Talaromyces marneffei Infections in 8 Chinese Children with Inborn Errors of Immunity

Talaromyces marneffei (TM) is an opportunistic fungus leading to multi-organ damages and poor prognosis in immunocompromised individuals. TM infections in children are rare and our knowledge to TM infection is insufficient. To investigate the clinical characteristics of TM-infected children and to explore the underlying mechanisms for host against TM, we analysed TM-infected patients diagnosed in our hospital.

Eight patients with TM infections have been identified in Shenzhen Children's Hospital during 2017-2021. Clinical data were collected from medical records. Immunological features were evaluated by flow cytometry. Literatures were also reviewed to summarize the reported inborn errors of immunity (IEIs) with TM infections.

All 8 children were HIV-negative. The most common symptom of TM infections was fever (8/8), followed by weight loss (7/8), pneumonia (7/8), hepatomegaly (7/8), splenomegaly (6/8), anemia (6/8), lymphadenopathy (5/8), thrombocytopenia (3/8), diarrhea (3/8), rashes or skin lesions (3/8), and osteolytic lesions (1/8). Five children died during the follow-ups. CD3+ T cells were decreased in 6 patients. Eight patients had reduced natural killer cells. All patients went gene sequencing and were finally diagnosed as IEIs, including STAT1 gain-of-function, IL-2 receptor common gamma chain deficiency, adenosine deaminase deficiency, CD40 ligand deficiency, and STAT3 deficiency. Another 4 types of IEIs (CARD9, IFN-γ receptor 1, RelB, and NFKB2 deficiency), have been reported with TM infections based on literature review.

TM infections resulted in systemic injuries and high mortality. The spectrum of IEIs underlying TM infections indicated that T cell-mediated immunity, IFN-γ, IL-17 signalings and NF-κB pathways were important for host responses against TM infection. In reverse, for HIV-negative children without other secondary immunodeficiencies, IEIs should be considered in TM-infected children.