S2.2c Talaromycosis in HIV-negative patients: challenges and counter-measures
Authors: Cao Cunwei 
Published: September 2022

Abstract

S2.2 Histoplasmosis and talaromycosis, September 21, 2022, 3:00 PM - 4:30 PM

Talaromycosis is an infection caused by the thermally dimorphic fungus Talaromyces marneffei (T. marneffei). It is endemic in tropical countries of Asia and Southeast Asia and has recently been recognized far beyond the traditional endemic areas. Talaromycosis was thought to be exclusively associated with HIV infection. However, an increasing number of T. marneffei infections have been reported in non-HIV-infected patients. Although the incidence of talaromycosis in non-HIV-infected patients is ˂ 10%, the atypical presentation of this disease can lead to misdiagnosis, inappropriate treatment, and poor outcomes, in addition to tremendous burden and suffering for patients and their families. Screening for immunodeficiencies in patients with talaromycosis is crucial in clinically suspicious cases. Our cohort studies identified three major immunodeficiencies in non-HIV patients with talaromycosis: (1) 85.9% anti-interferon-γ autoantibodies, (2) primary immunodeficiency disorders, and (3) tumors. In disseminated talaromycosis, most patients present with fever, anemia, weight loss, respiratory symptoms, hepatosplenomegaly, lymphadenopathy, and osteolytic destruction and are often misdiagnosed as tuberculosis and other diseases. Localized talaromycosis, on the other hand, is usually manifested by ulcers or masses in the mouth, throat, and external genitalia. Although antigen screening is an effective approach for diagnosing talaromycosis in patients with advanced HIV disease, pathogen-based detection is still limited by atypical clinical presentation. Direct microscopic examination, mycological culture, and histopathology are the standard traditional diagnostic methods used to isolate T. marneffei from clinical specimens, however, due to time-consuming, it might lead to delay diagnosis. Metagenomic next-generation sequencing (mNGS) technology has shown promising results as a rapid, convenient method for detecting T. marneffei from various types of specimens, leading to correct diagnosis and appropriate treatment. Based on our current retrospective study, mNGS has been shown to be equivalent and possibly superior to conventional fungal culture in terms of speed and specificity in the diagnosis of talaromycosis. In terms of final clinical diagnosis, mNGS showed a high sensitivity of 97.22% compared with conventional culture (61.11%). Correction of underlying immunodeficiencies and early use of antifungal agents are important treatment strategies for talaromycosis. Currently, there is no optimal therapeutic regimen for the treatment of talaromycosis in this specific group of patients. Amphotericin B is the first line to initial antifungal treatment, other antifungal agents such as voriconazole have shown good efficacy against talaromycosis. We investigated the efficacy of voriconazole in the treatment of talaromycosis using population pharmacokinetics. C-reactive protein (CRP) was found to significantly affect voriconazole plasma concentrations. Optimization of initial dosing based on CRP levels may be useful to guide voriconazole dosing in clinical practice. The mortality rate in non-HIV talaromycosis is higher than in the HIV population, which may be due to the nonspecific and complex clinical manifestations. Failure to initiate antifungal treatment in a timely manner often results in poor prognosis and even death. The course of treatment is protracted, unclear, and depends on the immune status of the patient. Diagnosis and treatment of talaromycosis remain a challenge. Optimization of diagnostic tools and treatment regimens to ensure early detection and prompt antifungal treatment should be considered.