HIV-negative case of Talaromyces marneffei pulmonary infection with a TSC2 mutation

Abstract

Talaromyces marneffei is a rare dimorphic pathogenic fungus that can induce severe infections in human immunodeficiency virus (HIV)-infected patients. However, such infections have also been reported in non-HIV hosts. This current case report describes a very rare case of a T. marneffei pulmonary infection in an HIV-negative patient with a mutation in the tuberous sclerosis complex subunit 2 (TSC2) gene. A 24-year-old male patient presented with cough and expectoration for 6 months. Computed tomography showed multiple ground-glass opacities and cystic and cavitated lesions in both lungs. Next generation sequencing (NGS) of the bronchoalveolar lavage fluid was performed to confirm T. marneffei pulmonary infection. The results were further verified using bronchoscopy specimen cultures. This was an HIV-negative patient without a travel history to endemic zones and his blood exon sequencing results showed a mutation in the TSC2 gene. To date, he has recovered well with voriconazole therapy. In summary, patients with TSC2 mutations that induce bronchopulmonary dysplasia may be potential hosts for T. marneffei. Early and timely diagnosis is important for improving prognosis. NGS plays a critical role in the diagnosis of T. marneffei pulmonary infection.

Keywords: HIV-negative; TSC2; Talaromyces marneffei; pulmonary infection.

Figure 1.

Representative computed tomography (CT) imaging scans of a 24-year-old male patient that presented with a 6-month history of recurrent cough and expectoration without fever, shortness of breath or chest pain. (A) CT scan taken in February 2019 showing multiple ground glass opacities, cystic changes and cavitated lesions in both lungs. (B) CT scan taken in March 2019 showing the ground glass shadows were absorbed. (C & D) CT scans taken during follow-up in September 2019 and June 2020, respectively, showing distinct resolution of lesions in both lungs, except for the cystic lesions.

Figure 2.

Representative bronchoscopic examinations of a 24-year-old male patient that presented with a 6-month history of recurrent cough and expectoration without fever, shortness of breath or chest pain demonstrated that both bronchi were clear (A–D). Endobronchial ultrasound showing a mass at the subbranch of the right lower lobe bronchial dorsal (E). The colour version of this figure is available at: http://imr.sagepub.com.

Figure 3.

Cultures of the bronchoalveolar lavage fluid (BALF) from a 24-year-old male patient that presented with a 6-month history of recurrent cough and expectoration without fever, shortness of breath or chest pain. (A) Fungal spores seen in phagocytes from BALF (red arrow) (scale bar 15 µm). (B) Culture of BALF revealed Talaromyces marneffei, which showed temperature-dependent dimorphic growth characteristics and the cells produced a soluble red pigment at 25 °C. (C) A mycelium was produced at temperatures between 25 °C and 30 °C. (D) Fungus growing as yeast-like cells at 37 °C. The colour version of this figure is available at: http://imr.sagepub.com.

Figure 4.

Sanger sequencing verification results for a 24-year-old male patient and his parents. The patient and his father carried a mutation in the tuberous sclerosis complex subunit 2 (TSC2) gene and his mother was wild-type. The colour version of this figure is available at: http://imr.sagepub.com.