The protozoan parasites Plasmodium , Leishmania , and Trypanosoma are transmitted by hematophagous insects and cause severe diseases in humans. These infections pose a global threat, particularly in low-resource settings, and are increasingly extending beyond the current endemic regions. Tropism of parasites is crucial for their development, and recent studies have revealed colonization of noncanonical tissues, aiding their survival and immune evasion. Despite receiving limited attention, cumulative evidence discloses the respiratory system as a significant interface for host–pathogen interactions, influencing the course of (co)infection and disease onset. Due to its pathophysiological and clinical implications, we emphasize that further research is needed to better understand the involvement of the respiratory system and its potential to improve prevention, diagnosis, treatment, and interruption of the chain of transmission. [ABSTRACT FROM AUTHOR]

Copyright of Balikesir Health Sciences Journal / Balıkesir Sağlık Bilimleri Dergisi is the property of Balikesir Health Sciences Journal (BAUN Health Sci J) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The socio-economic importance of parasitic diseases, above all malaria and intestinal helminthosis, is so great that this pathology creates an obstacle for the economic development of many countries of the world. Cases of introduction of tropical parasitic diseases in non-endemic countries seriously harm people's health. Considering the global importance of parasitic pathology, most countries of the world have set the problem of fighting parasitic diseases as a goal to be solved. Protozoan diseases and helminthoses, which are the subject of parasitology, are an important part of infectious pathology. According to the WHO, more than 4.5 billion people worldwide suffer from parasitic diseases. About one million parasitic patients are registered in Russia every year. Their actual number exceeds 20 million people. WHO shows that diseases caused by helminths are the third most important infectious and parasitic diseases in the world, and diseases caused by plasmodials take the fourth place (1.4 billion and 600 million cases, respectively). All this requires medical workers to be familiar with the modern principles of diagnosis, treatment and prevention of human parasitic diseases and makes it necessary to teach them. The developed new curriculum is recommended for the teaching of medical students, postgraduate training of doctors and teachers. [ABSTRACT FROM AUTHOR]

Copyright of Environmental & Social Management Journal / Revista de Gestão Social e Ambiental is the property of Environmental & Social Management Journal and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Elucidation of pathways regulating parasite cell death is believed to contribute to identification of novel therapeutic targets for protozoan diseases, and in this context, apoptosis-like cell death has been reported in different groups of protozoa, in which metacaspases seem to play a role. In the genus Plasmodium, apoptotic markers have been detected in P. falciparum and P. berghei, and no study focusing on P. vivax cell death has been reported so far. In the present study, we investigated the susceptibility of P. vivax to undergo apoptotic cell death after incubating mature trophozoites with the classical apoptosis inducer staurosporine. As assessed by flow cytometry assays, staurosporine inhibited parasite intraerythrocytic development, which was accompanied by a decrease in cell viability, evidenced by reduced plasmodial mitochondrial activity. However, typical signs of apoptosis, such as DNA fragmentation, chromatin condensation, and nuclear segregation, were not detected in the parasites induced to cell death, and no significant alteration in metacaspase gene expression (PvMCA1) was observed under cell death stimulus. Interestingly, dying parasites positively modulated cell death (eryptosis) of host erythrocytes, which was marked by externalization of phosphatidylserine and cell shrinkage. Our study shows for the time that P. vivax blood stages may not be susceptible to apoptosis-like processes, while they could trigger eryptosis of parasitized cells by undergoing cell death. Further studies are required to elucidate the cellular machinery involved in cell death of P. vivax parasites as well as in the modulation of host cell death. [ABSTRACT FROM AUTHOR]

Free-living amoebae (FLA) are isolated from the hospital environments and known as Trojan horses for medical essential microorganisms. This study aimed to investigate the prevalence and the presence of FLA and two critical agents of nosocomial infections, in the hospital wards. Sixty samples were collected from four communities and cultured onto non-nutrient agar (NNA). After total DNA extraction, FLA were characterized using PCR and sequencing. The presence of Candida albicans and Staphylococcus aureus was evaluated using real-time and conventional PCR, respectively. Acanthamoeba sp. was characterized in 30 (50%) samples. Two (6.6%) and one (3.3%) samples were positive for Vahlkampfiidae and Vermamoeba vermiformis, respectively. S. aureus was detected in 13 (43.3%) of samples, while none of them were positive for methicillin-resistant gene. C. albicans DNA was detected in one (3.3%) FLA-positive sample. The isolation of FLA from hospital suggests an essential role these eukaryotes in the inter-ward circulation of nosocomial infections. [ABSTRACT FROM AUTHOR]

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether tuft cells are required for the expulsion of the cestode, Hymenolepis diminuta, from the non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c and C57BL/6 mice infected with H. diminuta expelled the worms by 11 days post-infection (dpi) and displayed DCLK1+ (doublecortin-like kinase 1) tuft cell hyperplasia in the small intestine (not the colon) at 11 dpi. This tuft cell hyperplasia was dependent on IL-4Rα signalling and adaptive immunity, but not the microbiota. Expulsion of H. diminuta was slowed until at least 14 dpi, but not negated, in tuft cell-deficient Pou2f3-/- mice and was accompanied by delayed goblet cell hyperplasia and slowed small bowel transit. Worm antigen and mitogen evoked production of IL-4 and IL-10 by splenocytes from wild-type and Pou2f3-/- mice was not appreciably different, suggesting similar systemic immune reactivity to infection with H. diminuta. Wild-type and Pou2f3-/- mice infected with H. diminuta displayed partial protection against subsequent infection with the nematode Heligmosomoides bakeri. We speculate that, with respect to H. diminuta, enteric tuft cells are important for local immune events driving the rapidity of H. diminuta expulsion but are not critical in initiating or sustaining systemic Th2 responses that provide concomitant immunity against secondary infection with H. bakeri. Author summary: The small intestinal tuft cell is emerging as a versatile sentinel cell type in a variety of infections involving protozoans, nematodes, and certain bacteria. Whether the tuft cell responds to enteric cestode infections and the extent of its involvement in mediating the anti-helminth response is not yet characterized. Using mice infected with Hymenolepis diminuta, we show that tuft cells help accelerate expulsion of this lumen-dwelling cestode, by coordinating local events that form an integral part of the classical "weep and sweep" anti-helminthic response. We further show that although infection with H. diminuta induces both tuft cell hyperplasia as well as protection from subsequent infection with the nematode Heligmosmoides bakeri, the tuft cell is not solely responsible for mediating systemic and other local Th2 responses against H. diminuta. Our work reveals subtle roles for the tuft cell in initiating and coordinating host anti-parasitic activity in cestode infections. At the same time, we show that redundancies exist in the host's mucosal arsenal that ultimately mediate worm expulsion in tuft cell deficient mice. [ABSTRACT FROM AUTHOR]

Giardiasis is among the most prevalent protozoan infections around the globe infecting various species of mammals, birds, reptiles, amphibians, and humans. Among all the species of Giardia, only Giardia lamblia (assemblages A and B) have high zoonotic importance. It is an enteric disease marked by dysentery, abdominal cramps, perfused diarrhea, and anorexia. The giardiasis is majorly controlled by metronidazole, which plays a primary role in the control. The reports of resistance, ecotoxicity, and side effects of this drug necessitate the need for an alternative for the control of this disease; among all the alternatives, phytochemicals are the most promising substance to be used for future anti-giardiasis drug development. Plant preparations containing simple phenolics, alkaloids, saponins, flavonoids, and vitamins have been recently used by researchers. These drugs have been proven effective because of several direct and indirect mechanisms. Simple phenolics easily penetrate the cell of Giardia and disturb energy synthesis, flavonoids destroy the enzymatic process, and alkaloids disturb glycolysis. The vitamins alter the cell energy primarily. Because of these actions, they can be used for control of giardiasis. However, their pharmacological interactions and clinical toxicity studies are needed for their future use. [ABSTRACT FROM AUTHOR]

Chagas disease is a parasitic disease caused by the protozoan Trypanosoma cruzi with an acute, detectable blood parasites phase and a chronic phase, in which the parasitemia is not observable, but cardiac and gastrointestinal consequences are possible. Mice are the principal host used in experimental Chagas disease but reproduce the human infection depending on the animal and parasite strain, besides dose and route of administration. Lipidic mediators are tremendously involved in the pathogenesis of T. cruzi infection, meaning the prostaglandins and thromboxane, which participate in the immunosuppression characteristic of the acute phase. Thus, the eicosanoids inhibition caused by the nonsteroidal anti‐inflammatory drugs (NSAIDs) alters the dynamic of the disease in the experimental models, both in vitro and in vivo, which can explain the participation of the different mediators in infection. However, marked differences are founded in the various NSAIDs existing because of the varied routes blocked by the drugs. So, knowing the results in the experimental models of Chagas disease with or without the NSAIDs helps comprehend the pathogenesis of this infection, which still needs a better understanding. [ABSTRACT FROM AUTHOR]

Chemokines belong to the group of small proteins within the cytokine family having strong chemo-attractant properties. In most cases, the strong immuno-modulatory role of chemokines is crucial for generating the immune response against pathogens in various protozoan diseases. In this review, we have given a brief update on the classification, characterization, homeostasis, transcellular migration, and immuno-modulatory role of chemokines. Here we will evaluate the potential role of chemokines and their regulation in various protozoan diseases. There is a significant direct relationship between parasitic infection and the recruitment of effector cells of the immune response. Chemokines play an indispensable role in mediating several defense mechanisms against infection, such as leukocyte recruitment and the generation of innate and cell-mediated immunity that aids in controlling/eliminating the pathogen. This process is controlled by the chemotactic movement of chemokines induced as a primary host immune response. We have also addressed that chemokine expressions during infection are time-dependent and orchestrated in a systematic pattern that ultimately assists in generating a protective immune response. Taken together, this review provides a systematic understanding of the complexity of chemokines profiles during protozoan disease conditions and the rationale of targeting chemokines for the development of therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Leishmaniasis is a zoonotic protozoan infection which is endemic in parts of Europe. Dogs are commonly affected by Leishmania infantum and are regarded as the main reservoir for humans' infection. Sporadic human cases are reported annually, mainly from the endemic south part of Bulgaria. However, no recent data on canine leishmaniasis geographical distribution in Bulgaria have been published. The aim of this study was to investigate the current seroprevalence rate of L. infantum in stray dogs from areas where this infection was not previously reported. Results: The estimated overall seroprevalence rate was 8.3% (95% confidence interval [CI]: 2.6–14.0) with no significant difference between the two examined districts [χ2 (1, N = 90) = 0.32, p = 0.69]. In Sofia, the seropositivity was 7.2% (95% CI: 0.9–13.5) and in Sofia (stolitsa) 11.0% (95% CI: 0–23.0). No association between sex and serological status [χ2 (1, N = 90) = 1.83, p = 0.27] and age and seropositivity [χ2 (2, N = 90) = 1.98, p = 0.52] was detected. High levels of antibodies (fourfold increase from the assay's cut-off) were observed in half of the positive dogs. [ABSTRACT FROM AUTHOR]

This narrative review was aimed at collecting updated knowledge on the risk factors, illnesses caused, and measures for the prevention of protozoan infections transmitted by food and drinking water. Reports screened dated from 2019 to the present and regarded global prevalence in food handlers, occurrence in food and drinking water, impact on human health, and recently reported outbreaks and cases of severe infections attributable to the dietary route. Cryptosporidium spp., Cyclospora cayetanensis, Entamoeba histolytica, and Cystoisospora belli were the protozoans most frequently involved in recently reported waterborne and foodborne outbreaks and cases. Blastocystis hominis was reported to be the most widespread intestinal protozoan in humans, and two case reports indicated its pathogenic potential. Dientamoeba fragilis, Endolimax nana, and Pentatrichomonas hominis are also frequent but still require further investigation on their ability to cause illness. A progressive improvement in surveillance of protozoan infections and infection sources took place in developed countries where the implementation of reporting systems and the application of molecular diagnostic methods led to an enhanced capacity to identify epidemiological links and improve the prevention of foodborne and waterborne protozoan infections. [ABSTRACT FROM AUTHOR]

Background and Aim: These three parks in North-east Thailand, Kosamphi Forest Park, Kumphawapi Monkey Garden, and Dong Ling Don Chao Pu Park, are internationally recognized for sheltering long-tailed macaques. Overfeeding by tourists and locals significantly increases the frequency of human-macaque encounters. Being close to each other raises the chances of contracting gastrointestinal (GI) parasites. This study was designed to estimate the prevalence and range of GI parasite infections in long-tailed macaques among the three major natural habitats. Materials and Methods: Three hundred fecal samples were collected from long-tailed macaques, with 100 samples from each of the three study sites. The samples underwent Formalin-ethyl acetate concentration technique examination. Parasites were identified based on their morphology and size as observed under a light microscope. Results: About 66.67% of the population had GI parasitic infection. Balantidium coli had the highest occurrence (41.66%), whereas Strongyloides spp. (24.33%), Trichuris spp. (18.33%), Entamoeba coli (10.33%), and Endolimax nana (2.33%) followed next in prevalence. A higher rate of single infections (41%) was reported compared to mixed infections (25.66%). At Dong Ling Don Chao Pu Park, the prevalence rate of B. coli in long-tailed macaques was 70%, markedly higher than those reported at the other two study sites. In these areas, the first known case of B. coli infection occurred in long-tailed macaques. In the Kumphawapi Monkey Garden, the prevalence of Strongyloides spp. and Trichuris spp. infections was significantly greater (45% and 28%, respectively) compared to the other two areas. Conclusion: In northeast Thailand, long-tailed macaques are predominantly infected with B. coli, causing GI protozoal infections. In this primate population of the region, Strongyloides and Trichuris species are common helminths. This study offers new knowledge on parasitic loads in Thai long-tailed macaques, essential for devising effective One Health approaches to prevent and manage zoonotic diseases. [ABSTRACT FROM AUTHOR]

Malaria is an infection caused by the protozoan Plasmodium, transmitted to humans by Anopheles mosquitos. The diagnosis involves a combination of clinical observations, clinical history, and microscopic blood examination. In this study, we assessed Plasmodium falciparum infection in two patients of african origin with malaria diagnosis, using two different microscopic examination and hematological analyzers. The Sysmex XN-9000 is able of revealing, by the white cell differential (WDF) scattergram panel, an abnormal cluster indicative of the accumulation of plasmodium infected red blood cells, associated with a specific alarm signal on the Q-FLAG panel. The Mindray BC-6800 Plus also showed an anomalous cell cluster, linked to parasitized red blood cells in the differentiation channel (DIFF). Also in this case the cluster was associated with a specific alarm of 'Infected red blood cells' ('InR'), identifying the number and percentage of infected red blood cells. Microscopic analysis confirmed the presence of ring forms of the parasite in both cases. Both XN-9000 and BC-6800 Plus, which integrate cytofluorimetric and cytomorphological analysis, demonstrated the potential for rapid and accurate diagnosis of malaria infection. [ABSTRACT FROM AUTHOR]

Simple Summary: In the 21st century, one of society's most essential needs is safe food. This need is closely tied to understanding risks that affect both animals and humans. A major global concern is the spread of antibiotic resistance through food, such as raw milk and dairy products. In our research, we aim to track changes in antibiotic-resistant genes in raw milk and products made from raw milk. Our study follows the journey of milk "from farm to fork", starting at a small dairy farm, through processing, and finally to the consumer, using advanced genetic testing. We identified 112 antibiotic-resistance genes in total. We found that raw cheese had fewer resistant genes compared to raw milk. However, after one month of aging, the number of resistant genes in the cheese increased significantly, even surpassing the initial levels found in raw milk. This is particularly concerning for public health because of the presence of a highly dangerous type of antibiotic-resistance gene known for causing serious health issues. In conclusion, more research like ours is necessary to understand how antibiotic-resistance genes change during food production. It is also important to assess the risk of these genes spreading through raw food products and to ensure that food safety standards are maintained. A new approach to food safety, using advanced genetic testing, should be considered. Raw milk and dairy products can serve as potential vectors for transmissible bacterial, viral and protozoal diseases, alongside harboring antimicrobial-resistance genes. This study monitors the changes in the antimicrobial-resistance gene pool in raw milk and cheese, from farm to consumer, utilizing next-generation sequencing. Five parallel sampling runs were conducted to assess the resistance gene pool, as well as phage or plasmid carriage and potential mobility. In terms of taxonomic composition, in raw milk the Firmicutes phylum made up 41%, while the Proteobacteria phylum accounted for 58%. In fresh cheese, this ratio shifted to 93% Firmicutes and 7% Proteobacteria. In matured cheese, the composition was 79% Firmicutes and 21% Proteobacteria. In total, 112 antimicrobial-resistance genes were identified. While a notable reduction in the resistance gene pool was observed in the freshly made raw cheese compared to the raw milk samples, a significant growth in the resistance gene pool occurred after one month of maturation, surpassing the initial gene frequency. Notably, the presence of extended-spectrum beta-lactamase (ESBL) genes, such as OXA-662 (100% coverage, 99.3% identity) and OXA-309 (97.1% coverage, 96.2% identity), raised concerns; these genes have a major public health relevance. In total, nineteen such genes belonging to nine gene families (ACT, CMY, EC, ORN, OXA, OXY, PLA, RAHN, TER) have been identified. The largest number of resistance genes were identified against fluoroquinolone drugs, which determined efflux pumps predominantly. Our findings underscore the importance of monitoring gene pool variations throughout the product pathway and the potential for horizontal gene transfer in raw products. We advocate the adoption of a new approach to food safety investigations, incorporating next-generation sequencing techniques. [ABSTRACT FROM AUTHOR]

Background: Malaria is one of the most public health and life-threatening parasitic infections caused by the protozoan parasite. Since children are immunologically naive to the malaria parasite, they are the main vulnerable groups to be affected by malaria. Aim: This study aimed at determining the prevalence of malaria among children in urban area at Byahi Health Center, Rubavu district. Methods: Cross-sectional study was used to achieve the objectives. To obtain the information regarding social demographic characteristics, written questionnaires in native language were distributed to caregivers. Blood smears were collected and sent to laboratory department for analysis. Data were analyzed using Statistical package for the social sciences (SPSS). Results: Among 50 children who participated in the study, the majority were males over females with 58% and 42% respectively. The prevalence of malaria among children in urban area was higher with 30%. Among the participants, children of age range 1-5 years shown a high prevalence of malaria than those of 5-8 months with 13 and 2 positive cases respectively and children of 1-5 years old was statistically significant with a p-value (p 0.027). Conclusion: After getting the results above, we have seen that children from urban area are affected by malaria with the overall prevalence of 30%. There is a need of improving and rechecking the existing malaria in children, prevention and control measures of the country. Byahi health center should create awareness about the importance early malaria checkup recommended reducing malaria infection. The parents are recommended to protect their children and district leaders should make researcher in others school. It must be reported to Ministry of Health that malaria infection mostly affects children. [ABSTRACT FROM AUTHOR]

Babesiosis, a zoonotic blood protozoal disease, threatens humans and animals and is difficult to treat due to growing antimicrobial resistance. The study aimed to investigate the therapeutic efficacy of artesunate (AS), a well-known derivative of artemisinin, against Babesia microti (B. microti) using a murine infection model. Male BALB/c mice (6 weeks old; 15 per group) were chosen and randomly divided into 1) the control group, 2) the B. microti group, and 3) the B. microti + artesunate treatment groups. AS treatment at 2 mg/kg, 4 mg/kg, and 8 mg/kg of body weight significantly (p < 0.05) reduced the B. microti load in blood smears in a dose-dependent manner. Additionally, AS treatment mitigated the decrease in body weight and restored the normal state of the liver and spleen viscera index compared to the B. microti-infected group after 28 days. Hematological analysis revealed significant increases in RBC, WBC, and PLT counts post-AS treatment compared to the B. microti-infected group. Furthermore, AS administration resulted in significant reductions in total protein, bilirubin, ALT, AST, and ALP levels, along with reduced liver and spleen inflammation and lesions as observed through histopathological analysis. AS also elicited dose-dependent changes in mRNA and protein expression levels of apoptotic, proinflammatory, and anti-inflammatory cytokines in the liver compared to the control and B. microti-infected groups. Immunolabeling revealed decreased expression of apoptotic and inflammation-related proteins in AS-treated hepatic cytoplasm compared to the B. microti-infected group. AS also in dose-dependent manner decreased apoptotic protein and increased Bcl-2. Overall, these findings underscore the potential of AS as an anti-parasitic candidate in combating B. microti pathogenesis in an in vivo infection model, suggesting its promise for clinical trials as a treatment for babesiosis. [ABSTRACT FROM AUTHOR]

Leishmaniasis is a disease caused by a protozoan of the genus Leishmania, affecting millions of people, mainly in tropical countries, due to poor social conditions and low economic development. First-line chemotherapeutic agents involve highly toxic pentavalent antimonials, while treatment failure is mainly due to the emergence of drug-resistant strains. Leishmania arginase (ARG) enzyme is vital in pathogenicity and contributes to a higher infection rate, thus representing a potential drug target. This study helps in designing ARG inhibitors for the treatment of leishmaniasis. Py-CoMFA (3D-QSAR) models were constructed using 34 inhibitors from different chemical classes against ARG from L. (L.) amazonensis (LaARG). The 3D-QSAR predictions showed an excellent correlation between experimental and calculated pIC50 values. The molecular docking study identified the favorable hydrophobicity contribution of phenyl and cyclohexyl groups as substituents in the enzyme allosteric site. Molecular dynamics simulations of selected protein–ligand complexes were conducted to understand derivatives' interaction modes and affinity in both active and allosteric sites. Two cinnamide compounds, 7g and 7k, were identified, with similar structures to the reference 4h allosteric site inhibitor. These compounds can guide the development of more effective arginase inhibitors as potential antileishmanial drugs. [ABSTRACT FROM AUTHOR]

Background: Rodents are recognized as the hosts of many vector-borne bacteria and protozoan parasites and play an important role in their transmission and maintenance. Intensive studies have focused on their infections in vectors, especially in ticks, however, vector-borne bacterial and protozoan infections in rodents are poorly understood although human cases presenting with fever may due to their infection have been found. Methods: From May to October 2019, 192 wild rodents were trapped in wild environment of Guangxi Province, and the spleen samples were collected to reveal the presence of vector-borne bacterial and protozoan infections in them. The microorganisms in rodents were identified by detecting their DNA using (semi-)nested PCR. All the PCR products of the expected size were subjected to sequencing, and then analyzed by BLASTn. Furthermore, all the recovered sequences were subjected to nucleotide identity and phylogenetic analyses. Results: As a result, 192 rodents representing seven species were captured, and Bandicota indica were the dominant species, followed by Rattus andamanensis. Based on the (semi-)nested PCR, our results suggested that Anaplasma bovis, Anaplasma capra, Anaplasma ovis, Anaplasma phagocytophilum, "Candidatus Neoehrlichia mikurensis", "Candidatus E. hainanensis", "Candidatus E. zunyiensis", three uncultured Ehrlichia spp., Bartonella coopersplainsensis, Bartonella tribocorum, Bartonella rattimassiliensis, Bartonella silvatica, two uncultured Bartonella spp., Babesia microti and diverse Hepatozoon were identified in six rodent species. More importantly, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are zoonotic pathogens except Anaplasma bovis and Anaplasma ovis with zoonotic potential. Furthermore, dual infection was observed between different microorganisms, and the most common type of co-infection is between "Ca. N. mikurensis" and other microorganisms. Additionally, potential novel Bartonella species and Hepatozoon species demonstrated the presence of more diverse rodent-associated Bartonella and Hepatozoon. Conclusions: The results in this work indicated great genetic diversity of vector-borne infections in wild rodents, and highlighted the potential risk of human pathogens transmitted from rodents to humans through vectors. Author summary: Rodents are the important hosts of many pathogens, especially vector-borne pathogens, and can harbor and transmit them to humans and cause diseases. In China, little information is known about the infection of vector-borne pathogens in rodents although the rodent species are very diverse. In this study, seven wild rodent species were collected to identify the genetic diversity of vector-borne bacteria and protozoan. Interestingly, diverse vector-borne microorganisms, including four Anaplasma, five Ehrlichia, "Candidatus Neoehrlichia mikurensis", six Bartonella, Babesia microti and diverse Hepatozoon were identified in six rodent species. Furthermore, two potential novel Bartonella species were detected. All these data suggested great genetic diversity of vector-borne pathogens infections in rodents. Of them, six species (including two Anaplasma, two Bartonella, "Ca. N. mikurensis" and Bab. microti) are pathogenic to humans except A. bovis and A. ovis with zoonotic potential, suggesting significant risks to local human population. [ABSTRACT FROM AUTHOR]

Infection with the apicomplexan protozoan Toxoplasma gondii can be life-threatening in immunocompromised hosts. Transmission frequently occurs through the oral ingestion of T. gondii bradyzoite cysts, which transition to tachyzoites, disseminate, and then form cysts containing bradyzoites in the central nervous system, resulting in latent infection. Encapsulation of bradyzoites by a cyst wall is critical for immune evasion, survival, and transmission. O-glycosylation of the protein CST1 by the mucin-type O-glycosyltransferase T. gondii (Txg) GalNAc-T3 influences cyst wall rigidity and stability. Here, we report X-ray crystal structures of TxgGalNAc-T3, revealing multiple features that are strictly conserved among its apicomplexan homologues. This includes a unique 2nd metal that is coupled to substrate binding and enzymatic activity in vitro and cyst wall O-glycosylation in T. gondii. The study illustrates the divergence of pathogenic protozoan GalNAc-Ts from their host homologues and lays the groundwork for studying apicomplexan GalNAc-Ts as therapeutic targets in disease. A Toxoplasma gondii mucin-type O-glycosyltransferase uses a unique catalytic mechanism to modify bradyzoite cyst wall proteins. A second metal coupled to substrate binding is required for catalysis, while an active site glutamate suggests a double-displacement mechanism. [ABSTRACT FROM AUTHOR]

Background Prolonged diarrhoea is common amongst returning travellers and is often caused by intestinal protozoa. However, the epidemiology of travel-associated illness caused by protozoal pathogens is not well described. Methods We analysed records of returning international travellers with illness caused by Giardia duodenalis , Cryptosporidium spp. Cyclospora cayetanensis or Cystoisospora belli , reported to the GeoSentinel Network during January 2007–December 2019. We excluded records of travellers migrating, with an unascertainable exposure country, or from GeoSentinel sites that were not located in high-income countries. Results There were 2517 cases, 82.3% giardiasis (n  = 2072), 11.4% cryptosporidiosis (n  = 287), 6.0% cyclosporiasis (n  = 150) and 0.3% cystoisosporiasis (n  = 8). Overall, most travellers were tourists (64.4%) on long trips (median durations: 18–30 days). Cryptosporidiosis more frequently affected people < 18 years (13.9%) and cyclosporiasis affected people ≥ 40 years (59.4%). Giardiasis was most frequently acquired in South Central Asia (45.8%) and sub-Saharan Africa (22.6%), cryptosporidiosis in sub-Saharan Africa (24.7%) and South-Central Asia (19.5%), cyclosporiasis in South East Asia (31.3%) and Central America (27.3%), and cystoisosporiasis in sub-Saharan Africa (62.5%). Cyclosporiasis cases were reported from countries of uncertain endemicity (e.g. Cambodia) or in countries with no previous evidence of this parasite (e.g. French Guiana). The time from symptom onset to presentation at a GeoSentinel site was the longest amongst travellers with giardiasis (median: 30 days). Over 14% of travellers with cryptosporidiosis were hospitalized. Conclusions This analysis provides new insights into the epidemiology and clinical significance of four intestinal protozoa that can cause morbidity in international travellers. These data might help optimize pretravel advice and post-travel management of patients with travel-associated prolonged gastrointestinal illnesses. This analysis reinforces the importance of international travel-related surveillance to identify sentinel cases and areas where protozoal infections might be undetected or underreported. [ABSTRACT FROM AUTHOR]

Coccidiosis is an intestinal protozoan disease that affects the poultry industry worldwide. The severity of this disease varies depending on the identity of the infectious agents. Therefore, this study was carried out to identify the Eimeria species that affect broiler chickens, Gallus gallus domesticus, through morphological and molecular phylogenetic analyses. Twenty‐five faecal samples were collected from the broiler chickens in a commercial poultry farm in Riyadh (Saudi Arabia). Using the floatation technique, faeces were examined microscopically for the Eimeria occurrence. Identification of Eimeria species was performed based on morphological criteria and molecular tools (DNA amplification for the partial small subunit ribosomal RNA (18S rRNA), internal transcribed spacer (ITS)‐1, and mitochondrial cytochrome c oxidase I (COI) genes. In this study, 32% (8 out of 25) of collected samples were found to be positive for coccidiosis. After sporulation in potassium dichromate (K2Cr2O7), the sporulated oocysts were observed as ovoid and measured 18.37–23.19 µm (19.87) long and 15.07–18.67 µm (16.46) wide, with the anterior location of a polar granule and absence of micropyle. These Eimeria oocysts were assumed to size and shape characteristics of Eimeria acervulina. Molecular analysis was conducted on the sequences of the polymerase chain reaction products from the three genes studied (18S rRNA, ITS‐1, and COI). At the three genes, results showed that the resultant sequences clustered with E. acervulina from different regions confirming morphological description. This study highlighted the importance of molecular techniques to detect avian Eimeria species more than the traditional morphology‐based tool to optimise the appropriate anticoccidial strategies for long‐term control in the studied area. [ABSTRACT FROM AUTHOR]

Simple Summary: Toxoplasmosis is a globally distributed zoonosis caused by Toxoplasma gondii. This protozoan is capable of infecting mammals and birds and can cause significant impacts on human and animal health. Much of what is known about the parasite's biology, the immune mechanisms involved in toxoplasmosis, and the development of diagnostic tests for this protozoan disease is due to the maintenance of the parasite in laboratory mice. However, the increasing debate on the use of biomodels in scientific research has brought about the need to implement the principles of the 3Rs in laboratory protocols, such as experimental infections with T. gondii in murine models. Therefore, this study aimed to establish the humane endpoints for experimental infection with the T. gondii RH strain in Swiss Webster mice. The results presented here seek to disseminate the method we have proposed for the humane finalization of these animals in experimental protocols using this highly virulent strain as a method of refinement that seeks to enhance animal welfare. The highly virulent Toxoplasma gondii RH strain is maintained through successive passages in mice, but there is still a lack of studies that refine these procedures from a 3Rs perspective, where humanitarian ideals aim to minimize the stress, pain, or suffering of the animals used in the research without the loss of results. The aim of this study was to establish humane endpoints in Swiss Webster mice inoculated with the T. gondii RH strain. A total of 52 mice were infected with 5 × 106 tachyzoites/mL and monitored for periods of up to 5 days. The parameters body weight; hair condition; higher than normal body temperature; hypothermia; respiratory function; pain; soft stools or diarrhea; bloody diarrhea; tense, nervous, or in distress during handling; and ascites were recorded daily in score tables. The results showed that prominent piloerection, respiratory function, pain parameters, and ascites are important clinical signs to be used as a cut-off point for implementing euthanasia. The application of this refinement method helped to avoid animal suffering and pain without compromising the number of parasites recovered. We therefore suggest adopting these parameters in research protocols that require the maintenance of the T. gondii RH strain in murine models to avoid and reduce animal suffering. [ABSTRACT FROM AUTHOR]

Background: Blastocystis sp. is a zoonotic protozoan parasite, and there is limited information about its molecular prevalence and subtypes (STs) distribution in camels globally, especially in Iran. Objectives: This study aimed to examine the prevalence, STs distribution, and zoonotic potential of Blastocystis sp. in one‐humped and two‐humped camels in Ardabil province, northwestern Iran. Methods: A PCR‐sequencing tool using the SSU rRNA gene was employed to examine the occurrence and genetic variation of Blastocystis sp. in 150 faecal samples from Bactrian (Camelus bactrianus, 50 samples) and Dromedary (Camelus dromedarius, 100 samples) camels in Ardabil province. Results: The overall prevalence of Blastocystis sp. in camels was determined to be 12% (18/150) through microscopy and PCR analyses. Phylogenetically, this study identified three distinct zoonotic STs: ST7, ST10, and ST14. ST10 was the most prevalent, comprising 50% (9/18) of the isolated STs from camels. ST14 closely followed with 38.9% (7/18), while ST7 made up 11.1% (2/18) of the total STs. In brief, ST10, ST14, and ST7 represented 50% (7/14), 35.7% (5/14), and 14.3% (2/14) of the Blastocystis‐positive cases in one‐humped camels, respectively. Further, each of the ST10 and ST14 accounted for 50% (2/4) of the Blastocystis‐positive samples in two‐humped camels. An analysis of the available data reveals that out of the 37–44 identified Blastocystis STs, 15 (ST1–ST7, ST10, ST14, ST15, ST21, ST24, ST25, ST26, and ST30) have been reported in camels. The predominant STs observed are ST10 and ST14. Furthermore, among the 15 zoonotic STs (ST1–ST10, ST12–ST14, ST16, and ST23) of Blastocystis reported thus far, nine zoonotic STs (ST1–ST7, ST10, and ST14) have been found in camels. Conclusions: These findings indicate that camels serve as a proper reservoir for a diverse array of Blastocystis STs and thereby can play a significant role in the transmission of this protozoan infection to humans, animals, and water reservoirs. [ABSTRACT FROM AUTHOR]

The present study aimed to determine the prevalence rate of intestinal protozoan infection among children in Duhok Province, North of Iraq, from October 2022 to May 2023. This cross-sectional study was conducted on 740 children attending Hevi Pediatric Hospital, Duhok Province, Iraq. Firstly, all collected stool samples were examined directly by preparing a wet stool smear for the detection of the vegetative stage (Trophozoite) of both Entamoeba histolytica and Giardia lamblia. Thereafter, all stool samples were preserved at -22°C until further use for identifying cysts of protozoa and oocysts of Cryptosporidium parvum by the Telmman concentration stool method. The children were within the age range of 1-14 years. Out of 740 stool samples collected, 205 (27.7%) cases were positive for intestinal protozoan infections as follows: 160 (78.0%) children tested positive for E. histolytica, 35 (17.1%) were positive for C. parvum, and only 10 (4.9%) were positive for G. lamblia. Nonetheless, the results indicated a statistically significant difference between the prevalence of E. histolytica, C. parvum, and G. lamblia infections across different age groups (P<0.05). The highest infection rates of intestinal protozoa, namely E. histolytica, C. parvum, and G. lamblia, were reported in the age ranges of 5-9 years (53.75%, 25.0%, and 60.0%), 1-4 years (28.75%, 20.0%, and 30.0%), and 10-14 years (17.55%, 8.6%, and 10.0%), respectively. In this study, the prevalence of amoebiasis and cryptosporidiosis was reported to be higher than in other studies performed in Iraq, while the prevalence of giardiasis was reported at a lower rate than the rate reported previously in Iraq, especially in Duhok. These infections continue to pose a challenging public health issue, necessitating the implementation of stronger and more effective preventative measures. [ABSTRACT FROM AUTHOR]

Intestinal protozoan parasitic infections are considered one of the most frequent types of infection caused by these parasites and remain a major health problem for communities. This study aims to detect the frequency of intestinal protozoan infections infection among Zakho general population from October 2018 to June 2022. This cross-sectional study was performed on 2,118 patients referring to private medical diagnostic laboratories in Zakho, Kurdistan Region, Iraq. Samples of fecal matter were collected and subjected to analysis using two different techniques: direct observation under the microscope (wet mount) and formalin-ether concentration methods. Morphological characteristics of trophozoites and cysts were used to identify E. histolytica using microscopical examination. Out of 2,118 recruited samples, 1,155 (54.53%) were male, and 963 (45.47%) were female. The mean age of participants was 20.41 (±19.12), with ages ranging from 1 to 63 years. The overall prevalence of protozoan infections was 395/2118 (18.65%). Out of these, Entamoeba histolytica was the predominant pathogenic protozoa infection 271 (68.61%), followed by Giardia lamblia 100 (25.31%). A significant association was seen between Entamoeba histolytica and age groups (P=0.003) and gender (P=0.004). The highest infection rate was reported among the age group <15 years (55.72%). We also found a higher rate of Giardia infection among age group < 15 years (46%) with significant differences (P=0.002) and a higher rate of Giardia seen in females (55%) with significant association (P=0.014). The frequency of Giardia lamblia and E. histolytica infections in our study was higher than other studies reported in Iraq and other countries, and these infections continue to pose a difficult public health issue and necessitate the implementation of stronger and more effective preventative measures. [ABSTRACT FROM AUTHOR]

Theileriosis, a tick borne protozoan disease, drastically affects the productivity of bovine with massive economic repercussion. The current investigation was conducted to determine the molecular prevalence of T. annulata employing cytochrome b gene based PCR assay. Investigation was conducted on 150 blood samples of cattle obtained from three districts, viz. Rajnandgaon (50), Balod (50) and Kabirdham (50) of Chhattisgarh state. Initially microscopic examinations of smears were done followed by PCR analysis of DNA samples. The overall prevalence of tropical theileriosis in plain region of Chhattisgarh was found to be 27.3% (41/150) and 54.0% (81/150) by microscopy and PCR assay, respectively. Among districts, highest prevalence 32% and 60% was recorded in Kabirdham followed by 22% and 54% at Balod and 28% and 50% at Rajnandgaon, by microscopy and PCR assay, respectively. Observations showed that, more number of infected animals were from unorganized farm (62.6%) than organized farm (45%). Present study revealed crossbred cattle more susceptible to T. annulata infection than indigenous animals. [ABSTRACT FROM AUTHOR]

The article describes the case of a 74-year old woman diagnosed with granulomatosis with polyangiitis (GPA) and showed multiple cranial nerve manifestations and nasopharyngeal pseudotumor. The patient demonstrated left facial nerve palsy, hypoesthesia, inflammation and swelling at the left nasopharyngreal area, bilateral sensorineural hearing loss, and mass at the left lateral wall of nasopharynx. She was treated with methylprednisone and cyclosphosphamide. Other symptoms of GPA are indicated.

Malaria, leishmaniasis, and African trypanosomiasis are protozoan diseases that constitute major global health problems, especially in developing countries; however, the development of drug resistance coupled with the toxicity of current treatments has hindered their management. The involvement of certain enzymes (dihydrofolate reductase [DHFR]) or proteins (potassium channels) in the pathogenesis of these protozoan diseases is undeniable. In this study, a series of three DHFR inhibitors (6-5 fused heterocyclic derivatives X, Y, and Z) and one K+ channel blocker (E4031) were screened for their inhibitory effects on Leishmania donovani, Plasmodium falciparum, and Trypanosoma brucei. A resazurin assay was used to assess the antitrypanosomal and antileishmanial activities of the test compounds, whereas the antiplasmodial activity was evaluated through the SYBR Green I test. Moreover, the cytotoxicities of the test compounds were evaluated in Vero, Raw 264.7, and HepG-2 cells using a resazurin-based test, while their pharmacokinetic properties were predicted using the online tool, pkCSM. As a result, compound Y exhibited selective (selectivity index range: from 2.69 to >61.4; Vero, Raw 264.7, and HepG-2 cells) and broad-spectrum antiprotozoal activity against L. donovani promastigotes (IC50: 12.4 µM), amastigotes (IC50: 4.28 µM), P. falciparum (IC50: 0.028 µM), and T. brucei brucei (IC50: 0.81 µM). In addition, compound X inhibited the growth of P. falciparum (IC50: 0.0052 µM) and T. brucei brucei (IC50: 6.49 µM). In silico screening of the active antiprotozoal compounds revealed positive drug likeness scores, as none of the criteria for Lipinski’s rule were violated by these compounds. However, in-depth pharmacokinetic and mechanistic studies are warranted to support the discovery of novel antiprotozoal agents against malaria, leishmaniasis, and African trypanosomiasis by repurposing K+ channel blockers and DHFR inhibitors.