Primary prevention
Education on safe sex practices is important.[24] Consistent and correct use of condoms during sexual intercourse reduces the transmission of acquired syphilis.[1][25] However, orogenital sex is an important route of transmission and can occur despite the use of condoms.[1][14] There is no significant evidence to suggest that male circumcision reduces the incidence of syphilis.[26] National screening programs are in place prior to blood donation and as part of prenatal care during pregnancy.[27] Prenatal screening aims to identify and treat asymptomatic women, thus preventing transplacental transmission.[23]
One open-label randomized trial found that post-exposure prophylaxis (PEP) with a single dose of doxycycline in high-risk men who have sex with men reduced the risk of syphilis compared with no post-exposure prophylaxis at 10-month follow-up (hazard ratio: 0.27; 95% CI: 0.07 to 0.98; p = 0.047).[28] Subsequently, two further large randomized clinical trials have also demonstrated that doxycycline can prevent incident syphilis in men who have sex with men and transgender women.[29][30] On the basis of the observed efficacy of PEP with doxycycline for reducing the risk of syphilis infection, Centers for Disease Control and Prevention (CDC) recommends that men who have sex with men and transgender women who have had a syphilis, chlamydia, or gonorrhea infection within the previous 12 months should receive counseling that PEP with doxycycline can be used to prevent these infections.[31] PEP with doxycycline could also be discussed with men who have sex with men and transgender women who have not had a bacterial STI within the previous 12 months but who are likely to participate in sexual activities that are known to be high risk for exposure to STIs.[31] PEP with doxycycline can be self-administered within 72 hours of sexual intercourse. Individuals prescribed PEP with doxycycline should undergo STI testing every 3-6 months.
The table that follows summarizes recommendations on PEP with doxycycline from the CDC.[31]
Note that an individual patient may fall into more than one group and so interventions might be additive; please review all population and subpopulation groups to assess all that apply.
Man who has sex with men (MSM) or transgender woman; with known syphilis, chlamydia or gonorrhea infection in the past 12 months
All
Intervention
Counseling on postexposure prophylaxis (PEP) with doxycycline
Discuss with patients the benefits and harms of using doxycycline as PEP.
The following points may help to guide this discussion:
Infections with syphilis, chlamydia, and gonorrhea have increased in the US and disproportionately affect gay, bisexual, and other men who have sex with men and transgender women.
Recent evidence suggests that a single dose of oral doxycycline taken within 72 hours after sex reduces syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%.
Serious adverse effects of doxycycline are rare. Harms of doxycycline include photosensitivity and gastrointestinal symptoms including esophageal erosion and ulceration. Most adverse effects resolve with discontinuation of the medication.
There are no studies to date on long-term intermittent use of doxycycline and the microbiome; current data suggest overall benefit of the use of doxycycline PEP, but potential risks related to the development of resistance and changes to the microbiome will need to be monitored as guidelines are implemented.
Goal
Shared decision making; prevention of syphilis, chlamydia, and gonorrhea
Patient accepts PEP following shared decision making
Intervention
Offer prescription for PEP
Offer a prescription for self-administration of a single dose of oral doxycycline to be taken as soon as possible within 72 hours after having oral, vaginal, or anal sex.
Provide a prescription accounting for enough doses on the basis of the person’s anticipated sexual activity until their next visit, following shared decision making.
Goal
Comprehensive sexual health approach; reduced risk of infection with syphilis, gonorrhea, and chlamydia
PEP is recommended as part of a comprehensive sexual health approach.
This includes the following:
risk reduction counseling;
STI screening and treatment;
HIV screening according to current recommendations; and
recommended vaccination and linkage to HIV pre-exposure prophylaxis (PrEP), HIV care, or other services as appropriate.
It is recommended that individuals prescribed PEP with doxycycline undergo STI testing at baseline and every 3-6 months.
Assess the ongoing need for doxycycline PEP, and for any adverse effects, every 3-6 months.
MSM or transgender woman; no history of syphilis, chlamydia, or gonorrhea infection within the past 12 months, but likely to participate in sexual activities that increase the likelihood of exposure to STIs
All
Intervention
Consider counseling on postexposure prophylaxis (PEP) with doxycycline
Although not directly assessed in the trials included in the guideline, it is recommended that clinicians may consider discussing doxycycline PEP, using a shared decision-making approach, with this patient group.
The following points may help to guide this discussion:
Infections with syphilis, chlamydia, and gonorrhea have increased in the US and disproportionately affect gay, bisexual, and other men who have sex with men and transgender women.
Recent evidence suggests that a single dose of oral doxycycline taken within 72 hours after sex reduces syphilis and chlamydia infections by >70% and gonococcal infections by approximately 50%.
Serious adverse effects of doxycycline are rare. Harms of doxycycline include photosensitivity and gastrointestinal symptoms including esophageal erosion and ulceration. Most adverse effects resolve with discontinuation of the medication.
There are no studies to date on long-term intermittent use of doxycycline and the microbiome; current data suggest overall benefit of the use of doxycycline PEP, but potential risks related to the development of resistance and changes to the microbiome will need to be monitored as guidelines are implemented.
Goal
Shared decision making; prevention of syphilis, chlamydia, and gonorrhea
Patient accepts PEP following shared decision making
Intervention
Offer prescription for PEP
Offer a prescription for self-administration of a single dose of oral doxycycline to be taken as soon as possible within 72 hours after having oral, vaginal, or anal sex.
Provide a prescription accounting for enough doses on the basis of the person’s anticipated sexual activity until their next visit, following shared decision making.
Goal
Comprehensive sexual health approach; reduced risk of infection with syphilis, gonorrhea, and chlamydia
PEP is recommended as part of a comprehensive sexual health approach.
This includes the following:
risk reduction counseling;
STI screening and treatment;
HIV screening according to current recommendations; and
recommended vaccination and linkage to HIV pre-exposure prophylaxis (PrEP), HIV care, or other services as appropriate.
It is recommended that individuals prescribed PEP with doxycycline undergo STI testing at baseline and every 3-6 months.
Assess the ongoing need for doxycycline PEP, and for any side effects, every 3-6 months.
Sexually active adult within a population not already listed above (e.g., cisgender woman, cisgender heterosexual man, transgender man, or other queer or nonbinary person assigned female at birth)
All
Intervention
Use clinical judgement and shared decision making to inform use of postexposure prophylaxis (PEP) with doxycycline
The pharmacokinetics of doxycycline and experience in treating bacterial STIs suggest that doxycycline PEP should be effective in these populations, however supporting clinical data are insufficient to make recommendations.
Therefore, clinical judgement and shared decision making should inform the use of PEP with doxycycline is appropriate for individuals in these population groups.
Goal
Shared decision making; prevention of syphilis, chlamydia, and gonorrhea
Secondary prevention
All patients with syphilis should be screened for chlamydia, gonorrhea, and blood-borne viruses, such as hepatitis B and C. All patients with syphilis should be tested for HIV.[8] In geographic areas in which the prevalence of HIV is high, patients who have syphilis should be retested for HIV after 3 months, even if the first HIV test result is negative, and be offered HIV pre-exposure prophylaxis (PrEP).[8] Syphilis is an important facilitator of HIV transmission.[15] All patients with syphilis should be offered hepatitis B vaccination. Sexual contacts of patients with confirmed syphilis should be screened and offered presumptive treatment if follow-up may be problematic.[8]
Strengthening STI services may have an important role in controlling STIs.[104]
Preventive treatment when there has been sexual contact with an infected person:[8]
People exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis in a sexual partner should be treated presumptively, on the basis that they may be infected even if seronegative. It is estimated that 30% to 60% of sexual partners of people with early syphilis will develop the infection.[15]
People exposed more than 90 days before diagnosis of primary, secondary, or early latent syphilis in a sexual partner should be treated presumptively if syphilis serology is not available immediately and if follow-up may be problematic.
Treatment of long-term sexual partners of patients with latent syphilis is dependent on clinical evaluation and serology results.
At-risk time intervals:[8]
For primary syphilis: exposure 3 months before treatment, plus duration of symptoms.
For secondary syphilis: 6 months plus duration of symptoms.
For early latent syphilis: 1 year.
The identification and treatment of syphilis should be used as an opportunity to promote safe-sex awareness, encourage condom use, and highlight health impacts associated with high risk behavior, such as illicit drug use. Conditional cash incentives to encourage safe sexual practices have demonstrated potential in rural Tanzania.[105]
In the US, syphilis is a nationally notifiable disease, as per the Centers for Disease Control and Prevention. Providers should contact their local state health department for details.
In cases of sexual assault, UK guidelines recommend that prophylaxis should be considered if the perpetrator is known to have infectious syphilis.[106]
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