Prevalence of Aspergillus sensitization and Allergic Bronchopulmonary Aspergillosis in bronchial asthma: A systematic review of Indian studies.

Background: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in Indian asthmatic patients remains unknown. We systematically reviewed the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in Indian subjects with bronchial asthma. Methods: We searched the PubMed and Embase databases for studies from India reporting the prevalence of AS or ABPA in at least 50 asthmatics. The primary outcome of our study was to assess the prevalence of ABPA. The secondary outcomes were to evaluate the prevalence of AS in asthma and ABPA in Aspergillus-sensitized asthma. We pooled the prevalence estimates using a random effects model and examined the factors influencing the prevalence using multivariate meta-regression. Results: Of the 8,383 records retrieved, 34 studies with 14,580 asthmatics met the inclusion criteria. All the studies were from tertiary centers. The pooled prevalence of ABPA in asthmatics (26 studies; 5,554 asthmatics) was 16.2% [95% confidence interval (CI), 12.5-20.4]. The pooled prevalence of AS in asthma (29 studies; 13,405 asthmatics) was 30.9% (95% CI, 25.3-36.6), while the prevalence of ABPA in AS (20 studies; 1,493 asthmatics) was 48.2% (95% CI, 39.6-56.8). Meta-regression identified studies published after 2009 (OR 1.14; 95% CI, 1.02-1.28) and studies with severe asthmatics (OR 1.12; 95% CI, 1.00-1.26) as the only factors associated with higher ABPA prevalence. Conclusions: There is a high prevalence of ABPA in Indian asthmatic subjects at tertiary centers, underscoring the need for screening all asthmatic subjects in special asthma and chest clinics for ABPA.

Long-term follow-up of allergic bronchopulmonary aspergillosis treated with glucocorticoids: A study of 182 subjects.

BACKGROUND: The long-term outcomes of allergic bronchopulmonary aspergillosis (ABPA) are poorly characterised. METHODS: We retrospectively included treatment-naïve subjects of acute stage ABPA-complicating asthma from three randomised trials. All the subjects received oral prednisolone for 4 months and were monitored every 6 weeks for 6 months and then every 6 months. Our primary objective was to estimate the incidence rate and the frequency of subjects experiencing ABPA exacerbation. The key secondary objectives were to evaluate the factors predicting ABPA exacerbation and the changes in serum total IgE seen during treatment. RESULTS: We included 182 subjects. Eighty-one (44.5%) patients experienced 120 exacerbations during 512 patient-years of follow-up. The incidence rate of ABPA exacerbations was 234/1000 patient-years. Most (73/81, 90.1%) subjects experienced ABPA exacerbation within three years of stopping therapy. On multivariate logistic regression analysis, peripheral blood eosinophil count ≥1000 cells/µL (adjusted odds ratio [aOR] 2.43; 95% confidence interval (CI), 1.26-4.67), the extent of bronchiectasis (aOR 1.10; 95% CI, 1.03-1.18), age (aOR 0.97; 95% CI, 0.94-0.99), and female sex (aOR 2.16; 95% CI, 1.10-4.24) independently predicted ABPA exacerbation after adjusting for serum total IgE and high-attenuation mucus. The best cut-off for serum total IgE after 6 weeks for identifying treatment response and ABPA exacerbations was a 20% decline and a 50% increase, respectively. CONCLUSIONS: ABPA exacerbations were common within 3 years of stopping treatment. Age, female sex, peripheral blood eosinophilia and the extent of bronchiectasis predicted ABPA exacerbations. The optimal serum total IgE cut-off for defining ABPA response and exacerbations is a 20% decline and a 50% increase, respectively.

Clinical and Mycologic Characteristics of Emerging Mucormycosis Agent Rhizopus homothallicus.

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.

Prevalence of Aspergillus Sensitization and Allergic Bronchopulmonary Aspergillosis in Adults With Bronchial Asthma: A Systematic Review of Global Data.

BACKGROUND: The prevalence of allergic bronchopulmonary aspergillosis (ABPA) in asthmatic patients remains unclear and is likely different across geographic locales. OBJECTIVE: To systematically review the literature for estimating the prevalence of Aspergillus sensitization (AS) and ABPA in adults with bronchial asthma. METHODS: We searched the PubMed and Embase databases for studies reporting the prevalence of AS or ABPA in at least 50 asthmatic subjects. The primary outcome was to assess the prevalence of ABPA. The secondary outcome was to evaluate the prevalence of AS in asthma and that of ABPA in asthma with AS. We pooled the prevalence estimates using a random-effects model and examined the factors influencing the prevalence using multivariate meta-regression. RESULTS: Of the 11,801 records retrieved, 86 studies with 25,770 asthmatic subjects met the inclusion criteria. Most of the studies were from tertiary care centers. The pooled prevalence of ABPA in asthma (47 studies; 9822 asthmatic subjects) was 11.3% (95% CI, 8.7-14.2). The pooled prevalence of AS in asthma (73 studies; 23,003 asthmatic subjects) was 25.1% (95% CI, 20.5-30.0), whereas the prevalence of ABPA in AS (36 studies; 2954 asthmatic subjects) was 37.0% (95% CI, 27.9-46.6). Multivariate meta-regression identified studies published from India (odds ratio, 1.11; 95% CI, 1.01-1.23) as the only factor associated with higher ABPA prevalence. There was presence of significant statistical heterogeneity and publication bias. CONCLUSIONS: We found a high prevalence of ABPA in adult asthmatic subjects, underscoring the need for screening for ABPA in all asthmatic subjects seeking tertiary care.

Aspergillus Sensitization and Allergic Bronchopulmonary Aspergillosis in Asthmatic Children: A Systematic Review and Meta-Analysis.

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.

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.

Antifungal prescription practices and consumption in a tertiary care hospital of a developing country.

BACKGROUND: Antifungal stewardship is a less explored component of antimicrobial stewardship programmes, especially in developing countries. OBJECTIVE: We aimed to determine antifungal prescription practices in a tertiary centre of a developing country to identify the challenges for antifungal stewardship programmes. METHODS: Four single-day point prevalent surveys were performed in inpatient units and data were collected from medical records. Antifungal use was recorded in terms of consumption, therapeutic strategies and appropriateness. RESULTS: We found a 2.42%-point prevalence of antifungal prescriptions. Antifungal use was higher in children than adults (4.1% vs. 2.03%), medical than surgical units (3.7% vs. 1.24%) and ICUs than general wards (5.8% vs. 1.9%). The highest antifungal use was observed in the haematology-oncology units (29.3%) followed by emergency (16.2%) and gastroenterology units (11.6%). Among 215 prescriptions, amphotericin B was the most commonly prescribed (50.2%) followed by fluconazole (31.6%). The targeted antifungal therapy was practised more commonly (31.5%) than empiric (29.1%), pre-emptive (22.6%) and prophylactic (16.8%) therapy. Amphotericin B was commonly used for pre-emptive (p = .001) and targeted (p = .049) therapy, while fluconazole (p = .001) and voriconazole (p = .011) for prophylaxis. The prescriptions were inappropriate in 25.1% due to the wrong choice of antifungal (44.4%), indication (27.7%) and dosage (24%). The overall mean antifungal consumption was 2.71 DDD/1000 PD and 8.96 DOT/1000 PD. CONCLUSIONS: We report here the low prevalence of antifungal use at a tertiary care centre in a developing country. Though training for antifungal use would be important for antifungal stewardship, the challenge would remain with the affordability of antifungals.

Case report: Catheter related blood stream infection caused by Candida vulturna.

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.

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

Background: The 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. Objective: To evaluate the performance of several simplified criteria for diagnosing ABPA. Methods: We 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. Results: We 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. Conclusions: We 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.

Occurrence of Cystic Fibrosis Transmembrane Conductance Regulator Gene Mutations in Patients with Allergic Bronchopulmonary Aspergillosis Complicating Asthma.

BACKGROUND: Whether cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations contribute to the high prevalence of allergic bronchopulmonary aspergillosis (ABPA) in India remains unknown. We aimed to evaluate the occurrence of CFTR mutations in subjects with ABPA complicating asthma. METHODS: We sequenced the CFTR gene using genomic DNA from blood on the Illumina NextSeq500 platform. Before undertaking zygosity analysis by genome analysis toolkit, the known or novel single nucleotide polymorphisms (SNPs) and indels were called. For rigorous analysis, we included only high-quality SNPs (scores > 500) and coverage ranging from 30 × 150x. RESULTS: We included 18, 12, and eight adult participants of ABPA, asthma, and healthy controls, respectively. The frequency of SNPs was higher in asthmatic subjects than ABPA or healthy controls, albeit not statistically significant (9/12 [75%] vs. 11/18 [61.1%] vs. 3/8 [37.5%], p = 0.24). Of the 38 subjects, 23 yielded 50 variants (healthy controls [n = 5], ABPA [n = 22], asthma [n = 23]) corresponding to six SNPs not previously linked with ABPA. Of these, four SNPs (rs213950, rs200735475, rs1800113, and rs1800136) were catalogued in the NCBI database. We identified two novel SNPs (chr7:117250703, chr7:117282655) in four (ABPA [n = 1], asthma [n = 3]) subjects without corresponding reference SNP. Most SNPs (85.5%) were heterozygous. The frequency of SNPs was higher in ABPA subjects with high-attenuation mucus (52.2%) and bronchiectasis (39.1%) than serological ABPA (8.7%). CONCLUSIONS: Our study suggests the role of CFTR mutations in the pathogenesis of ABPA. The SNPs in the CFTR gene may contribute to disease severity in ABPA. Larger studies are required to confirm our findings.

Definition, diagnosis, and management of COVID-19-associated pulmonary mucormycosis: Delphi consensus statement from the Fungal Infection Study Forum and Academy of Pulmonary Sciences, India.

COVID-19-associated pulmonary mucormycosis (CAPM) remains an underdiagnosed entity. Using a modified Delphi method, we have formulated a consensus statement for the diagnosis and management of CAPM. We selected 26 experts from various disciplines who are involved in managing CAPM. Three rounds of the Delphi process were held to reach consensus (≥70% agreement or disagreement) or dissensus. A consensus was achieved for 84 of the 89 statements. Pulmonary mucormycosis occurring within 3 months of COVID-19 diagnosis was labelled CAPM and classified further as proven, probable, and possible. We recommend flexible bronchoscopy to enable early diagnosis. The experts proposed definitions to categorise dual infections with aspergillosis and mucormycosis in patients with COVID-19. We recommend liposomal amphotericin B (5 mg/kg per day) and early surgery as central to the management of mucormycosis in patients with COVID-19. We recommend response assessment at 4-6 weeks using clinical and imaging parameters. Posaconazole or isavuconazole was recommended as maintenance therapy following initial response, but no consensus was reached for the duration of treatment. In patients with stable or progressive disease, the experts recommended salvage therapy with posaconazole or isavuconazole. CAPM is a rare but under-reported complication of COVID-19. Although we have proposed recommendations for defining, diagnosing, and managing CAPM, more extensive research is required.

As the virus sowed, the fungus reaped! A comparative analysis of the clinico-epidemiological characteristics of rhino-orbital mucormycosis before and during COVID-19 pandemic.

BACKGROUND: The sudden surge of mucormycosis cases which happened during the second wave of COVID-19 pandemic was a significant public health problem in India. OBJECTIVES: The aim of this study was to analyse the clinico-epidemicological characteristics of the mucormycosis cases to determine the changes that had occurred due to COVID-19 pandemic. METHODOLOGY: A retrospective cross-sectional study was conducted at the Department of Otolaryngology Head and Neck Surgery, PGIMER, Chandigarh, India. Patients diagnosed with rhino-orbital mucormycosis were categorised into the following groups: Pre-pandemic(May 2019 to April 2020), Pandemic Pre-epidemic (May 2020 to April 2021) and Epidemic (1 May 2021 to 12 July 2021). The epidemiological, clinical and surgical data of all the patients were retrieved from the hospital records and analysed. RESULTS: The epidemic period had 370 cases, compared with 65 during pandemic period and 42 in the pre-pandemic period. Diabetes mellitus was seen in 87% of cases during epidemic period, 92.9% in the pre-pandemic period and 90.8% in the pre-pandemic pre-epidemic period. The proportion of patients suffering from vision loss, restricted extra-ocular movements, palatal ulcer and nasal obstruction was higher in the pre-epidemic groups, and the difference was significant (p, <.01). There was no history of oxygen use in 85.9% of patients and no steroid use in 76.5%. The death rates were the lowest during epidemic (10%). CONCLUSION: COVID-19 has caused a statistically significant increase in the number of mucormycosis infections. The mortality and morbidity which showed an increase during the first wave of COVID-19 decreased significantly during the epidemic period.

Pulmonary Artery Pseudoaneurysm in COVID-19-Associated Pulmonary Mucormycosis: Case Series and Systematic Review of the Literature.

Literature on COVID-19-associated pulmonary mucormycosis (CAPM) is sparse. Pulmonary artery pseudoaneurysm (PAP) is an uncommon complication of pulmonary mucormycosis (PM), and rarely reported in CAPM. Herein, we report five cases of CAPM with PAP managed at our center and perform a systematic review of the literature. We diagnosed PM in those with clinico-radiological suspicion and confirmed it by microbiology or histopathology. We encountered five cases of CAPM with PAP (size ranged from 1 × 0.8 cm to ~ 4.9 × 4.8 cm). All subjects had diabetes and were aged 55-62 years (75% men). In two cases, COVID-19 and mucormycosis were diagnosed simultaneously, while in three others, COVID-19 preceded PM. One subject who underwent surgery survived, while all others died (80% mortality). From our systematic review, we identified one additional case of CAPM with PAP in a transplant recipient. CAPM with PAP is rare with high mortality. Early diagnosis and multimodality management are imperative to improve outcomes.

Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.

BACKGROUND AND AIMS: Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. METHODS: Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). RESULTS: Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2  > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. CONCLUSIONS: FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.

Epidemiology and outcomes of allergic bronchopulmonary aspergillosis in the elderly.

BACKGROUND: The prevalence and outcomes of allergic bronchopulmonary aspergillosis (ABPA) in the elderly remain unknown. METHODS: We reviewed our database to identify the proportion of subjects diagnosed with ABPA at ≥60 years of age (ABPA-elderly). We compared the clinical features, treatment and outcomes of ABPA-elderly versus the non-elderly (ABPA diagnosed at <60 years of age). RESULTS: Between 2007 and 2019, we encountered 810 ABPA subjects with a mean age of 34.9 years (49.4% women). Of these, 43 (5.3%) were aged ≥60 years (ABPA-elderly). There was a trend towards lower median (interquartile range [IQR]) serum total IgE (4900 [2659-10000] vs. 7156 [23360-11963] IU/mL; P = .06) and Aspergillus fumigatus-specific IgE (12.3 [4.8-29.6] vs. 22.4 [7.7-41.5] kUA/L; P = .06) in the elderly than the non-elderly. Eosinophil counts were similar in the two groups. The median [IQR] number of segments involved by bronchiectasis (5 [2-9] vs. 7 [4-11]) was significantly lower in the ABPA-elderly (P = .001). The proportion of subjects experiencing ABPA exacerbations was significantly (P = .047) lower in the elderly (25.6%) vs. the non-elderly (40.8%). There was also a tendency towards a lower mean number of exacerbations in the elderly (155 vs. 208 exacerbation per 1000 person-years) than the non-elderly (P = .09). There was also a trend towards longer mean time to first exacerbation in the ABPA-elderly than the non-elderly (1612 vs. 1159 days). CONCLUSION: ABPA was uncommon in the elderly. The bronchiectasis is less extensive with a trend towards lower immunological severity and fewer exacerbations in the elderly than the non-elderly subjects with ABPA.

Serum iron indices in COVID-19-associated mucormycosis: A case-control study.

BACKGROUND: Whether dysregulated iron metabolism is associated with COVID-19-associated mucormycosis (CAM) remains unknown. Herein, we compare the serum iron indices in COVID-19 subjects with and without mucormycosis. METHODS: We conducted a case-control study enrolling COVID-19 participants with and without mucormycosis. We compared the baseline serum iron indices (iron, ferritin, total iron-binding capacity [TIBC], unsaturated iron-binding capacity and percentage transferrin saturation) between CAM cases and COVID-19 controls. Additionally, we performed a multivariate logistic regression analysis to assess whether any iron indices are associated with CAM. RESULTS: We enrolled 28 CAM cases (mean age 53.6 years old; 78.6% men) and 26 controls (mean age 57.2 years old; 73.1% men). Rhino-orbital (±cerebral) mucormycosis (85.7%) was the most clinical presentation. Diabetes mellitus was more frequent in the cases than controls (75% vs. 42.3%; p = .015). Hypoxaemia during COVID-19 illness was more common in controls than cases. The mean serum iron values (33 vs. 45 µg/dl, p = .03) and TIBC (166.6 vs. 201.6 µg/dl, p = .003) were significantly lower in CAM cases than controls. On multivariate analysis, we found a lower TIBC (odds ratio [OR] 0.97; 95% confidence interval [CI], 0.95-0.99) and diabetes mellitus (OR 5.23; 95% CI, 1.21-22.68) to be independently associated with CAM after adjusting for serum iron, ferritin and glucocorticoid therapy. The case fatality rate of CAM was 73.9%. The iron indices were not significantly different between CAM survivors and non-survivors. CONCLUSIONS: The CAM is associated with lower TIBC levels than COVID-19 subjects without mucormycosis, suggesting dysregulated iron metabolism in its pathogenesis. Further studies are required to confirm our preliminary observations.

Connecting the Dots: Interplay of Pathogenic Mechanisms between COVID-19 Disease and Mucormycosis.

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.

Role of pre-transplant chest high-resolution computed tomography and serum galactomannan index in predicting post-transplant invasive pulmonary aspergillosis in allogeneic hematopoietic cell transplant recipients.

INTRODUCTION: The role of pre-HCT chest high-resolution computed tomography (HRCT) and serum galactomannan index (GMI) in predicting the post-allogeneic hematopoietic cell transplant (HCT) invasive pulmonary aspergillosis (IPA) is debatable. METHODS: This was a single-center, prospective study from 2014 to 2019. The primary objective was to study if pre-HCT chest HRCT and serum GMI predicted IPA post-HCT. The secondary objective was day +100 mortality. All consecutive, consenting patients of ≥12 years of age undergoing allo-HCT were included and had pre-HCT chest HRCT and serum GMI. All patients received mold active antifungal prophylaxis. The EORTC/MSG criteria were used for the diagnosis of IPA. RESULTS: A total of 82 patients with median age 27 years (12-59 years) were included. The underlying diagnoses included hematological malignancies (79%) and aplastic anemia (21%). Fifteen percent of patients was treated for prior history of probable IPA (>6 weeks before HCT). Pre-HCT chest HRCT satisfied EORTC clinical criteria in 24% patients. Serum GMI ≥0.5 was seen in 27% of patients. Post-HCT probable IPA was seen in 24% of patients. There were more patients with pre-HCT chest HRCT findings satisfying EORTC clinical criteria (45% vs. 18%, P = .014) and GMI ≥0.5 (45% vs. 21%, P = .03) in the group with post-HCT IPA compared to those without IPA. There was higher day+100 mortality in patients with post-HCT IPA (55% vs. 18%, P = .001). CONCLUSIONS: The presence of EORTC clinical criteria on pre-HCT chest HRCT, serum GMI ≥0.5, and prior history of IPA predicted post-HCT IPA.

Epidemiology of Mucormycosis in India.

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.