Article Impact Level: HIGH Data Quality: STRONG Summary of The Lancet Microbe, 5(9), 100871. https://doi.org/10.1016/S2666-5247(24)00087-9 Dr. Arlene C. Seña et al.
Points
- The study investigated the global molecular epidemiology of Treponema pallidum subspecies pallidum (TPA), the causative agent of syphilis, by analyzing whole-genome sequences from 233 patients across China, Colombia, Malawi, and the USA.
- Whole-genome sequencing revealed a predominance of SS14-lineage strains with geographical clustering, while Nichols-lineage strains displayed greater genetic diversity.
- Phylogenomic analyses identified geographical differences in TPA strain diversity and highlighted specific single nucleotide variants (SNVs) in outer membrane proteins (OMPs), crucial to vaccine development.
- The study included a diverse participant pool, with 66% cisgender men, 43% identifying as gay or bisexual, and 24% co-infected with HIV.
- The findings emphasize the importance of population-specific genomic data in understanding syphilis epidemiology and guiding the development of effective syphilis vaccines.
Summary
This study investigated the global molecular epidemiology of Treponema pallidum subspecies pallidum (TPA), the causative agent of syphilis, to inform vaccine development efforts. The study enrolled 233 patients from clinics in China, Colombia, Malawi, and the USA between November 2019 and May 2022. Participants had laboratory-confirmed early-stage syphilis, including primary, secondary, or early latent syphilis. Whole-genome sequencing (WGS) was performed on various clinical specimens, such as lesion swabs and skin biopsies, to analyze the genetic diversity of TPA strains. The study included 113 participants for WGS analysis, revealing the predominance of SS14-lineage strains with geographical clustering. Furthermore, Nichols-lineage strains exhibited greater genetic diversity than SS14-lineage strains.
The median age of participants was 28 years, and 66% were cisgender men, with 43% identifying as gay, bisexual, or other sexuality. HIV co-infection was present in 24% of participants. Phylogenomic analyses showed distinct geographical patterns in TPA strain diversity, with significant differences in single nucleotide variants (SNVs) between TPA lineages and regions. Mapping these SNVs to three-dimensional protein models highlighted specific substitutions, some of which occurred in outer membrane proteins (OMPs), which are considered critical for vaccine development. The study’s findings provide insights into the genetic variability of TPA, underscoring the importance of lineage and geographical differences in understanding syphilis epidemiology.
This research demonstrates the global diversity of TPA strains, particularly between SS14 and Nichols lineages, and identifies mutations that may influence vaccine target development. The study highlights the need to explore further TPA OMP variability within populations, which could be crucial for designing effective vaccines and understanding syphilis pathogenesis. These findings emphasize the importance of population-specific genomic data in guiding syphilis vaccine research.
Link to the article: https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(24)00087-9/fulltext
References Seña, A. C., Matoga, M. M., Yang, L., Lopez-Medina, E., Aghakhanian, F., Chen, J. S., Bettin, E. B., Caimano, M. J., Chen, W., Garcia-Luna, J. A., Hennelly, C. M., Jere, E., Jiang, Y., Juliano, J. J., Pospíšilová, P., Ramirez, Lady, Šmajs, D., Tucker, J. D., Vargas Cely, F., … Parr, J. B. (2024). Clinical and genomic diversity of Treponema pallidum subspecies pallidum to inform vaccine research: An international, molecular epidemiology study. The Lancet Microbe, 5(9), 100871. https://doi.org/10.1016/S2666-5247(24)00087-9
