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副球孢子菌病的血清学诊断:医学真菌学参考中心之间实验室间变异性高。

Serological diagnosis of paracoccidioidomycosis: high rate of inter-laboratorial variability among medical mycology reference centers.

作者信息

Vidal Monica Scarpelli Martinelli, Del Negro Gilda Maria Barbaro, Vicentini Adriana Pardini, Svidzinski Teresinha Inez Estivalet, Mendes-Giannini Maria Jose, Almeida Ana Marisa Fusco, Martinez Roberto, de Camargo Zoilo Pires, Taborda Carlos Pelleschi, Benard Gil

机构信息

Medical Mycology Laboratory (IMTSP and LIM-53), Clinics Hospital of the Medical School and Tropical Medicine Institute, University of São Paulo (USP), São Paulo, São Paulo State, Brazil.

Mycoses Immunodiagnosis Laboratory, Adolfo Lutz Institute, São Paulo (IAL-SP), São Paulo, São Paulo State, Brazil.

出版信息

PLoS Negl Trop Dis. 2014 Sep 11;8(9):e3174. doi: 10.1371/journal.pntd.0003174. eCollection 2014 Sep.

Abstract

BACKGROUND

Serological tests have long been established as rapid, simple and inexpensive tools for the diagnosis and follow-up of PCM. However, different protocols and antigen preparations are used and the few attempts to standardize the routine serological methods have not succeeded.

METHODOLOGY/PRINCIPAL FINDINGS: We compared the performance of six Brazilian reference centers for serological diagnosis of PCM. Each center provided 30 sera of PCM patients, with positive high, intermediate and low titers, which were defined as the "reference" titers. Each center then applied its own antigen preparation and serological routine test, either semiquantitative double immunodifusion or counterimmmunoelectrophoresis, in the 150 sera from the other five centers blindly as regard to the "reference" titers. Titers were transformed into scores: 0 (negative), 1 (healing titers), 2 (active disease, low titers) and 3 (active disease, high titers) according to each center's criteria. Major discordances were considered between scores indicating active disease and scores indicating negative or healing titers; such discordance when associated with proper clinical and other laboratorial data, may correspond to different approaches to the patient's treatment. Surprisingly, all centers exhibited a high rate of "major" discordances with a mean of 31 (20%) discordant scores. Alternatively, when the scores given by one center to their own sera were compared with the scores given to their sera by the remaining five other centers, a high rate of major discordances was also found, with a mean number of 14.8 sera in 30 presenting a discordance with at least one other center. The data also suggest that centers that used CIE and pool of isolates for antigen preparation performed better.

CONCLUSION

There are inconsistencies among the laboratories that are strong enough to result in conflicting information regarding the patients' treatment. Renewed efforts should be promoted to improve standardization of the serological diagnosis of PCM.

摘要

背景

长期以来,血清学检测一直是用于荚膜组织胞浆菌病(PCM)诊断及随访的快速、简便且廉价的工具。然而,目前所使用的检测方案和抗原制剂各不相同,并且少数标准化常规血清学方法的尝试均未成功。

方法/主要发现:我们比较了巴西六个参考中心对PCM进行血清学诊断的性能。每个中心提供30份PCM患者血清,其滴度分别为高、中、低阳性,这些被定义为“参考”滴度。然后,每个中心将其自己的抗原制剂和血清学常规检测方法(半定量双向免疫扩散或对流免疫电泳),对来自其他五个中心的150份血清进行盲法检测,检测时不考虑“参考”滴度。根据每个中心的标准,将滴度转化为分数:0(阴性)、1(痊愈滴度)、2(活动性疾病,低滴度)和3(活动性疾病,高滴度)。主要不一致情况被认为存在于指示活动性疾病的分数与指示阴性或痊愈滴度的分数之间;当这种不一致与适当的临床及其他实验室数据相关联时,可能对应于对患者治疗的不同方法。令人惊讶的是,所有中心均表现出较高比例的“主要”不一致情况,平均有31个(20%)不一致分数。另外,当将一个中心对其自身血清给出的分数与其他五个中心对其血清给出的分数进行比较时,也发现了较高比例的主要不一致情况,在30份血清中平均有14.8份血清与至少一个其他中心存在不一致。数据还表明,使用对流免疫电泳(CIE)和分离株混合液作为抗原制剂的中心表现更佳。

结论

各实验室之间存在的不一致性非常严重,足以导致关于患者治疗的信息相互冲突。应重新做出努力以促进荚膜组织胞浆菌病血清学诊断的标准化。

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