Pulmonary Scedosporiosis in a patient with acute hematopoietic failure: diagnosis aided by next-generation sequencing Express News

Scedosporium species cause infections in both immunocompetent and immunocompromised hosts and produce a variety of clinical manifestations. Notably, Scedosporium is one of the major filamentous fungi that colonize the respiratory tract in patients with cystic fibrosis (Rougeron et al. 2018xRougeron et al., 2018Rougeron, A, Giraud, S, Alastruey-Izquierdo, A, Cano-Lira, J, Rainer, J, Mouhajir, A et al. Ecology of Scedosporium Species: Present Knowledge and Future Research. Mycopathologia. 2018;
183: 185–200
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). A recent worldwide cases review concluded that the mortality in patients with disseminated infections was 76% (Seidel et al. 2019xSeidel et al., 2019Seidel, D, Meißner, A, Lackner, M, Piepenbrock, E, Salmanton-García, J, Stecher, M et al. Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope ®. Crit Rev Microbiol [Internet]. 2019;
0: 1–21https://doi.org/10.1080/1040841X.2018.1514366 ()
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). In this case, though cystic fibrosis was likely to be excluded, the patient had severe inhibition of hematopoiesis and disseminated lung infections, which seemed to be indicators of poor prognosis.

Clinical diagnosis of Scedosporiosis requires conventional laboratory methods such as culture, direct microscopy and histopathology (Tortorano et al. 2014xTortorano et al., 2014Tortorano, AM, Richardson, M, Roilides, E, van Diepeningen, A, Caira, M, Munoz, P et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014;
20: 27–46
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). However, culture-based approach has inevitable limitations, such as relying on the growth of fungal hyphae, which may take several days until the final results. Besides, under microscopy, Scedosporium closely resembles Aspergillus with dichotomous branch and hyaline septate hyphae (Tortorano et al. 2014xTortorano et al., 2014Tortorano, AM, Richardson, M, Roilides, E, van Diepeningen, A, Caira, M, Munoz, P et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014;
20: 27–46
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), which makes it more difficult to obtain an accurate diagnosis of Scedosporiosis. The identification of S. apiospermum is critical because S. apiospermum has intrinsic resistance to many antifungal agents (Tortorano et al. 2014xTortorano et al., 2014Tortorano, AM, Richardson, M, Roilides, E, van Diepeningen, A, Caira, M, Munoz, P et al. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014;
20: 27–46
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).

To the best of our knowledge, this is the first case of pulmonary Scedosporiosis detected by NGS. NGS is an emerging culture-independent microbiological diagnostic approach (Lefterova et al. 2015xLefterova et al., 2015Lefterova, MI, Suarez, CJ, Banaei, N, and Pinsky, BA. Next-Generation Sequencing for Infectious Disease Diagnosis and Management. J Mol Diagnostics [Internet]. 2015;
17: 623–634https://doi.org/10.1016/j.jmoldx.2015.07.004 ()
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), and is relatively effective in cataloging and recognizing pathogens, especially for those uncommon or non-cultivable species (Besser et al. 2018xBesser et al., 2018Besser, J, Carleton, HA, Gerner-Smidt, P, Lindsey, RL, and Trees, E. Next-generation sequencing technologies and their application to the study and control of bacterial infections. Clin Microbiol Infect [Internet]. 2018;
24: 335–341https://doi.org/10.1016/j.cmi.2017.10.013 ()
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). Therefore, the application of NGS in clinical diagnostics is considered to be promising, not only owing to culture-independence, but also short turnaround time (Fan et al. 2018xFan et al., 2018Fan, S, Ren, H, Wei, Y, Mao, C, Ma, Z, Zhang, L et al. Next-generation sequencing of the cerebrospinal fluid in the diagnosis of neurobrucellosis. Int J Infect Dis [Internet]. 2018;
67: 20–24https://doi.org/10.1016/j.ijid.2017.11.028 ()
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) and high sensitivity (Jun et al. 2019xJun et al., 2019Jun, C, Huan, H, Wei, F, Duozhi, S, Chen, L, Yang, S et al. Detection of pathogens from resected heart valves of patients with infective endocarditis by next-generation sequencing. Int J Infect Dis [Internet]. 2019;
https://doi.org/10.1016/j.ijid.2019.03.007 ()
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). In this case, though only 3 reads were detected, the result of NGS coincided with that of traditional culture and also provided suggestion on specific species classification. Therefore, combination of NGS and traditional culture may be a better option for fungal diagnosis compared to traditional culture alone. Nevertheless, lack of classic molecular evidence for precise species identification remains one of the limitations of this case, and further clinical trials are expected to verify the sensitivity and specificity of NGS in diagnosis of fungal infections.

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