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Author affiliation: University of Wisconsin–Madison, Madison, Wisconsin, USA (T.L. Goldberg, L.A. Owens); Gorilla Doctors, Musanze, Rwanda (J. Nziza); Rwanda Development Board, Kigali, Rwanda (R. Muvunyi); Hunter College of City University of New York, New York, New York, USA (J.M. Rothman); New York Consortium in Evolutionary Primatology, New York (J.M. Rothman); Makerere University, Kampala, Uganda (P. Omeja); Vancouver Island University, Nanaimo, British Columbia, Canada (C.A. Chapman)
Yaws is a bacterial disease endemic to the tropics caused by Treponema pallidum pertenue, which is distinct from its conspecifics T. p. endemicum, the cause of bejel, and T. p. pallidum, the cause of syphilis (1,2). Yaws causes skin papules, crusts, and ulcers progressing to systemic infection and disfiguring skeletal disease (1). Yaws has been targeted for eradication by 2030, but challenges persist (3).
Eradicating yaws may be complicated by T. p. pertenue in wild nonhuman primates (4). Several monkey species across Africa have tested positive for serum antibodies to T. p. pertenue (5). Genetic analyses show phylogenetic interspersion of human and primate variants, implying historic host switching and, therefore, a potential reservoir role for primates (6–8). However, the host and geographic range of infection in African primates remain incompletely known, as does the extent of bacterial diversity in primates. Furthermore, few data exist on T. p. pertenue transmission within wild primates.
Figure 1
Figure 1. Primates in Kibale National Park, Uganda, showing clinical signs of yaws in study of yaws circulating in nonhuman primates, Uganda and Rwanda. A) Adult olive baboon (Papio anubis)…
We screened 103 serum samples collected during 2005–2014 from apparently healthy primates in Uganda and Rwanda (Appendix Figure 1) using a commercial serologic test validated for primates (Appendix). Overall, seroprevalence was 33.0%, with 32.8% prevalence in Uganda and 33.3% in Rwanda (Table 1). Prevalence did not differ significantly between male (33.8%) and female (31.6%) primates (p = 1.000) but was higher in adults (41.3%) than in younger primates (14.3%) (p = 0.0105 by Fisher exact test). Prevalence range was 0%–76.9% among host species (χ2= 27.1; d.f. 8; 2-tailed p = 0.0007). Seroprevalence was particularly high in olive baboons (Papio anubis; 76.9%) and vervet monkeys (Chlorocebus pygerythrus; 26.7%), which are common in the region and frequently live alongside humans; a vervet from Kigali, Rwanda’s densely populated capital, tested positive for T. p. pertenue. At least 1 animal of each species tested in Kibale National Park, Uganda, was positive; Kibale contains one of Africa’s most diverse primate communities, and skin lesions consistent with yaws have been documented there for >50 years (9) (Figure 1).
In July 2013 we observed an outbreak of yaws-like disease in a social group of Ugandan red colobus monkeys (Piliocolobus tephrosceles) in Kibale. Approximately half the animals displayed skin lesions, including papules, ulcers, and crusts visible on hairless regions (face, plantar surfaces of hands and feet, anogenital region (Figure 1), and ≈10% of animals were not seen again. Animals from the group had been sampled in 2012, before the outbreak, and again in 2014, after the outbreak. Seven animals (33.3%) seroconverted, and 2 seropositive animals from 2012 remained seropositive in 2014 (Table 2). Those data demonstrate active transmission of T. p. pertenue, persistence of antibodies for >2.4 years, and an incidence rate during this period of 4.3 (95% CI 1.9 – 9.0) cases/1,000 monkey-months.
We observed 2 more outbreaks in the same red colobus group in January 2015 and December 2017–January 2018; again, ≈50% of animals were affected and ≈10% were not seen again. An adult female red colobus was found moribund on January 12, 2015, and died several hours later. Another adult female was found freshly dead on December 26, 2017. We collected swabs of facial ulcers from both carcasses, placed them in RNAlater (Thermo Fisher Scientific, https://www.thermofisher.com), and stored them at −20°C. Samples tested positive by diagnostic PCR. Hybridization capture yielded bacterial genome sequences of 98% completeness for the 2015 sample and 86% for the 2017 sample (Appendix).
Figure 2
97% and containing 4,716 variable positions. Black dots on nodes indicate bootstrap values of 100%; gray dots indicate 75%–99% bootstrap values based on 1,000 bootstrap replicates; values <75% are not shown. Scale bar indicates nucleotide substitutions per site. Ca, Cercocebus atys; Cp, Chlorocebus pygerythrus; Cs, Cercocebus sabaeus; Hs, Homo sapiens; Pa, Papio anubis; Ps, Piliocolobus tephrosceles; Pt, Pan troglodytes." />
Figure 2. Maximum-likelihood phylogenetic tree of Treponema pallidum genomes from study of yaws circulating in nonhuman primates, Uganda and Rwanda. The tree shows relationships among T. p. pertenuegenomes…
A phylogenetic tree of reference sequences with >97% genome coverage showed the variant in the 2015 Ugandan red colobus to be a distinct lineage (Figure 2). Another phylogenetic tree (Appendix Figure 2) including the 86% complete 2017 outbreak sequence and a 57% complete Western red colobus (Procolobus badius) sequence showed the 2 Ugandan red colobus variants to be sister taxa but distinct from the Western red colobus variant. Despite the 2015 and 2017 outbreaks occurring in the same social group, the 2 outbreak sequences differed at 2,131/976,212 (0.2%) nucleotide positions (omitting gaps), demonstrating circulation of multiple T. p. pertenue variants among primates in the area.
Infection of primates with T. p. pertenue was widespread in Uganda and Rwanda at the time of sampling, similar to other locations in sub-Saharan Africa (5,6). Overall, one third of primates tested had antibodies to T. p. pertenue, comparable to 53% seroprevalence found in Tanzania primates (10). Seropositivity in Uganda and Rwanda increased with age and varied widely by species and location. Olive baboons had the highest rate of seropositivity (77%), followed by red-tailed guenons (55%) and vervet monkeys (27%). Olive baboons and vervet monkeys live alongside humans throughout their range, which could enable zoonotic transmission. All species tested from Kibale had >1 positive animal, which is consistent with historical reports of yaws-like disease in Kibale primates (9). Those species include the eastern chimpanzee (Pan troglodytes schweinfurthii); because western chimpanzees (P. t. verus) are also infected with T. p. pertenue (11), T. p. pertenue likely infects chimpanzees across their range. Although no L’Hoest’s monkeys (Allochrocebus lhoesti) from Rwanda were seropositive, L’Hoest’s monkeys in Kibale frequently display yaws-like lesions (Figure 1), again demonstrating wide geographic variation in infection.
Our results provide direct evidence of active T. p. pertenue circulation in Ugandan red colobus, in which yaws-like disease has been documented for >50 years (9). After an outbreak, 33% of red colobus in a social group seroconverted. Of interest, the 2015 and 2017 outbreak strains from this social group differed genetically. Although the rate of T. p. pertenue evolution in primates remains unknown, it is unlikely that the 2017 variant was a direct descendent of the 2015 variant, given >2,000 nt differences. We suspect that a diversity of T. p. pertenue variants circulates in and among primate species in the area. Moreover, the newly sequenced Ugandan red colobus variants were distinct from previously published sequences, including a variant from a West Africa red colobus monkey. Our phylogenetic analyses support the idea that T. p. pertenue evolution has been shaped by geography, reflected by subclades tending to consist of variants from similar locations, including interspersion of human and primate variants, as previous studies have also found (7,8). If so, T. p. pertenue may be maintained in primates through localized cycles of transmission, limited more by geographic distance than by host species.
Facial deformities of Kibale primates have been variously attributed to congenital malformation and agricultural chemicals (12,13). Our results, combined with growing evidence from across sub-Saharan Africa, strongly suggest that the actual cause is yaws. Ugandan red colobus monkeys are endangered, existing mostly in small, geographically isolated populations (9). The effects of lethal yaws outbreaks could be significant for these and other primates, especially for populations simultaneously facing habitat loss, fragmentation, hunting, and other anthropogenic stressors (14).
Uganda and Rwanda are considered previously endemic countries for yaws but not endemic as of February 2025 (3). The World Health Organization has targeted yaws eradication by 2030, but barriers remain, and primate reservoirs would add substantially to these barriers (3,4). Yaws outbreaks have not been reported recently in humans living near the primates tested, despite frequent close interaction (including direct contact). Examining host specificity of T. p. pertenue variants and epidemiologic barriers to zoonotic transmission would help elucidate whether primates could seed new human infections in currently endemic countries or reintroduce the disease to humans in previously endemic countries.
Dr. Goldberg is a professor of epidemiology at the University of Wisconsin–Madison School of Veterinary Medicine in Madison, Wisconsin, USA. His main research interests are the ecology and epidemiology of wildlife diseases that threaten human health, animal health, and wildlife conservation.
We thank the Uganda Wildlife Authority, the Uganda National Council for Science and Technology, and the Rwanda Development Board for granting permission to conduct this research. We thank David Hyeroba and the staff of the Kibale EcoHealth Project and the Kibale Fish and Monkey Project for assistance with fieldwork, and Makerere University Biological Field Station for logistic support. We thank Fabian Leendertz, Sebastien Calvignac-Spencer, and Jan Gogarten for generously providing guidance about target capture sequencing, Sascha Knauf for helpful advice about serologic methods, and Christopher Dunn for assisting with DNA sequencing. We thank Kevin Lee, Nancy Stevens, and Alicia Rich for kindly providing photographs, Alicia Rich for assisting with field efforts, and Tom Struhsaker for invaluable discussions about skin lesions observed in the primates of Kibale.
This paper is dedicated to the memory of Dr. Tony Mudakikwa, who championed the cause of One Health and wildlife conservation in East Africa.
Serum samples used for this study were from archived collections. Use of nonhuman primates for these prior investigations was approved by the Uganda Wildlife Authority, the Uganda National Council for Science and Technology, the Rwanda Development Board, and by the Institutional Animal Care and Use Committee (IACUC) of the University of Wisconsin-Madison (protocol no. V005039). All procedures complied with the American Society of Primatologists Ethical Principles for the Treatment of Non‐Human Primates. Samples were shipped in accordance with international laws and treaties, including the Convention on International Trade in Endangered Species of Wild Fauna and Flora (CITES) under permits 002290 and 003248 (Uganda), 00-RDB-TxC/V0/17 (Rwanda), and 17US16647C/9 and 17US18137C/9 (United States).
All raw sequence reads were deposited in the National Center for Biotechnology Information Sequence Read Achieve under BioProject PRJNA1165282 (accession nos. SAMN43929235 and SAMN43929236).
This research was funded by National Institutes of Health (grant no. TW009237) as part of the joint National Institutes of Health–National Science Foundation Ecology of Infectious Disease program and the UK Economic and Social Research Council (to T.L.G. and C.A.C.) and by the University of Wisconsin–Madison John D. MacArthur Professorship Chair (to T.L.G.).
