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WHO GUIDELINES FOR THE
Treatment of Treponema pallidum (syphilis)

[Texte complet / OMS]
2016

Sexually transmitted infections (STIs) are a major public health problem worldwide, affecting quality of life and causing serious morbidity and mortality. STIs have a direct impact on reproductive and child health through infertility, cancers and pregnancy complications, and they have an indirect impact through their role in facilitating sexual transmission of human immunodeficiency virus (HIV) and thus they also have an impact on national and individual economies. More than a million STIs are acquired every day. In 2012, an estimated 357 million new cases of curable STIs (gonorrhoea, chlamydia, syphilis and trichomoniasis) occurred among 15- to 49-year-olds worldwide, including 5.6 million cases of syphilis. There are an estimated 18 million prevalent cases of syphilis.

RECOMMENDATIONS
The current guidelines provide treatment recommendations for Treponema pallidum and congenital syphilis. The recommendations summarized in Table 1 apply to all adults and adolescents (10-19 years of age), including pregnant women, people living with HIV, people who are immunocompromised and key populations, including sex workers, men who have sex with men (MSM) and transgender persons.

The first eight recommendations apply to adults and adolescents (10-19 years of age), including people living with HIV, key populations (including sex workers, men who have sex with men and transgender persons), and pregnant women. Specific recommendations have also been developed for congenital syphilis caused by T. pallidum - recommendations 9 and 10 apply to infants (see section 4.3).

EARLY SYPHILIS (PRIMARY, SECONDARY AND EARLY LATENT SYPHILIS OF NOT MORE THAN TWO YEARS' DURATION) ADULTS AND ADOLESCENTS

RECOMMENDATION 1
In adults and adolescents with early syphilis, the WHO STI guideline recommends benzathine penicillin G 2.4 million units once intramuscularly over no treatment.
Strong recommendation, very low quality evidence

RECOMMENDATION 2
In adults and adolescents with early syphilis, the WHO STI guideline suggests using benzathine penicillin G 2.4 million units once intramuscularly over procaine penicillin G 1.2 million units 10-14 days intramuscularly.
Conditional recommendation, very low quality evidence

When benzathine or procaine penicillin cannot be used (e.g. due to penicillin allergy) or are not available (e.g. due to stock-outs), the WHO STI guideline suggests using doxycycline 100 mg twice daily orally for 14 days or ceftriaxone 1 g intramuscularly once daily for 10-14 days, or, in special circumstances, azithromycin 2 g once orally.
Conditional recommendation, very low quality evidence

RECOMMENDATION 3 : PREGNANT WOMEN
In pregnant women with early syphilis, the WHO STI guideline recommends benzathine penicillin G 2.4 million units once intramuscularly over no treatment. Strong recommendation, very low quality evidence

RECOMMENDATION 4 : PREGNANT WOMEN
In pregnant women with early syphilis, the WHO STI guideline suggests using benzathine penicillin G 2.4 million units once intramuscularly over procaine penicillin 1.2 million units intramuscularly once daily for 10 days.
Conditional recommendation, very low quality evidence

When benzathine or procaine penicillin cannot be used (e.g. due to penicillin allergy where penicillin desensitization is not possible) or are not available (e.g. due to stock-outs), the WHO STI guideline suggests using, with caution, erythromycin 500 mg orally four times daily for 14 days or ceftriaxone 1 g intramuscularly once daily for 10-14 days or azithromycin 2 g once orally.
Conditional recommendation, very low quality evidence

LATE SYPHILIS (INFECTION OF MORE THAN TWO YEARS' DURATION WITHOUT EVIDENCE OF TREPONEMAL INFECTION).ADULTS AND ADOLESCENTS

RECOMMENDATION 5
In adults and adolescents with late syphilis or unknown stage of syphilis, the WHO STI guideline recommends benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks over no treatment.
Strong recommendation, very low quality evidence Remarks: The interval between consecutive doses of benzathine penicillin should not exceed 14 days.

RECOMMENDATION 6
In adults and adolescents with late syphilis or unknown stage of syphilis, the WHO STI guideline suggests benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks over procaine penicillin 1.2 million units once daily for 20 days.
Conditional recommendation, very low quality evidence

When benzathine or procaine penicillin cannot be used (e.g. due to penicillin allergy where penicillin desensitization is not possible) or are not available (e.g. due to stock-outs), the WHO STI guideline suggests using doxycycline 100 mg twice daily orally for 30 days.
Conditional recommendation, very low quality evidence

RECOMMENDATION 7 : PREGNANT WOMEN
In pregnant women with late syphilis or unknown stage of syphilis, the WHO STI guideline recommends benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks over no treatment.
Strong recommendation, very low quality evidence

Remarks: The interval between consecutive doses of benzathine penicillin should not exceed 14 days.

RECOMMENDATION 8 : PREGNANT WOMEN
In pregnant women with late syphilis or unknown stage of syphilis, the WHO STI guideline suggests benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks over procaine penicillin 1.2 million units intramuscularly once daily for 20 days.
Conditional recommendation, very low quality evidence

When benzathine or procaine penicillin cannot be used (e.g. due to penicillin allergy where penicillin desensitization is not possible) or are not available (e.g. due to stock-outs), the WHO STI guideline suggests using, with caution, erythromycin 500 mg orally four times daily for 30 days.

CONGENITAL SYPHILIS

RECOMMENDATION 9 : CONGENITAL SYPHILIS INFANTS
In infants with confirmed congenital syphilis or infants who are clinically normal, but whose mothers had untreated syphilis, inadequately treated syphilis (including treatment within 30 days of delivery) or syphilis that was treated with non-penicillin regimens, the WHO STI guideline suggests aqueous benzyl penicillin or procaine penicillin. Conditional recommendation, very low quality evidence Dosages: • Aqueous benzyl penicillin 100 000-150 000 U/kg/day intravenously for 10-15 days • Procaine penicillin 50 000 U/kg/day single dose intramuscularly for 10-15 days Remarks: If an experienced venipuncturist is available, aqueous benzyl penicillin may be preferred instead of intramuscular injections of procaine penicillin.

RECOMMENDATION 10
In infants who are clinically normal and whose mothers had syphilis that was adequately treated with no signs of reinfection, the WHO STI guideline suggests close monitoring of the infants.
Conditional recommendation, very low quality evidence

Remarks: The risk of transmission of syphilis to the fetus depends on a number of factors, including maternal titres from non-treponemal tests (e.g. RPR), timing of maternal treatment and stage of maternal infection, and therefore this recommendation is conditional. If treatment is provided, benzathine penicillin G 50 000 U/kg/day single dose intramuscularly is an option.
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