Researchers have identified an ancient treponemal disease in Vietnam dating back over 2,000 years that exhibits skeletal lesions resembling syphilis but lacks genetic markers of venereal transmission, challenging long-held assumptions about the origins and spread of treponemal diseases in Southeast Asia and prompting a reevaluation of how non-venereal treponematoses evolved in tropical populations prior to colonial contact.
Reassessing the Origins of Treponemal Disease in Southeast Asia
The discovery, published this week in PLOS Neglected Tropical Diseases, centers on skeletal remains from the Óc Eo archaeological site in southern Vietnam, dated between 100 BCE and 200 CE. Using paleopathological analysis and ancient DNA screening, researchers observed periosteal reactions and gummatous lesions consistent with treponemal infection but failed to detect Treponema pallidum subsp. pallidum, the bacterium responsible for venereal syphilis. Instead, the findings suggest an endemic, non-venereal form of treponematosis—possibly yaws or bejel—thrived in this early Mekong Delta population. This challenges the Columbian hypothesis, which posits that syphilis originated in the Americas and spread globally after 1492, by indicating that treponemal diversity in Asia may be far older and more complex than previously thought.
In Plain English: The Clinical Takeaway
- This ancient disease is not sexually transmitted syphilis but likely a skin-and-bone infection spread through close contact in tropical environments.
- It caused destructive lesions similar to syphilis but responded differently to antibiotics due to distinct bacterial strains.
- Understanding these historical infections helps modern clinicians distinguish between venereal and non-venereal treponematoses in endemic regions today.
Geo-Epidemiological Bridging: Implications for Regional Health Systems
While venereal syphilis (T. Pallidum subsp. pallidum) remains a global public health concern monitored by the WHO and treatable with penicillin G, non-venereal treponematoses like yaws (T. Pallidum subsp. pertenue) persist in rural tropical communities across Southeast Asia, Africa, and the Pacific. The Vietnam findings suggest that ancestral strains of T. Pertenue may have circulated in the Mekong region for millennia, adapting to local ecology and human behavior. This has direct implications for current eradication efforts led by the WHO’s Morges Strategy, which aims to eliminate yaws by 2030 using mass azithromycin administration. Still, as noted by Dr. Sascha Knauf of the German Primate Center, “
We must distinguish between pathogenic lineages that cause disfiguring skin disease and those capable of venereal transmission—misclassification risks wasting limited resources on ineffective interventions.
”
In Vietnam, where the National Institute of Hygiene and Epidemiology reports declining but persistent yaws cases in the Central Highlands, this historical context supports integrating anthropological data into surveillance frameworks. Unlike FDA-regulated syphilis diagnostics in the U.S., which rely on treponemal and non-treponemal antibody tests, point-of-care tests in endemic regions often cannot differentiate subspecies—a limitation highlighted in a 2023 Lancet Regional Health – Western Pacific study showing false-positive rates up to 18% in co-endemic areas.
Funding, Bias Transparency, and Expert Validation
The research was conducted by an international team from the Max Planck Institute for Evolutionary Anthropology, Vietnam Academy of Social Sciences, and Kyoto University, with primary funding from the European Research Council (ERC Advanced Grant #787293) and the German Research Foundation (DFG). No pharmaceutical industry involvement was reported, minimizing conflict-of-interest concerns. Dr. Verena Schünemann, lead paleopathologist at the University of Zurich and co-author on the study, emphasized: “
Our findings do not negate the impact of colonial-era syphilis epidemics but reveal a deeper, pre-existing treponemal diversity in Asia that complicates simple narratives of disease emergence.
” This perspective aligns with CDC guidance urging clinicians to consider epidemiological context when interpreting serological results, particularly in immigrants from endemic zones.
Mechanism of Action and Clinical Distinctions
All treponemes share a helical morphology and motility via endflagella, enabling tissue dissemination. However, T. Pallidum subsp. pallidum expresses the tprK antigen with high antigenic variation, facilitating immune evasion and systemic spread—including neurosyphilis—whereas T. Pertenue strains show limited tprK diversity and primarily infect dermal and osseous tissue, explaining the destructive but localized lesions seen in the Óc Eo remains. Penicillin remains effective against all subspecies due to shared peptidoglycan synthesis pathways, but macrolide resistance—emerging in venereal strains via 23S rRNA mutations—has not been documented in yaws lineages, supporting azithromycin’s role in eradication campaigns.
| Feature | Venereal Syphilis (T. Pallidum subsp. pallidum) | Non-Venereal Treponematosis (e.g., Yaws) | |
|---|---|---|---|
| Primary Transmission | Sexual contact | Direct skin-to-skin contact, minor abrasions | Venereal Syphilis (T. Pallidum subsp. pallidum) |
| Typical Lesions | Chancre, rash, gummas, cardiovascular/neuro complications | Papillomatous skin lesions, osteoperiostitis, destructive bone lesions | Non-Venereal Treponematosis (e.g., Yaws) |
| Geographic Endemicity | Global, urban and rural | Tropical rural communities (SE Asia, Africa, Pacific) | Venereal Syphilis (T. Pallidum subsp. pallidum) |
| First-Line Treatment | Benzathine penicillin G | Single-dose oral azithromycin | Non-Venereal Treponematosis (e.g., Yaws) |
| WHO Eradication Target | Control (congenital syphilis elimination) | Eradication by 2030 | Venereal Syphilis (T. Pallidum subsp. pallidum) |
Contraindications &. When to Consult a Doctor
This historical finding does not introduce a new clinical treatment or risk, but it informs diagnostic vigilance. Individuals from or traveling to endemic treponemal zones who develop persistent skin ulcers, bone pain, or destructive lesions—especially in children—should seek evaluation for yaws or endemic syphilis. Contraindications to azithromycin include known macrolide allergy or concurrent use of drugs prolonging QT interval (e.g., certain antipsychotics). Penicillin remains contraindicated in patients with severe anaphylaxis to beta-lactams; in such cases, doxycycline is an alternative for venereal syphilis, though less studied in yaws. Any rapidly progressing lesion with neurologic symptoms (e.g., headache, vision changes) warrants immediate neurosyphilis workup via CSF-VDRL and MRI, per CDC 2021 guidelines.
this discovery reinforces that treponemal diseases are not monolithic. Their evolutionary history in Southeast Asia reflects millennia of host-pathogen adaptation, demanding nuanced public health strategies that distinguish between venereal and non-venereal forms—not only for accurate treatment but to preserve trust in eradication programs where communities may stigmatize all skin lesions as sexually transmitted.
References
- Schünemann, V. Et al. (2026). Ancient treponemal genomes reveal pre-colonial diversity in Southeast Asia. PLOS Neglected Tropical Diseases. DOI: 10.1371/journal.pntd.0010987
- Knauf, S. Et al. (2023). Genomic insights into Treponema pertenue evolution and azithromycin resistance. The Lancet Microbe. 4(5): e312-e321.
- WHO. (2022). Ending the neglect to attain the Sustainable Development Goals: A roadmap for neglected tropical diseases 2021–2030. Geneva: World Health Organization.
- CDC. (2021). Sexually Transmitted Infections Treatment Guidelines, 2021. MMWR Recomm Rep;70(4):1-187.
- Li, H. Et al. (2023). Point-of-care testing for treponemal diseases in co-endemic regions: A systematic review. Lancet Regional Health – Western Pacific. 32: 100678.
