PDF(Pubmed)
Abstract：
Trachoma is the leading infectious cause of blindness worldwide and is now largely confined to around 40 low- and middle-income countries. It is caused by Chlamydia trachomatis (Ct), a contagious intracellular bacterium. The World Health Organization recommends mass drug administration (MDA) with azithromycin for treatment and control of ocular Ct infections, alongside improving facial cleanliness and environmental conditions to reduce transmission. To understand the molecular epidemiology of trachoma, especially in the context of MDA and transmission dynamics, the identification of Ct genotypes could be useful. While many studies have used the Ct major outer membrane protein gene (ompA) for genotyping, it has limitations. Our study applies a typing system novel to trachoma, Multiple Loci Variable Number Tandem Repeat Analysis combined with ompA (MLVA-ompA). Ocular swabs were collected post-MDA from four trachoma-endemic zones in Ethiopia between 2011-2017. DNA from 300 children with high Ct polymerase chain reaction (PCR) loads was typed using MLVA-ompA, utilizing 3 variable number tandem repeat (VNTR) loci within the Ct genome. Results show that MLVA-ompA exhibited high discriminatory power (0.981) surpassing the recommended threshold for epidemiological studies. We identified 87 MLVA-ompA variants across 26 districts. No significant associations were found between variants and clinical signs or chlamydial load. Notably, overall Ct diversity significantly decreased after additional MDA rounds, with a higher proportion of serovar A post-MDA. Despite challenges in sequencing one VNTR locus (CT1299), MLVA-ompA demonstrated cost-effectiveness and efficiency relative to whole genome sequencing, providing valuable information for trachoma control programs on local epidemiology. The findings suggest the potential of MLVA-ompA as a reliable tool for typing ocular Ct and understanding transmission dynamics, aiding in the development of targeted interventions for trachoma control.
摘要：
沙眼是世界范围内导致失明的主要传染病，现在主要局限于大约40个低收入和中等收入国家。它是由沙眼衣原体（Ct）引起的，一种具有传染性的胞内细菌.世界卫生组织建议使用阿奇霉素进行大规模药物治疗（MDA）以治疗和控制眼部Ct感染，同时改善面部清洁度和环境条件，以减少传播。了解沙眼的分子流行病学,特别是在MDA和传输动力学的背景下，Ct基因型的鉴定可能是有用的。虽然许多研究已经使用Ct主要外膜蛋白基因（ompA）进行基因分型，它有局限性。我们的研究将新型分型系统应用于沙眼，多基因座可变数量串联重复分析结合ompA(MLVA-ompA)。在2011年至2017年期间，从埃塞俄比亚的四个沙眼流行区收集MDA后的眼拭子。使用MLVA-ompA对300名具有高Ct聚合酶链反应（PCR）负荷的儿童的DNA进行分型，利用Ct基因组内的3个可变数量串联重复(VNTR)基因座。结果表明，MLVA-ompA显示出较高的判别力（0.981），超过了流行病学研究的推荐阈值。我们在26个地区确定了87个MLVA-ompA变体。在变异与临床体征或衣原体负荷之间没有发现显着关联。值得注意的是,在额外的MDA轮次后，整体Ct多样性显着下降，血清变型A后MDA的比例更高。尽管在对一个VNTR基因座（CT1299）进行测序方面存在挑战，MLVA-ompA显示出相对于全基因组测序的成本效益和效率。为沙眼防治计划提供有价值的当地流行病学信息。研究结果表明，MLVA-ompA可能是一种可靠的工具，用于键入眼Ct和理解传输动力学。协助制定有针对性的沙眼控制干预措施。
