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Abstract：
BACKGROUND: Venereal syphilis, caused by the spirochete Treponema pallidum subsp. pallidum (TPA), is surging worldwide, underscoring the need for a vaccine with global efficacy. Vaccine development requires an understanding of syphilis epidemiology and clinical presentation as well as genomic characterization of TPA strains circulating within at-risk populations. The aim of this study was to describe the clinical, demographic, and molecular features of early syphilis cases in Cali, Colombia.
RESULTS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/μl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/μl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein\'s predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates.
CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.
RESULTS: We conducted a cross-sectional study to identify individuals with early syphilis (ES) in Cali, Colombia through a city-wide network of public health centers, private sector HIV clinics and laboratory databases from public health institutions. Whole blood (WB), skin biopsies (SB), and genital and oral lesion swabs were obtained for measurement of treponemal burdens by polA quantitative polymerase chain reaction (qPCR) and for whole-genome sequencing (WGS). Among 1,966 individuals screened, 128 participants met enrollment criteria: 112 (87%) with secondary (SS), 15 (12%) with primary (PS) and one with early latent syphilis; 66/128 (52%) self-reported as heterosexual, while 48 (38%) were men who have sex with men (MSM). Genital ulcer swabs had the highest polA copy numbers (67 copies/μl) by qPCR with a positivity rate (PR) of 73%, while SS lesions had 42 polA copies/μl with PR of 62%. WB polA positivity was more frequent in SS than PS (42% vs 7%, respectively; p = 0.009). Isolation of TPA from WB by rabbit infectivity testing (RIT) was achieved in 5 (56%) of 9 ES WB samples tested. WGS from 33 Cali patient samples, along with 10 other genomic sequences from South America (9 from Peru, 1 from Argentina) used as comparators, confirmed that SS14 was the predominant clade, and that half of all samples had mutations associated with macrolide (i.e., azithromycin) resistance. Variability in the outer membrane protein (OMP) and vaccine candidate BamA (TP0326) was mapped onto the protein\'s predicted structure from AlphaFold. Despite the presence of mutations in several extracellular loops (ECLs), ECL4, an immunodominant loop and proven opsonic target, was highly conserved in this group of Colombian and South American TPA isolates.
CONCLUSIONS: This study offers new insights into the sociodemographic and clinical features of venereal syphilis in a highly endemic area of Colombia and illustrates how genomic sequencing of regionally prevalent TPA strains can inform vaccine development.
摘要：
背景：性病梅毒，由螺旋体梅毒螺旋体亚种引起。苍白球（TPA），正在全球范围内风起云涌，强调需要一种具有全球效力的疫苗。疫苗开发需要了解梅毒流行病学和临床表现以及在高危人群中循环的TPA菌株的基因组特征。这项研究的目的是描述临床，人口统计学,和卡利早期梅毒病例的分子特征，哥伦比亚。
结果：我们进行了一项横断面研究，以确定卡利地区的早期梅毒（ES）个体，哥伦比亚通过全市范围的公共卫生中心网络，私营部门艾滋病毒诊所和公共卫生机构的实验室数据库。全血（WB），皮肤活检（SB），获得生殖器和口腔病变拭子，用于通过polA定量聚合酶链反应（qPCR）和全基因组测序（WGS）测量螺旋体负担。在接受筛查的1,966人中，128名参与者符合登记标准：112名（87%），中学（SS），15（12％）患有原发性（PS）和早期潜伏梅毒；66/128（52％）自我报告为异性恋，而48人（38%）是男男性行为者（MSM）。通过qPCR，生殖器溃疡拭子的polA拷贝数最高（67拷贝/μl），阳性率（PR）为73％，而SS病变有42个polA拷贝/μl，PR为62%。SS中WBpolA阳性比PS更频繁(42%对7%，分别为；p=0.009)。在测试的9个ESWB样品中的5个(56%)中实现了通过兔感染性测试(RIT)从WB分离TPA。来自33个卡利患者样本的WGS，以及来自南美的其他10个基因组序列（来自秘鲁的9个，1来自阿根廷)用作比较器，证实SS14是主要的进化枝，并且所有样本中有一半具有与大环内酯相关的突变(即，阿奇霉素)耐药性。外膜蛋白(OMP)和候选疫苗BamA(TP0326)的变异被定位到来自AlphaFold的蛋白质预测结构上。尽管在几个细胞外环（ECL）中存在突变，ECL4，一种免疫显性环和经过验证的调理靶，在这组哥伦比亚和南美TPA分离物中高度保守。
结论：这项研究为哥伦比亚高度流行地区的性病梅毒的社会人口统计学和临床特征提供了新的见解，并说明了区域流行的TPA菌株的基因组测序如何为疫苗开发提供信息。
结果：我们进行了一项横断面研究，以确定卡利地区的早期梅毒（ES）个体，哥伦比亚通过全市范围的公共卫生中心网络，私营部门艾滋病毒诊所和公共卫生机构的实验室数据库。全血（WB），皮肤活检（SB），获得生殖器和口腔病变拭子，用于通过polA定量聚合酶链反应（qPCR）和全基因组测序（WGS）测量螺旋体负担。在接受筛查的1,966人中，128名参与者符合登记标准：112名（87%），中学（SS），15（12％）患有原发性（PS）和早期潜伏梅毒；66/128（52％）自我报告为异性恋，而48人（38%）是男男性行为者（MSM）。通过qPCR，生殖器溃疡拭子的polA拷贝数最高（67拷贝/μl），阳性率（PR）为73％，而SS病变有42个polA拷贝/μl，PR为62%。SS中WBpolA阳性比PS更频繁(42%对7%，分别为；p=0.009)。在测试的9个ESWB样品中的5个(56%)中实现了通过兔感染性测试(RIT)从WB分离TPA。来自33个卡利患者样本的WGS，以及来自南美的其他10个基因组序列（来自秘鲁的9个，1来自阿根廷)用作比较器，证实SS14是主要的进化枝，并且所有样本中有一半具有与大环内酯相关的突变(即，阿奇霉素)耐药性。外膜蛋白(OMP)和候选疫苗BamA(TP0326)的变异被定位到来自AlphaFold的蛋白质预测结构上。尽管在几个细胞外环（ECL）中存在突变，ECL4，一种免疫显性环和经过验证的调理靶，在这组哥伦比亚和南美TPA分离物中高度保守。
结论：这项研究为哥伦比亚高度流行地区的性病梅毒的社会人口统计学和临床特征提供了新的见解，并说明了区域流行的TPA菌株的基因组测序如何为疫苗开发提供信息。
