marks-et-al-2014-yaws
marks-et-al-2014-yaws
marks-et-al-2014-yaws
Abstract
Yaws is a non-venereal endemic treponemal infection caused by Treponema pallidum sub-species pertenue, a spirochaete
bacterium closely related to Treponema pallidum ssp. pallidum, the agent of venereal syphilis. Yaws is a chronic, relapsing
disease predominantly affecting children living in certain tropical regions. It spreads by skin-to-skin contact and, like
syphilis, occurs in distinct clinical stages. It causes lesions of the skin, mucous membranes and bones which, without
treatment, can become chronic and destructive. Treponema pallidum ssp. pertenue, like its sexually-transmitted counter-
part, is exquisitely sensitive to penicillin. Infection with yaws or syphilis results in reactive treponemal serology and there
is no widely available test to distinguish between these infections. Thus, migration of people from yaws-endemic areas to
developed countries may present clinicians with diagnostic dilemmas. We review the epidemiology, clinical presentation
and treatment of yaws.
Keywords
Syphilis, Yaws, Treponema pallidum pertenue, non-venereal endemic syphilis, neglected tropical diseases
Yaws cool and dryness and may explain why skin lesions are
Yaws is a non-venereal endemic treponemal infection seen more often in the rainy season.4
caused by Treponema pallidum sub-species pertenue,1 a In the 1950s it was estimated that 50 million people
bacterium closely related to Treponema pallidum ssp. were infected with yaws. The World Health
pallidum, the agent of venereal syphilis. Yaws predom- Organization (WHO) tried to eliminate the disease
inantly affects children living in tropical regions of the through a mass treatment campaign using benzylpeni-
world. It causes lesions of the skin, mucous membranes cillin.2,5 Consequently, the number of infections world-
and bones which, without treatment, can become wide dropped significantly but yaws then fell off the
chronic and destructive. There is no widely available public health agenda. The next 30 years saw a resur-
test to distinguish yaws from syphilis. Thus, migration gence of cases and the disease is, again, a public health
of people from yaws-endemic areas to developed coun- problem in Africa,6 South-East Asia, the Pacific7,8 and
tries may present clinicians with diagnostic dilemmas. South America.9 The WHO estimates that 2.5 million
The other endemic treponemal infections are bejel individuals may currently be infected.2 A failure to
(endemic syphilis) caused by Treponema pallidum ssp.
endemicum and pinta caused by Treponema carateum.
1
Clinical Research Department, Faculty of Infectious and Tropical
Diseases, London School of Hygiene and Tropical Medicine, London, UK
Epidemiology 2
The Hospital for Tropical Diseases, Mortimer Market Centre, Mortimer
Market, London, UK
Yaws is currently thought to be endemic in at least 12 3
Department of Sexual Health and HIV, North Manchester General
countries2,3 (Table 1). The number of notified yaws Hospital, Manchester, UK
cases is almost certainly an underestimate of true dis-
ease incidence. Yaws primarily affects children living in Corresponding author:
Michael Marks, Clinical Research Department, Faculty of Infectious and
poor, densely-populated rural areas. The concentration Tropical Diseases, London School of Hygiene and Tropical Medicine,
of yaws in warm, humid climates is thought to be Keppel Street, London, UK.
explained by the sensitivity of T p pertenue to relative Email: michael.marks@lshtm.ac.uk
Marks et al. 697
Latent yaws
Individuals with latent yaws have reactive serological
tests but no clinical signs. It is not known how many
patients are infected without developing clinical dis-
ease. Patients with primary and secondary yaws may
pass into a period of latency after resolution of clinical
signs. As in syphilis, infectious relapses can occur, most
Figure 4. Secondary yaws: multiple small ulcerative lesions. commonly up to five years (rarely up to 10 years) after
Copyright Michael Marks. infection.1,20 Relapsing lesions tend to occur around the
axillae, anus and mouth.
Non-treponemal (cardiolipin) tests primary and secondary yaws, with a cure rate of
The venereal disease research laboratory (VDRL) and approximately 95%.38 No other treatment strategies
rapid plasma reagin (RPR) tests use an antigen of car- are supported by randomised controlled trials although
diolipin, lecithin and cholesterol. Patient-derived anti- data from case series suggest oral penicillin can be
bodies produced against lipid in the cell surface of successful.9
T pallidum react with antigen to cause visible floccula- Based on these findings, azithromycin is now central
tion. The VDRL is read microscopically whereas the to the WHO eradication plan for yaws, which aims to
RPR can be read with the naked eye. Although non- employ community mass treatment in endemic regions.
specific, VDRL/RPR titres best reflect disease activity. WHO plan to have no further cases of active yaws
Titres fall after treatment and may become zero, espe- worldwide by 2017 and to confirm eradication by
cially after treatment of early infection.31 RPR titres are 2020.39,40 Despite this optimism there are several bar-
generally higher in primary than secondary yaws.1 riers to a successful eradication programme including a
lack of accurate epidemiological data from many coun-
tries where yaws is reported, the absence of dedicated
Treponemal tests funding for eradication efforts and a concern that
These include the T pallidum haemagglutination resistance to azithromycin, well described in syphilis,41
(TPHA) and the T pallidum particle agglutination will emerge in yaws. Monitoring for this during the
(TPPA) tests. They are more specific than cardiolipin eradication programme will be essential. This ambi-
tests and usually remain positive after treatment. tious plan will require considerable input from NGOs,
Point-of-care tests have proved useful in syphilis and academic institutions and policy makers.
results of an initial study in Papua New Guinea suggest
they may also be of value in the diagnosis of yaws with
good sensitivity and specificity.32 Further studies of
Response to treatment
these tests in yaws are in progress. Treponemes disappear from lesions within 8–10 hours
of treatment with penicillin. Skin lesions begin to heal
within 2–4 weeks (Figure 8). In patients with secondary
Histology yaws, joint pains may begin to improve within as little
In early yaws there is marked epidermal hyperplasia as 48 hours.42 Bone changes are reversible if treated
and papillomatosis, often with focal spongiosis.33
Neutrophils accumulate in the epidermis, causing
microabscesses. A dense dermal infiltrate of plasma
cells is seen.34 In contrast with syphilis, there is little
endothelial cell proliferation or vascular obliteration.34
T pallidum can be identified in tissue sections using
Warthin-Starry or Levaditi silver stains. While T palli-
dum ssp. pertenue is found mainly in the epidermis, T
pallidum ssp. pallidum is identified more in the dermis.35
Direct and indirect immunofluorescence and immuno-
peroxidase tests using specific polyclonal antibodies to
T pallidum can also be used with histology specimens.36
Radiology
Bone involvement may be revealed by radiographs even
when clinical signs are absent (Figure 7).37
Treatment
Benzathine penicillin-G has been the mainstay of treat-
ment for yaws for over 60 years. Lower doses are used
compared to syphilis with a recommended dose of 0.6
MU for children (under 10) and 1.2 MU for older chil-
dren and adults. In a recent single-centre randomised
controlled trial, one dose of azithromycin 30 mg/kg was Figure 8. Primary yaws: healed Lesion. Copyright Michael
shown to be equivalent to penicillin in patients with Marks.
702 International Journal of STD & AIDS 26(10)
early enough. Following successful treatment the RPR this article: MM is supported by a Wellcome Trust Clinical
declines and at 12 months up to 90% of individuals Research Fellowship - WT102807. AWS is a Wellcome Trust
have either a four-fold reduction in RPR or become Intermediate Clinical Fellow (098521) at the London School
seronegative.43 Failure of skin lesions to heal or the of Hygiene & Tropical Medicine.
RPR to drop should be considered treatment failure
and an indication for repeat treatment. In endemic set-
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