View source for Yaws

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{{Other uses|Yaw (disambiguation)}}
{{Redirect|Parangi|the village in Iran|Parangi, Iran}}
{{Use dmy dates|date=August 2022}}
{{Infobox medical condition
| name            = Yaws
| image           = Yaws 01.jpg
| caption         = Nodules on the elbow resulting from a ''Treponema pallidum pertenue'' bacterial infection
| field           = [[Infectious disease (medical specialty)|Infectious disease]]
| synonyms        = Frambesia tropica, thymosis, polypapilloma tropicum,<ref>{{cite journal |last1=Maxfield |first1=L |last2=Crane |first2=JS |title=Yaws (Frambesia tropica, Thymosis, Polypapilloma tropicum, Parangi, Bouba, Frambosie, Pian) |date=January 2020 |journal=Stat Pearls |pmid=30252269}}</ref> non-venereal endemic syphilis,<ref name=yaws>{{cite journal |last1=Marks |first1=M |last2=Lebari |first2=D |last3=Solomon |first3=AW |last4=Higgins |first4=SP |title=Yaws |journal=International Journal of STD & AIDS |date=September 2015 |volume=26 |issue=10 |pages=696–703 |pmid=25193248 |doi=10.1177/0956462414549036 |doi-access=free |pmc=4655361}}</ref> parangi and paru (Malay),<ref name=Philippines/> bouba (Spanish),<ref name=Philippines/> frambösie,<ref name="Bolognia">{{cite book |vauthors=Rapini RP, Bolognia JL, Jorizzo JL |title=Dermatology: 2-Volume Set |publisher=Mosby |location=St. Louis |year=2007 |isbn=978-1-4160-2999-1}}</ref> pian<ref name="Andrews">{{cite book |vauthors=James WD, Berger TG |display-authors=etal |title=Andrews' Diseases of the Skin: clinical Dermatology |publisher=Saunders Elsevier |year=2006 |isbn=0-7216-2921-0 |oclc=62736861}}</ref> (French),<ref name=Philippines/> frambesia (German),<ref name=Philippines/> bakataw (Maguindanaoan)<ref name=Philippines/>
| symptoms        = Hard swelling of the skin, [[ulcer]], joint and bone pain<ref name=Mit2013/>
| complications   =
| onset           =
| duration        =
| causes          = ''[[Treponema pallidum]] pertenue'' spread by direct contact
| risks           =
| diagnosis       = Based on symptoms, blood [[antibody]] tests, [[polymerase chain reaction]]
| differential    =
| prevention      = Mass treatment
| treatment       =
| medication      = [[Azithromycin]], [[benzathine benzylpenicillin|benzathine penicillin]]
| prognosis       =
| frequency       = 46,000–500,000<ref name=Mit2012/><!-- cases per what? Year? -->
| deaths          =
}}
<!-- Definition and symptoms -->
'''Yaws''' is a tropical [[infection]] of the [[skin]], [[bone]]s, and joints caused by the [[spirochete]] [[bacterium]] ''[[Treponema pallidum]] pertenue''.<ref name=Mit2013>{{cite journal |vauthors=Mitjà O, Asiedu K, Mabey D |title=Yaws |journal=The Lancet |year=2013 |volume=381 |issue=9868 |pages=763–73 |pmid=23415015 |doi=10.1016/S0140-6736(12)62130-8 |s2cid=208791874}}</ref><ref name=Mit2012>{{cite journal |vauthors=Mitjà O, Hays R, Rinaldi AC, McDermott R, Bassat Q |title=New treatment schemes for yaws: the path toward eradication |journal=Clinical Infectious Diseases |year=2012 |volume=55 |issue=3 |pages=406–412 |format=pdf |pmid=22610931 |doi=10.1093/cid/cis444 |doi-access=free |url=http://cid.oxfordjournals.org/content/55/3/406.long |url-status=live |archive-url=https://web.archive.org/web/20140518070239/http://cid.oxfordjournals.org/content/55/3/406.long |archive-date=18 May 2014}}</ref> The disease begins with a round, hard swelling of the skin, {{cvt|2|to|5|cm|abbr=on}} in diameter.<ref name=Mit2013/> The center may break open and form an [[ulcer]].<ref name=Mit2013/> This initial skin lesion typically heals after 3–6 months. After weeks to years, joints and bones may become painful, [[fatigue (medical)|fatigue]] may develop, and new skin lesions may appear.<ref name=Mit2013/> The skin of the [[hand|palms]] of the hands and the soles of the feet may become thick and break open. The bones (especially those of the nose) may become misshapen. After 5 years or more, large areas of skin may die, leaving scars.<ref name=Mit2013/>

<!-- Spread and Diagnosis -->
Yaws is spread by direct contact with the fluid from a lesion of an infected person. The contact is usually nonsexual. The disease is most common among children, who spread it by playing together.<ref name=Mit2013/> Other related [[treponemal]] diseases are [[nonvenereal endemic syphilis|bejel]] (''T. pallidum endemicum''), [[pinta (disease)|pinta]] (''T. carateum''), and [[syphilis]] (''T. p. pallidum''). The appearance of the lesions often diagnoses yaws. Blood [[antibody]] tests may be useful, but cannot separate previous from current infections. [[Polymerase chain reaction]]  is the most accurate method of diagnosis.

<!-- Prevention and Treatment -->
No vaccine has yet been found.<ref name="historical">{{cite journal |last1=Asiedu |first1=Kingsley |last2=Fitzpatrick |first2=Christopher |last3=Jannin |first3=Jean |title=Eradication of Yaws: Historical Efforts and Achieving WHO's 2020 Target |journal=PLOS Neglected Tropical Diseases |date=25 September 2014 |volume=8 |issue=9 |pages=696–703 |issn=1935-2727 |pmid=25193248 |doi=10.1371/journal.pntd.0003016 |doi-access=free |pmc=4177727}}</ref> Prevention is, in part, done by curing those who have the disease, thereby decreasing the risk of transmission. Where the disease is common, treating the entire community is effective. Improving cleanliness and sanitation also decreases the spread. Treatment is typically with [[antibiotic]]s, including [[azithromycin]] by mouth or [[benzathine benzylpenicillin|benzathine penicillin]] by injection. Without treatment, physical deformities occur in 10% of cases.

<!-- Epidemiology -->
Yaws is common in at least 13 [[tropical countries]] as of 2012.<ref name=Mit2013/> Almost 85% of infections occurred in three countries—[[Ghana]], [[Papua New Guinea]], and [[Solomon Islands]].<ref>{{cite journal |last1=Mitjà |first1=O |last2=Marks |first2=M |last3=Konan |first3=DJ |last4=Ayelo |first4=G |last5=Gonzalez-Beiras |first5=C |last6=Boua |first6=B |last7=Houinei |first7=W |last8=Kobara |first8=Y |last9=Tabah |first9=EN |last10=Nsiire |first10=A |last11=Obvala |first11=D |last12=Taleo |first12=F |last13=Djupuri |first13=R |last14=Zaixing |first14=Z |last15=Utzinger |first15=J |last16=Vestergaard |first16=LS |last17=Bassat |first17=Q |last18=Asiedu |first18=K |title=Global epidemiology of yaws: a systematic review. |journal=The Lancet. Global Health |date=June 2015 |volume=3 |issue=6 |pages=e324-31 |pmid=26001576 |doi=10.1016/S2214-109X(15)00011-X |pmc=4696519}}</ref> The disease only infects humans.<ref name=WHO/> Efforts in the 1950s and 1960s by the [[World Health Organization]]  decreased the number of cases by 95%.<ref name=WHO/> Since then, cases have increased, but with renewed efforts to [[eradication of infectious diseases|globally eradicate]] the disease by 2020.<ref name=WHO/> In 1995, the number of people infected was estimated at more than 500,000.<ref name=Mit2012/> In 2016, the number of reported cases was 59,000.<ref name=WHO2018>{{cite web |title=Number of cases of yaws reported |work=World Health Organization Global Health Observatory |url=https://apps.who.int/gho/data/view.main.NTDYAWSNUMv |access-date=13 February 2019}}</ref> Although one of the first descriptions of the disease was made in 1679 by [[Willem Piso]], archaeological evidence suggests that yaws may have been present among human ancestors as far back as 1.6 million years ago.<ref name=Mit2013/>

==Signs and symptoms==
Yaws primarily occurs in children, most frequently in those aged 6–10.<ref name=WHO/>

Yaws is classified as primary, secondary, and tertiary; this can be clinically useful, but infected patients often have a mix of stages.<ref name=yaws/>

Within 9–90 days (but usually about 21 days<ref name=yaws/>) of infection, a painless but distinctive "mother yaw" [[nodule (medicine)|nodule]] appears.<ref name=yaws/> Initially [[erythematous|reddened and inflamed]],<ref name="advances"/> it may become a [[papilloma]], which can then become an [[ulcer (dermatology)|ulcer]],<ref name=WHO/> possibly with a yellow crust.<ref>{{cite journal |last1=Yotsu |first1=Rie R. |title=Integrated Management of Skin NTDs—Lessons Learned from Existing Practice and Field Research |journal=Tropical Medicine and Infectious Disease |date=14 November 2018 |volume=3 |issue=4 |pages=120 |issn=2414-6366 |pmid=30441754 |doi=10.3390/tropicalmed3040120 |doi-access=free |pmc=6306929}}</ref>{{better source needed|date=April 2020}} Mother yaws are most commonly found on the legs and ankles, and are rarely found on the genitals (unlike syphilis).<ref name=yaws/> The mother yaw enlarges and becomes warty in appearance. Nearby "daughter yaws" may also appear simultaneously.{{citation needed|date=April 2020}} This primary stage resolves completely, with scarring, within 3–6 months.<ref name="advances"/> The scar is often pigmented.<ref name=yaws/>

<gallery mode="packed" title="primary" yaws="" heights="150">
File:10.1177 0956462414549036-fig3-Papilloma of primary yaws.jpg|Papilloma mother yaw
File:Clinical presentation of skin NTDs tropicalmed-03-00120-g001 (cropped to yaws).jpg|Mother yaw nodule with central ulceration and a yellow crust
File:10.1177 0956462414549036-fig2-Ulcer of primary yaws.jpg|Ulcerated mother yaw
File:10.1177 0956462414549036-fig1-Ulcer of primary yaws.jpg|Ulcerated mother yaw
File:10.1177 0956462414549036-fig8-Primary yaws, healed Lesion.jpg|Healed primary yaw lesion, showing pigmented scar
</gallery>

The secondary stage occurs months to two years later (but usually 1–2 months later), and may thus begin when the mother's wound has not yet healed.<ref name=yaws/> It happens when the bacterium spreads in the blood and lymph. It begins as multiple, pinhead-like [[papules]]; these initial lesions grow and change in appearance and may last weeks before healing, with or without scarring.<ref name=yaws/>

Secondary yaws typically shows widespread skin lesions that vary in appearance, including "crab yaws" (areas of skin of abnormal color) on the palms of the hands and soles of the feet<ref name="advances"/> (named for the crab-like gait they cause people with painful soles to assume<ref name=yaws/>). These may show [[desquamation]].{{citation needed|date=April 2020}} These secondary lesions frequently ulcerate and are then highly infectious, but heal after 6 months or more.{{citation needed|date=April 2020}}

Secondary yaws affects the skin and bones.<ref name="advances"/> The most common bone-related problem is [[periostitis]], an inflammation around the bone, which often occurs in the bones of the fingers and the long bones of the lower arms and legs, causing [[dactylitis|swollen fingers]] and limbs.<ref name="advances"/> This causes pain at night and [[periosteal reaction|thickening of the affected bones]] (periostitis).<ref name=yaws/> About 75% of infected children surveyed in Papua New Guinea reported joint pain.<ref name=yaws/> [[Lymphadenopathy|Swollen lymph nodes]], fever, and malaise are also common.<ref name="advances"/>

A latent infection develops after primary and secondary yaws (and possibly, in some cases, without these phases).<ref name=yaws/> Within five years (rarely, within ten years<ref name=yaws/>), it can relapse and become active again, causing further secondary lesions, which may infect others.<ref name="advances"/> These relapse lesions are most commonly found around the armpits, mouth, and anus.<ref name=yaws/>

<gallery mode="packed" heights="150" title="Secondary" yaws="">
File:Hypopigmented patches with overlying pink papules with central depressions.jpg|Secondary yaws begin as multiple small lesions.
10.1177 0956462414549036-fig4-Secondary yaws- multiple small ulcerative lesions.jpg|The small lesions grow.
10.1177 0956462414549036-fig5-Secondary yaws- maculo-papular lesions with scaling.jpg|Secondary lesions vary in appearance (see [[Skin condition#Lesions|list of terms]])
File:Papulosquamous plaque and yellow-crusted nodules of secondary yaws on the leg (far view and close-up).jpg|Here, two different appearances (papulosquamous plaque and yellow-crusted [[nodule (medicine)|nodules]]) are seen in the same 10-year-old (large-scale of both, close-up of nodules)
File:Black-crusted erosion and surrounding hypopigmented patch on elbow.jpg|Hypopigmentation and a crusted erosion, elbow of a 5-year-old
File:Large, hypopigmented patches topped with scaly pink and brown papules on the dorsa of feet and ankles.jpg|Secondary yaws; [[hypopigmented]] areas of skin topped with pink and brown [[papule]]s, 9-year-old
File:Plantar yaw with moist yellow crusted erosion overlying pink granulation tissue.jpg|Erosion on the sole, close-up ([[:File:Plantar yaws lesions – deep punched-out erosions.jpg|large-scale]]). If deeper, it would be an ulcer
File:Moist, thick yellow crusted pink papilloma, 9-year-old boy.jpg|Secondary yaws papilloma (same 9-year-old as pictures of feet)
File:4150843630 bc699a7fa4 bPian.jpg|Secondary breakout in a 12-year-old  [[Javanese people|Javanese]] child (wax model)
File:Scars of yaws lesions on the legs of a female patient with a history of yaws skin lesions in childhood and positive non-treponemal and treponemal antibodies (latent yaws).jpg|Secondary yaws scars in an adult with a childhood history of yaws
</gallery>

An estimated 10% of people with yaws were formerly thought to develop tertiary disease symptoms, but more recently, tertiary yaws has been less frequently reported.<ref name="advances">{{cite journal |last1=Marks |first1=Michael |title=Advances in the Treatment of Yaws |journal=Tropical Medicine and Infectious Disease |date=29 August 2018 |volume=3 |issue=3 |pages=92 |issn=2414-6366 |pmid=30274488 |doi=10.3390/tropicalmed3030092 |doi-access=free |pmc=6161241}}</ref><ref name=yaws/>

Tertiary yaws can include [[gumma (pathology)|gummatous]] nodules. It most commonly affects the skin. The skin of the palms and soles may thicken ([[hyperkeratosis]]). Nodules ulcerating near joints can cause [[necrosis|tissue death]]. Periostitis can be much more severe. The shinbones may become bowed (saber shin)<ref name="advances"/> from chronic periostitis.<ref name=yaws/>

Yaws may or may not have [[cardiovascular]] or [[neurological]] effects; definitive evidence is lacking.<ref name=yaws/>

===Rhinopharyngitis mutilans===
'''Rhinopharyngitis mutilans''',<ref>{{cite journal |last1=L. H. |first1=Bittner |title=Some observations on the tertiary lesions of framboesia tropica, or yaws. |journal=The American Journal of Tropical Medicine and Hygiene |date=1926 |volume=1 |issue=2 |pages=123–130 |doi=10.4269/ajtmh.1926.s1-6.123}}</ref><ref name=IDN>{{cite book |last1=Berger |first1=Stephen |title=Infectious Diseases of Nauru |date=1 February 2015 |publisher=GIDEON Informatics Inc |isbn=9781498805742 |page=320 |url=https://books.google.com/books?id=LNt2BwAAQBAJ&q=%22Rhinopharyngitis+mutilans%22&pg=PA320 |access-date=31 October 2015}}</ref> also known as '''gangosa''', is a destructive [[ulcerative]] condition that usually originates about the [[soft palate]] and spreads into the [[hard palate]], [[pharynx#Nasopharynx|nasopharynx]], and [[human nose|nose]], resulting in mutilating [[cicatrice]]s, and outward to the face, eroding intervening [[bone]], [[cartilage]], and [[soft tissues]]. It occurs in the late stages of yaws, usually 5 to 10 years after the first symptoms of [[infection]]. This is now rare.<ref name=yaws/> Very rarely,<ref name=yaws/> yaws may cause [[exostosis|bone spurs]] in the upper jaw near the nose (gondou); gondou was rare even when yaws was a common disease.<ref name="advances"/>

<gallery mode="packed" heights="150" title="Tertiary" yaws="">
File:Medical diagnosis for the student and practitioner (1922) (14761746096).jpg|Deep ulceration occurs in tertiary yaws
File:Medical diagnosis for the student and practitioner (1922) (14804596673).jpg|Severe tertiary yaws; gangosa
File:Medical diagnosis for the student and practitioner (1922) p1117 (cropped to goundu).jpg|Goundu, a very rare yaws-caused deformity around the nose
</gallery>

==Cause==
Yaws is caused by infection with bacteria of the ''[[Treponema pallidum]]'' subspecies ''pertenue''.<ref name=WHO/> The initial yaws wound contains infectious bacteria, which are passed onto others through skin-to-skin contact, typically during play or other normal childhood interactions.<ref name=WHO/>{{sfn|Hotez|2022|p=218}} Early (primary and secondary) yaws lesions have a higher bacterial load, thus are more infectious.<ref name=yaws/> Both papillomas and ulcers are infectious.<ref name=WHO/> Infectivity is thought to last 12–18 months after infection, longer if a relapse occurs. Early yaws lesions are often itchy, and more lesions may [[Koebner phenomenon|form along lines that are scratched]]. Yaws may be evolving into less conspicuous lesions.<ref name=yaws/> After a new person is infected, an infectious papilloma will form within 9–90 days (on average 21 days).<ref name=WHO/>

''T. pallidum pertenue'' has been identified in nonhuman [[primates]] ([[baboons]], [[chimpanzee]]s, and [[gorilla]]s) and experimental [[inoculation]] of human beings with a [[simian]] isolate causes yaws-like disease. However, no evidence exists of cross-transmission between human beings and primates, but more research is needed to discount the possibility of a yaws animal reservoir in nonhuman primates.<ref name=Mit2013/>

==Diagnosis==
[[File:Psoriasiform epidermal hyperplasia and band-like lymphocytic infiltrates in papillary dermis.jpg|thumb|Lesion biopsy under a microscope, clear [[epidermal hyperplasia]]]]
{{Multiple image
| width =
| footer =
| image1 = 10.1177 0956462414549036-fig6-Secondary yaws- dactylitis.jpg
| alt1 = An irregularly-thickened first finger; proximal fingerbone is asymmetrically swollen
| caption1 = Dactylitis of secondary yaws due to periostitis
| image2 = 10.1177 0956462414549036-fig7-Secondary yaws- radiographic evidence of osteoperiostitis.jpg
| alt2 = radiograph showing the same hand with thickened bones
| caption2 =  Periostitis of secondary yaws may be visible on an X-ray, even if not otherwise visible<ref name=yaws/>
}}
Most often, the diagnosis is made clinically.<ref name=MedicineNet/> [[Dark field microscopy]] of samples taken from early lesions (particularly ulcerative lesions<ref name=MedicineNet/>{{verify source|date=April 2020}}) may show the responsible bacteria; the [[spirochaetes]] are only 0.3 μm wide by 6–20 μm long, so light-field microscopy does not suffice.<ref name=yaws/>

A microscopic examination of a biopsy of a yaw may show skin with clear [[epidermal hyperplasia]] (a type of skin thickening) and [[papillomatosis]] (a type of surface irregularity), often with focal [[spongiosis]] (an accumulation of fluid in a specific part of the epidermis). [[Immune system]] cells, [[neutrophil]]s and [[plasma cell]]s, accumulate in the skin, in densities that may cause microabscesses.{{citation needed|date=January 2021}}

[[Warthin–Starry stain|Warthin–Starry]] or Levaditi silver stains selectively stain ''T. pallidum'', and direct and indirect [[immunofluorescence]] and [[immunoperoxidase]] tests can detect [[polyclonal antibodies]] to ''T. pallidum''{{'s}}. Histology often shows some spatial features that distinguish yaws from syphilis (syphilis is more likely to be found in the dermis, not the epidermis, and shows more [[endothelial cell]] proliferation and [[blood vessel|vascular]] obliteration).<ref name=yaws/>

[[Serological testing|Blood-serum (serological) tests]] are increasingly done at the point of care. They include a growing range of [[treponemal]] and nontreponemal assays. Treponemal tests are more [[specificity (statistics)|specific]], and are positive for anyone who has ever been infected with yaws; they include the [[TPHA|''Treponema pallidum'' particle agglutination assay]]. Nontreponemal assays can be used to indicate the progress of an infection and a cure, and positive results weaken and may become negative after recovery, especially after a case is treated early.<ref name=advances/> They include the venereal disease research laboratory ([[VDRL]]; requires microscopy) and rapid plasma {{Not a typo|reagin}} ([[Rapid Plasma Reagin|RPR]]; naked-eye result) tests, both of which [[flocculate]] patient-derived [[antibodies]] with [[antigens]].<ref name=yaws/>

Serological tests cannot distinguish yaws from the closely related [[syphilis]];<ref name=yaws/> no test distinguishing yaws from syphilis is widely available. The two genomes differ by about 0.2%. [[Polymerase chain reaction|PCR]] and [[DNA sequencing]] can distinguish the two.<ref name=yaws/> There are also no common blood tests that distinguish among the four [[treponematosis|treponematoses]]: syphilis (''T. p. pallidum''), yaws (''T. p. pertenue''), bejel (''T. p. endemicum''), and pinta (''T. carateum'').<ref name=MedicineNet/>

''[[Haemophilus ducreyi]]'' infections can cause skin conditions that mimic primary yaws. People infected with ''Haemophilus ducreyi'' lesions may or may not also have latent yaws, and thus may or may not test positive on serological tests. This was discovered in the mid-2010s.<ref name=advances/> It seems that a recently diverged strain of ''Haemophilus ducreyi'' has evolved from being a sexually transmitted infection to being a skin ulcer pathogen that looks like yaws.<ref>{{cite journal |last1=Lewis |first1=David A. |last2=Mitjà |first2=Oriol |title=Haemophilus ducreyi: from sexually transmitted infection to skin ulcer pathogen |journal=Current Opinion in Infectious Diseases |date=February 2016 |volume=29 |issue=1 |pages=52–57 |issn=1473-6527 |pmid=26658654 |doi=10.1097/QCO.0000000000000226 |s2cid=1699547}}</ref>

Yaws has been reported in nonendemic countries.<ref name=yaws/>

==Treatment==
Treatment is normally by a single [[intramuscular injection]] of long-acting [[benzathine benzylpenicillin]], or less commonly by a course of other antibiotics, such as [[azithromycin]] or [[tetracycline]] tablets.{{citation needed|date=April 2020}} Penicillin has been the front-line treatment since at least the 1960s, but there is no solid evidence of the evolution of [[penicillin resistance]] in yaws.<ref name=advances/>

The historical strategy for the [[eradication of infectious diseases|eradication]] of yaws (1952–1964) was:<ref name=advances/><!--Table repeated verbatim from CC BY 4.0 source by Michael Marks-->
{| class="wikitable"
|-
! Prevalence of clinically active yaws !! Treatment strategy
|-
| Hyperendemic: above 10%  || Benzathine benzylpenicillin to the whole community
(total mass treatment)
|-
| Mesoendemic: 5–10%  || Treat all active cases, all children under 15, and all contacts of infectious cases
(juvenile mass treatment)
|-
| Hypoendemic: under 5%  || Treat all active cases and all household and other contacts
(selective mass treatment)
|}

Benzathine benzylpenicillin requires a [[cold chain]] and staff who can inject it, and there is a small risk of [[anaphylaxis]]. It was also not reliably available during the 2010s; there have been supply shortages.<ref name=advances/>

In the 2010s, a single oral dose of [[azithromycin]] was shown to be as effective as intramuscular penicillin.<ref>{{cite journal |vauthors=Mitjà O, Hays R, Ipai A, Penias M, Paru R, Fagaho D, deLazzari E, Bassat Q |title=Single-dose azithromycin versus benzathine benzylpenicillin for treatment of yaws in children in Papua New Guinea: an open-label, non-inferiority, randomised trial. |journal=The Lancet |date=28 January 2012 |volume=379 |issue=9813 |pages=342–47 |pmid=22240407 |doi=10.1016/S0140-6736(11)61624-3 |s2cid=17517869}}</ref><ref name=advances/> Unlike penicillin, there is strong evidence that yaws is evolving [[antibiotic resistance]] to azithromycin; there are two known mutations in the bacterium, each of which can cause resistance and make the treatment ineffective. This has threatened eradication efforts.<ref name=advances/>

Within 8–10 hours of penicillin treatment, bacteria can no longer be found in lesion biopsies.<ref name=yaws/> Primary and secondary lesions usually heal in 2–4 weeks; bone pain may improve within two days.<ref name=advances/> If treated early enough, bone deformities may reverse and heal.<ref name=yaws/> Primary and secondary stage lesions may heal completely, but the destructive changes of tertiary yaws are largely irreversible.{{citation needed|date=April 2020}}

If lesions do not heal, or RPR test results do not improve, this may indicate treatment failure or re-infection; the treatment is typically repeated.<ref name=yaws/> WHO guidelines say that any presumed treatment failures at 4 weeks require [[macrolide#Resistance|macrolide resistance]] testing.<ref name=WHO/>

<gallery mode="packed" heights="200">
File:Large "moist cauliflower" papillomas on left axilla.jpg|Secondary yaws in the left armpit of a ten-year-old, 2020
File:Yaws papillomas on axilla significantly reduced in size 2 weeks and completely resolved 3-and-a-half months after one-dose azithromycin was taken.jpg|Same person, 2 weeks and 3.5 months after a single-dose azithromycin
File:Yaws treatment.png|Before and two weeks after a single injection of benzathine penicillin, 1950s.
</gallery>

==Epidemiology==
[[File:Countries where yaws is endemic, 2022.png|alt=Status of yaws endemicity in the countries have reported a case of yaws at least once.|thumb|upright=1.8|Countries with yaws, currently and previously, {{as of|lc=yes|2022}}.<ref>{{cite web |title=Countries where yaws is endemic |website=Our World in Data |url=https://ourworldindata.org/grapher/status-of-yaws-endemicity |access-date=17 June 2024}}</ref>]]
{{Quote box|Where the road ends, yaws begins|—WHO saying, quoted by Kingsley Asiedu.<ref name="return"/>}}

Yaws is typically found in humid tropical<ref name=advances/> forest regions in [[South America]], [[Africa]], [[Asia]], and [[Oceania]].<ref name=historical/><ref name=WHO/>

Yaws primarily affects children, with up to 80% of cases in those under 15 years of age, and peak incidence in children aged six to ten.<ref name=WHO/> Boys and girls are impacted equally.<ref name=WHO/>

It is more common in remote areas, where access to treatment is poorer.<ref name=advances/> It is associated with poverty and poor sanitation facilities and personal hygiene.<ref name=historical/><ref name="global">{{cite journal |last1=Mitjà |first1=Oriol |last2=Marks |first2=Michael |last3=Konan |first3=Diby J P |last4=Ayelo |first4=Gilbert |last5=Gonzalez-Beiras |first5=Camila |last6=Boua |first6=Bernard |last7=Houinei |first7=Wendy |last8=Kobara |first8=Yiragnima |last9=Tabah |first9=Earnest N |last10=Nsiire |first10=Agana |last11=Obvala |first11=Damas |title=Global epidemiology of yaws: a systematic review |date=19 May 2015 |journal=The Lancet. Global Health |volume=3 |issue=6 |pages=e324–e331 |issn=2214-109X |first17=Quique |last18=Asiedu |first18=Kingsley |last17=Bassat |last16=Vestergaard |first16=Lasse S |last15=Utzinger |first15=Jürg |last14=Zaixing |first14=Zhang |last13=Djupuri |first13=Rita |last12=Taleo |first12=Fasiah |pmid=26001576 |doi=10.1016/S2214-109X(15)00011-X |doi-access=free |pmc=4696519}}</ref><ref name=WHO/>

Worldwide, almost 85% of yaws cases are in Ghana, Papua New Guinea, and the Solomon Islands. Rates in sub-Saharan Africa are low but tend to be concentrated in specific populations. {{as of|2015}}, it is estimated that about 89 million people live in yaws-endemic areas, but data are poor, and this is likely an overestimate.<ref name="global"/>

In the early 1900s, yaws was very common; in sub-Saharan Africa, it was more frequently treated than malaria, sometimes making up more than half of treatments.<ref name=historical/>

Mass treatment campaigns in the 1950s reduced the worldwide [[prevalence]] from 50 to 150 million to fewer than 2.5 million; however, during the 1970s, there were outbreaks in [[South-East Asia]], and there have been continued sporadic cases in South America. {{as of|2011}}, it was unclear how many people worldwide were currently infected.<ref name=Capuano2011/>

From 2008 to 2012, 13 countries reported over 300,000 new cases to the WHO. There was no system for certifying local elimination of yaws, and it is not known whether the lack of reports from some countries is because they stopped having yaws cases or because they stopped reporting them. It is estimated that if there is not an active surveillance programme, there is less than a 1-in-2 chance that a country will successfully report yaws cases (if it gets them) in over three-quarters of countries with a history of yaws. These countries are thought to need international assistance to mount effective surveillance.<ref name="surveillance">{{cite journal |last1=Fitzpatrick |first1=Christopher |last2=Asiedu |first2=Kingsley |last3=Solomon |first3=Anthony W. |last4=Mitja |first4=Oriol |last5=Marks |first5=Michael |last6=Van der Stuyft |first6=Patrick |last7=Meheus |first7=Filip |title=Prioritizing surveillance activities for certification of yaws eradication based on a review and model of historical case reporting |journal=PLOS Neglected Tropical Diseases |date=4 December 2018 |volume=12 |issue=12 |pages=e0006953 |issn=1935-2727 |pmid=30513075 |doi=10.1371/journal.pntd.0006953 |doi-access=free |pmc=6294396}}</ref>

==History==

{{Multiple image
| width =
| footer =
| image1 = J. L. M. Alibert, Description des maladies de la peau. Wellcome L0020973.jpg
| alt1 =
| caption1 = Yaws at the [[Hôpital Saint-Louis]], Paris. Date: 1806
| image2 = Don't show me Yaws.jpg
| alt2 = Outstretched arm with multiple raised pink lesions on its inner side
| caption2 = Page from Surgeon John O'Neill's illustrated journal of diseases on the West Coast of Africa, written during his time on HM Gun Boat ''Decoy''. Colour diagrams showing a "typical case of Framboesia or Yaws". Date: 1874
}}

Examination of remains of ''[[Homo erectus]]'' from [[Kenya]], which are about 1.6 million years old, has revealed signs typical of yaws. The genetic analysis of the yaws causative bacteria—''Treponema pallidum pertenue''—has led to the conclusion that yaws is the most ancient of the four known ''Treponema'' diseases. All other ''Treponema pallidum'' subspecies probably evolved from ''Treponema pallidum pertenue''. Yaws is believed to have originated in tropical areas of Africa and spread to other tropical areas of the world via immigration and the [[history of slavery|slave trade]]. The latter is likely the way it was introduced to [[Europe]] from [[Africa]] in the 15th century. The first unambiguous description of yaws was made by the [[Dutch people|Dutch]] physician [[Willem Piso]]. Yaws was clearly described in 1679 among [[African slaves]] by [[Thomas Sydenham]] in his [[epistle]] on [[venereal diseases]], although he thought that it was the same disease as [[syphilis]]. The causative agent of yaws was discovered in 1905 by [[Aldo Castellani]] in ulcers of patients from [[Ceylon]].<ref name=Mit2013/>

The current English name is believed to be of [[Island Caribs|Carib]] origin, from "yaya", meaning sore.<ref name=MedicineNet>{{cite web |title=Yaws |vauthors=Davis CP, Stoppler MC |publisher=MedicineNet.com |url=https://www.medicinenet.com/yaws/article.htm |access-date=5 August 2012 |url-status=live |archive-url=https://web.archive.org/web/20121008223230/http://www.medicinenet.com/yaws/page4.htm |archive-date=8 October 2012}}</ref>

Towards the end of the Second World War, yaws became widespread in the North of Malaya under Japanese occupation. After the country was liberated, the population was treated for yaws by injections of [[salvarsan]], of which there was a great shortage, so only those with stage 1 were treated.<ref>"All things uncertain: The story of the G.I.S."
by Phyllis Stewart Brown</ref>
{{clear}}

==Eradication==
[[File:COLLECTIE TROPENMUSEUM Een Europeaan vaccineert Indonesische patiënten met neosalvarsaan tegen de ziekte framboesia TMnr 10006691.jpg|250px|thumb|European doctor treats an Indonesian woman for yaws, early- to mid-20th-century.<!--no date on photo, but film processing method pretty much eliminates the late 20th and 21st century. Also seems fairly clear from the objects in the picture...-->]]
[[File:Anbumani Ramadoss and the Minister of State for Health & Family Welfare, Smt. Panabaka Lakshmi releasing the document "Yaws elimination in India – a step towards eradication", in New Delhi on September 19, 2006.jpg|thumb|upright=1.5|After eliminating yaws in India, the Indian government releases a report called "Yaws elimination in India – a step towards eradication". 2006]]
{{Multiple image
| width =
| footer = Yaws before and after treatment with [[neosalvarsan]], an obsolete treatment
| image1 = COLLECTIE TROPENMUSEUM Een framboesia tropica-patiënt voor de behandeling met neosalvarsaan TMnr 10006692.jpg
| alt1 =
| caption1 =
| image2 = COLLECTIE TROPENMUSEUM Een framboesia tropica-patiënt na de behandeling met neosalvarsaan TMnr 10006693.jpg
| alt2 =
| caption2 =
}}

A series of WHO yaws control efforts, which began shortly after the creation of the WHO in 1948, succeeded in eradicating the disease locally from many countries, but have not lasted long enough to eradicate it globally. The Global Control of Treponematoses (TCP) programme by the WHO and the [[United Nations Children's Fund|UNICEF]] was launched in 1952 and continued until 1964. A 1953 questionnaire-based estimate was that there were 50–150 million yaws cases in 90 countries.<ref name="global"/> The global prevalence of yaws and the other endemic treponematoses, [[nonvenereal endemic syphilis|bejel]] and [[pinta (disease)|pinta]], was reduced by the Global Control of Treponematoses (TCP) programme between 1952 and 1964 from about 50 million cases to about 2.5 million (a 95% reduction).<ref name="who_yaws2012">{{cite web |title=WHO renews efforts to achieve global eradication of yaws by 2020 |url=https://www.who.int/news/item/19-10-2012-who-renews-efforts-to-achieve-global-eradication-of-yaws-by-2020}}</ref>  However, "premature integration of yaws and other endemic treponematoses activities into weak primary health-care systems, and the dismantling of the vertical eradication programmes after 1964, led to the failure to finish with the remaining 5% of cases"<ref name="who_yaws2012"/> and also led to a resurgence of yaws in the 1970s, with the largest number of case found in the Western Africa region.<ref name=Capuano2011>{{cite journal |last1=Capuano |first1=C |last2=Ozaki |first2=M |title=Yaws in the Western Pacific Region: A Review of the Literature |journal=Journal of Tropical Medicine |year=2011 |volume=2011 |page=642832 |pmid=22235208 |doi=10.1155/2011/642832 |doi-access=free |pmc=3253475}}</ref><ref name=Rinaldi2008>{{cite journal |author=Rinaldi A |title=Yaws: a second (and maybe last?) chance for eradication |journal=[[PLOS Neglected Tropical Diseases]] |volume=2 |issue=8 |page=e275 |year=2008 |pmid=18846236 |doi=10.1371/journal.pntd.0000275 |doi-access=free |pmc=2565700}}</ref> Following the cessation of this program, resources, attention and commitment for yaws gradually disappeared, and yaws remained at a low prevalence in parts of Asia, Africa, and the Americas with sporadic outbreaks. With few cases, mainly affecting poor, remote communities with little access to treatment, yaws became poorly known, yaws knowledge and skills died out even among health professionals, and yaws eradication was not seen as a high priority. Although a single injection of long-acting penicillin or other [[beta-lactam]] antibiotic cures the disease and is widely available, and the disease is highly localised, many eradication campaigns ended in complacency and neglect; even in areas where transmission was successfully interrupted, re-introduction from infected areas occurred. Yaws eradication remained a priority in South-East Asia.<ref name="return">{{cite journal |last1=Asiedu |first1=Kingsley |title=The return of yaws |journal=Bulletin of the World Health Organization |date=July 2008 |volume=86 |issue=7 |pages=507–8 |pmid=18670660 |doi=10.2471/blt.08.040708 |doi-access=free |pmc=2647480}}</ref><ref name=Asiedu2008/>  In 1995, the WHO estimated 460,000 worldwide cases.<ref name=WHO2017>{{cite web |title=Integrating neglected tropical diseases in global health and development |url=http://www.who.int/neglected_diseases/resources/9789241565448/en/ |access-date=12 September 2017}}</ref>

In the Philippines, yaws stopped being listed as a [[notifiable disease]] in 1973; as of 2020, it is still present in the country.<ref name=Philippines>{{cite journal |last1=Dofitas |first1=BL |last2=Kalim |first2=SP |last3=Toledo |first3=CB |last4=Richardus |first4=JH |title=Yaws in the Philippines: first reported cases since the 1970s. |journal=Infectious Diseases of Poverty |date=30 January 2020 |volume=9 |issue=1 |pages=1 |pmid=31996251 |doi=10.1186/s40249-019-0617-6 |doi-access=free |pmc=6990502}}</ref>

[[India]] implemented a successful yaws eradication campaign that resulted in the 2016 certification by the WHO that India was free of yaws.<ref name=":0">{{cite journal |last=Friedrich |first=M. J. |title=WHO Declares India Free of Yaws and Maternal and Neonatal Tetanus |date=20 September 2016 |journal=JAMA |volume=316 |issue=11 |pages=1141 |issn=1538-3598 |pmid=27654592 |doi=10.1001/jama.2016.12649 |url=https://pubmed.ncbi.nlm.nih.gov/27654592}}</ref><ref name="Asiedu2008">{{cite journal |author=Asiedu K |title=Yaws eradication: past efforts and future perspectives |journal=[[Bulletin of the World Health Organization]] |volume=86 |issue=7 |pages=499–500 |year=2008 |last2=Amouzou |first2=B |last3=Dhariwal |first3=A |last4=Karam |first4=M |last5=Lobo |first5=D |last6=Patnaik |first6=S |last7=Meheus |first7=A |pmid=18670655 |doi=10.2471/BLT.08.055608 |pmc=2647478 |url=https://www.who.int/bulletin/volumes/86/7/08-055608/en/index.html |access-date=2 April 2009 |url-status=dead |archive-url=https://web.archive.org/web/20090421201956/http://www.who.int/bulletin/volumes/86/7/08-055608/en/index.html |archive-date=21 April 2009}}</ref><ref>{{cite web |archiveurl=https://web.archive.org/web/20081108054616/http://www.searo.who.int/LinkFiles/Yaws_yaws.pdf |title=World Health Organization South-East Asia &#124; World Health Organization |archivedate=8 November 2008 |website=who.int |url=https://www.who.int/southeastasia |url-status=dead}}</ref> In 1996 there were 3,571 yaws cases in India; in 1997 after a serious elimination effort began the number of cases fell to 735. By 2003, the number of cases was 46. The last clinical case in India was reported in 2003 and the last latent case in 2006;<ref name="Akbar2011">{{cite news |last=Akbar |first=S |title=Another milestone for India: Yaws eradication |date=7 August 2011 |work=The Asian Age |url=http://www.asianage.com/health-fitness/another-milestone-india-yaws-eradication-116 |access-date=5 August 2012 |url-status=live |archive-url=https://web.archive.org/web/20111011105128/http://www.asianage.com/health-fitness/another-milestone-india-yaws-eradication-116 |archive-date=11 October 2011}}</ref> certification by the WHO was achieved in 2016.<ref name=":0"/><ref>{{cite journal |title=Yaws Eradication Programme (YEP) |publisher=NCDC, Dte. General of Health Services, Ministry of Health & Family Welfare, Government of India |url=http://www.ncdc.gov.in/index3.asp?sslid=330&subsublinkid=304 |access-date=18 January 2014 |url-status=live |archive-url=https://web.archive.org/web/20140202175956/http://www.ncdc.gov.in/index3.asp?sslid=330&subsublinkid=304 |archive-date=2 February 2014}}</ref>

In 2012 the WHO officially targeted yaws for eradication by 2020 following the development of orally administered azithromycin as a treatment, but missed that target.<ref name=WHO2012>{{cite journal |title=Eradication of yaws – the Morges Strategy. |journal=Weekly Epidemiological Record |volume=87 |issue=20 |year=2012 |format=pdf |url=https://www.who.int/wer/2012/wer8720.pdf?ua=1 |access-date=6 May 2014 |url-status=live |archive-url=https://web.archive.org/web/20140508031005/http://www.who.int/wer/2012/wer8720.pdf?ua=1 |archive-date=8 May 2014}}</ref><ref name=Maurice2012>{{cite journal |last=Maurice |first=J |title=WHO plans new yaws eradication campaign |journal=The Lancet |year=2012 |pages=1377–78 |volume=379 |issue=9824 |pmid=22509526 |doi=10.1016/S0140-6736(12)60581-9 |doi-access=free |s2cid=45958274}}</ref><ref name=Rinaldi2012>{{cite journal |author=Rinaldi A |title=Yaws eradication: facing old problems, raising new hopes |journal=[[PLOS Neglected Tropical Diseases]] |volume=6 |issue=11 |page=e18372 |year=2012 |pmid=23209846 |doi=10.1371/journal.pntd.0001837 |doi-access=free |pmc=3510082}}</ref> The Morges approach (named after [[Morges]], Switzerland, where a meeting on it was held<ref>{{cite web |title=Summary report of a consultation on the eradication of yaws |website=WHO |url=http://www9.who.int/neglected_diseases/resources/who_htm_ntd_idm_2012.2/en/ |url-status=dead |archive-url=https://web.archive.org/web/20170422173656/http://www.who.int/neglected_diseases/resources/who_htm_ntd_idm_2012.2/en/ |archive-date=22 April 2017}}</ref>) involved mass treatment with [[azithromycin]]. This was safe, but ran into problems with antibiotic resistance, and did not fully interrupt transmission.<ref name="advances"/>

The discovery that oral antibiotic [[azithromycin]] can be used instead of the previous standard, injected [[penicillin]], was tested on [[Lihir Island]] from 2013 to 2014;<ref>[http://www.trust.org/item/20130509121147-ausc2/ Drug and a syphilis test offer hope of yaws eradication] {{Webarchive|url=https://web.archive.org/web/20130813211123/http://www.trust.org/item/20130509121147-ausc2/ |date=13 August 2013}}, Thomas Reuter Foundation, accessed 10 May 2013</ref> a single oral dose of the macrolide antibiotic reduced disease prevalence from 2.4% to 0.3% at 12 months.<ref>{{cite journal |vauthors=Mitjà O, Houinei W, Moses P, Kapa A, Paru R, Hays R, Lukehart S, Godornes C, Bieb SV, Grice T, Siba P, Mabey D, Sanz S, Alonso PL, Asiedu K, Bassat Q |title=Mass treatment with single-dose azithromycin for yaws |journal=The New England Journal of Medicine |volume=372 |issue=8 |pages=703–10 |date=February 2015 |pmid=25693010 |doi=10.1056/NEJMoa1408586 |hdl=2445/68722 |hdl-access=free |s2cid=5762563}}</ref> The WHO now recommends both treatment courses (oral azithromycin and injected penicillin), with oral azithromycin being the preferred treatment.<ref name=WHO>{{cite web |title=Yaws |publisher=World Health Organization |date=12 January 2023 |accessdate=24 May 2024 |url=https://www.who.int/news-room/fact-sheets/detail/yaws}}</ref>

{{as of|2020}}, there were 15 countries known to be endemic for yaws, with the recent discovery of endemic transmission in [[Liberia]] and the [[Philippines]].<ref name="who_yaws">{{cite web |title=Yaws |website=who.int |url=https://www.who.int/news-room/fact-sheets/detail/yaws}}</ref> In 2020, 82,564 cases of yaws were reported to the WHO, and 153 cases were confirmed. The majority of the cases are reported from [[Papua New Guinea]] and with over 80% of all cases coming from one of three countries in the 2010–2013 period: Papua New Guinea, Solomon Islands, and Ghana.<ref name="who_yaws"/><ref>{{cite journal |last1=Mitjà |first1=Oriol |last2=Marks |first2=Michael |last3=Konan |first3=Diby J P |last4=Ayelo |first4=Gilbert |last5=Gonzalez-Beiras |first5=Camila |last6=Boua |first6=Bernard |last7=Houinei |first7=Wendy |last8=Kobara |first8=Yiragnima |last9=Tabah |first9=Earnest N |last10=Nsiire |first10=Agana |last11=Obvala |first11=Damas |title=Global epidemiology of yaws: a systematic review |date=19 May 2015 |journal=The Lancet. Global Health |volume=3 |issue=6 |pages=e324–e331 |last16=Vestergaard |first16=Lasse S |last17=Bassat |first17=Quique |last18=Asiedu |first18=Kingsley |last15=Utzinger |first15=Jürg |last14=Zaixing |first14=Zhang |last13=Djupuri |first13=Rita |last12=Taleo |first12=Fasiah |pmid=26001576 |doi=10.1016/S2214-109X(15)00011-X |pmc=4696519}}</ref> A WHO meeting report in 2018 estimated the total cost of elimination to be US$175 million (excluding Indonesia).<ref name="who2018_yaws_meeting">{{cite book |title=Report of a global meeting on yaws eradication surveillance, monitoring and evaluation: Geneva, 29–30 January 2018 |date=2018 |publisher=World Health Organization |last1=Organization |first1=World Health |hdl=10665/276314}}</ref>

In the South-East Asian Regional Office of the WHO, regional eradication efforts are focused on the remaining endemic countries in this region ([[Indonesia]] and [[East Timor]])<ref>{{cite journal |last1=Asiedu |first1=Kingsley |last2=Amouzou |first2=Bernard |last3=Dhariwal |first3=Akshay |last4=Karam |first4=Marc |last5=Lobo |first5=Derek |last6=Patnaik |first6=Sarat |last7=Meheus |first7=André |title=Yaws eradication: past efforts and future perspectives |journal=Bulletin of the World Health Organization |date=July 2008 |volume=86 |issue=7 |pages=499–499A |pmid=18670655 |doi=10.2471/BLT.08.055608 |pmc=2647478}}</ref><ref>{{cite book |title=Regional strategic plan for elimination of yaws from South-East Asia Region 2012-2020 |date=2013 |publisher=WHO Regional Office for South-East Asia |hdl=10665/205830}}</ref> after [[India]] was declared free of yaws in 2016.<ref>{{cite journal |last1=Friedrich |first1=M.J. |title=WHO Declares India Free of Yaws and Maternal and Neonatal Tetanus |journal=JAMA |date=20 September 2016 |volume=316 |issue=11 |pages=1141 |pmid=27654592 |doi=10.1001/jama.2016.12649}}</ref><ref name="who2018_yaws_meeting"/>

Although yaws is highly localized and [[eradication of infectious diseases|eradication]] may be feasible, humans may not be the only [[reservoir of infection]].<ref name=Capuano2011/>
{{Clear}}

==References==
{{Reflist}}

===Works cited===
*{{cite book |vauthors=Hotez PJ |title=Forgotten People, Forgotten Diseases: The Neglected Tropical Diseases and Their Impact on Global Health and Development |publisher=John Wiley & Sons |date=2022 |isbn=9781683673897 |edition=3 |chapter=12. The Newest NTDs and a Plea to "Repair the World" |pages=217–226}}

==External links==
{{Commons category}}
* {{cite web |title=''Treponema pallidum subsp. pertenue'' |work=NCBI Taxonomy Browser |id=168 |url=https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&id=168}}
{{Medical resources
| ICD11       = {{ICD11|1C1D}}
| ICD10       = {{ICD10|A|66||a|60}}
| ICD9        = {{ICD9|102}}
| MedlinePlus = 001341
}}
{{Gram-negative non-proteobacterial diseases}}
{{Eradication of infectious disease}}
{{Bacterial cutaneous infections}}

{{Authority control}}
[[Category:Bacterium-related cutaneous conditions]]
[[Category:Infectious diseases with eradication efforts]]
[[Category:Syphilis]]
[[Category:Tropical diseases]]
[[Category:Wikipedia infectious disease articles ready to translate]]
[[Category:Wikipedia medicine articles ready to translate]]