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哥伦比亚卡利的二期梅毒:疾病发病机制的新概念。

Secondary syphilis in cali, Colombia: new concepts in disease pathogenesis.

机构信息

Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia.

出版信息

PLoS Negl Trop Dis. 2010 May 18;4(5):e690. doi: 10.1371/journal.pntd.0000690.

Abstract

Venereal syphilis is a multi-stage, sexually transmitted disease caused by the spirochetal bacterium Treponema pallidum (Tp). Herein we describe a cohort of 57 patients (age 18-68 years) with secondary syphilis (SS) identified through a network of public sector primary health care providers in Cali, Colombia. To be eligible for participation, study subjects were required to have cutaneous lesions consistent with SS, a reactive Rapid Plasma Reagin test (RPR-titer > or = 1 : 4), and a confirmatory treponemal test (Fluorescent Treponemal Antibody Absorption test- FTA-ABS). Most subjects enrolled were women (64.9%), predominantly Afro-Colombian (38.6%) or mestizo (56.1%), and all were of low socio-economic status. Three (5.3%) subjects were newly diagnosed with HIV infection at study entry. The duration of signs and symptoms in most patients (53.6%) was less than 30 days; however, some patients reported being symptomatic for several months (range 5-240 days). The typical palmar and plantar exanthem of SS was the most common dermal manifestation (63%), followed by diffuse hypo- or hyperpigmented macules and papules on the trunk, abdomen and extremities. Three patients had patchy alopecia. Whole blood (WB) samples and punch biopsy material from a subset of SS patients were assayed for the presence of Tp DNA polymerase I gene (polA) target by real-time qualitative and quantitative PCR methods. Twelve (46%) of the 26 WB samples studied had quantifiable Tp DNA (ranging between 194.9 and 1954.2 Tp polA copies/ml blood) and seven (64%) were positive when WB DNA was extracted within 24 hours of collection. Tp DNA was also present in 8/12 (66%) skin biopsies available for testing. Strain typing analysis was attempted in all skin and WB samples with detectable Tp DNA. Using arp repeat size analysis and tpr RFLP patterns four different strain types were identified (14d, 16d, 13d and 22a). None of the WB samples had sufficient DNA for typing. The clinical and microbiologic observations presented herein, together with recent Cali syphilis seroprevalence data, provide additional evidence that venereal syphilis is highly endemic in this region of Colombia, thus underscoring the need for health care providers in the region to be acutely aware of the clinical manifestations of SS. This study also provides, for the first time, quantitative evidence that a significant proportion of untreated SS patients have substantial numbers of circulating spirochetes. How Tp is able to persist in the blood and skin of SS patients, despite the known presence of circulating treponemal opsonizing antibodies and the robust pro-inflammatory cellular immune responses characteristic of this stage of the disease, is not fully understood and requires further study.

摘要

梅毒是一种由苍白密螺旋体(Tp)引起的多阶段、性传播疾病。在此,我们描述了一组 57 例(年龄 18-68 岁)二期梅毒(SS)患者,这些患者是通过哥伦比亚卡利市的公共初级卫生保健机构网络发现的。为了有资格参与研究,研究对象必须具有符合 SS 的皮肤损伤、反应性快速血浆反应素试验(RPR 滴度≥1:4)和确认性密螺旋体试验(荧光密螺旋体抗体吸收试验-FTA-ABS)。大多数入组的患者为女性(64.9%),主要为非裔哥伦比亚人(38.6%)或混血儿(56.1%),且均处于低社会经济地位。有 3 名(5.3%)患者在研究入组时被新诊断为 HIV 感染。大多数患者(53.6%)的症状和体征持续时间不到 30 天;然而,一些患者报告有几个月的症状(5-240 天)。SS 的典型掌跖疹是最常见的皮肤表现(63%),其次是躯干、腹部和四肢弥漫性低色素或高色素斑和丘疹。有 3 名患者有斑片状脱发。对一组 SS 患者的全血(WB)样本和皮肤活检材料进行了实时定性和定量 PCR 方法检测 Tp DNA 聚合酶 I 基因(polA)靶标。在研究的 26 个 WB 样本中,有 12 个(46%)可检测到 Tp DNA(血液中 Tp polA 拷贝/ml 范围为 194.9 至 1954.2),且在采集后 24 小时内提取 WB DNA 时 7 个(64%)为阳性。在 8/12(66%)可用于检测的皮肤活检样本中也存在 Tp DNA。对所有可检测到 Tp DNA 的皮肤和 WB 样本进行了菌株分型分析。通过 arp 重复大小分析和 tpr RFLP 模式,鉴定出了 4 种不同的菌株类型(14d、16d、13d 和 22a)。没有 WB 样本有足够的 DNA 进行分型。本文介绍的临床和微生物学观察结果,以及最近卡利梅毒血清流行率数据,进一步证明了生殖器梅毒在哥伦比亚该地区高度流行,因此强调了该地区医疗保健提供者需要敏锐地意识到 SS 的临床症状。本研究还首次提供了定量证据,证明相当一部分未经治疗的 SS 患者有大量循环螺旋体。Tp 如何能够在 SS 患者的血液和皮肤中持续存在,尽管已知存在循环密螺旋体的调理抗体和该疾病阶段特有的强烈促炎细胞免疫反应,这尚未完全了解,需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dd68/2872645/371b5615186a/pntd.0000690.g001.jpg

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