uses antibodies tagged with fluorescein, which attach to specific syphilis proteins, while pcr uses techniques to detect the presence of specific syphilis genes. these tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis. prevention vaccine as of 2018, there is no vaccine effective for prevention. several vaccines based on treponemal proteins reduce lesion development in an animal model but research continues. sex condom use reduces the likelihood of transmission during sex, but does not eliminate the risk. the centers for disease control and prevention (cdc) states, "correct and consistent use of latex condoms can reduce the risk of syphilis only when the infected area or site of potential exposure is protected. however, a syphilis sore outside of the area covered by a latex condom can still allow transmission, so caution should be exercised even when using a condom." abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis. the cdc states, "the surest way to avoid transmission of sexually transmitted diseases, including syphilis, is to abstain from sexual contact or to be in a long-term mutually monogamous relationship with a partner who has been tested and is known to be uninfected." congenital disease portrait of a man affected with what is now believed to have been congenital syphilis c. 1820 congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected. the united states preventive services task force (uspstf) strongly recommends universal screening of all pregnant women, while the world health organization (who) recommends all women be tested at their first antenatal visit and again in the third trimester. if they are positive, it is recommended their partners also be treated. congenital syphilis is still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others receive does not include screening. it still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy. several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries. point-of-care testing to detect syphilis appeared to be reliable although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies. screening the cdc recommends that sexually active men who have sex with men be tested at least yearly. the uspstf also recommends screening among those at high risk. syphilis is a notifiable disease in many countries, including canada, the european union, and the united states. this means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. physicians may also encourage patients to send their partners to seek care. several strategies have been found to improve follow-up for sti testing, including email and text messaging of reminders for appointments. 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. 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 inunction or when inhaled as a suffumigation. 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. mercury salts such as mercury (ii) chloride were still in prominent medical use as late as 1916, and considered effective and worthwhile treatments. early infections the first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose of intramuscular benzathine benzylpenicillin. the bacterium is highly vulnerable to penicillin when treated early, and a treated individual is typically rendered non-infective in about 24 hours. doxycycline and tetracycline are alternative choices for those allergic to penicillin; due to the risk of birth defects, these are not recommended for pregnant women. resistance to macrolides, rifampicin, and clindamycin is often present. ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment. it is recommended that a treated person avoid sex until the sores are healed. in comparison to azithromycin for treatment in early infection, there is lack of strong evidence for superiority of azithromycin to benzathine penicillin g. 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 penicillin g for a minimum of 10 days. if a person is allergic to penicillin, ceftriaxone may be used or penicillin desensitization attempted. other late presentations may be treated with once-weekly intramuscular benzathine penicillin for three weeks. treatment at this stage solely limits further progression of the disease and has a limited effect on damage which has already occurred. 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. jarisch–herxheimer reaction jarisch–herxheimer reaction in a person with syphilis and human immunodeficiency virus one of the potential side effects of treatment is the jarisch–herxheimer reaction. it frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and a fast heart rate. it is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria. pregnancy penicillin is an effective treatment for syphilis in pregnancy but there is no agreement on which dose or route of delivery is most effective. epidemiology main article: epidemiology of syphilis syphilis deaths per million persons in 2012 0–0 1–1 2–3 4–10 11–19 20–28 29–57 58–138 age-standardized disability adjusted life years from syphilis per 100,000 inhabitants in 2004 no data <35 35–70 70–105 105–140 140–175 175–210 210–245 245–280 280–315 315–350 350–500 >500 in 2012, about 0.5% of adults were infected with syphilis, with 6 million new cases. in 1999, it is believed to have infected 12 million additional people, with greater than 90% of cases in the developing world. it affects between 700,000 and 1.6 million pregnancies a year, resulting in spontaneous abortions, stillbirths, and congenital syphilis. during 2015, it caused about 107,000 deaths, down from 202,000 in 1990. in sub-saharan africa, syphilis contributes to approximately 20% of perinatal deaths. rates are proportionally higher among intravenous drug users, those who are infected with hiv, and men who have sex with men. in the united states about 55,400 people are newly infected each year as of 2014. african americans accounted for almost half of all cases in 2010. as of 2014, syphilis infections continue to increase in the united states. in the united states as of 2020, rates of syphilis have increased by more than threefold; in 2018 approximately 86% of all cases of syphilis in the united states were in men. in 2021, preliminary cdc data illustreted that 2,677 cases of congenital syphilis were found in the population of 332 million in the united state. syphilis was very common in europe during the 18th and 19th centuries. flaubert found it universal among nineteenth-century egyptian prostitutes. in the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotics, until the 1980s and 1990s. since 2000, rates of syphilis have been increasing in the us, canada, the uk, australia and europe, primarily among men who have sex with men. rates of syphilis among us women have remained stable during this time, while rates among uk women have increased, but at a rate less than that of men. increased rates among heterosexuals have occurred in china and russia since the 1990s. this has been attributed to unsafe sexual practices, such as sexual promiscuity, prostitution, and decreasing use of barrier protection. left untreated, it has a mortality rate of 8% to 58%, with a greater death rate among males. the symptoms of syphilis have become less severe over the 19th and 20th centuries, in part due to widespread availability of effective treatment, and partly due to virulence of the bacteria. with early treatment, few complications result. syphilis increases the risk of hiv transmission by two to five times, and coinfection is common (30–60% in some urban centers). in 2015, cuba became the first country to eliminate mother-to-child transmission of syphilis. history main article: history of syphilis portrait of gerard de lairesse by rembrandt van rijn, circa 1665–67, oil on canvas. de lairesse, himself a painter and art theorist, had congenital syphilis that deformed his face and eventually blinded him. paleopatholgists have known for decades that syphilis was present in the americas before european contact. the situation in europe and afro-eurasia has been murkier and caused considerable debate. according to the columbian theory, syphilis was brought to spain by the men who sailed with christopher columbus in 1492 and spread from there, with a serious epidemic in naples beginning as early as 1495. contemporaries believed the disease sprang from american roots, and in the sixteenth century physicians wrote extensively about the new disease inflicted on them by the returning explorers. most historians and paleopathologists initially accepted the columbian theory, but over several decades beginning in the 1960s examples of probable treponematosis—the parent disease of syphilis, bejel, and yaws—in skeletal remains have shifted opinion. as a result the pre-columbian hypothesis is now more widely accepted. it argues that treponemal disease in the form of bejel and yaws was a common childhood ailment in europe and afro-eurasia beginning in ancient times. largely benign if still unpleasant, infections occurred among the young, transmitted via shared drinking vessels or bedding with only a small bacterial load. in adulthood, people infected as children had a certain degree of immunity that prevented serious symptoms upon reinfection. once living conditions began to change with urbanization, however, and certain more elite social groups separated themselves from their inferiors and regularly practiced better hygiene, treponematosis was driven out of the age group in which it had become endemic. it then began to appear in adults as syphilis. because they had never been exposed as children, they were not able to fend off serious illness. spreading the disease via sexual contact also led to victims being infected with a massive bacterial load from open sores on the genitalia. adults in higher socioeconomic groups then became very sick with painful and debilitating symptoms lasting for decades. often they died of the disease, as did their children who were infected with congenital syphilis. the difference between rural and urban populations was first noted by ellis herndon hudson, a clinician who published extensively about the prevalence of treponematosis, including syphilis, in times past. the importance of bacterial load was first noted by the physician ernest grin in 1952 in his study of syphilis in bosnia. the most compelling evidence for the validity of the pre-columbian hypothesis is the presence of syphilitic-like damage to bones and teeth in medieval skeletal remains. while the absolute number of cases is not large, they keep turning up, most recently in 2015. at least fifteen cases of acquired treponematosis based on evidence from bones, and six examples of congenital treponematosis based on evidence from teeth, are now widely accepted. in several of the twenty-one cases the evidence may also indicate syphilis. a healthy man and a diseased man torture christ before his crucifixion. books of hours, c. 1375-1435 (detail). france. (getty museum open content program). a man with a diseased penis torments christ. diptych with the passion of christ c. 1400 (detail). austria, styria. (cleveland museum of art open access program) in 2020, a group of leading paleopathologists concluded that enough evidence had been collected to prove that treponemal disease, almost certainly including syphilis, had existed in europe prior to the voyages of columbus. there is an outstanding issue, however. damaged teeth and bones may seem to hold proof of pre-columbian syphilis, but there is a possibility that they point to an endemic form of treponemal disease instead. as syphilis,