Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts

Camargo, José F.; Ahmed, Asim A.; Morris, Michele; Anjan, Shweta; Anderson, Anthony D.; Prado, Clara E.; Dalai, Sudeb C.; Martínez, Octavio; Komanduri, Krishna V.

doi:10.12688/f1000research.19766.2

Cited by 19 publications

(23 citation statements)

References 34 publications

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“…The sensitivity of Karius testing drops significantly with use of antimicrobials within 2 weeks of testing 7 and with antifungals for Aspergillus . 9 , 12 Our case demonstrates that the presence of empirical antifungal agents at the time of testing does not preclude a clinically actionable result, but detection may occur in the range of other asymptomatic organisms (<300 MPM).…”

Section: Discussionmentioning

confidence: 79%

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case

Arrighi‐Allisan¹,

Vidaurrazaga²,

Chavez³

et al. 2022

Journal of Neurosurgery: Case Lessons

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BACKGROUND Cladophialophora bantiana is a dematiaceous, saprophytic fungus and a rare but reported cause of intracranial abscesses due to its strong neurotropism. Although it predominantly affects immunocompetent individuals with environmental exposure, more recently, its significance as a highly lethal opportunistic infection in transplant recipients has been recognized. Successful treatment requires timely but often challenging diagnosis, followed by complete surgical excision. Next-generation sequencing of microbial cell-free DNA (cfDNA) from plasma is a novel diagnostic method with the potential to identify invasive fungal infections more rapidly and less invasively than conventional microbiological testing, including brain biopsy. OBSERVATIONS The authors described the case of a recipient of a liver transplant who presented with seizures and was found to have innumerable ring-enhancing intracranial lesions. The Karius Test, a commercially available method of next-generation sequencing of cfDNA, was used to determine the causative organism. Samples from the patient’s plasma identified C. bantiana 6 days before culture results of the surgical specimen, allowing optimization of the empirical antifungal regimen, which led to a reduction in the size of the abscesses. LESSONS The authors’ findings suggest that microbial cfDNA sequencing may be particularly impactful in improving the management of brain abscesses in which the differential diagnosis is wide because of immunosuppression.

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Section: Discussionmentioning

confidence: 79%

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case

Arrighi‐Allisan¹,

Vidaurrazaga²,

Chavez³

et al. 2022

Journal of Neurosurgery: Case Lessons

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“…However, others have reported potential increased diagnostic yield of plasma mcfDNA sequencing compared with SOC tests in certain clinical scenarios (14)(15)(16)58). Some have noted the test to be commonly applied in managing severely ill, especially IC, patients (59), who are more likely to be infected with unusual, and difficult to diagnose pathogens (60,61).…”

Section: Discussionmentioning

confidence: 99%

Plasma Microbial Cell-free DNA Sequencing from Over 15,000 Patients Identified a Broad Spectrum of Pathogens

Park¹,

Chang²,

Ledeboer

et al. 2023

Preprint

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Microbial cell-free DNA (mcfDNA) sequencing is an emerging infectious disease diagnostic tool which enables unbiased pathogen detection from plasma. The Karius Test®, a commercial mcfDNA sequencing assay developed by and available since 2017 from Karius, Inc. (Redwood City, CA), detects and quantifies mcfDNA as molecules/μl in plasma. The commercial sample data and results for all tests conducted from April 2018 through mid-September 2021 were evaluated for laboratory performance metrics, reported pathogens, and data from test requisition forms. A total of 18,690 reports were generated from 15,165 patients in a hospital setting among 39 states and the District of Columbia. The median time from sample receipt to reported result was 26 hours (IQR 25–28), and 96% of samples had valid test results. Almost two-thirds (65%) of patients were adults, and 29% at the time of diagnostic testing had ICD10 codes representing a diverse array of clinical scenarios. There were 10,752 (58%) reports that yielded at least one taxon for a total of 22,792 detections spanning 701 unique microbial taxa. The 50 most common taxa detected included 36 bacteria, 9 viruses, and 5 fungi. Opportunistic fungi (374Aspergillusspp., 258Pneumocystis jirovecii, 196Mucorales, and 33 dematiaceous fungi) comprised 861 (4%) of all detections. Additional diagnostically challenging pathogens (247 zoonotic and vector borne pathogens, 144Mycobacteria, 80Legionellaspp., 78 systemic dimorphic fungi, 69Nocardiaspp., and 57 protozoan parasites) comprised 675 (3%) of all detections. We report the largest cohort of patients tested using plasma mcfDNA sequencing. The wide variety of pathogens detected by plasma mcfDNA sequencing reaffirm our understanding of the ubiquity of some infections while also identifying taxa less commonly detected by conventional methods.

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“…So, a prompt and accurate diagnosis of meningitis of multipathogenic infections in HIV-infected patients is still difficult to achieve. NGS, as a highly sensitive, culture-independent and unbiased method, can identify all potentially known, new or unexpected pathogens (9,10).…”

Section: Discussionmentioning

confidence: 99%

Case Report: Streptococcus Suis Meningitis Diagnosed in a HIV-Infected Patient With Cryptococcal Meningitis Using Next-Generation Sequencing

et al. 2021

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Background: Streptococcus suis has been recognized as a zoonotic pathogen that may cause infections in humans. Although rarely described, it is not surprising that both cryptococcal and streptococcus suis meningitis infections can co-exist in a HIV-infected patient with a low CD4 count. However, a fast and accurate diagnose of meningitis of multipathogenic infections is challenging. In this report, we describe such a case of a HIV-infected patient with meningitis of multipathogenic infections.Case Presentation: The patient was a 34-year-old Chinese male who was diagnosed with cryptococcal meningitis and HIV at the same time about 1 year ago. During the same time period, he had received (with good compliance) fluconazole and tenofovir-lamivudine- dolutegravir based antiretroviral therapy (ART). However, symptom of progressively worsening occipital headache appeared after he was exposed to a truck which was used for transporting pigs. Initial workup indicated an increase of the cerebrospinal fluid (CSF) opening pressure (OP) and an increase in the number of lymphocytes and proteins in CSF. A magnetic resonance imaging (MRI) scan revealed that partial cerebellar surface enhancement. The cryptococcus capsular antigen test of CSF was positive. The results of the India Ink microscopy for cryptococcus, nucleic acid of CMV and EBV and mycobacterium tuberculosis (MTB) tests of CSF were negative. The results of the bacteria and fungi smear and culture of CSF were also negative. Eventually, streptococcus suis was detected using next-generation sequencing (NGS) in CSF. The diagnosis of Streptococcus suis meningitis was made based on the patient's contact history with carrier pigs and the clinical findings addressed above. The treatment of 2 weeks of intravenous ceftriaxone and 1 week of oral moxifloxacin resulted in improvement of the condition of CSF. The anti-fungal treatment using fluconazole continued until the CFS OP went down to a normal level and the cryptococcus capsular antigen test of CSF was negative 6 months later.Conclusion: This case highlights that NGS might be beneficial to HIV-infected patients who have meningitis with negative CSF culture results. Multiple etiologies for such condition in the immunocompromised patients must be taken into consideration and early stage NGS is recommended.

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Next-generation sequencing of microbial cell-free DNA for rapid noninvasive diagnosis of infectious diseases in immunocompromised hosts

Cited by 19 publications

References 34 publications

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case

Utility of liquid biopsy in diagnosing isolated cerebral phaeohyphomycosis: illustrative case

Plasma Microbial Cell-free DNA Sequencing from Over 15,000 Patients Identified a Broad Spectrum of Pathogens

Case Report: Streptococcus Suis Meningitis Diagnosed in a HIV-Infected Patient With Cryptococcal Meningitis Using Next-Generation Sequencing

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