Syphilis

The approximate size of Treponema is 10 um X 0.2 um. Therefore, dark field microscopy, which takes advantage of the Tyndall Effect, must be used to observe Treponema cells. The cells can also be observed microscopically after staining with specific anti-treponemal antibodies labeled with florescent dyes. The spirochetes are able to swim in viscous environments (e.g. oral cavity, intestinal tract), but are only able to spin in water due to the lack of friction. Any contact with air, antiseptics, or sunlight will kill the microbe. T. pallidum requires the presence of tissue culture cells, a microaerobic environment and serum components for growth. Its fastidious nature may account for its obligate parasitism and rapid death outside the host. If kept outside of the body in a moist dark place it will live no more than two hours. This microorganism is responsible for natural disease in humans only, although rabbits can be infected experimentally. T. pallidum cannot be grown in cell free cultures. Limited growth has been achieved in cultured rabbit epithelial cells, but replication is slow (doubling time, 30 hours) and can be maintained for only a few generations.

Several gene products have been specifically associated with virulent strains, although their role in pathogenesis remains to be unknown. The outer membrane proteins are associated with adherence to the surface of host cells, and virulent spirochetes produce hyaluronidase, which may facilitate perivascular infiltration. Virulent spirochetes are also coated with host cell fibronectin, which can protect against phagocytosis.

Syphilis was an epidemic in late Fifteenth century Europe. The rapid spread and considerable effects of the disease throughout Europe coined the term Great Pox, in contrast to another epidemic, smallpox. The disease received its present name from the poem by Fracastoro in 1530 about the afflicted shepherd, "Syphilus". The late complications of syphilis were recognized early, and were frequently mentioned by many Elizabethan authors.

The late-Fifteenth century European epidemic occurred at the same time Columbus returned from the Americas in 1493. Some historians have speculated that the disease was transmitted from natives in the West Indies, and carried back to a nonimmune population in Europe. Europe was engaged in wars at the time, and the movement of the troops and their camp followers created a perfect route for the bacterium to spread. However, there are biblical and ancient Chinese writings which are consistent with descriptions of late syphilis, and it is known that other Old World illnesses such as tuberculosis or leprosy have similar descriptions. On the other hand, no illness suggestive of syphilis has been described in early American natives. These and other considerations lead to a conclusion that venereal syphilis did not arise suddenly in Europe after 1493, but may have been endemic already.

From the Sixteenth century until well into the Nineteenth century, most doctors assumed gonorrhea and syphilis were types of the same disease. Only in 1837 did the eminent French venereologist Phillipe Ricord discover the specificity of the two diseases through a series of experimental inoculations from syphilitic chancres. Ricord was also among the first physicians to differentiate primary, secondary, and tertiary syphilis, the three stages of infection. By the late Nineteenth century the dangers of syphilis had been identified in a series of studies. Because syphilis infections seem to disappear after the initial inflammatory reaction, people were given a false sense of "recovery" from the disease, yet the severity of the disease continued to increase.

Rudolph Virchow, one of the leading figures in the development of modern germ theory, discovered that the infection could be transferred through the blood to the internal organs, and that syphilis was in fact a systemic condition. Later research showed syphilis to be the cause of a variety of serious illnesses. By 1876, cardiovascular syphilis had been clearly documented in the medical literature. If spread to the spinal cord, the infection can cause muscular incoordination and partial paralysis. Ultimately affecting the brain, syphilis can also lead to insanity in some cases. By the early Twentieth century, doctors reported that mental institutions were filled with patients whose illnesses could be traced to syphilitic infections.

Most physicians treated syphilis with mercury, either orally, in vapor baths, or topically. They based the use of mercury on the ancient theory of humors and health. Mercury caused salivation, which was believed to remove the humors causing the illness. Hot vapor baths worked in a similar way by causing profuse perspiration. Modern observers have suggested that high doses of heavy metal therapy probably neared lethal rates, with many symptoms linked to syphilis.

In 1910, Paul Ehrlich's chemotherapeutic breakthrough, the discovery of Salvarsan, was the peak of the campaign against syphilis. Ehrlich's prediction of the discovery of specific chemotherapeutic agents for specific diseases-"magic bullets" to root out and destroy infecting organisms, was the promise of modern medicine. The so-called biomedical model of disease and treatment stems from Ehrlich's initial discovery.

Penicillin, discovered to be effective in treating syphilis and gonorrhea in 1943, seemed to be the ultimate answer in the search for a magic bullet, but this did not turn out to be the case. Unfortunately, the promise of the magic bullet has never been fulfilled. The control of many infectious diseases through antibiotics revealed a whole new set of systemic and chronic diseases, unresponsive to these drugs, due to the rapid development of drug resistance among microbes. Today, sexually transmitted diseases are a significant problem in spite of antibiotics. Furthermore, even if magic bullets are effective against certain microorganisms, they cannot combat the social and cultural determinants of these infections.

Syphilis results in the formation of lesions throughout the body. The bacteria usually enter the body during sexual intercourse, through the mucosal membranes of the vagina or urethra, but may rarely be transmitted through scar wound or scratches. Bacteria may also pass from an infected pregnant woman across the placenta to the developing fetus resulting in congenital syphilis. Hence, the disease is passed on through infectious blood, mucosal or sexual contact. T. pallidum tends to invade the interstitial spaces of tissue at the site of infection and to move rapidly to other locations. Both of these activities are aided by the active, "cork-screw" motility of T. pallidium, which allows it to bore its way through tissues. Following inoculation, T. pallidium penetrates intact mucous membranes or broken skin, begins to divide slowly and disseminates. Syphilis has three distinct stages and a latency stage between the second and third stages, during all of which the principal pathogen is T. pallidum.

Primary Syphilis: 10-60 days after exposure to syphilis, the area of infection is marked by the appearance of a hard, slightly elevated, round, ulcerous development called a "chancre." (French canker, a destructive sore) The chancre represents the primary site of initial replication. The chancre usually appears on the penis, labia, cervix, anorectal region, or around the mouth. A chancre, however, can form anywhere on exposed skin. The chancre will heal within 4-6 weeks, even without treatment, but may leave a scar. The lymph nodes also become inflamed. Histologic examination of the lesions reveals endarteritis (inflammation of the inner wall of an artery) and periarteritis (inflammation of membranous sac surrounding the heart), characteristic of syphilitic lesions at all stages, and infiltration of the ulcer with polymorphonuclear leukocytes and macrophages. Ingestion of the spirochete by the phagocytic cells is often seen, but the organisms frequently survive.

One out of three people exposed to primary syphilis becomes infected. Unless syphilis is treated early in this stage, it will progress into secondary syphilis.

The Latency Stage: There are no obvious symptoms during this stage, yet T. pallidium is still present in the host's body, lodging itself into the host's tissue. This stage can range from a few months to a lifetime, during which the infected person tests positive for the disease. There is a debate if this stage is contagious. It is generally believed that the individual is not infectious, yet still has a chance of spreading the disease to those in sexual contact with him/her. However, this stage almost always passes the disease to the fetus. Approximately 50-70% of carriers in this stage will not progress to tertiary syphilis.

Tertiary Syphilis: Death in adults is due to the variable occurrence of later complications of syphilis in the skin, bones, central nervous system, heart and blood vessels. Gumma lesions are also present in this stage of syphilis, and if left untreated, they frequently lead to destruction of soft tissue or bone. The pathogenesis of gummas is uncertain; what is known is that spirochetes can be demonstrated in lesions. Lesions of late benign syphilis sometimes occur for an extended period from as few as 2 to over 40 years from onset of infection. Gummas of critical organs, like the heart, brain and liver, can be fatal. This stage of syphilis can lead to cardiovascular syphilis, neurosyphilis, or death.

Congenital Syphilis: In utero infections can lead to significant fetal disease, with death, multi-organ deformities, or latent infections. Most infected infants are born without clinical evidence of disease, but then develop rhinitis followed by a widespread papular rash. Late bony destruction and cardiovascular syphilis are common in untreated infants who survive the initial course of the disease. Infants can also be treated, but antibiotics may be harmful due to their effects on the normal flora that may otherwise antagonize the growth of T. pallidum.

Syphilis is found worldwide, and is the third most common sexually transmitted disease in the United States (after gonorrhea and Chlamydia). More than 35,000 cases of primary and secondary syphilis were reported in the United States in 1987, for an incidence of 14.6 cases per 100,000 persons between 15 to 64 years of age. In 1995, the incidence of primary and secondary syphilis in the United States declined to 6.3 cases per 100,000 persons.

However, the large number of unreported infections contributes to a gross underestimation of the true incidence of this disease. The highest incidence of disease is in Black and Hispanic populations and in urban areas.

Between 1994 and 1995, the overall rate of congenital syphilis decreased from 55.6 to 39.0 cases per 100, 000 live births.

Locally, Madison, Wisconsin had 11 cases of syphilis reported to the Public Health Department in 1996. The Madison five-year average from 1990-1995, was 15 cases of reported syphilis. The Madison Public Health Department reports these cases to the State Division of Health who conducts the followup reports on these cases.

Culture: Efforts to culture T. pallidium have been generally unsuccessful and should not be attempted.

Serology: The diagnosis of syphilis in most patients is made by serological testing. The two general types of tests are biologically nonspecific (nontreponemal) tests and the specific treponemal tests.

Nontreponemal tests measure IgG and IgM antibodies (reagin antibodies) developed against lipids from damaged cells during the early stage of the disease. The antigen used for the nontreponemal tests is cardiolipin, derived from beef heart. The two tests used commonly are the Venereal Disease Research Laboratory (VDRL) test and the rapid plasma reagin (RPR) test. Both tests measure coagulation of cardiolipin antigen by the patient's serum. Both tests are rapid, although complement in serum must be inactivated for 30 minutes before the VDRL test can be performed. Only the VDRL test can be used to test cerebrospinal fluid from patients with suspected neurosyphilis.

Treponemal tests are specific antibody tests used to confirm positive reactions with the VDRL or RPR tests. The treponemal tests can be positive before the nontreponemal tests become positive in early syphilis. Treponemal test may also remain positive when the nonspecific tests revert to negative in some patients who have late syphilis. The tests most commonly used are Fluorescent Treponemal Antibody Absorption (FTA-ABS)test and the Microhemagglultination Test for T. pallidum (MHA-TP). The MHA-TP is technically easier to perform and interpret than the FTA-ABS tests.

Immunity and Possible Vaccines

Syphilis has the properties of an invasive disease. In the early stages, large numbers of organisms accumulate at sites of infection, and millions of treponemes move throughout the body. Most of the tissue damage appears to be primarily due to the continuing immune response. Other mechanisms and cellular reactions are undoubtedly involved, however, since characteristic lesions occur in congenital syphilis and in immuno- compromised individuals. An acquired immunity, the occurrence of resistance to re-infection, has long been recognized by physicians, and was confirmed in the rabbit model in the early part of this century. It is accepted that significant immunity develops 3-6 months, post infection in humans. However, it is important to recognize that this immunity is partial, as the immune response is capable of stopping T. pallidium infection in most individuals. In addition, immunity to re-infection is incomplete, and re-exposure to syphilis can bring about an asymptomatic infection. Finally, resistance usually occurs following treatment and is extremely difficult to induce by artificial immunization.

In contemplating the potential usefulness of vaccination against syphilis, four basic issues must be considered. First, conditions must be avoided which prevent primary or secondary lesions but permit the establishment of latent infection. If vaccination permits the occurrence of asymptomatic infection, vaccinated individuals exposed to syphilis could eventually develop tertiary manifestations, by far the most dangerous stage of the disease. Second, vaccination would under most circumstances lead to serologic reactivity in the treponemal tests, presenting a diagnostic problem. Third, resistance to re-infection fades in syphilis patients following treatment; by inference, resistance due to vaccination may also be transient. Fourth, syphilis has a low incidence in the general population in most countries, and vaccination would have to be targeted at high risk populations.

Treatment, Prevention and Control

Penicillin is the drug of choice for untreated infections with T. pallidium; long-acting benzathine penicillin is used for the early stages of syphilis, and penicillin G is recommended for congenital and late syphilis. Tetracycline, erythromycin, and chloramphenicol can be used as alternative antibiotics for patients allergic to penicillin. Only penicillin or chloramphenicol can be used for patients with neurosyphilis.

Although we fortunately have a cure for syphilis, the ultimate goal is to prevent and control the spread of this infectious disease. I believe the most important step in this process is education. If the public is more educated on how to prevent from contracting this damaging and possibly lethal disease, they may be more apt to protect themselves during sexual acts or abstain from at-risk sexual behavior. The education may include abstinence, using a condom if sexually active, or regularly having a professional health examination. The theme of education has definitely made a tremendous impact on the control of syphilis with the epidemic of HIV. HIV awareness is becoming more and more common in schools, outreach programs, community programs, detention centers, public and private health services, occupational training, military bases and across the world. This education and awareness has drastically decreased the occurrences of syphilis and HIV, so that syphilis is not a major health concern as it once was in the Fifteenth century. However, we cannot turn our back and ignore this infectious disease, since anyone who is engaging in risky sexual behavior is at risk for contracting syphilis as well as other sexually transmitted diseases. We still have many people to educate about this and other dangerous sexually transmitted diseases.

STD Hotline: 1-800-227-8922

Herpes Hotline: 1-919-361-8488

AIDS Hotline: 1-800-342-AIDS

For more information and local Madison testing:

Blue Bus Clinic
University of Wisconsin
608-262-7330

Planned Parenthood
416 W. Mifflin
608-256-7257

Madison Public Health Department
233 North Street
608-244-5519

1. Holmes, Mardh, Sparling, Wiesner, Cates, Lemon and Stamm. Sexually Transmitted Diseases. McGraw-Hill Information Services, Inc. 1990.

2. Sun, Tsieh M.D. Sexually Related Infectious Diseases, Clinical and Laboratory Aspects. Frield, Rich and Associates, Inc. 1986.

3. Thompson, S.E., S.A. Larson and A.A. Moreland. Syphilis. Chapter 1 in Morse, et al, Sexually Transmitted Diseases. J.B. Lippincott. 1990.

4. Wright, D.J.M. Immunology of Sexually Transmitted Diseases. Kluwer Academic Publishers. 1988.