BACKGROUND: Talaromyces marneffei (TM) infection is an opportunistic infection that typically affects individuals with compromised immune systems. TM is an invasive fungal infection associated with high mortality in patients with advanced human immunodeficiency virus (HIV) disease. Syphilis, caused by Treponema pallidum, is a re-emerging infectious disease with diverse clinical manifestations. While primary syphilis often goes unnoticed, secondary syphilis is characterized by systemic symptoms and variable skin lesions, earning it the epithet “the great imitator.” In areas where TM is non-endemic, misdiagnosis between these 2 diseases can occur.

CASE REPORT: A 37-year-old male patient visited the dermatology department due to a rash. He was initially diagnosed with secondary syphilis based on positive serological tests for syphilis. However, his symptoms did not improve after ampicillin treatment. Instead, he developed fever and cough. It is regrettable that a skin rash biopsy was not performed to further clarify the patient’s condition. Through targeted next-generation sequencing (tNGS) and blood culture, he was diagnosed with concurrent disseminated TM infection. Despite continuous antifungal therapy, his blood cultures remained positive for 11 weeks. Fortunately, he ultimately had a good outcome.

CONCLUSIONS: Early detection results from tNGS facilitate timely clinical diagnosis of patients with HIV co-infected with multiple pathogens. When fungal drug susceptibility testing is not feasible, persistently positive blood culture results can be problematic; however, an extended duration of blood culture positivity may indicate the efficacy of the current treatment. It is essential to ensure an adequate duration of antifungal therapy and conduct a comprehensive post-treatment evaluation, as the current evidence is only derived from single cases. The use of blood culture positivity as a marker for treatment response still requires further validation with a larger number of cases.

Keywords: Talaromyces, Blood Culture, syphilis