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Treponema Pallidum

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Treponema pallidum, the etiologic agent of syphilis, is a member of the order of Spirochaetales.

Syphilis

Mary Allen Staat

INTRODUCTION
Syphilis is a sexually transmitted disease caused by Treponema pallidum. The organism is a thin, delicate spirochete 5 to 20 um long that has the appearance of a helical coil on darkfield microscopy or immunofluorescence. Human beings are the only host. The organism is readily destroyed at a temperature of 42°C (107.6°F), by soap and water, and by drying. Nearly all transmission is through sexual contact, although very close physical contact between mucous membranes might also permit transmission. Transmission by transfusion has been documented. Congenital syphilis may occur transplacentally or by passage through an infected birth canal. Long, clinically latent periods are common; the infection may persist through the patient’s lifetime with a variety of clinical manifestations.

Over the past decade there has been a decline in the number of reported cases of syphilis in the United States, reflected also in the decreasing number of infants with congenital syphilis. While the national rate of syphilis has declined to the lowest level ever recorded, rates still remain high in certain US counties. Pediatricians may have to treat children or adolescents with acquired syphilis or infants with congenital syphilis, but the most common presenting problem is the management of a well-appearing infant born to a serologically positive mother.

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ACQUIRED SYPHILIS

Children and adolescents who acquire syphilis follow a clinical course similar to adults. In infected children, sexual abuse must be presumed; laws require that a report be made and an investigation take place.

The incubation period is approximately 3 weeks (10-90 days) followed by the appearance of the primary stage, which is characterized by a painless indurated chancre that appears at the site of contact - the glans penis, the labia, or within the vagina. Primary lesions may also appear on the lips or tongue, within the anus, or on the cervix. Regional lymph nodes are usually very enlarged, hard, and painless. The chancre is usually positive for spirochetes when examined by either darkfield microscopy or immunofluorescence - the best ways to make the diagnosis. The serologic tests for syphilis (STS) may not yet be positive during the primary stage. The chancre usually disappears in 3 to 5 weeks without treatment, to be followed by the secondary stage. Secondary syphilis usually appears 6 to 10 weeks after the infection. It is characterized by malaise, fever, adenopathy, and a generalized cutaneous rash that may be macular, papular, papulosquamous, or bullous. Mucous patches are also common. Alopecia and condylomas may occur later. The patient is very infectious at this stage: the lesions are often positive for Treponema by either darkfield microscopy or immunofluorescence. The STSs are always positive at this stage. As the secondary stage subsides, the patient enters the latent phase. The patient continues to be seropositive without clinical manifestations. Late manifestations of syphilis (tertiary stage) are gummatous lesions, which are probably the result of hypersensitivity, as well as cardiovascular disease and neurosyphilis, both the result of longstanding vascular capillary disease and endarteritis. Tertiary syphilis is not a disease of children and thus is beyond the scope of this text.

DIAGNOSIS The diagnosis depends on correlating clinical findings with those of the serologic tests and the results of examination of the spinal fluid.

Serologic Tests There are two general categories of serologic tests for syphilis.

Nontreponemal antigen tests use a component of normal tissue (eg, beef-heart cardiolipin) as an antigen to measure reagin, a nonspecific antibody formed by syphilitic patients. The most common nontreponemal tests are Venereal Disease Research Laboratory (VDRL) and the rapid plasma reagin (RPR) flocculation tests. Older tests that use complement fixation (Kolmer and Wassermann) are less commonly used. The VDRL test usually becomes positive 4 to 6 weeks after the infection (several weeks after the primary lesion appears) and is almost always positive at a high titer (greater than 1:32) during the secondary stage. The titer often falls during the latent phase, as it does following therapy. False-positive reactions are encountered in nonvenereal treponemal infections, and, more importantly, in a wide variety of disease states, including infectious mononucleosis, collagen vascular diseases, malaria, drug addiction, many febrile diseases, and, occasionally, in pregnancy. The RPR test is a simpler test than the traditional VDRL, capable of automation, and in all respects comparable to VDRL.

Of the treponemal antigen tests, the most widely used is the fluorescent treponemal antibody absorption test (FTA-ABS). It is both sensitive and specific for treponemal antibody and is used extensively to determine whether positive nontreponemal antigen tests are, in fact, false-positives. The test is positive in most patients with primary syphilis and in virtually all patients with secondary disease; it usually remains permanently positive despite successful treatment. False-positive tests occur rarely in mixed connective tissue and autoimmune disease and other spirochetal diseases including Lyme disease. A microhemagglutination assay for antibody to T. pallidum (MHA-TP) is comparable to the FTA-ABS test. These assays measure IgG and, therefore, do not distinguish disease in an infant from passively transferred maternal antibody. Antitreponemal IgM antibody testing using a method recognized by the Centers for Disease Control and Prevention as a standard may be used to determine whether an infant has congenital syphilis. These tests, however, are not yet widely available.

Other Laboratory Tests Examination of dried smears of fluid or smears taken from syphilitic lesions can be performed by either darkfield microscopy or immunofluorescence to provide an early and specific diagnosis. The spinal fluid should be examined in selected patients because of the frequency and importance of neurosyphilis. Positive findings include an elevated cell count, an increase in the total protein and gamma globulin, and a positive reagin (VDRL) test. The VDRL is the preferred test to examine the spinal fluid; the FTA-ABS is highly sensitive but less specific (more false-positives).

TREATMENT Early syphilis (primary, secondary, or latent of less than 1 year’s duration) should be treated with a single injection of 2.4 million units of benzathine penicillin given intramuscularly for adults or teenagers. Syphilis of more than 1 year’s duration should be treated with benzathine penicillin 2.4 million units intramuscularly once a week for 3 consecutive weeks. Penicillin is the best therapeutic agent and the only one shown to protect the fetus. In penicillin-allergic individuals, tetracycline given orally for 2 weeks provides an alternative. Erythromycin for a similar period of time has also been used. The treatment of neurosyphilis and that of pregnant women requires a different therapeutic approach and is not dealt with here. Penicillin treatment may be complicated by a Jarisch-Herxheimer reaction manifested by fever and an aggravated clinical picture. It is ascribed to sudden massive destruction of spirochetes and release of their toxic products. Corticosteroid treatment is helpful in ameliorating this reaction. Sexual partners should be treated. Syphilis is a reportable disease. When syphilis is diagnosed, the patient should be examined for other sexually transmitted diseases, including HIV.

CONGENITAL SYPHILIS

Congenital syphilis results from the transplacental infection of the developing fetus. An infected pregnant woman has a high probability of transmitting the infection to the fetus (90% probability during the secondary stage). Treponema organisms can cross the placenta at any stage of pregnancy, but appear to elicit little tissue response before the 15th week of gestation. Adequate treatment of the mother with penicillin protects the fetus, but the mother may become reinfected. Fetal mortality is high in this infection - 25% of infected infants die in utero; another 25% die perinatally. The signs and symptoms are varied and may appear at any time between birth and 3 months of life, with 5 weeks as the median time of onset for those infants appearing normal at birth.

CLINICAL MANIFESTATIONS

Early Congenital (Prenatal) Syphilis The most severely infected infants are stillborn. Most live-born syphilitic infants have no visible lesions at birth. When lesions are present, they are most commonly on the skin and in the bones. In the first week of life, syphilis may produce bullous lesions of the skin on the palms and soles. No other syphilitic skin lesion at any age forms bullae or vesicles. The more usual pattern of skin involvement is a diffuse, symmetric, copper-colored maculopapular rash that is most intense on the face, palms, and soles. It is an infiltrative lesion that when gently scraped with a scalpel yields serum teeming with treponemas. Thus, either darkfield microscopy or direct fluorescent antibody examination may result in a rapid and definitive diagnosis. If left untreated, about 90% of syphilitic infants will eventually have some kind of skin lesion. Many varieties of papular skin rashes may occur and recur over the next months, with a high predilection for mucocutaneous sites - oral and anal. Perioral lesions may result in scarring, with fissures that persist. The recurrences become progressively less symmetric with time. The perianal condylomatous lesion (condyloma latum), so common in adults, is also seen in infancy (

Fig. 13-9).

A characteristic mucous membrane lesion of infants that has no counterpart in the adult is snuffles, a rhinitis producing a serous discharge that frequently becomes secondarily infected. Postinflammatory scarring beneath the nose is called rhagades. The lesion may extend to the nasal cartilage and cause sufficient damage to result in saddle-nose deformity.

Congenital syphilis produces widespread lesions in the skeleton, resulting in osteochondritis at metaphyseal plates, a generalized symmetric periosteal elevation, and symmetrically occurring osteomyelitic lesions on radiographs. The humerus is the most commonly involved bone, with the tibia next; indeed, if other bones are involved, these two are almost sure to be involved as well. A bilateral moth-eaten appearance of the medial aspects of the proximal tibia that is highly characteristic of congenital syphilis has been described. More than 90% of infants with congenital syphilis show skeletal lesions. The lesions typically begin between 1 and 3 months of age; the process is usually self-limited, with healing occurring spontaneously over the next few months. The rate of healing is not noticeably affected by treatment. Radiographic findings usually disappear by 5 months of age. The bone lesions are often asymptomatic. Occasionally, there is pain, often manifested by a pseudoparalysis that may be unilateral, involving either an arm or a leg (Parrot paralysis). Later in infancy, there may be recurring isolated bone lesions; dactylitis, frequently asymmetric, is a typical example.

Central nervous system involvement with abnormal cerebrospinal fluid findings are present in 40 to 60% of infants with syphilis. Jaundice as a manifestation of syphilitic hepatitis sometimes appears early in congenital syphilis and is resolved with treatment. Syphilitic pneumonitis or pneumonia alba is usually present in fatal cases, but is otherwise uncommon. Other viscera are involved less commonly. Splenomegaly and generalized lymphadenopathy are frequent manifestations of the early systemic illness. The epitrochlear nodes commonly enlarge. Involvement of the kidney, when present, takes the form of a glomerulonephritis that presents as nephrotic syndrome. Syphilis is responsible for almost half of all nephrotic syndrome in patients less than 6 months of age.

Late Congenital Syphilis Late congenital syphilis may be suspected from the stigmata, from the presence of continued active disease, or from persistently positive STSs in an asymptomatic child. In the 19th century, Hutchinson described certain complications of congenital syphilis, which are known as Hutchinson’s triad: Hutchinson’s incisors, interstitial keratitis, and eighth nerve deafness. The most common stigmata are Hutchinson teeth, a screwdriver or peg-shaped deformity of the upper central incisors of the second dentition (

Fig. 13-10). Molars may have extra cusps that are poorly formed and that crumble under normal use. All syphilitic teeth demonstrate deficient enamel and decay more readily than normal teeth. Hutchinson incisors are visible by radiography in its preeruptive site from about 1 year of age.

Interstitial keratitis begins between 3 and 20 years of age (most commonly between 6 and 14 years). It is an intense inflammatory vascular infiltration of the cornea accompanied by an iritis, which may be followed by a dense cicatricial scar that produces blindness. Although usually bilateral, it may appear in one eye before it appears in the other eye. The lesion is not prevented by treatment given after the first year of disease. Early stages are characterized by marked photophobia, lacrimation, and a hazy appearance of the cornea. Later, scarring occurs.

Other active forms of late disease are gummas and osteitis, which are among the late benign syphilitic lesions. The palate and nasal septum are predilectional sites for destructive gummas, with saddle nose and perforated palatal deformities possible end results. Persistent periostitis gives rise to thickened clavicles and to a usually asymmetric saber shin. Clutton joints are symmetric synovial effusions, usually of the knees, that are sometimes painless, but which are more often warm and painful.

A more important form of active late congenital syphilis involves the central nervous system, with the most common type being meningovascular. Paresis, a potentially more dangerous form of central nervous system syphilis, occurs in juveniles, and may be detected in a preparetic state by examination of the CSF. The examination shows complement-fixing antibody, pleocytosis, and elevation of protein concentration. If untreated, parenchymal involvement may be severe and, eventually, irreversible. Juvenile tabes rarely occurs.

Any form of late congenital syphilis may have become spontaneously seronegative by the time the disease is recognized. Paradoxically, some patients become serofast, signifying an indefinitely high serologic titer unresponsive to treatment, even though therapy is otherwise successful.

DIAGNOSIS The serologic tests for syphilis were described earlier. Both treponemal and nontreponemal antibodies are transmitted from the mother to the infant. If the infant is not infected, the maternal antibodies disappear by 4 months of age. In an infected infant, a rising VDRL or RPR titer can be anticipated.

An accurate diagnosis is difficult, particularly in the first few days or weeks of life, unless Treponema are visible in lesions. If Treponema are not found, one must consider the status of the maternal infection, whether the mother has been treated, the serologic tests in the infant, the clinical findings in the infant, and the results of bone radiographs and examination of the CSF. Usually one can conclude that infection in the infant is possible, probable, or unlikely. In 1996, the CDC introduced a revised surveillance definition that also provides a good guideline for treatment (

Table 13-46). Refer to the American Academy of Pediatrics Red Book for current guidelines on the treatment of congenital infection.

TREATMENT Because the probability of neurosyphilis cannot be definitively ruled out in most neonates, benzathine penicillin should not be used because it does not provide a treponemacidal level in the cerebrospinal fluid (CSF). The regimens of choice in proven or probable congenital syphilis are:

  • Aqueous crystalline penicillin G, 100,000 to 150,000 U/kg/d (administered as 50,000 U/kg IV every 12 hours during the first 7 days of life and every 8 hours thereafter) for 10 to 14 days; or
  • Procaine penicillin G, 50,000 U/kg intramuscularly daily in a single dose for 10 to 14 days. Adequate CSF concentrations may not be achieved with this regimen.Follow-up is particularly important for these infants. They should be seen frequently; careful developmental evaluation, including vision and hearing testing, should be carried out. Nontreponemal tests should be repeated 3, 6, and 12 months after therapy. The titers are expected to decline and become nonreactive or stabilize at very low levels. In infants with congenital neurosyphilis, or in those children not evaluated for neurosyphilis, the CSF should also be examined toward the end of therapy. Repeat treatment should be considered if the STS titer increases or fails to decrease fourfold within 1 year.

Alternative Treatments When Intravenous Penicillin Is Not Available Penicillin G is the treatment of choice for congenital syphilis and neurosyphilis, and every effort should be made to treat these infections with penicillin G. Because of recent shortages of penicillin G, the CDC and American Academy of Pediatrics developed guidelines for use of alternative treatments when intravenous penicillin is not available. For infants with clinical or laboratory evidence of congenital syphilis, local sources should be sought for aqueous crystalline penicillin G. If intravenous penicillin is not available or is limited, procaine penicillin G at 50,000 U/kg/dose given intramuscularly in a single dose each day for 10 days can be given as a substitute for all or some of the doses. If neither aqueous nor procaine penicillin G is available, ampicillin may be given intravenously at 200 mg/kg/d in four divided doses for 10 to 14 days. Alternatively, ceftriaxone may be given at a dose of 75 mg/kg/d intramuscularly or intravenously for 10 to 14 days in infants <30 days; for older infants, a single dose of 100 mg/kg/d should be given. The use of ampicillin and ceftriaxone have not been well studied; thus, if these regimens are used, careful follow-up should be done to include a repeat CSF exam at 6 months of age if the initial exam was abnormal.

The recommended treatment for neurosyphilis is intravenous aqueous penicillin G. If this is not available, procaine penicillin G at 2.4 million units intramuscularly each day, plus probenicid 500 mg four times a day, for 10 to 14 days is recommended. If this regimen cannot be tolerated, then ampicillin or ceftriaxone can be used with careful clinical follow-up. It is recommended that an expert be consulted when nonstandard treatments are used.

PREVENTION Serologic tests for syphilis should be performed in all pregnant women prior to delivery and are required by law in many states. No infant should leave the hospital without the serologic status of the infant’s mother having been documented at least once during pregnancy. Serologic testing also should be performed at delivery in communities and populations at risk for congenital syphilis. Serologic tests can be nonreactive among infants infected late during their mother’s pregnancy. Penicillin is the only drug that, when given during pregnancy, reliably protects the fetus. If other drugs such as erythromycin are used, the infant should be treated again after birth. The infected pregnant woman’s sexual partners must also be treated because the mother could become reinfected and could also reinfect her infant after penicillin therapy. Because most open lesions and possibly blood are contagious, standard precautions are recommended for all patients with suspected or proven syphilis until therapy has been administered for at least 24 hours.

References

American Academy of Pediatrics: Syphilis. In: PETER G , ed: 1997 Red Book: Report of the Infectious Diseases, 24th ed. Elk Grove Village, IL, American Academy of Pediatrics, 504-514, 1997

Centers for Disease Control and Prevention: 1998 sexually transmitted diseases treatment guide. MMWR Morb Mortal Wkly Rep 47(#RR1), 1998

DORFMAN DH , GLASER JH: Congenital syphilis presenting in infants after the newborn period. N Engl J Med 323:1299-1302, 1990

LEWIS LL: Congenital syphilis: serologic diagnosis in the young infant. Infect Dis Clin North Am 6:31-39, 1992

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Provided by ArmMed Media
Revision date: Sept. 19, 2012
Last revised: by Alexander D. Davtyan, M.D

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