Genomic characterization of recurrent mold infections in thoracic transplant recipients

Abstract

Invasive mold disease in thoracic organ transplant recipients is a well-recognized complication, but the long-term persistence of molds within the human body and evasion of host defenses has not been well-described. We present 2 cases of invasive mold disease (Verruconis gallopava and Aspergillus fumigatus) in thoracic transplant recipients who had the same mold cultured years prior to the invasive disease presentation. The paired isolates from the index and recurrent infections in both patients were compared using whole-genome sequencing to determine if the same strain of mold caused both the index and recurrent infections. In Case 1, the isolates were found to be of the same strain indicating that the initial colonizing isolate identified pre-transplant eventually caused invasive mold disease post-transplant while in Case 2, the 2 isolates were not of the same strain. These results demonstrate the distinct possibility of molds both persisting within the human body for years prior to invasive mold disease or the long-term risk of recurrent, persistent infection with more than one strain. Further studies of long-term molecular epidemiology of IMD and risk factors for mold persistence in transplant recipients are encouraged.

Patient notification about suspected hospital-associated outbreaks of invasive mold infections: Considerations for public health and hospital personnel

“…IMI signs and symptoms are often nonspecific and sometimes insidious at the outset, making it difficult to establish an onset date in many cases. In addition, the incubation period for several IMIs, particularly noncutaneous mucormycosis, is not well defined, 3,38 largely because it is difficult to ascertain an exposure date. For this reason, investigators typically use a wide exposure window (e.g., 14 days or longer) when evaluating exposures as potential sources.…”

The Cystic Fibrosis treatment, Trikafta, affects growth, viability, and cell wall ofAspergillus fumigatusbiofilms

“…Due its frequent isolation from sputum samples of pwCF and its known role as a human fungal pathogen, the impact of A. fumigatus within the CF lung and subsequent pathogenesis is of particular importance. Invasive infections caused by A. fumigatus typically only occur in individuals with compromised immune systems, such as in chemotherapeutic or organ transplant patients (5)(6)(7)(8)(9). After A. fumigatus conidia germinate in the lung environment and form hyphae, a biofilm that is resistant to antifungal therapy develops (10,11), which leads to high mortality (12)(13)(14)(15).…”