Advances in the diagnosis of endemic treponematoses: yaws, bejel, and pinta

Abstract

Improved understanding of the differential diagnosis of endemic treponematoses is needed to inform clinical practice and to ensure the best outcome for a new global initiative for the eradication of yaws, bejel, and pinta. Traditionally, the human treponematoses have been differentiated based upon their clinical manifestations and epidemiologic characteristics because the etiologic agents are indistinguishable in the laboratory. Serological tests are still considered standard laboratory methods for the diagnosis of endemic treponematoses and new rapid point-of-care treponemal tests have become available which are extremely useful in low-resource settings. In the past ten years, there has been an increasing effort to apply polymerase chain reaction to treponematoses and whole genome fingerprinting techniques have identified genetic signatures that can differentiate the existing treponemal strains; however, definitive diagnosis is also hampered by widespread unavailability of molecular diagnostics. We review the dilemmas in the diagnosis of endemic treponematoses, and advances in the discovery of new diagnostic tools.

Figure 1. Countries with reported data on yaws, bejel, and pinta from 1980 to 2012 –, .

Data are number of cases reported in a year, unless otherwise indicated. Prev: prevalence. CR: Case report. ND: No data. Shading indicates the countries where cases of endemic treponematoses have been reported within the last 30 years. In some countries the transmission may be restricted to small areas, rather than affecting the entire country. India interrupted transmission in 2004 and declared elimination in 2006. Since 2004, no new cases have been reported. The principal sources of data are WHO reports , , and scientific articles identified through searches of PubMed about epidemiology of yaws –, bejel –, and pinta –, .

Figure 2. Common yaws, bejel, and pinta lesions in 2013.

Papillomatous primary yaws lesion (A); disseminated papilloma of secondary yaws (B); labial mucosal plaques of primary bejel (C); disfiguring infiltration of the nose, glabella, and forehead in a patient with secondary bejel (D); squamous plaque of primary pinta (E); late achromic pinta (F). Sources of photographs: O. Mitjà, Papua New Guinea (A, B); A. Abdolrasouli, Iran (C, D); F. Gómez, Mexico (E, F). The individuals photographed for this publication were informed of the purpose of the photograph and they agreed to have their photograph taken and potentially published.

Figure 3. Identified genetic loci showing sequence differences in T. p. pertenue and T. p. endemicum

, . These regions are potentially suitable for detection of TPE or TEN strains; however, further testing of these regions in additional strains is needed. Indels specific to tested TPE and TEN strains are shown in red and green, respectively. Only genetic differences consistently present between all completely sequenced TPE and TPA strains are shown. In the case of TEN, only one strain (Bosnia A) has been analyzed on a genome level. Coordinates of insertions in the TPE genomes are taken from the Samoa D genome (GenBank acc. no. CP002374.1): 148701–148781, 331996–332630, 594549–594600, 629981–629992, 945694–945717; coordinates of deletions (CP002374.1): 72694–72695, 150386–150387, 153904–154035, 158201–158202, 279101–279102, 348027–348028, 492496–492501, 1125682–1125683; coordinates of repetitions (CP002374.1): 462430–463149, 498895–499200, 1051990–1052003. Coordinates of cumulated SNPs (defined as ten or more nucleotide changes present in the 100-bp genome window, CP002374.1): 135500–135599, 148700–148799, 153800–153899, 154000–154099, 331200–331399, 331700–332899, 493000–493099, 672000–672199, 672500–673699, 675300–675899, 800500–800599, 936700–936799, 938000–938099. For TEN Bosnia A, only coordinates of insertions, deletions, and repetitions are shown; coordinates of insertions (according to CP002374.1): 148701–148781, 331996–332630, 594549–594600; coordinates of deletions: 72694–72695, 72719–72734, 94986–94998, 150386–150387, 153904–154035, 279101–279102, 492496–492501, 945694–945717; coordinates of repetitions: 462430–463149, 498895–499200,1051990–1052003. N/A, not applicable.