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Nonvenereal endemic treponematoses: yaws, endemic syphilis (bejel), and pinta 

Nonvenereal endemic treponematoses: yaws, endemic syphilis (bejel), and pinta
Chapter:
Nonvenereal endemic treponematoses: yaws, endemic syphilis (bejel), and pinta
Author(s):

David A. Warrell

DOI:
10.1093/med/9780199204854.003.070635_update_001

Update:

Differences between T. p. pallidum and T. p. pertenue strains—explored by comparing their whole genomes.

Updated on 31 May 2012. The previous version of this content can be found here.
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Essentials

The endemic treponematoses are chronic, granulomatous diseases caused by morphologically and serologically identical spirochaetes of the genus Treponema. They are spread by intimate but nonsexual contact and sometimes by fomites, mainly among children. Treponema pallidum subsp. pertenue causing yaws (framboesia), T. pallidum subsp. endemicum causing endemic syphilis (bejel) and T. carateum causing pinta (carate) are distinguishable from T. pallidum subsp. pallidum, causing venereal syphilis, by their epidemiology and pathological effects and genomic structure (e.g. the arp gene).

Despite the successful WHO/UNICEF mass penicillin treatment campaign (1952–64), there has been a resurgence of yaws, mainly in West Africa. Children living in rural areas in warm, humid climates in tropical countries are most affected by yaws. About 10% of untreated cases develop late, disfiguring, or crippling lesions of skin, bone, and cartilage.

Endemic syphilis occurs in arid areas of the Sahel and Arabian peninsula. It presents with buccal mucocutaneous lesions from contaminated cups. Late systemic effects are much less common than in venereal syphilis. Pinta persists in small foci in southern Mexico and South America, causing hypo- or hyper-pigmented skin lesions. Single-dose benzathine penicillin is effective treatment.

Prevention is by improving hygiene and eliminating the reservoir of infection by mass treatment.

Acknowledgement: The author gratefully acknowledges inclusion of material from previous editions by his late friend and colleague Dr Peter L Perine.

Introduction

Syphilis (Chapter 7.6.36) and the nonvenereal treponematoses are distinguishable by their epidemiological characteristics and the pattern of infection produced in humans and experimentally infected laboratory animals (Table 7.6.35.1). Yaws is caused by Treponema pallidum subsp. pertenue, a spirochaete that is morphologically identical to T. pallidum subsp. pallidum (the cause of venereal syphilis), T. pallidum subsp. endemicum (the cause of nonvenereal syphilis or bejel), and T. carateum (the cause of pinta). None is cultivable in vitro. They share common antigens so that infection by one species produces varying degrees of cross-immunity to the others. They are serologically indistinguishable. Pathogenic treponemes can be differentiated by polymerase chain reaction using acidic repeat protein (arp) gene sequences. The genomes of eight treponemes have been compared. Restriction target site analysis revealed a high genome structure similarity of all strains. Most of the genetic differences between T. p. pallidum and T. p. pertenue strains were accumulated in six genomic regions and are likely to contribute to the marked differences in pathogenicity between these strains. These regions of sequence divergence might be used for the molecular detection and discrimination of syphilis and yaws strains. The treponemes of yaws, syphilis, and pinta are fragile and readily killed by exposure to atmospheric oxygen, drying, mild detergents, or antiseptics. They cannot penetrate intact skin, but gain entry to the body through small abrasions and lacerations. They prefer cooler temperatures, below 37° C, which may explain their predilection for the skin and bones of the extremities. All cause chronic granulomatous diseases that exhibit primary, secondary, and tertiary (late) stages separated by quiescent or latent periods. Most of their pathological effects are immune-mediated, the peak of the immune response preceding healing. Some spirochaetes survive in tissues and can cause exacerbations as immunity declines.

Table 7.6.35.1 Major features of the treponematoses

Feature

Venereal syphilis

Yaws

Endemic syphilis

Pinta

Organism

T. pallidum subsp. pallidum

T. pallidum subsp. pertenue

T. pallidum subsp. endemicum

T. carateum

Age of infection (years)

20–40

5–15

2–10

10–30

Occurrence

Worldwide

Africa, South America, Oceania, Asia

Africa, Middle East

Central and South America

Climate

All

Warm, humid

Dry, arid

Warm, rural

Direct transmission:

Venereal

Common

No

Rare

No

Nonvenereal

Rare

Common

Rare

Common

Congenital

Yes

No

?

No

Indirect transmission:

Contaminated utensils

Rare

Rare

Common

No

Insects

No

Rare

No

?

Reservoir of infection

Adults

Infectious and latent cases; ?nonhuman primates

Infectious and latent cases

Ratio infectious:latent cases

1:3

1:3–5

1:2

?

Late complications:

Skin

+

+

+

+

Bone, cartilage

+

+

+

No

Neurological

+

No

?

No

Cardiovascular

+

No

?

No

Yaws

Epidemiology

Yaws is a chronic infection by T. pallidum subsp. pertenue of skin, bone, and cartilage and periodically the organism spreads systemically. It is nonvenereal and noncongenital and is predominantly a disease of children. Seventy-five per cent of those acutely infected are below the age of 15 years and the peak incidence is between the ages of 6 and 10 years. In endemic areas more than 80% of the population are infected. The organism is transmitted by direct contact of broken skin with an infectious lesion or by fingers or bites contaminated with lesion exudate or rarely indirectly through fomites. Spread is promoted by crowded, unhygienic conditions. In humid, warm environments the early lesion tends to proliferate and teems with spirochaetes, thus increasing the infectious reservoir, whereas in dry, arid climates or seasons the reverse is true. Yaws is rarely fatal but frequently disfiguring and debilitating.

During the 1952–64 World Health Organization UNICEF campaign, an estimated 152 million people were examined and 46.1 million clinical cases, latent infections, and contacts were treated with penicillin in 46 countries, reducing the global prevalence by 95% from 50 to 2.5 million cases and greatly diminishing the yaws reservoir in West and Central Africa, Central and South America, and Oceania. This campaign initiated development of primary health care in many countries. Unfortunately, since the late 1970s there has been a resurgence, initially after control was delegated to national authorities. Seven West African countries started new mass treatment campaigns in the 1980s, but by 1995 the estimated global prevalence of infectious cases was 460 000, with 400 000 of them being in West Africa. Yaws was eliminated in India by 2004, but it persists in rural populations in West Africa (e.g. 26 000 new cases in Ghana in 2005), Ethiopia, South-East Asia (5000 new cases in Indonesia, East Timor), Papua New Guinea (18 000 new cases), Solomon Islands, Vanuatu, and Ecuador. The current worldwide prevalence of infectious cases of yaws may be c.500 000. Some African countries such as Nigeria, previously rendered yaws-free by mass treatment campaigns, have experienced a sharp rise in the incidence of venereal syphilis, perhaps reflecting the decline of herd immunity to yaws. Yaws is also prevalent in some gorilla populations.

Pathogenesis

The lesions of yaws and the other treponematoses are due largely to the host’s immune response to the treponeme. None of these treponemes carries or produces toxic substances. They have the ability to invade living cells without causing apparent injury. Cell destruction and tissue damage are probably due to the action of immune cells that injure normal tissue in the process of killing treponemes.

Host immunity reaches its highest level after several months of infection, just before disseminated lesions heal and latency begins. Thereafter the host is immune to reinfection and is not contagious, but since not all treponemes are killed, infectious lesions may reappear as immunity wanes over time. Most patients with yaws experience two or three infectious relapses during the first 5 years of infection.

Clinical features

Primary yaws

After an incubation period of 3 to 5 weeks, the initial lesion in yaws usually appears on the extremities. Characteristically, the primary lesion is a single painless papule that appears at the site of infection and enlarges to form a raspberry-like (framboesia) vegetative lesion called a papilloma. This is round to oval, elevated, and not indurated, ranging in size from 1 to 3 cm in diameter (Fig. 7.6.35.1). The surface teems with spirochaetes and is often covered by a thin yellow crust that is easily removed. It may ulcerate as it enlarges and becomes secondarily infected with other microorganisms. Lymph nodes draining the initial lesion may enlarge and become tender, but systemic symptoms are rare.

Fig. 7.6.35.1 Primary yaws lesion with ulceration and satellites.

Fig. 7.6.35.1
Primary yaws lesion with ulceration and satellites.

(Courtesy of Dr B Hudson, Sydney, Australia.)

Secondary yaws

Secondary or disseminated ulceropapillomatous or maculopapular lesions appear after 2 to 6 months, often without any intervening latent period, on the skin of moist areas such as the axillae, joint flexures, genitalia, and the gluteal cleft (Fig. 7.6.35.2a,b). They also occur on the soles and palms and, because they are tender, may interfere with gait and use of the hands. Papillomas in different stages of development persist for 6 to 8 months and heal without scars unless they become secondarily infected. Despite the size and number of lesions, children with generalized papillomas experience little discomfort or other constitutional symptoms.

Fig. 7.6.35.2 (a,b) Early ulceropapillomatous secondary yaws.

Fig. 7.6.35.2
(a,b) Early ulceropapillomatous secondary yaws.

(Courtesy of Dr B Hudson, Sydney, Australia.)

When the climate is arid, yaws lesions are commonly slightly raised scaly pigmented macules measuring between 1 and 4 cm in diameter. They have the same distribution as papillomas and may appear together with lesions of different morphology in the same patient (maculopapular yaws).

The periosteum and bones of the extremities are frequently inflamed during early yaws causing swelling, night pain, and tenderness. There is dactylitis of the proximal phalanges (Fig. 7.6.35.4). Painful osteoperiostitis of the legs, affecting mainly the tibias and fibulas, is especially common (Fig. 7.6.35.5). Hypertrophic osteitis of the maxilla, either side of the bridge of the nose, can cause grotesque swellings (‘goundo’). Scaly tender hyperkeratotic lesions of the palms and soles also occur and may be incapacitating. Hyperkeratotic and bone lesions are not contagious, and macular lesions are only minimally so.

Fig. 7.6.35.4 Dactylitis.

Fig. 7.6.35.4
Dactylitis.

(Courtesy of Dr B Hudson, Sydney, Australia.)

Fig. 7.6.35.5 (a,b) Osteoperiostitis.

Fig. 7.6.35.5
(a,b) Osteoperiostitis.

(Courtesy of Dr B Hudson, Sydney, Australia.)

One or more relapses of secondary-type lesions usually occur during the first 5 years of infection, each separated by a period of latency. The lesions of late yaws occur thereafter in about 10% of untreated cases.

Late yaws

The lesions are not infectious because they contain few treponemes. Cutaneous plaques produce atrophic scars. Subcutaneous granulomatous nodules erode skin and produce deep ulcers that destroy underlying tissue and cause disfigurement. Hyperkeratotic palmar and plantar yaws (Fig. 7.6.35.3) are incapacitating and often prevent the use of the hands or the ability to walk normally. The weight is placed on the sides of the feet, which produces a gait much like that of a crab (‘crab yaws’).

Fig. 7.6.35.3 Plantar papillomas with hyperkeratotic, macular, early plantar yaws (‘crab yaws’). These lesions are painful.

Fig. 7.6.35.3
Plantar papillomas with hyperkeratotic, macular, early plantar yaws (‘crab yaws’). These lesions are painful.

(Courtesy of Dr B Hudson, Sydney, Australia.)

The granulomas of late yaws have a histological appearance that is similar to the gummas of syphilis. These proliferative lesions may involve the palate and destroy the soft tissues of the nose, causing a terrible disfiguration called gangosa (Fig. 7.6.35.6a,b). Gummatous periostitis of the skull, fingers, and long bones is erosive and often retards or stops growth. Active periostitis is occasionally found in young and middle-aged adults who had yaws in childhood. Burnt out osteitis leads to a characteristic deformity ‘sabre tibia’.

Fig. 7.6.35.6 (a,b) Gangosa (rhinopharyngitis mutilans) of endemic syphilis and yaws.

Fig. 7.6.35.6
(a,b) Gangosa (rhinopharyngitis mutilans) of endemic syphilis and yaws.

(Courtesy of Dr B Hudson, Sydney, Australia.)

Endemic syphilis

T. pallidum subsp. endemicum is transmitted by nonvenereal contact among children. In contrast to yaws, transmission by contaminated drinking vessels may be more common than by direct contact with infectious lesions. The disease tends to be familial, with spread of infection from children to adults rather than to the community in general. The lesions are virtually indistinguishable from early yaws, and the two diseases may occur at different times in the same population but not in the same person. Venereal syphilis can be acquired by children through social contact with adults who have venereal syphilis, and then be spread by nonvenereal person-to-person contact if levels of sanitation and personal hygiene are low.

Several variants of endemic syphilis are recognized by their geographical distribution: bejel of the eastern Mediterranean, North Africa, and Niger; and njovera or dichuchwa of Africa. Bejel is the only type of endemic syphilis still prevalent. It is found in seminomadic people such as the Tuareg, living in the Sahelian nations of Mauritania, Mali, Niger, Burkina Faso, and Senegal where dramatic increases in the number of cases of endemic syphilis have been reported. In Naimey (Niger), seroprevalence was 12% among children under 5 years of age. The disease is also prevalent among the nomadic tribes of the Arabian peninsula, where late complications such as osteoperiostitis predominate.

Clinical features

The initial lesions of endemic syphilis usually appear at the mucocutaneous borders of the mouth or on the oral mucous membranes (mucous patches) as the result of transmission by contaminated drinking vessels. Late ulceronodules and osteoperiostitis are seen in late endemic syphilis, but cardiovascular and neurological complications are extremely rare.

Pinta (carate)

T. carateum resides only in the skin. This peculiar tissue tropism is unexplained. It is probably an inherent property of the treponeme, acting in contact with climatic factors. Pinta is confined to remote parts of Central and South America, principally in the semiarid region of the Tepalcatepec Basin of southern Mexico and focal areas of Colombia, Peru, Ecuador, and Venezuela. Pinta is probably transmitted by direct skin or mucous membrane contact, by insect bites, and perhaps by tribal rituals resulting in skin scratches.

Clinical features

After an incubation period of 15 to 30 days, the primary lesions, single or few in number, are seen on the dorsal surfaces of the limbs, face, chest, or gluteal area, usually of children or young adults (Fig. 7.6.35.7). The lesion is an itchy erythematous papule or depigmented macule that enlarges slowly over a period of several weeks or months to form an erythematous plaque, sometimes with regional lymphadenopathy but without systemic symptoms. Satellite papules form at its edge and undergo a similar type of evolution. The plaques coalesce to form violaceous pigmented plaques that, in several years, slowly depigment from lighter shades of blue to white, leaving symmetrical atrophic depigmented scars.

Fig. 7.6.35.7 (a–c) Early lesions of pinta in Yaruro people of north-western Venezuela.

Fig. 7.6.35.7
(a–c) Early lesions of pinta in Yaruro people of north-western Venezuela.

(Courtesy of Prof. Rolando Hernández Pérez, Hospital Universitario ‘Dr. Luis Razetti’ Barinas, Universidad de los Andes, Venezuela.)

Rapid dissemination of lesions may occur months or up to about 4 years after the primary lesions, frequently affecting scalp, nails, and mucous membranes (Fig. 7.6.35.8). Depigmented, pigmented, and erythematous-desquamative lesions may occur simultaneously in the same patient. Late lesions are symmetrical, depigmented, atrophic, or hyperkeratotic.

Fig. 7.6.35.8 (a–c) Disseminated lesions of pinta in Yaruro people of north-western Venezuela.

Fig. 7.6.35.8
(a–c) Disseminated lesions of pinta in Yaruro people of north-western Venezuela.

(Courtesy of Prof. Rolando Hernández Pérez, Hospital Universitario ‘Dr. Luis Razetti’ Barinas, Universidad de los Andes, Venezuela.)

Diagnosis

The diagnosis of yaws and other endemic treponematoses is made by a combination of clinical assessment, of positive dark-ground examination of early lesions and exudates which are usually teeming with treponemes, and of reactive serological tests for syphilis.

Early yaws, endemic syphilis, and pinta are not difficult to diagnose in endemic areas where the disease is familiar. The most difficult diagnostic problem arises when someone who had yaws as a child emigrates to an area of the world where the disease never existed. Such a person usually has reactive serological tests for syphilis and may have a few atrophic scars suggestive of earlier infection. What are the chances that this patient has or has had venereal syphilis? Should they be treated for latent yaws or syphilis? The patient’s social and medical history should be carefully reviewed. Clinical findings suggestive of old yaws (scars, inactive tibial periostitis), and the absence of signs of congenital and venereal syphilis support the diagnosis of inactive or treated yaws.

If the patient has a reagin titre (Venereal Disease Research Laboratory (VDRL), rapid plasma reagin (RPR)) of less than 1:8 dilutions, they probably do not have active latent yaws or syphilis. If they received at least one therapeutic dose of long-acting penicillin in their native country during a yaws campaign, they require no further treatment. On the other hand, if the patient is a contact of a case of infectious venereal syphilis, they should be treated as being potentially infected with syphilis because T. pallidum subsp. pallidum occasionally superinfects people who had yaws as children. If treatment is given, the patient should receive a certificate stating the drug and dosage used and the results of their serological tests to prevent unnecessary future treatment.

Differential diagnosis

Ulceronodular skin lesions of yaws and endemic syphilis resemble tropical ulcers. Yaws lesions are not as painful, necrotic, or deep as tropical ulcers, which are usually singular and restricted to the lower one-third of the leg. Plantar warts are frequently confused with plantar papillomas of yaws, and both conditions may occur in the same patient. Pinta must be differentiated from other hypopigmented and hyperpigmented skin lesions including vitiligo, indeterminate leprosy, pityriasis alba, and psoriasis.

Treatment

Long-acting benzylpenicillin given by intramuscular injection is the recommended treatment for all the endemic treponematoses. The preparation used in previous mass treatment campaigns was penicillin aluminium monostearate (PAM), but benzathine penicillin is currently recommended because it is longer acting and more readily available than is PAM. People who have active infections or who are noninfectious should be given 1.2 mega units in a single intramuscular injection; children under 10 years of age receive 0.6 mega units. Patients allergic to penicillin may be given tetracycline or erythromycin, 500 mg by mouth four times daily for 2 weeks; children under 10 years of age should be given erythromycin in dosages adjusted for their age. Treatment failures have been reported in Papua New Guinea.

Prevention and control

Transmission is reduced as personal hygiene among children improves. Prevention of yaws and other endemic treponematoses in a community requires elimination of the reservoir of infection, often by treating the entire population with penicillin. This has succeeded in some countries, notably recently with yaws in India.

Further reading

Antal GM, Lukehart SA, Meheus AZ (2002). The endemic treponematoses. Microbes Infect, 4, 83–94.Find this resource:

Engelkens HJ, Vuzevski VD, Stolz E (1999). Non-venereal treponematoses in tropical countries. Clin Dermatol, 17, 105–6, 143–52.Find this resource:

Farnsworth N, Rosen T (2006). Endemic treponematosis: review and update. Clin Dermatol, 24, 181–90.Find this resource:

Guthe T (1969). Clinical, serological and epidemiological features of framboesia tropica (yaws) and its control in rural communities. Acta Derm Venereol, 49, 343–68.Find this resource:

Hackett CJ, Loewenthal LJA (1960). Differential diagnosis of yaws. World Health Organization, Geneva.Find this resource:

    Harper KN, et al. (2008). On the origin of the treponematoses: a phylogenetic approach. PLoS Negl Trop Dis, 2, e148.Find this resource:

    Harper KN, et al. (2008). The sequence of the acidic repeat protein (arp) gene differentiates venereal from nonvenereal Treponema pallidum subspecies, and the gene has evolved under strong positive selection in the subspecies that causes syphilis. FEMS Immunol Med Microbiol, 53, 322–32.Find this resource:

    Padilha Gonçalves A, Basset A, Maleville J (1992). Tropical treponematoses. In: Canizares O, Harman RRM (eds) Clinical tropical dermatology, 2nd edition, pp. 129–50. Blackwell, Boston.Find this resource:

      Perine PL, et al. (1984). Handbook of endemic treponematoses: yaws, endemic syphilis and pinta. World Health Organization, Geneva.Find this resource:

        Smajs D, Norris SJ, Weinstock GM (2011). Genetic diversity in Treponema pallidum: Implications for pathogenesis, evolution and molecular diagnostics of syphilis and yaws. Infect Genet Evol, 2011 Dec 15. [Epub ahead of print]Find this resource:

          Walker SL, Hay RJ (2000). Yaws: a review of the last 50 years. Int J Dermatol, 39, 258–60.Find this resource: