Rapid and precise diagnosis of T. marneffei pulmonary infection in a HIV-negative patient with autosomal-dominant STAT3 mutation: a case report

Abstract

Background: Talaromyces marneffei, also named Penicillium marneffei, is an opportunistic pathogen that can cause systemic or limited infection in human beings. This infection is especially common in human immunodeficiency virus (HIV)-infected hosts; however, it has also been recently reported in HIV-negative hosts. Here, we report a very rarely seen case of T. marneffei pulmonary infection in a non-HIV-infected patient with signal transducer and activator of transcription 3 (STAT3) mutation.

Case presentation: A 34-year-old woman was admitted to our hospital for uncontrollable nonproductive cough and dyspnea with exercise. She had been immunocompromised since infancy. Computerized tomography scan showed multiple ground glass opacities with multiple bullae in both lungs. Next generation sequencing (NGS) of the bronchoalveolar lavage fluid identified T. marneffei nucleotide sequences. Culture of bronchoscopy specimens further verified the results. The patient was HIV negative, and blood gene detection indicated STAT3 mutation. To date, following the application of itraconazole, the patient has recovered satisfactorily.

Conclusion: In clinical practice, T. marneffei infection among HIV-negative individuals is relatively rare, and we found that patients who are congenitally immunocompromised due to STAT3 mutation may be potential hosts. Early diagnosis and timely treatment are expected to improve the prognosis of T. marneffei infection. NGS is a powerful technique that may play an important role in this progress. The reviews of this paper are available via the supplemental material section.

Keywords: Talaromyces marneffei; human immunodeficiency virus (HIV)-negative; next generation sequencing; signal transducer and activator of transcription 3 mutation.

Figure 1.

(A) Past chest CT scan (1 January 2019) showing multiple disseminated ground glass opacities with multiple bullae. (B, C) Chest CT scan during follow up (26 January 2019 and 27 April 2019, respectively) showing distinct resolution of both lungs. CT, computed tomography.

Figure 2.

Bronchoscopy showed local uneven membrane surface (A), hypoechoic areas in group 7, 4R, and 11Rs mediastinal lymph nodes through CP-EBUS (B), and hypoechoic shadow in the dorsal segment of the right lower lobe through RP-EBUS (C). CP-EBUS, convex-probe endobronchial ultrasound; RP-EBUS, radial-probe endobronchial ultrasound.

Figure 3.

Culture of BALF revealed Talaromyces marneffei, which shows temperature-dependent dimorphic character, growing as yeast-like cells at 37°C (A) and as a mycelium at temperatures between 25°C and 30°C (B); the cells produced red pigment at 25°C (C). BALF, bronchoalveolar lavage fluid.

Figure 4.

(A) Family map and Sanger sequencing. (B) Illustration of the functional structure of STAT3: p.R31Q in red and other known pathogenic, or likely pathogenic mutations, in black. (C) The labeling of p.R31Q on the structure of STAT3 modeled by the I-TASSER algorithm. STAT3, signal transducer and activator of transcription 3.