Syphilis is an infectious, systemic, sexually transmitted disease caused by the syphilis spirochete. The widespread prevalence and spread of syphilis has become a serious public health problem in countries around the world, including our own. Proper and standardized treatment protocols for syphilis are receiving widespread attention from people in all countries.
Most countries in the world have developed treatment protocols for syphilis, which vary from country to country and region to region.
Current syphilis treatment in China
In 2003, the Department of Disease Control of the Ministry of Health of China revised and promulgated the National Standard Syphilis Diagnostic Criteria and Treatment Principles of the People’s Republic of China, penicillin is still the drug of choice for the treatment of syphilis.
Early syphilis (including stage I and II, latent syphilis within 2 years) treatment is preferred to benzathine penicillin or procaine penicillin.
For late syphilis (stage III skin, mucous membrane, bone syphilis, late latent syphilis or latent syphilis where the stage of disease cannot be determined) and stage II recurrent syphilis, benzathine penicillin or procaine penicillin are recommended, and the course of treatment must be longer than that for early syphilis.
Treatment of syphilis in pregnancy is the same as above. One course of treatment is required in the first 3 months and one in the last 3 months of pregnancy.
Treatment of neurosyphilis requires that the cerebrospinal fluid penicillin concentration be maintained several times the minimum spirochete killing concentration (0.018μg/ml) during the treatment period, and a high-dose intravenous penicillin regimen (20-24 million U) can result in a peak cerebrospinal fluid spirochete killing level of more than 0.31μg/ml.
Cardiovascular syphilis treatment Penicillin should be started in small doses, taking care to avoid gihai reactions.
Early congenital syphilis (within 2 years of age) with abnormal cerebrospinal fluid is treated with aqueous penicillin or procaine penicillin; those with normal cerebrospinal fluid are treated with benzathine penicillin.
Late congenital syphilis (over 2 years of age), with aqueous penicillin or procaine penicillin.
2006 CDC Syphilis Treatment Guidelines
I. Overview
The signs and symptoms of syphilis are complex, and patients may present with stage I manifestations, stage II manifestations, or stage III manifestations at the time of presentation. The lack of clinical manifestations of latent infection is determined by serologic testing. It is classified as early latent syphilis, late latent syphilis or latent syphilis with an unclear course. Treatment of late latent syphilis and stage III syphilis may require a longer duration of treatment.
II. Diagnostic and serological tests
Dark-field and direct fluorescent antibody (DFA) tests of skin lesions or tissue secretions are confirmatory methods for the diagnosis of early syphilis. Non-syphilis spirochete test titers are often correlated with disease severity to the extent that high titers should be reported. Antibody titers for syphilis spirochetal tests do not correlate with disease activity and therefore should not be used as a criterion to judge the effectiveness of treatment. No single test can diagnose neurosyphilis alone. A negative FTA-ABS can rule out neurosyphilis.
III. 2006 CDC syphilis treatment protocol
1. Repeat treatment for latent syphilis: Repeat treatment is required for those with normal cerebrospinal fluid examination but with the following conditions
(1) A 4-fold increase in antibody potency in the serologic test for non-syphilis spirochete antigens.
(2) Initially high antibody potency (1:32) that has not decreased 4-fold 12-24 months after treatment.
(3) The presence of signs or symptoms suggestive of syphilis progression.
(4) Antibody potency has not decreased despite negative cerebrospinal fluid tests and multiple treatments.
2. Syphilis in pregnancy
All pregnant women should be screened for syphilis serology at their first prenatal visit. All pregnant women should be screened for syphilis serology at least once during pregnancy. For pregnant women in areas with high prevalence of syphilis or at high risk of syphilis, screening should be done at 28-32 weeks of gestation and again before delivery. Anyone with a history of stillbirth after 20 weeks of gestation should be screened for syphilis serology.
(1) Treatment principles and recommended regimen: treat with the appropriate penicillin regimen according to the different stages of syphilis in pregnancy and increase the course of treatment if necessary.
(2) Penicillin allergy: desensitization followed by penicillin treatment.
(3) Follow up and efficacy evaluation.
Quantitative non-spirochete serologic tests are repeated at 28-32 weeks of gestation and during delivery to evaluate the efficacy. Monthly quantitative non-spirochete serologic tests are required for pregnant women in high-risk groups or areas with a high incidence of syphilis to detect reinfection in a timely manner.
3. Congenital syphilis
Prenatal serologic screening of pregnant women is effective in preventing and detecting congenital syphilis.
Serologic screening of pregnant women in areas with a high prevalence of syphilis at least once at 28 weeks of gestation and once before delivery.
HIV testing is mandatory for all pregnant women.
Routine screening of neonatal serum and cord blood is not recommended because the mother’s serologic response is more sensitive than that of the neonate, especially if the mother’s serologic antibody titer is relatively low.
Analysis of syphilis treatment failure
Although penicillin has been used for syphilis treatment for more than 60 years, there have been no reports of penicillin-resistant syphilis spirochetes so far.
2, benzathine penicillin is still the drug of choice for the treatment of syphilis. It is the best choice in terms of treatment cost and patient compliance. However, the drug cannot enter the cerebrospinal fluid, so it cannot be used in patients with abnormal cerebrospinal fluid. Alternative drugs are effective, but their optimal dose and duration of treatment have not been determined.
3.Serum fixation or serum resistance
Serum fixation: 6 months for early syphilis and 12 months for late syphilis is serum fixation if the serum is still not negative.
Serum resistance: early syphilis 1 year, late syphilis 2 years serum has not been negative for serum resistance. Once serum fixation occurs, penicillins are still the main treatment. High-dose penicillin treatment of patients with late serum fixation has achieved good results. The occurrence of syphilis serum fixation is related to cellular immunosuppression of the organism, so it is recommended to add immunomodulators to the conventional antisepsis treatment for such patients for adjuvant therapy. The application of potassium iodide, prednisone, and tretinoin can accelerate the decrease of RPR and syphilis spirochete latex agglutinin test (TPPA) titers in syphilis patients after penicillin treatment.
3.Syphilis with HIV co-infection
The incidence of syphilis with HIV co-infection has increased significantly in the United States and Europe since 2000, especially in gay men who have a high rate of co-infection. HIV can change the clinical manifestations of syphilis, and syphilis can change the course of HIV transmission.
HIV-infected patients may present with atypical serologic test results (abnormally high, abnormally low, or fluctuating titers). An increase in concomitant HIV infection will lead to a new peak in syphilis morbidity and mortality. Patients with HIV infection often have atypical or bizarre symptoms or false-positive or false-negative serology, and the WHO and CDC recommend CSF evaluation in mixed infections and in either the late or unclear stages of syphilis.
4. Syphilis recurrence or reinfection: After a period of syphilis treatment, there are still potential foci in the body, and recurrence and reinfection lead to long-term failure of RPR to turn negative. Identification of recurrence and reinfection of the disease after syphilis treatment is difficult, and potential syphilis lesions, often leading to serum fixation.
5, biological false positive (BFP): positive syphilis seropositivity test caused by biological pathogenic factors other than syphilis spirochetes or other disease factors is called biological false positive (BFP) reaction. It can be divided into acute biological false positive reaction, mostly seen in viral diseases; chronic biological false positive reaction is common in leprosy, systemic lupus erythematosus, allergic vasculitis, scleroderma, dermatomyositis, as well as tumors, HIV and intravenous drug use, BFP duration can be up to several years or lifelong.
6. Insufficient amount of early syphilis treatment and irregular treatment. Early detection and treatment are essential for a complete cure of syphilis. In recent years, the rate of female syphilis and neonatal syphilis in the United States has steadily decreased. Serologic testing for antibodies to pale spirochetes or non-pale spirochetes remains an important diagnostic method. Extensive blood screening and standardized treatment will play a heavy role in the prevalence and control of syphilis.
7, syphilis clinical manifestations are complex, easy to misdiagnose and miss diagnosis. Extensive blood screening and standardized treatment. Especially for those whose serologic reaction has not turned negative, cerebrospinal fluid testing should be performed to exclude neurosyphilis, and long-term clinical and serologic observation should be conducted to strictly prevent the occurrence of late syphilis.
Toxic side effects of syphilis treatment drugs
1. Penicillin allergy
Especially for patients with positive penicillin skin test and must use (such as pregnant women with syphilis), try to perform desensitization before treatment. This desensitization therapy is only effective for type I metaplasia, but not for type IV metaplasia. If it is longer than this time period, it is necessary to re-treat the desensitization.
2, penicillin toxic reactions.
In the past, it was thought that penicillin adverse reactions were mainly allergic reactions, and toxic reactions occurred less frequently, but with the emergence of drug-resistant strains and increased dosage of antibiotics, toxic reactions increased significantly.
Therefore, in the application of penicillin in the process of allergic reaction to penicillin or the primary disease can not explain the symptoms and signs, should be highly alert to the toxic reactions of penicillin.
3.Jihai reaction (Jarisch-Herxheimer reaction).
Definition: It is an acute metabolic inflammatory reaction caused by the death of a large number of bacteria into the blood and tissues after treatment. It is often accompanied by fever, headache, myalgia and other symptoms and usually occurs within the first 24 hours after treatment, most commonly in early syphilis.
The reaction is easily confused with an allergic reaction to drugs. The reaction is a self-limiting process and should be distinguished from an allergic reaction to penicillin.
Jihai’s reaction can lead to preterm delivery and fetal distress in pregnant women, even with this anxiety the duration of antibiotic treatment for syphilis should be ensured and treatment of penicillin should not be abandoned or postponed
4.Allergic gastroenteritis
As penicillin can also destroy the beneficial bacteria in the human intestinal tract that help digestion while sterilizing, so that the intestinal flora is out of balance, causing gastrointestinal diseases. Mainly manifested as abdominal pain, diarrhea, nausea, vomiting and other gastrointestinal symptoms.
5. Cyanotic dermatitis
A rare complication caused by intramuscular injection, manifested as severe pain at the site of injection, and cyanotic plaques. It is often caused by intramuscular injection of benzathine penicillin.
6.Vascular vagal seizure (penicillin encephalopathy)
Definition: When the concentration of penicillin in the cerebrospinal fluid exceeds 8-10 u/ml, it can stimulate the excitation of the central nervous system, resulting in headache, high fever, spasm, convulsion, even coma, respiratory and circulatory failure, and meningeal irritation, etc. It is called penicillin encephalopathy.