1411CHAPTER 182 Syphilis

Both are reactive in persons with any treponemal infection, including

syphilis, yaws, pinta, and endemic syphilis.

The most widely used lipoidal antibody tests are the RPR and VDRL

tests, which measure IgG and IgM directed against a cardiolipinlecithin-cholesterol antigen complex. The RPR test is easier to perform

and uses unheated serum or plasma; it is the test of choice for rapid

serologic diagnosis in a clinical setting. The VDRL test remains the

standard for examining CSF and is superior to the RPR for this purpose. Either test is recommended for screening and for quantitation of

serum antibody. The titer reflects disease activity, rising during early

syphilis, often exceeding 1:32 in secondary syphilis, and declining

slowly thereafter without therapy. After treatment for early syphilis,

a persistent fall by fourfold or more (e.g., a decline from 1:32 to 1:8)

is considered an adequate response. VDRL titers do not correspond

directly to RPR titers, and sequential quantitative testing (as for

response to therapy) must employ a single test. A reactive VDRL/RPR

screening test must be confirmed by a treponemal test to rule out a

biological false-positive reaction.

Treponemal tests measure antibodies to native or recombinant T.

pallidum antigens and include the fluorescent treponemal antibody–

absorbed (FTA-ABS) test and the T. pallidum particle agglutination

(TPPA) test, both of which are more sensitive for primary syphilis than

the lipoidal tests. When used to confirm reactive lipoidal test results,

treponemal tests have a very high positive predictive value for diagnosis of syphilis.

Treponemal enzyme or chemiluminescence immunoassays (EIAs/

CIAs), based largely on reactivity to recombinant antigens, are now

widely used as screening tests by large laboratories. When these tests

are used for screening, a high proportion of sera reactive by EIA/CIA

are nonreactive by lipoidal tests. Such sera should be examined in the

TPPA test, which includes different antigens and a different platform.

If the TPPA test is nonreactive, the patient is unlikely to have syphilis;

if it is reactive, the patient is likely to have current or past syphilis.

Both lipoidal and treponemal tests may be nonreactive in early primary syphilis, although treponemal tests are slightly more sensitive

(85–90%) during this stage than lipoidal tests (~80%). All tests are

reactive during secondary syphilis. (Fewer than 1% of patients with

high titers have a lipoidal test that is nonreactive or weakly reactive

with undiluted serum but is reactive with diluted serum—the prozone

phenomenon.) VDRL and RPR sensitivity and titers may decline in

untreated persons with late latent syphilis, but treponemal tests remain

reactive in late syphilis. After treatment for early syphilis, lipoidal

test titers will generally decline or the tests will become nonreactive,

whereas treponemal tests often remain reactive after therapy and are

not helpful in determining the infection status of persons with past

syphilis. There is some concern in the literature about persons in whom

the lipoidal test titer fails to become nonreactive or remains reactive in

low titer after treatment. The implications in such cases are unclear, but

re-treatment rarely achieves the desired goal and is not recommended

in the absence of clinical findings.

False-Positive Serologic Tests for Syphilis The lipid antigens

of nontreponemal tests are similar to those found in human tissues,

and these tests may be reactive (usually with titers ≤1:8) in persons

without treponemal infection, largely limited to persons with autoimmune conditions or injection drug use. Among patients being screened

for syphilis because of risk factors, clinical suspicion, or history of

exposure, ~1% of reactive tests are falsely positive. In a patient with a

false-positive nontreponemal test, syphilis is excluded by a nonreactive

treponemal test.

False-positive reactions may also occur with treponemal tests, particularly the EIA/CIA tests. Screening a low-prevalence population for

syphilis with a treponemal test may result in true-positive reactions

being outnumbered by false-positive reactions, leading to unnecessary

treatment. Thus, screening with lipoidal tests is highly recommended.

■ EVALUATION FOR NEUROSYPHILIS

Involvement of the CNS is detected by examination of CSF for mononuclear pleocytosis (>5 white blood cells/μL), increased protein concentration (>45 mg/dL), or CSF VDRL reactivity. Elevated CSF cell

counts and protein concentrations are not specific for neurosyphilis

and may be confounded by HIV co-infection. Because CSF pleocytosis

may also be due to HIV, some studies have suggested using a CSF white

cell cutoff of 20 cells/μL as diagnostic of neurosyphilis in HIV-infected

patients with syphilis. The CSF VDRL test is highly specific and, when

reactive, is considered diagnostic of neurosyphilis; however, this test is

insensitive and may be nonreactive even in cases of symptomatic neurosyphilis. The RPR test should not be substituted for the VDRL test for

CSF examination. The FTA-ABS test on CSF is reactive far more often

than the CSF VDRL test in all stages of syphilis, but reactivity may

reflect passive transfer of serum antibody into the CSF. A nonreactive

FTA-ABS test on CSF, however, may be used to rule out asymptomatic

neurosyphilis. Measuring CXCL13 in CSF has been demonstrated to

distinguish between neurosyphilis and HIV-related CSF abnormalities.

All T. pallidum–infected patients with signs or symptoms consistent

with neurologic disease (e.g., meningitis, hearing loss) or ophthalmic

disease (e.g., uveitis, iritis) should have a CSF examination, regardless of disease stage. The appropriate management of asymptomatic

persons is less clear. Lumbar puncture on all asymptomatic patients

with untreated syphilis is impractical and unnecessary. Even at high

doses, penicillin G benzathine fails to result in treponemicidal drug

levels in CSF, and viable T. pallidum have been isolated from the CSF

of patients (with and without HIV infection) after penicillin G benzathine treatment for early syphilis. Therefore, it is important to identify

those persons at higher risk for having or developing neurosyphilis

so that appropriate treatment may be given. Large-scale prospective

studies have provided evidence-based guidelines for determining

which syphilis patients may benefit most from CSF examination. Specifically, patients with RPR titers of ≥1:32 are at higher risk of having

neurosyphilis (11-fold and 6-fold higher in HIV-infected and HIVuninfected persons, respectively), as are HIV-infected patients with

CD4+ T-cell counts of ≤350/μL. Persons with active tertiary syphilis

and those in whom treatment failure is suspected should also have their

CSF examined to determine appropriate therapy.

■ EVALUATION OF HIV-INFECTED PATIENTS FOR

SYPHILIS

Because persons at highest risk for syphilis are also at increased risk

for HIV infection, these two infections frequently coexist. There is

evidence that syphilis and other genital ulcer diseases are important

risk factors for acquisition and transmission of HIV infection. Some

manifestations of syphilis may be altered in patients with concurrent

untreated HIV infection, and multiple cases of neurologic relapse after

standard therapy have been reported in these patients.

Persons with newly diagnosed HIV infection should be tested for

syphilis; conversely, all patients with newly diagnosed syphilis should

be tested for HIV infection. Some authorities, persuaded by reports of

persistent T. pallidum in CSF of HIV-infected persons after standard

therapy for early syphilis, recommend CSF examination for evidence of

neurosyphilis for all co-infected patients, regardless of the stage of syphilis, with treatment for neurosyphilis if CSF abnormalities are found.

Others, on the basis of their own clinical experience, think that standard

therapy—without CSF examination—is sufficient for all cases of early

syphilis in HIV-infected patients without neurologic signs or symptoms. As described above, RPR titer and CD4+ T-cell count can be used

to identify patients at higher risk of neurosyphilis for lumbar puncture,

although some cases of neurosyphilis will be missed even when these

criteria are used. Serologic testing after treatment is important for all

patients with syphilis, particularly for those also infected with HIV.

TREATMENT

Syphilis

TREATMENT OF ACQUIRED SYPHILIS

The CDC’s 2015 guidelines for the treatment of syphilis are summarized in Table 182-1 and are discussed below. Penicillin G is

the drug of choice for all stages of syphilis. T. pallidum is killed by

very low concentrations of penicillin G, although a long period of

1412 PART 5 Infectious Diseases

exposure to penicillin is required because of the unusually slow

rate of multiplication of the organism. The efficacy of penicillin

against syphilis remains undiminished after 75 years of use, and

there is no evidence of penicillin resistance in T. pallidum. Other

antibiotics effective in syphilis include the tetracyclines and the

cephalosporins. Aminoglycosides and spectinomycin inhibit T. pallidum only in very large doses, and the sulfonamides and most

quinolones are inactive. Azithromycin showed significant promise

as an effective oral agent against T. pallidum; however, strains harboring 23S rDNA mutations that confer macrolide resistance are

widespread. Such strains represent >80–90% of recent isolates from

large U.S., European, and Chinese cities, although the prevalence

of resistant strains varies by geographic location. Routine treatment of syphilis with azithromycin is not recommended. Careful

follow-up of any patient treated for syphilis with azithromycin must

be assured.

Early Syphilis Patients and Their Contacts Penicillin G benzathine is the most widely used agent for the treatment of early syphilis (2.4 million units; Table 182-1), and for preventive treatment

of individuals exposed to infectious syphilis within the previous

3 months. The regimens recommended for prevention are the same as

those recommended for early syphilis. Penicillin G benzathine cures

>95% of cases of early syphilis, although clinical relapse can follow

treatment, particularly in patients with untreated HIV infection.

Because the risk of neurologic relapse may be higher in HIVinfected patients, CSF examination is recommended for HIVseropositive individuals with syphilis of any stage, particularly those

with a serum RPR titer of ≥1:32 or a CD4+ T-cell count of ≤350/μL.

Therapy appropriate for neurosyphilis should be given if there is

any evidence of CNS infection.

Late Latent Syphilis or Syphilis of Unknown Duration If the

CSF is normal or is not examined, the recommended treatment

is penicillin G benzathine (7.2 million units total; Table 182-1).

If CSF abnormalities are found, the patient should be treated for

neurosyphilis.

Tertiary Syphilis CSF examination should be performed. If the

CSF is normal, the recommended treatment is penicillin G benzathine (7.2 million units total; Table 182-1). If CSF is abnormal, the

patient should be treated for neurosyphilis. The clinical response

to treatment for benign tertiary syphilis is usually impressive, but

responses in cardiovascular syphilis are not dramatic because aortic

aneurysm and aortic regurgitation cannot be reversed by antibiotics.

Syphilis in Penicillin-Allergic Patients For penicillin-allergic

patients with syphilis, a 2-week (early syphilis) or 4-week (late or

late latent syphilis) course of therapy with doxycycline or tetracycline

is recommended (Table 182-1). These regimens appear to be quite

effective in early syphilis but have not been tested for late or late latent

syphilis, and compliance may be problematic. Limited studies suggest

that ceftriaxone (1 g/d, given IM or IV for 8–10 days) is effective for

early syphilis. These nonpenicillin regimens have not been carefully

evaluated in HIV-infected individuals and should be used with caution. If compliance and follow-up are not assured, penicillin-allergic

HIV-infected persons with late latent or late syphilis should be

desensitized and treated with penicillin.

Neurosyphilis Penicillin G benzathine, even at high doses, does

not produce treponemicidal concentrations of penicillin G in CSF

and should not be used for treatment of neurosyphilis. Asymptomatic

neurosyphilis may relapse as symptomatic disease after treatment

with benzathine penicillin, and the risk of relapse may be higher in

HIV-infected patients. Both symptomatic and asymptomatic neurosyphilis should be treated with aqueous penicillin (Table 182-1).

Administration of either IV aqueous crystalline penicillin G or of

IM aqueous procaine penicillin G plus oral probenecid in recommended doses is thought to ensure treponemicidal concentrations

of penicillin G in CSF. The clinical response to penicillin therapy

for meningeal syphilis is dramatic, but treatment of neurosyphilis

with existing parenchymal damage may only arrest disease progression. No data suggest that additional therapy (e.g., penicillin

G benzathine for 3 weeks) would be beneficial after treatment for

neurosyphilis.

The use of antibiotics other than penicillin G for the treatment

of neurosyphilis has not been studied, although limited data suggest that 1−2 g/d of IV ceftriaxone for 10−14 days may be used.

In patients with confirmed penicillin allergy, desensitization and

treatment with penicillin are recommended.

Management of Syphilis in Pregnancy Every pregnant woman

should undergo a lipoidal screening test at her first prenatal visit

and, if at high risk of re-exposure, again in the third trimester

and at delivery. In the untreated pregnant patient with presumed

syphilis, expeditious treatment appropriate to the stage of the disease is essential. Patients should be warned of the risk of a JarischHerxheimer reaction, which may be associated with mild premature contractions but rarely results in premature delivery.

Penicillin is the only recommended agent for the treatment of

syphilis in pregnancy. If the patient has a documented penicillin

allergy, desensitization and penicillin therapy should be undertaken

according to the CDC’s 2015 guidelines. After treatment, a quantitative nontreponemal test should be repeated monthly throughout

pregnancy to assess therapeutic efficacy. Treated women whose

antibody titers rise by fourfold or whose titers do not decrease by

fourfold over a 3-month period should be re-treated.

EVALUATION AND MANAGEMENT OF CONGENITAL

SYPHILIS

Whether or not they are infected, newborn infants of women with

reactive serologic tests may themselves have reactive tests because

of transplacental transfer of maternal IgG antibodies.

TABLE 182-1 Recommendations for the Treatment of Syphilisa

STAGE OF SYPHILIS

PATIENTS WITHOUT

PENICILLIN ALLERGY

PATIENTS WITH CONFIRMED

PENICILLIN ALLERGY

Primary, secondary,

or early latent

CSF normal or not

examined: Penicillin G

benzathine (single dose

of 2.4 mU IM)

CSF abnormal: Treat as

neurosyphilis.

CSF normal or not examined:

Doxycycline (100 mg PO bid)

or tetracycline HCl (500 mg PO

qid) for 2 weeks

CSF abnormal: Treat as

neurosyphilis.

Late latent (or

latent of unknown

duration),

cardiovascular, or

benign tertiary

CSF normal or not

examined: Penicillin G

benzathine (2.4 mU IM

weekly for 3 weeks)

CSF abnormal: Treat as

neurosyphilis.

CSF normal and patient

not infected with HIV:

Doxycycline (100 mg PO bid)

or tetracycline HCl (500 mg PO

qid) for 4 weeks

CSF normal and patient

infected with HIV: Desensitize

and treat with penicillin

if compliance cannot be

assured.

CSF abnormal: Treat as

neurosyphilis.

Neurosyphilis

(asymptomatic or

symptomatic)

Aqueous crystalline

penicillin G (18–24 mU/d

IV, given as 3–4 mU q4h

or continuous infusion)

for 10–14 days

or

Aqueous procaine

penicillin G (2.4 mU/d IM)

plus oral probenecid

(500 mg qid), both for

10–14 days

Desensitize and treat with

penicillin.

Syphilis in

pregnancy

According to stage Desensitize and treat with

penicillin.

a

See text for indications for CSF examination.

Abbreviations: CSF, cerebrospinal fluid; mU, million units.

Source: Adapted from the 2015 Sexually Transmitted Diseases Treatment Guidelines

from the Centers for Disease Control and Prevention. Available from https://www.

cdc.gov/std/tg2015/default.htm.

1413CHAPTER 183 Endemic Treponematoses

For asymptomatic infants born to women treated adequately

with penicillin during the first or second trimester of pregnancy,

monthly quantitative nontreponemal tests may be performed to

monitor for appropriate reduction in antibody titers. Rising or

persistent titers indicate infection, and the infant should be treated.

Detection of neonatal IgM antibody is insensitive, and no commercially available test is currently recommended.

An infant should be treated at birth if (1) the treatment status of

the seropositive mother is unknown; (2) the mother received inadequate or nonpenicillin therapy; (3) the mother received penicillin

therapy in the third trimester; or (4) the infant may be difficult

to follow. The CSF should be examined to obtain baseline values

before treatment. Penicillin is the only recommended drug for the

treatment of syphilis in infants. Specific recommendations for the

treatment of infants and older children are included in the CDC’s

2015 treatment guidelines.

JARISCH-HERXHEIMER REACTION

A dramatic although self-limited reaction consisting of fever,

chills, myalgia, headache, tachycardia, increased respiratory rate,

increased circulating neutrophil count, and vasodilation with mild

hypotension may follow the initiation of treatment for syphilis.

This reaction is thought to be a response to lipoproteins released

by dying T. pallidum organisms. The Jarisch-Herxheimer reaction

occurs in ~50% of patients with primary syphilis, 90% of those

with secondary syphilis, and a lower proportion of persons with

later-stage disease. Defervescence takes place within 12–24 h. In

secondary syphilis, erythema and edema of cutaneous lesions may

increase. Patients should be warned to expect such developments,

which can be managed with symptom-based treatment. Steroid

therapy is not required for this mild transient reaction.

FOLLOW-UP EVALUATION OF RESPONSES TO THERAPY

Efficacy of treatment should be assessed by clinical evaluation and

monitoring of the quantitative VDRL or RPR titer for a fourfold

decline (e.g., from 1:32 to 1:8). Patients with primary or secondary syphilis should be examined 6 and 12 months after treatment,

and persons with latent or late syphilis at 6, 12, and 24 months.

More frequent clinical and serologic examination (3, 6, 9, 12, and

24 months) is recommended for patients concurrently infected with

HIV, regardless of the stage of syphilis.

After successful treatment of seropositive first-episode primary

or secondary syphilis, the VDRL or RPR titer progressively declines;

the test becomes nonreactive by 12 months in 40–75% of seropositive primary cases and in 20–40% of secondary cases. In patients

with HIV infection or a history of prior syphilis, VDRL and RPR

tests are less likely to become nonreactive. Rates of decline of

serologic titers appear to be slower, and serologically defined treatment failures more common, among HIV-infected patients than

among those without HIV co-infection; however, effective ART

may reduce these differences. Re-treatment should be considered

if serologic responses are not adequate or if clinical signs persist or

recur. Because it is difficult to differentiate treatment failure from

reinfection, the CSF should be examined, with treatment for neurosyphilis if CSF is abnormal and treatment for late latent syphilis if

CSF is normal. A minority of patients treated for early syphilis may

experience a one-dilution titer increase within 14 days after treatment; however, this early elevation does not significantly affect the

serologic outcome at 6 months after treatment. Patients treated for

late latent syphilis frequently have low initial VDRL or RPR titers

and may not have a fourfold decline after therapy with penicillin.

In such patients, re-treatment is not warranted unless the titer rises

or signs and symptoms of syphilis appear. Because treponemal tests

may remain reactive despite treatment for seropositive syphilis,

these tests are not useful in following the response to therapy.

The activity of neurosyphilis (symptomatic or asymptomatic)

correlates best with CSF pleocytosis, and this measure provides the

most sensitive index of response to treatment. Repeat CSF examinations should be performed every 6 months until the cell count is

normal. An elevated CSF cell count falls to normal in 3–12 months

in adequately treated HIV-uninfected patients. The persistence of

mild pleocytosis in HIV-infected patients may be due to the presence of HIV in CSF; this scenario may be difficult to distinguish

from treatment failure. Elevated levels of CSF protein fall more

slowly, and the CSF VDRL titer declines gradually over several

years. In patients treated for neurosyphilis, a fourfold reduction in

serum RPR titer has been positively correlated with normalization

of CSF abnormalities; this correlation is stronger in HIV-uninfected

patients and in HIV-infected patients receiving effective ART.

IMMUNITY TO SYPHILIS

The rate of development of acquired resistance to T. pallidum after natural or experimental infection depends on both the size of the infecting inoculum and the duration of infection before treatment. Both

humoral and cellular responses are important in the healing of early

lesions. Cellular infiltration, predominantly by T lymphocytes and

macrophages, produces an interferon γ–dominated cytokine milieu

and results in the clearance of organisms by activated macrophages.

Specific antibodies to surface antigens enhance phagocytosis. Antigenic variation of the TprK protein contributes to development of subsequent stages of syphilis, persistence of infection, and susceptibility

to reinfection with another strain. Comparative genomic studies have

revealed genes with sequence variations among T. pallidum strains,

leading to development of molecular typing methods used to examine

syphilis outbreaks. Recent work has demonstrated that immunization

with the outer-membrane protein Tp0751 significantly reduces dissemination of T. pallidum during syphilis infection in an animal model.

Vaccine studies with this and other antigens are underway.

■ FURTHER READING

Beale MA et al: Genomic epidemiology of syphilis reveals independent emergence of macrolide resistance across multiple circulating

lineages. Nat Commun 10:3255, 2019.

Dombrowski JC et al: Prevalence estimates of complicated syphilis.

Sex Transm Dis 42:702, 2015.

Edmondson DG et al: Long-term in vitro culture of the syphilis spirochete Treponema pallidum subsp. pallidum. mBio 9:e01153, 2018.

Kenyon C et al: Repeat syphilis is more likely to be asymptomatic in HIV-infected individuals: A retrospective cohort analysis

with important implications for screening. Open Forum Infect Dis

5:ofy096, 2018.

Marra CM et al: Previous syphilis alters the course of subsequent

episodes of syphilis. Clin Infect Dis 71:1243, 2020.

The endemic treponematoses are chronic diseases that are transmitted by direct contact, usually during childhood and, like syphilis, can

cause severe late manifestations years after initial infection. These

diseases are caused by very close relatives of Treponema pallidum

subspecies pallidum, the etiologic agent of venereal syphilis (Chap.

182). Yaws, pinta, and endemic syphilis (bejel) have traditionally been

distinguished from venereal syphilis by mode of transmission, age of

acquisition, geographic distribution, and clinical features; however,

there is overlap for each of these factors. Our “knowledge” about these

infections is based on observations by health care workers who have

visited endemic areas during the past 70 years. Except for the ongoing

programs of mass drug administration (MDA) for yaws eradication

promoted by the World Health Organization (WHO), virtually no

well-designed studies of the natural history, diagnosis, or treatment of

183 Endemic Treponematoses

Sheila A. Lukehart, Lorenzo Giacani

1414 PART 5 Infectious Diseases

and persons with latent infections were treated. This campaign reduced

the prevalence of active yaws from >20% to <1% in many areas. In

subsequent decades, lack of focused surveillance and diversion of

resources resulted in documented resurgence of these infections in

some regions. Of nearly 100 countries previously endemic for yaws,

there are 15 countries with current yaws cases, and three others with

suspected cases; there are no data for the remaining countries. In

2018, a total of 80,472 suspected cases were reported, primarily from

countries in which focused yaws detection and treatment trials are

ongoing. Areas of resurgent yaws morbidity in Africa include Ivory

Coast, Ghana, Togo, Benin, Central African Republic, Nigeria, and

Democratic Republic of the Congo. The prevalence of endemic syphilis is estimated to be >10% in some regions of northern Ghana, Mali,

Niger, Burkina Faso, and Senegal, although data are scarce. In Asia

and the Pacific Islands, reports document active outbreaks of yaws in

TABLE 183-1 Comparison of the Treponemes and Associated Diseases

FEATURE VENEREAL SYPHILIS YAWS ENDEMIC SYPHILIS (BEJEL) PINTA

Organism T. pallidum subsp. pallidum T. pallidum subsp. pertenue T. pallidum subsp. endemicum T. carateum

Common modes of transmission Sexual, transplacental Skin-to-skin Mouth-to-mouth or via shared

drinking/eating utensilsa

Skin-to-skin

Usual age of acquisition Sexual maturity or in utero Early childhood Early childhood, recently

adulthood

Late childhood

Primary lesion Cutaneous ulcer (chancre) Papilloma, often ulcerative Mucosal papule, rarely seen Nonulcerating papule with

satellites, pruritic

Common location Genital, oral, anal Extremities Oral Extremities, face

Secondary lesions Cutaneous rash and

mucocutaneous lesions;

condylomata lata

Cutaneous papillomatous or

ulcerative lesions; condylomata

lata, osteoperiostitis

Mucocutaneous lesions

(mucous patch, split

papule, condylomata lata);

osteoperiostitis

Pintides, pigmented, pruritic

Infectious relapses ~25% Common Unknown Unknown

Late complications Gummas, cardiovascular

and central nervous system

involvementb

Destructive gummas of skin,

bone, cartilage

Destructive gummas of skin,

bone, cartilage

Nondestructive, dyschromic,

achromic macules

a

Sexual transmission has been recently postulated for endemic syphilis (see text). b

Central nervous system involvement and congenital infection in the endemic

treponematoses have been postulated by some investigators (see text).

Number of reported cases, 2016

≥10,000

1000-9999

<1000

Not reported since 2012

Not reported*

Countries with suspected cases

Previously endemic countries (current status unknown)

Non-endemic countries

FIGURE 183-1 Geographic distribution of yaws in 2016. *No data reported since 2008 (Timor Leste) or 2009 (Democratic Republic of Congo). (Adapted from http://www.who.

int/yaws/epidemiology/Yaws_map_2012.png?ua=1. 2016 data available at http://apps.who.int/gho/data/node.main.NTDYAWSNUM?lang=en and http://apps.who.int/gho/

data/node.main.NTDYAWSEND?lang=en. Reprinted with permission from World Health Organization.)

these infections have been conducted. The classically defined treponemal infections are compared and contrasted in Table 183-1.

■ EPIDEMIOLOGY

Generally, yaws flourishes in moist tropical areas (Fig. 183-1); endemic

syphilis has been found primarily in arid climates of West Africa and the

Middle East; and pinta has been found in temperate foci in the Americas. Because no recent epidemiologic data are available for bejel and

pinta, the current extent of these infections as classically described is

unknown. The endemic treponematoses have traditionally been limited

to rural areas of developing nations and have been seen in developed

countries primarily among recent immigrants from endemic regions.

In a WHO-sponsored mass eradication campaign from 1952 to

1969, >160 million people in Africa, Asia, and South America were

examined for treponemal infections, and >50 million cases, contacts,