Isolation, characterization, and pathogenicity assay of Acanthamoeba and its endosymbionts in respiratory disorders and COVID-19 hospitalized patients, northern Iran.

Acanthamoeba spp., are common free-living amoebae found in nature that can serve as reservoirs for certain microorganisms. The SARS-CoV-2 virus is a newly emerged respiratory infection, and the investigation of parasitic infections remains an area of limited research. Given that Acanthamoeba can act as a host for various endosymbiotic microbial pathogens and its pathogenicity assay is not fully understood, this study aimed to identify Acanthamoeba and its bacterial and fungal endosymbionts in patients with chronic respiratory disorders and hospitalized COVID-19 patients in northern Iran. Additionally, a pathogenicity assay was conducted on Acanthamoeba isolates. Urine, nasopharyngeal swab, and respiratory specimens were collected from two groups, and each sample was cultured on 1.5% non-nutrient agar medium. The cultures were then incubated at room temperature and monitored daily for a period of two weeks. Eight Acanthamoeba isolates were identified, and PCR was performed to confirm the presence of amoebae and identify their endosymbionts. Four isolates were found to have bacterial endosymbionts, including Stenotrophomonas maltophilia and Achromobacter sp., while two isolates harbored fungal endosymbionts, including an uncultured fungus and Gloeotinia sp. In the pathogenicity assay, five isolates exhibited a higher degree of pathogenicity compared to the other three. This study provides significant insights into the comorbidity of acanthamoebiasis and COVID-19 on a global scale, and presents the first evidence of Gloeotinia sp. as a fungal endosymbiont. Nevertheless, further research is required to fully comprehend the symbiotic patterns and establish effective treatment protocols.

A fatal Candida albicans pericarditis presenting with cardiac tamponade after COVID-19 infection and cardiothoracic surgery.

BACKGROUND: Candida pericardial infection is a rare clinical entity usually related to recent cardiothoracic surgery and chronic debilitating conditions. During the COVID-19 pandemic, invasive fungal infections have been on the rise, likely due to a combination of factors such as immunosuppression, underlying conditions like diabetes, and surgical procedures. CASE PRESENTATION: Herein, we report a 67-year-old diabetic woman with a history of COVID-19 infection who received a high dose of corticosteroids a few months before admission, and previous myocardial infarction for more than 12 years. The patient had a positive cardiac tamponade with signs of dyspnea, chest pain, and low blood pressure. Echocardiographic data were more in favor of constrictive pericarditis. The patient underwent urgent echocardiography-guided pericardiocentesis and then broad-spectrum antibiotic treatment was prescribed. Repeated echocardiography implied a persistent pericardial effusion 10 days later. Subxiphoid aspirates and biopsied tissues showed budding yeast cells and yeast colonies grew on culture media identified as Candida albicans. CONCLUSION: This report should bring to the attention of physicians toward the possibility of Candida pericardial infection presenting with cardiac tamponade after COVID-19 infection and cardiothoracic surgery. Echocardiographic assessment, prompt pericardiotomy, molecular-based identification of causative agent, and early administration of appropriate antifungal treatment should improve the patient's survival.

Evaluation of the effect of sofosbuvir and daclatasvir in hospitalized COVID-19 patients: a randomized double-blind clinical trial (DISCOVER).

BACKGROUND: The combination of sofosbuvir and daclatasvir has shown preliminary efficacy for hospitalized patients with COVID-19 in four open-label studies with small sample sizes. This larger trial aimed to assess if the addition of sofosbuvir/daclatasvir to standard care improved clinical outcomes in hospitalized patients with COVID-19. METHODS: This was a placebo-controlled, double-blind, randomized clinical trial in adults hospitalized with COVID-19 at 19 hospitals in Iran. Patients were randomized to oral sofosbuvir/daclatasvir 400/60 mg once-daily or placebo in addition to standard of care. Patients were included if they had positive PCR or diagnostic chest CT, O2 saturation <95% and compatible symptoms. The primary outcome was hospital discharge within 10 days of randomization. Secondary outcomes included mortality and time to clinical events. The trial is registered on the Iran Registry of Clinical Trials under IRCT20200624047908N1. RESULTS: Between July and October 2020, 1083 patients were randomized to either the sofosbuvir/daclatasvir arm (n = 541) or the placebo arm (n = 542). No significant difference was observed in the primary outcome of hospital discharge within 10 days, which was achieved by 415/541 (77%) in the sofosbuvir/daclatasvir arm and 411/542 (76%) in the placebo arm [risk ratio (RR) 1.01, 95% CI 0.95-1.08, P = 0.734]. In-hospital mortality was 60/541 (11%) in the sofosbuvir/daclatasvir arm versus 55/542 (10%) in the placebo arm (RR 1.09, 95% CI 0.77-1.54, P = 0.615). No differences were observed in time to hospital discharge or time to in-hospital mortality. CONCLUSIONS: We observed no significant effect of sofosbuvir/daclatasvir versus placebo on hospital discharge or survival in hospitalized COVID-19 patients.

Comparative analysis of galactomannan lateral flow assay, galactomannan enzyme immunoassay and BAL culture for diagnosis of COVID-19-associated pulmonary aspergillosis.

BACKGROUND: Galactomannan Enzyme Immunoassay (GM-EIA) is proved to be a cornerstone in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA), its use is limited in middle and low-income countries, where the application of simple and rapid test, including Galactomannan Lateral Flow Assay (GM-LFA), is highly appreciated. Despite such merits, limited studies directly compared GM-LFA with GM-EIA. Herein we compared the diagnostic features of GM-LFA, GM-EIA and bronchoalveolar lavage (BAL) culture for CAPA diagnosis in Iran, a developing country. MATERIALS/METHODS: Diagnostic performances of GM-LFA and GM-EIA in BAL (GM indexes ≥1) and serum (GM indexes >0.5), i.e. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) and areas under the curve (AUC), were evaluated using BAL (n = 105) and serum (n = 101) samples from mechanically ventilated COVID-19 patients in intensive care units. Patients were classified based on the presence of host factors, radiological findings and mycological evidences according to 2020 ECMM/ISHAM consensus criteria for CAPA diagnosis. RESULTS: The Aspergillus GM-LFA for serum and BAL samples showed a sensitivity of 56.3% and 60.6%, specificity of 94.2% and 88.9%, PPV of 81.8% and 71.4%, NPV of 82.3% and 83.1%, when compared with BAL culture, respectively. GM-EIA showed sensitivities of 46.9% and 54.5%, specificities of 100% and 91.7%, PPVs of 100% and 75%, NPVs of 80.2% and 81.5% for serum and BAL samples, respectively. CONCLUSION: Our study found GM-LFA as a reliable simple and rapid diagnostic tool, which could circumvent the shortcomings of culture and GM-EIA and be pivotal in timely initiation of antifungal treatment.

Association of T. gondii infection with suicide: a systematic review and meta-analysis.

BACKGROUND: Findings on the association between Toxoplasma gondii (T. gondii) infection and suicide are contradictory. This paper aimed to resolve this uncertainty by conducting a meta-analysis. METHODS: We found the relevant studies using keywords include "Toxoplasmosis" and "Suicide" and the related synonyms in international databases such as ISI, Medline, and Scopus. The eligible studies were included in the meta-analysis phase. The random effect approach was applied to combine the results. RESULTS: Out Of 150 initial studies, 15 were included in the meta-analysis. Odds of suicide in people with T. gondii infection was 43% (OR: 1.43, 95%CI; 1.15 to 1.78) higher than those without this infection. The test for publication bias was not statistically significant, which indicates the absence of likely publication bias. CONCLUSION: This study confirms that T. gondii infection is a potential risk factor for suicide. To reduce cases of suicide attributable to T. gondii infection, it is recommended to implement some measures to prevent and control the transmission of the disease.

Febuxostat therapy in outpatients with suspected COVID-19: A clinical trial.

BACKGROUND: The aim of this clinical trial was to evaluate the effects of febuxostat (FBX) in comparison with hydroxychloroquine (HCQ) on clinical symptoms, laboratory tests and chest CT findings in outpatients with moderate symptoms of COVID-19 infection. METHODS: We conducted a clinical trial involving adult outpatients with the moderate respiratory illness following COVID-19 infection. Patients were randomly assigned to receive either FBX or HCQ for 5 days. The measured variables were needs to hospitalisation, clinical and laboratory data including fever, cough, breathing rate, C-Reactive Protein level, lymphocytes count at onset of admission and was well as at 5 days of treatments. In addition, CT findings were evaluated on admission and 14 days after initiation of treatment. RESULTS: Sixty subjects were enrolled in the study with a 1 to 1 ratio in FBX and HCQ groups. On admission, fever (66.7%), cough (87%), tachypnoea (44.4%), dyspnoea (35%), elevated CRP value (94.4%) and lung involvement according to chest CT (100%) were documented in enrolled patients with insignificant difference between FBX and HCQ groups. Fever, cough and tachypnoea were significantly mitigated in both groups after five days of treatments without any significant differences between groups. The mean percentages of lung involvement were significantly reduced to 7.3% and 8% after 14 days of treatment with FBX and HCQ, respectively. In adult outpatients with moderate COVID-19 infection, the effectiveness of FBX and HCQ was not different in terms of resolution of clinical manifestations, laboratory tests and lung CT findings. CONCLUSION: This trial suggests that FBX is as an alternative treatment to HCQ for COVID-19 infection and may be considered in patients with a contraindication or precaution to HCQ.

Evaluation of hepatic injury in chronic hepatitis B and C using APRI and FIB-4 indices compared to fibroscan results.

Background: Hepatitis B (HBV) and hepatitis C viruses (HCV) are significant causes of liver disease worldwide. Liver fibrosis (LF) is a complication of chronic liver damage caused by HBV and HCV due to our limited knowledge comparing the diagnostic performance of platelet to aspartate aminotransferase ratio index (APRI) and fibrosis-4 (FIB-4) index with fibroscan. Methods: This study evaluated liver damage in HBV and HCV using APRI, FIB-4, and fibroscan indices. This retrospective cohort descriptive-analytical study was conducted on patients with HBV and HCV. This study uses laboratory results and imaging to investigate liver damage in chronic HBV and HCV patients. APRI and FIB-4 were computed based on laboratory results. Results: A total of 185 patients (82 hepatitis B and 103 hepatitis C) were included in the study. Thirteen patients had liver cirrhosis. There was no statistically significant difference between the fibroscan results in the two groups (P=0.99). The HBV group's mean APRI and FIB-4 were lower than HCV, but no significant difference was observed (P>0.05). Our results in HBV and HCV patients showed that APRI and FIB-4 accomplished well anticipating cirrhosis with an area under the receiver operating characteristic curve (AUC) of 0.771-0.845 and 0.871-0.910, respectively. Conclusion: Fibroscan is a powerful tool superior to APRI and FIB-4 in predicting LF and cirrhosis. Nevertheless, APRI and FIB-4 are inexpensive and non-invasive indicators with acceptable efficacy in predicting advanced fibrosis or cirrhosis. However, these two measures are not reliable in low-grade fibrosis.

Irritable Bowel Syndrome Associated with Blastocystis hominis or Without Relationship to It? A Case-Control Study and Minireview.

BACKGROUND: Blastocystis hominis (B. hominis) is a protozoan parasite that has a worldwide distribution. Some studies have suggested a link between B. hominis and the development of irritable bowel syndrome (IBS). The objective of this study was to determine the prevalence of B. hominis in patients with IBS compared to healthy individuals. MATERIAL AND METHODS: A total of 65 stool samples from patients with IBS and 65 samples from healthy individuals in northern Iran were examined. The samples were tested using various methods including direct smear, formalin ether sedimentation and culture to detect the presence of B. hominis. Additionally, polymerase chain reaction (PCR) was performed on all culture-positive isolates to confirm the results and identify the genotype. RESULTS: B. hominis was detected in 15.38% of IBS patients and 9.2% of the healthy group. The culture in RPMI1640 was found to be better than the formalin ether and direct smear methods. Positive samples were confirmed using the molecular method. No significant difference was observed in the order of B. hominis infection between the two groups. CONCLUSIONS: The results of our study indicate that no significant difference was observed in the order of B. hominis infection between IBS patients and healthy groups. Therefore, further study is necessary to determine the potential pathogenic effects of this parasite and its role in causing IBS.

Vulvovaginitis due to Enterobius vermicularis in a girl and epidemic enterobiasis in her family.

Key Clinical Message: Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by Enterobius vermicularis. All members of her family were also infected by this helminth. Treatment with mebendazole was administered to all family members and it was found that the entire family had been cured. Abstract: Vulvovaginitis, an inflammation of the vulvovaginal mucous membranes, is a common reason for pediatric gynecology consultations. One of the causes of this condition is a parasitic worm known as Enterobius vermicularis (E. vermicularis). In girls, adult worms can infiltrate the vagina and release eggs, leading to the development of vulvovaginitis. Furthermore, these worms have the ability to invade the endometrial cavity too. Here we present a case of a 4-year-old girl who suffered from vulvovaginitis caused by E. vermicularis. All members of her family were also infected by this parasitic helminth. In the vaginal sample, apart from the eggs, the female adult worm was observed under the microscope. Treatment with mebendazole was administered to all family members, and their progress was followed for a period of 3 weeks, during which it was found that the entire family had been cured. This patient experienced significant improvement in symptoms related to severe anxiety, nervousness, vaginal inflammation, itching, and vulvovaginitis caused by E. vermicularis. To prevent infection by E. vermicularis, it is crucial to disinfect underwear and bed sheets. In kindergartens, the spread of this parasite should not be underestimated, and asymptomatic individuals who have been exposed to infected persons should receive treatment to prevent an epidemic. Maintaining cleanliness and hygiene, especially after using the toilet, is of the most importance, particularly for girls who are more susceptible to E. vermicularis infection. Additionally, it is essential for all family members to be aware of the transmission routes of this parasite.

New-onset chronic inflammatory demyelinating polyradiculoneuropathy after COVID-19 infection: a case report.

Introduction and importance: SARS-CoV-2 infection, besides respiratory symptoms, as cardinal manifestation, may present with neurological involvement. Immune-mediated polyradiculoneuropathy is one of the important neurological complications manifested by COVID-19 mainly includes Guillain-Barré syndrome (GBS), treatment-related fluctuation of GBS, and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Also, there are several reports of COVID-19 vaccine-related GBS and CIDP. According to possible severe manifestations of neuropathies like respiratory failure, considering these complications for early diagnosis and treatment is very important. Case presentation: The authors presented a 67-year-old woman with severe weakness in upper and lower extremities, the patient was diagnosed as case with CIDP initiated after COVID-19 virus infection and/or vaccination that experienced one relapse in 11 months. In both episodes, treatment with intravenous immunoglobulin started and the patient respond. Clinical discussion: To the best of our knowledge, this is one of the first reported cases with a typical chronic course of CIDP associated with COVID-19 virus infection and/or vaccination. Conclusion: Considering this complication and differentiation between GBS and CIDP, and then initiating maintenance therapy can prevent long-term disability.

Fatal Disseminated Strongyloidiasis in an Immunosuppressed Patient During COVID-19 Pandemic.

INTRODUCTION: This report presents a fatal case of disseminated strongyloidiasis in a patient with myasthenia gravis and diabetes mellitus who had received corticosteroid therapy. CASE REPORT: The patient was a 67-year-old woman living in a rural area endemic for Strongyloides stercoralis in northern Iran. Disseminated strongyloidiasis was diagnosed in the advanced stage of the disease, with enormous numbers of larvae demonstrated in direct smears prepared from stool samples and stomach biopsy. Despite treatment with ivermectin and antibiotics, the patient succumbed to the severity of the infection. CONCLUSION: Clinicians working in endemic areas should be mindful of the possibility of gastric involvement in strongyloidiasis, even if symptoms are nonspecific. We recommend that high-risk individuals be screened for S. stercoralis prior to immunosuppressive therapy in endemic regions to raise awareness and prevent similar cases.

Clinic-mycological spectrum of Candida infection in diabetic foot ulcers in a tertiary care hospital.

Background and Purpose: In diabetic foot ulcers, if fungal agents, such as Candida species penetrate the cutaneous or depth of the ulcer, it can increase the wound severity and make it more difficult to heal. Materials and Methods: A cross-sectional study was performed on 100 diabetic patients with a foot ulcer from December 2019 to November 2020 in northern Iran. Patient data and wound grades were recorded in a questionnaire. Candida infection was confirmed by direct microscopic examination and culture. To identify the causative agent, polymerase chain reaction-restriction fragment length polymorphism using MspI enzyme and the partial amplification of hyphal wall proteins (HWP1) gene were performed. Results: Mean age of the participants was 62.1 ± 10.8 years old, and 95% of them had type 2 diabetes. Moreover, more than 83% of them had diabetes for a duration of 10 years. In addition, 59% of the patients were male, and 66% > of them had poor education levels. Besides, 99% of them were married, and 52% were rural. Furthermore, 95% of the participants had neuropathic symptoms and 88% used antibiotics. The HbA1C level was > 9% in 69% of them, and the mean ulcer grade of the patients was 2.6±1.05. Candida infection was detected in 13% of the deep tissue and 7% of the tissue surrounding the wound. The predominant Candida isolate was C. parapsilosis (71.5%) and C. albicans (14.3%). Infections caused by filamentous fungi were not detected. There was a statistically significant relationship between Candida infection and gender, rural lifestyle, HbA1C, and ulcer grade. Conclusion: Mycological evaluations of diabetic foot ulcers are often ignored. The present study revealed that C. parapsilosis is the most common causative agent of deep-seated foot ulcer infection in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections, early diagnosis, and prompt treatment can help accelerate wound healing and prevent amputation.

New-onset myasthenia gravis after novel coronavirus 2019 infection.

In the years since the start of the COVID-19 pandemic, numerous neurological manifestations have been reported following this novel virus. Myasthenia gravis is one of them. Here, we present the patient that was referred to us with myasthenia gravis symptoms after a COVID-19 infection.

Rhino-orbito-cerebral mucormycosis in a post-COVID-19 diabetic patient: Rare case from Iran.

Rhino-orbito-cerebral mucormycosis (ROCM) is a progressive and life-threatening disease that is caused by a fungal infection. Every uncontrolled diabetic patient with a skin lesion on their head and neck, sinusitis symptoms, headache, and orbital edema should be evaluated for mucormycosis.

Multivesicular hepatic human hydatid cyst from Iran: First genotyping-based confirmation.

Cystic echinococcosis is one of the most important zoonotic parasitic diseases caused by the tapeworm Echinococcus granulosus. To date, the genotype of multivesicular CE has not been identified. In this regard, the genotyping of multivesicular types of CE could help clinicians understand and manage the disease effectively.

First Autochthonous case of Emerged Zoonotic Cutaneous Leishmaniasis in Mazandaran Province, Northern Iran: kDNA-PCR Evidence Base.

BACKGROUND: In the last decade, several cases of cutaneous leishmaniasis (CL) have been recorded by the provincial health center of Mazandaran Province, northern Iran. However, there is no documented report of autochthonous CL in the province yet. CASE PRESENTATION: The patient, a 59-year-old female, known case of diabetes mellitus, lived in therural area of Kiasar district (in theeastern part of the Mazandaran) with 5 skin lesions suspected of having vasculitis, without ahistory of traveling to the endemic areas of CL,was admitted to Imam Khomeini teaching hospital, Sari. To rule out CL, fine needle aspiration(FNA)procedure was used aseptically for the patient. Laboratory investigations showed Leishman bodies (amastigotes) by direct smear preparation, and species identification confirmed Leishmania major (L. major) by polymerase chain reaction (PCR)molecular method. Accordingly, this is the first documented report of autochthonous CL in Mazandaran Province. CONCLUSION: Overall, due to the abundance of probable rodent reservoir hosts and confirmation of infectionof sandflies (Phlebotomus papatasi) withL. major in the Kiasar district, where our patient was livingthere, it seems that CL emerged in the eastern part of the province. Therefore, further studies on rodents and sandflies fauna in terms of emerging leishmanial infection in the area is recommended.

Massive cutaneous complications due to snakebite: A case report and literature review.

Wound infections due to snake bites such as cellulitis and necrotizing fasciitis, although not common, are seen in snake bites and if left untreated can cause serious complications.

Evaluation of the effectiveness of N-acetylcysteine on accelerating the recovery of renal failure in patients with leptospirosis, a randomized clinical trial study.

BACKGROUND: Limited studies have been conducted on patients with renal function recovery regarding severe leptospirosis. The purpose of this study is to evaluate the effectiveness of N-acetylcysteine (NAC) in accelerating the reduction of serum creatinine in patients with leptospirosis. PATIENTS AND METHODS: This is a clinical trial study involving 64 patients with leptospirosis, with microscopic agglutination tests used to confirm the diagnosis of acute kidney injury. NAC was given to patients with a glomerular filtration rate of less than 60 ml/min at 1200 mg every 12 h, and it lasted for 48 h. Next, 32 patients were measured and the relationship between the length of hospitalization, age, and sex was also examined. Additionally, the two groups of case and control were compared in terms of the rate of decrease in serum creatinine level in three different time periods. The Shapro-Wilk test was used to investigate the distribution of data. RESULTS: No significant differences were observed in the decrease in serum creatinine level on the first, third, and seventh days of hospitalization and also in the use of NAC between the case and control groups (P = 0.255). In addition, the use of NAC had no significant effect on reducing the length of hospitalization (P = 0.067). CONCLUSION: Recovery of acute kidney injury following leptospirosis and drugs that accelerate the healing process in these patients require further studies with greater sample size and longer follow-up time.

Catastrophic Candida prosthetic valve endocarditis and COVID-19 comorbidity: A rare case.

BACKGROUND AND PURPOSE: Coronavirus disease 2019 (COVID-19) and Candida prostatic valve endocarditis present various clinical manifestations which may overlap; hence, discrimination between them is extremely difficult. CASE REPORT: The case was a 66-year-old man with a past medical history of mitral and aortic valves replacement one year before COVID-19 co-infection. He was admitted with fever (for 7 days), shortness of breath, cough, seizure, lethargy, headache, and 85% oxygen saturation. Transesophageal echocardiography revealed multiple large-sized, highly mobile masses on both sides of the mechanical mitral valve highly suggestive of vegetation. Chest computed tomography scanning showed simulating scattered COVID-19 peripheral ground-glass opacities confirmed by reverse-transcription polymerase chain reaction. The set of blood cultures yielded yeast colonies that were identified as Candida tropicalis. The patient died of septic shock shortly after receiving antifungal therapy. CONCLUSION: This case emphasized the importance of early diagnosis and implementation of antifungal treatment, particularly in patients with prosthetic cardiac valves, to reduce their unfavorable outcomes in COVID-19 patients.

Atorvastatin therapy in COVID-19 adult inpatients: A double-blind, randomized controlled trial.

INTRODUCTION: Efficacious therapies are urgently required to tackle the coronavirus disease 2019 (COVID-19). This trial aims to evaluate the effects of atorvastatin in comparison with standard care for adults hospitalized with COVID-19. METHODS: We conducted a randomized controlled clinical trial on adults hospitalized with COVID-19. Patients were randomized into a treatment group receiving atorvastatin + lopinavir/ritonavir or a control group receiving lopinavir/ritonavir alone. The primary outcome of the trial was the duration of hospitalization. The secondary outcomes were the need for interferon or immunoglobulin, receipt of invasive mechanical ventilation, and O2 saturation (O2sat), and level of C-reactive protein (CRP) which were assessed at the onset of admission and on the 6th day of treatment. RESULTS: Forty patients were allocated and enrolled in the study with a 1 to 1 ratio in atorvastatin + lopinavir/ritonavir and lopinavir/ritonavir groups. Clinical and demographic characteristics were similar between the two groups. CRP level was significantly decreased in the lopinavir/ritonavir + atorvastatin group (P < 0.0001, Cohen's d = 0.865) so that there was a significant difference in CRP level on the 6th day between the two groups (P = 0.01). Nevertheless, there was no significant difference in O2sat on day 6. Although the duration of hospitalization in the lopinavir/ritonavir + atorvastatin group was significantly reduced compared to the control group (P = 0.012), there was no significant difference in the invasive mechanical ventilation reception and the need for interferon and immunoglobulin. CONCLUSION: Atorvastatin + lopinavir/ritonavir may be more effective than lopinavir/ritonavir in treating COVID-19 adult hospitalized patients.