A global call for talaromycosis to be recognised as a neglected tropical disease.

Talaromycosis (penicilliosis) is an invasive mycosis that is endemic in tropical and subtropical Asia. Talaromycosis primarily affects individuals with advanced HIV disease and other immunosuppressive conditions, and the disease disproportionally affects people in low-income and middle-income countries, particularly agricultural workers in rural areas during their most economically productive years. Approximately 17 300 talaromycosis cases and 4900 associated deaths occur annually. Talaromycosis is highly associated with the tropical monsoon season, when flooding and cyclones can exacerbate the poverty-inducing potential of the disease. Talaromycosis can present as localised or disseminated disease, the latter causing cutaneous lesions that are disfiguring and stigmatising. Despite up to a third of diagnosed cases resulting in death, talaromycosis has received little attention and investment from regional and global funders, policy makers, researchers, and industry. Diagnostic and treatment modalities remain extremely insufficient, however control of talaromycosis is feasible with known public health strategies. This Viewpoint is a global call for talaromycosis to be recognised as a neglected tropical disease to alleviate its impact on susceptible populations.

Peryton: a manual collection of experimentally supported microbe-disease associations.

We present Peryton (https://dianalab.e-ce.uth.gr/peryton/), a database of experimentally supported microbe-disease associations. Its first version constitutes a novel resource hosting more than 7900 entries linking 43 diseases with 1396 microorganisms. Peryton's content is exclusively sustained by manual curation of biomedical articles. Diseases and microorganisms are provided in a systematic, standardized manner using reference resources to create database dictionaries. Information about the experimental design, study cohorts and the applied high- or low-throughput techniques is meticulously annotated and catered to users. Several functionalities are provided to enhance user experience and enable ingenious use of Peryton. One or more microorganisms and/or diseases can be queried at the same time. Advanced filtering options and direct text-based filtering of results enable refinement of returned information and the conducting of tailored queries suitable to different research questions. Peryton also provides interactive visualizations to effectively capture different aspects of its content and results can be directly downloaded for local storage and downstream analyses. Peryton will serve as a valuable source, enabling scientists of microbe-related disease fields to form novel hypotheses but, equally importantly, to assist in cross-validation of findings.

Estimates of serious fungal infection burden in Côte d'Ivoire and country health profile.

Due to limited access to more powerful diagnostic tools, there are few data on the burden of fungal infections in Côte d'Ivoire, despite a high HIV and TB burden and many cutaneous diseases. Here we estimate the burden of serious fungal infections in this sub-Saharan country with a health profiling description. National demographics were used and PubMed searches to retrieve all published articles on fungal infections in Côte d'Ivoire and other bordering countries in West Africa. When no data existed, risk populations were used to estimate frequencies of fungal infections, using previously described methodology by LIFE (www.LIFE-Worldwide.org). The population of Côte d'Ivoire is around 25 million; 37% are children (≤14 years), and 9% are>65 years. Tinea capitis in children is common, measured at 13.9% in 2013. Considering the prevalence of HIV infection (2.6% of the population, a total of ∼500,000) and a hospital incidence of 12.7% of cryptococcosis, it is estimated that 4590 patients per year develop cryptococcosis. For pneumocystosis, it is suggested that 2640 new cases occur each year with the prevalence of 11% of newly diagnosed HIV adults, and 33% of children with HIV/AIDS. Disseminated histoplasmosis is estimated a 1.4% of advanced HIV disease - 513 cases. An estimated 6568 news cases of chronic pulmonary aspergillosis (CPA) occur after pulmonary tuberculosis (a 5-year prevalence of 6568 cases [26/100,000]). Allergic bronchopulmonary aspergillosis (ABPA) and severe asthma with fungal sensitisation (SAFS) were estimated in 104/100,000 and 151/100,000 respectively, in 1,152,178 adult asthmatics. Vulvovaginal candidiasis (VVC) is common and recurrent VVC affects ∼6% of women in their fertile years - 421,936 women. An unknown number develop candidaemia and invasive aspergillosis. The annual incidence of fungal keratitis is estimated at 3350. No cases of sporotrichosis, mucormycosis and chromoblastomycosis are described, although some cases of mycetoma and Conidiobolus infection have been reported. This study indicates that around to 7.25% (1.8 million) of the population is affected by a serious fungal infection, predominently tinea capitis in children and rVVC in women. These data should be used to inform epidemiological studies, diagnostic needs and therapeutic strategies in Côte d'Ivoire.

The High Diversity and Variable Susceptibility of Clinically Relevant Acremonium-Like Species in China.

Acremonium-like fungi are emerging as important opportunistic pathogens in cutaneous, subcutaneous and serious invasive infections, especially in immunocompromised and debilitated individuals, and Acremonium infections are usually resistant to antifungal therapy. Several molecular studies have demonstrated that many species in the genus Acremonium are polyphyletic, and currently, the genus is restricted to the family Bionectriaceae (Hypocreales). Molecular identification and in vitro antifungal susceptibility tests of Acremonium-like fungi isolated from human clinical specimens in China were performed in this study. Three genetic loci: the large subunit ribosomal RNA gene (LSU), ribosomal internal transcribed spacer and elongation factor 1-α (EF1-α), were used to assess their taxonomic position for correct identification among various species. The multilocus study of twenty-eight strains showed that these strains were distributed in three main lineages: egyptiacum, Cordycipitaceae and Sarocladium; Acremonium egyptiacum and Sarocladium kiliense were the main species of these strains, and three isolates were too phylogenetically distant to be considered undescribed species. Relatively low minimum inhibitory concentrations (MICs) of 0.25-2 and 0.031-0.5 µg/mL were found for voriconazole and terbinafine for most species, respectively. Varied antifungal activities of ciclopirox olamine, amorolfine and posaconazole were found in our study. However, no antifungal effect of sertaconazole, itraconazole or fluconazole was observed against most strains. This is the first study on Acremonium-like species diversity by multilocus sequence analyses and antifungal susceptibility of clinically relevant isolates in China.

Definition of Opportunistic Infections in Immunocompromised Children on the Basis of Etiologies and Clinical Features: A Summary for Practical Purposes.

Opportunistic Infections (OIs) still remain a major cause of morbidity and death in children with either malignant or nonmalignant disease. OIs are defined as those infections occurring due to bacteria, fungi, viruses or commensal organisms that normally inhabit the human body and do not cause a disease in healthy people, but become pathogenic when the body's defense system is impaired. OIs can also be represented by unusually severe infections caused by common pathogens. An OI could present itself at the onset of a primary immunodeficiency syndrome as a life-threatening event. More often, OI is a therapyassociated complication in patients needing immunosuppressive treatment, among long-term hospitalised patients or in children who undergo bone marrow or solid organ transplantation. The aim of the present review is to provide a comprehensive and 'easy to read' text that briefly summarises the currently available knowledge about OIs in order to define when an infection should be considered as opportunistic in pediatrics as a result of an underlying congenital or acquired immune-deficit.

Estudio Trasversal: Micosis Superficiales en Niños Escolares de una Parroquia Rural de Cuenca, Ecuador / Cross - Sectional - Research: Superficial Mycoses in Scholar Children of a Rural Parish in Cuenca, Ecuador

INTRODUCCIÓN: Las micosis superficiales constituyen un importante problema de salud a nivel mundial, siendo mayor su frecuencia en niños y adultos jóvenes. Existen escasos estudios científicos publicados en Ecuador sobre esta patología, en particular en la provincia del Azuay. El objetivo del estudio fue determinar la frecuencia de micosis superficiales en niños escolares y sus agentes etiológicos. MÉTODO: Se realizó un estudio descriptivo transversal, con 294 pacientes, las edades entre 3 y 14 años, pertenecieron a una escuela fiscal de la parroquia rural "El Valle", provincia del Azuay - Cuenca, Ecuador. Se examinó físicamente a cada participante para caracterizar lesiones sugestivas de micosis; a las muestras tomadas de las lesiones, se aplicó las técnicas de diagnóstico micológico como análisis directo, cultivo e identificación de agentes fúngicos mediante caracterización macroscópica y microscópica de las colonias. RESULTADOS: De los 294 pacientes evaluados (72.8 % hombres), 234 (79.6 %) presentaron lesiones sugestivas de micosis superficial; en 179 participantes (60.9 %) se identificó al menos un agente fúngico en las muestras analizadas, sin diferencias significativas entre género y edad (p: > 0.05). Los dermatofitos fueron los hongos más frecuentes (58.2 %), siendo Trichophyton schoenleinii y Trichophyton mentagrophytes las especies mayormente reportadas. CONCLUSIONES: Se concluyó que las micosis superficiales afectaron a más de la mitad de los niños en edad escolar en la población estudiada. Los dermatofitos son los principales agentes etiológicos aislados, de los cuales se identificaron ciertas especies que varían en frecuencia con relación a lo reportado en otros países de Latinoamérica.

BACKGROUND: Superficial mycoses constitute a health problem worldwide, being a major frequency in children and young adults. There are few scientific studies published in Ecuador on this pathology, in particularin the province of Azuay. The aimofthe study was to determine the frequency of superficialmycoses in school children and their etiological agents. METHODS: A cross-sectional descriptive study was carried out, with 294 patients, aged between3and14 years,belongingtoafiscal schoolinthe ruralparish"ElValle",provinceofAzuay - Cuenca, Ecuador. Each participant was physically examined to characterize lesions suggestive of mycosis; to the samples taken from the lesions, the techniques of mycological diagnosis were applied as direct analysis, culture, and identification of fungal agents by means of macroscopic andmicroscopic characterization ofthe colonies. RESULTS: The 294 patients evaluated (72.8 % men), 234 participants (79.6 %) had lesions suggestive of superficialmycosis; in the 179 participants atleast one fungal agent was identified in the analyzed samples (60.9 %), with no significant differences between gender and age (p: > 0.05). Dermatophytes were the most frequently identified fungal agent (58.2%, n= 201), with Trichophyton schoenleinii and Trichophytonmentagrophytes being themostfrequently reported species. CONCLUSIONS: Itis concluded that superficialmycoses affectedmore than half of school-age children in the study population. Dermatophytes were the main isolated etiological agents, from which certain species had been identified that vary in frequency in relation to thatreported in other Latin American countries.

A seven-year retrospective analysis of the clinicopathological and mycological manifestations of fungal rhinosinusitis in a single-centre tropical climate hospital.

OBJECTIVE: To evaluate the clinicopathological and mycological manifestations of fungal rhinosinusitis occurring in the Tengku Ampuan Rahimah Hospital, in Klang, Malaysia, which has a tropical climate. METHODS: Records of patients treated from 2009 to 2016 were analysed retrospectively. Data from the records were indexed based on age, gender, clinical presentations, symptom duration, clinical signs and mycological growth. RESULTS: Of 80 samples, 27 (33.75 per cent) had fungal growth. Sixteen patients were classified as having non-invasive fungal rhinosinusitis and 11 as having invasive fungal rhinosinusitis. The commonest clinical presentation was nasal polyposis in non-invasive fungal rhinosinusitis patients (p < 0.05) and ocular symptoms in invasive fungal rhinosinusitis patients (p < 0.05). The commonest organism was aspergillus sp. (p < 0.05) in non-invasive fungal rhinosinusitis and mucorales in invasive fungal rhinosinusitis. CONCLUSION: There is an almost equal distribution of both invasive and non-invasive fungal rhinosinusitis, as seen in some Asian countries. Invasive fungal rhinosinusitis, while slightly uncommon when compared to non-invasive fungal rhinosinusitis, is potentially life threatening, and may require early and extensive surgical debridement. The clinical presentation of nasal polyposis was often associated with non-invasive fungal rhinosinusitis, whereas ocular symptoms were more likely to be associated with invasive fungal rhinosinusitis.

AIDS-Related Mycoses: Current Progress in the Field and Future Priorities.

Opportunistic fungal infections continue to take an unacceptably heavy toll on the most disadvantaged living with HIV-AIDS, and are a major driver for HIV-related deaths. At the second EMBO Workshop on AIDS-Related Mycoses, clinicians and scientists from around the world reported current progress and key priorities for improving outcomes from HIV-related mycoses.

Acute Invasive Fungal Rhinosinusitis: Presentation of 19 Cases, Review of the Literature, and a New Classification System.

PURPOSE: The aim of this study was to determine the correlation between acute invasive fungal rhinosinusitis (AIFRS) and underlying diseases, micro-organisms, presenting symptoms, extent of disease, radiologic findings, and outcomes and propose a new classification system. MATERIALS AND METHODS: The data of 19 AIFRS cases were analyzed retrospectively. Magnetic resonance imaging and computed tomography were performed in all patients preoperatively. All patients underwent at least 1 surgical debridement. RESULTS: Hematologic diseases were the most common (52%) underlying diseases. Patients with type 2 diabetes and those with multiple etiologies causing immunosuppression had the lowest survival. Aspergillus and Mucoraceae species were isolated in 9 patients but were not associated with poor prognosis. Headache and nasal discharge or crusting were the most common presenting symptoms. Premaxillary involvement was significantly correlated with poor prognosis (P = .001). Unilateral involvement was correlated with poor prognosis, although this finding was not significant (P = .111). The overall mortality rate was 61.2%. Patients with neutropenia that was corrected had 80% survival (P = .014). Cessation of corticosteroids and regulating blood glucose levels in patients with immunosuppression from corticosteroid use resulted in 75% survival. CONCLUSION: There is no single curative treatment for AIFRS. For a favorable prognosis, underlying conditions must be treated in addition to surgical debridement and antifungals.

[Antifungal medication: new substances, new experiences]. / Antimykotika ­ neue Substanzen, neue Erfahrungen.

The incidence of life threatening invasive fungal infections in patients with hematological malignancies during intensive chemotherapy or after hematopoetic stem cell transplantation, patients after solid organ transplantation, ICU patients and premature infants is rising. Mortality rates of invasive fungal infections, caused by Aspergillus species or mucormycetes, may reach 100%, in spite of considerable progress in diagnosis, antifungal prophylaxis and therapy. Comprehensive, profound knowledge of specific diagnostic and current treatment algorithms is essential to improve the prognosis of patients suffering from systemic fungal infections; this article encompasses recent developments in the field of antifungal treatment.

Global food and fibre security threatened by current inefficiencies in fungal identification.

Fungal pathogens severely impact global food and fibre crop security. Fungal species that cause plant diseases have mostly been recognized based on their morphology. In general, morphological descriptions remain disconnected from crucially important knowledge such as mating types, host specificity, life cycle stages and population structures. The majority of current fungal species descriptions lack even the most basic genetic data that could address at least some of these issues. Such information is essential for accurate fungal identifications, to link critical metadata and to understand the real and potential impact of fungal pathogens on production and natural ecosystems. Because international trade in plant products and introduction of pathogens to new areas is likely to continue, the manner in which fungal pathogens are identified should urgently be reconsidered. The technologies that would provide appropriate information for biosecurity and quarantine already exist, yet the scientific community and the regulatory authorities are slow to embrace them. International agreements are urgently needed to enforce new guidelines for describing plant pathogenic fungi (including key DNA information), to ensure availability of relevant data and to modernize the phytosanitary systems that must deal with the risks relating to trade-associated plant pathogens.This article is part of the themed issue 'Tackling emerging fungal threats to animal health, food security and ecosystem resilience'.

Posaconazole: Use in the Prophylaxis and Treatment of Fungal Infections.

Posaconazole, a fluorinated triazole antifungal drug, is approved by the U.S. Food and Drug Administration (FDA) for (1) prophylaxis against Aspergillus and Candida infections in immunocompromised patients at high risk for these infections and (2) oropharyngeal candidiasis (OPC), including cases refractory to fluconazole and/or itraconazole. The European Medicines Agency (EMA) has approved posaconazole for (1) treatment of aspergillosis, fusariosis, chromoblastomycosis, and coccidioidomycosis in patients who are refractory to or intolerant of other azoles or amphotericin B; (2) first-line therapy for OPC for severe disease or in those unlikely to respond to topical therapy; and (3) prophylaxis of invasive fungal infections in high-risk hematologic patients and stem cell transplant recipients. In addition to approved indications, posaconazole has been used with success as salvage therapy for invasive mold infections and endemic mycoses in patients who are refractory to or intolerant of other antifungal agents, and as prophylaxis or salvage therapy in children, for whom indications are more limited owing to a paucity of data. Posaconazole has potent in vitro activity against a broad range of fungi and molds, including Aspergillus, Candida, Cryptococcus, filamentous fungi, and endemic mycoses including coccidioidomycosis, histoplasmosis, and blastomycosis. Importantly, posaconazole is much more active than other azoles against many Mucorales species and the combination of posaconazole with other antifungal agents may be synergistic. Hence, posaconazole is a potential candidate as a single or combination agent for difficult-to-treat fungal infections. Posaconazole has an excellent safety profile; to date, serious side effects are rare, even with prolonged use. However, newer posaconazole formulations achieve higher blood levels and it remains to be seen whether this may lead to an increase in the rate of adverse effects. Currently, posaconazole is used predominantly for prophylaxis and salvage therapy of fungal infections in adults. Indications for use as initial therapy of fungal infections and for broader use in children will depend on the accrual of additional clinical data.

Voriconazole: How to Use This Antifungal Agent and What to Expect.

Voriconazole is an important agent in the antifungal armamentarium. It is the treatment of choice for invasive aspergillosis, other hyaline molds, and many brown-black molds. It is also effective for infections caused by Candida species, including those that are fluconazole resistant, and for infections caused by the endemic mycoses, including those that occur in the central nervous system. It has the advantage of being available in both an intravenous and an oral formulation that is well absorbed. Drawbacks to the use of voriconazole are that it has unpredictable, nonlinear pharmacokinetics with extensive interpatient and intrapatient variation in serum levels. Some of the adverse effects seen with voriconazole are related to high serum concentrations, and, as a result, therapeutic drug monitoring is essential when using this agent. Drug-drug interactions are common, and possible interactions must be sought before voriconazole is prescribed. With prolonged use, newly described adverse effects, including periostitis, alopecia, and development of skin cancers, have been noted.

Overview of Fungal Infections--The Italian Experience.

The incidence of severe fungal infections has increased worldwide and represents a serious threat, especially among immunocompromised and critically ill patients. Most common pulmonary fungal infections include aspergillosis, cryptococcosis, and Pneumocystis jiroveci pneumonia. Among nosocomial bloodstream infections, Candida spp. is the most common isolated fungus. Mortality rates up to 60% in critically ill patients with Candida infections and 90% in hematological patients with invasive aspergillosis are reported. Furthermore, fungal infections contribute to high morbidity and prolonged hospitalizations. Since standard cultural methods can show low sensitivity or provide delayed responses, new non-culture-dependent methods such as galactomannan ß-D-glucan are now available. Novel antifungal compounds (e.g., amphotericin B lipid formulations, last-generation azoles, and echinocandins) have been introduced in the recent years. Nevertheless, despite new advances the appropriate use of diagnostic assays along with a thorough therapeutic management remain the key to ensure an early appropriate targeted treatment that represents the crucial factor to attain a successful approach to severe fungal infections.

A five-year survey of dematiaceous fungi in a tropical hospital reveals potential opportunistic species.

Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤ 1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance.

[Pulmonary fungal infection in patients with AIDS]. / Infections fongiques pulmonaires chez les patients séropositifs pour le VIH.

Fungal infections are the most common opportunistic infections (OI) occurring during the course of HIV infection, though their incidence has decreased dramatically with the introduction of highly active antiretroviral therapy (cART). Most cases occur in untreated patients, noncompliant patients or patients whose multiple antiretroviral regimens have failed and they are a good marker of the severity of cellular immunodepression. Pneumocystis jiroveci pneumonia is the second most frequent OI in France and cryptococcosis remains a major problem in the Southern Hemisphere. With the increase in travel, imported endemic fungal infection can occur and may mimic other infections, notably tuberculosis. Fungal infections often have a pulmonary presentation but an exhaustive search for dissemination should be made in patients infected with HIV, at least those at an advanced stage of immune deficiency. Introduction of cART in combination with anti-fungal treatment depends on the risk of AIDS progression and on the risk of cumulative toxicity and the immune reconstitution inflammatory syndrome (IRIS) if introduced too early. Fungal infections in HIV infected patients remain a problem in the cART era. IRIS can complicate the management and requires an optimised treatment regime.

Migration and mycoses.

In recent years, the incidence of fungal infections of the skin, one of the most frequent forms of infection, has been steadily increasing in Europe. One of the main factors contributing to this increase is the gradual raise of migratory flows towards Europe. In the last decades Italy has witnessed an ever-increasing growth of the migrant population, and has become, to this day, one of the European countries with the highest number of immigrants. This phenomenon has had significant implications in clinical practice of dermatologic mycology as it is increasingly common to see unusual clinical isolate causal agents absent in our latitudes until a short time ago. This review provides an update on the epidemiology, classification, pathogenesis, clinical manifestations and treatment of the most important dermato-mycosis observed in the immigrant population, through the most typical cases, investigated by microscopic and cultural findings. These diseases continue to expand and are often difficult to detect. The special relationship between host-environment interaction-parasite plays a crucial role as, even more than in other categories, it is widely widespread among the immigrants.

The morbidity and mortality of patients with fungal infections before and during extracorporeal membrane oxygenation support.

OBJECTIVE: To evaluate the prevalence of fungal infections (both pre-cannulation and post-cannulation) while on extracorporeal membrane oxygenation support and the associated morbidity and mortality. DESIGN: Retrospective cohort study. PATIENT AND METHODS: The Extracorporeal Life Support Organization database is an international voluntary registry of clinical data for patients placed on extracorporeal membrane oxygenation. The database was queried for all patients on extracorporeal membrane oxygenation from 1997 to 2009. Patient and extracorporeal membrane oxygenation data collected included age, support type, length of support, infection status and organism code, discharge status, complications, and component failures. Outcomes of interest were mortality, extracorporeal membrane oxygenation-related patient complications, and mechanical component failures. RESULTS: From 1997 to 2009, there were 21,073 patients' extracorporeal membrane oxygenation runs analyzed of which 12,933 were in the neonatal group (0-30 days), 6,073 were in the pediatric group (31 days to <18 yrs old), and 2,067 were in the adult group (≥18 yrs). The prevalence of fungal infection during extracorporeal membrane oxygenation varied by age group and timing of infection and ranged from 0.04% to 5%. Fungal infections pre-extracorporeal membrane oxygenation and on-extracorporeal membrane oxygenation conferred a statistically significant higher relative risk of mortality for all age groups and varied by support type and timing of infection. Extracorporeal membrane oxygenation-related complications and component failures were not statistically significantly affected by infection status. CONCLUSIONS: Fungal infection before or during extracorporeal membrane oxygenation increases the odds of mortality and the magnitude of this effect is dependent upon age-group and timing of infection. This increased mortality was not the result of increased patient or mechanical complications during extracorporeal membrane oxygenation. For patients with fungal infections pre-extracorporeal membrane oxygenation, 82%-89% demonstrated presumed clearance during extracorporeal membrane oxygenation. Although the risk of mortality increased with fungal infections, it does not appear that fungal infection before or during extracorporeal membrane oxygenation is a contraindication to initiation or continuation of support.