秘鲁亚马逊地区人类免疫缺陷病毒感染者神经感染的临床和宏基因组学特征
Clinical and Metagenomic Characterization of Neurological Infections of People With Human Immunodeficiency Virus in the Peruvian Amazon.
作者信息
Steinberg Hannah E, Ramachandran Prashanth S, Diestra Andrea, Pinchi Lynn, Ferradas Cusi, Kirwan Daniela E, Diaz Monica M, Sciaudone Michael, Wapniarski Annie, Zorn Kelsey C, Calderón Maritza, Cabrera Lilia, Pinedo-Cancino Viviana, Wilson Michael R, Asayag Cesar Ramal, Gilman Robert H, Bowman Natalie M
机构信息
Department of Microbiology and Immunology, University of Illinois Chicago, Chicago, Illinois, USA.
Department of Infectious Diseases, The Peter Doherty Institute for Immunity and Infection, University of Melbourne, Melbourne, Australia.
出版信息
Open Forum Infect Dis. 2023 Oct 27;10(11):ofad515. doi: 10.1093/ofid/ofad515. eCollection 2023 Nov.
BACKGROUND
Neurological opportunistic infections cause significant morbidity and mortality in people with human immunodeficiency virus (HIV) but are difficult to diagnose.
METHODS
One hundred forty people with HIV with acute neurological symptoms from Iquitos, Peru, were evaluated for cerebral toxoplasmosis with quantitative polymerase chain reaction (qPCR) of cerebrospinal fluid (CSF) and for cryptococcal meningitis with cryptococcal antigen test (CrAg) in serum or CSF. Differences between groups were assessed with standard statistical methods. A subset of samples was evaluated by metagenomic next-generation sequencing (mNGS) of CSF to compare standard diagnostics and identify additional diagnoses.
RESULTS
Twenty-seven participants were diagnosed with cerebral toxoplasmosis by qPCR and 13 with cryptococcal meningitis by CrAg. Compared to participants without cerebral toxoplasmosis, abnormal Glasgow Coma Scale score ( = .05), unilateral focal motor signs ( = .01), positive Babinski reflex ( = .01), and multiple lesions on head computed tomography (CT) ( = .002) were associated with cerebral toxoplasmosis. Photophobia ( = .03) and absence of lesions on head CT ( = .02) were associated with cryptococcal meningitis. mNGS of 42 samples identified 8 cases of cerebral toxoplasmosis, 7 cases of cryptococcal meningitis, 5 possible cases of tuberculous meningitis, and incidental detections of hepatitis B virus (n = 1) and pegivirus (n = 1). mNGS had a positive percentage agreement of 71% and a negative percentage agreement of 91% with qPCR for . mNGS had a sensitivity of 78% and specificity of 100% for diagnosis.
CONCLUSIONS
An infection was diagnosed by any method in only 34% of participants, demonstrating the challenges of diagnosing neurological opportunistic infections in this population and highlighting the need for broader, more sensitive diagnostic tests for central nervous system infections.
背景
神经机会性感染在人类免疫缺陷病毒（HIV）感染者中会导致显著的发病率和死亡率，但难以诊断。
方法
对来自秘鲁伊基托斯的140例有急性神经症状的HIV感染者进行评估，通过脑脊液（CSF）的定量聚合酶链反应（qPCR）检测脑弓形虫病，并通过血清或CSF中的隐球菌抗原检测（CrAg）检测隐球菌性脑膜炎。采用标准统计方法评估组间差异。对一部分样本进行CSF的宏基因组下一代测序（mNGS），以比较标准诊断方法并确定其他诊断。
结果
27例参与者通过qPCR被诊断为脑弓形虫病，13例通过CrAg被诊断为隐球菌性脑膜炎。与无脑弓形虫病的参与者相比，格拉斯哥昏迷量表评分异常（P = 0.05）、单侧局灶性运动体征（P = 0.01）、巴宾斯基反射阳性（P = 0.01）以及头部计算机断层扫描（CT）上的多发病变（P = 0.002）与脑弓形虫病相关。畏光（P = 0.03）和头部CT无病变（P = 0.02）与隐球菌性脑膜炎相关。42份样本的mNGS鉴定出8例脑弓形虫病、7例隐球菌性脑膜炎、5例可能的结核性脑膜炎，以及偶然检测到的乙型肝炎病毒（n = 1）和佩吉病毒（n = 1）。mNGS与qPCR对......的阳性百分比一致性为71%，阴性百分比一致性为91%。mNGS对......诊断的敏感性为78%，特异性为100%。
结论
仅34%的参与者通过任何方法确诊感染，这表明在该人群中诊断神经机会性感染具有挑战性，并突出了对中枢神经系统感染进行更广泛、更敏感诊断测试的必要性。
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