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We retrospectively reviewed consecutive cases of mucormycosis reported from a tertiary-care center in India to determine the clinical and mycologic characteristics of emerging Rhizopus homothallicus fungus. The objectives were ascertaining the proportion of R. homothallicus infection and the 30-day mortality rate in rhino-orbital mucormycosis attributable to R. homothallicus compared with R. arrhizus. R. homothallicus accounted for 43 (6.8%) of the 631 cases of mucormycosis. R. homothallicus infection was independently associated with better survival (odds ratio [OR] 0.08 [95% CI 0.02–0.36]; p = 0.001) than for R. arrhizus infection (4/41 [9.8%] vs. 104/266 [39.1%]) after adjusting for age, intracranial involvement, and surgery. We also performed antifungal-susceptibility testing, which indicated a low range of MICs for R. homothallicus against the commonly used antifungals (amphotericin B [0.03–16], itraconazole [0.03–16], posaconazole [0.03–8], and isavuconazole [0.03–16]). 18S gene sequencing and amplified length polymorphism analysis revealed distinct clustering of R. homothallicus.

Abstract Objective: We aimed to assess risk of COVID-19 infection & seroprotection status in healthcare workers (HCWs) in both hospital and community settings following an intensive vaccination drive in India. Setting: Tertiary Care Hospital Methods: We surveyed COVID-19 exposure risk, personal protective equipment (PPE) compliance, vaccination status, mental health & COVID-19 infection rate across different HCW cadres. Elecsys® test for COVID-19 spike (Anti-SARS-CoV-2S; ACOVs) and nucleocapsid (Anti-SARS-CoV-2; ACOV) responses following vaccination and/or COVID-19 infection were measured in a stratified sample of 386 HCW. Results: We enrolled 945 HCWs (60.6% male, age 35.9 ± 9.8 years, 352 nurses, 211 doctors, 248 paramedics & 134 support staff). Hospital PPE compliance was 90.8%. Vaccination coverage was 891/945 (94.3%). ACOVs neutralizing antibody was reactive in 381/386 (98.7%). ACOVs titer (U/ml) was higher in the post-COVID-19 infection group (N =269; 242.1 ± 35.7 U/ml) than in the post-vaccine or never infected subgroup (N = 115, 204.1 ± 81.3 U/ml). RT PCR + COVID-19 infections were documented in 224/945 (23.7%) and 6 HCWs had disease of moderate severity, with no deaths. However, 232/386 (60.1%) of HCWs tested positive for nucleocapsid ACOV antibody, suggesting undocumented or subclinical COVID-19 infection. On multivariate logistic regression, only female gender [aOR 1.79, 95% CI 1.07–3.0, P = .025] and COVID-19 family contact [aOR 5.1, 95% CI 3.84–9.5, P < .001] were predictors of risk of developing COVID-19 infection, independent of association with patient-related exposure. Conclusion: Our HCWs were PPE compliant and vaccine motivated, with immunization coverage of 94.3% and seroprotection rate of 98.7%. There was no relationship between HCW COVID-19 infection to exposure characteristics in the hospital. Vaccination reduced disease severity and prevented death in HCW.

Introdução: As Infecções Fúngicas Invasivas (IFIs) na região da Ásia e do Pacífico são uma ameaça para pacientes com doenças malignas, diabetes mellitus não controlada ou infecção pelo vírus da imunodeficiência humana não diagnosticada/não tratada e Síndrome da Imunodeficiência Adquirida (HIV/AIDS). O acesso adequado e precoce a ferramentas de diagnóstico e antifúngicos é essencial para o manejo clínico das IFIs e a sobrevivência desses pacientes. Métodos: A pesquisa sobre a capacidade de diagnóstico de IFIs foi realizada online e pode ser acessada em www.clinicalsurveys.net/uc/IFI_management_capacity/. O objetivo da pesquisa foi coletar os seguintes dados: perfil da instituição, percepções sobre a IFIs na respectiva instituição, dados de diagnóstico microbiológico ‒ exame micológico direto, cultura e identificação de fungos, de agentes etiológicos, dados de diagnóstico não-microbiológicos ‒ sorologia, detecção de antígenos e disponibilidade de testes moleculares e a disponibilidade local de drogas antifúngicas. Resultados: Um total de 235 centros de 40 países/territórios da Ásia/Pacífico respondeu ao questionário. Mais da metade deles pertencia a seis países: Índia (25%), China (17%), Tailândia (5%), Indonésia, Irã e Japão (4%). Candida spp. (93%) e Aspergillus spp. (75%) foram considerados os patógenos mais relevantes relacionados às IFIs. A maioria das instituições tinha acesso a microscopia (98%) ou ao diagnóstico por cultura (97%). Além disso, 79% delas tinham acesso à detecção de antígenos, 66% testes moleculares e 63% a testes de anticorpos. O acesso a antifúngicos variou entre os países/territórios. Pelo menos um triazólico estava disponível em 93% dos locais estudados, sendo voriconazol, o triazólico mais frequentemente utilizado (89%), enquanto 80% tinham pelo menos uma formulação de anfotericina B disponível e 72% pelo menos uma equinocandina. Conclusões: Atualmente, com base nas respostas fornecidas, os recursos disponíveis para o diagnóstico e o tratamento da IFI variam nos países/territórios da Ásia/Pacífico. Fatores econômicos ou geográficos podem desempenhar um papel fundamental na incidência e no tratamento clínico das IFIs em países da região Ásia/Pacífico. A cooperação regional pode ser uma boa estratégia para superar as deficiências.

We performed a case–control study across 25 hospitals in India for the period of January–June 2021 to evaluate the reasons for an COVID-19–associated mucormycosis (CAM) outbreak. We investigated whether COVID-19 treatment practices (glucocorticoids, zinc, tocilizumab, and others) were associated with CAM. We included 1,733 cases of CAM and 3,911 age-matched COVID-19 controls. We found cumulative glucocorticoid dose (odds ratio [OR] 1.006, 95% CI 1.004–1.007) and zinc supplementation (OR 2.76, 95% CI 2.24–3.40), along with elevated C-reactive protein (OR 1.004, 95% CI 1.002–1.006), host factors (renal transplantation [OR 7.58, 95% CI 3.31–17.40], diabetes mellitus [OR 6.72, 95% CI 5.45–8.28], diabetic ketoacidosis during COVID-19 [OR 4.41, 95% CI 2.03–9.60]), and rural residence (OR 2.88, 95% CI 2.12–3.79), significantly associated with CAM. Mortality rate at 12 weeks was 32.2% (473/1,471). We emphasize the judicious use of COVID-19 therapies and optimal glycemic control to prevent CAM.

Background: Interferon-gamma (IFN-γ) down-regulates plasma procalcitonin (PCT), marker of inflammation. Chronic pulmonary aspergillosis (CPA) is associated with low IFN-γ levels. Thus, plasma PCT may be elevated in CPA and could have a role in diagnosing and monitoring treatment response in CPA. Herein, we investigate the diagnostic performance of plasma PCT in CPA. Methods: We extracted the demographic, clinical, radiological, treatment outcomes, and plasma PCT levels of CPA subjects and controls (previously treated pulmonary tuberculosis with radiological abnormalities on CT chest [diseased controls] and treatment naïve active pulmonary tuberculosis [PTB]). We treated CPA subjects with six months of oral itraconazole. We took 0.25 ng/mL as a cut-off value for PCT. The study’s primary objective was to ascertain the diagnostic performance of PCT in diagnosing CPA. The key secondary outcome was to study the change in the plasma PCT levels after itraconazole therapy. Results: We included 190 CPA cases and 40 controls (diseased controls [n = 20] and active PTB [n = 20]). PCT was elevated (≥0.25 ng/mL) in only 7 (3.7%) subjects with CPA. The sensitivity and specificity of PCT (≥0.25 ng/mL) were 3.7% (1.5–7.4%) and 100 (91.2–100%), respectively. The area under the curve for plasma PCT was 0.48 (95% confidence interval, 0.39–0.58). The plasma PCT values were available in 93 subjects at six months. There was a significant decline in the median plasma levels of PCT after treatment; however, the PCT levels either increased or remained the same in 45% of the subjects. Conclusion: Plasma procalcitonin has poor performance in diagnosing and following subjects with CPA.

Candida vulturna is a newly emerging candida species belong to Candida haemulonii species complex of Metschnikowiaceae family. Numerous clinical samples have been reported to isolate C. vulturna since discovery. We report a case of catheter related blood stream infection in which C. vulturna was isolated from blood in patient after prolong antibiotic therapy for recurrent infection of retroperitoneal cyst. The blood isolate was identified to species level by molecular assay targeting D1/D2 regions of 26s rDNA gene. The patient improved with administration of intravenous micafungin despite lack of antifungal susceptibility breakpoints.

ABSTRACT Candida auris exhibits resistance to multiple antifungal drug classes and sterilization agents, posing threats to the immunocompromised worldwide. Among the four major geographical clades, the East Asian clade 2 isolates of C. auris are mostly drug susceptible. In this study, we experimentally evolved one such drug-susceptible isolate for multiple generations in the presence of the antifungal compound fluconazole and analyzed changes in the karyotype, DNA sequence, and gene expression profiles in three evolved drug-resistant isolates. Next-generation sequencing and electrophoretic karyotyping confirm the presence of segmental aneuploidy as supernumerary chromosomes originating from centromere-inclusive chromosomal duplication events in two such cases. A 638-kb region and a 675-kb region, both of which originated from chromosome 5 and contained its centromere region, are instances of supernumerary chromosome formation identified in two evolved fluconazole-resistant isolates. Loss of the supernumerary chromosomes from the drug-resistant isolates results in a complete reversal of fluconazole susceptibility. Transcriptome analysis of the third isolate identified overexpression of drug efflux pumps as a possible non-aneuploidy-driven mechanism of drug resistance. Together, this study reveals how both aneuploidy-driven and aneuploidy-independent mechanisms may operate in parallel in an evolving population of C. auris in the presence of an antifungal drug, in spite of starting from the same strain grown under similar conditions, to attain various levels of fluconazole resistance. IMPORTANCE Fungal pathogens develop drug resistance through multiple pathways by acquiring gene mutations, increasing the copy number of genes, or altering gene expression. In this study, we attempt to understand the mechanisms of drug resistance in the recently emerged superbug, C. auris. One approach to studying this aspect is identifying various mechanisms operating in drug-resistant clinical isolates. An alternative approach is to evolve a drug-susceptible isolate in the presence of an antifungal compound and trace the changes that result in drug resistance. Here, we evolve a drug-susceptible isolate of C. auris in the laboratory in the presence of a widely used antifungal compound, fluconazole. In addition to the already known changes like overexpression of drug efflux pumps, this study identifies a novel mechanism of azole resistance by the emergence of additional chromosomes through segmental duplication of chromosomal regions, including centromeres. The centric supernumerary chromosome helps stable amplification of a set of genes with an extra copy to confer fluconazole resistance.

During September–December 2020, we conducted a multicenter retrospective study across India to evaluate epidemiology and outcomes among cases of coronavirus disease (COVID-19)–associated mucormycosis (CAM). Among 287 mucormycosis patients, 187 (65.2%) had CAM; CAM prevalence was 0.27% among hospitalized COVID-19 patients. We noted a 2.1-fold rise in mucormycosis during the study period compared with September–December 2019. Uncontrolled diabetes mellitus was the most common underlying disease among CAM and non-CAM patients. COVID-19 was the only underlying disease in 32.6% of CAM patients. COVID-19–related hypoxemia and improper glucocorticoid use independently were associated with CAM. The mucormycosis case-fatality rate at 12 weeks was 45.7% but was similar for CAM and non-CAM patients. Age, rhino-orbital-cerebral involvement, and intensive care unit admission were associated with increased mortality rates; sequential antifungal drug treatment improved mucormycosis survival. The COVID-19 pandemic has led to increases in mucormycosis in India, partly from inappropriate glucocorticoid use.

IntroductionRecently, India witnessed an unprecedented surge of coronavirus disease 2019 (COVID-19)-associated mucormycosis (CAM) cases. In addition to patient management issues, environmental Mucorales contamination possibly contributed to the outbreak. A recent study evaluated environment contamination by Mucorales in the hospital setting. However, a considerable number of CAM patients were never admitted to a hospital before the development of the disease. The present study, therefore, planned to evaluate Mucorales contamination of patients’ residences.MethodsThe residential environment of 25 patients with CAM living in north India was surveyed. Air samples were collected from indoor and immediate outdoor vicinity of the patients’ residence and cultured on Dichloran Rose–Bengal Chloramphenicol (DRBC) agar with benomyl for selective isolation of Mucorales. Surface swab samples were also collected from the air coolers fitted in those residences and cultured on DRBC agar. The isolates were identified by phenotypic and genotypic methods. Amplified fragment length polymorphism (AFLP) was employed to evaluate the genetic relatedness of the environmental and patients’ clinical isolates.ResultsThe median spore count (mean ± SD, cfu/m3) of Mucorales in the air of patients’ bedrooms was significantly higher than in the air in other rooms in those residences (3.55 versus 1.5, p = 0.003) or the air collected directly from the front of the air cooler (p < 0.0001). The Mucorales spore count in the environment did not correlate with either ventilation of the room or hygiene level of the patients’ residences. Rhizopus arrhizus was isolated from the environment of all patients’ residences (n = 25); other Mucorales species isolated were Cunninghamella bertholletiae (n = 14), Rhizopus microsporus (n = 6), Rhizopus delemar (n = 6), Syncephalastrum racemosum (n = 1), Lichtheimia corymbifera (n = 1), and Mucor racemosus (n = 1). Genetic relatedness was observed between 11 environmental isolates from the patients’ bedrooms and respective clinical isolates from patients.DiscussionThe study supported the view that the patients might have acquired Mucorales from the home environment during the post-COVID-19 convalescence period. Universal masking at home during patients’ convalescence period and environmental decontamination could minimize exposure in those susceptible patients.

Wickerhamomyces anomalus, previously known as Candida pelliculosa, occasionally causes candidemia in humans, primarily infecting neonates, and infants. The mortality rate of these invasive infections is high, and isolates with a reduced susceptibility to fluconazole have been reported. W. anomalus outbreaks are regularly reported in healthcare facilities, especially in neonatal intensive care units (NICUs). In order to rapidly genotype isolates with a high-resolution, we developed and applied a short tandem repeat (STR) typing scheme for W. anomalus. Six STR markers were selected and amplified in two multiplex PCRs, M3 and M6, respectively. In total, 90 W. anomalus isolates were typed, leading to the identification of 38 different genotypes. Four large clusters were found, unveiling simultaneous outbreak events spread across multiple units within the same hospital. STR typing results of 11 isolates were compared to whole-genome sequencing (WGS) single nucleotide polymorphism (SNP) calling, and the identified genotypic relationships were highly concordant. We performed antifungal susceptibility testing of these isolates, and a reduced susceptibility to fluconazole was found for two (2.3%) isolates. ERG11 genes of these two isolates were examined using WGS data, which revealed a novel I469L substitution in one isolate. By constructing a homology model for W. anomalus ERG11p, the substitution was found in close proximity to the fluconazole binding site. In summary, we showed multiple W. anomalus outbreak events by applying a novel STR genotyping scheme.

Objectives: Increasing incidence of azole resistance in Candida tropicalis, especially to fluconazole, has been seen in Asian countries including India. Limited knowledge is available on the molecular mechanisms associated with the development of azole resistance in C. tropicalis. The present study examined the dynamics of in vitro azole resistance in C. tropicalis after prolonged treatment with fluconazole. Methods: Nine fluconazole-susceptible isolates of C. tropicalis were used in this study. Fluconazole resistance was induced experimentally in C. tropicalis isolates. The stability of induced resistance and cross-resistance to other azoles was examined. The molecular mechanisms of azole resistance were assessed by measuring the expression and mutation analysis of different genes. Results: Varying degrees of resistance [five with minimum inhibitory concentrations (MICs) ≤32 mg/L and four with MICs ≥128 mg/L] were noticed, and the resistance was developed in 3 months. Of the nine resistant isolates, four induced resistant isolates with MICs ≥128 mg/L presented temporal resistance stability up to 10 subcultures. These four isolates presented cross-resistance to other azoles and also an inducible overexpression of transporters (CDR1, CDR2, CDR3 and MDR1), ergosterol biosynthesis pathway genes (ERG1, ERG2, ERG3 and ERG11), transcription factors (TAC1 and UPC2) and stress-responsive genes (HSP90 and MKC1) was noticed. No mutations were seen in any of the four genes (ERG1, ERG3, ERG11 and UPC2) tested. Conclusions: Candida tropicalis isolates adapt themselves in the presence of continuous drug exposure and switch back to being susceptible in the absence of the drug. The acquisition of resistance in C. tropicalis is mediated by the overexpression of different resistance-related genes without any molecular alterations.

Background: Invasive fungal diseases (IFD) are a serious threat, but physicians in Asia lack access to many advanced diagnostics in mycology. It is likely that they face other impediments in the management of IFD. A gap analysis was performed to understand the challenges Asian physicians faced in medical mycology. Methods: The Asia Fungal Working Group (AFWG) conducted a web-based survey on management practices for IFD among clinicians in China, India, Indonesia, Philippines, Singapore, Taiwan and Thailand. Findings: Among 292 respondents, 51.7% were infectious disease (ID) specialists. Only 37% of respondents had received formal training in medical mycology. They handled only around 2–4 proven cases of each fungal infection monthly, with invasive candidiasis the most common. For laboratory support, the majority had access to direct microscopy (96%) and histopathology (87%), but galactomannan and azole levels were available to 60% and 25% of respondents, respectively. The majority (84%) used clinical parameters for treatment response monitoring, and 77% followed the Infectious Diseases Society of America guidelines. The majority (84%) did not use the services of an ID physician. Where febrile neutropenia was concerned, 74% of respondents used the empirical approach. Only 30% had an antifungal stewardship program in their hospital. Eighty percent could not use preferred antifungals because of cost. Interpretation: The survey identified inadequacies in medical mycology training, non-culture diagnostics, access to antifungal drugs, and local guidelines as the major gaps in the management of IFDs in Asian countries. These gaps are targets for improvement.

Introduction: Fungi are ubiquitous organisms and significantly alter the post-transplant course. They are a major cause of morbidity and mortality and more so in developing countries. Aims: To study the clinical profile, etiology, risk factors, treatment, and outcome of fungal infections in post-renal transplant recipients. Materials and Methods: This was a cross-sectional observational retrospective study from January 2014 to June 2017 wherein renal transplant recipients with invasive fungal infection were included and were followed. Results: Amongst 550 renal transplant recipients, 56 (10.2%) patients developed invasive fungal infection. Mean age of patients was 40.61 ± 10.06 (13-66) years and mean duration of acquiring infection post-transplant was 25.33 ± 23.65 (1-96) months. Male to female ratio was 3:1. Fever was the commonest presentation observed in 89.3% patients. Cough (76.8%), breathlessness (64.3%), sputum (55.3%), hypoxia (50%), and hemoptysis (10.7%) were other common clinical symptoms at presentation. Mean serum creatinine at presentation was 1.70 mg/dl. Most common invasive fungal infection isolated was Mucormycosis 15 (26.7%), foolwed by Aspergillosis 13 (23.2%), Pneumocystis jiroveci 12 (21.4%), Cryptococcus 6 (10.7%), Candida 4 (7.1%), Histoplasmosis 3 (5.3%), Phaeohypomycosis 2 (3.5%), and 5 (8.9%) patients had undetermined fungal etiology. Twenty (35.7%) patients had evidence of dual infection. Use of antithymocyte globulin 27 (48.2%), post-transplant diabetes mellitus 18 (32.1%), Cytomegalovirus (CMV) infection 16 (28.5%), anti-rejection therapy 9 (16%), and Hepatitis C infection 7 (12.5%) were some identified risk factors. Ten (17.8%) patients had graft loss and 12 (21.4%) patients died in the study period. Conclusions: Invasive fungal infection is a serious threat to renal transplant recipients. Patient and graft survival is significantly affected by fungal infection in developing world.

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 95% for three of the seven and

This study was designed to understand the molecular mechanisms of azole resistance in Candida tropicalis using genetic and bioinformatics approaches. Thirty-two azole-resistant and 10 azole-susceptible (S) clinical isolates of C. tropicalis were subjected to mutation analysis of the azole target genes including ERG11. Inducible expression analysis of 17 other genes potentially associated with azole resistance was also evaluated. Homology modeling and molecular docking analysis were performed to study the effect of amino acid alterations in mediating azole resistance. Of the 32 resistant isolates, 12 (37.5%) showed A395T and C461T mutations in the ERG11 gene. The mean overexpression of CDR1, CDR3, TAC1, ERG1, ERG2, ERG3, ERG11, UPC2, and MKC1 in resistant isolates without mutation (R-WTM) was significantly higher (p

Background: The prevalence of aspergillus sensitization (AS) and allergic bronchopulmonary aspergillosis (ABPA) in asthmatic children remains unclear. Objective: To systematically review the literature to estimate the prevalence of AS and ABPA in children with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in pediatric asthma. The primary outcome was to assess the prevalence of AS, while the secondary outcome was to evaluate the prevalence of ABPA. We pooled the prevalence estimates using a random effects model. We also calculated the heterogeneity and publication bias. Results: Of the 11,695 records retrieved, 16 studies with 2468 asthmatic children met the inclusion criteria. Most studies were published from tertiary centers. The pooled prevalence of AS in asthma (15 studies; 2361 subjects) was 16.1% (95% confidence intervals [CI], 9.3–24.3). The prevalence of AS was significantly higher in prospective studies, studies from India, and those from developing countries. The pooled prevalence of ABPA in asthma (5 studies; 505 children) was 9.9% (95% CI, 0.81–27.6). There was significant heterogeneity and publication bias for both outcomes. Conclusions: We found a high prevalence of AS and ABPA in asthmatic children. There is a need for community-based studies from different ethnicities using a standard methodology to ascertain the true prevalence of AS and ABPA in pediatric asthma.

Serum 1,3-β-d-glucan(BDG) is a broad fungal biomarker for invasive fungal disease (IFD). More data is still required to support the Fujifilm Wako assay as a valuable alternative to the widely used Fungitell assay. We included archived serum samples from 157 individuals (97 cases; 33-IA, 64-IC, and 60 controls) for the comparative performance evaluation of the Fungitell assay and the Fujifilm Wako assay for IFD diagnosis. The BDG value was significantly higher in patients with IFD vs. controls (70.79 pg/mL vs. 3.03 pg/mL, p: 0.0002). An area under the curve (AUC) for the IFD, IC, and IA diagnosis was 0.895, 0.910, and 0.866, respectively, for the Fujifilm Wako assay. Based on the highest Youden’s index (0.667), a cutoff of 5 pg/mL was selected as the optimum for the Fujifilm Wako assay with good sensitivity (79.4%), specificity (88.3%) and agreement (84.7%, Cohen’s k:0.691) with the Fungitell assay. The mean run-time of the Fujifilm Wako assay was 70.12 min, and real-time observation allowed earlier time to result in Fujifilm Wako vs. Fungitell assay (37 vs. 120 min, p: < 0.0001). Thus, our findings support the diagnostic value of the Fujifilm Wako assay for the diagnosis of IFD. However, there is still a need to validate diagnostic protocols to optimize their use in multi-centre studies with different patient groups.

Objectives: The clinical profile, molecular characteristics and antifungal susceptibility patterns of the Mucoraceous mould, Syncephalastrum spp are poorly characterized. The present study provides a comprehensive overview of these aspects of this rare fungus. Methods: We characterized 8 clinical isolates of Syncephalestrum spp by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), 28S rDNA sequencing, Amplified Fragment Length Polymorphism (AFLP, n = 7) and in-vitro antifungal susceptibility testing. Clinical details of these eight cases were reviewed with all cases of Syncephalestrum infections reported in the literature till August 2020. Results: S. racemosum (n = 4) and S. monosporum (n = 4) were identified by MALDI-TOF, sequencing and AFLP also clearly differentiated the two. All isolates were uniformly susceptible to amphotericin B and terbinafine. Analysis of clinical details in our eight patients with 43 more cases reported in the literature revealed that most of the reports were (78.4%) from India and cutaneous mucormycosis was the most common (37.3%) presentation followed by rhino-orbito-cerebral (23.5%) and pulmonary(17.6%) infection. Association of trauma with skin infection (p:0.042); immunosuppression/steroid use (p:0.005) and neutropenia (p:0.000) with pulmonary infection was seen. Conclusion: S. racemosum, S. monosporum give rise to human infections. The improved database of MALDI-TOF could distinguish the two species. Such rare and emerging infections merit careful consideration and clinical attention.

Conidiobolomycosis is a rare fungal infection that affects adults in tropical regions. We report a 42-year-old male patient who was referred to the Sulaiman Al Habib Hospital, Dubai, United Arab Emirates (UAE), in 2013 with excessive nasal bleeding and a suspected nasal tumour. He reported having briefly visited central India nine months previously. Computed tomography and magnetic resonance imaging showed a highly vascularised mass in the nasal cavity. However, after surgical excision, initial treatment with amphotericin B deoxycholate was unsuccessful and the disease progressed, leading to external and internal nasal deformation and necessitating further excision and facial reconstruction. Histopathological analysis of the second biopsy revealed Splendore-Hoeppli changes consistent with a fungal infection. Microbiological findings subsequently confirmed Conidiobolus coronatus. Subsequently, the patient was successfully treated with a combination of itraconazole and fluconazole. To the best of the authors’ knowledge, this is the first report of a case of rhinofacial conidiobolomycosis from the UAE. Keywords: Nasal Obstruction; Conidiobolus; Zygomycosis; Antifungal Agents; Case Report; United Arab Emirates.

Invasive mycosis is a serious complication of solid organ transplantation. Fungal infections even if appropriately diagnosed and treated with current antifungal agents, have a high mortality rate. A high index of suspicion is required and an attempt should be made to confirm the microbiological diagnosis from each site involved to rule out multiple infections. We report here a 41-year-old allograft recipient, who presented with fever associated with chills and one episode of generalized tonic clonic seizure 1-year post transplantation. Neuroimaging revealed a brain abscess, stereotactic biopsy from which yielded Scedosporium apiospermum on fungal culture. Whole blood quantitative cytomegalovirus (CMV) polymerase chain reaction done was positive. He also developed pulmonary aspergillosis and secondary hemophagocytosis later in the course of his hospital stay. His tacrolimus and mycophenolate were stopped and he was managed with i.v ganciclovir, amphoterecin b, voriconazole, high dose i.v immunoglobulins and surgical draingae of abscess. With all measures, he showed improvement in his general and neurological condition and maintained good graft function. Scedosporium is a rare cause of brain abscess. CMV co-infection leads to increased chances of other opportunistic infections. Good microbiological workup from each site involved in immunosuppressed subjects is the need of the hour as early diagnosis can lead to lesser mortality and morbidity.

Introduction: Renal transplant recipients now have better graft survival rates, but continue to develop opportunistic infections. The present study was aimed at finding the incidence of opportunistic infections in the tropical environment in live-related transplant recipients. Materials and Methods: The study was carried out retrospectively with the help of medical records at a tertiary care hospital in North India from 2006 to 2010. The demographic and transplant details were noted, and data were analyzed for any possible risk factor. Results: A total of 1270 patients were studied, of which 231 infectious episodes were detected in 196 (15.4%) patients. Within 1 month, 11.7% of patients had infection, whereas 68.4% of patients had at least one infectious episode within the first 6 months of transplant. Bacterial infection (5.9%) followed by tuberculosis (4.9%), viral (3.8%), and fungal (2.1%) were the infections encountered. Aspergillosis (32.1%) was the most common fungal infection, followed by candidiasis and mucormycosis. The most common site of involvement was lung (26.4%), followed by urinary tract (13.0%). The overall patient survival was nearly 90%. Only 20% of patients had functional graft on follow-up in whom the graft was directly involved by a particular infection. Conclusions: Posttransplant infections continue to affect graft and patient survival. Higher rates are seen in the first 6 months posttransplant.

Candida auris

Objectives Healthcare personnel (HCP) are at an increased risk of acquiring COVID-19 infection especially in resource-restricted healthcare settings, and return to homes unfit for self-isolation, making them apprehensive about COVID-19 duty and transmission risk to their families. We aimed at implementing a novel multidimensional HCP-centric evidence-based, dynamic policy with the objectives to reduce risk of HCP infection, ensure welfare and safety of the HCP and to improve willingness to accept and return to duty.Setting Our tertiary care university hospital, with 12 600 HCP, was divided into high-risk, medium-risk and low-risk zones. In the high-risk and medium-risk zones, we organised training, logistic support, postduty HCP welfare and collected feedback, and sent them home after they tested negative for COVID-19. We supervised use of appropriate personal protective equipment (PPE) and kept communication paperless.Participants We recruited willing low-risk HCP, aged

Increasing reports of azole resistance in Candida tropicalis, highlight the development of rapid resistance detection techniques. Nonsynonymous mutations in the lanosterol C14 alpha-demethylase (ERG11) gene is one of the predominant mechanisms of azole resistance in C. tropicalis. We evaluated the tetra primer-amplification refractory mutation system-PCR (T-ARMS-PCR), restriction site mutation (RSM), and high-resolution melt (HRM) analysis methods for rapid resistance detection based on ERG11 polymorphism in C. tropicalis. Twelve azole-resistant and 19 susceptible isolates of C. tropicalis were included. DNA sequencing of the isolates was performed to check the ERG11 polymorphism status among resistant and susceptible isolates. Three approaches T-ARMS-PCR, RSM, and HRM were evaluated and validated for the rapid detection of ERG11 mutation. The fluconazole MICs for the 12 resistant and 19 susceptible isolates were 32-256 mg/L and 0.5-1 mg/L, respectively. The resistant isolates showed A339T and C461T mutations in the ERG11 gene. The T-ARMS-PCR and RSM approaches discriminated all the resistant and susceptible isolates, whereas HRM analysis differentiated all except one susceptible isolate. The sensitivity, specificity, analytical sensitivity, time, and cost of analysis suggests that these three methods can be utilized for the rapid detection of ERG11 mutations in C. tropicalis. Additionally, an excellent concordance with DNA sequencing was noted for all three methods. The rapid, sensitive, and inexpensive T-ARMS-PCR, RSM, and HRM approaches are suitable for the detection of azole resistance based on ERG11 polymorphism in C. tropicalis and can be implemented in clinical setups for batter patient management.

ABSTRACT Candida auris has emerged as a serious threat to the health care settings. Advancements in molecular biology have provided several insights into the evolution of C. auris since it was first described in 2009. However, the simultaneous emergence of four different clades of the fungus at distinct geographical locations remains a mystery. The hypotheses already proposed by researchers fall short of explaining how and why C. auris emerged. In this article, we theorize that C. auris emerged from a common ancestor, subsequently migrated to specific geographical locations, and diversified genetically. This hypothesis is supported by genomic insights, historical events, and indirect scientific facts. C. auris adapted to humans at locations and times coinciding with the divergence from the most recent common ancestor, emerging almost simultaneously as an opportunist pathogen due to antiseptic practices. Future research will support or refute this hypothesis.

Abstract Background Laryngeal aspergillosis is uncommon and is usually secondary to pulmonary involvement in immunocompromised patients. Primary laryngeal aspergillosis in immunocompetent individuals is extremely rare, with a few cases documented over the last five decades. Case presentation We report a case of primary localised laryngeal aspergillosis in a 21-year-old apparently immunocompetent student. Septate hyphae were observed on histopathology of the laryngeal lesion, which was further confirmed as Aspergillus fumigatus after extraction of fungal DNA from formalin fixed paraffin embedded tissue (FFPET) and sequencing. The patient responded well to oral itraconazole therapy over a month. Conclusions Since last few decades, cases of primary laryngeal aspergillosis in immunocompetent individuals are on the rise, globally. This is the first case of invasive laryngeal aspergillosis reported in Nepal. The extraction of DNA from tissue and sequencing helps to identify the etiological agent, when culture fails to isolate the fungus.

Coronavirus disease (COVID-19)-associated mucormycosis (CAM) is an emerging threat globally, especially in India. More than 40,000 CAM cases have been reported in India. The emergence of CAM cases in India has been attributed to environmental, host, and iatrogenic factors. Mucorales spore burden has been reported globally; however, their presence is higher in tropical countries such as India, contributing to the emergence of CAM. Before the COVID-19 pandemic, patients with diabetes mellitus, haematological malignancies, solid organ transplants, corticosteroid therapy and neutropenia were more prone to mucormycosis, whereas in COVID-19 patients, virus-induced endothelial dysfunction, hyperglycaemia, and immune dysfunction following corticosteroid use increase the risk of acquiring mucormycosis. The interaction of Mucorales spores with the epithelial cells, followed by endothelial invasion, is a crucial step in the pathogenesis of mucormycosis. Endothelial damage and increased endothelial receptor expression induced by COVID-19 infection may predispose patients to CAM. COVID-19 infection may directly induce hyperglycaemia by damaging beta cells of the pancreas or by corticosteroid therapy, which may contribute to CAM pathogenesis. Iron acquisition from the host, especially in diabetic ketoacidosis (DKA) or deferoxamine therapy, is an important virulence trait of Mucorales. Similarly, the hyperferritinaemia caused by COVID-19 may act as a source of iron for Mucorales growth and invasion. In addition, corticosteroid treatment reduces or abolishes the innate immune functions of phagocytic cells contributing to the pathogenesis of CAM. This review aims to discuss primarily the host and iatrogenic factors shared between COVID-19 and mucormycosis that could explain the emergence of CAM.

Abstract Background Apophysomyces species are prevalent in tropical countries and A. variabilis is the second most frequent agent causing mucormycosis in India. Among Apophysomyces species, A. elegans, A. trapeziformis and A. variabilis are commonly incriminated in human infections. The genome sequences of A. elegans and A. trapeziformis are available in public database, but not A. variabilis. We, therefore, performed the whole genome sequence of A. variabilis to explore its genomic structure and possible genes determining the virulence of the organism. Results The whole genome of A. variabilis NCCPF 102052 was sequenced and the genomic structure of A. variabilis was compared with already available genome structures of A. elegans, A. trapeziformis and other medically important Mucorales. The total size of genome assembly of A. variabilis was 39.38 Mb with 12,764 protein-coding genes. The transposable elements (TEs) were low in Apophysomyces genome and the retrotransposon Ty3-gypsy was the common TE. Phylogenetically, Apophysomyces species were grouped closely with Phycomyces blakesleeanus. OrthoMCL analysis revealed 3025 orthologues proteins, which were common in those three pathogenic Apophysomyces species. Expansion of multiple gene families/duplication was observed in Apophysomyces genomes. Approximately 6% of Apophysomyces genes were predicted to be associated with virulence on PHIbase analysis. The virulence determinants included the protein families of CotH proteins (invasins), proteases, iron utilisation pathways, siderophores and signal transduction pathways. Serine proteases were the major group of proteases found in all Apophysomyces genomes. The carbohydrate active enzymes (CAZymes) constitute the majority of the secretory proteins. Conclusion The present study is the maiden attempt to sequence and analyze the genomic structure of A. variabilis. Together with available genome sequence of A. elegans and A. trapeziformis, the study helped to indicate the possible virulence determinants of pathogenic Apophysomyces species. The presence of unique CAZymes in cell wall might be exploited in future for antifungal drug development.

Antimicrobial resistance, a major public health concern, largely arises from excess use of antibiotic and antifungal drugs. Lack of routine diagnostic testing for fungal diseases exacerbates the problem of antimicrobial drug empiricism, both antibiotic and antifungal. In support of this contention, we cite 4 common clinical situations that illustrate this problem: 1) inaccurate diagnosis of fungal sepsis in hospitals and intensive care units, resulting in inappropriate use of broad-spectrum antibacterial drugs in patients with invasive candidiasis; 2) failure to diagnose chronic pulmonary aspergillosis in patients with smear-negative pulmonary tuberculosis; 3) misdiagnosis of fungal asthma, resulting in unnecessary treatment with antibacterial drugs instead of antifungal drugs and missed diagnoses of life-threatening invasive aspergillosis in patients with chronic obstructive pulmonary disease; and 4) overtreatment and undertreatment of Pneumocystis pneumonia in HIV-positive patients. All communities should have access to nonculture fungal diagnostics, which can substantially benefit clinical outcome, antimicrobial stewardship, and control of antimicrobial resistance.

We report invasive candidiasis caused by Candida viswanathii over 2 time periods during 2013–2015 in a tertiary care hospital in Chandigarh, India. Molecular typing revealed multiple clusters of the isolates. We detected high MICs for fluconazole in the second time period.

ATP-binding cassette (ABC) superfamily members have a key role as nutrient importers and exporters in bacteria. However, their role as drug exporters in eukaryotes brought this superfamily member to even greater prominence. The capacity of ABC transporters to efflux a broad spectrum of xenobiotics represents one of the major mechanisms of clinical multidrug resistance in pathogenic fungi including Candida species. Candida auris, a newly emerged multidrug-resistant fungal pathogen of humans, has been responsible for multiple outbreaks of drug-resistant infections in hospitals around the globe. Our study has analyzed the entire complement of ABC superfamily transporters to assess whether these play a major role in drug resistance mechanisms of C. auris. Our bioinformatics analyses identified 28 putative ABC proteins encoded in the genome of the C. auris type-strain CBS 10913T; 20 of which contain transmembrane domains (TMDs). Quantitative real-time PCR confirmed the expression of all 20 TMD transporters, underlining their potential in contributing to the C. auris drug-resistant phenotype. Changes in transcript levels after short-term exposure of drugs and in drug-resistant C. auris isolates suggested their importance in the drug resistance phenotype of this pathogen. CAUR_02725 orthologous to CDR1, a major multidrug exporter in other yeasts, showed consistently higher expression in multidrug-resistant strains of C. auris. Homologs of other ABC transporter genes, such as CDR4, CDR6, and SNQ2, also displayed raised expression in a sub-set of clinical isolates. Together, our analysis supports the involvement of these transporters in multidrug resistance in C. auris.

Mucormycosis is an angioinvasive disease caused by saprophytic fungi of the order Mucorales. The exact incidence of mucormycosis in India is unknown due to the lack of population-based studies. The estimated prevalence of mucormycosis is around 70 times higher in India than that in global data. Diabetes mellitus is the most common risk factor, followed by haematological malignancy and solid-organ transplant. Patients with postpulmonary tuberculosis and chronic kidney disease are at additional risk of developing mucormycosis in this country. Trauma is a risk factor for cutaneous mucormycosis. Isolated renal mucormycosis in an immunocompetent host is a unique entity in India. Though Rhizopus arrhizus is the most common etiological agent of mucormycosis in this country, infections due to Rhizopus microsporus, Rhizopus homothallicus, and Apophysomyces variabilis are rising. Occasionally, Saksenaea erythrospora, Mucor irregularis, and Thamnostylum lucknowense are isolated. Though awareness of the disease has increased among treating physicians, disease-associated morbidity and mortality are still high, as patients seek medical attention late in the disease process and given the low affordability for therapy. In conclusion, the rise in the number of cases, the emergence of new risk factors and causative agents, and the challenges in managing the disease are important concerns with mucormycosis in India.

Invasive candidiasis remains one of the most prevalent systemic mycoses, and several studies have documented the presence of mixed yeast (MY) infections. Here, we describe the epidemiology, clinical, and microbiological characteristics of MY infections causing invasive candidiasis in a multicenter prospective study. Thirty-four centers from 14 countries participated. Samples were collected in each center between April to September 2018, and they were sent to a reference center to confirm identification by sequencing methods and to perform antifungal susceptibility testing, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). A total of 6895 yeast cultures were identified and MY occurred in 150 cases (2.2%). Europe accounted for the highest number of centers, with an overall MY rate of 4.2% (118 out of 2840 yeast cultures). Of 122 MY cases, the most frequent combinations were Candida albicans/C. glabrata (42, 34.4%), C. albicans/C. parapsilosis (17, 14%), and C. glabrata/C. tropicalis (8, 6.5%). All Candida isolates were susceptible to amphotericin B, 6.4% were fluconazole-resistant, and two isolates (1.6%) were echinocandin-resistant. Accurate identification of the species involved in MY infections is essential to guide treatment decisions.

The association of vitamin D deficiency in the pathogenesis of invasive and allergic pulmonary aspergillosis is known. Whether vitamin D deficiency is prevalent in chronic pulmonary aspergillosis (CPA) remains unknown. We evaluated the prevalence of vitamin D deficiency in subjects with CPA. We compared the clinicoradiological features, microbiology, the immunological response, and the severity of CPA in those with or without vitamin D deficiency. We measured plasma vitamin D levels in 230 consecutive treatment-naïve subjects with CPA and 78 controls (28 with prior tuberculosis (TB); 50 healthy controls). We defined vitamin D deficiency as 25(OH)D3 level n = 150) and was also not different between healthy (70%) or diseased (61%) controls. We did not find any difference in the clinicoradiological features, microbiology, immunological response, and severity of CPA between vitamin D sufficient and deficient groups. The prevalence of vitamin D deficiency is high in subjects with CPA, albeit similar to controls. Vitamin D deficiency does not affect the disease severity in subjects with CPA.

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.

IntroductionDisseminated histoplasmosis, a disease that often resembles and is mistaken for tuberculosis, is a major cause of death in patients with advanced HIV disease. Histoplasma antigen detection tests are an important addition to the diagnostic arsenal for patients with advanced HIV disease and should be considered for inclusion on the World Health Organization Essential Diagnostics List.ObjectiveOur objective was to systematically review the literature to evaluate the diagnostic accuracy of Histoplasma antigen tests in the context of advanced HIV disease, with a focus on low- and middle-income countries.MethodsA systematic review of the published literature extracted data on comparator groups, type of histoplasmosis, HIV status, performance results, patient numbers, whether patients were consecutively enrolled or if the study used biobank samples. PubMed, Scopus, Lilacs and Scielo databases were searched for published articles between 1981 and 2018. There was no language restriction.ResultsOf 1327 screened abstracts we included a total of 16 studies in humans for further analysis. Most studies included used a heterogeneousgroup of patients, often without HIV or mixing HIV and non HIV patients, with disseminated or non-disseminated forms of histoplasmosis. Six studies did not systematically use mycologically confirmed cases as a gold standard but compared antigen detection tests against another antigen detection test. Patient numbers were generally small (19-65) in individual studies and, in most (7/10), no confidence intervals were given. The post test probability of a positive or negative test were good suggesting that this non invasive diagnostic tool would be very useful for HIV care givers at the level of reference hospitals or hospitals with the infrastructure to perform ELISA tests. The first results evaluating point of care antigen detection tests using a lateral flow assay were promising with high sensitivity and specificity.ConclusionsAntigen detection tests are promising tools to improve detection of and ultimately reduce the burden of histoplasmosis mortality in patients with advanced HIV disease.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Introduction: Malassezia a commensal yeast, can become pathogenic leading to different clinical forms of dermatosis. Being an obligatory lipophilic, the lipolytic enzymes produced by them help in their growth by obtaining useful lipids from the environment further contributing to the pathogenesis of dermatosis. There are no comparative reports concerning secreted lipase activities of Malassezia species associated with Seborrhoeic Dermatitis/Dandruff (SD/D). Aim: To analyse and compare lipase activities of Malassezia spp. isolated from SD/D patient’s lesional area and Healthy Controls (HC) and correlates this feature in pathogenesis of SD/D. Materials and Methods: Lipase activities of Malassezia species isolated from lesional area of SD/D patients and HC were analysed and compared. Extracellular proteins of Malassezia spp. were extracted from the Leeming and Notman agar after removing and weighing the yeast cells from the agar surface. The lipase activity was measured using an assay based on hydrolysis of p-Nitrophenylpalmitate (pNPP). ANOVA test and GraphPad were used for statistical analysis. Results: Malassezia furfur wet fungal weight was higher (1.1±0.13 g) compared to M. globosa (0.36±0.4 g) and M. restricta (0.26±0.4 g). The mean extracellular lipase activity of M. globosa (0.15 U) and M. restricta (0.18 U) was significantly higher than M. furfur (0.08 U) isolates (p

Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied.Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene.Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V.Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.

Parathyridaria percutanea is an emerging fungus causing subcutaneous phaeohyphomycoses in renal transplant recipients in India. We identified P. percutanea from a patient with subcutaneous phaeohyphomycosis. From our culture collection, we identified the same fungus from 4 similar patients. We found 5 cases previously described in literature.

ABSTRACT Cryptococcosis is a major fungal disease caused by members of the Cryptococcus gattii and Cryptococcus neoformans species complexes. After more than 15 years of molecular genetic and phenotypic studies and much debate, a proposal for a taxonomic revision was made. The two varieties within C. neoformans were raised to species level, and the same was done for five genotypes within C. gattii. In a recent perspective (K. J. Kwon-Chung et al., mSphere 2:e00357-16, 2017, https://doi.org/10.1128/mSphere.00357-16 ), it was argued that this taxonomic proposal was premature and without consensus in the community. Although the authors of the perspective recognized the existence of genetic diversity, they preferred the use of the informal nomenclature “C. neoformans species complex” and “C. gattii species complex.” Here we highlight the advantage of recognizing these seven species, as ignoring these species will impede deciphering further biologically and clinically relevant differences between them, which may in turn delay future clinical advances.

Background and Aims: Allergic bronchopulmonary aspergillosis (ABPA) is an immunological disorder caused by hypersensitivity against Aspergillus fumigatus. The pathogenesis of ABPA remains unknown. Few studies have investigated the role of environmental factors in pathogenesis of ABPA. Herein, we investigate the role of environmental factors in ABPA. Materials and Methods: In this prospective case-control study, consecutive patients with asthma (Aspergillus sensitized and unsensitized) and ABPA were investigated using a standardized questionnaire to enquire into their demographic characteristics, clinical details, exposure to organic matter and living conditions (home environment, presence of moisture in the walls, and others). Asthma severity and control was assessed using the 2002 The Global Initiative for Asthma (GINA) recommendations and asthma control test, respectively. Results: During the study period, 202 subjects of asthma (103 and 99 Aspergillus unsensitized and sensitized asthma, respectively) and 101 ABPA with a mean (SD) age of 35.3 (14.7) years were included. The baseline characteristics were similar in the two groups except for a higher prevalence of severe persistent asthma in the ABPA group (79% vs. 44%, P = 0.0001). No significant differences in environmental factors were noted in the ABPA population compared to asthmatic patients except for a higher rural residence in ABPA (47% vs. 66%, P = 0.007). Conclusions: The study found no significant environmental differences in ABPA compared to asthmatic patients. It is likely that environmental factors are not the primary pathogenetic factors in causation of ABPA.

Aim: To report the management of recurrent postoperative fungal endophthalmitis (POFE) after failed pars plana vitrectomy (PPV) and antifungal therapy. Settings and Design: Tertiary Care Referral Centre in North India. Retrospective, single institution, interventional case-series. Materials and Methods: Six patients with microbiologically proven recurrent post-operative fungal endophthalmitis refractory to conventional management were included. The final recurrence was managed with intraocular lens (IOL) explantation and re-PPV. Main outcome measures included preserved globe anatomy, visual acuity and retinal status. ′Anatomical success′ was defined as preserved anatomy of the globe, and absence of signs of inflammation. ′Functional success′ was defined as an attached retina and a best corrected visual acuity of better than 20/400. Results: Of the six cases of POFE, five were culture positive [Aspergillus flavus (1), Aspergillus fumigatus (2), Candida albicans (1) and Candida glabrata (1)] and one was smear positive for yeast. All recurred (mean recurrences, 4) despite a mean of 2.17 PPVs and intravitreal amphotericin B. No recurrences were observed after IOL explantation with re - PPV (median follow-up, 37 months). Pre-study defined criteria for successful ′anatomical′ and ′functional′ outcomes were achieved in 83.3% and 50% respectively. Conclusion: This report highlights the effective role of combined IOL explantation with PPV in managing recurrent POFE.

The diagnosis of fungal Neglected Tropical Diseases (NTD) is primarily based on initial visual recognition of a suspected case followed by confirmatory laboratory testing, which is often limited to specialized facilities. Although molecular and serodiagnostic tools have advanced, a substantial gap remains between the desirable and the practical in endemic settings. To explore this issue further, we conducted a survey of subject matter experts on the optimal diagnostic methods sufficient to initiate treatment in well-equipped versus basic healthcare settings, as well as optimal sampling methods, for three fungal NTDs: mycetoma, chromoblastomycosis, and sporotrichosis. A survey of 23 centres found consensus on the key role of semi-invasive sampling methods such as biopsy diagnosis as compared with swabs or impression smears, and on the importance of histopathology, direct microscopy, and culture for mycetoma and chromoblastomycosis confirmation in well-equipped laboratories. In basic healthcare settings, direct microscopy combined with clinical signs were reported to be the most useful diagnostic indicators to prompt referral for treatment. The survey identified that the diagnosis of sporotrichosis is the most problematic with poor sensitivity across the most widely available laboratory tests except fungal culture, highlighting the need to improve mycological diagnostic capacity and to develop innovative diagnostic solutions. Fungal microscopy and culture are now recognized as WHO essential diagnostic tests and better training in their application will help improve the situation. For mycetoma and sporotrichosis, in particular, advances in identifying specific marker antigens or genomic sequences may pave the way for new laboratory-based or point-of-care tests, although this is a formidable task given the large number of different organisms that can cause fungal NTDs.

Aspergillus flavus is the second most common etiological agent of invasive aspergillosis (IA) after A. fumigatus. However, most literature describes IA in relation to A. fumigatus or together with other Aspergillus species. Certain differences exist in IA caused by A. flavus and A. fumigatus and studies on A. flavus infections are increasing. Hence, we performed a comprehensive updated review on IA due to A. flavus. A. flavus is the cause of a broad spectrum of human diseases predominantly in Asia, the Middle East, and Africa possibly due to its ability to survive better in hot and arid climatic conditions compared to other Aspergillus spp. Worldwide, ~10% of cases of bronchopulmonary aspergillosis are caused by A. flavus. Outbreaks have usually been associated with construction activities as invasive pulmonary aspergillosis in immunocompromised patients and cutaneous, subcutaneous, and mucosal forms in immunocompetent individuals. Multilocus microsatellite typing is well standardized to differentiate A. flavus isolates into different clades. A. flavus is intrinsically resistant to polyenes. In contrast to A. fumigatus, triazole resistance infrequently occurs in A. flavus and is associated with mutations in the cyp51C gene. Overexpression of efflux pumps in non-wildtype strains lacking mutations in the cyp51 gene can also lead to high voriconazole minimum inhibitory concentrations. Voriconazole remains the drug of choice for treatment, and amphotericin B should be avoided. Primary therapy with echinocandins is not the first choice but the combination with voriconazole or as monotherapy may be used when the azoles and amphotericin B are contraindicated.