Department of Respiratory Infection, Guangzhou Medical University, No.9, Jinsui Road, Zhujiang New City, Tianhe District, Guangzhou, 510120, Guangdong, China.
Pediatric Intensive Care Unit, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, No.9, Jinsui Road, Zhujiang New City, Tianhe District, Guangzhou, 510120, Guangdong, China.
BMC Infect Dis. 2021 Mar 20;21(1):287. doi: 10.1186/s12879-021-05978-z.
Talaromyces marneffei (T. marneffei) is an opportunistic pathogen that infects immunodeficient children. The aim of the study is to determine the clinical features and peripheral immune state of Talaromyces marneffei (T. marneffei) infections in children for early detection and diagnosis.
We retrospectively reviewed 21 pediatric patients who were diagnosed with T. marneffei infections and were followed up in the Guangzhou Women and Children's Medical Center from January 2010 to January 2020. For each patient, we collected and analyzed clinical characteristics, peripheral immunological results, genetic tests, complications and prognosis.
Common clinical features of the patients included fever (20/21, 95.24%), cough (17/21, 80.95%) and hepatomegaly (17/21, 80.95%). Severe complications included septic shock (12/21, 57.14%), hemophagocytic lymphohistiocytosis (HLH) (11/21, 52.38%), acute respiratory distress syndrome (ARDS) (10/21, 47.62%), multiple organ dysfunction syndrome (MODS) (9/21, 42.86%), and disseminated intravascular coagulation (DIC) (7/21, 33.33%). Eleven children (11/21, 52.38%) eventually died of T. marneffei infections. All patients were HIV negative. Seven cases revealed reduced antibody levels, especially IgG. Higher levels of IgE were detected in 9 cases with an obvious increase in two patients. Ten patients showed decreased complement C3 levels, some of whom had low C4 levels. Three patients displayed decreased absolute T lymphocyte counts, including the CD 4+ and CD 8+ subsets. A reduction in NK cells was present in most patients. No patient had positive nitro blue tetrazolium (NBT) test results. Nine patients were screened for common genetic mutations. Of the cases, one case had no disease-specific gene mutation. Four children had confirmed hyperimmunoglobulin M syndrome (HIGM) with CD40LG variation, one case had severe combined immunodeficiency (SCID), and one case had hyper-IgE syndrome (HIES). One patient was identified as having a heterozygous mutation in STAT3 gene; however, he showed no typical clinical manifestations of HIES at his age. One patient had a mutated COPA gene with uncertain pathogenic potential. Another patient was diagnosed with HIES that depended on her clinical features and the National Institutes of Health (NIH) scoring system.
T. marneffei infections in HIV-negative children induced severe systemic complications and poor prognosis. Children with T. marneffei infections commonly exhibited abnormal immunoglobulin levels in peripheral blood, particularly decreased IgG or increased IgE levels, further suggesting possible underlying PIDs in these patients.
马尔尼菲青霉（Talaromyces marneffei，T. marneffei）是一种机会性致病真菌，可感染免疫功能低下的儿童。本研究旨在明确儿童马尔尼菲青霉感染的临床特征和外周免疫状态，以便早期发现和诊断。
我们回顾性分析了 2010 年 1 月至 2020 年 1 月在广州市妇女儿童医疗中心接受治疗的 21 例马尔尼菲青霉感染患儿的临床资料。分析每位患儿的临床特征、外周免疫、基因检测、并发症和预后。
患儿的常见临床表现包括发热（20/21，95.24%）、咳嗽（17/21，80.95%）和肝大（17/21，80.95%）。严重并发症包括感染性休克（12/21，57.14%）、噬血细胞性淋巴组织细胞增生症（HLH）（11/21，52.38%）、急性呼吸窘迫综合征（ARDS）（10/21，47.62%）、多器官功能障碍综合征（MODS）（9/21，42.86%）和弥散性血管内凝血（DIC）（7/21，33.33%）。11 例患儿（11/21，52.38%）最终因马尔尼菲青霉感染死亡。所有患儿均 HIV 阴性。7 例患儿出现抗体水平降低，特别是 IgG。9 例患儿 IgE 水平明显升高，其中 2 例患儿 IgE 显著升高。10 例患儿补体 C3 水平降低，部分患儿 C4 水平降低。3 例患儿出现绝对 T 淋巴细胞计数减少，包括 CD4+和 CD8+亚群。大多数患儿 NK 细胞减少。无患儿 NBT 试验结果阳性。9 例行常见基因突变筛查，其中 1 例患儿无疾病特异性基因突变。4 例患儿确诊为高免疫球蛋白 M 综合征（HIGM），伴 CD40LG 变异，1 例患儿为严重联合免疫缺陷病（SCID），1 例患儿为高 IgE 综合征（HIES）。1 例患儿 STAT3 基因杂合突变，但无典型 HIES 临床表现。1 例患儿 COPA 基因突变，潜在致病性不确定。另 1 例患儿根据临床特征和美国国立卫生研究院（NIH）评分系统诊断为 HIES。
HIV 阴性儿童感染马尔尼菲青霉可引起严重的全身并发症和不良预后。外周血免疫球蛋白水平异常常见，特别是 IgG 降低或 IgE 升高，提示患儿可能存在潜在的 PID。
