Synergistic activity of crocin and crocin loaded in niosomes alone and in combination with fluconazole against Candida albicans isolates: In vitro and in silico study.

INTRODUCTION: Since the drug resistance in Candida species is becoming a serious clinical challenge, novel alternative therapeutic options, particularly herbal medicine, have attracted increasing interest. This study aimed to pinpoint the potential antifungal activity of crocin (Cro), the efficacy of the niosomal formulation of Cro (NCro), and the synergistic activity of both formulations in combination with fluconazole (FLC) against susceptible and resistant C. albicans isolates. MATERIAL AND METHODS: NCro was formulated using the heating method. The in vitro antimycotic activity of Cro, NCro, and FLC was evaluated. Checkerboard and isobologram assays evaluated the interaction between both formulations of Cro and FLC. Necrotic and apoptotic effects of different agents were analyzed using the flow cytometry method. In silico study was performed to examine the interactions between Lanosterol 14 alpha-demethylase and Cro as a part of our screening compounds with antifungal properties. RESULTS: NCro exhibited high entrapment efficiency up to 99.73 ± 0.54, and the mean size at 5.224 ± 0.618 µm (mean ± SD, n = 3). Both formulations of Cro were shown to display good anticandidal activity against isolates. The synergistic effect of the NCro in combination with FLC is comparable to Cro (P-value =0.03). Apoptotic indicators confirmed that tested compounds caused cell death in isolates. The docking study indicated that Cro has interactivity with the protein residue of 14α-demethylase. CONCLUSION: The results showed a remarkable antifungal effect by NCro combined with FLC. Natural compounds, particularly nano-sized carrier systems, can act as an effective therapeutic option for further optimizing fungal infection treatment.

Global Dilemma and Needs Assessment Toward Achieving Sustainable Development Goals in Controlling Leishmaniasis.

Leishmaniasis is a disease of poverty that imposes a devastating medical, social, and economic burden on over 1 billion people nationwide. To date, no in-depth study to analyze the major global challenges and needs assessment has been carried out. This investigation aimed to explore a comprehensive narrative review of leishmaniasis's main challenges and initially highlight obstacles that might impede the implementation of control measures. Also, we propose a specific list of priorities for needs assessment. The presence of socioeconomic factors, multiple clinical and epidemiological forms, various Leishmania species, the complexity of the life cycle, the absence of effective drugs and vaccines, and the lack of efficient vector and reservoir control make this organism unique and sophisticated in playing a tangled role to react tricky with its surrounding environments, despite extensive efforts and implementation of all-inclusive former control measures. These facts indicate that the previous strategic plans, financial support, and basic infrastructures connected to leishmaniasis surveillance are still insufficient. Strengthening the leishmaniasis framework in a context of accelerated programmatic action and intensification of cross-cutting activities along with other neglected tropical diseases (NTDs) is confidently expected to result in greater effectiveness, cost-benefit, and fruitful management. Sensitive diagnostics, effective therapeutics, and efficacious vaccines are vital to accelerating advancement toward elimination, and reducing morbidity/mortality and program costs. Collective actions devoted by all sectors and policy-makers can hopefully overcome technical and operational barriers to guarantee that effective and coordinated implementation plans are sustained to meet the road map for NTDs 2021- 2030 goals.

Cutaneous Leishmaniasis Hampers COVID-19: A Controlled Cross-Sectional Study in High-Burden Endemic Areas of Iran.

INTRODUCTION: Emerging infectious diseases such as SARS-CoV-2 can cause pandemics and create a critical risk for humans. In a previous pilot study, we reported that the immunological responses induced by cutaneous leishmaniasis (CL) could decrease the incidence and severity of COVID-19. In this large-scale case-control study, we assessed the possible relationship between mortality and morbidity of COVID-19 in healed CL persons suffering scars compared to cases without CL history. METHODS: This controlled cross-sectional study was conducted between July 2020 and December 2022 in the endemic and high-burden areas of CL in southeastern Iran. In the study, 1400 previous CL cases with scars and 1,521,329 subjects who had no previous CL were analyzed. We used R 4.0.2 to analyze the data. Firth's bias reduction approach corresponding to the penalization of likelihood logistic regression by Jeffreys was also employed to influence the variables in the dataset. Also, a Bayesian ordinal logistic regression model was performed to explore the COVID-19 severity in both case and referent groups. RESULTS: The occurrence and severity rate of COVID-19 in CL scar cases are significantly less than in the non-CL control group, while in the CL scar subjects, patients with critical conditions and mortality were not observed. The morbidity (OR = 0.11, CI 0.06-0.20 and P < 0.001) and severity of COVID-19 in previous cases with CL scars were significantly diminished than that in the control group (credible interval - 2.57, - 1.62). CONCLUSIONS: The results represented a durable negative relationship between cured CL and COVID-19 incidence and severity. Additional studies seem necessary and should be designed to further validate the true impact and underlying mechanistic action of CL on COVID-19.

A prospective longitudinal study on the elimination trend of rural cutaneous leishmaniasis in southeastern Iran: Climate change, population displacement, and agricultural transition from 1991 to 2021.

Leishmaniasis is a complex disease. Any change in weather conditions affects the humans' social and agricultural expansion and, consequently, the parasite's life cycle in terms of ecology, biodiversity, social stigma, and exclusion. This population-based prospective longitudinal investigation was conducted between 1991 and 2021 in a well-defined CL (cutaneous leishmaniasis) focus in Bam County, southeastern Iran. A robust health clinic and health surveillance system were responsible for the ongoing systematic documentation, detection, identification, and management of CL cases. The exponential smoothing method via the state space model was used in the univariate time series. The TTR, smooth, and forecast packages were used in R software. Landsat satellite images from 1991, 2001, 2011, and 2021 were employed in the physical development. During this period, the temperature increased while the rainfall and humidity decreased. The findings showed a downward trend in the standardized drought index. Also, the results showed that climate warming and ecological changes profoundly affected the area's agricultural patterns and topographical features. Furthermore, the last three decades witnessed an elimination trend for zoonotic CL (ZCL) and the predominance of anthroponotic CL (ACL). The present findings showed that the critical factors in the predominance of ACL and elimination of ZCL were rising temperature, drought, migration, unplanned urbanization, earthquake, and agrarian reform. The wall-enclosed palm tree gardens excluded the primary ZCL reservoir host. They controlled the disease while providing suitable conditions for the emergence/re-emergence of ACL in the newly established settlements and the unplanned ecozone. Therefore, robust health infrastructures, sustained financial support, and evidence-based research studies are crucial to facilitating the necessary surveillance, monitoring, and evaluation to control and eliminate the disease.

Antileishmanial potentials of azacitidine and along with meglumine antimoniate on Leishmania major: In silico prediction and in vitro analysis.

This study aimed to investigate the in vitro and in silico antileishmanial activity of azacitidine (AZA) on Leishmania major promastigotes and amastigotes. The in silico method was used to evaluate the possibility of the interaction of AZA into the binding pocket of inducible nitric oxide synthase (iNOS), a leading defensive oxidative metabolite. Following that, in vitro anti-promastigote, and anti-amastigote activity of AZA was determined using an MTT assay and a macrophage model, respectively. Cytotoxic effects of AZA and meglumine antimoniate (MA) were also assessed by MTT assay on murine macrophages. All experiments were performed in triplicate. The results showed that AZA interacted with Ser133, Gln134, and Lys13 amino acids of iNOS, and the molecular docking score was obtained at -241.053 kcal/mol. AZA in combination with MA significantly (P<0.001) inhibited the growth rate of nonclinical promastigote (IC50 247.6±7.3 µM) and 8.5-fold higher of clinical intramacrophage amastigote stage (29.8±5.3 µM), compared to the untreated group. A significant upsurge of Th1 subsets and transcription genes and a meaningful decline in Th2 cytokines subclasses at the equivalent concentrations of AZA and MA was observed (P<0.001). The apoptosis effect of AZA along with MA was significantly induced on L. major in a dose-dependent manner (P<0.001). The present study demonstrated that AZA possesses antileishmanial activity in in vitro and in silico models. However, AZA combined with MA was more effective than AZA alone in inhibiting the growth rate of promastigotes and amastigotes of L. major. This study indicates that AZA in combination with MA demonstrated a potent antileishmanial mechanism, promoting immune response and enhancing an immunomodulatory role toward the Th1 pathway. This experimental study is a basic study for applying more knowledge about the mechanisms of AZA along with MA in animal models in the future.

Monitoring of airborne fungi during the second wave of COVID-19 in selected wards of the referral university hospital in southeastern Iran.

Microbiological monitoring of the air hospital is essential for prevention and control, due to the possible airborne route of infection transmission, especially in high-risk wards. This study aimed to monitor the airborne fungi during the second wave of the COVID-19 pandemic in selected wards of the biggest university educational hospital in Kerman, southeastern Iran. This study was conducted in 11 different wards, separated into the patient room and nursing station, of the Afzalipour hospital from May to August 2021. Fungal isolates were characterized to the species level by conventional and sequencing methods. Out of 93 obtained fungal colonies, 70 (75.3%) isolates were filamentous and 23 (24.7%) isolates were yeast. Aspergillus species were the predominant fungal isolates among the filamentous colonies (n=19; 27.1%), and Naganishia albida (formerly Cryptococcus albidus) was identified as the most common yeast isolate (n=13/23; 56.8%). The infectious ward was the most contaminated unit (n=19/93), while the least contaminated units were the neonatal intensive care unit (n=3/93), and oncology (n=3/93). The statistical findings displayed that the number of fungal isolates in patients' rooms is significantly higher than in nurses' stations (p-value=0.013). Our study demonstrated the presence of diverse fungal species in all wards of the hospital. Considering the presence of airborne fungi in hospitals and related public health problems is one of the critical issues for health systems management. In this regard, efficient monitoring of airborne fungi might play an influential role in hospital infection control and surveillance, particularly in high-risk hospitalization patients in critical wards.

Poor adherence is a major barrier to the proper treatment of cutaneous leishmaniasis: A case-control field assessment in Iran.

Leishmaniasis is an overlooked, poverty-stricken, and complex disease with growing social and public health problems. In general, leishmaniasis is a curable disease; however, there is an expansion of unresponsive cases to treatment in cutaneous leishmaniasis (CL). One of the effective and ignored determinants in the treatment outcome of CL is poor treatment adherence (PTA). PTA is an overlooked and widespread phenomenon to proper Leishmania treatment. This study aimed to explore the effect of poor adherence in unresponsiveness to treatment in patients with anthroponotic CL (ACL) by comparing conventional statistical modalities and machine learning analyses in Iran. Overall, 190 cases consisting of 50 unresponsive patients (case group), and 140 responsive patients (control group) with ACL were randomly selected. The data collecting form that included 25 queries (Q) was recorded for each case and analyzed by R software and genetic algorithm (GA) approaches. Complex treatment regimens (Q11), cultural and lay views about the disease and therapy (Q8), life stress, hopelessness and negative feelings (Q22), adverse effects of treatment (Q13), and long duration of the lesion (Q12) were the most prevalent significant variables that inhibited effective treatment adherence by the two methods, in decreasing order of significance. In the inherent algorithm approach, similar to the statistical approach, the most significant feature was complex treatment regimens (Q11). Providing essential knowledge about ACL and treatment of patients with chronic diseases and patients with misconceptions about chemical drugs are important issues directly related to the disease's unresponsiveness. Furthermore, early detection of patients to prevent the long duration of the disease and the process of treatment, efforts to minimize side effects of treatment, induction of positive thinking, and giving hope to patients with stress and anxiety by medical staff, and family can help patients adhere to the treatment.

Vulvovaginal candidiasis in Iranian women: Molecular identification and antifungal susceptibility pattern.

AIM: Vulvovaginal candidiasis (VVC), is a common fungal infection that remains a global concern. The objectives of this study were molecular identification and assessment of the antifungal susceptibility profile of Candida species, causing VVC in southeast Iran. METHODS: A cross-sectional investigation was carried out on 119 nonpregnant females suspected of VVC between February 2019 and May 2021. Yeast samples were characterized to the species level by conventional and molecular methods. All Candida isolates were examined for in vitro susceptibility profile to six conventional antifungal drugs using Clinical and Laboratory Standards Institute guidelines. RESULTS: Out of 119 subjects, 52 (43.7%) cases were affected by VVC, out of whom 11 (21.15%) cases had recurrent vulvovaginal candidiasis (RVVC). The species distribution was as follows; Candida albicans (n = 21; 40.4%), C. glabrata (n = 11; 21.2%), C. tropicalis (n = 9; 17.3%), C. parapsilosis (n = 5; 9.7%), C. africana (n = 3; 5.7%), C. famata (n = 1; 1.9%), C. lusitaniae (n = 1; 1.9%), and C. dubliniensis (n = 1; 1.9%). The resistance rate of Candida isolates to fluconazole, itraconazole, and voriconazole were 15.38%, 11.5%, and 3.8%, respectively. Resistance to fluconazole was obtained in 46% (5/11) of RVVC cases but only in 7% (3/41) of VVC cases. CONCLUSION: This study demonstrated that the majority of VVC cases were caused by non-albicans Candida species which also were resistant to some antifungal agents. Hence, our findings revealed the importance of conducting periodical epidemiological studies to determine changes in species distribution. Moreover, for effective management of treatment and infection, it is imperative to evaluate the susceptibility profiles of Candida species isolated from VVC patients.

MGL_3741 gene contributes to pathogenicity of Malassezia globosa in pityriasis versicolor.

Dihydroxyacid dehydratase (DHAD) is a key enzyme in biosynthetic pathway of isoleucine and valine. This pathway is absent in human but exists in various organisms such as fungi. Using RNA-seq analysis in this study, we identified MGL_3741gene which encodes DHAD protein in Malassezia globosa (M. globosa). Furthermore, we found that mentioned gene is homologous to the Ustilago maydis, Saccharomyces cerevisiae, Aspergillus flavus, and Aspergillus fumigatus ILV3P. For understanding the probable role of this gene in pathogenicity of M. globosa, we applied Real-time PCR to investigate the differentially expressed of the MGL_3741 gene in healthy and pathogenic states. Our results indicate a significant difference between two mentioned stats. These results revealed that ILV3-like gene in M. globosa can be related to the pathogenicity of this yeast.

Microsatellite genotyping of clinical Candida parapsilosis isolates.

BACKGROUND AND PURPOSE: Candida parapsilosis is a predominant species found in nosocomial infection, particularly in hospitalized patients. The molecular epidemiology of the clinical strains of this species has not been well studied. The present study was performed with the aim of investigating the microsatellite genotyping of Candida parapsilosis among the Iranian clinical isolates. MATERIALS AND METHODS: This study was conducted on 81 independent clinical C. parapsilosis isolates that were genotyped by using a panel of six microsatellite markers. RESULTS: The short tandem repeat (STR) typing of clinical C. parapsilosis isolates demonstrated 68 separate genotypes, among which 57 genotypes were observed once and the remaining 11 cases were identified for multiple times. The Simpson's diversity index for the panel of combined six markers yielded a diversity index of 0.9951. The heterogeneity was observed among the Iranian and the Netherlands clinical C. parapsilosis isolates. CONCLUSION: As the findings indicated, the clinical C. parapsilosis isolates from Iran showed a high genetic diversity. It can be concluded that molecular epidemiology could be useful for screening during outbreak investigation where C. parapsilosis is involved.