scholarly journals Fungal Genomics in Respiratory Medicine: What, How and When?

Author(s):  
Amelie P. Brackin ◽  
Sam J. Hemmings ◽  
Matthew C. Fisher ◽  
Johanna Rhodes

AbstractRespiratory infections caused by fungal pathogens present a growing global health concern and are a major cause of death in immunocompromised patients. Worryingly, coronavirus disease-19 (COVID-19) resulting in acute respiratory distress syndrome has been shown to predispose some patients to airborne fungal co-infections. These include secondary pulmonary aspergillosis and mucormycosis. Aspergillosis is most commonly caused by the fungal pathogen Aspergillus fumigatus and primarily treated using the triazole drug group, however in recent years, this fungus has been rapidly gaining resistance against these antifungals. This is of serious clinical concern as multi-azole resistant forms of aspergillosis have a higher risk of mortality when compared against azole-susceptible infections. With the increasing numbers of COVID-19 and other classes of immunocompromised patients, early diagnosis of fungal infections is critical to ensuring patient survival. However, time-limited diagnosis is difficult to achieve with current culture-based methods. Advances within fungal genomics have enabled molecular diagnostic methods to become a fast, reproducible, and cost-effective alternative for diagnosis of respiratory fungal pathogens and detection of antifungal resistance. Here, we describe what techniques are currently available within molecular diagnostics, how they work and when they have been used.


Author(s):  
Sony Paul ◽  
Iyanar Kannan

Background and Purpose: Opportunistic fungal infections have been on a growingtrend since the last two decades. Among the opportunistic fungal agents, Candidaspecies, Cryptococcus neoformans, and Aspergillus fumigatus account for most of thelife-threatening infections in immunocompromised individuals. Regarding this, thepresent study aimed to investigate the molecular identification and antifungalsusceptibility pattern of Candida species isolated from HIV-infected patients.Materials and Methods: This study was conducted on 80 clinical samples collectedfrom HIV-infected patients with suspected candidiasis referring to Tagore MedicalCollege and Hospital, Rathinamangalam and Government Hospital of ThoracicMedicine, in Chennai, India, for 18 months (i.e., May 2016-December 2017). Phenotypicand molecular identification was accomplished using internal transcribed spacer region 1(ITS1) and ITS4 primers. The antifungal susceptibility pattern of the isolates against fourantifungal agents was also determined by both disk diffusion and broth dilution methods.Results: In the present study, the prevalence of candidiasis was obtained as 75% (n=60).Candida tropicalis was the predominant identified species. All the emerging species(i.e., Kodamaea ohmeri, Hanseniaspora opuntiae, and C. orthopsilosis) were identifiedthrough molecular identification since the phenotypic identification was inconclusive. Interms of the susceptibility pattern, 63.3% and 18.3% of the isolates were resistant tofluconazole and voriconazole, respectively. Candida albicans was also found to beresistant to amphotericin B.Conclusion: Molecular assay led to the identification of K. ohmeri, H. opuntiae, and C.orthopsilosis, which were multidrug-resistant. This study highlighted the need for theprompt and timely identification of clinical yeast isolates given the emergence of manyrare species and their capability of causing life-threatening infections and outbreaks. Inthe laboratories where molecular diagnostic methods are not available, alternativeservices of reference laboratories can be utilized as cost-effective measures. With regardto the growing prevalence of antifungal drug resistance, antifungal susceptibility testingshould be made mandatory for effective patient management.



2021 ◽  
Vol 17 (2) ◽  
pp. 118-124
Author(s):  
Amirmehdi Sarvestani ◽  
Mohammad Almasian ◽  
Amirhossein Nafari

Background: The prevalence of fungal infections has been increasing in recent years. Cystic fibrosis (CF) is a genetic disorder that affects organs such as the intestines, liver, pancreas, and especially the lungs. Introduction: Fungal pathogens are becoming a challenge in CF. Advanced medical science is associated with longer life expectancy in some patient groups. Method: A review was conducted on studies found on online databases, including Google Scholar, PubMed, and Scopus. Internet-based searches were performed on these databases for cystic fibrosis, respiratory infections, and fungal infection profiling to identify all relevant studies published between 2010 and 2020. Result: Fungal pathogens most frequently isolated from the respiratory tract include the Aspergillus genus, the Candida genus, Scedosporium apiospermum, and the Rasamsonia genus. In cystic fibrosis, these organisms usually colonize the respiratory and intestinal tracts and cause hypersensitivity responses and invasive diseases. Conclusion: Fungus-patient interactions are complicated and depend on various factors. Moreover, the emergence of drug-resistant species is a serious health issue, and the development of new treatments is crucial.



2021 ◽  
Vol 30 (3) ◽  
pp. 127-134
Author(s):  
Shaimaa A.S. Selem ◽  
Neveen A. Hassan ◽  
Mohamed Z. Abd El-Rahman ◽  
Doaa M. Abd El-Kareem

Background: In intensive care units, invasive fungal infections have become more common, particularly among immunocompromised patients. Early identification and starting the treatment of those patients with antifungal therapy is critical for preventing unnecessary use of toxic antifungal agents. Objective: The aim of this research is to determine which common fungi cause invasive fungal infection in immunocompromised patients, as well as their antifungal susceptibility patterns in vitro, in Assiut University Hospitals. Methodology: This was a hospital based descriptive study conducted on 120 patients with clinical suspicion of having fungal infections admitted at different Intensive Care Units (ICUs) at Assiut University Hospitals. Direct microscopic examination and inoculation on Sabouraud Dextrose Agar (SDA) were performed on the collected specimens. Isolated yeasts were classified using phenotypic methods such as chromogenic media (Brilliance Candida agar), germ tube examination, and the Vitek 2 system for certain isolates, while the identification of mould isolates was primarily based on macroscopic and microscopic characteristics. Moulds were tested in vitro for antifungal susceptibility using the disc diffusion, and yeast were tested using Vitek 2 device cards. Results: In this study, 100 out of 120 (83.3%) of the samples were positive for fungal infection. Candida and Aspergillus species were the most commonly isolated fungal pathogens. The isolates had the highest sensitivity to Amphotericin B (95 %), followed by Micafungin (94 %) in an in vitro sensitivity survey. Conclusion: Invasive fungal infections are a leading cause of morbidity and mortality in immunocompromised patients, with Candida albicans being the most frequently isolated yeast from various clinical specimens; however, the rise in resistance, especially to azoles, is a major concern.



2021 ◽  
Vol 8 ◽  
Author(s):  
Renato L. Santos ◽  
Tayse D. Souza ◽  
Juliana P. S. Mol ◽  
Camila Eckstein ◽  
Tatiane A. Paíxão

Canine brucellosis is an infectious and zoonotic disease caused by Brucella canis, which has been reported worldwide, and is a major public health concern due to close contact between dogs and humans. In dogs, canine brucellosis manifests with abortion outbreaks, reproductive failure, enlargement of lymph nodes, and occasionally affects the osteoarticular system, although the occurrence of asymptomatic infections in dogs are not uncommon. In humans, the disease is associated with a febrile syndrome, commonly with non-specific symptoms including splenomegaly, fatigue, and weakness. Infection of dogs occurs mostly by the oronasal route when in contact with contaminated tissues such as aborted fetuses, semen, urine, and vaginal secretions. In humans, contact with contaminated fluids from infected dogs is an important source of infection, and it is an occupational risk for veterinarians, breeders, laboratory workers, among other professionals who deal with infected animals or biological samples. The diagnosis in dogs is largely based on serologic methods. However, serologic diagnosis of canine brucellosis remains very challenging due to the low accuracy of available tests. Molecular diagnostic methods have been increasingly used in the past few years. Treatment of infected dogs is associated with a high frequency of relapse, and should be employed only in selected cases. Currently there are no commercially available vaccines for prevention of canine brucellosis. Therefore, development of novel and improved diagnostic methods as well as the development of efficacious and safe vaccination protocols are needed for an effective control of canine brucellosis and its associated zoonotic risk.



Author(s):  
Behnam Honarvar ◽  
Kamran Bagheri Lankarani ◽  
Mehdi Taghavi ◽  
Ghasem Vahedi ◽  
Esmaeil Mortaz

Invasive fungal infections (IFIs) are among the life-threatening issues in patients with impaired immune system. High administration of antifungals in these patients imposes a heavy economic burden on the national health system. In addition, despite the usually expensive antifungal regimens, the mortality rate due to fungal infections is still high, resulting in the loss of hundreds of lives per year.Survival rate is an indicator of the success of national healthcare policies. Early diagnosis of IFI is critical because any delays may be fatal. The weakness of the old-fashioned culture-based diagnostic methods lies in their time-consuming laboratory procedures. To overcome this problem, several diagnostic approaches have been developed to facilitate the early diagnosis of invasive candidiasis as the most prevalent IFI.These methods are based on the detection of serologic and molecular footprints. However, nowadays, antibiotic resistance and proper and cost-effective use of antibiotics are given special attention in national healthcare policies. The instructions for controlling these indices have been collected under the name of antibiotic stewardship. The present review study was targeted toward providing insight into novel diagnostic biomarkers and antifungal stewardship programs. The simultaneous investigation of these two issues facilitates the achievement of a novel health policy for the treatment of systemic candidiasis in immunocompromised patients.



2019 ◽  
Vol 8 (1) ◽  
pp. 6-15
Author(s):  
P. M. Ridzuan ◽  
C. M. Nazira ◽  
Manuel Ruth ◽  
C. N. Abdul Rassip ◽  
M. H Nur Raihan ◽  
...  

Dermatomycosis is a fungal infection of the skin, hair and nail caused by Trichophyton, Microsporum and Epidermophyton. These organisms are found in the environment, humans and animals in forms of yeast or mold. There are many factors that contribute to the growth of fungal infections in human body. But still majority of virulent factors and mechanisms of the diseases of fungi are not clear. This review paper describes types of fungal infections, their classification, epidemiology and new insights into pathogenesis with the focus on molecular mechanisms of the diseases. Furthermore, traditional and novel molecular diagnostic methods and the variety of drug treatment and the development of resistance against these drugs are discussed.



2021 ◽  
Vol 42 (03) ◽  
pp. 471-482
Author(s):  
Cassie C. Kennedy ◽  
Kelly M. Pennington ◽  
Elena Beam ◽  
Raymund R. Razonable

AbstractInvasive fungal infections threaten lung transplant outcomes with high associated morbidity and mortality. Pharmacologic prophylaxis may be key to prevent posttransplant invasive fungal infections, but cost, adverse effects, and absorption issues are barriers to effective prophylaxis. Trends in fungal infection diagnostic strategies utilize molecular diagnostic methodologies to complement traditional histopathology and culture techniques. While lung transplant recipients are susceptible to a variety of fungal pathogens, Candida spp. and Aspergillus spp. infections remain the most common. With emerging resistant organisms and multiple novel antifungal agents in the research pipeline, it is likely that treatment strategies will continue to evolve.



2021 ◽  
Vol 12 ◽  
Author(s):  
Akanksha Roberts ◽  
Raghuraj Singh Chouhan ◽  
Deepshikha Shahdeo ◽  
Narlawar Sagar Shrikrishna ◽  
Veerbhan Kesarwani ◽  
...  

Coronavirus disease 2019 (COVID-19), which started out as an outbreak of pneumonia, has now turned into a pandemic due to its rapid transmission. Besides developing a vaccine, rapid, accurate, and cost-effective diagnosis is essential for monitoring and combating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its related variants on time with precision and accuracy. Currently, the gold standard for detection of SARS-CoV-2 is Reverse Transcription Polymerase Chain Reaction (RT-PCR), but it lacks accuracy, is time-consuming and cumbersome, and fails to detect multi-variant forms of the virus. Herein, we have summarized conventional diagnostic methods such as Chest-CT (Computed Tomography), RT-PCR, Loop Mediated Isothermal Amplification (LAMP), Reverse Transcription-LAMP (RT-LAMP), as well new modern diagnostics such as CRISPR–Cas-based assays, Surface Enhanced Raman Spectroscopy (SERS), Lateral Flow Assays (LFA), Graphene-Field Effect Transistor (GraFET), electrochemical sensors, immunosensors, antisense oligonucleotides (ASOs)-based assays, and microarrays for SARS-CoV-2 detection. This review will also provide an insight into an ongoing research and the possibility of developing more economical tools to tackle the COVID-19 pandemic.



2018 ◽  
Author(s):  
Zeinab Mamouei ◽  
Abdullah Alqarihi ◽  
Shakti Singh ◽  
Shuying Xu ◽  
Michael K. Mansour ◽  
...  

AbstractInvasive fungal infections due to Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans, constitute a substantial threat to hospitalized, immunocompromised patients. Further, the presence of drug-recalcitrant biofilms on medical devices, and emergence of drug-resistant fungi such as Candida auris, introduce treatment challenges with current antifungal drugs. Worse, currently there is no approved drug capable of obviating preformed biofilms which increases the chance of infection relapses. Here, we screened a small molecule Prestwick Chemical Library, consisting of 1200 FDA approved off-patent drugs, against C. albicans, C. auris and A. fumigatus, to identify those that inhibit growth of all three pathogens. Inhibitors were further prioritized for their potency against other fungal pathogens, and their ability to kill preformed biofilms. Our studies identified the bis-biguanide Alexidine dihydrochloride (AXD), as a drug with the highest antifungal and anti-biofilm activity against a diverse range of fungal pathogens. Finally, AXD significantly potentiated the efficacy of fluconazole against biofilms, displayed low mammalian cell toxicity, and eradicated biofilms growing in mice central venous catheters in vivo, highlighting its potential as a pan-antifungal drug.ImportanceThe prevalence of fungal infections has seen a rise in the past decades due to advances in modern medicine leading to an expanding population of device-associated and immunocompromised patients. Furthermore, the spectrum of pathogenic fungi has changed, with the emergence of multi-drug resistant strains such as C. auris. High mortality related to fungal infections point to major limitations of current antifungal therapy, and an unmet need for new antifungal drugs. We screened a library of repurposed FDA approved inhibitors to identify compounds with activities against a diverse range of fungi, in varied phases of growth. The assays identified Alexidine dihydrochloride (AXD) to have pronounced antifungal activity including against preformed biofilms, at concentrations lower than mammalian cell toxicity. AXD potentiated the activity of fluconazole and amphotericin B against Candida biofilms in vitro, and prevented biofilm growth in vivo. Thus AXD has the potential to be developed as a pan-antifungal, anti-biofilm drug.





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