Drysdale Simon B, Kelly Dominic F, Morgan Marcus, Peto Tim, Crook Derrick, Matthews Philippa C, Walker Timothy M
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
NIHR Oxford Biomedical Research Centre, Oxford University, Oxford, UK.
Wellcome Open Res. 2020 Oct 15;5:242. doi: 10.12688/wellcomeopenres.16280.1. eCollection 2020.
(BCG) is a live-attenuated vaccine used world-wide for prevention of tuberculosis disease. In some immunocompromised hosts it has the potential to cause disease. As with other members of the complex it has the potential for acquiring drug resistance. We reviewed 10 years of paediatric clinical BCG strains referred to our clinical microbiology laboratory in Oxford where they underwent whole genome sequencing. We present a case series comparing clinical, pathogen genetic and pathogen phenotypic data, and consider the clinical implications. We identified 15 BCG isolates from 8 children under 16 years old. Only one child had clinical disease with the other seven reported as local inoculation-site reactions. Case 1 suffered disseminated disease secondary to an undiagnosed IL-12/IFNγ receptor defect and the BCG isolates evolved two different rifampicin resistance mutations. Across all 15 isolates, phenotypic resistance to each first line drug was seen. BCG is a safe and effective vaccine in children. Most clinical specimens in our series were not related to disease. However, in the context of rare pathogen-specific immunocompromise, BCG can cause pathology and acquire drug resistance under selection from therapy.
卡介苗（BCG）是一种减毒活疫苗，在全球范围内用于预防结核病。在一些免疫功能低下的宿主中，它有可能引发疾病。与该菌属的其他成员一样，它有获得耐药性的可能。我们回顾了10年间转诊至牛津临床微生物实验室的儿科临床卡介苗菌株，这些菌株在该实验室进行了全基因组测序。我们展示了一个病例系列，比较了临床、病原体基因和病原体表型数据，并探讨了其临床意义。我们从8名16岁以下儿童中鉴定出15株卡介苗分离株。只有一名儿童患有临床疾病，其他7名报告为局部接种部位反应。病例1因未诊断出的白细胞介素-12/干扰素γ受体缺陷而患上播散性疾病，卡介苗分离株出现了两种不同的利福平耐药突变。在所有15株分离株中，均观察到对每种一线药物的表型耐药。卡介苗在儿童中是一种安全有效的疫苗。我们系列中的大多数临床标本与疾病无关。然而，在罕见的病原体特异性免疫功能低下的情况下，卡介苗在治疗选择压力下可导致病变并获得耐药性。
