Taylor Margaret G, Nicholas Sarah K, Forbes Satter Lisa R, Martinez Caridad, Cameron Lindsay H
From the Department of Pediatrics, Section of Infectious Diseases, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
Department of Pediatrics, Section of Immunology Allergy and Retrovirology, Baylor College of Medicine, Texas Children's Hospital, Houston, Texas.
Pediatr Infect Dis J. 2022 May 1;41(5):430-435. doi: 10.1097/INF.0000000000003465.
Infants with inborn errors of immunity (IEI), born in countries where Bacillus-Calmette-Guerin (BCG) vaccination is recommended at birth, are at risk of developing infectious complications following vaccination. A prompt diagnosis of disseminated BCG infection in these infants is essential, as many will require stem cell transplantation (SCT) for the immunologic cure. In patients with IEI, the mortality risk from disseminated mycobacterial infection is high, both before and following SCT.
A 7-month-old Qatari infant with an IEI, homozygous IKBKB gene mutation, was evaluated at our institution for SCT. He had a history of recurrent pneumonias, but pretransplant evaluation revealed negative cultures from bronchoalveolar fluid, blood and urine. At 8 months of age, the infant developed skin nodules of unclear etiology, prompting additional evaluation.
Given his profound immunosuppression and receipt of broad-spectrum antimicrobials, plasma metagenomic next-generation sequencing (mNGS) was obtained and identified Mycobacterium tuberculosis complex within 72 hours. A skin biopsy was performed, and antimycobacterial therapy was initiated. Mycobacterium bovis-BCG was confirmed from cultures 3 weeks later. Treatment was complicated by elevated serum liver transaminases and aminoglycoside-associated high-frequency hearing loss. The infant completed 14 months of treatment from engraftment. Evaluation for active BCG infection after SCT was negative.
In an infant with a unique IEI, plasma mNGS provided the first diagnosis of disseminated BCG infection. We believe that early initiation of antimycobacterial treatment improved the infant's clinical outcome. Plasma mNGS testing should be considered as a noninvasive screen for infectious pathogens in children with IEIs before SCT.
患有先天性免疫缺陷（IEI）的婴儿出生在推荐出生时接种卡介苗（BCG）的国家，接种疫苗后有发生感染并发症的风险。对这些婴儿的播散性卡介苗感染进行快速诊断至关重要，因为许多婴儿需要进行干细胞移植（SCT）以实现免疫治愈。在患有IEI的患者中，播散性分枝杆菌感染的死亡风险在SCT前后都很高。
一名7个月大的卡塔尔婴儿患有IEI，IKBKB基因纯合突变，在我们机构接受SCT评估。他有反复肺炎病史，但移植前评估显示支气管肺泡灌洗液、血液和尿液培养均为阴性。8个月大时，婴儿出现病因不明的皮肤结节，促使进行进一步评估。
鉴于其严重免疫抑制且接受了广谱抗菌药物治疗，进行了血浆宏基因组下一代测序（mNGS），并在72小时内鉴定出结核分枝杆菌复合群。进行了皮肤活检，并开始抗分枝杆菌治疗。3周后培养证实为牛型卡介苗。治疗过程中出现血清肝转氨酶升高和氨基糖苷类药物相关的高频听力损失等并发症。婴儿从移植开始完成了14个月的治疗。SCT后活动性卡介苗感染评估为阴性。
在一名患有独特IEI的婴儿中，血浆mNGS首次诊断出播散性卡介苗感染。我们认为早期开始抗分枝杆菌治疗改善了婴儿的临床结局。血浆mNGS检测应被视为SCT前对患有IEI的儿童进行感染病原体的非侵入性筛查方法。
