Krumova Stefka, Pavlova Adelina, Yotovska Kamelia, Genova-Kalou Petia
Clin Lab. 2019 Jan 1;65(1). doi: 10.7754/Clin.Lab.2018.180617.
Fever of unknown origin (FUO) is one of the greatest challenges for clinicians and patients. There are more than 200 etiological agents of FUO, among these the most common is the role of infection, neoplasms, and diseases of connective tissue. The aim of the present study is to investigate the role of the infectious agents parvovirus B19 (B19V) and Coxiella burnetii (C. burnetii) in the development of fever of unknown origin by a set of immunoenzymatic and molecular methods.
The present study included a total of 70 adult patients diagnosed with FUO and hospitalized in Bulgarian Hospitals. A control group of 26 healthy people were also included. Serological (indirect enzyme immunoassay test for detection of B19V and C. burnetii Ph. II specific IgM/IgG) and molecular (extraction and detection of infectious nucleic acids) methods were used.
From all patients with FUO, a positive result for B19V-IgM was obtained in 18/70 (25.71%, 95% CI: 15.47 - 35.95) and the highest percentage was found in age groups 0 - 9 and 10 - 19 years. Protective B19V immunity and past viral infection was reported in 41/70 (58.57%, 95% CI: 47.03 - 70.11), and this percentage corresponded with the control group 16/26 (61.54%, 95% CI: 42.84 - 80.24). Anti-C. burnetii Ph. II-IgM was demonstrated in 13/70 (18.57%, 95% CI: 9.46 - 27.68). A relatively high percentage of affected patients were ≤ 40 years. Anti-C. burnetii Ph. II-IgG was detected in 24/70 (34.29%, 95% CI: 23.17 - 45.41). The control group has a 100% negative result for acute B19V and C. burnetii infection. A positive B19V-DNA result was obtained in 12/70 (17.14%, 95% CI: 8.31 - 25.97) patients. In 11/12 (91.67%) it was in combination with positive B19V-IgM marker. Of the total 70 sera tested, a positive PCR results for C. burnetii-DNA were obtained in 11 (15.71%, 95% CI: 7.18 - 24.24). According to clinical manifestation and concomitant symptoms, a high percentage of B19V and C. burnetii positives were associated with FUO and fever, headache, chills, and rash.
It is of particular importance for a correct diagnosis of FUO to use a combined laboratory approach to prove acute or persistent infection and to test for a set of etiological agents.
不明原因发热（FUO）是临床医生和患者面临的最大挑战之一。FUO有200多种病因，其中最常见的是感染、肿瘤和结缔组织疾病。本研究旨在通过一系列免疫酶和分子方法研究细小病毒B19（B19V）和伯氏考克斯体（C. burnetii）在不明原因发热发生中的作用。
本研究共纳入70例诊断为FUO并在保加利亚医院住院的成年患者。还纳入了26名健康人的对照组。采用血清学方法（间接酶免疫测定法检测B19V和伯氏考克斯体Ⅱ相特异性IgM/IgG）和分子方法（提取和检测感染性核酸）。
在所有FUO患者中，18/70（25.71%，95%CI：15.47 - 35.95）的B19V-IgM检测结果为阳性，0 - 9岁和10 - 19岁年龄组的阳性率最高。41/70（58.57%，95%CI：47.03 - 70.11）的患者报告有B19V保护性免疫和既往病毒感染，该百分比与对照组16/26（61.54%，95%CI：42.84 - 80.24）相当。13/70（18.57%，95%CI：9.46 - 27.68）的患者检测到抗伯氏考克斯体Ⅱ相-IgM。受影响患者中≤40岁的比例相对较高。24/70（34.29%，95%CI：23.17 - 45.41）的患者检测到抗伯氏考克斯体Ⅱ相-IgG。对照组急性B19V和伯氏考克斯体感染的检测结果均为阴性。12/70（17.14%，95%CI：8.31 - 25.97）的患者B19V-DNA检测结果为阳性。在11/12（91.67%）的患者中，其与B19V-IgM标志物阳性同时出现。在总共检测的70份血清中，11份（15.71%，95%CI：7.18 - 至24.24）的伯氏考克斯体-DNA PCR检测结果为阳性。根据临床表现和伴随症状，B19V和伯氏考克斯体阳性患者中很大一部分与FUO以及发热、头痛、寒战和皮疹有关。
采用联合实验室方法来证明急性或持续性感染并检测一系列病原体对于正确诊断FUO尤为重要。
