Corrigendum: Azole-resistance in aspergillus terreusand related species: An emerging problem or a rare phenomenon? (Frontiers in Microbiology (2018) 9 (516) DOI: 10.3389/fmicb.2018.00516)

Raquel Sabino was not included as an author in the published article. The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated. © 2019 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Lo Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Sabino, Lass-Flörl and Lackner

Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon?

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. © 2018 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Lass-Flörl and Lackner

Azole-resistance in Aspergillus terreus and related species: An emerging problem or a rare Phenomenon?

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. © 2018 Zoran, Sartori, Sappl, Aigner, Sánchez-Reus, Rezusta, Chowdhary, Taj-Aldeen, Arendrup, Oliveri, Kontoyiannis, Alastruey-Izquierdo, Lagrou, Cascio, Meis, Buzina, Farina, Drogari-Apiranthitou, Grancini, Tortorano, Willinger, Hamprecht, Johnson, Klingspor, Arsic-Arsenijevic, Cornely, Meletiadis, Prammer, Tullio, Vehreschild, Trovato, Lewis, Segal, Rath, Hamal, Rodriguez-Iglesias, Roilides, Arikan-Akdagli, Chakrabarti, Colombo, Fernández, Martin-Gomez, Badali, Petrikkos, Klimko, Heimann, Uzun, Roudbary, de la Fuente, Houbraken, Risslegger, Lass-Flörl and Lackner

Global Retinoblastoma Presentation and Analysis by National Income Level

Importance: Early diagnosis of retinoblastoma, the most common intraocular cancer, can save both a child's life and vision. However, anecdotal evidence suggests that many children across the world are diagnosed late. To our knowledge, the clinical presentation of retinoblastoma has never been assessed on a global scale. Objectives: To report the retinoblastoma stage at diagnosis in patients across the world during a single year, to investigate associations between clinical variables and national income level, and to investigate risk factors for advanced disease at diagnosis. Design, Setting, and Participants: A total of 278 retinoblastoma treatment centers were recruited from June 2017 through December 2018 to participate in a cross-sectional analysis of treatment-naive patients with retinoblastoma who were diagnosed in 2017. Main Outcomes and Measures: Age at presentation, proportion of familial history of retinoblastoma, and tumor stage and metastasis. Results: The cohort included 4351 new patients from 153 countries; the median age at diagnosis was 30.5 (interquartile range, 18.3-45.9) months, and 1976 patients (45.4) were female. Most patients (n = 3685 84.7%) were from low-and middle-income countries (LMICs). Globally, the most common indication for referral was leukocoria (n = 2638 62.8%), followed by strabismus (n = 429 10.2%) and proptosis (n = 309 7.4%). Patients from high-income countries (HICs) were diagnosed at a median age of 14.1 months, with 656 of 666 (98.5%) patients having intraocular retinoblastoma and 2 (0.3%) having metastasis. Patients from low-income countries were diagnosed at a median age of 30.5 months, with 256 of 521 (49.1%) having extraocular retinoblastoma and 94 of 498 (18.9%) having metastasis. Lower national income level was associated with older presentation age, higher proportion of locally advanced disease and distant metastasis, and smaller proportion of familial history of retinoblastoma. Advanced disease at diagnosis was more common in LMICs even after adjusting for age (odds ratio for low-income countries vs upper-middle-income countries and HICs, 17.92 95% CI, 12.94-24.80, and for lower-middle-income countries vs upper-middle-income countries and HICs, 5.74 95% CI, 4.30-7.68). Conclusions and Relevance: This study is estimated to have included more than half of all new retinoblastoma cases worldwide in 2017. Children from LMICs, where the main global retinoblastoma burden lies, presented at an older age with more advanced disease and demonstrated a smaller proportion of familial history of retinoblastoma, likely because many do not reach a childbearing age. Given that retinoblastoma is curable, these data are concerning and mandate intervention at national and international levels. Further studies are needed to investigate factors, other than age at presentation, that may be associated with advanced disease in LMICs. © 2020 American Medical Association. All rights reserved

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)