An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections

Jenks, Jeffrey D.; White, P. Lewis; Kidd, Sarah E.; Goshia, Tyler; Fraley, Stephanie I.; Hoenigl, Martin; Thompson, George R.

doi:10.1080/14737159.2023.2267977

Cited by 16 publications

(15 citation statements)

References 177 publications

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“…PPV and NPV were noted to be 84% and 99%, respectively, in a setting with a 10% prevalence of candidemia, whereas in low prevalence settings, PPV dropped to 15–31% [ 53 , 54 ]. Meta-analysis delineating its role in diagnosing IC revealed sensitivity and specificity as 91% and 94%, respectively, while sensitivity and specificity rose to 95% and 92% in candidemia [ 1 ]. The test has been included in the EORTC/MSG guidelines for diagnosis of IC [ 15 ].…”

Section: Molecular Diagnosis Of Common Fungal Infectionsmentioning

confidence: 99%

“…The rise has been attributed to the increased number of immunocompromised patients, immunosuppression, transplants, usage of steroids, and, in recent times, usage of immunomodulatory agents. Besides increasing immunosuppression, fungal infections are also increasingly being reported among patients with severe influenza, COVID-19, admission to ICUs, and patients with solid organ malignancy [ 1 ]. Another substantial factor contributing to the increased prevalence is the emergence of antifungal resistance.…”

Section: Introductionmentioning

confidence: 99%

“…Non-culture-based diagnostic modalities include nucleic-acid-based molecular techniques, serological, metabolomics, nano-diagnostic approaches, and hybridisation. Serological diagnosis exploiting biomarkers like cryptococcal lateral flow assays, galactomannan (GM), and 1,3, beta-D-glucan (BDG) detection has shown satisfactory results; however, it lacks sensitivity in antifungal therapy for moulds in HIV-negative and non-neutropenic patients [ 1 ]. Recently, candidalysin has been identified as a novel biomarker that can help in diagnosing C. albicans infections [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Nucleic-Acid-Based Molecular Fungal Diagnostics: A Way to a Better Future

Gudisa,

Harchand,

Rudramurthy

2024

Diagnostics

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The world has seen a tremendous increase in the number of fungal infections during the past two decades. Recently, the World Health Organisation released the pathogen priority list for fungal infections, signifying the importance of these infections in the fields of research and public health. Microbiology laboratories demand an upgrade in the diagnostic system to keep up with the increased burden of these infections. Diagnosis of fungal infections using conventional techniques has always faced limitations in terms of specificity, sensitivity, and turnaround time. Although these methods are the core pillars of the diagnosis, there is an increased need for molecular approaches. Molecular techniques have revolutionised the field of fungal diagnostics. The diverse array of molecular techniques, including techniques like Polymerase Chain Reaction (PCR), have emerged as a cornerstone in fungal diagnostics. Molecular techniques have transformed fungal diagnostics, providing powerful tools for the rapid and accurate identification of pathogens. As these technologies continue to evolve, their integration into routine clinical practice holds the promise of improving patient outcomes through timely and targeted antifungal interventions. This review will cover the molecular approaches involved in fungal diagnostics, moving from the basic techniques to the advanced-level nucleic-acid-based molecular approaches providing a high throughput and decreased turnaround time for the diagnosis of serious fungal infections.

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Section: Molecular Diagnosis Of Common Fungal Infectionsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nucleic-Acid-Based Molecular Fungal Diagnostics: A Way to a Better Future

Gudisa,

Harchand,

Rudramurthy

2024

Diagnostics

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“…Invasive mold infections (IMI) cause millions of infections globally and account for an estimated 1.6 million deaths annually(Bongomin et al 2017). Patients at risk from IMIs, including both severely immunocompromised and also more immunocompetent individuals(Jenks et al 2023), are increasing. IMIs in more immunocompetent persons/those receiving systemic corticosteroids are characterized by early tissue invasive growth in the lungs with bloodstream invasion potentially occurring later although not universally, while early angioinvasive growth is more common in severely immunocompromised persons (Jenks and Hoenigl 2018).…”

Section: Introductionmentioning

confidence: 99%

“…Incubation of fungal cultures for four weeks is considered best practice to maximize the recovery of slow growing species, with most detected by day 14 (Zhu and Qi, n.d.). BAL antigen tests, such as galactomannan (GM), can be helpful but are only positive for a limited number of specific mold organisms, and are further limited by variable turnaround times and lower sensitivity for individuals on mold-active antifungal prophylaxis or treatment (Jenks et al 2023). The absence of rapid and accessible fungal diagnostics often results in empiric utilization of systemic antifungals, mostly targeted against Aspergillus spp., some of which are lacking activity against other molds (Denning et al 2017).…”

Section: Introductionmentioning

confidence: 99%

Universal Digital High Resolution Melt for the detection of pulmonary mold infections

Goshia,

Aralar,

Wiederhold

et al. 2023

Preprint

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BackgroundInvasive mold infections (IMIs) such as aspergillosis, mucormycosis, fusariosis, and lomentosporiosis are associated with high morbidity and mortality, particularly in immunocompromised patients, with mortality rates as high as 40% to 80%. Outcomes could be substantially improved with early initiation of appropriate antifungal therapy, yet early diagnosis remains difficult to establish and often requires multidisciplinary teams evaluating clinical and radiological findings plus supportive mycological findings. Universal digital high resolution melting analysis (U-dHRM) may enable rapid and robust diagnosis of IMI. This technology aims to accomplish timely pathogen detection at the single genome level by conducting broad-based amplification of microbial barcoding genes in a digital polymerase chain reaction (dPCR) format, followed by high-resolution melting of the DNA amplicons in each digital reaction to generate organism-specific melt curve signatures that are identified by machine learning.MethodsA universal fungal assay was developed for U-dHRM and used to generate a database of melt curve signatures for 19 clinically relevant fungal pathogens. A machine learning algorithm (ML) was trained to automatically classify these 19 fungal melt curves and detect novel melt curves. Performance was assessed on 73 clinical bronchoalveolar lavage (BAL) samples from patients suspected of IMI. Novel curves were identified by micropipetting U-dHRM reactions and Sanger sequencing amplicons.ResultsU-dHRM achieved an average of 97% fungal organism identification accuracy and a turn-around-time of 4hrs. Pathogenic molds (Aspergillus, Mucorales, LomentosporaandFusarium)were detected by U-dHRM in 73% of BALF samples suspected of IMI. Mixtures of pathogenic molds were detected in 19%. U-dHRM demonstrated good sensitivity for IMI, as defined by current diagnostic criteria, when clinical findings were also considered.ConclusionsU-dHRM showed promising performance as a separate or combination diagnostic approach to standard mycological tests. The speed of U-dHRM and its ability to simultaneously identify and quantify clinically relevant mold pathogens in polymicrobial samples as well as detect emerging opportunistic pathogens may provide information that could aid in treatment decisions and improve patient outcomes.

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Diagnostic Studies: Role of Biomarkers

White

2024

Pulmonary Aspergillosis

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An update on current and novel molecular diagnostics for the diagnosis of invasive fungal infections

Cited by 16 publications

References 177 publications

Nucleic-Acid-Based Molecular Fungal Diagnostics: A Way to a Better Future

Nucleic-Acid-Based Molecular Fungal Diagnostics: A Way to a Better Future

Universal Digital High Resolution Melt for the detection of pulmonary mold infections

Diagnostic Studies: Role of Biomarkers

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