CT694 and pgp3 as serological tools for monitoring trachoma programs.

CT694 and pgp3 as serological tools for monitoring trachoma programs.
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DOI:
10.1371/journal.pntd.0001873
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发表时间:
2012
影响因子:
3.8
通讯作者:
Lammie PJ
Lammie PJ
中科院分区:
医学2区
文献类型:
--
作者:
Goodhew EB;Priest JW;Moss DM;Zhong G;Munoz B;Mkocha H;Martin DL;West SK;Gaydos C;Lammie PJ

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为沙眼项目确定终点可能是一个挑战,因为在没有可检测到的细菌的情况下,感染的临床迹象可能会持续存在。以抗体为基础的检测可为项目末期阶段的监测提供另一种检测策略。基于抗体的分析,特别是ELISA,已经被证明对证明沙眼衣原体生殖道感染是有用的,但还没有被广泛探索到眼部沙眼衣原体感染。采用基于抗体的多重试验检测沙眼衣原体Pgp3和CT694两种抗原,检测经多轮阿奇霉素治疗后采集的坦桑尼亚儿童(n = 160)血斑中的沙眼衣原体抗体。使用来自坦桑尼亚的沙眼衣原体阳性儿童(n = 11)和美国非流行儿童组的对照血清(n = 122)的样本,对Pgp3和CT694的抗体反应被确定为91%的敏感性和98%的特异性。坦桑尼亚儿童的抗体反应与临床沙眼、聚合酶链式反应阳性和年龄有关。一般来说,眼部病变较重(Tf/TI = 2或最严重)的儿童对PGP3(p = 0.0041)和CT694(p = 0.0282)的抗体应答中位数高于正常检查儿童(Tf/TI = 0)。然而,在没有眼部病理的儿童中,44%的抗体检测呈阳性,这表明以前有过感染。三岁以下儿童的抗体效价中位数显著低于年龄较大的儿童。(两种抗原的P<均为0.0001)。以抗体为基础的多重检测是评估沙眼传播的一种敏感和特异的辅助工具。该检测还可以扩展到包括代表不同疾病的抗原,从而允许在NTD项目中进行可靠的监测。沙眼是一种由沙眼衣原体反复感染引起的眼部疾病,主要见于儿童和妇女。反复感染后形成的疤痕会导致睫毛在眼皮下翻转,可能会导致角膜混浊和失明。多个组织加大了努力,以实现世界卫生组织到2020年消除沙眼的目标。随着大规模药物管理的进行,可能很难评估传播是否已经减少到足以停止治疗而不复发。在这种低流行率的情况下,敏感和具体的监测工具很重要。目前,临床诊断是通过检查眼睑内侧的毛囊和炎症来进行的,感染的评估最好是使用商业试剂盒的聚合酶链式反应分析。这些检测结果并不总是一致的,这表明需要更多的监测工具。利用多重检测平台,我们比较了参与大规模治疗计划的160名坦桑尼亚儿童对两种衣原体抗原的抗体反应与眼科检查和聚合酶链式反应结果。抗体反应被证明是感染和疾病状态的良好指示器,抗体检测可能是有用的监测工具。
Defining endpoints for trachoma programs can be a challenge as clinical signs of infection may persist in the absence of detectable bacteria. Antibody-based tests may provide an alternative testing strategy for surveillance during terminal phases of the program. Antibody-based assays, in particular ELISAs, have been shown to be useful to document C. trachomatis genital infections, but have not been explored extensively for ocular C. trachomatis infections. An antibody-based multiplex assay was used to test two C. trachomatis antigens, pgp3 and CT694, for detection of trachoma antibodies in bloodspots from Tanzanian children (n = 160) collected after multiple rounds of mass azithromycin treatment. Using samples from C. trachomatis-positive (by PCR) children from Tanzania (n = 11) and control sera from a non-endemic group of U.S. children (n = 122), IgG responses to both pgp3 and CT694 were determined to be 91% sensitive and 98% specific. Antibody responses of Tanzanian children were analyzed with regard to clinical trachoma, PCR positivity, and age. In general, children with more intense ocular pathology (TF/TI = 2 or most severe) had a higher median antibody response to pgp3 (p = 0.0041) and CT694 (p = 0.0282) than those with normal exams (TF/TI = 0). However, 44% of children with no ocular pathology tested positive for antibody, suggesting prior infection. The median titer of antibody responses for children less than three years of age was significantly lower than those of older children. (p<0.0001 for both antigens). The antibody-based multiplex assay is a sensitive and specific additional tool for evaluating trachoma transmission. The assay can also be expanded to include antigens representing different diseases, allowing for a robust assay for monitoring across NTD programs. Trachoma is an ocular disease caused by repeated infections with the bacteria Chlamydia trachomatis that is observed mostly in children and women. Scarring after repeated infections causes eyelashes to turn under the lid, possibly leading to corneal opacity and blindness. Efforts have increased by multiple organizations to meet the World Health Organization's goal of eliminating trachoma by 2020. As mass drug administration is carried out, it can be difficult to assess whether transmission has lessened enough to stop treatment without resurgence of disease. In this low prevalence setting, sensitive and specific surveillance tools are important. Currently, clinical diagnosis is carried out by examination of the inside of the eyelid for follicles and inflammation, and infection is best assessed using PCR analysis with commercial kits. These test results do not always align, indicating a need for additional tools for surveillance. Using the multiplex assay platform, we compared antibody responses to two chlamydial antigens with eye exams and PCR results of 160 Tanzanian children participating in a mass treatment program. Antibody responses were shown to be a good indicator of infection and disease status and antibody tests may be useful as surveillance tools.
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