Drug development challenges and strategies to address emerging and resistant fungal pathogens

McCarthy, Matthew W; Walsh, Thomas J.

doi:10.1080/14787210.2017.1328279

Cited by 41 publications

(27 citation statements)

References 104 publications

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“…Genomic analyses demonstrated the presence of a number of genes associated with virulence factors and reduced antifungal susceptibility in other Candida species. The possibility of the development of further antifungal resistance remains a significant concern and highlights the need for the development of novel antifungal agents (82). Further genome analysis to understand the development of resistance mechanisms and the impact upon the fitness of the organism is important to help in the development of appropriate antifungal recommendations for at-risk populations.…”

Section: Discussionmentioning

confidence: 99%

Candida auris: a Review of the Literature

et al. 2018

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The emerging pathogen has been associated with nosocomial outbreaks on five continents. Genetic analysis indicates the simultaneous emergence of separate clades of this organism in different geographical locations. Invasive infection and colonization have been detected predominantly in patients in high-dependency settings and have garnered attention due to variable antifungal resistance profiles and transmission within units instituting a range of infection prevention and control measures. Issues with the identification of using both phenotypic and molecular techniques have raised concerns about detecting the true scale of the problem. This review considers the literature available on and highlights the key unknowns, which will provide direction for further work in this field.

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Section: Discussionmentioning

confidence: 99%

Candida auris: a Review of the Literature

et al. 2018

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“…This approach has been used previously for aggregation of clinical trial data for malaria, and in this instance has allowed IPD pooled meta-analysis to inform treatment guidelines with greater statistical power than would otherwise be possible [57]. Centralized patient registries have also been suggested for clinical trials of other tropical diseases [58], rare diseases [10] and resistant pathogens [59], where fragmented data reporting also occurs. Importantly, in outbreak settings, centralized databases should also be used to facilitate and advocate for ethical data collection and storage practices.…”

Section: Discussionmentioning

confidence: 99%

A systematic review and meta-analysis of patient data from the West Africa (2013–16) Ebola virus disease epidemic

Rojek

Salam

Ragotte

et al. 2019

Clinical Microbiology and Infection

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Background: Over 28 000 individuals were infected with Ebola virus during the West Africa (2013e2016) epidemic, yet there has been criticism of the lack of robust clinical descriptions of Ebola virus disease (EVD) illness from that outbreak. Objectives: To perform a meta-analysis of published data from the epidemic to describe the clinical presentation, evolution of disease, and predictors of mortality in individuals with EVD. To assess the quality and utility of published data for clinical and public health decision-making. Data sources: Primary articles available in PubMed and published between January 2014 and May 2017. Eligibility: Studies that sequentially enrolled individuals hospitalized for EVD and that reported acute clinical outcomes. Methods: We performed meta-analyses using random-effect models and assessed heterogeneity using the I 2 method. We assessed data representativeness by comparing meta-analysis estimates with WHO aggregate data. We examined data utility by examining the availability and compatibility of data sets. Results: In all, 3653 articles were screened and 34 articles were included, representing 16 independent cohorts of patients (18 overlapping cohorts) and at least 6168 individuals. The pooled estimate for case fatality rate was 51% (95% CI 46%e56%). However, pooling of estimates for clinical presentation, progression, and predictors of mortality in individuals with EVD were hampered by significant heterogeneity, and inadequate data on clinical progression. Our assessment of data quality found that heterogeneity was largely unexplained, and data availability and compatibility were poor. Conclusions: We have quantified a missed opportunity to generate reliable estimates of the clinical manifestations of EVD during the West Africa epidemic. Clinical data standards and data capture platforms are urgently needed.

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“…There are ongoing initiatives to develop antifungal vaccines and drugs with the potential to control invasive mycoses [46]. However, the distance between promising laboratory results and the translation of knowledge into benefits to the general population is unquestionably long.…”

Section: Perspectivesmentioning

confidence: 99%

Fungal diseases as neglected pathogens: A wake-up call to public health officials

2020

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Fungal diseases: A real threat to public healthHuman fungal diseases differ fundamentally from other infections in diverse ways. As eukaryotic pathogens, fungi share many similarities with their host cells, which impairs the development of antifungal compounds. Fungal tropism is highly variable, as pathogens infect a wide range of cell types. A single fungal pathogen can infect multiple tissues in the same patient (depending on the host's immunological status) and can undergo morphogenic shifts during infection. Fungi are still underappreciated as major pathogens by both the public and public health officials. Diseases caused by protozoa, bacteria, and viruses have been recognized as important public health issues for centuries. For instance, syphilis, influenza, and Chagas disease have been documented for over 100 years [1], while invasive mycoses were only widely acknowledged as medically important pathogens in the 1980s [2]. Viral diseases of major population impact (such as smallpox, influenza and-more recentlydengue, Zika, Chikungunya, and coronavirus) have affected millions of people with significant effects on human health in developed, developing, and less developed nations [3,4]. These conditions have boosted the generation of knowledge, which has led to the eradication of smallpox [5], the wide availability of effective vaccines [6], and the development of diagnostic and preventive tools against influenza [7] and, more recently, Zika [8]. Bacterial diseases have profoundly impacted human health at different times in history, and although the phenomenon of antimicrobial resistance is a matter of extreme concern, there are several effective tools for the prevention, treatment, and diagnosis of bacterial infections [9]. Human parasitosis have been recognized to negatively impact public health in different parts of the globe for decades, which has stimulated the ongoing development of vaccines, new drugs, and diagnostic tests for malaria, sleeping sickness, leishmaniasis, filariasis, and Chagas disease [10]. Fungal infections, however, are part of a different scenario. These diseases, for most of recorded history as well as the majority of the last century, have been rare or had a low impact on human health.The increase in the number of immunocompromised patients, some of whom are highly susceptible to fungal infections, has totally changed this picture. The invasive diseases caused by fungi, the so-called systemic mycoses, profoundly impact human health. Moreover, the Global Action Fund for Fungal Infections (GAFFI) also highlights the devastating impact of focal fungal diseases in individuals who often have intact immune systems. GAFFI estimates that more than 1 million eyes go blind each year due to fungal keratitis [11]. Nearly one billion people have skin mycoses, which makes this disease only slightly less common on the planet than headaches and dental caries. Fungal spores contribute to significant reactive airway diseases in over 10 million individuals. In total, the GAFFI estimates that over 300 mi...

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Drug development challenges and strategies to address emerging and resistant fungal pathogens

Cited by 41 publications

References 104 publications

Candida auris: a Review of the Literature

Candida auris: a Review of the Literature

A systematic review and meta-analysis of patient data from the West Africa (2013–16) Ebola virus disease epidemic

Fungal diseases as neglected pathogens: A wake-up call to public health officials

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