Phylogenetic analysis and antimony resistance of Leishmania major isolated from humans and rodents.

Cutaneous Leishmaniasis (CL) is one of the world's neglected diseases which is caused by Leishmania spp. The aim of this study was to assess molecular profile and antimony resistance of Leishmania isolated from human and rodent hosts. Samples were collected from suspected CL patients referred to health centres and wild rodent's traps in Gonbad-e-Qabus region, north-eastern Iran. Smears were subjected to PCR-RFLP to identify Leishmania species. In addition, ITS1-PCR products were sequenced for phylogenetic analysis. Clinical isolates and rodent samples were subjected to MTT assay to determine IC50 values and in vitro susceptibilities. Expression levels of antimony resistance-related genes were determined in CL isolates. Out of 1,949 suspected patients with CL and 148 rodents, 1,704 (87.4%) and 6 (4.05%) were positive with direct smear, respectively. Digestion patterns of BusRI (HaeIII) endonuclease enzyme were similar to what expected for Leishmania major. Phylogenetic analysis revealed that the highest interspecies similarity was found between current L. major sequences with L. major obtained from Russia and Uzbekistan. Out of 20 L. major samples tested, 13 (65%) were resistant to meglumine antimoniate (MA) treatment, with an activity index (AI) exceeding 4. The remaining 7 samples (35%) responded to MA treatment and were classified as sensitive isolates, with a confirmed sensitive phenotype based on their AI values. The comparison expression analysis of three major antimony resistance-associated genes in unresponsive clinical isolates demonstrated significant fold changes for TDR1 (4.78-fold), AQP1 (1.3-fold), and γ-GCS (1.17-fold) genes (P < 0.05). Herein, we demonstrate genetic diversity and antimony resistance of L. major isolated from human and reservoir hosts in north-eastern Iran, which could be the basis for planning future control strategies.

Potential Association Between Latent Toxoplasma gondii Infection and Suicide Attempts: A Case-Control Registry-Based Study.

Toxoplasma gondii is a ubiquitous parasitic protozoan that may be an important cause of neurological and psychiatric diseases. The purpose of this case-control registry-based study was to evaluate the prevalence of T. gondii infection and related risk factors among subjects who attempted suicide by drug use and a control group at the Iranian National Registry Center for Toxoplasmosis in Mazandaran Province, northern Iran. Baseline data were collected from participants using a questionnaire, and a blood sample was taken from each individual. The plasma was prepared for serological analysis, whereas the buffy coat was used for molecular analysis. Out of 282 individuals (147 cases with suicide attempters [SA] and 135 controls), 42.9% of patients and 16.3% of control subjects were positive for anti-Toxoplasma immunoglobin G (IgG), but all participants were negative for T. gondii DNA and anti-Toxoplasma immunoglobin M. Based on multiple logistic regressions, IgG seropositivity in SA in the age group of 20-30 years was 3.22 times higher than that in the control group (p < 0.001). These findings suggest that latent T. gondii infection among SA is significantly higher than that in healthy individuals, indicating a potential association between latent toxoplasmosis and SA at least in the studied area. Further research is needed to shed light on the potential association between T. gondii and suicide among different populations and areas of the world.

Synthesis and in vitro anti-Toxoplasma gondii activity of a new series of aryloxyacetophenone thiosemicarbazones.

A new series of aryloxyacetophenone thiosemicarbazones 4a-q have been synthesized as anti-Toxoplasma gondii agents. All compounds showed significant inhibitory activity against T. gondii-infected cells (IC50 values 1.09-25.19 µg/mL). The 4-fluorophenoxy derivative (4l) was the most potent compound with the highest selectivity toward host cells (SI = 19), being better than standard drug pyrimethamine. SAR study indicated that the concurrence of proper substituents on both aryl ring of phenoxyacetophenone is important for potency and safety profile. Further in vitro experiments with the representative compounds 4l and 4p revealed that these compounds at the concentration of 5 µg/mL can significantly reduce the viability of T. gondii tachyzoites, as well as their infectivity rate and intracellular proliferation, comparable to those of pyrimethamine.

The effect of edelfosine on GRA1 and MIC3 expressions in acute toxoplasmosis.

Phosphoinositide-dependent phospholipase-C (PI-PLC) triggers the calcium signaling pathway which plays an important role in dense granule and microneme secretion and pathogenesis of Toxoplasma gondii (T. gondii). There are limited data about the effects of phospholipid analogues against T. gondii. The current study assessed the effect of edelfosine, as a phospholipid analogue, on GRA1 and MIC3 expressions using in vitro and in vivo models of acute toxoplasmosis. Infected Vero cells were treated by edelfosine in two subgroups: 24 h following the cell infection and treatment at the same time of cell infection. Animal study was performed on forty mice in four groups including non-infected, infected untreated, infected edelfosine-treated, and infected pyrimethamine-treated. Gene and protein expression analyses were done using quantitative real-time PCR and western blot, respectively. Edelfosine significantly reduced the GRA1 (P < 0.01) and MIC3 (P < 0.01) mRNA and protein expressions in 24 h following the cell infection and at the same time of cell infection groups. In vivo study showed that the edelfosine significantly reduced the GRA1 expression in eye, and MIC3 expression in brain and liver. Moreover, the edelfosine-treated infected mice had significant higher survival rate compared with uninfected mice. The reducing effect of edelfosine on GRA1 and MIC3 mRNA and protein levels 24 h following the cell infection was more than treatment at the same time of cell infection group. Moreover, the effect of edelfosine on GRA1 and MIC3 expression in animal tissues was variable. These data showed that the edelfosine may decrease the T. gondii excretory/secretory antigens through inhibition of PI-PLC.

In vitro and in vivo evaluation of kojic acid against Toxoplasma gondii in experimental models of acute toxoplasmosis.

As current toxoplasmosis chemotherapies have many side effects along with toxicity on patients, we examined the anti-Toxoplasma effect of a biologically important natural antibiotic, kojic acid, in vitro and in vivo. Vero cells were incubated with different concentrations of kojic acid or pyrimethamine (positive control), and the cellular viability was determined. Next, Vero cells were infected with T. gondii (RH strain) and treated with drugs. Then, we calculated the infection index, T. gondii intracellular proliferation and the number and measure of plaque. Moreover, the effect of kojic acid on survival times, serum levels of IFN-γ and TNF-α and histopathological changes in the liver and spleen of Balb/c mice infected with T. gondii were determined. Kojic acid reduced the infection index, intracellular proliferation, the number and measure of plaque in vitro when compared to untreated infected cells. Kojic acid (100 mg/kg/day) also showed a better survival rate than infected untreated control mice (P < 0.05). IFN-γ and TNF-α secretions were significantly increased by kojic acid treatment in comparison to untreated groups (P < 0.05). In addition, its inhibitory effects on inflammatory alterations, apoptosis, and necrosis have been shown in sections of liver and spleen. We conclude that kojic acid exhibit potent anti-Toxoplasma activity with direct and indirect effects on the parasite, although further studies are needed before consideration of clinical trials.

Effects of Aloe vera and Eucalyptus methanolic extracts on experimental toxoplasmosis in vitro and in vivo.

Toxoplasmosis is a worldwide disease caused by the protozoan parasite Toxoplasma gondii (T. gondii), which is most commonly treated by pyrimethamine and sulfadiazine. However, this treatment presents several adverse side effects; Thus, new drugs with lower toxicities are urgently needed. In this study the anti-T. gondii activity of A. vera and Eucalyptus extracts were evaluated in vitro using a MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) assay and in vivo by measuring the survival rates of mice infected with 2 × 103 tachyzoites of RH strain of T. gondii and then injected intraperitoneally by different concentrations of extracts for 4 days. Biochemical parameters such as Ferric Reducing Antioxidant Potential (FRAP) and malondialdehyde (MDA) assay were also evaluated. As results, in the in vitro assay, the IC50 values were 13.2, 24.7, 2.63 µg/ml, and the selectivity indexes were 3.3, 2.4, 3.03 for the A. vera, Eucalyptus and pyrimethamine, respectively. The mice treated with Eucalyptus showed a better survival rate than others (P < 0.05). The increased weight of liver and spleen, due to infection, was reduced by treatments. In FRAP assay Eucalyptus showed a better antioxidant activity than the other extracts. MDA levels in both liver and spleen were reduced by treatment. The results show that A. Vera and Eucalyptus possess anti-T. gondii activities in vitro and in vivo, in addition, Eucalyptus shows antioxidant activity with a higher survival rate. Therefore, Eucalyptus may be a useful candidate for treating Toxoplasma infection. Moreover, further studies are required to investigate the fractionations of this plant against T. gondii.

Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review.

Currently, there is no approved therapy that can eradicate Toxoplasma gondii tissue cysts, which are responsible for chronic infection. This systematic review was performed to assess drugs or compounds that can be used as anti-T. gondii tissue cysts in vitro and in vivo. English electronic databases (i.e., PubMed, Science Direct, Scopus, Google Scholar, and Web of Science) were systematically searched for articles published up to 2017. A total of 55 papers published from 1987 to 2017 were eligible for inclusion in this systematic review. Among the drugs, atovaquone and azithromycin were found effective after long-term inoculation into mice; however, clinical cases of resistance to these drugs have been reported. Also, FR235222, QUI-11, tanshinone IIA, and hydroxyzine were shown to be effective against Toxoplasma cysts, but their effectiveness in vivo remains unknown. Additionally, compound 32, endochin-like quinolones, miltefosine, and guanabenz can be used as effective antiparasitic with the unique ability to reduce brain tissue cysts in chronically infected mice. Importantly, these antimicrobial agents are significant criteria for drug candidates. Future studies should focus on the biology and drug susceptibility of the cyst form of T. gondii in chronic toxoplasmosis patients to find more effective strategies that have sterilizing activity for eliminating T. gondii tissue cysts from the host, preventing disease relapse and potentially shortening the required duration of drug administration. Graphical abstract.

Evaluation of Propranolol Effect on Experimental Acute and Chronic Toxoplasmosis Using Quantitative PCR.

Current therapies against toxoplasmosis are limited, and drugs have significant side effects and low efficacies. We evaluated the potential anti-Toxoplasma activity of propranolol at a dose of 2 or 3 mg/kg of body weight/day in vivo in the acute and chronic phases. Propranolol as a cell membrane-stabilizing agent is a suitable drug for inhibiting the entrance of Toxoplasma gondii tachyzoites into cells. The acute-phase assay was performed using propranolol, pyrimethamine, and propranolol plus pyrimethamine before (pretreatment) and after (posttreatment) intraperitoneal challenge with 1 × 103 tachyzoites of the virulent T. gondii strain RH in BALB/c mice. Also, in the chronic phase, treatment was performed 12 h before intraperitoneal challenge with 1 × 106 tachyzoites of the virulent strain RH of T. gondii in rats. One week (in the acute phase) and 2 months (in the chronic phase) after postinfection, tissues were isolated and DNA was extracted. Subsequently, parasite load was calculated using quantitative PCR (qPCR). In the acute phase, in both groups, significant anti-Toxoplasma activity was observed using propranolol (P < 0.001). Propranolol in the pretreatment group showed higher anti-Toxoplasma activity than propranolol in posttreatment in brain tissues, displaying therapeutic efficiency on toxoplasmosis. Also, propranolol combined with pyrimethamine reduced the parasite load as well as significantly increased survival of mice in the pretreatment group. In the chronic phase, anti-Toxoplasma activity and decreased parasite load in tissues were observed with propranolol. In conclusion, the presented results demonstrate that propranolol, as an orally available drug, is effective at low doses against acute and latent murine toxoplasmosis, and the efficiency of the drug is increased when it is used in combination therapy with pyrimethamine.

Evaluation of the effects of nano-TiO2 on bioactivity and mechanical properties of nano bioglass-P3HB composite scaffold for bone tissue engineering.

To emulate bone structure, porous composite scaffold with suitable mechanical properties should be designed. In this research the effects of nano-titania (nTiO2) on the bioactivity and mechanical properties of nano-bioglass-poly-3-hydroxybutyrate (nBG/P3HB)-composite scaffold were evaluated. First, nBG powder was prepared by melting method of pure raw materials at a temperature of 1400 °C and then the porous ceramic scaffold of nBG/nTiO2 with 30 wt% of nBG containing different weight ratios of nTiO2 (3, 6, and 9 wt% of nTiO2 with grain size of 35-37 nm) was prepared by using polyurethane sponge replication method. Then the scaffolds were coated with P3HB in order to increase the scaffold's mechanical properties. Mechanical strength and modulus of scaffolds were improved by adding nTiO2 to nBG scaffold and adding P3HB to nBG/nTiO2 composite scaffold. The results of the compressive strength and porosity tests showed that the best scaffold is 30 wt% of nBG with 6 wt% of nTiO2 composite scaffold immersed for 30 s in P3HB with 79.5-80 % of porosity in 200-600 µm, with a compressive strength of 0.15 MPa and a compressive modulus of 30 MPa, which is a good candidate for bone tissue engineering. To evaluate the bioactivity of the scaffold, the simulated body fluid (SBF) solution was used. The best scaffold with 30 wt% of nBG, 6 wt% of P3HB and 6 wt% of nTiO2 was immersed in SBF for 4 weeks at an incubation temperature of 37 °C. The bioactivity of the scaffolds was characterized by AAS, SEM, EDXA and XRD. The results of bioactivity showed that bone-like apatite layer formed well at scaffold surface and adding nTiO2 to nBG/P3HB composite scaffold helped increase the bioactivity rate.

Evaluation of mechanical property and bioactivity of nano-bioglass 45S5 scaffold coated with poly-3-hydroxybutyrate.

One of the major challenges facing researchers of tissue engineering is scaffold design with desirable physical and mechanical properties for growth and proliferation of cells and tissue formation. In this research, firstly, nano-bioglass powder with grain sizes of 55-56 nm was prepared by melting method of industrial raw materials at 1,400 °C. Then the porous ceramic scaffold of bioglass with 30, 40 and 50 wt% was prepared by using the polyurethane sponge replication method. The scaffolds were coated with poly-3-hydroxybutyrate (P3HB) for 30 s and 1 min in order to increase the scaffold's mechanical properties. XRD, XRF, SEM, FE-SEM and FT-IR were used for phase and component studies, morphology, particle size and determination of functional groups, respectively. XRD and XRF results showed that the type of the produced bioglass was 45S5. The results of XRD and FT-IR showed that the best temperature to produce bioglass scaffold was 600 °C, in which Na2Ca2Si3O9 crystal is obtained. By coating the scaffolds with P3HB, a composite scaffold with optimal porosity of 80-87% in 200-600 µm and compression strength of 0.1-0.53 MPa was obtained. According to the results of compressive strength and porosity tests, the best kind of scaffold was produced with 30 wt% of bioglass immersed for 1 min in P3HB. To evaluate the bioactivity of the scaffold, the SBF solution was used. The selected scaffold (30 wt% bioglass/6 wt% P3HB) was maintained for up to 4 weeks in this solution at an incubation temperature of 37 °C. The XRD, SEM EDXA and AAS tests were indicative of hydroxyapatite formation on the surface of bioactive scaffold. This scaffold has some potential to use in bone tissue engineering.

Is GRA6 Gene a Suitable Marker for Molecular Typing of Toxoplasma Gondii? A Scoping Systematic Review.

Toxoplasmosis is a zoonotic disease with a worldwide prevalence that is caused by Toxoplasma gondii. This study aimed to summarize available data on genotyping T. gondii strains based on the GRA6 gene marker in different hosts around the world. We conducted a comprehensive literature search using five international databases (PubMed, Scopus, Science Direct, Web of Science, and Google Scholar) from inception until December 2021. We identified 32 papers eligible for inclusion in this systematic review. The majority of studies (50%) were carried out in Iran (n = 16) to identify T. gondii genotypes based on the GRA6 gene. Other countries with reported studies include China, Japan, Sweden, and Italy (n = 2 each). Out of 3,434 samples collected from various hosts, most studies (n = 11) focused on human samples (34.4%), followed by ovine (n = 7), pig (n = 4), goat (n = 3) and soil and cattle (n = 2).Using various molecular methods such as conventional PCR, nested-PCR, real-time PCR, microsatellite analysis, and Restriction Fragment Length Polymorphism (RFLP), we found DNA positive results in 805 out of 3,434 samples. Of these, 285 (35.40%), 207 (25.71%), 182 (22.60%), 65 (8.07%), and 18 (2.23%) were infected with types I, II, III, mix I, II, III, and mix II, III, respectively. Our data demonstrate that the GRA6 gene marker has sufficient polymorphism to detect three types of T. gondii genotypes in various hosts. Identifying the specific genotype could be valuable in developing new strategies for treatment, vaccination, diagnosis, control, and prevention of T. gondii infection.

Relationship between Toxoplasma gondii infection and psychiatric disorders in Iran: A systematic review with meta-analysis.

BACKGROUND: Toxoplasma gondii, a ubiquitous parasitic protozoan, may be an important cause of neurological and psychiatric diseases. The present systematic review and meta-analysis, therefore, was conducted to investigate the scientific evidence regarding the potential association between T. gondii infection and psychiatric disorders in Iran. METHODS: We systematically reviewed articles from world-wide databases, including PubMed, Scopus, Science Direct, Web of Science, Google Scholar, and Iranian national databases up to July 30th, 2021. The Newcastle Ottawa Scale (NOS) was used to assess the quality of included studies. The common odds ratio (OR) was estimated using inverse variance and a random-effects model. Heterogeneity was assessed using the χ2-based Cochrane test (Q) and the I2 index. Also, sensitivity analyses and publication bias were calculated. Moreover, subgroup analysis was performed based on the type of disorder and quality score of different eligible studies. RESULTS: 16 studies were included in this meta-analysis. Our meta-analyses found that the OR of the risk of anti- T. gondii IgG and IgM in psychiatric patients compared to the control group was 1.56 (95% CI; 1.23-1.99) and 1.76 (95% CI: 1.19-2.61), respectively. Subgroup analysis based on the type of disorder showed that the OR of the risk of anti- T. gondii IgG in Iranian schizophrenia patients and other psychiatric disorders compared to the control group were 1.50 (95% CI; 1.09-2.07) and 2.03 (95% CI: 1.14-3.60), respectively, which are statistically significant. Also, the OR of the risk of anti- T. gondii IgM in Iranian schizophrenia and depression patients compared to the control group was 1.54 (95% CI; 0.9-2.64) and 1.03 (95% CI: 0.2-5.24), respectively, which are not statistically significant. Additionally, subgroup analysis based on quality scores showed no significant influence on the results according to the moderate quality studies. However, this association was significant according to the high quality studies. The obtained results of Egger's test were 1.5 (95% CI; -0.62-3.73, P = 0.15) and 0.47 (95% CI; -0.82-1.76, P = 0.45), respectively, indicating publication bias. The significant results of the heterogeneity analysis confirmed a high level of heterogeneity in the IgG test (P = 0.000, I2 = 66.6%). However, no significant results from the test of heterogeneity were detected in the IgM test (P = 0.15, I2 = 27.5%). The results of the sensitivity analysis showed that the impact of each study on the meta-analysis was not significant on overall estimates. CONCLUSIONS: Despite the limited number of studies, these outcomes supported a possible link between T. gondii infection and psychiatric disorders in Iran. However, more high-quality investigations are needed in the future.

Status of human cystic echinococcosis based on hospital records in Mazandaran Province: A first registry-based evidence.

Background: Human cystic echinococcosis, as an emerging neglected parasitic disease, is caused by tapeworms of the genus Echinococcus spp. Because of the medical and economic importance, this study aims to review the epidemiology and clinical features of hydatidosis in patients admitted to medical and surgical wards in three referral teaching hospitals over 15 years in Mazandaran Province, northern Iran. Methods: Data were collected from hospital records that were accessible via the hospital information system (HIS) between 2005 and 2019 (15 years).The demographic information (age, sex, living area, and occupation), dog contact, number of the cysts, types of organs involved, and history of disease recurrence were assessed. Results: One hundred twenty-one patients with human cystic echinococcosis (CE) were involved in the study, from whom 58 patients (47.93%) were male and 63 (52.07%) were female. The majority of patients were rural residents (64.46%) and also housewife (28.10%). Based on the results, only about 16.53% of the patients had history of close contacts with dogs. The liver was the organ involved in the most cases of CE. There were statistically significant differences between residence, occupation, history of close contacts with dogs, type of organs involved, number of cysts and history of disease recurrence (P < 0.05). Conclusions: Our data provides valuable registry-based information about CE in an endemic region. The data highlights that most patients lived in rural areas and were housewives. Additionally, they had a low rate of disease recurrence but a high rate of close contact with dogs. Moreover, further monitoring on registry-based program and strengthening the HIS in the provincial hospitals in the studied area are required.

Credible Serological Evidence of Latent Toxoplasma Infection Among Women with Primary Infertility: A Ten-Year Registry-Based Study.

BACKGROUND: Some evidence reveled that chronic infection with Toxoplasma gondii (T. gondii) has recently been associated with infertility in human and experimental model. This baseline study aimed to investigate serological evidence of Toxoplasma infection among infertile women who admitted to the in vitro fertilization (IVF) clinic at Imam Khomeini Hospital, Mazandaran province, Sari, northern Iran. SUBJECTS AND METHODS: In this retrospective (descriptive-analytical) study, all infertile women referred to the IVF clinic during 2010-2019 (10 years), constitute the study population. All data including demographic and some related characteristics were collected into a questionnaire and registered at the Iranian National Registry Center for Toxoplasmosis (INRCT) at the Mazandaran University of Medical Sciences, northern Iran. The existence of anti-Toxoplasma antibodies (IgG and IgM) was explored using a commercially available enzyme-linked immune sorbent assay (ELISA) kit (PishtazTeb, Iran), based on the manufacturer's protocol. RESULTS: Of 520 infertile women, anti-T. gondii IgG, IgM and both IgG and IgM antibodies were detected among 342/520 (65.77%), 1/520 (0.19) and 4/520 (0.77) infertile women, respectively. Primary and secondary infertility was detected in 74.56% and 25.44% of IgG seropositive infertile women, respectively. Also, most of the IgG seropositive subjects had no history of abortion, polycystic ovary syndrome (PCO), fibroma, contraceptive use and varicocele in spouse as primary cause of infertility. Furthermore, serum levels of prolactin and antimullerian (AMH) hormones were normal in 81.29 and 80.12% of infertile women with anti- T. gondii IgG, respectively. There was also a statistically significant difference between the seroprevalence of Toxoplasma infection and these variables associated to primary infertility (P < 0.05). CONCLUSION: According to the high prevalence (about two thirds) of chronic T. gondii infection among infertile women, particularly those with a history of abortion and primary infertility, it can be concluded that latent Toxoplasma infection pose a risk to infertile woman in the study area. Therefore, we advise that screening and treatment of Toxoplasma infection among infertile women must be favorably considered.

Green synthesis of nano-liposomes containing Bunium persicum and Trachyspermum ammi essential oils against Trichomonasvaginalis.

BACKGROUND: Trichomonas vaginalis, a parasitic flagellated protozoan, is one of the main non-viral sexually transmitted diseases worldwide. Treatment options for trichomoniasis are limited to nitroimidazole compounds. However, resistance to these drugs has been reported, which requires the development of new anti-Trichomonas agents that confer suitable efficacy and less toxicity. METHODS: In the present work, we assessed the effectiveness of the liposomal system containing essential oils of Bunium persicum and Trachyspermum ammi against T. vaginalis in vitro. The chemical composition of B. persicum and T. ammi were analyzed using gas chromatography-mass spectrometry (GC-MS). Liposomal vesicles were prepared with phosphatidylcholine) 70%) and cholesterol)30%) using the thin-film method. The essential oils of B. persicum and T. ammi were loaded into the liposomes using the inactive loading method. Liposomal vesicles were made for two plants separately. Their physicochemical features were tested using Zeta-Sizer, AFM and SEM. The anti-Trichomonas activity was determined after 12 and 24 h of parasite cultures in TYI-S-33 medium. RESULTS: After 12 and 24 h of administration, the IC50 of the B. persicum essential oil nano-liposomes induced 14.41 µg/mL and 45.19 µg/mL, respectively. The IC50 of T. ammi essential oil nano-liposomes induced 8.08 µg/mL and 25.81 µg/mL, respectively. CONCLUSIONS: These data suggested that nano-liposomes of the essential oils of B. persicum and T. ammi may be a promising alternative to current treatments for Trichomonas infection.

Role of neglected parasitic diseases in the era of COVID-19 pandemics.

There are some doubts about the exact relationship between neglected infectious diseases (NIDs) and COVID-19 disease, which remains to be clearly defined. The present review summarized the effect of parasitic infections as the risk factors or protective agents in the COVID-19 pandemic. Parasites could proficiently modulate immune responses. Thus, parasitic infections could have a different impact on the incidence and clinical severity of COVID-19 in different regions of the world. Also, restoring programs to prevent, treat, and control NIDs, in particular helminths, could help in reducing the incidence and mortality of COVID-19 in endemic areas and help to increase vaccination effectiveness. Changes in the gut microbiome associated with helminth infection may have systemic immunomodulatory effects toward suppressing host immune responses, reducing vaccine efficacy and increasing the severity of other infectious diseases. The cytokine storm observed in severe cases of COVID-19 is characterized by a predominance of proinflammatory cytokines, such as IL-6. However, it is possible that helminth infection could change the outcome of infection by modifying the Th2 response to limit the inflammatory component; this would be particularly apparent in areas endemic for helminthic infections, which suggests a possible protective effect against COVID-19. Because parasitic infections affect more than 2 billion people throughout the world, their impact on COVID-19-associated effects on public health could be considerable. Further studies with larger sample sizes would be needed to explore the possible role of neglected parasitic infections in the COVID-19 pandemic.

The Potential Role of the Serotonin Transporter as a Drug Target against Parasitic Infections: A Scoping Review of the Literature.

BACKGROUND: Several in vitro and in vivo biological activities of serotonin, 5- hydroxytryptamine (5-HT), as a bioactive molecule, and its transporter (5-HT-Tr) were evaluated in parasitic infections. OBJECTIVE: Herein, the roles of 5-HT and 5-HTR in helminths and protozoan infections with medical and veterinary importance are reviewed. METHODS: We searched information in 4 main databases and reviewed published literature about the serotonin transporter's role as a promising therapeutic target against pathogenic parasitic infections between 2000 and 2021. RESULTS: Based on recent investigations, 5-HT and 5-HT-Tr play various roles in parasite infections, including biological function, metabolic activity, organism motility, parasite survival, and immune response modulation. Moreover, some of the 5-HT-TR in Schistosoma mansoni showed an excess of favorite substrates for biogenic amine 5-HT compared to their mammalian hosts. Furthermore, the main neuronal protein related to the G protein-coupled receptor (GPCR) was identified in S. mansoni and Echinococcus granulosus, playing main roles in these parasites. In addition, 5-HT increased in toxoplasmosis, giardiasis, and Chagas disease. On the other hand, in Plasmodium spp., different forms of targeted 5-HTR stimulate Ca2+ release, intracellular inositol triphosphate (ITP), cAMP, and protein kinase A (PKA) activity. CONCLUSION: This review summarized the several functional roles of the 5-HT and the importance of the 5-HT-TR as a drug target with minimal harm to the host to fight against helminths and protozoan infections. Hopefully, this review will shed light on research regarding serotonin transporter-based therapies as a potential drug target soon.

Evaluation of Bacterial Coinfection and Antibiotic Resistance in Patients with COVID-19 Under Mechanical Ventilation.

Patients with confirmed SARS-CoV-2 are principally at risk of emerging superinfections, particularly those caused by Gram-negative bacteria. Therefore, in this retrospective cohort study, we investigated the presence of bacteria in endotracheal aspirate samples in severe COVID-19 patients under mechanical ventilation between 20 February 2020 and 21 September 2020 in Mazandaran Heart Center Hospital, Iran. Outcomes were compared between ICU patients with confirmed SARS-CoV-2 (corona group) and those who suffer from other disease (non-corona group). Out of 38 subjects who met the diagnostic criteria for ventilator-associated pneumonia (VAP) in ICU, 22 and 16 patients in corona and non-corona groups, respectively, were enrolled in the study. Hospital length of stay in 27% of case in corona group was > 10 days. Also, SOFA score was > 10 in 64% and 25% of corona and non-corona groups, respectively (P < 0.05). Moreover, the number of death was significantly higher among corona patients (45%) than non-corona group (6%) in ICU (P < 0.05). Acinetobacter spp. were the most common bacteria in nine corona patients (41%) that were 100% resistant to amikacin, gentamycin, cefixime, and imipenem antibiotics. The prevalence of antibiotic resistance among pathogens isolated from patients with COVID-19 under mechanical ventilation in ICU highlighted the importance of preventing coinfections caused by this pathogen, suggesting an essential standardized approach to antibiotic stewardship in patients with COVID-19 for successful treatment.

Aurothiomalate-Based Drugs as Potentially Novel Agents Against Leishmania major: A Mini Review.

PURPOSE: Leishmaniasis is a major public health problem worldwide in many parts of the world. Current anti-leishmanial drugs have only limited clinical efficacy. Aurothiomalate derivatives are useful for treating rheumatoid arthritis, but have emerged as a promising therapeutic candidate for leishmaniasis. This paper gives a review of the literature about the usefulness of aurothiomalate derivatives against leishmaniasis. METHODS: In this study, we reviewed the proposed mechanisms of action of aurothiomalate and related compounds on the metabolism of L. major and collected data by searching relevant articles. RESULTS: Aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms: first, cytotoxic effects on parasites via thiomalate's false substrate role in the citric acid cycle against malate; and second, immunosuppressive and anti-inflammatory effects of aurothiomalate derivatives with prostaglandin production inhibitory effects. CONCLUSIONS: The current study documented that aurothiomalate-based drugs could be effective against leishmaniasis through two direct and indirect mechanisms of action. Gold thiomalate as a promising hit should be evaluated against L. major in vitro and in vivo conditions in the future.

More Than Seventy Years of Research (1948-November 2021) on Toxoplasma gondii in Iran: A Narrative Review.

In this review, we intend to provide a summary of the activities of researchers in the field of Toxoplasma gondii in Iran, during the past 70 years. Most studies have been limited to epidemiological studies (mostly using ELISA and IFA methods). Designing a standard and reliable method using the specific antigens of this parasite is essential. So far, studies in the field of drug effects have not been able to introduce an effective drug with few side effects. Various types of vaccines have been developed, such as recombinant and DNA vaccines. However, none of them had a good efficacy. The use of multi-epitope vaccines as potential vaccines against toxoplasmosis is recommended. At present, limited studies have been conducted on the patterns of transmission and genetic diversity of isolated isolates in Iran. Future research to determine the genotype of T. gondii could play an important role in the study of population structure, and biological characteristics of this parasite. It is hoped that the results of this study will help control, prevent, and reduce the burden of disease caused by this parasite.