Nonhuman primates across sub-Saharan Africa are infected with the yaws bacterium Treponema pallidum subsp. pertenue

Dear Editor, The bacterium Treponema pallidum (TP) causes human syphilis (subsp. pallidum; TPA), bejel (subsp. endemicum; TEN), and yaws (subsp. pertenue; TPE) (1). Although syphilis has reached a worldwide distribution (2), bejel and yaws have remained endemic diseases. Bejel affects individuals in dry areas of Sahelian Africa and Saudi Arabia, whereas yaws affects those living in the humid tropics (1). Yaws is currently reported as endemic in 14 countries, and an additional 84 countries have a known history of yaws but lack recent epidemiological data (3,4). Although this disease was subject to global eradication efforts in the mid-20th century, it later reemerged in West Africa, Southern Asia, and the Pacific region (5). New large-scale treatment options triggered the ongoing second eradication campaign, the goal of which is to eradicate yaws globally by 2020 (5). References: (1) Giacani, L. & Lukehart, S.A. The endemic treponematoses. Clin. Microbiol. Rev. 27, 89–115 (2014). (2) Arora, N. et al. Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster. Nat. Microbiol. 2, 16245 (2016). (3) Marks, M. Yaws: towards the WHO eradication target. Trans. R Soc. Trop. Med. Hyg. 110, 319–320 (2016). (4) World Health Organization. Eradication of yaws: procedures for verification and certification of interruption of transmission (World Health Organization, Geneva, 2018). (5) Asiedu, K., Fitzpatrick, C. & Jannin, J. Eradication of yaws: historical efforts and achieving WHO’s 2020 target. PLoS Negl. Trop. Dis. 8, e3016 (2014)

Widespread Treponema pallidum Infection in Nonhuman Primates, Tanzania

We investigated Treponema pallidum infection in 8 nonhuman primate species (289 animals) in Tanzania during 2015–2017. We used a serologic treponemal test to detect antibodies against the bacterium. Infection was further confirmed from tissue samples of skin-ulcerated animals by 3 independent PCRs (polA, tp47, and TP_0619). Our findings indicate that T. pallidum infection is geographically widespread in Tanzania and occurs in several species (olive baboons, yellow baboons, vervet monkeys, and blue monkeys). We found the bacterium at 11 of 14 investigated geographic locations. Anogenital ulceration was the most common clinical manifestation; orofacial lesions also were observed. Molecular data show that nonhuman primates in Tanzania are most likely infected with T. pallidum subsp. pertenue–like strains, which could have implications for human yaws eradication

Validation of serological tests for the detection of antibodies against Treponema pallidum in nonhuman primates.

There is evidence to suggest that the yaws bacterium (Treponema pallidum ssp. pertenue) may exist in non-human primate populations residing in regions where yaws is endemic in humans. Especially in light of the fact that the World Health Organizaiton (WHO) recently launched its second yaws eradication campaign, there is a considerable need for reliable tools to identify treponemal infection in our closest relatives, African monkeys and great apes. It was hypothesized that commercially available serological tests detect simian anti-T. pallidum antibody in serum samples of baboons, with comparable sensitivity and specificity to their results on human sera. Test performances of five different treponemal tests (TTs) and two non-treponemal tests (NTTs) were evaluated using serum samples of 57 naturally T. pallidum-infected olive baboons (Papio anubis) from Lake Manyara National Park in Tanzania. The T. pallidum particle agglutination assay (TP-PA) was used as a gold standard for comparison. In addition, the overall infection status of the animals was used to further validate test performances. For most accurate results, only samples that originated from baboons of known infection status, as verified in a previous study by clinical inspection, PCR and immunohistochemistry, were included. All tests, TTs and NTTs, used in this study were able to reliably detect antibodies against T. pallidum in serum samples of infected baboons. The sensitivity of TTs ranged from 97.7-100%, while specificity was between 88.0-100.0%. The two NTTs detected anti-lipoidal antibodies in serum samples of infected baboons with a sensitivity of 83.3% whereas specificity was 100%. For screening purposes, the TT Espline TP provided the highest sensitivity and specificity and at the same time provided the most suitable format for use in the field. The enzyme immune assay Mastblot TP (IgG), however, could be considered as a confirmatory test

Performance characteristics of the serological tests used in this study, as reported by the manufacturer. Sen = Sensitivity, Spec = Specificity, n.p. = not provided.

<p>Performance characteristics of the serological tests used in this study, as reported by the manufacturer. Sen = Sensitivity, Spec = Specificity, n.p. = not provided.</p

Multiple comparisons of log anti-<i>T</i>. <i>pallidum</i> titers in 4 groups with a different stage of genital ulceration in baboons

<p>([CNA] = clinically non-affected (n = 20), [INI] = initial (n = 14), [MOD] = moderate (n = 7), and [SEV] = severe genital ulceration (n = 16); for stage definition see [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003637#pntd.0003637.ref018" target="_blank">18</a>]), GU = genital ulceration. Anti-<i>T</i>. <i>pallidum</i> antibody quantification was investigated using the Serodia TP-PA. Kruskal-Wallis test using Dunn’s correction for multiple comparison: CNA vs. SEV mean rank diff. = -30.04, p ≤ 0.0001; CNA vs. MOD mean rank diff. = -19.95, p ≤ 0.05; INI vs. SEV mean rank diff. = -17.56, p ≤ 0.05. (mean ± SEM).</p

Definitions used to determine the infectious stage of baboons.

<p>Definitions used to determine the infectious stage of baboons.</p

<i>T</i>. <i>pallidum</i> test algorithm for the screening of wild non-treated baboons.

<p>Based on the test performances Espline TP is recommended as the initial screening test followed by a confirmatory test e.g. Mastablot TP IgG that has been identified as most reliable standard. Dashed lines indicate reported results, while continuous lines represent the workflow.</p

Comparison of treponemal serological tests with the results of the Serodia TP-PA.

<p>Comparison of treponemal serological tests with the results of the Serodia TP-PA.</p

Comparison of the serological tests with the consensus of infection status (Table 2).

<p>Comparison of the serological tests with the consensus of infection status (<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003637#pntd.0003637.t002" target="_blank">Table 2</a>).</p