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Syphilis

DEFINITION

Syphilis, a chronic systemic infection caused by Treponema pallidum subspecies pallidum, is usually sexually transmitted and is characterized by episodes of active disease interrupted by periods of latency. After an incubation period averaging 2–6 weeks, a primary lesion appears—often associated with regional lymphadenopathy—and then resolves without treatment. The secondary stage, with generalized mucosal and cutaneous lesions and generalized lymphadenopathy, is followed by a latent period of subclinical infection lasting years or decades. Central nervous system (CNS) involvement may occur early in infection and may be symptomatic or asymptomatic. In the preantibiotic era, one-third of untreated patients developed tertiary syphilis, characterized by destructive mucocutaneous, skeletal, or parenchymal lesions; aortitis; or late CNS manifestations.

ETIOLOGY

The Spirochaetales include four genera that are pathogenic for humans and for a variety of other animals: Leptospira species (leptospirosis, Chap. 179); Borrelia species (relapsing fever and Lyme disease, Chaps. 180 and 181); Brachyspira species (gastrointestinal infections); and Treponema species (syphilis and the endemic treponematoses; see also Chap. 178). The Treponema subspecies include T. pallidum subsp. pallidum (venereal syphilis); T. pallidum subsp. pertenue (yaws); T. pallidum subsp. endemicum (endemic syphilis or bejel); and T. carateum (pinta). Until recently, the subspecies were distinguished primarily by the clinical syndromes they produce, but molecular signatures can now differentiate the three T. pallidum subspecies when assessed by polymerase chain reaction (PCR) or gene sequencing. The crossing of subspecies boundaries by some gene sequence “signatures” in certain strains demonstrates a genetic “continuum” among strains and subspecies of the pathogenic treponemes. Other Treponema species found in the human mouth, genital mucosa, and gastrointestinal tract have been associated with disease (e.g., periodontitis), but their role as primary etiologic agents is unclear.

T. pallidum subspecies are thin spiral organisms, with a cell body surrounded by a trilaminar cytoplasmic membrane, a delicate peptidoglycan layer, and a lipid-rich outer membrane. Endoflagella wind around the cell body in the periplasmic space and are responsible for motility.

Image not available. The T. pallidum subspecies cannot be cultured in vitro. Genome sequencing revealed severely limited metabolic capabilities, including a lack of genes required for de novo synthesis of most amino acids, nucleotides, and lipids. Genes encoding enzymes of the Krebs cycle and oxidative phosphorylation are absent. The organisms contain numerous compensatory genes predicted to encode transporters of amino acids, carbohydrates, and lipids. In addition, genome analyses and other studies have revealed the existence of a 12-member gene family (tpr) with similarities to variable outer-membrane antigens of other spirochetes. One member, TprK, has discrete variable regions that undergo antigenic variation during infection, providing a mechanism for immune evasion.

The only known natural host for T. pallidum subsp. pallidum (referred to hereafter as T. pallidum) is the human. T. pallidum can infect many mammals, but only humans, higher apes, and a few laboratory animals regularly develop syphilitic ...

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