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

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

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

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 = 10-90 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

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

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)

Yaws predominently affects humid, tropical areas in Africa, Asia, and the Western Pacific -epidemiological map showing at least 88-90 countries within the tropical belt were endemic for Yaws in the 1950s now only 13-14 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

From 1948-2012 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

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 http://thelancet.com/journals/lancet/article/PIIS0140-6736(12)62130-8/fulltext

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

Resources Mitjà, O., Asiedu, K., & Mabey, D. (2013). Yaws. The Lancet, 381(9868), 763-73. doi:http://dx.doi.org/10.1016/S0140-6736(12)62130-8 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: 10.1371/journal.pntd.0003016 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. 2016. Microbial antigenic variation mediated by homologous DNA recombination Cornelis Vink, Gloria Rudenko, H. Steven Seifert FEMS Microbiology Reviews Sep 2012, 36 (5) 917-948; DOI: 10.1111/j.1574-6976.2011.00321.x http://www.who.int/mediacentre/factsheets/fs316/en/ https://www.google.com/search?q=TprK&biw=1189&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiPgJbS8prMAhWDpB4KHYnPBbwQ_AUIBigB#tbm=isch&q=TprK+gene&imgrc=EKStSxJbfI7SOM%3A http://www.who.int/yaws/epidemiology/en/ https://www.google.com/search?q=yaws+immune+system+evasion&biw=1189&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi_r-jh6prMAhVDrB4KHfcuCNoQ_AUIBigB#tbm=isch&q=children+with+yaws&imgrc=O8zItwAVaQebaM%3A https://www.google.com/search?q=treponema+bacteria&biw=1194&bih=625&source=lnms&tbm=isch&sa=X&sqi=2&ved=0ahUKEwjwoKCmpI3MAhWD1B4KHe7aAtYQ_AUIBigB#imgrc=CWdrePEN_GRudM%3A https://www.google.com/search?q=yaws+eradication&biw=1194&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi2z7PypI3MAhXBGR4KHQ3GBEoQ_AUIBygC#imgrc=6j7BGyk-8M3z1M%3A https://www.google.com/search?q=yaws+eradication&biw=1194&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwi2z7PypI3MAhXBGR4KHQ3GBEoQ_AUIBygC#imgrc=oEkhCo_BvdiyWM%3A https://www.google.com/search?q=mother+yaws&biw=1190&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwiD17nZlY3MAhUIGR4KHb6GA9QQ_AUIBigB#imgrc=x0VarsO2J7R46M%3A http://emedicine.medscape.com/article/225576-clinical#b4 https://www.google.com/search?q=yaws+deformities&biw=1189&bih=625&source=lnms&tbm=isch&sa=X&sqi=2&ved=0ahUKEwi0hOzl05rMAhUBXD4KHWMsBDwQ_AUIBigB#imgrc=8jIcn4768JuRzM%3A https://www.google.com/search?q=yaws+distribution&biw=1189&bih=625&source=lnms&tbm=isch&sa=X&ved=0ahUKEwjxkrb-05rMAhVCFR4KHVXaA50Q_AUIBigB#imgrc=XMLP6E60q3Z36M%3A