背景:宏基因组下一代测序(mNGS)在诊断感染病原体方面表现出色。我们旨在评估mNGS在非HIV感染儿童中诊断jirovecii肺孢子虫肺炎(PJP)的性能。
方法:回顾性纳入2018年3月至2021年12月入住儿科重症监护病房的36名PJP儿童和61名非PJP儿童。总结PJP患儿的临床特点。1,3-β-D葡聚糖(BDG)测试和支气管肺泡灌洗液(BALF)mNGS用于评估PJP诊断性能。还回顾了mNGS结果后对PJP儿童的抗菌管理修改。
结果:通过mNGS(36/36)在所有PJP儿童中均检测到了肺孢子虫。mNGS的敏感性为100%(95%置信区间[CI]:90.26-100%)。BDG的敏感性为57.58%(95%CI:39.22-74.52%)。在26例(72.2%)混合感染的PJP患者中,BALF-mNGS检测到24例(66.7%)。根据mNGS结果调整了13例患者(36.1%)的抗菌药物管理。36名PJP儿童包括17名(47.2%)原发性免疫缺陷和19名(52.8%)继发性免疫缺陷,其中19人(52.8%)存活,17人(47.2%)死亡。与生存亚组相比,非生存亚组的原发性免疫缺陷发生率较高(64.7%vs.31.6%,P=0.047),年龄较小(7个月vs.39个月,P=0.011),较低的体重(8.0公斤与12.0kg,P=0.022),和较低的T淋巴细胞计数。
结论:在没有HIV感染的免疫抑制儿童中,PJP的死亡率很高,早期诊断具有挑战性。BALF-mNGS可以帮助识别PJP并指导临床管理。
BACKGROUND: Metagenomic next-generation sequencing (mNGS) excels in diagnosis of infection pathogens. We aimed to evaluate the performance of mNGS for the diagnosis of Pneumocystis jirovecii pneumonia (PJP) in non-HIV infected children.
METHODS: Totally 36 PJP children and 61 non-PJP children admitted to the pediatric intensive care unit from March 2018 to December 2021 were retrospectively enrolled. Clinical features of PJP children were summarized. 1,3-β-D glucan (BDG) test and bronchoalveolar lavage fluid (BALF) mNGS were used for evaluation of PJP diagnostic performance. Antimicrobial management modifications for PJP children after the mNGS results were also reviewed.
RESULTS: Pneumocystis jirovecii was detected in all PJP children by mNGS (36/36), and the sensitivity of mNGS was 100% (95% confidence interval [CI]: 90.26-100%). The sensitivity of BDG was 57.58% (95% CI: 39.22-74.52%). Of the 26 (72.2%) PJP patients with mixed infection, twenty-four (66.7%) were detected by BALF-mNGS. Thirteen patients (36.1%) had their antimicrobial management adjusted according to the mNGS results. Thirty-six PJP children included 17 (47.2%) primary
immunodeficiency and 19 (52.8%) secondary
immunodeficiency, of whom 19 (52.8%) survived and 17 (47.2%) died. Compared to survival subgroup, non-survival subgroup had a higher rate of primary
immunodeficiency (64.7% vs. 31.6%, P = 0.047), younger age (7 months vs. 39 months, P = 0.011), lower body weight (8.0 kg vs. 12.0 kg, P = 0.022), and lower T lymphocyte counts.
CONCLUSIONS: The mortality rate of PJP in immunosuppressed children without HIV infection is high and early diagnosis is challenging. BALF-mNGS could help identify PJP and guide clinical management.