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Endemic Treponematoses
The endemic treponematoses comprise yaws, endemic syphilis, and pinta and are caused by Treponema pallidum subsp. pertenue, Treponema pallidum subsp. endemicum, and Treponema carateum . Nearly eliminated in the 1960s by an eradication campaign led by the World Health Organization (WHO), these relatively uncommon diseases are now often seen among children living in low-income and middle-income countries. The bacteria that cause the endemic treponematoses are morphologically and serologically indistinguishable from T. pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, and important parallels are found between the natural history of these diseases and syphilis. Similarly, the tools for management are adapted almost entirely from tools historically used as part of syphilis control efforts. Nonetheless, the endemic treponematoses differ from syphilis in terms of epidemiology, clinical manifestations, and at the level of the bacterial genome.
Disease rates have again increased more recently. Based on the successful eradication of yaws in India and the potential for recently described oral azithromycin therapy to facilitate control and prevention, the WHO announced a new effort to eradicate yaws.
Microbiology
Within the genus Treponema, four bacteria are presently recognized as human pathogens: T. pallidum subsp. pallidum, T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum. Much remains to be learned about these organisms. They cannot be cultured in vitro, and current understanding of their biology is based on the careful study of relatively few clinical isolates, most often propagated in laboratory animals (e.g., rabbits, hamsters, and guinea pigs). Although sequencing of the T. pallidum genome showed more than 99% DNA homology, several genetic loci have been identified that may permit differentiation of T. pallidum subsp. pallidum from the other subspecies ( T. pertenue and T. endemicum ). T. carateum isolates are not available for study at the present time, and any molecular similarities and differences have yet to be compared with the T. pallidum subspecies. In the future, application of evolving molecular diagnostic methods to the study of human treponemes promises to provide new insights into the biology of these organisms.
Morphology
T. pallidum and the treponemes causing endemic treponematoses are long, thin (8–13 × 0.15 µm), motile bacteria that cannot be seen with Gram stain and are best seen in specimens of a lesion exudate with a Warthin-Starry silver stain, darkfield microscopic examination, or fluorescent antibody techniques. Their regular, spiral morphology and characteristic corkscrew motility are helpful for recognition in clinical specimens.
Antibiotic Sensitivity
Based on clinical and serologic response to therapy as well as studies performed in experimental animals, these treponemes are sensitive to penicillins and tetracyclines. Because the organisms cannot be propagated in vitro, data on minimal inhibitory and bactericidal concentrations are unavailable. Sulfa drugs and fluoroquinolone antimicrobials have not been found to be active against T. pallidum subsp. pallidum . Clinical and laboratory resistance (mutations of 23S ribosomal RNA gene) to erythromycin and other macrolide antibiotics has been shown for multiple isolates of T. pallidum subsp. pallidum from North America and Western Europe, but similar resistance among the endemic treponematoses was not documented until 2018. With the adoption by the WHO of azithromycin as the preferred treatment for yaws, close monitoring for macrolide resistance will be important.
Epidemiology
The endemic treponematoses are diseases of low-income and middle-income countries, with varied geographic distribution. However, the true scope of disease is unknown because endemic treponematoses are not notifiable diseases in most countries. Yaws appears to have worldwide distribution (Central and South America, Asia, Africa, and Pacific Islands) and is found in warm, humid climates with heavy rainfall including tropical regions and rainforests. Of 13 endemic countries that reported to the WHO between 1990 and 2014, prevalence of active yaws disease ranged from 0.31% to 14.54%, and prevalence of latent yaws ranged from 2.45% to 31.05% with a higher burden of infection in the Pacific Islands. Endemic syphilis is less common than yaws and occurs primarily in dry, arid areas among nomadic and seminomadic rural populations. The disease has been most common in North Africa, Southwest Asia, and the eastern Mediterranean region. In contrast to the global distribution of yaws and endemic syphilis, pinta is limited to the Western Hemisphere. The disease has been described in Mexico, Caribbean islands (including Cuba), and Central and South American countries. The prevalence of pinta is unknown at the present time because of the lack of surveillance data. However, substantial numbers of cases including a case series of more than 200 patients have been described in rural Brazil. Within these regions, each of the endemic treponematoses disproportionately impacts impoverished people living in remote areas. Limited access to hygienic facilities has been associated with increased infection rates.
Transmission
Similar to syphilis, the endemic treponematoses are acquired and spread through direct contact with infectious exudates from patients with active infection or who have relapsed after latent infection (infected but asymptomatic). In the case of endemic syphilis, transmission is possible via fomites (see “ Endemic Syphilis [Bejel] ”). However, in contrast to syphilis, little evidence exists that transmission of endemic treponematoses occurs via blood, blood products, or transplacentally from untreated pregnant women to unborn children. Protective immunity induced by infection has been shown only in rabbit experimental models conducted in the early 20th century; however, a later study in hamsters concluded that immunity was not absolute.
Clinical Manifestations
The endemic treponematoses can be characterized by several common clinical characteristics as well as characteristics that distinguish them from one another. Although there are several important differences, there are numerous parallels between the well-described course of untreated syphilis ( T. pallidum subsp. pallidum infection) and the natural history of the endemic treponematoses. Similar to syphilis, each is a chronic bacterial infection that progresses through a series of well-described clinical stages, predictably progressing from an early, localized stage to a later, more widespread stage. Early in the course of infection, even before primary lesions develop, the treponemes spread hematogenously throughout the body; without treatment, they subsequently give rise to secondary and late manifestations of infection. Once primary lesions develop, regional lymphadenopathy follows. As in the case of syphilis, primary lesions of yaws and pinta resolve spontaneously without treatment; then in the secondary stage, skin lesions may recur up to 5 years, with the frequency of these recurrences declining with time. Recurrent secondary manifestations of early endemic treponematoses are primarily dermatologic; however, a substantial proportion of persons also develop osteitis or other bony or cartilaginous lesions. Primary and secondary lesions may resolve, and a patient's infection may become latent, where the patient harbors infection without exhibiting signs and symptoms.
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