Diagnosis of central nervous system invasive aspergillosis in a liver transplant recipient using microbial cell‐free next generation DNA sequencing

Abstract

Invasive aspergillosis (IA) is in an important opportunistic infection affecting transplant patients. 1,2 While all solid organ transplant recipients are at risk for invasive aspergillosis, liver transplant patients appear to be at particularly high risk for disseminated disease and have poor outcomes, with mortality ranging from 64% to 100%. 1,3 For liver transplant recipients, time to onset of IA after transplant is decreased when compared to other organ transplant recipients. 1,3,4 Additionally, liver disease itself, in the absence of a transplant, portends an increased risk for IA. [1][2][3]5,6 Typically, IA is caused by Aspergillus fumigatus and the most frequent manifestation of infection is invasive pulmonary disease. 1 However, disseminated aspergillosis including, intraabdominal, intravascular and neurological involvement is not uncommon. [1][2][3][4]6 While pulmonary IA can be relatively simple to diagnose with use of respiratory samples, serum antigens and imaging, central nervous system (CNS) IA can pose diagnostic challenges which are associated with delayed diagnosis and poor outcomes. 1,3,[5][6][7] Microbial cell-free DNA sequencing (mcfDNA) is a diagnostic modality that has recently shown value as an adjunctive test for the diagnosis of fungal pneumonia in stem-cell transplant patients. 8 When compared to standard diagnostic methods, use of mcfDNA had a 51% sensitivity and 100% specificity. Herein, we present a case demonstrating the utility of this novel diagnostic technique in the diagnosis of fungal brain abscesses in a patient who had recently undergone liver transplantation.

Clinical impact of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay on treatment decisions: a single-center retrospective study

“…In theory, KT may have greater impact in these patients given the broader differential of infectious pathogens and lower sensitivity of conventional diagnostics to detect them. This finding appears consistent with Rossoff et al who found that KT testing netted a higher yield of clinically relevant pathogens in immunocompromised patients (61%) than in immunocompetent patients (35%) [ 10 ] as well as prior reports of utility in diagnosing mold infections in immunocompromised patients and opportunistic infections in HIV patients [ 3 , 6 , 12 – 14 ].…”

Rapid Genomic Diagnosis of Fungal Infections in the Age of Next-Generation Sequencing

“…Lastly, publications were searched using specific fungal names and after manual examination five extra articles were added. Therefore, in total 52 articles were included in this review [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

“…It was a case of allergic bronchopulmonary mycosis where A. fumigatus and Schizophyllum commune sequences were detected in the homogenised sputum and mucoid plugs of the patient [ 26 ]. Since then, up to the time of writing, a total of 319 cases of fungal infections diagnosed by NGS were described in the literature, with some in case reports and others in case series or cohorts [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. In 40 out of the 319 cases (12.5%), more than 1 fungus was detected by NGS [ 26 , ...…”

“…In recent years, commercial services for NGS-based pathogen detection such as the Karius Test, whose pathogen list includes over 400 fungi, have emerged, which makes the costs for testing individual samples more favourable. This cell-free DNA test was developed based on blood samples from patients with invasive infections for pathogen detection, and it has been successfully applied for the diagnosis of fungal infection in several cases [ 36 , 47 , 69 ].…”

“… Distribution of fungal species detected by next-generation sequencing from clinical samples of patients with suspected infections reported in the literature [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ]. There was a total of 319 cases with 365 fungi detected.…”