Two cases of Talaromyces marneffei tracheobronchial infection in HIV-negative patients

Abstract

Objectives: In recent years, the incidence and prevalence of Talaromyces marneffei (TM) have been on the rise. This infection predominantly affects immunocompromised or immunodeficient individuals, especially those with acquired immunodeficiency syndrome (AIDS). There has been a notable increase in the incidence of TM and its associated infections. The majority of cases occur within immunocompromised or immunodeficient populations, with a high prevalence among AIDS patients. However, cases are also occasionally detected in HIV - negative individuals. Due to the insidious and slow - growing nature of TM, the disease can be misdiagnosed as other conditions such as tuberculosis, bacterial pneumonia, and lung cancer, particularly in non - endemic regions. Such misdiagnosis significantly impacts the patient’s prognosis.

Methods: Two HIV-negative patients with TM infection from non - endemic areas were hospitalized with a high suspicion of co-infection with lung cancer and poor symptomatic treatment response. These patients underwent a comprehensive diagnostic workup, including lung puncture biopsy, sputum, blood, pleural, and peritoneal fluid cultures, as well as Metagenomics Next Generation Sequencing (mNGS) analysis. Eventually, both patients were diagnosed with TM tracheobronchial infection.

Results: The patients were treated with voriconazole antifungal therapy, combined with methylprednisolone (used for reducing inflammation, relieving spasms, and treating asthma) and acyclovir (used for treating viral infections). The 49 - year - old patient was cured and discharged from the hospital, while the 79 - year - old male patient’s condition continued to deteriorate, and he ultimately died.

Conclusion: It has been determined that TM infection, presenting primarily with respiratory symptoms, is highly susceptible to misdiagnosis in the early stages of the disease. This can lead to treatment delays and a negative impact on the prognosis. It is crucial for medical professionals to be more aware of the possibility of TM infection in non - HIV - infected and non - endemic populations. Collecting respiratory and lung tissue specimens from the infection sites at the earliest possible stage is essential for diagnosing TM infection. Integrating mNGS and mass spectrometry results is crucial for improving the detection and early diagnosis of TM infection, which is of great value for enhancing the efficacy of clinical treatment and the prognosis of patients.

Clinical trial number: Not applicable.

Keywords: Talaromyces marneffei; Antifungal therapy; HIV-negative patient; Tracheobronchial infection.

Fig. 1

(A-D)The enhanced CT scan of the chest in Case 1 shows the presence of a lung cancer lesion in the upper lobe of the right lung, accompanied by obstructive pneumonia and atelectasis. Moreover, it reveals right hilar and mediastinal lymph node metastases

Fig. 2

(A-B) In Case 1, fibreoptic bronchoscopy demonstrated infiltrative stenosis of the bronchus in the apical segment of the right upper lobe. In addition, infiltrative neoplastic nodules were observed at the openings, highly suspicious of right lung cancer.(C-D) In Case 2, fibreoptic microscopy revealed localised granulomatous hyperplasia of the right upper lobe bronchus, with luminal narrowing, granulomatous elevation with ulcer - like changes, and mucosal swelling

Fig. 3

(A) Gram staining of a sputum smear revealed dachshund - like yeast - like cells with a central septum. (B) The results of blood and pleural fluid cultures were positive, and red mycelium was visible microscopically upon Gram-staining. (C) Talaromyces marneffei shows filamentous growth at 28°C. (D) At 36°C,Talaromyces marneffei exhibits yeast-like characteristics. (E) PTalaromyces marneffei stains dark blue in lactophenol cotton blue

Fig. 4

The Bruker MALDI-TOF MS analysis yielded a score of 2.3, identifying the organism as Talaromyces marneffei

Fig. 5

The key points in the treatment of the patient in case 1 are shown as a time line

Fig. 6

(A-D) In Case 2, the contrast - enhanced CT images of the patient’s chest revealed an obstructive pneumonia infection presenting as a tumourous lesion. The right pleural cavity showed a minimal amount of fluid accumulation, while the pleura of the right upper lung exhibited suspicious nodular changes and pleural metastases, necessitating drainage

Fig. 7

The key points in the treatment of the patient in case 2 are shown as a time line