Syphilis medical therapy

File:Syphilis-poster-wpa-cure.jpg

Depression-era U.S. poster advocating early syphilis treatment

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

History

There were originally no effective treatments for syphilis. The Spanish priest Francisco Delicado wrote El modo de adoperare el legno de India (Rome, 1525) about the use of Guaiacum in the treatment of syphilis. He himself suffered from syphilis. Another common remedy was mercury: the use of which gave rise to the saying "A night in the arms of Venus leads to a lifetime on Mercury". It was administered multiple ways including by mouth and by rubbing it on the skin. One of the more curious methods was fumigation, in which the patient was placed in a closed box with his head sticking out. Mercury was placed in the box and a fire was started under the box which caused the mercury to vaporize. It was a grueling process for the patient and the least effective for delivering mercury to the body.

As the disease became better understood, more effective treatments were found. The first antibiotic to be used for treating disease was the arsenic-containing drug Salvarsan, developed in 1908 by Sahachiro Hata while working in the laboratory of Nobel prize winner Paul Ehrlich. This was later modified into Neosalvarsan. Unfortunately, these drugs were not 100% effective, especially in late disease. It had been observed that some who develop high fevers could be cured of syphilis. Thus, for a brief time malaria was used as treatment for tertiary syphilis because it produced prolonged and high fevers. This was considered an acceptable risk because the malaria could later be treated with quinine which was available at that time. This discovery was championed by Julius Wagner-Jauregg, who won the 1927 Nobel Prize for Medicine for his work in this area. Malaria as a treatment for syphilis was usually reserved for late disease, especially neurosyphilis, and then followed by either Salvarsan or Neosalvarsan as adjuvant therapy. These treatments were finally rendered obsolete by the discovery of penicillin, and its widespread manufacture after World War II allowed syphilis to be effectively and reliably cured.

Current treatment

The first-choice treatment for all manifestations of syphilis remains penicillin in the form of penicillin G. The effect of penicillin on syphilis was widely known before randomized clinical trials were used; as a result, treatment with penicillin is largely based on case series, expert opinion, and years of clinical experience. Parenteral penicillin G is the only therapy with documented effect during pregnancy. For early syphilis, one dose of penicillin is sufficient.

Non-pregnant individuals who have severe allergic reactions to penicillin (e.g., anaphylaxis) may be effectively treated with oral tetracycline or doxycycline although data to support this is limited. Ceftriaxone may be considered as an alternative therapy, although the optimal dose is not yet defined. However, cross-reactions in penicillin-allergic patients with cephalosporins such as ceftriaxone are possible. Azithromycin was suggested as an alternative. However, there have been reports of treatment failure due to resistance in some areas. If compliance and follow-up cannot be ensured, the CDC recommends desensitization with penicillin followed by penicillin treatment. All pregnant women with syphilis should be desensitized and treated with penicillin. Follow-up includes clinical evaluation at 1 to 2 weeks followed by clinical and serologic evaluation at 3, 6, 9, 12, and 24 months after treatment.

Late latent and infections of unknown duration

Late latent syphilis is defined as latency for greater than one year. If CSF examination yields no evidence of neurosyphilis, then penicillin G is recommended as weekly doses for 3 weeks. If allergic, then tetracycline or doxycycline may also be used for this stage, but for 28 days instead of the normal 14. As with before, the data to support use of tetracycline and ceftriaxone are limited.

Neurosyphilis

For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice. The recommended regimen is intravenous treatment every 4 hours or continuously for 10-14 days. If intravenous administration is not possible, then procaine penicillin is an alternative (administered daily with probenecid for two weeks). Procaine injections are painful, however, and patient compliance may be difficult to ensure. To approximate the 21-day course of therapy for late latent disease and to address concerns about slowly dividing treponemes, most experts now recommend 3 weekly doses of benzathine penicillin G after the completion of a 14-day course of aqueous crystalline or aqueous procaine penicillin G for neurosyphilis. No oral antibiotic alternatives are recommended for the treatment of neurosyphilis. The only alternative that has been studied and shown to be effective is intramuscular ceftriaxone daily for 14 days.

Alternative regimens

Alternative regimens such as tetracyclines are not well studied in HIV infection and a careful follow-up is recommended. Tetra-cyclines are contraindicated in pregnancy.

HIV-infected patients with early syphilis may have a higher risk of neurological complications and a higher rate of treatment failure with currently recommended regimens. The magnitude of these risks, however, although not precisely defined, is probably small. Skin testing or desensitization is recommended in latent syphilis and neurosyphilis in other patients with HIV infection.

Jarisch-Herxheimer reaction

Before administering any treatment, clinicians should warn all patients about the possibility of a Jarisch-Herxheimer reaction, which occurs most often in secondary syphilis and with penicillin therapy, and may be more common in HIV-infected patients. This reaction is characterized by fever, fatigue, and transient worsening of any mucocutaneous symptoms, and usually subsides within 24 hours. These symptoms can be alleviated with acetaminophen (paracetamol) and should not be mistaken for drug allergy. In addition, clinicians should inform HIV-infected patients that currently recommended regimens may be less effective for them than for patients without HIV infection and that close serologic follow-up is therefore essential.

Tuskegee syphilis study

Main article: Tuskegee Study of Untreated Syphilis in the Negro Male

One of the best-documented cases of unethical human medical experimentation in the twentieth century was the Tuskegee syphilis study. The study took place in Tuskegee, Alabama and was supported by the Tuskegee Institute and the U.S. Public Health Service (PHS).

The study began in 1932 using a group of 600 black sharecroppers. Of these 600, 399 of the men had the disease and 201 were uninfected control patients. The PHS stated at first that treatment was supposed to be a part of the study, but they were unable to produce any useful data. It was then discovered that the PHS had decided to leave the men untreated and follow the course of the disease to these men's eventual deaths. They thought they were receiving experimental treatment for "bad blood" in exchange for free meals and a $50 death benefit. However, the study was designed to measure the progression of untreated syphilis and to determine whether syphilis caused cardiovascular damage more often than neurological damage, and to determine if the natural course of the disease was different in black men versus white men. By 1947 penicillin had become the standard treatment of syphilis. The men were never advised that they had syphilis, nor were they offered a treatment including Salvarsan or the other arsenical drugs that were in use at the beginning of the study.

The original study was meant to last six to nine months, but continued for 40 years, ending in 1972, long after wives and children had been infected, and many of the men had died of syphilis. It was estimated that more than one hundred men and women died as a result of this study. The study ended because of a story printed in the Washington Star. A class-action lawsuit was then filed against the federal government for the study. This lawsuit was settled out of court and the living subjects and their descendants were awarded a total of ten million dollars. After the settlement was awarded, the government passed the National Research Act, which required the government to review and approve all medical studies involving human subjects.

Application of mercury.

References

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