Background: COVID-19–associated mucormycosis (CAM) has emerged as a challenging complication as the current pandemic has increased the population requiring treatment with corticosteroids. CAM has caused a massive outbreak in India, reported to be causing cases in Iran, Egypt and the Netherlands. Objectives: to describe CAM cases occurring in a single centre in Western Mexico. Methods: Our group carried out a retrospective study from May 2020 to May 2021 to identify CAM cases in patients with previous COVID-19 diagnosis. Results: Six CAM cases occurred in a single centre in Western Mexico during the study period, most of them with diabetes (n = 5/6) and all received corticosteroid therapy even when only three had severe COVID-19. After analysing local COVID-19 burden, it was estimated that in this region, CAM was 300 times more frequent among COVID individuals than the estimates for general population. Conclusion: Similar to large reports in India and other countries, CAM cases reported in this study were diagnosed in individuals with diabetes, hyperglycaemic status and with history of previous use of corticosteroids. Identifying these individuals at risk can help the early identification of CAM. In addition, strict glycaemic control and avoidance of unnecessary corticosteroid in non-severe COVID-19 cases could help in preventing this complicated fungal infection.

An increasing number of outbreaks due to resistant non-albicans Candida species have been reported worldwide. Between 2014 and 2016, Candida isolates causing invasive candidiasis were recovered in a Mexican hospital. Isolates were identified to species level and antifungal susceptibility was determined. In the time period studied, 74 invasive candidiasis cases were identified, with 38% (28/74) caused by Candida parapsilosis, out of which 54% (15/28) were fluconazole resistant. The ERG11 gene was sequenced for 12 recoverable fluconazole-resistant C. parapsilosis isolates and SNPs identified. The 12 isolates had one common silent point mutation in ERG11 (T591C) and seven isolates had an additional (A395T) mutation, which corresponded to Y132F. Four of the isolates carrying this mutation were closely related within the same cluster by microsatellite typing. This is the first report of an invasive candidiasis outbreak in Mexico due to azole-resistant C. parapsilosis associated with the Y132F substitution.

Malassezia species are a major part of the normal mycobiota and colonize mainly sebum-rich skin regions of the body. This group of fungi cause a variety of infections such as pityriasis versicolor, folliculitis, and fungaemia. In particular, Malassezia sympodialis and its allergens have been associated with non-infective inflammatory diseases such as seborrheic dermatitis and atopic eczema. The aim of this study was to investigate the host response to M. sympodialis on oily skin (supplemented with oleic acid) and non-oily skin using an ex vivo human skin model. Host-pathogen interactions were analyzed by SEM, histology, gene expression, immunoassays and dual species proteomics. The skin response to M. sympodialis was characterized by increased expression of the genes encoding β-defensin 3 and RNase7, and by high levels of S100 proteins in tissue. Supplementation of oleic acid onto skin was associated with direct contact of yeasts with keratinocytes and epidermal damage. In oily conditions, there was increased expression of IL18 but no expression of antimicrobial peptide genes in the skin’s response to M. sympodialis. In supernatants from inoculated skin plus oleic acid, TNFα, IL-6, and IL1-β levels were decreased and IL-18 levels were significantly increased.

ORF3a has been identified as a viroporin of SARS-CoV-2 and is known to be involved in various pathophysiological activities including disturbance of cellular calcium homeostasis, inflam-masome activation, apoptosis induction and disruption of autophagy. ORF3a-targeting antibodies may specifically and favorably modulate these viroporin-dependent pathological activities. How-ever, suitable viroporin-targeting antibodies are difficult to generate because of the well-recognized technical challenge associated with isolating antibodies to complex transmembrane proteins. Here we exploited a naïve human single chain antibody phage display library, to isolate binders against carefully chosen ORF3a recombinant epitopes located towards the extracellular N terminal and cytosolic C terminal domains of the protein using peptide antigens. These binders were subjected to further characterization using enzyme-linked immunosorbent assays and surface plasmon resonance analysis to assess their binding affinities to the target epitopes. Binding to full-length ORF3a protein was evaluated by western blot and fluorescent microscopy using ORF3a transfected cells and SARS-CoV-2 infected cells. Co-localization analysis was also performed to evaluate the “pairing potential” of the selected binders as possible alternative diagnostic or prognostic biomarkers for COVID-19 infections. Both ORF3a N and C termini, epitope-specific monoclonal antibodies were identified in our study. Whilst the linear nature of peptides might not always represent their native conformations in the context of full protein, with carefully designed selection protocols, we have been successful in isolating anti-ORF3a binders capable of recognising regions of the transmembrane protein that are exposed either on the “inside” or “outside” of the infected cell. Their therapeutic potential will be discussed.

Teaching and learning anatomy by using human cadaveric specimens has been a foundation of medical and biomedical teaching for hundreds of years. Therefore, the majority of institutions that teach topographical anatomy rely on body donation programmes to provide specimens for both undergraduate and postgraduate teaching of gross anatomy. The COVID-19 pandemic has posed an unprecedented challenge to anatomy teaching because of the suspension of donor acceptance at most institutions. This was largely due to concerns about the potential transmissibility of the SARS-CoV-2 virus and the absence of data about the ability of embalming solutions to neutralise the virus. Twenty embalming solutions commonly used in institutions in the United Kingdom and Ireland were tested for their ability to neutralise SARS-CoV-2, using an established cytotoxicity assay. All embalming solutions tested neutralised SARS-CoV-2, with the majority of solutions being effective at high-working dilutions. These results suggest that successful embalming with the tested solutions can neutralise the SARS-CoV-2 virus, thereby facilitating the safe resumption of body donation programmes and cadaveric anatomy teaching.

Lower respiratory infections are the most important cause of death due to a transmissible disease. We present a case of severe influenza and coccidioidomycosis lung coinfection in a 65-year-old Mexican migrant. This case highlights the challenges that respiratory viruses impose on the diagnosis of fungal infections and on the multidisciplinary management of these infections. In addition, this case shows how medical complications and superinfections could be potentially prevented if flu vaccination is provided.

Human skin fungal infections (SFIs) affect 25% of the world's population. Most of these infections are superficial. The main limitation of current animal models of human superficial SFIs is that clinical presentation is different between the different species and animal models do not accurately reflect the human skin environment. An ex vivo human skin model was therefore developed and standardised to accurately model SFIs. In this manuscript, we report our protocol for setting up ex vivo human skin infections and report results from a primary superficial skin infection with Trichophyton rubrum, an anthropophilic fungus. The protocol includes a detailed description of the methodology to prepare the skin explants, establish infection, avoid contamination, and obtain high quality samples for further downstream analyses. Scanning electronic microscopy (SEM), histology and fluorescent microscopy were applied to evaluate skin cell viability and fungal morphology. Furthermore, we describe a broad range of assays, such as RNA extraction and qRT-PCR for human gene expression, and protein extraction from tissue and supernatants for proteomic analysis by liquid chromatography-mass spectrometry (LC-MS/MS). Non-infected skin was viable after 14 days of incubation, expressed genes and contained proteins associated with proliferative, immune and differentiation functions. The macroscopic damage caused by T. rubrum had a similar appearance to the one expected in clinical settings. Finally, using this model, the host response to T. rubrum infection can be evaluated at different levels.

Mucormycosis is a difficult to diagnose rare disease with high morbidity and mortality. Diagnosis is often delayed, and disease tends to progress rapidly. Urgent surgical and medical intervention is lifesaving. Guidance on the complex multidisciplinary management has potential to improve prognosis, but approaches differ between health-care settings. From January, 2018, authors from 33 countries in all United Nations regions analysed the published evidence on mucormycosis management and provided consensus recommendations addressing differences between the regions of the world as part of the “One World One Guideline” initiative of the European Confederation of Medical Mycology (ECMM). Diagnostic management does not differ greatly between world regions. Upon suspicion of mucormycosis appropriate imaging is strongly recommended to document extent of disease and is followed by strongly recommended surgical intervention. First-line treatment with high-dose liposomal amphotericin B is strongly recommended, while intravenous isavuconazole and intravenous or delayed release tablet posaconazole are recommended with moderate strength. Both triazoles are strongly recommended salvage treatments. Amphotericin B deoxycholate is recommended against, because of substantial toxicity, but may be the only option in resource limited settings. Management of mucormycosis depends on recognising disease patterns and on early diagnosis. Limited availability of contemporary treatments burdens patients in low and middle income settings. Areas of uncertainty were identified and future research directions specified.

In individuals with HIV/AIDS, 47% of the deaths are attributed to invasive fungal infections (IFIs), despite antiretroviral (ARV) therapy. This is a retrospective study carried out in the Hospital Regional de Alta Especialidad Oaxaca (HRAEO), southwest Mexico, where IFIs that occurred during 2016–2017 are described. A total of 55 individuals were included. Histoplasmosis (36%) and possible-IFIs in neutropenic fever (20%) were the most frequent cases, followed by cryptococcosis (14%). The HIV/AIDS subpopulation corresponded with 26 cases (47%), all from an indigenous origin. The incidence of IFIs among them was 24% (95% CI = 15–33%). The CD4+ T cells median was 35 cells/mL (IQR 12–58). Four cases (15%) of unmasking IRIS were identified, three of histoplasmosis and one coccidioidomycosis. Co-infections were found in 52% (12/23), and tuberculosis in 50% (6/12) was the most frequent. The mortality rate was 48%. The general characteristics of the HIV individuals who died were atypical pneumonia (70% vs. 9%, p = 0.01), acute kidney injury, (70% vs. 9%, p = 0.008) and ICU stay (80% vs. 9%, p = 0.002). In conclusion, IFIs are diagnosed in one out of four individuals with HIV/AIDS along with other complicated infectious conditions, leading to major complications and a high mortality rate.

Mucormycosis is an emerging infectious disease with high rates of associated mortality and morbidity. Little is known about the characteristics of mucormycosis or entomophthoromycosis occurring in Mexico. A search strategy was performed of literature published in journals found in available databases and theses published online at Universidad Nacional Autónoma de México (UNAM) library website reporting clinical cases or clinical case series of mucormycosis and entomophthoromycosis occurring in Mexico between 1982 and 2016. Among the 418 cases identified, 72% were diabetic patients, and sinusitis accounted for 75% of the reported cases. Diabetes mellitus was not a risk factor for entomophthoromycosis. Mortality rate was 51% (125/244). Rhizopus species were the most frequent isolates (59%, 148/250). Amphotericin B deoxycholate was used in 89% of cases (204/227), while surgery and antifungal management as combined treatment was used in 90% (172/191). In diabetic individuals, this combined treatment approach was associated with a higher probability of survival (95% vs 66%, OR = 0.1, 95% CI, 0.02–0.43’ P =. 002). The most common complications were associated with nephrotoxicity and prolonged hospitalization due to IV antifungal therapy. An algorithm is proposed to establish an early diagnosis of rhino-orbital cerebral (ROC) mucormycosis based on standardized identification of warning signs and symptoms and performing an early direct microbiological exam and histopathological identification through a multidisciplinary medical and surgical team. In summary, diabetes mellitus was the most common risk factor for mucormycosis in Mexico; combined antifungal therapy and surgery in ROC mucormycosis significantly improved survival.

Background: Invasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim to report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. Methods: This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. Results: Two-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p < 0.0001). The overall incidence of IFIs was 4.8 cases (95% CI = 0.72–8.92) per 1000 discharges and 0.7 cases (95% CI = 0.03–1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI = −1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI = −3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI = −0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). Conclusions: IFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

Metabolic control improves outcomes associated with mucormycosis. The aim of this study was to compare the in vitro proliferation of Rhizopus oryzae in blood of individuals with and without diabetes at different glycaemic levels. Ninety-five individuals were included. Blood samples from each participant were incubated with sporangiospores of R. oryzae. The germination, filamentation and growth of R. oryzae were compared at different time points. Four groups were defined, one without (group A, n = 30) and three with diabetes: group B (HbA1c ≤7%, N = 24), group C (HbA1c 7.1–9%, N = 20) and group D (HbA1c > 9%, N = 21). The percentage of germinated sporangiospores was higher in the group a after 6 h (group a 56% ± 3, group B 35% ± 4, group C 48% ± 4, group D 46% ± 1.4, p = 0.01), 12 h (group a 54% ± 1.4, group B 19% ± 4, group C 16% ± 1, group D 9.5% ± 5, p 

Serious fungal infections (SFIs) could be more frequent than are recognised. Estimates of the incidence and prevalence of SFIs are essential in order to identify public health problems. We estimated the rates of SFIs in Mexico, following a methodology similar to that used in prior studies. We obtained information about the general population and populations at risk. A systematic literature search was undertaken to identify epidemiological reports of SFIs in Mexico. When Mexican reports were unavailable, we based our estimates on international literature. The most prevalent SFIs in Mexico are recurrent vulvovaginal candidiasis (5999 per 100 000) followed by allergic bronchopulmonary aspergillosis (60 per 100 000), chronic pulmonary aspergillosis (15.9 per 100 000), fungal keratitis (10.4 per 100 000), invasive candidiasis (8.6 per 100 000) and SFIs in HIV (8.2 per 100 000); coccidioidomycosis (7.6 per 100 000), IA (4.56 per 100 000). These correspond to 2 749 159 people affected in any year (2.45% of the population), probably >10 000 deaths and 7000 blind eyes. SFIs affect immunocompromised and healthy populations. Most are associated with high morbidity and mortality rates. Validation of these estimates with epidemiological studies is required. The burdens indicate that an urgent need to improve medical skills, surveillance, diagnosis, and management of SFIs exists.

With increased use of expanded-spectrum triazoles for antifungal prophylaxis, the epidemiology of invasive fungal infections (IFIs) after allogeneic haematopoietic stem cell transplantation (HSCT) continues to evolve. To define the contemporary epidemiology of IFIs in this population, we reviewed all European Organization for Research and Treatment of Cancer-Mycoses Study Group proven and probable IFIs in adults transplanted from 2002 to 2011 and determined the incidence and risk factors for IFI and post-IFI mortality. All patients received antifungal prophylaxis. Fifty-three (14%) of 378 allogeneic HSCT recipients developed an IFI. There were 62 IFI episodes, of which aspergillosis (n = 31; 50%) and candidaemia (n = 15; 24%) were most common. Sixteen episodes (26%) were caused by other fungi, including Mucorales (n = 6; 10%) and the following uncommon pathogens: Trichosporon asahii, Arthrographis sp. Cladosporium sp. Geosmithia argillacea and Hormographiella aspergillata. Independent IFI risk factors were hospitalisation in an intensive care unit [ICU; odds ratio (OR) = 6.0], graft-versus-host disease (OR = 5.3), central venous catheter use (OR = 5.2) and hypoalbuminaemia (OR = 0.3 g-1 dl-1 increase in albumin). The 90-day mortality rate after IFI was 57%. Non-cytomegalovirus systemic viral co-infection (OR = 3.5) and stay in an ICU (OR = 2.9) were independent risk factors for death. Despite antifungal prophylaxis, IFIs remain common after allogeneic HSCT and previously uncommon pathogens are emerging.

Introduction: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). Objective: to determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. Design: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. Methods: all patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. Results: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥16 (OR = 6.94, CI95% = 2.34-20.58, p

The pathogenic role of invasive fungal infections (IFIs) has increased during the past two decades in Latin America and worldwide, and the number of patients at risk has risen dramatically. Working habits and leisure activities have also been a focus of attention by public health officials, as endemic mycoses have provoked a number of outbreaks. An extensive search of medical literature from Latin America suggests that the incidence of IFIs from both endemic and opportunistic fungi has increased. The increase in endemic mycoses is probably related to population changes (migration, tourism, and increased population growth), whereas the increase in opportunistic mycoses may be associated with the greater number of people at risk. In both cases, the early and appropriate use of diagnostic procedures has improved diagnosis and outcome. © 2012 Springer Science+Business Media, LLC.