Factors influencing mortality in COVID-19-associated mucormycosis: The international ID-IRI study.

The emergence of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), triggered a global pandemic. Concurrently, reports of mucormycosis cases surged, particularly during the second wave in India. This study aims to investigate mortality factors in COVID-19-associated mucormycosis (CAM) cases, exploring clinical, demographic, and therapeutic variables across mostly Asian and partly African countries. A retrospective, cross-sectional analysis of CAM patients from 22 medical centers across eight countries was conducted, focusing on the first 3 months post-COVID-19 diagnosis. Data collected through the ID-IRI included demographics, comorbidities, treatments, and outcomes. A total of 162 CAM patients were included. The mean age was 54.29 ± 13.04 years, with 54% male. Diabetes mellitus (85%) was prevalent, and 91% had rhino-orbital-cerebral mucormycosis. Surgical debridement was performed in 84% of the cases. Mortality was 39%, with advanced age (hazard ratio [HR] = 1.06, [P < .001]), rituximab use (HR = 21.2, P = .05), and diabetic ketoacidosis (HR = 3.58, P = .009) identified as risk factors. The mortality risk increases by approximately 5.6% for each additional year of age. Surgical debridement based on organ involvement correlated with higher survival (HR = 8.81, P < .001). The utilization of rituximab and diabetic ketoacidosis, along with advancing age, has been associated with an increased risk of mortality in CAM patients. A combination of antifungal treatment and surgical intervention has demonstrated a substantial improvement in survival outcomes.

Over a third of patients who developed mucormycosis after COVID-19 died. Older people, those on specific immunosuppressive treatments, and those with diabetic ketoacidosis had a higher risk of death. However, undergoing surgery as part of treatment significantly improved survival.

Self-reported antibiotic stewardship and infection control measures from 57 intensive care units: An international ID-IRI survey.

We explored the self-reported antibiotic stewardship (AS), and infection prevention and control (IPC) activities in intensive care units (ICUs) of different income settings. A cross-sectional study was conducted using an online questionnaire to collect data about IPC and AS measures in participating ICUs. The study participants were Infectious Diseases-International Research Initiative (IDI-IR) members, committed as per their institutional agreement form. We analyzed responses from 57 ICUs in 24 countries (Lower-middle income (LMI), n = 13; Upper-middle income (UMI), n = 33; High-income (HI), n = 11). This represented (~5%) of centers represented in the ID-IRI. Surveillance programs were implemented in (76.9%-90.9%) of ICUs with fewer contact precaution measures in LMI ones (p = 0.02); (LMI:69.2%, UMI:97%, HI:100%). Participation in regional antimicrobial resistance programs was more significantly applied in HI (p = 0.02) (LMI:38.4%,UMI:81.8%,HI:72.2%). AS programs are implemented in 77.2% of institutions with AS champions in 66.7%. Infectious diseases physicians and microbiologists are members of many AS teams (59%&50%) respectively. Unqualified healthcare professionals(42.1%), and deficient incentives(28.1%) are the main barriers to implementing AS. We underscore the existing differences in IPC and AS programs' implementation, team composition, and faced barriers. Continuous collaboration and sharing best practices on APM is needed. The role of regional and international organizations should be encouraged. Global support for capacity building of healthcare practitioners is warranted.

Evaluation of a human gut-associated phage and gut dominant microbial phyla in the metabolic syndrome.

BACKGROUND & AIMS: Metabolic syndrome (MetS) is an expanding public health problem worldwide and is reasoned one of the risk factors of cardiovascular disease. Recent evidence suggests that dysbiosis of the gut microbiota may play an essential role in metabolic disorders. The objective of this study was to assess the differences in the two gut dominant phyla and a gut-associated phage between MetS and healthy control subjects. METHODS: The study included 60 subjects among whom 30 were MetS, and 30 were healthy control subjects. The entire studied group was subjected to clinical, laboratory assessment, and anthropometric evaluation. Stool samples were collected from both MetS and healthy control subjects. The Firmicutes, Bacteroidetes, and crAssphage were assessed by quantitative PCR (qPCR). RESULTS: The MetS group had significantly higher body mass index, fasting plasma glucose, triglyceride, and waist circumference were compared with healthy controls (Pv < 0.05). The relative abundance of the Firmicutes phyla and crAssphage were high in the MetS group and only crAssphage were statistically significantly high in the MetS group compared to the healthy controls (Pv < 0.05). The quantity of Bacteroidetes phyla was low in the MetS group compared to the healthy controls, though there were no significant differences between the two groups (Pv > 0.05). CONCLUSION: The results of this study indicate that adults with MetS have a different gut microbial composition in comparison to healthy controls. This could be probably considered when creating approaches to control MetS by modifying the gut microbiota.

Case fatality and mortality rates, socio-demographic profile, and clinical features of COVID-19 in the elderly population: A population-based registry study in Iran.

We aimed to investigate COVID-19 case fatality rate (CFR), mortality, and screening in the older population of East Azerbaijan Province. We conducted a population-based registry study from Death Registration System in the elderly population (N = 433 445) from the outbreak that emerged up to May 30, 2021 (before vaccination). We analyzed CFR and mortality rates due to COVID-19 as well as the case findings and characteristics in the elderly population. Logistic regression analysis was carried out for the association between COVID-19 mortality and effective factors. During the study, the province had 18 079 confirmed cases and 4390 deaths. The male to female CFR risk ratio was 3.2. The overall CFR and mortality rates were 24% and 1%, respectively. CFR and mortality ranged from 9.56% to 0.37% in the 60-64 age group to 70% and 2.6% in the age group ≥85 years, respectively. We found a significant trend in CFR and mortality of COVID-19 with advanced age. Male sex, advanced age, marital status, and living alone were associated with an increased risk of COVID-19 fatality. COVID-19 mortality measures were higher in the older population of this province. Advanced treatment supports and interventions are needed to reduce mortality rates of COVID-19 in the elderly population.

Health workers readiness and practice in malaria case detection and appropriate treatment: a meta-analysis and meta-regression.

BACKGROUND: Health workers (HWs) appropriate malaria case management includes early detection and prompt treatment with appropriate anti-malarial drugs. Subsequently, HWs readiness and practice are considered authentic evidence to measure the health system performance regarding malaria control programme milestones and to issue malaria elimination certification. There is no comprehensive evidence based on meta-analysis, to measure the performance of HWs in case management of malaria. This study aimed to evaluate HWs performance in early malaria case detection (testing) and the appropriate treatment. METHODS: The published literature in English was systematically searched from Medline, Scopus, Embase, and Malaria Journal up to 30th December 2020. The inclusion criteria were any studies that assessed HWs practice in early case detection by malaria testing and appropriate treatment. Eligibility assessment of records was performed independently in a blinded, standardized way by two reviewers. Pooled prevalence estimates were stratified by HWs cadre type. Meta-regression analysis was performed to explore the impact of the appropriateness of the method and risk of bias as potential sources of the heterogeneity in the presence of effective factors. RESULTS: The study pooled data of 9245 HWs obtained from 15 included studies. No study has been found in eliminating settings. The pooled estimate for appropriate malaria treatment and malaria testing were 60%; 95% CI: 53-67% and 57%; 95% CI: 49-65%, respectively. In the final multivariable meta-regression, HWs cadre and numbers, appropriateness of study methods, malaria morbidity and mortality, total admissions of malaria suspected cases, gross domestic product, availability of anti-malarial drugs, and year of the publication were explained 85 and 83% of the total variance between studies and potential sources of the heterogeneity for malaria testing and treating, respectively. CONCLUSION: HWs adherence to appropriate malaria case management guidelines were generally low while no study has been found in eliminating countries. Studies with the inappropriateness methods and risk of bias could be overestimating the actual proportion of malaria appropriate testing and treating. Strategies that focus on improving readiness and early identification of acute febrile diseases especially in the countries that progress to malaria elimination should be highly promoted.

Profiles of multidrug-resistant organisms among patients with bacteremia in intensive care units: an international ID-IRI survey.

Evaluating trends in antibiotic resistance is a requisite. The study aimed to analyze the profile of multidrug-resistant organisms (MDROs) among hospitalized patients with bacteremia in intensive care units (ICUs) in a large geographical area. This is a 1-month cross-sectional survey for blood-borne pathogens in 57 ICUs from 24 countries with different income levels: lower-middle-income (LMI), upper-middle-income (UMI), and high-income (HI) countries. Multidrug-resistant (MDR), extensively drug-resistant (XDR), or pan-drug-resistant isolates were searched. Logistic regression analysis determined resistance predictors among MDROs. Community-acquired infections were comparable to hospital-acquired infections particularly in LMI (94/202; 46.5% vs 108/202; 53.5%). Although MDR (65.1%; 502/771) and XDR (4.9%; 38/771) were common, no pan-drug-resistant isolate was recovered. In total, 32.1% of MDR were Klebsiella pneumoniae, and 55.3% of XDR were Acinetobacter baumannii. The highest MDR and XDR rates were in UMI and LMI, respectively, with no XDR revealed from HI. Predictors of MDR acquisition were male gender (OR, 12.11; 95% CI, 3.025-15.585) and the hospital-acquired origin of bacteremia (OR, 2.643; 95%CI, 1.462-3.894), and XDR acquisition was due to bacteremia in UMI (OR, 3.344; 95%CI, 1.189-5.626) and admission to medical-surgical ICUs (OR, 1.481; 95% CI, 1.076-2.037). We confirm the urgent need to expand stewardship activities to community settings especially in LMI, with more paid attention to the drugs with a higher potential for resistance. Empowering microbiology laboratories and reports to direct prescribing decisions should be prioritized. Supporting stewardship in ICUs, the mixed medical-surgical ones in particular, is warranted.

Vaccination with rEGVac elicits immunoprotection against different stages of Echinococcus granulosus life cycle: A pilot study.

Vaccination against dog-sheep transmission cycle is necessary to control cystic echinococcosis (CE) infection. A multi-epitope multi-antigenic recombinant vaccine was developed-comprising the three putative vaccine antigens EG95, Eg14-3-3 and EgEnolase-was cloned and expressed. In a pilot experiment, the multi-antigen vaccine was assessed in 15 dogs and 15 sheep (five experimental groups and three animals in each group) by two subcutaneous doses 28 days apart. To evaluate the efficacy of the vaccine candidate first immunological analysis were done comprising IgG and IgE antibodies and the cytokine IL-4 in sera of the immunized dogs and sheep. Serum IgG, IgE, and IL-4, in particular in the dogs, were increased after the two rounds of vaccine candidate injection, while the total number of hydatid cysts was reduced (~85.43%). This pilot trial indicated significant immune protection efficacy against E. granulosus especially in dogs, while its efficacy in sheep was not as high as dogs. The multi-antigenic candidate vaccine is proposed as a protective vaccine modality in both dogs and sheep.

Managing adult patients with infectious diseases in emergency departments: international ID-IRI study.

We aimed to explore factors for optimizing antimicrobial treatment in emergency departments. A single-day point prevalence survey was conducted on January 18, 2020, in 53 referral/tertiary hospitals in 22 countries. 1957 (17%) of 11557 patients presenting to EDs had infections. The mean qSOFA score was 0.37 ± 0.74. Sepsis (qSOFA ≥ 2) was recorded in 218 (11.1%) patients. The mean qSOFA score was significantly higher in low-middle (1.48 ± 0.963) compared to upper-middle (0.17 ± 0.482) and high-income (0.36 ± 0.714) countries (P < 0.001). Eight (3.7%) patients with sepsis were treated as outpatients. The most common diagnoses were upper-respiratory (n = 877, 43.3%), lower-respiratory (n = 316, 16.1%), and lower-urinary (n = 201, 10.3%) infections. 1085 (55.4%) patients received antibiotics. The most-commonly used antibiotics were beta-lactam (BL) and BL inhibitors (n = 307, 15.7%), third-generation cephalosporins (n = 251, 12.8%), and quinolones (n = 204, 10.5%). Irrational antibiotic use and inappropriate hospitalization decisions seemed possible. Patients were more septic in countries with limited resources. Hence, a better organizational scheme is required.

A domain-based vaccine construct against SARS-CoV-2, the causative agent of COVID-19 pandemic: development of self-amplifying mRNA and peptide vaccines.

Introduction: Coronavirus disease 2019 (COVID-19) is undoubtedly the most challenging pandemic in the current century with more than 293,241 deaths worldwide since its emergence in late 2019 (updated May 13, 2020). COVID-19 is caused by a novel emerged coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Today, the world needs crucially to develop a prophylactic vaccine scheme for such emerged and emerging infectious pathogens. Methods: In this study, we have targeted spike (S) glycoprotein, as an important surface antigen to identify its B- and T-cell immunodominant regions. We have conducted a multi-method B-cell epitope (BCE) prediction approach using different predictor algorithms to discover the most potential BCEs. Besides, we sought among a pool of MHC class I and II-associated peptide binders provided by the IEDB server through the strict cut-off values. To design a broad-coverage vaccine, we carried out a population coverage analysis for a set of candidate T-cell epitopes and based on the HLA allele frequency in the top most-affected countries by COVID-19 (update 02 April 2020). Results: The final determined B- and T-cell epitopes were mapped on the S glycoprotein sequence, and three potential hub regions covering the largest number of overlapping epitopes were identified for the vaccine designing (I531-N711; T717-C877; and V883-E973). Here, we have designed two domain-based constructs to be produced and delivered through the recombinant protein- and gene-based approaches, including (i) an adjuvanted domain-based protein vaccine construct (DPVC), and (ii) a self-amplifying mRNA vaccine (SAMV) construct. The safety, stability, and immunogenicity of the DPVC were validated using the integrated sequential (i.e. allergenicity, autoimmunity, and physicochemical features) and structural (i.e. molecular docking between the vaccine and human Toll-like receptors (TLRs) 4 and 5) analysis. The stability of the docked complexes was evaluated using the molecular dynamics (MD) simulations. Conclusion: These rigorous in silico validations supported the potential of the DPVC and SAMV to promote both innate and specific immune responses in preclinical studies.

A novel in silico minigene vaccine based on CD4+ T-helper and B-cell epitopes of EG95 isolates for vaccination against cystic echinococcosis.

EG95 oncospheral antigen plays a crucial role in Echinococcus granulosus pathogenicity. Considering the diversity of antigen among different EG95 isolates, it seems to be an ideal antigen for designing a universal multivalent minigene vaccine, so-called multi-epitope vaccine. This is the first in silico study to design a construct for the development of global EG95-based hydatid vaccine against E. granulosus in intermediate hosts. After antigen sequence selection, the three-dimensional structure of EG95 was modeled and multilaterally validated. The preliminary parameters for B-cell epitope prediction were implemented such as the possible transmembrane helix, signal peptide, post-translational modifications and allergenicity. The high ranked linear and conformational B-cell epitopes derived from several online web-servers (e.g., ElliPro, BepiPred v1.0, BcePred, ABCpred, SVMTrip, IEDB algorithms, SEPPA v2.0 and Discotope v2.0) were utilized for multiple sequence alignment and then for engineering the vaccine construct. T-helper based epitopes were predicted by molecular docking between the high frequent ovar class II allele (Ovar-DRB1*1202) and hexadecamer fragments of the EG95 protein. Having used the immune-informatics tools, we formulated the first EG95-based minigene vaccine based on T-helper epitope with high-binding affinity to the ovar MHC allele. This designed construct was analyzed for different physicochemical properties. It was also codon-optimized for high-level expression in Escherichia coli k12. Taken all, we propose the present in silico vaccine constructs as a promising platform for the generation of broadly protective vaccines for species and genus-specific immunization of the natural hosts of the parasite.

Analysis of CTLA-4+49A/G gene polymorphism in cases with leprosy of Azerbaijan, Northwest Iran.

Leprosy, which is developed by the obligate intracellular Mycobacterium leprae (ML); has different manifestations, associated with the host immune responses. The protective immune response against ML includes T-cell-mediated immunity. The CTLA-4 has a great impact as a negative regulator of the immune response and maintenance of peripheral tolerance. This study analyzed the relationship between CTLA-4+49A/G gene polymorphism and clinical manifestation of leprosy disease and susceptibility among the Azeri population living Northwest Iran. One hundred and ninety-two leprosy patients and 185 healthy controls participated in the study. CTLA-4+49A/G genotyping was conducted via tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) analysis. The allelic and genotypic frequencies of +49A/G gene polymorphism were similar in controls and patients. However, older ages, older age of onset and over-representation in male were observed in lepromatous leprosy patient carriers of GG genotype. The current study demonstrates that although CTLA-4+49A/G polymorphism was not correlated with a higher genetic risk for leprosy, the presence of a GG genotype was associated with older ages, older age of onset and over-representation in male in Iranian Azeri population.

Comparison of IIF, ELISA and IgG avidity tests for the detection of anti-Toxoplasma antibodies in single serum sample from pregnant women.

A valid estimate of test efficiency is needed to choose adequate screening and detecting strategies in diagnosis of acute toxoplasmosis. Therefore, in the present study we evaluated the efficiency of diagnostic laboratory methods to detect anti-toxoplasma antibodies in single serum samples of pregnant women by indirect immunofluorescence test (IIF), enzyme-linked immunosorbent assay (ELISA) and IgG avidity tests in north-western Iran. In an analytical-descriptive study, during March 2010 to April 2013, 391 pregnant women aged 21 to 35 years who were referred by gynaecologists or infectious disease specialists for anti-toxoplasma antibody evaluation were studied. A peripheral blood sample was collected from individuals and serum was prepared immediately for anti-toxoplasma antibody evaluation by IIF, ELISA and IgG avidity tests. ELISA and IgG avidity tests were used as gold standard. Evaluation of anti-toxoplasma antibodies by IIF revealed that 280 cases (71.61%) were seropositive and 111 (28.38%) seronegative, while evaluation by ELISA revealed that 267 cases (68.28%) were seropositive and 124 (31.70%) seronegative; 65 (16.62%) were IgM positive by both IIF and ELISA tests. There were 45 (69.23%) and 7 (10.76%) IgM positive suspected cases respectively in IIF and ELISA confirmed by the IgG avidity test for recent toxoplasmosis. This study highlights how to manage and evaluate pregnant women who are suspected to be infected with toxoplasmosis by using diagnostic tests, especially in a single serum sample indication.

Virulence and antimicrobial resistance in enterococci isolated from urinary tract infections.

PURPOSE: Urinary tract infection (UTI) is the most common nosocomial infection among hospitalized patients. Meanwhile, most frequent infections involving enterococci affect the urinary tract. The aims of this study were to investigate the susceptibility pattern of isolated enterococci from UTI and the prevalence of virulence genes. METHODS: The study used enterococci isolated from urinary tract infections obtained from 3 university teaching hospitals in Northwest Iran. The antimicrobial susceptibility of the strains was determined using the disc diffusion method. Multiplex PCR was performed for the detection of genus- species specific targets, and potential virulence genes. RESULTS: Of 188 enterococcal isolates, 138 (73.4%) and 50 (26.6%) were Enterococcus faecalis and E. faecium, respectively. Antibiotic susceptibility testing showed high resistance to amikacin (86.2%), rifampicin (86.2%) and erythromycin (73.9%), irrespective of species. In total, 68.1% were positive for gelE, and 57.4%, 53.2%, 56.4%, and 52.1% of isolates were positive for cpd, asa1, ace, and esp, respectively. CONCLUSION: The study revealed that most of UTI isolates were multidrug resistance against the antibiotics tested and antibiotic resistance was more common among E. faecium isolates than E. faecalis. A significant correlation was found between UTI and the presence of gelE among E. faecalis strains (p < 0.001).

Methicillin resistant and susceptible Staphylococcus aureus: Appraising therapeutic approaches in the Northwest of Iran.

BACKGROUND AND OBJECTIVES: Staphylococcus aureus is a versatile organism causing mild to life threatening infections. The major threat of this organism is its multidrug resistance. The present study was carried out to investigate in - vitro activity of conventional antibiotics routinely prescribed for methicillin resistant S. aureus (MRSA) and methicillin sensitive S. aureus (MSSA) infections in the Northwest of Iran and other alternating therapeutic agents which are recommended for Gram positive organisms. MATERIALS AND METHODS: Clinical isolates of S. aureus were subjected to multiplex PCR for simultaneous speciation and detection of methicillin resistance. Antibacterial susceptibility pattern was determined using disk diffusion. The Minimum Inhibitory Concentrations (MICs) were determined using E-test strips. RESULTS: The results revealed presence of nuc gene in all S. aureus isolates detected phenotypically earlier whereas, mecA gene was observed in 54% of strains. On disk diffusion and MIC determination assay, all MRSA and MSSA strains were susceptible to mupirocin (except one MRSA strain), linezolid and teicoplanin. Six vancomycin intermediate S. aureus strains were detected (VISA) with MIC= 4µg/mL, 5 of them being MRSA. In disk diffusion assay, 17.3% and 3.7% of isolates showed resistance to rifampin and fusidic acid, respectively. However, MIC50 and MIC90 tests shows promising in - vitro impact. CONCLUSION: In - vitro mupirocin was found as an effective prophylactic ointment for nasal S. aureus eradication. Our data emphasize the performance of surveillance exercises to outline the existing antibiotics prescription policies and to slow down the emergence of multidrug resistant strains.

The efficacy of permethrin 5% vs. oral ivermectin for the treatment of scabies.

Human scabies is caused by an infestation of the skin by the human itch mite (Sarcoptes scabiei var. hominis). The aim of this study is to compare the efficacy and safety of permethrin 5% lotion with oral ivermectin for the treatment of scabies. In total, 60 patients with scabies were enrolled, and randomized into two groups: The first group and their family contacts received 5% permethrin cream twice with a one week interval, and the other received a single dose of oral ivermectin. Treatment was evaluated at intervals of 2 and 4 weeks. A single dose of ivermectin provided a cure rate of 62.4%, which increased to 92.8% with 2 doses at a 2-week interval. Treatment with two applications of permethrin with a one week interval was effective in 96.9% of patients. Permethrin-treated patients recovered earlier. Two applications of permethrin with a one week interval is more effective than a single dose of ivermectin. Two doses of ivermectin is as effective as a single application of permethrin.