Editing Syphilis (section)

==Treatment==

===Historic use of mercury===
As a form of [[chemotherapy]], elemental mercury had been used to treat skin diseases in Europe as early as 1363.<ref>{{cite journal|title=Syphilis – Its early history and Treatment until Penicillin and the Debate on its Origins|author=John Frith |journal=History|volume=20|number=4|url=https://jmvh.org/article/syphilis-its-early-history-and-treatment-until-penicillin-and-the-debate-on-its-origins/}}</ref> As syphilis spread, preparations of mercury were among the first medicines used to combat it. Mercury is in fact highly anti-microbial: by the 16th century it was sometimes found to be sufficient to halt development of the disease when applied to ulcers as an [[wikt:inunction|inunction]] or when inhaled as a [[wikt:suffumigation|suffumigation]]. It was also treated by ingestion of mercury compounds.<ref>{{cite web |date=30 April 2019 |title=Sex and syphilis |url=https://wellcomecollection.org/articles/XMF0JBEAAI--0OGQ |access-date=22 November 2023 |website=Wellcome Collection}}</ref> Once the disease had gained a strong foothold, however, the amounts and forms of mercury necessary to control its development exceeded the human body's ability to tolerate it, and the treatment became worse and more lethal than the disease. Nevertheless, medically directed [[mercury poisoning]] became widespread through the 17th, 18th, and 19th centuries in Europe, North America, and India.<ref>{{cite journal|title=Mercury as an Antisyphilitic Chemotherapeutic Agent|journal=Journal of the Royal Society of Medicine|author=G J O'Shea|year=1990 |volume=83|issue=June 1990|pages=392–395 |pmid=2199676 |pmc=1292694 |s2cid=19322310 |doi=10.1177/014107689008300619}}</ref> Mercury salts such as [[mercury (II) chloride]] were still in prominent medical use as late as 1916, and considered effective and worthwhile treatments.<ref>{{cite journal|journal=JAMA|author=P. I. Nixon|title=The Intravenous Use of Mercuric Chlorid |date=20 May 1916|volume=LXVI|issue=21|page=1622|doi=10.1001/jama.1916.25810470004018d |url=https://jamanetwork.com/journals/jama/article-abstract/438477}}</ref>

===Early infections===
The first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose of [[Intramuscular injection|intramuscular]] [[benzathine benzylpenicillin]].<ref name=CDC2015a/> The bacterium is highly vulnerable to penicillin when treated early, and a treated individual is typically rendered non-infective in about 24 hours.<ref>{{cite web|url=https://www.canada.ca/en/public-health/services/infectious-diseases/sexual-health-sexually-transmitted-infections/canadian-guidelines/syphilis/treatment-follow-up.html|title=Syphilis guide: Treatment and follow-up|date=7 July 2022|publisher=Government of Canada}}</ref> [[Doxycycline]] and [[tetracycline]] are alternative choices for those allergic to penicillin; due to the risk of [[birth defect]]s, these are not recommended for pregnant women.<ref name=CDC2015a>{{cite web|last1=Center for Disease Control and Prevention (CDC)|title=Syphilis-CDC fact sheet|url=https://www.cdc.gov/std/syphilis/stdfact-syphilis-detailed.htm|website=CDC|access-date=1 March 2015|url-status=live|archive-url=https://web.archive.org/web/20150225182123/http://www.cdc.gov/std/syphilis/stdfact-syphilis-detailed.htm|archive-date=25 February 2015}}</ref> [[Antibiotic resistance|Resistance]] to [[macrolide]]s, [[rifampicin]], and [[clindamycin]] is often present.<ref name=ST10/> [[Ceftriaxone]], a third-generation [[cephalosporin]] [[antibiotic]], may be as effective as penicillin-based treatment.<ref name=Kent08/> It is recommended that a treated person avoid sex until the sores are healed.<ref name=CDC2014/> In comparison to azithromycin for treatment in early infection, there is lack of strong evidence for superiority of azithromycin to benzathine penicillin G.<ref>{{Cite journal |last1=Bai |first1=Zheng Gang |last2=Wang |first2=Baoxi |last3=Yang |first3=Kehu |last4=Tian |first4=Jin Hui |last5=Ma |first5=Bin |last6=Liu |first6=Yali |last7=Jiang |first7=Lei |last8=Gai |first8=Qiong Yan |last9=He |first9=Xiaodong |last10=Li |first10=Youping |date=13 June 2012 |title=Azithromycin versus penicillin G benzathine for early syphilis |journal=The Cochrane Database of Systematic Reviews |issue=6 |pages=CD007270 |doi=10.1002/14651858.CD007270.pub2 |issn=1469-493X |pmid=22696367|pmc=11337171 }}</ref>

===Late infections===
For neurosyphilis, due to the poor penetration of benzathine penicillin into the [[central nervous system]], those affected are given large doses of [[Intravenous therapy|intravenous]] [[penicillin G]] for a minimum of 10 days.<ref name=Kent08/><ref name=ST10/> If a person is allergic to penicillin, ceftriaxone may be used or penicillin [[Desensitization_(medicine)|desensitization]] attempted.<ref name=Kent08/> Other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks.<ref name=Kent08/> Treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred.<ref name=Kent08/> Serologic cure can be measured when the non-treponemal titers decline by a factor of 4 or more in 6–12 months in early syphilis or 12–24 months in late syphilis.<ref name=NEJM2020/>

===Jarisch–Herxheimer reaction===
[[File:Jarisch-Herxheimer reaction in patient (cropped).jpg|thumb|right|Jarisch–Herxheimer reaction in a person with syphilis and human immunodeficiency virus<ref>{{cite journal |last1=D'Eça Júnior |first1=A |last2=Rodrigues |first2=LDS |last3=Costa |first3=LC |title=Jarisch–Herxheimer reaction in a patient with syphilis and human immunodeficiency virus infection. |journal=Revista da Sociedade Brasileira de Medicina Tropical |date=2017 |volume=51 |issue=6 |pages=877–878 |doi=10.1590/0037-8682-0419-2017 |pmid=30517548|doi-access=free }}</ref>]]
One of the potential side effects of treatment is the [[Jarisch–Herxheimer reaction]].<ref name=Kent08/> It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and a [[tachycardia|fast heart rate]].<ref name="Kent08"/> It is  results from the release of pro-inflammatory cytokines by the immune system in response to [[lipoprotein]]s released from rupturing syphilis bacteria.<ref name=Radolf2006>{{cite book |editor1= Radolf, JD |editor2=Lukehart SA |year=2006 |title=Pathogenic ''Treponema'': Molecular and Cellular Biology |publisher=Caister Academic Press |isbn= 978-1-904455-10-3}}</ref>

===Pregnancy===
Penicillin is an effective treatment for syphilis in pregnancy<ref>{{cite journal |last1=Alexander|first1=JM|last2=Sheffield|first2=JS|last3=Sanchez|first3=PJ|last4=Mayfield|first4=J|last5=Wendel GD|first5=Jr|title=Efficacy of treatment for syphilis in pregnancy.|journal=Obstetrics and Gynecology|date=January 1999|volume=93|issue=1|pages=5–8|pmid=9916946|doi=10.1016/s0029-7844(98)00338-x}}</ref> but there is no agreement on which dose or route of delivery is most effective.<ref name=Walk2001>{{cite journal |last1=Walker|first1=GJ|title=Antibiotics for syphilis diagnosed during pregnancy.|journal=The Cochrane Database of Systematic Reviews|date=2001|volume=2010|issue=3|pages=CD001143|pmid=11686978|doi=10.1002/14651858.CD001143|pmc=8407021}}</ref>