High diversity amongst African Treponema pallidum genomes provides a window into global transmission dynamics of syphilis: A genomic epidemiology study

Technical Deep Dive: High Diversity of African Treponema pallidum Genomes

Overview

This study provides a comprehensive genomic analysis of the Treponema pallidum bacterium that causes syphilis, focusing on samples from 6 African countries. The researchers generated 147 novel African T. pallidum genomes and analyzed them alongside 1062 genomes from 24 non-African countries. The key findings are:

• African T. pallidum strains show remarkable diversity, with 20 sublineages found exclusively in Africa.
• Only 16.2% of African syphilis cases are caused by sublineages that also circulate globally, while 83.8% are from locally circulating African strains.
• Macrolide resistance, a major public health concern, is much less common in Africa (20.1%) compared to the global average (68.6%).
• Cataloging African T. pallidum diversity will require intensive local sampling in many African countries, as sublineage sharing between countries is low.

These insights have important implications for genomic surveillance, vaccine design, and antibiotic resistance monitoring and treatment strategies in Africa.

Problem & Context

Syphilis is a re-emerging public health issue globally, with rates rising dramatically since the early 2000s. Understanding the genetic diversity and transmission dynamics of the causative bacterium, Treponema pallidum, is crucial for informing prevention and control strategies. While over 1000 T. pallidum genomes are now available from high-income countries, genomic data from Africa remains limited.

Methodology

The researchers combined 1198 samples from a genital ulcer study in 4 African countries (Botswana, Ghana, Uganda, Zimbabwe) with 276 samples from South African national surveillance to generate 147 novel African T. pallidum genomes, spanning 2006-2023. They analyzed these along with 167 previously published African genomes and 1062 genomes from 24 non-African countries.

Data & Experimental Setup

• Samples were collected from 1198 participants in 4 African countries (Botswana, Ghana, Uganda, Zimbabwe) as part of a genital ulcer study from 2022-2023.
• An additional 276 samples were obtained from national syphilis surveillance in South Africa.
• These 1474 samples were used to generate 147 novel African T. pallidum genomes.
• The 147 novel genomes were analyzed alongside 167 previously published African genomes and 1062 genomes from 24 non-African countries.

Results

Contrasting with previous studies showing global circulation of highly similar T. pallidum strains, the researchers found remarkable diversity among African T. pallidum:

• Of 56 identified T. pallidum sublineages:
  • 20 were exclusively found in the 6 African countries
  • 31 were found only in the 24 non-African countries
  • 5 were found in both Africa and the rest of the world
• 83.8% of African syphilis cases were caused by locally circulating African sublineages, with limited sharing between Africa and the rest of the world.
• Macrolide resistance, a major public health concern, was much less common in Africa (20.1%) compared to the global average (68.6%).
• Where macrolide resistance did occur in Africa, it was strongly linked to the introduction of globally circulating resistant sublineages.

Interpretation

The high diversity of African T. pallidum, with the majority of strains being locally confined, stands in contrast to the global circulation of highly similar strains observed in previous studies. This suggests that cataloging the full diversity of African T. pallidum will require intensive local sampling in many African countries, as sublineage sharing between countries is low.

The lower prevalence of macrolide resistance in Africa, and its strong association with the introduction of globally circulating resistant strains, indicates that antibiotic resistance in Africa may be more driven by the importation of resistant strains rather than de novo emergence. This provides an opportunity to tailor treatment guidelines based on local resistance data.

These findings highlight the importance of genomic surveillance and data-driven strategies for syphilis control and intervention in Africa, including the design of vaccines that provide broad global coverage.

Limitations & Uncertainties

• The study only included samples from 6 African countries, and more extensive sampling across the continent is needed to fully characterize African T. pallidum diversity.
• The reasons behind the observed differences in macrolide resistance prevalence between Africa and the rest of the world are not fully explored and would require further investigation.
• The study does not provide information on the clinical outcomes or epidemiological factors associated with the different T. pallidum sublineages.

What Comes Next

The study's findings point to several important next steps:

• Expand genomic surveillance of T. pallidum in Africa to more comprehensively catalog the diversity of strains circulating on the continent.
• Investigate the factors driving the observed differences in macrolide resistance prevalence between Africa and other regions.
• Explore the potential clinical and epidemiological implications of the different T. pallidum sublineages identified in this study.
• Use the insights from African T. pallidum genomic diversity to inform the design of vaccines and other intervention strategies that can provide broad global coverage.