Virulence and resistance factors of Nakaseomyces glabratus (formerly known as Candida glabrata) in Europe: A systematic review.

BACKGROUND: Nakaseomyces glabratus (N. glabratus) formerly known as Candida glabrata (C. glabrata), is an endogenous opportunistic pathogen, which is generally located in the gastrointestinal tract but can spread in immunocompromised patients. N. glabratus is the second most common pathogen that causes candidemia in several countries. N. glabratus virulence factors may increase antifungal resistance and reduce the number of available treatment options. High resistance to azoles and increasing resistance to echinocandins have been previously reported in N. glabratus. OBJECTIVE: To establish the distribution of N. glabratus isolates in Europe and its drug susceptibility/resistance in each country over the last 7 years. METHODS: The search was performed across three databases: PubMed, Scopus and Scielo, using the MeSH terms: "Candida glabrata", "Nakaseomyces glabratus", "Europe", "resistance" and "Epidemiology" exclusively in English. All available information from January 2002 to December 2022 was included, excluding reviews, meta-analyses and book chapters. RESULTS: Fifty-seven articles with information on antifungal susceptibility in Europe were retrieved and analysed with a total of 15,400 reported C. glabrata isolates. Remarkably, nations that presented the maximum number of cases during the study period included the United Kingdom (n = 7241, 47.02%), France (n = 3190, 20.71%), Spain (n = 900, 5.84%), Hungary (n = 745, 4.84%) and Italy (n = 486, 3.16%). C. glabrata isolates presented resistance to azoles [voriconazole (n = 2225, 14.45%), fluconazole (n = 1612, 10.47%), itraconazole (n = 337, 2.19%) and clotrimazole (n = 89, 0.58%)], increased resistance to echinocandins, especially to anidulafungin (n = 138, 0.89%), and high sensitivity to amphotericin B. CONCLUSION: The number of candidemia cases associated with triazole-resistant N. glabratus isolates have been increasing in Europe. Therefore, echinocandins and amphotericin B can be considered optional empirical treatments; however, antifungal susceptibility testing is required to determine the best therapeutic options.

Disseminated Sporotrichosis: An Important Differential Diagnosis for Venous Ulcers.

The authors present the case of a 45-year-old immunosuppressed man with lower extremity ulcers. Initially treated as venous ulcers, the wounds were later correctly diagnosed as cutaneous disseminated sporotrichosis. After appropriate treatment with systemic antifungals was initiated, the patient healed within 4 months.

First Report of Bacillary Angiomatosis by Bartonella elizabethae in an HIV-Positive Patient.

We present the case of an HIV-positive patient who developed polymorphous lesions in which the evidence in the skin biopsy corresponds to the diagnosis of bacillary angiomatosis, and further tests proved the pathological agent involved in this case is not the usual Bartonella species, B. henselae and B. quintana, but B. elizabethae. As far as we know, this is the first case of bacillary angiomatosis secondary to this etiological agent.

Evaluation of improvement of onychomycosis in HIV-infected patients after initiation of combined antiretroviral therapy without antifungal treatment.

Onychomycosis in HIV-infected patients has a prevalence of 20-44% and is more frequently seen with CD4(+) T cell counts ≤450 cel µl(-1). There are case reports of improvement in onychomycosis after initiation of combined antiretroviral therapy (cART), but there are no prospective studies that prove the existence and frequency of this phenomenon. The aim of this study was to evaluate if HIV-infected patients with onychomycosis who begin cART improve and/or cure without antifungal treatment. We included HIV-infected patients with onychomycosis who had not started cART and nor received antifungal therapy during 6 months prior to the study. We evaluated affected the nails with the Onychomycosis Severity Index (OSI); nail scrapings were collected and direct microscopy with potassium hydroxide (KOH) as well as mycological culture were performed. We repeated these procedures at 3 and 6 months to assess changes. CD4 T cell counts and HIV viral load were obtained. A total of 16 patients were included, with male gender predominance (68.7%); distal and lateral subungual onychomycosis (DLSO) was the most common form (31.3%). Trichophyton rubrum was the most frequently isolated microorganism. OSI decreased 21.5% at 3 months and 40% at 6 months after initiation of antiretrovirals (P = 0.05). We found a non-significant tendency towards improvement with higher CD4(+) T cell counts and with viral loads <100 000 copies ml(-1). This could be due to the increase in CD4(+) T cells, decreased percentage of Treg (CD4(+)CD25(+)) among CD4(+) Tcells and/or a decreased viral load; further studies are necessary to prove these hypothesis.

Histoplasmosis and skin lesions in HIV: a safe and accurate diagnosis.

Human histoplasmosis is caused by the dimorphic fungus Histoplasma capsulatum. This infection can run asymptomatic or be life-threatening, depending fundamentally on the host's immune status. Immunocompromised patients can present disseminated disease to the skin, making the biopsy an accessible approach. The current diagnosis gold standard is fungal culture which takes several days or weeks to grow and must be handled in a biosafe laboratory which is avoided if we use the technique here described. We propose the use of molecular biology for diagnosis confirmation, considering it can shorten diagnosis lapse, has good specificity and sensitivity and reduces the risk of infection for the medical and laboratory personnel. Seven paraffin-embedded skin biopsy samples were included from patients with confirmed HIV and histoplasmosis diagnosis. Total DNA was isolated and molecular typing of H. capsulatum var. capsulatum. All samples were positive. This is a safe and accurate method for skin histoplasmosis diagnosis.

[Cutaneous coccidioidomycoses: Six Mexican cases report]. / Coccidioidomicosis cutánea: Comunicación de seis casos mexicanos.

Coccidioidomycosis is a systemic airborne mycosis that may involve secondarily other organs through systemic dissemination. Fungi Coccidioides immitis and C. posadasii are the etiologic agents. The former is ubiquitous from the area of California in North America, and the latter is found elsewhere in the world. Primary cutaneous infection is rare. We present six Mexican male cases, residents of Tijuana B.C. Three of them with primary pulmonary infection and further cutaneous dissemination, and three cases of primary cutaneous coccicioidomycosis. In half the cases C. posadasii was isolated. The clinical suspicion is basic for reaching the diagnosis, and we must always keep in mind that the cutaneous manifestations are widely varied and that the lesions are more severe when systemic dissemination occurs.

siRNAs from miRNA sites mediate DNA methylation of target genes.

Arabidopsis microRNA (miRNA) genes (MIR) give rise to 20- to 22-nt miRNAs that are generated predominantly by the type III endoribonuclease Dicer-like 1 (DCL1) but do not require any RNA-dependent RNA Polymerases (RDRs) or RNA Polymerase IV (Pol IV). Here, we identify a novel class of non-conserved MIR genes that give rise to two small RNA species, a 20- to 22-nt species and a 23- to 27-nt species, at the same site. Genetic analysis using small RNA pathway mutants reveals that the 20- to 22-nt small RNAs are typical miRNAs generated by DCL1 and are associated with Argonaute 1 (AGO1). In contrast, the accumulation of the 23- to 27-nt small RNAs from the miRNA-generating sites is dependent on DCL3, RDR2 and Pol IV, components of the typical heterochromatic small interfering RNA (hc-siRNA) pathway. We further demonstrate that these MIR-derived siRNAs associate with AGO4 and direct DNA methylation at some of their target loci in trans. In addition, we find that at the miRNA-generating sites, some conserved canonical MIR genes also produce siRNAs, which also induce DNA methylation at some of their target sites. Our systematic examination of published small RNA deep sequencing datasets of rice and moss suggests that this type of dual functional MIRs exist broadly in plants.

Bacteria-responsive microRNAs regulate plant innate immunity by modulating plant hormone networks.

MicroRNAs (miRNAs) are key regulators of gene expression in development and stress responses in most eukaryotes. We globally profiled plant miRNAs in response to infection of bacterial pathogen Pseudomonas syringae pv. tomato (Pst). We sequenced 13 small-RNA libraries constructed from Arabidopsis at 6 and 14 h post infection of non-pathogenic, virulent and avirulent strains of Pst. We identified 15, 27 and 20 miRNA families being differentially expressed upon Pst DC3000 hrcC, Pst DC3000 EV and Pst DC3000 avrRpt2 infections, respectively. In particular, a group of bacteria-regulated miRNAs targets protein-coding genes that are involved in plant hormone biosynthesis and signaling pathways, including those in auxin, abscisic acid, and jasmonic acid pathways. Our results suggest important roles of miRNAs in plant defense signaling by regulating and fine-tuning multiple plant hormone pathways. In addition, we compared the results from sequencing-based profiling of a small set of miRNAs with the results from small RNA Northern blot and that from miRNA quantitative RT-PCR. Our results showed that although the deep-sequencing profiling results are highly reproducible across technical and biological replicates, the results from deep sequencing may not always be consistent with the results from Northern blot or miRNA quantitative RT-PCR. We discussed the procedural differences between these techniques that may cause the inconsistency.

Novel presentation of immune reconstitution inflammatory syndrome: folliculitis secondary to Malassezia spp.

Folliculitis, as a manifestation of immune reconstitution inflammatory syndrome (IRIS) during antiretroviral therapy, has only been described in its aseptic form. Here, we describe folliculitis associated with Malassezia spp. as a distinct manifestation of IRIS. The distinction between these two types of IRIS folliculitis is relevant for treatment.

Rhinocerebral mucormycosis to the rise? The impact of the worldwide diabetes epidemic.

The authors present seven cases of rhinocerebral mucormycosis associated to diabetes mellitus, which is a disease with epidemic proportions affecting individuals worldwide, particularly in developing countries, and which poses significant morbidity and mortality. Mucormycosis is an opportunistic fungal infection with high mortality and requires an invasive therapeutic approach to save the patient's life with significant morbidity and sequelae, thus prevention is crucial.

Subclinical Onychomycosis in Apparently Healthy Adults.

INTRODUCTION: Onychomycosis is a frequent chronic nail infection, with a worldwide prevalence of 5.5% making it the most common nail disease, and its incidence increases with age. Clinically, it causes discoloration and thickening of the nail plate and may be accompanied by onycholysis. However, little is known of the subclinical infection. METHODS: We studied adult male and female outpatients auto-referred as healthy and that had healthy appearing toenails. Nail distal clippings were obtained from the right first toenail. This sample was stained with PAS and observed by an expert dermatopathologist searching for fungal structures. RESULTS: A total of 32 samples were included: 8 from men (25%) and 24 from women (75%), with ages ranging from 27 to 66 years (mean age of 43 years). Twenty-four patients did not present any histopathological finding suggestive of infection (75%), while 7 patients had a single finding (spores or hyphae) (21.8%), and 1 patient had both findings (3.12%). DISCUSSION/CONCLUSION: We found 4 patients with yeasts, 3 with hyphae, and 1 patient with a combined infection with both yeasts and hyphae (3.1%). These add up to 25% of the clinically apparent healthy nails. Our results show that we still have much to learn from the initial stages of onychomycosis and that our population probably has higher incidence of this nail disease, so we must be alert to subtle nail changes. As our participants signed an informed consent, we will contact those that resulted positive for follow up consultations.

Rhino-Orbital mucormycosis in an immunocompetent pediatric patient with hyperglycemia of the hospitalized patient.

INTRODUCTION: Acute invasive rhino-orbital mucormycosis usually affects diabetic or neutropenic patients, and only exceptionally develops in immunocompetent adults and children. METHODOLOGY: A 12-years-old immunocompetent female, presented with complicated rhinosinusitis with a subperiosteal orbital abscess, without improvement after initial medical and surgical management, the patient also developed hyperglycemia of the hospitalized patient that represented a challenging and potentially lethal clinical scenario. RESULTS: Diagnosed with an unsuspected rhino-orbital mucormycosis by direct microscopy and PCR, she survived after amphotericin B and surgical treatment. CONCLUSIONS: In cases with torpid clinical evolution, even in apparently immunocompetent patients, appropriate multidisciplinary workup must be performed to rule out opportunistic etiologies including mucormycosis to improve survival.

[Prevalence of anogenital condylomas in patients with HIV infection in a center for sexually transmitted infections in Leon, Guanajuato, Mexico]. / Prevalencia de condilomas ano-genitales en pacientes con infección por VIH en un centro para infecciones de transmisión sexual en León, Guanajuato, México.

BACKGROUND: Condylomas are the most frequent sexually transmitted infection worldwide, and thus, have a close relation to HIV infection. The site and serology vary, and some pose higher risk of malignancy. AIM: To describe the prevalence, characteristics and associated factors to the presence of anogenital condylomas in patients with HIV/AIDS. METHODS: Descriptive cross-sectional study conducted in the period from June to December 2014. Adult HIV/AIDS positive patients from "CAPASITS" in Leon, Mexico, from both sexes were included. A questionnaire was performed that included: identification data, and risk factors related to anogenital condylomas. Anogenital area was examined for condylomas. Descriptive statistics were carried out according to the type and distribution of the variables, and the CD4 lymphocyte medians of patients with and without condylomas were compared using U- Mann-Whitney test. RESULTS: A total of 213 HIV/AIDS patients were included; 181 (85%) were male. The prevalence of anogenital condylomas was 30% (IC95%: 23-36%), predominating in the anal region, observed in 21% of the cases. A significant difference was found between median CD4 cell count of patients with and without condylomas (425 vs 510 CD4/mL, p= 0.034). CONCLUSION: A high prevalence of patients with anogenital condylomas was obtained. The presence of condylomas was higher in patients with lower CD4 count. Considering the high prevalence, the application of the vaccine is recommended in this patient group.

Molecular identification of yeasts from the order Trichosporonales causing superficial infections.

BACKGROUND: The molecular reclassification of the order Trichosporonales placed the medically relevant Trichosporon species into three genera of the family Trichosporonaceae: Cutaneotrichosporon, Trichosporon, and Apiotrichum. From the clinical and epidemiological standpoint, it is important to identify any species of the family Trichosporonaceae because they present different antifungal susceptibility profiles. In Mexico, little is known about trichosporonosis etiology because the fungi are identified through phenotypic methods. AIMS: To identify at a molecular level 12 yeast isolates morfologically compatible with Trichosporon, obtained from patients with superficial infections. METHODS: The yeast isolates were obtained from patients with white piedra, onychomycosis, and hand and foot dermatomycosis, and were identified morphologically and genotypically (sequencing of the IGS1 region and phylogenetic analysis using the Maximum Likelihood Method). The phylogenetic analysis included 40 yeast sequences from the order Trichosporonales and one from Cryptococcus neoformans as outgroup. RESULTS: Based on the molecular analysis, we identified three (25%) Trichosporon inkin isolates, two (16.7%) Trichosporon asteroides, two (16.7%) Cutaneotrichosporon mucoides, and one each (8.3%) of Trichosporon aquatile, Trichosporon asahii, Apiotrichum montevideense, Cutaneotrichosporon cutaneum, and Cutaneotrichosporon jirovecii. CONCLUSIONS: The molecular characterization of the isolates showed a broad diversity of species within the order Trichosporonales, particularly among onychomycosis. It is essential to identify these yeasts at the species level to delve into their epidemiology.

Clinical, mycological and histological aspects of white onychomycosis.

Fungal leuconychia defines the clinical manifestations of white changes in onychomycosis. This uncommon clinical aspect is mostly seen, although not exclusively, in immunosuppressed patients. The principal isolated organism is Trichophyton spp. but the entity can also be caused by non-dermatophyte moulds. The mechanism of infection is unclear; it could be acquired through the proximal nail fold, or, as more recently proposed, may be secondary to lymphatic or vascular dissemination. To analyse the clinical, mycological and histopathological features of fungal leuconychia, we included 10 patients with the clinical diagnosis of fungal leuconychia. Direct examination of culture and nail plate biopsy were performed. Nine patients had confirmed fungal leuconychia. Four had a positive culture and all had positive haematoxylin-eosin (H&E) and Periodic Acid Schiff (PAS) stains for fungal elements with varying degrees of nail plate invasion. Seven of our patients were immunosuppressed and the isolated aetiological agents are the same as previously reported. The direct examination is reliable, fast and inexpensive to establish the diagnosis. The correlation of onychomycosis with histology, stained with H&E and PAS was 100%. We think that the site of nail plate invasion provides more information to support the theory that the infection reaches the ungual apparatus through systemic dissemination.

[Erythema multiforme secondary to cutaneous Trichophyton mentagrophytes infection]. / Eritema multiforme secundario a infección por Trichophyton mentagrophytes.

Erythema multiforme is an acute self-limited cutaneous syndrome associated in more than 50% of the cases with herpes simplex virus infection; but it can also be a consequence of other infectious agents or drugs. We report on a 24 year-old female patient with erythema multiforme secondary to Trichophyton mentagrophytes var. mentagrophytes cutaneous infection acquired from contact with animals in a research laboratory.

Subclinical Onychomycosis: Not Present in HIV-Positive Population?

BACKGROUND: Onychomycosis is one of the most common nail diseases and constitutes up to 50% of all nail conditions. It is a chronic fungal nail infection common in the HIV-infected population. Few studies have found fungal organisms in the nail without clinical evidence, and thus, termed subclinical onychomycosis. OBJECTIVES: We analyzed the nails of the HIV population in our hospital, searching for subclinical onychomycosis. METHOD: A distal nail clipping was stained with PAS and observed by a trained dermatopathologist. RESULTS: All of our samples (n = 48) turned out to be negative for fungal structures. CONCLUSIONS: The epidemiology of onychomycosis is changing, treatment options are much better now, and diagnosis and infection detection are being done earlier. Therefore, we will continue to further study this disease in other patient populations so that we can compare our results and see whether the incidence of onychomycosis in the HIV population is now similar to that in those without HIV infection of the same age.

Isolation of Malassezia spp. in HIV-positive patients with and without seborrheic dermatitis.

BACKGROUND: Malassezia, a skin saprophyte, is frequently isolated from patients with seborrheic dermatitis, which is one of the most common dermatoses in HIV-infected patients. Its role in pathophysiology has not been defined. OBJECTIVE: To determine whether patients living with HIV and seborrheic dermatitis have more Malassezia than those without seborrheic dermatitis. METHOD: This is an descriptive, observational, prospective cross-sectional study to which all adult patients living with HIV that attend the infectious disease outpatient clinic at the Dr. Manuel Gea González General Hospital were invited. Patients presenting with scale and erythema were included in Group 1, while patients without erythema were included in Group 2. Samples were taken from all patients for smear and culture. RESULTS: Thirty patients were included in each group. All patients with seborrheic dermatitis had a positive smear, with varying amounts of yeasts. In the control group, 36.7% of patients had a negative smear. The results are statistically significant, as well as the number of colonies in the cultures. Study limitations The study used a small sample size and the subspecies were not identified. CONCLUSIONS: Patients with clinical manifestations of seborrheic dermatitis have larger amounts of Malassezia. Further studies need to be performed to analyze if the greater amount is related to imbalances in the microbiota of the skin.