International Society For Human And Animal Mycology Research Articles

Revised ISHAM-ABPA working group clinical practice guidelines for diagnosing, classifying and treating allergic bronchopulmonary aspergillosis/mycoses.

The International Society for Human and Animal Mycology (ISHAM) working group proposed recommendations for managing allergic bronchopulmonary aspergillosis (ABPA) a decade ago. There is a need to update these recommendations due to advances in diagnostics and therapeutics. An international expert group was convened to develop guidelines for managing ABPA (caused by Aspergillus spp.) and allergic bronchopulmonary mycosis (ABPM; caused by fungi other than Aspergillus spp.) in adults and children using a modified Delphi method (two online rounds and one in-person meeting). We defined consensus as ≥70% agreement or disagreement. The terms "recommend" and "suggest" are used when the consensus was ≥70% and <70%, respectively. We recommend screening for A. fumigatus sensitisation using fungus-specific IgE in all newly diagnosed asthmatic adults at tertiary care but only difficult-to-treat asthmatic children. We recommend diagnosing ABPA in those with predisposing conditions or compatible clinico-radiological presentation, with a mandatory demonstration of fungal sensitisation and serum total IgE ≥500 IU·mL-1 and two of the following: fungal-specific IgG, peripheral blood eosinophilia or suggestive imaging. ABPM is considered in those with an ABPA-like presentation but normal A. fumigatus-IgE. Additionally, diagnosing ABPM requires repeated growth of the causative fungus from sputum. We do not routinely recommend treating asymptomatic ABPA patients. We recommend oral prednisolone or itraconazole monotherapy for treating acute ABPA (newly diagnosed or exacerbation), with prednisolone and itraconazole combination only for treating recurrent ABPA exacerbations. We have devised an objective multidimensional criterion to assess treatment response. We have framed consensus guidelines for diagnosing, classifying and treating ABPA/M for patient care and research.

Clinical Spectrum of Aspergillosis in Children with Severe Asthma: A Retrospective Observational Study

Introduction: Aspergillus species can affect the respiratory system of genetically predisposed asthma patients. Allergic Broncho-Pulmonary Aspergillosis (ABPA) is one of the manifestations of aspergillosis. Most research on ABPA has been conducted in the adult population, with very few studies including paediatric patients. Aim: To examine the clinical spectrum of aspergillosis in severely asthmatic children aged between 2 and 18 years admitted to the Paediatric Intensive Care Unit (PICU). Materials and Methods: This retrospective observational study was conducted from September 2021 to August 2022. Out of 76 children aged between 2 and 18 years who presented with asthma over one year, 24 children fulfilling the inclusion criteria (severe asthma requiring PICU admission) were included in the study by convenient sampling. Children were diagnosed with ABPA and Severe Asthma with Fungal Sensitisation (SAFS) based on the ISHAM (International Society for Human and Animal Mycology) work group criteria (history of asthma, raised Aspergillus-specific and total Immunoglobulin E (IgE), presence of Aspergillus-specific IgG, eosinophilia, and positive radiological findings). Descriptive statistics elaborated in the form of mean and standard deviation. Results: A total of 24 patients with acute severe asthma were admitted to the PICU over one year. Nearly 60% (15/24) of the patients fulfilled the criteria for subgroup A (comprising poorly controlled asthma, eosinophilia, or positive radiological findings). Among them, six (25%) patients had total serum IgE levels &gt; 1000 IU/mL, three (12.5%) had levels between 500- 1000 IU/mL, and six (25%) had levels &lt;500 IU/mL. Among these patients, 60% (9/15) had elevated Aspergillus-specific IgE and IgG levels. As per the ISHAM work group criteria, 6/24 (25%) patients were diagnosed with S-ABPA (Serological ABPA) and 3/24 (12.5%) patients were diagnosed with SAFS. Conclusion: Aspergillus sensitivity is increasingly being detected in asthmatic children, requiring further work-up, especially in patients with poorly controlled asthma.

618. The current state of laboratory mycology in Asia/Pacific: a survey from the EuropeanConfederation of Medical Mycology (ECMM) and International Society for Human andAnimal Mycology (ISHAM)

Abstract Background Invasive fungal infections (IFI) in Asia/Pacific are a threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for the IFI clinical management and patient survival. Methods The IFI diagnostic capacity survey was online accessible at www.clinicalsurveys.net/uc/IFI_management_capacity/. The survey aimed to collect the following dimensions: a) institution profile, b) perceptions on IFI in the respective institution, c) microscopy, d) culture and fungal identification capacity, e) serology, f) antigen detection, g) molecular tests availability, and h) therapeutic drug monitoring. Results As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half of them were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan (4%, each). Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of them had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% at least one echinocandin. Conclusion Currently, based on the provided replies, the resources available for the IFI diagnosis and management vary in Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings. Disclosures Martin Hoenigl, n/a, Astellas: Grant/Research Support|Euroimmun: Grant/Research Support|F2G: Grant/Research Support|Gilead: Grant/Research Support|Immy: Grant/Research Support|MSD: Grant/Research Support|Mundipharma: Grant/Research Support|Pfizer: Grant/Research Support|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds

A Pathology-based Case Series of Influenza- and COVID-19-associated Pulmonary Aspergillosis: The Proof Is in the Tissue.

Invasive pulmonary aspergillosis has emerged as a frequent coinfection in severe COVID-19, similarly to influenza; yet the clinical invasiveness is more debated. We investigated the invasive nature of pulmonary aspergillosis in histology specimens of influenza and COVID-19 intensive care unit (ICU) fatalities in a tertiary care center. In this monocentric, descriptive, retrospective case series we included adult ICU patients with PCR-proven influenza/COVID-19 respiratory failure that underwent postmortem examination and/or tracheobronchial biopsy during ICU admission from September 2009 until June 2021. Diagnosis of probable/proven viral-associated pulmonary aspergillosis (VAPA) was made based on the ICM-IAPA and ECMM/ISHAM-CAPA consensus criteria. All respiratory tissues were independently reviewed by two experienced pathologists. In the 44 patients of the autopsy-verified cohort, 6 proven influenza-associated and 6 proven COVID-19-associated pulmonary aspergillosis diagnoses were identified. Fungal disease was identified as missed-diagnosis upon autopsy in 8% of proven cases (n=1/12), yet most frequently found as confirmation of probable antemortem diagnosis (n=11/21, 52%) despite receiving antifungal treatment. Bronchoalveolar lavage galactomannan testing showed highest sensitivity for VAPA diagnosis. Among both viral entities, an impeded fungal growth was the predominant histologic pattern of pulmonary aspergillosis. Fungal tracheobronchitis was histologically indistinguishable in influenza (n=3) and COVID-19 (n=3) cases, yet macroscopically more extensive at bronchoscopy in influenza setting. Proven invasive pulmonary aspergillosis diagnosis was found regularly and with a similar histological pattern in influenza and in COVID-19 ICU case-fatalities. Our findings highlight an important need for VAPA awareness with an emphasis on mycological bronchoscopic work-up. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).

Invasive Pulmonary Aspergillosis in Patients with and without SARS-CoV-2 Infection

The recent European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) 2020 consensus classification proposes criteria to define coronavirus 2019 (COVID-19)-associated invasive pulmonary aspergillosis (CAPA), including mycological evidence obtained via non-bronchoscopic lavage. Given the low specificity of radiological findings in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, this criterion makes it difficult to differentiate between invasive pulmonary aspergillosis (IPA) and colonization. This unicenter and retrospective study includes 240 patients with isolates of any Aspergillus species in any respiratory samples during a 20-month study (140 IPA and 100 colonization). Mortality was high in the IPA and colonization groups (37.1% and 34.0%, respectively; p = 0.61), especially in patients with SARS-CoV-2 infection, where mortality was higher in colonized patients (40.7% vs. 66.6.%; p: 0.021). Multivariate analysis confirmed the following variables to be independently associated with increased mortality: age > 65 years, acute or chronic renal failure at diagnosis, thrombocytopenia (<100,000 platelets/µL) at admission, inotrope requirement, and SARS-CoV-2 infection, but not the presence of IPA. This series shows that the isolation of Aspergillus spp. in respiratory samples, whether associated with disease criteria or not, is associated with high mortality, especially in patients with SARS-CoV-2 infection, and suggests an early initiation of treatment given its high mortality rate.

The current state of laboratory mycology in Asia/Pacific: A survey from the European Confederation of Medical Mycology (ECMM) and International Society for Human and Animal Mycology (ISHAM)

Introduction: Invasive fungal infections (IFIs) in Asia/Pacific are a particular threat to patients with malignancies, uncontrolled diabetes mellitus or undiagnosed/untreated human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS). Adequate and early access to diagnostic tools and antifungals is essential for IFI clinical management and patient survival.Methods: Details on institution profile, self-perception on IFI, and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring for IFI were collected in a survey.Results: As of June 2022, 235 centres from 40 countries/territories in Asia/Pacific answered the questionnaire. More than half the centres were from six countries: India (25%), China (17%), Thailand (5%), Indonesia, Iran, and Japan (4% each). Candida spp. (93%) and Aspergillus spp. (75%) were considered the most relevant pathogens. Most institutions had access to microscopy (98%) or culture-based approaches (97%). Furthermore, 79% of centres had access to antigen detection, 66% to molecular assays, and 63% to antibody tests. Access to antifungals varied between countries/territories. At least one triazole was available in 93% of the reporting sites (voriconazole [89%] was the most common mould-active azole), whereas 80% had at least one amphotericin B formulation, and 72% had at least one echinocandin.Conclusion: According to the replies provided, the resources available for IFI diagnosis and management vary among Asia/Pacific countries/territories. Economical or geographical factors may play a key role in the incidence and clinical handling of this disease burden. Regional cooperation may be a good strategy to overcome shortcomings.

Genotypic Diversity and Antifungal Susceptibility of Clinical Isolates of Cryptococcus Gattii Species Complex from Argentina.

The aim of this study was to determine the genotypic diversity of 22 Cryptococcus gattii species complex clinical isolates from Argentina and to place these genotypes within the diversity of clinical, veterinary and environmental isolates from Latin America. Mating type and antifungal susceptibility of the isolates were also determined. By URA5-RFLP, nine isolates were identified as molecular type VGI, 10 as VGII, one as VGIII and two as VGIV. Multilocus sequence typing (MSLT), following the International Society for Human and Animal Mycology (ISHAM) consensus MLST scheme, was used to determine the genotypic diversity. Our results suggest that, in Argentina, VGI isolates have low genetic diversity, while VGII isolates have high genetic diversity. Both isolates identified as VGIV by URA5-RFLP were genotyped by MLST as belonging to the currently named VGVI clade. From all isolates, eight sequence types (STs) were unique for Argentina, while five STs have been reported already in other countries, being of high interest the genotypes ST20 and ST7 since they belong to the subtypes VGIIa and VGIIb, respectively, which are associated with hypervirulent strains responsible for outbreaks in North America. To note, geographical analysis showed that some genotypes may be associated with some regions in Argentina. Most isolates were MATα, but we are reporting one isolate MATa for the first time in the country. Antifungal susceptibility tests showed that itraconazole, voriconazole and posaconazole had high activity against all isolates, while amphotericin B, fluconazole and 5-fluorocytosine were the least active drugs against all studied isolates.

Proportion of Allergic Bronchopulmonary Aspergillosis Presenting as Difficult-to-control Asthma in Patients Attending a Tertiary Care Centre using the Modified ISHAM Criteria: A Cross-sectional Study

Introduction: Difficult-to-control asthmatics, as defined by the Global Initiative for Management of Asthma (GINA), belong to a subset of patients whose symptoms remain uncontrolled despite adhering to maximal optimised therapy. Complex hypersensitivity reactions in response to airway colonization with Aspergillus fumigatus, which occurs in patients with asthma or cystic fibrosis, are established factors for a poor response to treatment and frequent exacerbations. Only limited data related to Allergic Bronchopulmonary Aspergillosis (ABPA) is available from India, particularly from Kerala. Aim: To assess the occurrence of ABPA in patients with difficultto-control asthma using the modified ISHAM criteria. Materials and Methods: This cross-sectional analysis was conducted in the Department of Pulmonary Medicine, Institute of Chest Diseases, Government Medical College, Kozhikode, Kerala, India from February 2019 to July 2020. The study population comprised asthmatics attending the Pulmonary Medicine Outpatient Services who were on regular medications, including optimal doses of inhaled corticosteroid and longacting beta-agonist combinations. Patients with two or more exacerbations per year requiring systemic steroids for symptom control and a positive skin test for Aspergillus fumigatus antigen were further analysed using the modified International Society for Human and Animal Mycology (IHAM) criteria to determine the proportion of difficult-to-control asthmatics with ABPA. A total of 185 subjects were enrolled. Twelve patients opted out of the study, and the remaining 173 patients were screened using the modified ISHAM criteria. Statistical analysis was performed using Stastistical Packages of Social Sciences (SPSS) software version 21.0. Continuous parameters were expressed as mean and median, while categorical parameters were measured as frequency and percentages. Results: It was observed that 104 (60.1%) patients belonged to the age group between 41-60 years, while approximately 60 patients (34.7%) were below 40 years of age. Among the 173 patients, 86 (49.7%) tested positive for Aspergillus fumigatus antigen. Applying the ISHAM criteria, it was found that only 17 (9.8%) of these patients satisfied the criteria for co-existent ABPA. A total of 101 patients (58.4%) required at least one hospital admission, while 4 (2.3%) patients required more than three hospital admissions per year. Total 21 (12.1%) patients had IgE specific to Aspergillus fumigatus, while total IgE levels were elevated in 46 (26.6%) cases. Thirty-six cases (20.8%) had a high peripheral eosinophil count. Conclusion: This study suggests the possibility of the treating physician overlooking 10% of asthmatics in this region who are being managed as difficult-to-control asthma, but who have co-existent ABPA. This subset should be identified early in the course and managed separately for better treatment response.

The adequacy of current diagnostic criteria for making a diagnosis of ABPA.

Currently, there are four different diagnostic criteria systems for allergic bronchopulmonary aspergillosis (ABPA): The Rosenberg-Patterson, Seropositive ABPA (ABPA-S), Central Bronchiectasis and ABPA (ABPA-CB), and the International Society for Human and Animal Mycology (ISHAM) ABPA study group criteria. This study aims to retrospectively compare these four diagnostic criteria in ABPA patients. Patients who were followed up with the diagnosis of ABPA were retrospectively re-evaluated using these four diagnostic criteria, and the superiority of these criteria to each other was determined. A total of 10 ABPA patients were included in the study. Seven patients were diagnosed according to ISHAM ABPA study group diagnostic criteria and six patients according to the Rosenberg-Patterson diagnostic criteria. None of the patients fulfilled the criteria when evaluated individually with ABPA-S and ABPA-CB. Of patients diagnosed by ISHAM, five had a total IgE level above 1000 IU/mL and two had below 1000 IU/mL. We demonstrated that the diagnostic criteria developed by the ISHAM ABPA study group were superior to the others in diagnosing ABPA in cases with a total IgE level above 1000 IU/mL. However, all these criteria seem to be sufficient to diagnose ABPA in patients with a total IgE below 1000 IU/mL. We believe the necessity to demonstrate presence of Aspergillus fumigatus precipitating antibodies or specific IgG positivity should be questioned particularly in patients with radiologic findings compatible with ABPA and a total IgE level below 1000 IU/mL.

Evaluation of Simpler Criteria for Diagnosing Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

BackgroundThe modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown.ObjectiveTo evaluate the performance of several simplified criteria for diagnosing ABPA.MethodsWe compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and <5%, respectively, on an MDT evaluation.ResultsWe analyzed data from 543 asthmatic subjects (58.8% women; mean age, 36.8 years). Using LCA, the sensitivity of the A.fumigatus-specific IgE-based criteria ranged from 92-99%, while the specificity varied between 92% and 100%. The MDT diagnosed ABPA in 106 (19.5%) subjects. Using MDT as the reference standard, the correct classification and false-negative rates were >95% for three of the seven and <5% for four of the seven newer criteria.ConclusionsWe found several of the newly developed criteria to perform, like the modified ISHAM-AWG criteria, for diagnosing ABPA complicating asthma. A prospective study in current clinical algorithms is required for validating our observations.

Multi-locus sequence typing reveals genotypic similarity in Nigerian Cryptococcus neoformans AFLP1/VNI of environmental and clinical origin.

IntroductionPigeon droppings are among the major environmental sources of Cryptococcus neoformans AFLP1/VNI, from where the organism infects susceptible humans and animals resulting in cryptococcosis. Until now, C. neoformans AFLP1B/VNII was the only molecular type reported in Nigeria. Effective clinical treatment of this infection has occasionally been stymied by the emergence of antifungal non-susceptible, and resistant strains of C. neoformans AFLP1/VNI.Hypothesis/Gap StatementPigeon droppings harbour C. neoformans and HIV/AIDS patients are among the susceptible population to develop cryptococcal infection. Epidemiological data on cryptococcal prevalence is limited in Nigeria.AimTo investigate the environmental prevalence of C. neoformans in South-eastern Nigeria and compare the isolates with other lineages by using molecular and microbiological tools.MethodologyA total of 500 pigeon droppings and 300 blood samples of HIV/AIDS patients were collected, respectively, from five market squares and three tertiary healthcare centres within the Nsukka area of South-eastern Nigeria. The antifungal susceptibility of the C. neoformans isolates to amphotericin B, fluconazole, 5-fluorocytosine, itraconazole, voriconazole, posaconazole, and isavuconazole was investigated based on the CLSI M27-A3 protocol. Yeasts were identified by MALDI-TOF MS, thereafter Cryptococcus MLST was performed according to the International Society for Human and Animal Mycology (ISHAM) consensus scheme.Results C. neoformans was recovered from 6 (1.2 %) pigeon droppings and 6 (2 %) blood cultures of HIV/AIDS patients. Molecular analyses indicated that all cryptococcal isolates belong to serotype A and the AFLP1/VNI molecular type with sequence type (ST)32. Infection with C. neoformans was independent of sex and age of the patients investigated. All C. neoformans isolates were susceptible to the seven antifungal agents.ConclusionThis is the first report on the prevalence of C. neoformans AFLP1/VNI (ST32) in environmental and clinical samples from Nigeria. The antifungal susceptibility indicates that antifungal resistance by C. neoformans is yet a rare occurrence in Nigeria.

ECMM/ISHAM recommendations for clinical management of COVID-19 associated mucormycosis in low- and middle-income countries.

Reports are increasing on the emergence of COVID‐19–associated mucormycosis (CAM) globally, driven particularly by low‐ and middle‐income countries. The recent unprecedented surge of CAM in India has drawn worldwide attention. More than 28,252 mucormycosis cases are counted and India is the first country where mucormycosis has been declared a notifiable disease. However, misconception of management, diagnosing and treating this infection continue to occur. Thus, European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology (ISHAM) felt the need to address clinical management of CAM in low‐ and middle‐income countries. This article provides a comprehensive document to help clinicians in managing this infection. Uncontrolled diabetes mellitus and inappropriate (high dose or not indicated) corticosteroid use are the major predisposing factors for this surge. High counts of Mucorales spores in both the indoor and outdoor environments, and the immunosuppressive impact of COVID‐19 patients as well as immunotherapy are possible additional factors. Furthermore, a hyperglycaemic state leads to an increased expression of glucose regulated protein (GRP‐ 78) in endothelial cells that may help the entry of Mucorales into tissues. Rhino‐orbital mucormycosis is the most common presentation followed by pulmonary mucormycosis. Recommendations are focused on the early suspicion of the disease and confirmation of diagnosis. Regarding management, glycaemic control, elimination of corticosteroid therapy, extensive surgical debridement and antifungal therapy are the standards for proper care. Due to limited availability of amphotericin B formulations during the present epidemic, alternative antifungal therapies are also discussed.

The Current State of Laboratory Fungal Diagnostics and Availability of Antifungal Treatment in Africa: A ECMM and ISHAM Survey

Background: Africa is a favourable environment for fungal infections, given the high burden of risk factors. The diversity of clinical manifestations of fungal diseases represent a diagnostic and therapeutic challenge, especially in low- and middle-income countries. Studies assessing the current state of mycological laboratory capacities and antifungal treatment availability on the African continent are lacking. Methods: An online survey was developed asking about antifungal drug availability and laboratory infrastructure. The survey was directly sent to 164 African members and contacts of International Society for Human and Animal Mycology (ISHAM) and the European Confederation of Medical Mycology (ECMM), two of the leading societies in the mycology field, in 2019-2020. Institutions were classified whether they were able to potentially achieve Blue status, which is the entry level of the ECMM Excellence Centres initiative. Results: We have received 40 responses (24.4% response rate) from 21 African countries. Only five institutions (12·5%) located in Cameroon, Kenya, Nigeria, Sudan, and Uganda potentially fulfil the minimum laboratory requirements for ECMM Excellent Centres Blue status. Difficulties included lack of access to susceptibility testing for both yeasts and moulds (available in 30% of institutions), and Aspergillus antigen detection (available in 47.5% of institutions as in- house or outsourced test), whilst institutions reported higher availability of cryptococcosis diagnostic tools (60·0% antigen detection and 77·5% India Ink). Whilst fluconazole was available in 90% of institutions, access to mould-active antifungal drugs such as amphotericin B deoxycholate, itraconazole, voriconazole and posaconazole (available for 52·5%, 52·5%, 35·0% and 5.0% of institutions, respectively) was more limited. Interpretation: The region has huge gaps in diagnostic and treatment access. United and targeted efforts are mandatory to face the growing challenges in medical mycology and to further improve diagnostic and treatment resources across Africa. Funding: None to declare. Declaration of Interest: In the last 5 years, DF has received payment for research grants, lectures, advisory boards, and/or travel reimbursements, not related to this study, from Pfizer, GSK, Gilead, MSD and United Medical. AA received honoraria from Pfizer and Gilead and travel grant from Astellas, not related to this study. JS has received research grants by the Ministry of Education and Research (BMBF) and Basilea Pharmaceuticals Inc. and has received travel grants by German Society for Infectious Diseases (DGI e.V.) and Meta-Alexander Foundation, not related to this study. JG has received funds for participating at educational activities organized on behalf of Astellas, Gilead, MSD, Scynexis, and Biotoscana-United Medical; he has also received research funds from FIS, Gilead, Scynexis, and Cidara, outside the submitted work. JFM received grants from F2G and Pulmozyme. He has been a consultant to Scynexis and Merck and has received speaker’s fees from United Medical, TEVA and Gilead. NPG has current research grants from the National Institutes of Health, Centers for Disease Control and Prevention, Bill and Melinda Gates Foundation and the UK Medical Research Council, not related to this study. ROO has received payment for research grants, lectures, advisory boards, and/or travel reimbursements, not related to this study, from Pfizer and Gilead. BKO has received research funds from FIT, UK not related to this work and funds to organize a symposium from IMMY. COM has received research grants from, presented for and been on advisory boards for Pfizer (Australia), Gilead Sciences and Merck, Sharp and Dohme, not related to this study. All funds are paid directly to her institution. ACP has received research grants, given paid talks and consulted for Pfizer, Gilead, MSD, United Medical, Teva, and IMMY, not related to this study.

Guideline for the management of feline sporotrichosis caused by Sporothrix brasiliensis and literature revision.

We herein present a Brazilian guideline for the management of feline sporotrichosis, a mycosis caused by Sporothrix brasiliensis. This guideline is an effort of a national technical group organized by the Working Group on Sporothrix and Sporotrichosis of the International Society for Human and Animal Mycology (ISHAM). This publication intends to provide information on clinical-epidemiological aspects of this zoonosis, as well as a literature revision. Moreover, it gives some practical information on diagnosis and treatment of feline sporotrichosis. It also contains information that can be helpful for the prevention and control of S. brasiliensis transmission.

New clinical diagnostic criteria for allergic bronchopulmonary aspergillosis/mycosis and its validation

There are several clinical diagnostic criteria for allergic bronchopulmonary aspergillosis (ABPA). However, these criteria have not been validated in detail, and no criteria for allergic bronchopulmonary mycosis (ABPM) are currently available. This study proposes new diagnostic criteria for ABPA/ABPM, consisting of 10 components, and compares its sensitivity and specificity to existing methods. Rosenberg-Patterson criteria proposed in 1977, the International Society for Human and Animal Mycology (ISHAM) criteria proposed in 2013, and this new criteria were applied to 79 cases with pathological ABPM and the control population with allergic mucin in the absence of fungal hyphae (n= 37), chronic eosinophilic pneumonia (n= 64), Aspergillus-sensitized severe asthma (n= 26), or chronic pulmonary aspergillosis (n= 24). These criteria were also applied to the 179 cases with physician-diagnosed ABPA/ABPM in a nationwide Japanese survey. The sensitivity for pathological ABPM with Rosenberg-Patterson criteria, ISHAM criteria, and this new criteria were 25.3%, 77.2%, and 96.2%, respectively. The sensitivity for physician-diagnosed ABPA/ABPM were 49.2%, 82.7%, and 94.4%, respectively. The areas under the curve for the receiver-operating characteristic curves were 0.85, 0.90, and 0.98, respectively. The sensitivity for ABPM cases that were culture-positive for non-Aspergillus fungi were 13.0%, 47.8%, and 91.3%, respectively. The new diagnostic criteria, compared with existing criteria, showed better sensitivity and specificity for diagnosing ABPA/ABPM.

Which Are the Optimal Criteria for the Diagnosis of Allergic Bronchopulmonary Aspergillosis? A Latent Class Analysis

The ideal criteria for diagnosing allergic bronchopulmonary aspergillosis (ABPA) remain unknown because of the lack of a criterion standard. Latent class analysis using a probabilistic modeling technique can circumvent the need for a reference standard. To compare the diagnostic performance of various criteria used for evaluating ABPA. We prospectively enrolled consecutive cases of bronchial asthma and performed a series of investigations used for the diagnosis of ABPA. We used latent class analysis to analyze the performance of various existing and novel diagnostic criteria. Of the 543 subjects (mean age, 37 years; 319 women), 338 (62.2%) and 205 (37.8%) were labeled as "mild-to-moderate" and "severe" asthma cases, respectively. The subjects with severe asthma had a longer duration of asthma and a higher number of exacerbations in the previous year. The prevalence of Aspergillus fumigatus sensitization was 41% and 30%, using the A fumigatus-specific IgE and skin test, respectively. The prevalence of ABPA was 16%, using both the Rosenberg-Patterson and the International Society for Human and Animal Mycology (ISHAM)-ABPA Working Group criteria. The ISHAM criteria were slightly more sensitive (89% vs 81%) and specific (99% vs 98%) than the Patterson criteria. We obtained optimal diagnostic performance by altering the existing ISHAM criteria (serum total IgE >500 international units/mL, excluding the skin test, and using computed tomography of thorax instead of chest radiograph). The ISHAM-ABPA Working Group criteria were only marginally better than the Patterson criteria in diagnosing ABPA among patients with asthma younger than 66 years. The diagnostic performance however improved by modifying the prevailing ISHAM criteria, but with increased cost.

International Society for Human and Animal Mycology (ISHAM)-New Initiatives.

Fungal infections have emerged as major threat to human beings. The world is not ready to face this formidable challenge due to limited awareness, insufficient laboratories, and difficulty in managing mycoses especially in developing countries. The International Society for Human and Animal Mycology (ISHAM) has undertaken several new initiatives to overcome these gaps, including a global outreach program with national affiliated mycology societies and other regional groups. ISHAM is working closely with the European Confederation of Medical Mycology (ECMM) and Global Action Fund for Fungal Infections (GAFFI) to enhance these efforts. The society has launched laboratory e-courses and is in the process of the development of clinical e-courses. ISHAM has partnered with regional conferences in South America and Asia by sponsoring international experts and young delegates. The society also supports young people from less developed countries to undergo training in laboratories of excellence. ISHAM facilitated the formation of the INFOCUS-Latin American Clinical Mycology Working Group (LATAM) and the Pan-African Mycology Working Group. The society appointed country ambassadors to facilitate coordination with national societies. Still, the task is enormous and ISHAM calls for strong advocacy and more coordinated activities to attract the attention of people from all disciplines to this neglected field.

Indoor Dust as a Source of Virulent Strains of the Agents of Cryptococcosis in the Rio Negro Micro-Region of the Brazilian Amazon.

Cryptococcosis, a potentially fatal mycosis in humans, is acquired via exposure to exogenous environmental sources. This study aimed to investigate the frequency, genetic diversity, and virulence of cryptococcal strains isolated from indoor dust in the Rio Negro micro-region of the Brazilian Amazon. A total of 8.9% of the studied houses were positive, recovering nine Cryptococcus neoformans VNI and 16 C. gattii VGII isolates, revealing an endemic pattern in domestic microenvironments. The International Society for Human and Animal Mycology (ISHAM) consensus multilocus sequence typing (MLST) scheme for the C. neoformans/C. gattii species complexes identified two sequence types (STs), ST93 and ST5, amongst C. neoformans isolates and six STs amongst C. gattii isolates, including the Vancouver Island Outbreak ST7 (VGIIa) and ST20 (VGIIb), the Australian ST5, and ST264, ST268 and ST445, being unique to the studied region. Virulence studies in the Galleria mellonella model showed that five C. gattii strains and one C. neoformans strain showed a similar pathogenic potential to the highly virulent Vancouver Island outbreak strain CDR265 (VGIIa). The findings of this study indicate that humans can be exposed to the agents of cryptococcosis via house dust, forming the basis for future studies to analyze the impact of early and continuous exposure to indoor dust on the development of subclinical or clinical infections.

Editorial

In this issue, guidelines on two more very important conditions in veterinary dermatology are published. These documents adopt the same successful format developed and sponsored by the World Association for Veterinary Dermatology (WAVD) as used for the guidelines on infections caused by meticillin-resistant staphylococci, and on dermatophytosis of small animals that were published in Veterinary Dermatology volume 28, issue three of June 2017.1 The new guidelines deal with the diagnosis and treatment of demodicosis in dogs and cats, chaired by Ralf Mueller, and the biology, diagnosis and treatment of Malassezia dermatitis in dogs and cats, chaired by Ross Bond. They have already been presented in draft form at the North American Veterinary Dermatology Forum in Maui, Hawaii, and at the ESVD-ECVD Congress in Dubrovnik, Croatia, in 2018. The Malassezia guidelines were also presented at the Malassezia workshop of the International Society for Human and Animal Mycology (ISHAM) in Utrecht, the Netherlands in 2018. The guidelines comprehensively review the literature relating to these diseases, focusing on clinical signs, diagnosis and treatment, and they concisely summarise the consensus recommendations providing easy access to this essential information at the beginning of each text. Importantly, they also identify areas where lack of knowledge makes treatment and prevention of these conditions more difficult and where further research is needed. The Malassezia guidelines provide, in addition, a detailed review of the biology of this genus and illustrate the emerging knowledge that has led to the development of its taxonomy and the identification of multiple species of the organism. This examination of historical aspects of Malassezia yeasts as skin pathogens illustrates the way in which World War I and World War II retarded knowledge of the organism and its diseases both in animals and in man. The demodicosis guidelines also touch on sociological factors when they describe how the use of the isoxazoline drug, fluralaner, could be used to allow breeding of healthy puppies from bitches that are susceptible to generalised demodicosis and would otherwise have offspring likely to develop this disease. However, the authors warn against the temptation to adopt this approach as it would be likely to further increase susceptible canine populations. The importance of sociological factors in the management of disease both in animals and in man was a feature examined by Tony Barnett in an editorial accompanying the first set of WAVD guidelines.2 He reminded us that preparation of guidelines and their adoption depend not only on scientific knowledge and the approach taken by clinicians but also on attitudes towards the diseases and their control amongst dog breeders and owners. Such attitudes influence the demand for fashionable breeds, possibly promoting the breeding of dogs with increased susceptibility to diseases such as Malassezia dermatitis and demodicosis. We still need to find ways of informing potential owners about such issues and enabling them to understand the suffering and difficulties of management which are imposed on such animals. The WAVD has a continuing programme of guideline preparation aimed at promoting best practice in veterinary dermatology. Two more guidelines are currently reaching the final stages. They will deal with equine hypersensitivity, chaired by Rosanna Marsella, and best clinical practices in otitis of dogs and cats, chaired by Jim Noxon and will be presented at the 9th World Congress of Veterinary Dermatology in Sydney, Australia, in October 2020. All of the WAVD guidelines are to be published in Veterinary Dermatology with open access or free access so as to maximise their availability to and use by veterinary practitioners, both specialists and those in general practice, and also to research workers.

Bridging the knowledge gap on mycoses in Africa: Setting up a Pan-African Mycology Working Group.

Most African countries have poorly funded and overburdened health systems. Additionally, a high prevalence of HIV in Sub-Saharan Africa contributes to a high burden of opportunistic fungal infections. Data generated by GAFFI from 15 of 57 African countries revealed that an estimated 47 million Africans suffer from fungal diseases, of whom an estimated 1.7 million suffer from a serious fungal infection annually. Almost all African countries lack a surveillance system for fungal infections with the exception of South Africa. South Africa is also the only African country with a national mycology reference laboratory. Across the continent, there is a pervasive picture of inadequate/poor diagnostic capacity, low level of awareness among healthcare workers and policymakers and unavailability and non-accessibility to essential antifungal medications. Recent outreach efforts by the International Society for Human and Animal Mycology (ISHAM) and the European Confederation of Medical Mycology (ECMM) have aimed to increase involvement of African countries and experts in global initiatives such as "One World One Guideline" and also the ECMM Academy. Recently, under the auspices of ISHAM, the African sub-region created a network of mycology experts whose goal is to organise and engage African leaders in the field of medical mycology. The aim of this ISHAM Working Group was to facilitate interaction and synergy among regional leaders in order to develop educational programmes for capacity building to aid in the diagnosis and care of patients with fungal infections in Africa. The working group will also encourage country initiatives to develop clinical guidelines, to support surveys and to support the establishment of reference mycology laboratories.