Epidemiologic and Genomic Reidentification of Yaws, Liberia

Abstract

We confirmed endemicity and autochthonous transmission of yaws in Liberia after a population-based, community-led burden estimation (56,825 participants). Serologically confirmed yaws was rare and focal at population level (24 cases; 2.6 [95% CI 1.4-3.9] cases/10,000 population) with similar clinical epidemiology to other endemic countries in West Africa. Unsupervised classification of spatially referenced case finding data indicated that yaws was more likely to occur in hard-to-reach communities; healthcare-seeking was low among communities, and clinical awareness of yaws was low among healthcare workers. We recovered whole bacterial genomes from 12 cases and describe a monophyletic clade of Treponema pallidum subspecies pertenue, phylogenetically distinct from known TPE lineages, including those affecting neighboring nonhuman primate populations (Taï Forest, Côte d'Ivoire). Yaws is endemic in Liberia but exhibits low focal population prevalence with evidence of a historical genetic bottleneck and subsequent local expansion. Reporting gaps appear attributable to challenging epidemiology and low disease awareness.

Keywords: Liberia; Treponema pallidum; West Africa; accessibility; bacteria; bottleneck; case detection; case finding; genome; neglected tropical diseases; nonhuman primate; pertenue; sequencing; yaws.

Figure 1

Clinical presentation and serological results of the first confirmed case of yaws since the 1970s and first whole Treponema pallidum subspecies pertenue (TPE) genome from Liberia. A) Papillomatous yaws lesion below the right knee. B) Paired serological results from this case. Dual path platform syphilis lateral flow assay (ChemBio, https://chembio.com) shows antibody binding to treponemal and nontreponemal antigen indicative of active yaws infection. A complete genome sequence was recovered from this case (Figure 3).

Figure 2

Spatial occurrence and accessibility of yaws endemic communities in Maryland County, Liberia. A) All survey cluster centroids (n = 92). Yaws endemic clusters are shown by large gray circles. All survey clusters were classified based on accessibility criteria into high access (pink), low access (blue), and very low access (yellow) using open-source GIS datasets. Black features are OpenStreetMap defined buildings (©OSM Contributors) to provide indication of structural density. B, C) Main urban centers of Maryland County: Pleebo (B) and Harper (C). Inset: Results of divisive hierarchical classification. The axes of this plot show the principal components and proportion of variance explained by each component.

Figure 3

Spatial and phylogenetic distribution of 12 whole genome TPE sequences isolated from serologically confirmed yaws cases in Maryland County, Liberia. Genomes are extremely closely related but show evidence of geographical separation. A) Regional map with study area highlighted in red. B) Maryland County, indicating sampling location of Treponema genome (colored by survey cluster). C) Maximum-likelihood whole genome phylogeny of Liberia genomes, scaled by substitutions per site, showing phylogenetic relationships of patient samples. Ultra-fast bootstrap values >95% are indicated on the tree. Map tiles by Stamen Design (CC-BY 3.0), map data by OpenStreetMap (ODbl). TPE, Treponema pallidum subspecies pertenue.

Figure 4

Global context of whole Treponema pallidum subspecies pertenue (TPE) genomes from Liberia. Liberia genomes form a monophyletic clade, genetically distant from publicly available genomes including 3 isolated from nonhuman primates in nearby Taï National Park (Côte d’Ivoire). Plot shows a maximum-likelihood phylogeny of 12 Liberia genomes contextualized with 34 published global genomes, scaled by substitutions per site. Ultra-fast bootstrap values >95% are indicated on the tree. Colored tracks show country of sampling and original host organism. Novel Liberia genomes from this study are indicated with blue labels.