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  • 1
    In: Mycoses, Wiley, Vol. 59, No. 7 ( 2016-07), p. 450-466
    Abstract: Aspergillus fumigatus is a widespread opportunistic fungal pathogen causing an alarmingly high mortality rate in immunocompromised patients. Nosocomial infections by drug‐resistant A. fumigatus strains are of particular concern, and there is a pressing need to understand the origin, dispersal and long‐term evolution of drug resistance in this organism. The objective of this study was to investigate the diversity and putative origins of triazole resistance of A. fumigatus from India. Eighty‐nine isolates, including 51 multiple triazole resistant ( MTR ) isolates and 38 azole‐susceptible isolates, were genotyped using multilocus sequence typing ( MLST ), mating typing and PCR fingerprinting. MLST resolved the 51 MTR isolates into three genotypes, two of which have susceptible counterparts, suggesting that MTR isolates originated multiple times in India. The multiple‐origin hypothesis was further supported by the diversity of sequences at the triazole target gene CYP 51A among the MTR isolates, and by PCR fingerprints. Interestingly, there is abundant evidence for mating and recombination in natural population of A. fumigatus in India, suggesting that sexual spread of TR 34 /L98H, the dominant MTR allele, is possible. Our results call for greater attention to MTR in A. fumigatus and for better management of antifungal drug use.
    Type of Medium: Online Resource
    ISSN: 0933-7407 , 1439-0507
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2020780-3
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  • 2
    In: Canadian Journal of Microbiology, Canadian Science Publishing, Vol. 64, No. 2 ( 2018-02), p. 119-130
    Abstract: Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen that can cause aspergillosis in humans. Over the last decade there have been increasing global reports of treatment failure due to triazole resistance. An emerging hypothesis states that agricultural triazole fungicide use causes clinical triazole resistance. Here we test this hypothesis in Hamilton, Ontario, Canada, by examining a total of 195 agricultural, urban, and clinical isolates using 9 highly polymorphic microsatellite markers. For each isolate, the in vitro susceptibilities to itraconazole and voriconazole, 2 triazole drugs commonly used in the management of patients, were also determined. Our analyses suggested frequent gene flow among the agricultural, urban environmental, and clinical populations of A. fumigatus and found evidence for widespread sexual recombination within and among the different populations. Interestingly, all 195 isolates analyzed in this study were susceptible to both triazoles tested. However, compared with the urban population, agricultural and clinical populations showed significantly reduced susceptibility to itraconazole and voriconazole, consistent with ecological niche-specific selective pressures on A. fumigatus populations in Hamilton. Frequent gene flow and genetic recombination among these populations suggest greater attention should be paid to monitor A. fumigatus populations in Hamilton and other similar jurisdictions.
    Type of Medium: Online Resource
    ISSN: 0008-4166 , 1480-3275
    RVK:
    Language: English
    Publisher: Canadian Science Publishing
    Publication Date: 2018
    detail.hit.zdb_id: 280534-0
    detail.hit.zdb_id: 1481972-7
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Elsevier BV ; 2015
    In:  Infection, Genetics and Evolution Vol. 36 ( 2015-12), p. 199-209
    In: Infection, Genetics and Evolution, Elsevier BV, Vol. 36 ( 2015-12), p. 199-209
    Type of Medium: Online Resource
    ISSN: 1567-1348
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2015
    detail.hit.zdb_id: 2057622-5
    SSG: 12
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  • 4
    In: The Lancet, Elsevier BV, Vol. 389, No. 10084 ( 2017-05), p. 2105-2116
    Type of Medium: Online Resource
    ISSN: 0140-6736
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2018
    In:  Infection and Drug Resistance Vol. Volume 11 ( 2018-09), p. 1549-1555
    In: Infection and Drug Resistance, Informa UK Limited, Vol. Volume 11 ( 2018-09), p. 1549-1555
    Type of Medium: Online Resource
    ISSN: 1178-6973
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2018
    detail.hit.zdb_id: 2494856-1
    SSG: 15,3
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2018
    In:  Genes Vol. 9, No. 7 ( 2018-07-19), p. 359-
    In: Genes, MDPI AG, Vol. 9, No. 7 ( 2018-07-19), p. 359-
    Abstract: The United Nations’ One Health initiative advocates the collaboration of multiple sectors within the global and local health authorities toward the goal of better public health management outcomes. The emerging global health threat posed by Aspergillus species is an example of a management challenge that would benefit from the One Health approach. In this paper, we explore the potential role of molecular epidemiology in Aspergillus threat management and strengthening of the One Health initiative. Effective management of Aspergillus at a public health level requires the development of rapid and accurate diagnostic tools to not only identify the infecting pathogen to species level, but also to the level of individual genotype, including drug susceptibility patterns. While a variety of molecular methods have been developed for Aspergillus diagnosis, their use at below-species level in clinical settings has been very limited, especially in resource-poor countries and regions. Here we provide a framework for Aspergillus threat management and describe how molecular epidemiology and experimental evolution methods could be used for predicting resistance through drug exposure. Our analyses highlight the need for standardization of loci and methods used for molecular diagnostics, and surveillance across Aspergillus species and geographic regions. Such standardization will enable comparisons at national and global levels and through the One Health approach, strengthen Aspergillus threat management efforts.
    Type of Medium: Online Resource
    ISSN: 2073-4425
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2527218-4
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  • 7
    Online Resource
    Online Resource
    American Society for Microbiology ; 2017
    In:  mSphere Vol. 2, No. 1 ( 2017-02-22)
    In: mSphere, American Society for Microbiology, Vol. 2, No. 1 ( 2017-02-22)
    Abstract: Aspergillus fumigatus is a ubiquitous opportunistic fungal pathogen capable of causing invasive aspergillosis, a globally distributed disease with a mortality rate of up to 90% in high-risk populations. Effective control and prevention of this disease require a thorough understanding of its epidemiology. However, despite significant efforts, the global molecular epidemiology of A. fumigatus remains poorly understood. In this study, we analyzed 2,026 A. fumigatus isolates from 13 countries in four continents using nine highly polymorphic microsatellite markers. Genetic cluster analyses suggest that our global sample of A. fumigatus isolates belonged to eight genetic clusters, with seven of the eight clusters showing broad geographic distributions. We found common signatures of sexual recombination within individual genetic clusters and clear evidence of hybridization between several clusters. Limited but statistically significant genetic differentiations were found among geographic and ecological populations. However, there was abundant evidence for gene flow at the local, regional, and global scales. Interestingly, the triazole-susceptible and triazole-resistant populations showed different population structures, consistent with antifungal drug pressure playing a significant role in local adaptation. Our results suggest that global populations of A. fumigatus are shaped by historical differentiation, contemporary gene flow, sexual reproduction, and the localized antifungal drug selection that is driving clonal expansion of genotypes resistant to multiple triazole drugs. IMPORTANCE The genetic diversity and geographic structure of the human fungal pathogen A. fumigatus have been the subject of many studies. However, most previous studies had relatively limited sample ranges and sizes and/or used genetic markers with low-level polymorphisms. In this paper, we characterize a global collection of strains of A. fumigatus using a panel of 9 highly polymorphic microsatellite markers. Using these markers, we analyze 2,026 isolates, which is ~3 times the number of isolates reported so far in previous studies. Our analyses suggest that A. fumigatus contains historically differentiated genetic populations but that its evolution is significantly impacted by contemporary forces such as widespread gene flow and local antifungal drug pressure. In the wake of a global rise in resistance to azoles in fungal pathogens, our findings should aid in developing management strategies to mitigate current increases to azole resistance.
    Type of Medium: Online Resource
    ISSN: 2379-5042
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2017
    detail.hit.zdb_id: 2844248-9
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  • 8
    In: Infection and Immunity, American Society for Microbiology, Vol. 84, No. 4 ( 2016-04), p. 906-916
    Abstract: Nasopharyngeal colonization by the Gram-positive bacterium Streptococcus pneumoniae is a prerequisite for pneumonia and invasive pneumococcal diseases. Colonization is asymptomatic, involving dynamic and complex interplay between commensals, the host immune system, and environmental factors. The elderly are at an increased risk of developing pneumonia, which might be due to changes in the respiratory microbiota that would impact bacterial colonization and persistence within this niche. We hypothesized that the composition of the upper respiratory tract (URT) microbiota changes with age and subsequently can contribute to sustained colonization and inefficient clearance of S. pneumoniae . To test this, we used a mouse model of pneumococcal colonization to compare the composition of the URT microbiota in young, middle-aged, and old mice in the naive state and during the course of colonization using nasal pharyngeal washes. Sequencing of variable region 3 (V3) of the 16S rRNA gene was used to identify changes occurring with age and throughout the course of S. pneumoniae colonization. We discovered that age affects the composition of the URT microbiota and that colonization with S. pneumoniae is more disruptive of preexisting communities in older mice. We have further shown that host-pathogen interactions following S. pneumoniae colonization can impact the populations of resident microbes, including Staphylococcus and Haemophilus . Together, our findings indicate alterations to the URT microbiota could be detrimental to the elderly, resulting in increased colonization of S. pneumoniae and decreased efficiency in its clearance.
    Type of Medium: Online Resource
    ISSN: 0019-9567 , 1098-5522
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2016
    detail.hit.zdb_id: 1483247-1
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  • 9
    Online Resource
    Online Resource
    Global Health and Education Projects, Inc. (GHEP) ; 2017
    In:  International Journal of Maternal and Child Health and AIDS (IJMA) Vol. 6, No. 2 ( 2017-12-31), p. 121-129
    In: International Journal of Maternal and Child Health and AIDS (IJMA), Global Health and Education Projects, Inc. (GHEP), Vol. 6, No. 2 ( 2017-12-31), p. 121-129
    Abstract: Background and Introduction: Emigration of healthcare workers from developing countries is on the rise and there is an urgent need for policies that increase access to and continuity of healthcare. In this commentary, we highlight some of the negative impacts of emigration on maternal and child health and discuss whether team-based healthcare delivery could possibly mitigate the shortfall of maternal and child health professionals in developing countries.Methodology: We cross-examine the availability of supporting structures to implement team-based maternal and child healthcare delivery in developing countries. We briefly discuss three key supporting structures: culture of sharing, telecommunication, and inter-professional education. Supporting structures are examined at system, organizational and individual levels. We argue that the culture of sharing, limited barriers to inter-professional education and increasing access to telecommunication will be advantageous to implementing team-based healthcare delivery in developing countries.Conclusion and Global Health Implications: Although most developing countries may have notable supporting structures to implement team-based healthcare delivery, the effectiveness of such models in terms of cost, time and infrastructure in resource limited settings is still to be evaluated. Hence, we call on usual stakeholders, government, regulatory colleges and professional associations in countries with longstanding emigration of maternal and child healthcare workers to invest in establishing comprehensive models needed to guide the development, implementation and evaluation of team-based maternal and child healthcare delivery.Key words: Emigration • Skilled health workers • Developing countries • Maternal and child health • Newborn •Team-based health careCopyright © 2017 Owusu et al. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0. 
    Type of Medium: Online Resource
    ISSN: 2161-864X , 2161-8674
    URL: Issue
    Language: Unknown
    Publisher: Global Health and Education Projects, Inc. (GHEP)
    Publication Date: 2017
    detail.hit.zdb_id: 2715876-7
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2017
    In:  Mycoses Vol. 60, No. 11 ( 2017-11), p. 739-748
    In: Mycoses, Wiley, Vol. 60, No. 11 ( 2017-11), p. 739-748
    Abstract: Aspergillus fumigatus is a saprophytic fungus that can cause lethal invasive aspergillosis in immunocompromised patients. Recent studies have shown that Eurasian and North American populations of A. fumigatus often consist of genetically diverse strains. However, very little is known about African populations of A. fumigatus . Here, we characterise the genetic diversity and triazole susceptibility of A. fumigatus in Cameroon, West Africa. A total of 495 soil samples were obtained from nine collection sites in three Cameroonian regions. Nine microsatellite markers were used to genotype all 51 identified A. fumigatus isolates. In vitro susceptibility to itraconazole and voriconazole was tested using micro broth dilution. The 51 Cameroonian A. fumigatus isolates belonged to 45 genotypes. Consistent with recombination, 32 of 36 possible pairwise loci combinations are phylogenetically incompatible. Interestingly, evidence for geographic sub‐structuring was found within Cameroon and the sub‐population with the most evidence of recombination was also the least susceptible sub‐population to the triazole antifungals tested. Furthermore, the Cameroonian sample was significantly differentiated from those in Eurasia and North America. Overall, our results indicate the genetic uniqueness of Cameroonian A. fumigatus populations and that additional novel genetic diversity likely exist in other parts of Africa.
    Type of Medium: Online Resource
    ISSN: 0933-7407 , 1439-0507
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
    detail.hit.zdb_id: 2020780-3
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