Letter to the Editor: Diagnosis of Aspergillus flavus -Induced Pneumonia Through Metagenomic Next-Generation Sequencing: A Case Report

To the Editor:

A spergillus flavus is the second most common cause of aspergillosis in humans, but it typically results in superficial infections rather than lung-related diseases. ¹ Moreover, conventional diagnostic methods such as fungal culture are often time-consuming and yield low detection rates of Aspergillus flavus in bronchoalveolar lavage fluid (BALF) or sputum samples. ² We present here a case of pneumonia caused by Aspergillus flavus, which was identified using metagenomics next-generation sequencing (mNGS) on BALF samples, underscoring the critical role of mNGS in modern diagnostics.

A 67-year-old male was admitted to our hospital presenting with a 15-day history of persistent cough and dyspnea. He had previously failed to respond to antibiotic therapy administered at a local hospital. His medical history included a total resection of rectal adenocarcinoma (TNM staging of T2aN0M0) three years prior, as well as a diagnosis of type 2 diabetes mellitus two years ago. Upon admission, physical examination revealed audible crackles in his lungs. Laboratory tests showed an elevated neutrophil count of 7.8 × 10⁹/L (normal range, 1.8–6.3 × 10⁹/L), neutrophil proportion of 91.9% (normal range, 40%–75%), C-reactive protein level of 23.92 mg/L (normal range, 0–10 mg/L), and cancer antigen 724 of 143 IU/mL (normal range, 0–6 IU/mL). The interferon-γ release assay (IGRA) was negative. Chest computed tomography (CT) imaging revealed evidence of bilateral pneumonia (Fig. 1A). An initial diagnosis of bacterial pneumonia was made, and the patient was treated with intravenous antibiotic agents, including piperacillin (4 g per 8 hours) and tazobactam (0.5 g per 8 hours). Despite this, he continued to experience persistent cough and dyspnea.

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FIG. 1.

Images of patient's medical records. (A) Chest computed tomography (CT) imaging revealed pneumonia features. (B) Metagenomics next-generation sequencing (mNGS) identified Aspergillus flavus from bronchoalveolar fluid (BALF) samples.

A subsequent fiberoptic bronchoscopy showed no obstructions in the airways. Moreover, the tuberculin test, along with bacterial cultures from sputum and BALF samples, returned negative results, leaving the cause of his pneumonia undetermined. However, subsequent mNGS of the BALF identified 6,600 sequence reads corresponding to Aspergillus flavus. The total length of the sequence coverage for this species was 539,807 bp, with a coverage of 1.43% and an average depth of 1.02 × (Fig. 1B). No sequences corresponding to other pathogens were detected. Given these findings, a diagnosis of Aspergillus flavus-associated pneumonia was made. On the fourth day after admission, intravenous voriconazole (0.2 g per 12 hours) was added to the patient's treatment regimen. The patient's symptoms improved, and he was discharged from our hospital five days later. He continued antifungal treatment with oral voriconazole at home, and his symptoms progressively alleviated during follow-up.

In contrast to Aspergillus fumigatus as the principal agent of invasive pulmonary aspergillosis, Aspergillus flavus typically settles in the upper respiratory tract. ³ For diffuse infiltrates of Aspergillus flavus infection, bronchoscopy with bronchoalveolar lavage is recommended. ² Traditional fungal culture methods using BALF or sputum samples have proven to be less sensitive and require a long turnaround time. However, mNGS is capable of detecting a wide range of pathogens with high sensitivity within a short time. The case presented here underscores the efficiency of mNGS in rapidly identifying rare pathogens, such as Aspergillus flavus, from BALF samples.