Abstract：
BACKGROUND: In high-resource settings, the survival of children with immunocompromise (IC) has increased and immunosuppressive therapies are increasingly being used. This study aimed to determine the clinical characteristics, performance of diagnostic tools, and outcome of IC children with tuberculosis (TB) in Europe.
METHODS: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020.
RESULTS: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004).
CONCLUSIONS: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.
METHODS: Multicenter, matched case-control study within the Pediatric Tuberculosis Network European Trials Group, capturing TB cases <18 years diagnosed 2000-2020.
RESULTS: A total of 417 TB cases were included, comprising 139 children who are IC (human immunodeficiency virus, inborn errors of immunity, drug-induced immunosuppression, and other immunocompromising conditions) and 278 non-IC children as controls. Nonrespiratory TB was more frequent among cases than controls (32.4% vs 21.2%; P = .013). Patients with IC had an increased likelihood of presenting with severe disease (57.6% vs 38.5%; P < .001; odds ratio [95% confidence interval], 2.073 [1.37-3.13]). Children with IC had higher rates of false-negative tuberculin skin test (31.9% vs 6.0%; P < .001) and QuantiFERON-TB Gold assay (30.0% vs 7.3%; P < .001) results at diagnosis. Overall, the microbiological confirmation rate was similar in IC and non-IC cases (58.3% vs 49.3%; P = .083). Although the mortality in children with IC was <1%, the rate of long-term sequelae was significantly higher than in non-IC cases (14.8% vs 6.1%; P = .004).
CONCLUSIONS: Children with IC and TB in Europe have increased rates of nonrespiratory TB, severe disease, and long-term sequelae. Immune-based TB tests have poor sensitivity in those children. Future research should focus on developing improved immunological TB tests that perform better in patients with IC, and determining the reasons for the increased risk of long-term sequelae, with the aim to design preventive management strategies.
摘要：
背景：在高资源环境中，免疫功能低下（IC）儿童的存活率增加，并且越来越多地使用免疫抑制疗法。本研究旨在确定临床特征，欧洲IC儿童结核病诊断工具的性能和结局。
方法：多中心，儿科结核病网络欧洲试验组(ptbnet)内的匹配病例对照研究，捕获结核病病例<18年诊断2000-2020年。
结果：纳入417例TB病例，包括139名IC儿童(艾滋病毒，天生的豁免权错误，药物诱导的免疫抑制和其他免疫受损状况）和278名非IC儿童作为对照。非呼吸性结核病在病例中比对照组更常见(32.4%vs.21.2%；p=0.013）。IC患者出现严重疾病的可能性增加(57.6%vs.38.5%；p<0.001；OR[95%CI]：2.073[1.37-3.13]）。IC患儿结核菌素皮肤试验假阴性率较高(31.9%vs.6.0%；p<0.001）和QuantiFERON-TB金测定（30.0%vs.7.3%；p<0.001）诊断时的结果。总的来说,IC和非IC病例的微生物确诊率相似(58.3%vs.49.3%；p=0.083）。虽然IC儿童的死亡率<1%，长期后遗症的发生率明显高于非IC病例(14.8%vs.6.1%；p=0.004）。
结论：欧洲患有结核病的IC儿童非呼吸道结核病的发病率增加，严重疾病,和长期后遗症。在这些儿童中，基于免疫的结核病测试的敏感性较差。未来的研究应该集中在开发改进的免疫结核病测试，在IC患者中表现更好，并确定长期后遗症风险增加的原因，旨在设计预防性管理策略。
方法：多中心，儿科结核病网络欧洲试验组(ptbnet)内的匹配病例对照研究，捕获结核病病例<18年诊断2000-2020年。
结果：纳入417例TB病例，包括139名IC儿童(艾滋病毒，天生的豁免权错误，药物诱导的免疫抑制和其他免疫受损状况）和278名非IC儿童作为对照。非呼吸性结核病在病例中比对照组更常见(32.4%vs.21.2%；p=0.013）。IC患者出现严重疾病的可能性增加(57.6%vs.38.5%；p<0.001；OR[95%CI]：2.073[1.37-3.13]）。IC患儿结核菌素皮肤试验假阴性率较高(31.9%vs.6.0%；p<0.001）和QuantiFERON-TB金测定（30.0%vs.7.3%；p<0.001）诊断时的结果。总的来说,IC和非IC病例的微生物确诊率相似(58.3%vs.49.3%；p=0.083）。虽然IC儿童的死亡率<1%，长期后遗症的发生率明显高于非IC病例(14.8%vs.6.1%；p=0.004）。
结论：欧洲患有结核病的IC儿童非呼吸道结核病的发病率增加，严重疾病,和长期后遗症。在这些儿童中，基于免疫的结核病测试的敏感性较差。未来的研究应该集中在开发改进的免疫结核病测试，在IC患者中表现更好，并确定长期后遗症风险增加的原因，旨在设计预防性管理策略。
