1. Yaws (& Other Endemic Treponematoses)
Nikita Hall
4/19/16
BIOL 402-Infectious Disease
UNC-Chapel Hill

2. Treponemas are a group of bacteria that cause three different human diseases:
Endemic Syphillis (Bejel)
Pinta*
Yaws* (most common)
*The majority of this presentation will be focused on Yaws
*All three are non-venereal (spread via direct, nonsexual contact)
*caused by spiral-shaped bacteria (spirochetes)
Based on clinical manifestations and serological tests, there are three types of (non-venereal) chronic bacterial infections caused by pathogenic treponemes

3. Pinta is a chronic skin disease caused by the bacterium Treponema carateum, and is the most benign infection of the three.
-most benign
-the skin is the only organ involved/damaged
-initial lesion is a papule/enlarges to pruritic plaques in early stage pinta
-altered pigmentation is the late stage of the disease (lesions become pigmented-copper, grey, slate blue)(achromic or hyperpigmented)
*endemic to Mexico, Central America, and South America

4. Yaws, caused by Treponema pallidum pertenue, is the most common, causing painful lesions, and in 10% of cases, deformities and disability.
-subspecies pertenue
-affects skin, bone, and carilage
-deformities involve bone and cartilage, primarily of the legs, nose, skull, etc.
when untreated
occurs around 5 years after initial lesions
school absenteeism
adults miss work
Clinical manifestations occur in three stages:
-primary lesion (“mother yaw”)-localized papule; incubation period = days
-secondary-plaques form
-tertiary-disfiguring deformities occur when disease is left untreated/ nodules with massive necrotic tissue damage/scarring/ destructive chronic osteitis-bowing of the tibia/attacks bones and joints/cardiovascular disease/CNS reported but not confirmed as causative

5. Yaws is transmitted by direct, skin-to-skin contact, and often affects children under the age of 15
in 75% of new cases.
children in the community
schools
other public places
children are more likely to touch/have direct contact with others

6. The structure of the bacterium and its survival mechanisms contribute to its pathogenesis.
Small break in the skin  epithelial cells  extracellular matrix  lymph nodes  dissemates widely
*treponemes have characteristic corkscrew motility due to endoflagella (allowing them to swim efficiently in connective tissue)
*low metabolic rate-maintains infection with few viable cells, avoiding immune system response stimulation during latent disease
*induce depression of mitogenic response of lymphoid cells (won’t produce as many innate immune cells)
*antigenic variation in candidate outer-membrane protein antigenic targets (TprK = immune evasion)
TprK=Treponema pallidum repeat protein K
-encodes an outer membrane protein
*the most variable Treponema protein (several variants within one strain of TPA)(increased sequence diversity/extreme variability of the TprK gene via gene conversion events (undergoes antigenic variation to promote chronic infection)(allows for re-infection of hosts who have already been infected)

7. Yaws predominently affects humid, tropical areas in Africa, Asia, and the Western Pacific
-epidemiological map showing at least countries within the tropical belt were endemic for Yaws in the 1950s
now only countries are currently endemic for Yaws
Ecuador and India-interrupted transmission in 2003
however, estimated 89 million people live in those areas
73 previously endemic countries need to be assessed to ensure the status of interruption of transmission
the stall in surveillance has made Yaws known as a neglected tropical disease
*Certain factors attribute to the distribution & spread of Yaws:
over-crowding
poor hygeine
low socio-economic conditions
rainy season-higher prevelance of cases

8. From Yaws was treated by a long-acting intramuscular injection of Benzathine Penicillin which cured 95% of cases.
-mass treatment using one intramuscular dose/injection of Penicillin –method for past 60 years (.6 MU in patients younger than 10 years, 1.2 MU in patients older than 10)
-cure rates for patients with early, active yaws lesions > 95%
-development of penicillin resistance unlikely
-tetracycline, erythromycin and doxycycline were also available for those who were allergic to penicillin
-relapse is rare

9. In 2012, a single oral dose of Azithromycin antibiotic was shown to be as effective to cure Yaws.
-Humans as sole resevoir
-As of 2012-study by Oriol Mitja shows single oral dose of Azithromycin (30 mg/kg; max 2 g)(17 cents) is just as effective to cure the disease (safe and easy to give)(The Morges strategy)(total community treatment-entire endemic community/ total targeted treatment-targets active clinical cases and their contacts in households, schools, etc.)
*both methods of treatment are effective and cheap
-India has eradicated the disease
-Remains in South-East Asia, Sub-Saharan Africa, and the Western-Pacific region (tropical habitats)
-WHO-projects global eradication by the year 2020
*need to know the geographical extent of the disease
*mapping of populations where yaws is knowns or suspected
*reporting and routine survellaince
*mass treatment with azithromycin
*availability and accessibility to Azithromycin
*funding and political commitment (political will)
*follow-up with treatment failure to monitor macrolide resistance

10. Prevention can also be effective
Early diagnosis & treatment
Improved hygiene/standard of living
Health education
Promote community support

11. Resources
Mitjà, O., Asiedu, K., & Mabey, D. (2013). Yaws. The Lancet, 381(9868), doi:
Asiedu K, Fitzpatrick C, Jannin J (2014) Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target. PLoS Negl Trop Dis 8(9): e3016. doi: /journal.pntd
Šmajs, David, Steven J. Norris, and George M. Weinstock. “Genetic Diversity in Treponema Pallidum: Implications for Pathogenesis, Evolution and Molecular Diagnostics of Syphilis and Yaws.” Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 12.2 (2012): 191–202. PMC. Web. 19 Apr
Microbial antigenic variation mediated by homologous DNA recombination
Cornelis Vink, Gloria Rudenko, H. Steven Seifert
FEMS Microbiology Reviews Sep 2012, 36 (5)  ; DOI:  /j x