In this survey of wild East African baboons, we found that exposure to T. pallidum
, confirmed via a highly sensitive and specific serological test, was common at all but one of the sites we investigated in Tanzania (). By contrast, infection appeared to be absent at all but one of the sites examined in Kenya, supporting previous findings 
. In addition, at all of the Tanzanian sites that exhibited positive serology, clinical signs of infection consistent with those described by Knauf et al
, including necrotizing dermatitis that led to severe mutilation of the external genital organs, were noted (). In 2006, we found that 9.3% of females (14/150) and 10.6% of males (16/150) at LMNP had suffered severe, macroscopically-evident disease-related damage to the genitalia, raising the possibility of significant infection-related morbidity and, perhaps in the most severe cases, even mortality.
Geographic location of African sites where baboons have tested seropositive for T. pallidum antibodies.
Reports of genital-associated disease in nonhuman primates with a suspected link to T. pallidum
first appeared in print in the late 1980s, in the form of a report on baboon health at GSNP 
. Reports of a similar disease at LMNP surfaced in 1994 
, and signs of the disease at other Tanzanian sites were not reported until the present study. Given these recent discoveries, we might expect this seemingly-unusual type of T. pallidum
infection to be caused by a novel strain, perhaps one that is spreading in East African baboons. However, if a novel T. pallidum
baboon strain emerged recently in Tanzania and spread rapidly across the country, one would expect isolates to be nearly identical genetically, especially given the low level of polymorphism typically found among strains of this bacterium 
and the small number of genes examined in this study. Instead, we found that the strains causing the disease in LMNP and SNP were genetically distinct, differing at four of 25 polymorphic sites used in the phylogeny (, ). While it is possible that recent, rapid evolution of the pathogen could explain the polymorphism, the fact that two synonymous substitutions in the LMNP strain are shared by human strains of ssp. pertenue
as well makes this possibility seem unlikely, as it would require convergent evolution at sites that contain polymorphisms which are presumably neutral. It is more likely that the LMNP strain diverged from the SNP strain some time ago, and the former represents the non-human primate strain that shared the most recent common ancestor with human yaws-causing strains. Explanations that could potentially reconcile the high level of polymorphism between the T. pallidum
strains responsible for the baboon disease in Tanzania with the seemingly recent appearance of the infection include a genetically heterogeneous bacterial population which seeded outbreaks at the sites studied, recent changes in host or environmental characteristics that fostered genital manifestations of the disease, or some combination of these factors.
The simian strain from LMNP could not be distinguished from human subsp. pertenue strains in our phylogeny (). It falls within a polytomy that contains this baboon strain as well as all human subsp. pertenue strains. A relatively small number of polymorphic regions were examined in this study and bootstrap values at many of the nodes on our phylogeny were low (<70%); we expect that the position of this and other baboon strains relative to human strains may be clarified by sequencing additional polymorphic regions. If baboons are an important source of human infection, one might have expected human subsp. pertenue strains from West Africa to resemble the Fribourg-Blanc baboon strain collected in Guinea rather than other human subsp. pertenue strains from distant locations such as Samoa and Indonesia. Instead, all human T. pallidum strains appear to share a common origin. If further evidence demonstrates that the LMNP strain, like the other baboon strains, diverged prior to all human strains, and that the baboon strains form a paraphyletic group from which human strains are excluded, this will provide further support for the hypothesis that the T. pallidum strains that infect baboons have inhabited their hosts for a long period of time, are genetically diverse, and are distinct from human strains. Further, if T. pallidum strain phylogenies are congruent with host phylogenies, the evidence will indicate that this pathogen has evolved with its primate hosts, including humans, over millions of years.
While our study offers a preliminary overview of seroprevalence and manifestations of T. pallidum
infection in the wild baboons of Tanzania and Kenya, there are some limitations. First, in order to investigate the prevalence of T. pallidum
infection at all of the Kenyan sites and one of the Tanzanian sites (Mikumi), we relied on banked serum samples collected by various researchers over the years. Samples from a number of the sites, including Mikumi, Mosiro, Lake Magadi, Gilgil, and Nanyuki, were several decades old (). The temporal and spatial distribution of the disease may well be dynamic. Therefore, it is possible that sites that showed no evidence of infection at the time samples were gathered may be affected now, and it is also possible that baboons at Nanyuki, which showed a high prevalence of T. pallidum
infection in 1977, may not be affected today. Second, the sampling scheme was not uniform at each site (), and, at many of the sites, reliable estimates for infection prevalence in the population as a whole could not be calculated. At GSNP, LMNP, and SNP, the number of animals from which serum was collected was relatively small, and at times animals with lesions were sampled purposively, which may have artificially inflated seroprevalence. In addition, a 1
1 sex ratio was pursued when gathering serum samples at these sites, but in the typical baboon troop, which has a multi-male – multi-female social structure, females outnumber males. Finally, while positive serology provides a strong indication that a baboon has been exposed to T. pallidum
, it does not necessarily mean that an animal is currently infected.
It is possible that the species of the baboon host has an effect upon the clinical manifestations and seroprevalence of infection. Previously, the only reports of T. pallidum
-linked, genital-associated disease have been in olive baboons (Papio anubis
. While other baboon species, such as the Guinea baboon (Papio papio
), also carry the pathogen 
, their clinical signs, when present at all, have been described as small ulcers primarily on the muzzle 
. Perhaps genetic differences between species of baboons 
influence susceptibility to the disease and/or lead to different clinical manifestations. In our study, each of the four Tanzanian sites affected by the genital disease was inhabited by olive baboons (). The single Tanzanian site that was not affected, Mikumi National Park, is exclusively inhabited by yellow baboons (Papio cynocephalus cynocephalus
). It also lay further south than the other sites (). Additional studies should help determine what role the host species plays in determining disease dynamics and presentation.
At present, there is no clear geographical trend differentiating affected and non-affected sites (), and it is not apparent which factors govern the presence or absence of the infection in a given baboon population. Additional investigations that utilize both a standardized sampling procedure and a full spectrum of diagnostic methods for the detection of T. pallidum
are needed, as in 
. Careful examination of the characteristics of affected and non-affected baboon troops could shed light on risk factors for infection. The genital lesions associated with the disease and its predilection for sexually active animals suggest sexual transmission 
. A careful study documenting the age of infection in affected troops as well as a thorough investigation of other factors that may lead to infection (e. g., vectors) could help determine if this is the dominant mode of transmission. Studies on the mode of spread, as well as spatial and temporal trends in disease prevalence, may help us better understand why infection is almost entirely limited to the Tanzanian side of the Kenyan/Tanzanian border; Masai Mara, a site where no evidence of the infection has been observed up to the present date, is geographically contiguous with SNP, a site that yielded abundant evidence of infection. Longitudinal studies could elucidate the level of morbidity and mortality associated with this infection. Given the damage to the reproductive organs associated with the disease () and evidence that even non-genital-associated T. pallidum
lesions may affect reproductive success in gorillas 
, the possible deleterious effects of treponemal infection upon reproduction may be particularly important to examine in affected baboon populations. Finally, additional sequencing of T. pallidum
strains collected from humans and baboons, as well as genetic characterization of T. pallidum
strains in additional affected nonhuman primate species such as patas monkeys, gorillas, and chimpanzees 
could further clarify the relationship between human and nonhuman primate strains. If sexual transmission of the infection in baboons is demonstrated, then the strains responsible along with subsp. pallidum
strains in humans may represent an example of the parallel evolution of sexual transmission in T. pallidum
. By comparing the differences found between sexually and non-sexually transmitted baboon strains to the differences identified between subsp. pallidum
strains and the non-sexually transmitted human subsp. pertenue
strains, it may be possible to learn more about the genetic basis of pathogenesis and sexual transmission in this pathogen.
In conclusion, this study demonstrates that a genital ulcer-associated T. pallidum
infection in wild baboons is present at multiple sites in Tanzania and is linked to severe structural damage of the genitalia in a significant proportion of the animals observed. T. pallidum
strains from two affected Tanzanian sites were compared and found to be genetically distinct. In addition, the phylogeny created in this study suggests that baboon strains may have diverged prior to human strains, but the low resolution of the tree prevents firm conclusions from being drawn. Clearly, further research is needed to understand the nature of T. pallidum
infection in wild baboons. The importance of learning more about this disease becomes apparent when one considers 1) T. pallidum
's potentially deleterious effect upon other susceptible non-human primate species, such as chimpanzees 
and gorillas 
; and 2) the close proximity of some infected baboon troops to the habitat of these endangered species. Moreover, it will be essential to clarify the relationship between treponemal infections in humans and non-human primates, given the World Health Organization's plans to launch a second yaws eradication campaign