Case report: Diagnosis of Talaromyces marneffei infection in an HIV-negative patient with septic shock and high-titer anti-interferon gamma autoantibodies by metagenomic next-generation sequencing

Abstract

Background: Sepsis is a life-threatening condition caused by a dysfunctional response to infection from the host. Septic shock, a subset of sepsis, caused by Talaromyces marneffei infection (talaromycosis) has rarely been reported. Owing to its slow culture and low yield, talaromycosis is typically misdiagnosed in HIV-negative patients as other infections, such as tuberculosis, bacterial pneumonia, and lung cancer, especially in non-endemic regions. Early and accurate diagnosis as well as efficient treatment options are required to improve prognosis.

Method: A 30-year-old HIV-negative Chinese woman from a non-endemic area of T. marneffei was initially misdiagnosed with tuberculosis. She had a poor response to anti-tuberculosis treatment. On July 16, 2022, she was admitted to our hospital; the patient developed septic shock on the third day after hospitalization and was ultimately diagnosed with talaromycosis via metagenomic next-generation sequencing (mNGS).

Result: The condition of the patient improved after appropriate treatment with amphotericin B. Furthermore, enzyme-linked immunosorbent assay results confirmed that the patient had a high-titer of anti-interferon gamma (IFN-γ) autoantibodies.

Conclusion: HIV-negative individuals with anti-IFN-γ autoantibodies typically have relapsing, refractory, and fatal infections, such as talaromycosis, which is typically misdiagnosed in the initial course of the disease. This can lead to septic shock. Clinicians should be aware that they may encounter HIV-negative patients with T. marneffei infection in non-endemic areas. Thus, mNGS is an effective technology for detecting T. marneffei infection. Additionally, the detection of anti-IFN-γ autoantibodies in these patients would aid in knowing their susceptibility to fatal infections.

Keywords: HIV-negative patient; Talaromyces marneffei; anti-interferon gamma autoantibodies; metagenomic next-generation sequencing; septic shock.

Figure 1

Chest computed tomography imaging results of the patient. (A) The chest CT before anti-tuberculosis treatment. (B) The chest CT before anti-Talaromyces marneffei treatment. Chest CT scans showed scattered patches, nodules, and ground-glass shadows in the left upper lobe with ill-defined borders and thickening of some interlobular septa. (C) The chest CT after 2 weeks of cumulative treatment with amphotericin B. The lesions in the left upper lobe of the lung were absorbed after two weeks of treatment with amphotericin B. (D) Chest CT scans of the local hospital after discharging from hospital 5 months. The lesions in the left upper lobe of the lung had been absorbed furthermore. (E). The MRI of spine showed the lesions of thoracic vertebra. (F). The MRI of spine showed the lesions of thoracic vertebra were absorbed after anti-fungal treatment.

Figure 2

Positron emission tomography/X-ray computed tomography imaging results of the patient. (A) Thoracic (T-6) vertebral body showing low metabolism. (B) Left upper lobe of the lung showing high metabolism. (C) Osteolytic damage found in the vertebrae.

Figure 3

Specific stains of lung tissues. (A). Hexamine silver staining of lung tissues was positive suspiciously; (B). Periodic acid-Schiff (PAS) of lung tissues was positive suspiciously.

Figure 4

(A) T. marneffei coverage map. The identified reads were mapped to the T. marneffei reference genome (GenBank accession no. MN700106.1). The abscissa is the genome position of the T. marneffei reference genome. The left-side scale shows the number of matched mNGS sequences in the alignment. The right-side scale shows the sequencing depth (i.e., the number of times the base pair site has been sequenced). The blue bars show the number of matched mNGS sequences corresponding to various positions in the genome of the fungus. The red line represents the average sequence depth distribution at different positions in the fungal genome. The yellow line represents the median sequence depth distribution at different positions in the fungal genome. M, position in the genome in millions of base pairs (x-axis scale); (B) The OD of anti-IFN-γ-autoantibodies of this patient.

Figure 5

Timeline of the patient with relevant data on the episodes and interventions.