Which of the following statements about the ways in which syphilis is transmitted is true?

Latent Syphilis

By definition, latent syphilis is the stage at which there are no clinical signs of syphilis. Latency, which begins when the first attack of secondary syphilis has passed and may last for a lifetime, is usually detected by reactive serologic tests for syphilis (seeDiagnosis). Congenital syphilis must also be excluded before the diagnosis of latent syphilis can be made. Patients may or may not have a clinical history of earlier primary or secondary syphilis manifestations.

Latency has been divided into two stages: early and late. Most infectious relapses occur in the first year, and epidemiologic evidence shows that the most infectious period is during the first year of infection. Early latency is therefore defined as the first year after resolution of the primary or secondary lesions or as a newly reactive serologic test response for syphilis in an otherwise asymptomatic individual who has had a negative serologic test result within the preceding year. Late latent syphilis, or, more accurately, latent syphilis of unknown duration, is ordinarily not infectious, except for pregnant women, who can transmit infection to the fetus despite long-standing infection.

Latent Syphilis

Latent syphilis is defined as an untreated infection in which the patient displays seroreactivity but no clinical evidence of disease. This stage of the infection is divided into early latent syphilis (disease acquired within the preceding year) and late latent syphilis (disease present for longer than 1 year) or latent syphilis of unknown duration. During the first 4 years of latent syphilis, patients may exhibit mucocutaneous relapses and are considered infectious. After 4 years, relapses do not occur, and patients are considered noninfectious (except for blood transfusions and pregnant women).7,22 The latent stage may last for many years or, in fact, for the remainder of the person's life. In some untreated patients, however, progression to tertiary syphilis occurs.

Latent Syphilis

Latent syphilis is, by definition, the stage during which serologic tests are reactive without clinical manifestations. Important to note, the term does not mean that the disease process is quiescent, only that clinical signs and symptoms are not evident. Stokes described syphilis as “the relapsing disease par excellence,” recognizing that the immune system may require years before it can contain the spirochete, even if unable to fully eradicate it in many instances.1 The Oslo Study is only one of several in the prepenicillin era that documented a high rate of relapse in early syphilis. Although the percentages differ, they concurred insofar as the preponderance of relapses occurred during the first 1 to 2 years,1 observations that led to the somewhat arbitrary 1-year demarcation between early latent and late latent syphilis. However, the fact that asymptomatic pregnant women can transmit the infection to their infants in utero 5 or more years after infection clearly demonstrates that recurrent episodes of “silent” spirochetemia occur for prolonged periods.1,60 In reality, there is no clear biologic demarcation between early latency, when the disease is still systemically active, and late latency, when it is active but anatomically contained.

Mucocutaneous relapses are by far the most common form of infectious relapse and the ones with greatest public health significance because of their potential for disease transmission.229 The cutaneous lesions of secondary relapses tend to be less florid than initial secondary outbreaks, asymmetrically distributed, and often confined to the mouth, genital, and anal regions. Relapsing lesions have a greater tendency to assume annular forms; mucous patches and condylomata lata also are common. Late mucocutaneous relapses can manifest as localized destructive lesions, resembling gummas. A small percentage of relapses involve noncutaneous sites, such as bone (usually tibial periostitis), eye (usually iritis), liver, other viscera, and the CNS. These are probably flare-ups of infectious foci established earlier.

Latent Syphilis

Latent syphilis is by definition the stage during which serologic tests are reactive without clinical manifestations. Importantly, the term does not mean that the disease process is quiescent, only that clinical signs and symptoms are not evident. Stokes described syphilis as “the relapsing disease par excellence,” recognizing that the immune system may require years before it can contain the spirochete, even if unable to fully eradicate it in many instances.1 The Oslo Study is only one of several in the prepenicillin era, which documented a high rate of relapse in early syphilis. Although the percentages differ, they concurred insofar as the preponderance of relapses occurred during the first 1 to 2 years,1 observations that led to the somewhat arbitrary 1-year demarcation between early latent and late latent syphilis. However, the fact that asymptomatic pregnant women can transmit the infection to their infants in utero 5 or more years into the disease clearly demonstrates that recurrent episodes of “silent” spirochetemia occur for prolonged periods.1,46 In reality, there is no clear biologic demarcation between early latency, when the disease is still systemically active, and late latency, when it is active but anatomically contained.

Mucocutaneous relapses are by far the most common form of infectious relapse and the ones with greatest public health significance because of their potential for disease transmission.148 The cutaneous lesions of secondary relapses tend to be less florid than the initial secondary outbreaks, asymmetrically distributed, and often confined to the mouth, genital, and anal regions. Relapsing lesions have a greater tendency to assume annular forms, while mucus patches and condylomata lata are also common. Late mucocutaneous relapses can manifest as localized destructive lesions, resembling gummas. A small percentage of relapses involve noncutaneous sites, such as bone (usually tibial periostitis), eye (usually iritis), liver, other viscera, and the CNS. These are probably “flare-ups” of infectious foci established earlier.

Latent Syphilis

Latent syphilis is defined as syphilis characterized by seroreactivity without other evidence of disease. Patients who have latent syphilis and who acquired syphilis within the preceding year are classified as having early latent syphilis. In latent syphilis, the clinician depends on the accuracy of the patient's history that there were characteristic signs and symptoms or that the blood test, the result of which has been discovered to be positive, was nonreactive at a specific time (Table 10.12).

Early latent syphilis can be diagnosed if, within the year preceding the evaluation, the patient reports the following:

There was a documented seroconversion (i.e., RPR, VDRL not a false-positive test result) without evidence of active disease or 4-fold or greater increase in titer of a nontreponemal test. Often the physician is unable to confirm the specific time interval of conversion.

Unequivocal symptoms of primary or secondary syphilis were present.

A sex partner was documented to have primary, secondary, or early latent syphilis.

By convention, early latent syphilis is of 1-year or less duration and late latent syphilis is of more than 4 years’ duration. The periods of 1 and 4 years were established to help predict a patient's chance of experiencing relapse with signs of secondary infectious syphilis. Approximately 25% of untreated patients in the secondary stage may experience a relapse, most of them (approximately 90%) during the first year, a small percentage in the second year, and none after the fourth year. The patient who experiences a relapse with secondary syphilis is infectious.

Patients who have latent syphilis of unknown duration should be treated as if they have late latent syphilis. Nontreponemal serologic titers (i.e., RPR, VDRL) usually are higher during early latent syphilis than late latent syphilis. However, early latent syphilis cannot be reliably distinguished from late latent syphilis solely on the basis of nontreponemal titers. All patients with latent syphilis should undergo careful examination of all accessible mucosal surfaces (i.e., the oral cavity, the perineum in women, and underneath the foreskin in uncircumcised men) to evaluate for internal mucosal lesions. All patients who have syphilis should be tested for HIV infection.

CLINICAL SYPHILIS

Clinically, syphilis is divided into three stages; primary, secondary and tertiary.

Primary syphilis occurs with sexual exposure, and the characteristic local lesion or chancre, usually on the genitalia, contains the infectious organisms. From this lesion the treponema disseminate throughout the body, while the primary lesion heals spontaneously in a few weeks.

Following an interval of several months secondary syphilis occurs. This is characterized by a generalized skin rash, mucous membrane lesions, lymph node enlargement and fever. The lesions of primary and secondary syphilis are highly infectious. Again, as with primary syphilis, these signs and symptoms regress without treatment, although there can be relapses. Following secondary syphilis there is a period of latency, which may last for years, during which there are no observable signs or symptoms of disease.

Latent syphilis does not progress in two-thirds of the patients; however, in the remaining one-third tertiary syphilis supervenes. There are three forms of tertiary syphilis:

Late benign syphilis is a chronic disorder in which lesions, called gummas, can occur anywhere in or on the body, tending to progress by erosion of underlying tissue or bone.

Cardiovascular syphilis is a chronic disorder, with involvement of the main artery carrying blood from the heart to the body (the aorta).

Neurosyphilis appears in three different clinical forms. The first is meningovascular syphilis, which can present as an acute to subacute meningitis or even as a stroke. The second is tabes dorsalis, in which the patient experiences difficulty in walking and maintaining balance. The third is general paresis, which is the form that the psychiatrist sees; this was the major target for Wagner-Jauregg's therapeutic studies. These patients are usually demented and have lost all contact with reality. They may claim to be Napoleon or the King of England, or have other grandiose delusions.

Latent syphilis

Latent syphilis is the period of quiescence after completion of the secondary stage of disease, during which there are no clinical manifestations. An exposure history and a reactive serologic test for syphilis is the only way of establishing the diagnosis. Not infrequently, no history of primary or secondary syphilis can be obtained, and, in such a case, a true-positive serology must be distinguished from a false-positive one (see laboratory section on interpretation of test results).

Latency is divided into early and late phases. WHO designates two years after first suspected exposure as the cut-off point for early and late latency.15 Early latency encompasses the first year after secondary infection. It is during this period that relapses of secondary disease are most likely to occur in the untreated patient. Occasionally, infection of a partner may occur during early latency, and the pregnant woman is at risk of transmitting the disease to her fetus. The patient in late latency (more than 1 year into the latent period) has a decreasing risk of transmission to partner or fetus as latency progresses.

Latent Syphilis in Pregnancy

Subclinical or latent syphilis is defined as the period after infection when patients are seroreactive, but show no clinical manifestations of disease. This latent phase can last for years [193,209]. This latent period is sometimes interrupted during the first few (<4) years by recurrences of symptoms of secondary syphilis. Treponemes can still be present in the blood intermittently and be passed across the placenta to the fetus during latent syphilis in a pregnant woman. The first year after infection is considered early latent, and the subsequent period is late latent syphilis. This classification is based on the time period of communicability (not just to the fetus), which is higher in the first year after infection compared with later time points [50]. If the duration of syphilis infection cannot be determined, the disease is classified as latent syphilis of unknown duration. Approximately 60% of untreated patients in the late latent stage continue to have an asymptomatic course, whereas 30% to 40% develop symptoms of late or tertiary disease. Progression of disease from late latent to late symptomatic syphilis usually is prevented if appropriate antimicrobial therapy is given at this stage [50].

Latent Syphilis

By definition, latent syphilis is the stage at which there are no clinical signs of syphilis and the CSF is normal. Latency, which begins when the first attack of secondary syphilis has passed and may last for a lifetime, is usually detected by reactive serologic tests for syphilis (see Diagnosis). Congenital syphilis must also be excluded before the diagnosis of latent syphilis can be made. Patients may or may not have a clinical history of earlier primary or secondary syphilis.

Latency has been divided into two stages: early and late. Most infectious relapses occur in the first year, and epidemiologic evidence shows that the most infectious period is during the first year of infection. Early latency is therefore defined as the first year after resolution of the primary or secondary lesions, or as a newly reactive serologic test for syphilis in an otherwise asymptomatic individual who has had a negative serologic test within the preceding year. Late latent syphilis is ordinarily not infectious, except for pregnant women, who can transmit infection to the fetus after many years. Most cases of latent syphilis are most accurately called latent syphilis of unknown duration and should be treated in the same manner as late latent syphilis (see later).

MANAGEMENT

Primary, secondary, and latent syphilis are treated with benzathine penicillin; neurosyphilis is treated with intravenous aqueous crystalline penicillin G, 3 to 4 million units every 4 hours for 10 to 14 days. An alternative regimen is procaine penicillin, 2.4 million units intramuscularly daily with probenecid and 500 mg orally four times a day, both for 10 to 14 days. Patients with a history of penicillin allergies should be skin tested and desensitized if necessary.85,91 The frequency with which intravenous antibiotics are unsuccessful in the therapy of neurosyphilis is extremely low. In instances in which a progression of clinical disease or persistence of a CSF lymphocytic pleocytosis or a reactive CSF‐VDRL is present, re‐treatment of the patient with an additional 24 million units/day for 10 days is reasonable. The initial CSF pleocytosis will resolve 6 months after penicillin therapy in 80% of patients. Serial CSF‐VDRL titers should decrease with treatment. Re‐examination of the CSF should occur in HIV‐infected patients with neurosyphilis.