Emergence of Next-Generation Sequencing for Laboratory Diagnosis of Talaromyces marneffei

The first case of Talaromyces marneffei infection diagnosed by next-generation sequencing (NGS) was reported in 2018. By 31st December 2024, the number of T. marneffei infections picked up by NGS has increased to a total of at least 241. Most cases were reported from China, reflecting both the regional importance of this infection and its widespread use of NGS for laboratory diagnosis of infectious diseases. Among the cases with clinical details reported, 136 were HIV-negative, which was probably the main reason why T. marneffei was not suspected and the diagnosis was subsequently made with the use of NGS. For these 136 HIV-negative patients, 62 were confirmed to have other forms of immunodeficiencies, such as anti-interferon gamma autoantibodies and post-renal/liver transplantation. The clinical presentations were usually non-specific. At least 18 patients were clinically diagnosed as tuberculosis, and empirical anti-tuberculosis therapy was prescribed to 13 patients and NGS was performed because they did not respond to or deteriorated while on anti-tuberculosis treatment. Apart from infectious diseases, at least another 11 patients were initially misdiagnosed to have benign or malignant tumours, the most common being carcinoma of the lung. The median time for detection of T. marneffei by NGS was 2 (range 1-6) days, which is significantly shorter than the median time for detection by fungal culture [7 (range 5-17) days] (P < 0.0001 by Mann-Whitney U test). NGS has emerged as a promising diagnostic tool for T. marneffei infections, especially for picking up cases in HIV-negative patients and rapid diagnosis.