In silico design of a novel peptide-based vaccine against the ubiquitous apicomplexan Toxoplasma gondii using surface antigens.

Human toxoplasmosis is a global public health concern and a commercial vaccine is still lacking. The present in silico study was done to design a novel vaccine candidate using tachyzoite-specific SAG1-realted sequence (SRS) proteins. Overlapping B-cell and strictly-chosen human MHC-I binding epitopes were predicted and connected together using appropriate spacers. Moreover, a TLR4 agonist, human high mobility group box protein 1 (HMGB1), and His-tag were added to the N- and C-terminus of the vaccine sequence. The final vaccine had 442 residues and a molecular weight of 47.71 kDa. Physico-chemical evaluation showed a soluble, highly antigenic and non-allergen protein, with coils and helices as secondary structures. The vaccine 3D model was predicted by ITASSER server, subsequently refined and was shown to possess significant interactions with human TLR4. As well, potent stimulation of cellular and humoral immunity was demonstrated upon chimeric vaccine injection. Finally, the outputs showed that this vaccine model possesses top antigenicity, which could provoke significant cell-mediated immune profile including IFN-γ, and can be utilized towards prophylactic purposes. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-023-00140-w.

Promising effects of parasite-derived compounds on tumor regression: a systematic review of in vitro and in vivo studies.

The parasites are repeatedly confronting their host to take advantage of nutrients for multiplication and survival. In this sense, a wide spectrum of molecules is released from both sides, with immune-regulatory activity, accompanying this biological battle. Such parasites and their valuable molecules can be directed toward microbial-based cancer therapy. Herein, we contrived a systematic review to gather information on the antitumor activity of parasite-derived compounds. Following systematic search in Web of Science, ScienceDirect, Scopus, PubMed, ProQuest and Embase until 31 December 2019, a total number of 51 articles (54 datasets) were finally included in this review. Thirteen parasitic agents were found to possess possible antitumor activity, comprising protozoan species Toxoplasma gondii, Trypanosoma cruzi, Trichomonas vaginalis, Acanthamoeba castellanii, Besnoitia jellisoni, Leishmania major, Plasmodium yoelii, and Plasmodium lophurae, as well as parasitic helminths Toxocara canis, Echinococcus granulosus, Taenia crassiceps, Trichinella spiralis, and Schistosoma mansoni. Most experiments were done based on antigenic preparations from T. gondii (16 studies), E. granulosus (10 studies), T. spiralis (8 studies), and T. cruzi (6 studies). Possible antitumor properties of the selected parasites were revealed in this review. However, precise molecular basis of anticancer activity for each parasite remains to be elucidated in the future.

Prevalence of urinary schistosomiasis in women: a systematic review and meta-analysis of recently published literature (2016-2020).

BACKGROUND: Urinary schistosomiasis is a serious threat in endemic territories of Africa and the Middle East. The status of female urinary schistosomiasis (FUS) in published literature between 2016 and 2020 was investigated. METHODS: A systematic search in PubMed, Scopus, Google Scholar, and Web of Science, based on the 'Preferred Reporting Items for Systematic Reviews and Meta-analyses' checklist, and a meta-analysis using random-effects model to calculate the weighted estimates and 95% confidence intervals (95% CIs) were done. RESULTS: Totally, 113 datasets reported data on 40,531 women from 21 African countries, showing a pooled prevalence of 17.5% (95% CI: 14.8-20.5%). Most studies (73) were performed in Nigeria, while highest prevalence was detected in Mozambique 58% (95% CI: 56.9-59.1%) (one study). By sample type and symptoms, vaginal lavage [25.0% (95% CI: 11.4-46.1%)] and hematuria 19.4% (95% CI: 12.2-29.4%) showed higher FUS frequency. Studies using direct microscopy diagnosed a 17.1% (95% CI: 14.5-20.1%) prevalence rate, higher than PCR-based studies 15.3% (95% CI: 6.1-33.2%). Except for sample type, all other variables had significant association with the overall prevalence of FUS. CONCLUSIONS: More studies are needed to evaluate the true epidemiology of FUS throughout endemic regions.

Prevalence of Cryptosporidium spp. in children and the elderly in southwestern Iran.

Aim: The current study investigated the prevalence of Cryptosporidium spp. among children under 6 and adults over 60 years of age with diarrhea in the southwest of Iran. Background: Cryptosporidiosis is an opportunistic parasitic infection caused by the species Cryptosporidium that causes gastrointestinal complications and diarrhea. Methods: This cross-sectional study was conducted in Khuzestan province between January 2020 to December 2020. Out of 350 patients referring to medical centers with clinical signs of diarrhea, 57.4% were under six years of age and 42.6% were more than 60 years old. Fecal samples were examined using Modified Ziehl-Neelsen (MZN) staining and nested-PCR techniques. Results: The overall prevalence of Cryptosporidium spp. infection in the study population was 0.9% as determined by microscopic and molecular methods (3/47). Conclusion: The study results confirm the prevalence of parasitic infections as reported in previous studies in other regions of Iran. Preventive health measures are necessary.

Development of a chimeric vaccine candidate based on Toxoplasma gondii major surface antigen 1 and apicoplast proteins using comprehensive immunoinformatics approaches.

This study was aimed at designing and evaluation of a multimeric vaccine construct against Toxoplasma gondii via utilization of SAG1 along with apicoplast ribosomal proteins (S2, S5 and L11). Top-ranked MHC-I and MHC-II binding as well as shared, immunodominant linear B-cell epitopes were predicted and joined together via appropriate linkers. Also, TLR-4 agonist (RS-09 synthetic protein) and His-tag were added to the N- and C-terminal of the vaccine sequence. The finally-engineered chimeric vaccine had a length of 291 amino acids with a molecular weight of 31.46 kDa. Physico-chemical features showed a soluble, highly-antigenic and non-allergenic candidate. Secondary and tertiary structures were predicted, and subsequent analyses confirmed the construct stability that was capable to properly interact with human TLR-4. Immunoinformatics-based simulation displayed potent stimulation of T- and B-cell mediated immune responses upon vaccination with the proposed multi-epitope candidate. In conclusion, obtained information demonstrated a highly antigenic vaccine candidate, which could develop high levels of IFN-γ and other components of cellular immune profile, and can be directed for toxoplasmosis prophylactic purposes.

Bioinformatics features and immunogenic epitopes of Echinococcus granulosus Myophilin as a promising target for vaccination against cystic echinococcosis.

Cystic echinococcosis (CE) is a neglected zoonosis especially in underdeveloped countries around the world. Hence, immunization strategies are beneficial to avert the infection. The present investigation was aimed to predict the primary biochemical characteristics of the EgMyophilin and its potential B-cell and human leukocyte antigen (HLA)-binding epitopes as a promising vaccine candidate. Different web servers were used to predict physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, tertiary model refinement and validations. B-cell and HLA-binding epitopes were predicted and screened in terms antigenicity, allergenicity, solubility (B-cell) or hydrophobicity (T-cell). The 89.82 KDa protein was non-allergenic, hydrophilic, stable, with improved thermotolerance and 94 post-translational modification sites. The secondary structure included 42.94% alpha helix, 42.82% random coil and 41.23% extended strand. Based on Ramachandran plot output for refined model, 96.2%, 99.5%, and 0.45% of amino acid residues were incorporated in the favored, allowed, and outlier regions of the refined model, respectively. After epitope screening, four B-cell and five HLA-binding epitopes possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against CE. More empirical studies are required using the EgMyophilin alone or in combination with other antigens/epitopes in the future.

Leishmaniasis and Trace Element Alterations: a Systematic Review.

Leishmaniasis is a worldwide prevalent parasitic infection caused by different species of the genus Leishmania. Clinically, the disease divided into three main forms, including visceral leishmaniasis (VL), cutaneous leishmaniasis (CL), and mucocutaneous leishmaniasis (MCL). There is no vaccine for human leishmaniasis and their treatment is challenging. Trace elements (TEs) alteration, including the selenium (Se), zinc (Zn), copper (Cu), ron (Fe), and magnesium (Mg) have been detected in patients with CL and VL as well as canine leishmaniasis. Because TEs play a pivotal role in the immune system, and host immune responses have crucial roles in defense against leishmaniasis, this systematic review aimed to summarize data regarding TEs alteration in human and animal leishmaniasis as well as the role of these elements as an adjuvant for treatment of leishmaniasis. In a setting of systematic review, we found 29 eligible articles (any date until October 1, 2020) regarding TEs in human CL (N = 12), human VL (N = 4), canine leishmaniasis (N = 3), and treatment of leishmaniasis based on TEs (N = 11), which one study examined the TEs level both in CL and VL patients. Our analysis demonstrated a significantly decreased level of Fe, Zn, and Se among human CL and canine leishmaniasis, and Zn and Fe in patients with VL. In contrast, an increased level of Cu in CL patients and Cu and Mg in VL patients and canine leishmaniasis was observed. Treatment of CL based zinc supplementation revealed enhancement of wound healing and diminished scar formation in human and experimentally infected animals. The results of this systematic review indicate that the TEs have important roles in leishmaniasis, which could be assessed as a prognosis factor in this disease. It is suggested that TEs could be prescribed as an adjuvant for the treatment of CL and VL patients.

Global seroprevalence of Neospora spp. in horses and donkeys: A systematic review and meta-analysis.

Neospora infections due to Neospora caninum and N. hughesi are prevalent among equids of the world. The disease may affect reproductive and neurological consequences. The present systematic review and meta-analysis was performed to evaluate the global Neospora seroprevalence among horses and donkeys. A number of 57 out of 1575 total retrieved studies were included by searching the PubMed, Scopus, Science Direct, Web of Science and ProQuest. A total of 25,783 horses and 4377 donkeys were examined serologically, yielding a weighted seroprevalence of 13.46 % (95 % CI: 10.26 %-17.42 %) globally. Subgroup analysis revealed that there were statistically significant differences in the overall prevalence of Neospora spp. in the examined animals according to year, continent, WHO region, country, host, and diagnostic method. Age and sex in horses as well as sex in donkeys were significantly associated with the Neospora seroprevalence (P < 0.001). Our findings showed a relatively high exposure to Neospora spp. in horses and donkeys worldwide. Considering the possible economic impact, as well as the importance in animal health, more studies are needed to clarify the species causing equine neosporosis, correlate serological findings with clinical outcomes and assess the risk factors, in order to define adequate prevention and control strategies.

Toxoplasma gondii ROP38 protein: Bioinformatics analysis for vaccine design improvement against toxoplasmosis.

Rhoptry proteins (ROPs) play a significant role in various stages of Toxoplasma gondii (T. gondii) life cycle, being critical for both invasion and intracellular survival. ROP38 is a key manipulator of host gene expression and has a function in tachyzoite to bradyzoite conversion. In this study, we've employed various bioinformatics online tools for immunogenicity prediction of ROP38 protein, comprising physico-chemical, antigenic and allergenic profiles, transmembrane domain, subcellular localization, post-translational modification (PTM) sites, secondary and 3D structure, B-cell, MHC-binding and cytotoxic T-lymphocyte (CTL) epitopes. The findings showed 54 PTM sites without a transmembrane domain. Also, ROP38 was proved a non-allergenic and antigenic protein. The protein had Sec signal peptide (Sec/SPI) with 0.8762 likelihood. The secondary structure included 52.68% random coil, 29.57% alpha helix and 17.74% extended strand. Based on Ramachandran plot output for refined model, 95.3%, 3.4%, and 1.4% of amino acid residues were incorporated in the favored, allowed, and outlier regions, respectively. B-cell epitopes TFPGDDIQTSS (67-72) and KAKNKWGRTRYTLQG (207-221) as well as T-cell epitope LSPVGFFTAL (6-15) possessed the highest antigenic index in the protein sequence. This paper is a premise for further researches, and provides insights for the development of a suitable vaccine against toxoplasmosis. More empirical studies are required using the ROP38 alone or in combination with other antigens/epitopes in the future.

Filarial worms: a systematic review and meta-analysis of diversity in animals from Iran with emphasis on human cases.

Current systematic review and meta-analysis demonstrate the prevalence reports of filariasis in animals in Iran along with human cases. Studies were screened, relevant papers were selected and the random-effect model was used by forest plot with 95% confidence interval (CI). Of 17 records of human case-reports, particularly from Khuzestan province (5 cases), Dirofilaria repens was the most detected parasite (10 cases) with higher involvement of the right eye (7 cases) than other organs. Eleven animal species were reported to be parasitised by filarioids in Iran. The prevalence of Dirofilaria immitis in canids was 14.69% (95% CI: 10.33-19.67), with highest rates (20.92%; 95% CI: 13.84-29.03) in free-ranging dogs. Male (10.07%; 95% CI: 5.10-16.47) and more than 1-year old (20.77%; 95% CI: 8.66-36.42) dogs were more likely to be found infected. The frequency of other filarioids of zoonotic interest was: Acanthocheilonema reconditum in dogs 2.15% (95% CI: 0.71-4.33), Dipetalonema evansi in camels 10.16% (95% CI: 4.73-17.34), Onchocerca cervicalis in horses 3.63% (95% CI: 1.44-6.75%) and Onchocerca fasciata 16.57% (95% CI: 10.12-24.24%) in camels. Still, our knowledge on parasitic filariae in Iran is limited and more investigation is needed in both human and animal populations.

Is there association between Trichomonas vaginalis infection and prostate cancer risk?: A systematic review and meta-analysis.

We performed a systematic review and meta-analysis to reveal the association between Trichomonas vaginalis (TV) infection and the risk of prostate cancer (PCa) development. Systematic searching (PubMed/Medline, Scopus, Embase, Web of Science, Cinhal, Wiley, Cochrane, Psychoinfo, ProQuest and Google Scholar) was done, up to March 2018 for case-control studies. Random effects model was applied to define odds ratios and their 95% confidence intervals. In total, 6 enteries were included in our meta-analysis, comprising 5590 individuals (2677 PCa cases and 2913 control individuals) examined for trichomoniasis, with a total positivity of 469 (17.51%) and 482 (16.54%) individuals, respectively. Totally, such association was documented in three countries, including USA (4 studies), Kuwait (one study) and Taiwan (one study). Based on pooled estimations, however a 1.17-time increase of PCa was observed among individuals with a previous exposure of TV, it was not statistically significant [OR = 1.17 (95% CI: 1.01 to 1.36)]. Egger's regression test demonstrated no publication bias among studies. Also, year of publication for included records was not significantly correlated to the relationship between trichomoniasis and PCa. Any further inferences should be based on future investigations for better understanding this relationship and shedding light on the cryptic pathogenesis of TV in PCa patients.

In-vitro and In-vivo Antileishmanial Activity of a Compound Derived of Platinum, Oxaliplatin, against Leishmania Major.

This study aimed to evaluate the antileishmanial efficacy of oxaliplatin against Leishmania major (L. major) both in-vitro and in-vivo. The IC50, CC50, and SI of oxaliplatin against promastigotes, murine macrophages, Raw 264.7 cells, and intramacrophage amastigotes of L. major were investigated in-vitro. The effects of this drug on intracellular amastigotes were also assayed, and the percentage of infectivity and IIR were calculated. Flow cytometry was performed to assay apoptosis, using 50 and 100 µg/mL of oxaliplatin in the promastigotes and macrophages. In-vivo, the BALB/c mice were classified into three groups, receiving oxaliplatin, glucantime, and phosphate-buffered saline for one month, respectively. The lesion size, IFN-γ, and IL-4 levels, and parasite burden were also evaluated in the animals. After 72 h, the IC50 and CC50 of oxaliplatin against promastigotes and macrophages were respectively 0.5 and 66.78 µg/mL. The apoptosis of promastigotes and macrophages using 50 µg/mL of oxaliplatin was 7.25% and 2.14%, respectively, while apoptosis induced at 100 µg/mL was 15.48% and 2.80%, respectively. Similar to the glucantime group, the mice treated with oxaliplatin showed a lower parasite burden and smaller lesions, compared with the PBS group (p < 0.01). Furthermore, higher IFN-γ levels were reported in mice receiving oxaliplatin in comparison with those receiving PBS (p < 0.01). The current findings indicated the efficacy of oxaliplatin against promastigote and amastigote forms of Leishmania and L. major-induced leishmaniasis.

The effect of different parameters under ultrasound irradiation for synthesis of new nanostructured Fe3O4@bio-MOF as an efficient anti-leishmanial in vitro and in vivo conditions.

In this work, a magnetic bio-metal-organic framework (MBMOF) nanocomposite with porous-layer open morphology is synthesized through a simple sonochemical approach and its effects on Leishmania major (MRHO/IR/75/ER) under both in vitro and in vivo conditions are investigated. The effects of sonication time, initial concentration of reagents and sonication power on size and morphology of MBMOF nanocomposites have been investigated and optimized. A comparison was then made between the structural information of the nanostructures and that of the bio-metal-organic framework crystals. Using the powder X-ray diffraction (PXRD), field emission scanning electron microscope (FE-SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy dispersive analysis of X-ray (EDAX), vibrating sample magnetometer (VSM), thermogravimetric analysis (TGA), and Brunauer-Emmet-Teller (BET) techniques, the prepared MBMOF nanocomposites were characterized. The mean numbers of promastigotes (cell/ml) in different MBMOF concentrations (3.12, 6.25, 12.5, 25, 50, 100, 200 and 400 µg mL-1) were determined by direct counting after 24, 48 and 72 h. Using MTT assays, the cytotoxic impacts of the MBMOF nanocomposites on promastigotes, intracellular amastigotes, and J774 macrophages were estimated. In order to investigate their therapeutic effects, the prepared MBMOF nanocomposites (25 and 12.5 µg mL-1) were used as ointment three times a week to treat Leishmania major in BALB/c mice. The lesion size and weight of mice were assessed before and during the treatment. The parasitic loads were measured in spleen and liver through the culture. After 72 h, the INF-γ and IL-4 cytokines levels in the supernatant of the spleen culture were measured. To the best of the authors' knowledge, this study is the first to attempt to synthesize the bio-MOFs through an in-situ sonosynthesis route under ultrasound irradiation and examine their cytotoxicity effects on Leishmania major under in vitro and in vivo conditions.

Identification of Leishmania Species Isolated from Human Cutaneous Leishmaniasis in Mehran, Western Iran Using Nested PCR.

BACKGROUND: The incidence of cutaneous leishmaniasis in the city of Mehran has risen sharply in recent years because the city borders Iraq, which has allowed entrance of different Leishmania strains. These strains have different shapes, periods of disease, and healing of lesions. The present study identified and determined cutaneous leishmaniasis species in this region. METHODS: This cross-sectional study was carried out by preparing slides from 92 patients with suspected cutaneous leishmaniasis lesions from Mehran during 2012-2013. Parasite genomic DNA was extracted and CSB2XF and CSB1XR primers were used to amplify the Leishmania minicircle kDNA regions. The parasite species were detected by specific 13Z and LIR primers by applying nested PCR technique. RESULTS: All banding patterns were diagnosed as L. major parasite by comparison of standard models with amplified fragments 560 bp in length from bands. The patients were 56.5% male and 43.5% female. The most frequently-infected age group was the 21-30 years group at a rate of 27.2%. About 56.3% of patients had a single lesion and a significant correlation was observed between age and number of lesions (P > 0.05). CONCLUSION: The nested PCR technique was shown to be an effective method with high sensitivity and specificity for identification of human Leishmania parasites. Molecular analysis revealed that parasites isolated from Mehran were identified as L. major and the disease was rural in form.