Syphilis

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Syphilis
Classification and external resources

Electron micrograph of Treponema pallidum
ICD-10 A50.-A53.
ICD-9 090-097
DiseasesDB 29054
MedlinePlus 001327
eMedicine med/2224 emerg/563 derm/413
MeSH D013587

Syphilis is a sexually transmitted infection caused by a bacterium, Treponema pallidum. Congenital syphilis is when the bacteria is transmitted from a mother to her fetus during pregnancy, or when the baby is born.

There are four stages of syphilis, the primary, secondary, latent, and tertiary stages. In each stage, the signs and symptoms of syphilis are different. In the primary stage, a person usually has just a firm, painless, non-itchy skin ulceration, or wound, called a "chancre".

In the secondary stage, a person usually gets a rash, which usually appears on the palms of the hands and the soles of the feet. It may also appear on other parts of the body. In the "latent" stage, the syphilis has few or no symptoms: it is not visible or obvious.

When syphilis reaches the tertiary stage, which is the most severe, it causes many serious symptoms. These can include problems with the nervous system (the brain and nerves) and problems with the heart.

Syphilis is usually diagnosed with blood tests. However, the bacteria that causes syphilis can also be seen under a microscope. Most people who have syphilis can be treated and cured with antibiotics.

By 1999 syphilis infected about 12 million people worldwide. More than 90 percent of these cases involved people in the developing world. Cases of syphilis decreased dramatically after penicillin became available in the 1940s, but since 2000 the rates of infection have increased.

Some people with syphilis also have human immunodeficiency virus, or HIV. Both infections are got by having unprotected sex.[1] prostitution and promiscuity (having sex with many different people).[2][3][4]

Stages of syphilis[change | change source]

Primary[change | change source]

Primary stage syphilis sore (chancre) on the surface of a tongue.

After a person gets syphilis, the disease begins in the primary stage. People usually get primary syphilis by having direct sexual contact with infectious lesions - wounds caused by syphilis - on the genitals of a person who already has syphilis.[5] Later, a skin sore or lesion, called a chancre, appears at the place on the body that came into contact with the infected wounds.[6] The classic type the chancre gradually gets bigger in size until it becomes an ulcer.[7]

The chancres can be painful or tender and the sores can appear somewhere other than the genitals. In women, the most common place that the chancres appear is the cervix - the bottom of the uterus. The lymph nodes around the area that becomes infected usually become enlarged[6] (get bigger) about 7 to 10 days after the chancre forms.[7] If the person does not get treatment, their wound(s) can last for three to six weeks.[6]

Secondary[change | change source]

Secondary stage syphilis sores (lesions) on the soles of the feet called plantar lesions.~CDC
Secondary stage syphilis sores (lesions) on the soles of the feet called plantar lesions.~CDC
Secondary syphilis can cause rash-like lesions on the palms of the hands.
Secondary syphilis can cause rash-like lesions on the palms of the hands.
Reddish papules and nodules over much of the body due to secondary syphilis

If a person does not get treatment, syphilis will progress (or get worse) into the secondary stage about four to ten weeks after the person first got infected.[6] Secondary syphilis can appear in many different ways, but symptoms usually involve the skin, mucous membranes (like the nose, throat, genitals, or anus), and lymph nodes.[8] Sometimes, there is a reddish-pink, non-itchy rash on the chest, back and extremities (hands and feet), including the palms and soles.[6][9] All these lesions are infectious: they can spread infection. The bacteria lives inside the wounds.

The symptoms of secondary syphilis usually get better after three to six weeks.[10] However, in about 25% of cases (1 out of every 4), these symptoms can return. Many people who have secondary syphilis (40–85% of women, 20–65% of men) do not report having had the classic chancre during the primary stage of syphilis.[8]

Latent[change | change source]

A person qualifies as having latent syphilis when he has no symptoms of the disease, but blood tests show that he has syphilis.[5] Latent syphilis is described as either early or late, depending on how long it has been since the person was in the secondary syphilis stage In the United States, latent syphilis is called "early" if it has been less than one year since the secondary stage. It is called "late" if it has been more than one year since the secondary stage.[10] In the United Kingdom, latent syphilis is called early if it has been less than two years since the secondary stage, and it is called late if it has been more than two years.[7] In the early latent syphilis stage, a person can have a relapse of symptoms, meaning that his symptoms can come back after having gotten better. Late latent syphilis does not have any specific symptoms, and it is not as contagious (meaning that it does not spread as easily) as early latent syphilis.[10]

Tertiary[change | change source]

If a person with syphilis does not get treatment, the disease can progress (or get worse) to tertiary syphilis about three to 15 years after the person first got infected. There are three different forms of tertiary syphilis. Without treatment, one-third of people who are infected with syphilis (one in every three people with syphilis) get tertiary disease.[10] People with tertiary syphilis are not infectious (they cannot infect other people with syphilis at this stage).[6]

Neurosyphilis is an infection that involves the central nervous system (the brain and spinal cord). It can appear early, either without symptoms or in the form of syphilitic meningitis. This is a type of infection in the brain which can be very dangerous.

Neurosyphilis can also appear late, and in the late form it can cause various serious problems. For example, it can cause meningovascular syphilis, which leads to seizures and a loss of motivation (meaning that the person does not feel like doing anything). Late neurosyphilis can also cause general paresis, which leads to dementia (which causes problems with the way a person thinks, acts, and behaves toward other people) and tabes dorsalis (which causes poor balance and lightning-like pains in the lower extremities (the parts of the body that are farthest away from the heart, like the feet)).[6] Late neurosyphilis can also cause Argyll Robertson pupils, which causes a person's pupils (the black circles in the middle of their eyes) to be smaller than usual; the pupils also constrict (or get smaller) when the person focuses their eyes on objects that are close by, but they do not constrict after seeing bright lights, like normal pupils do.

The third type of tertiary syphilis - cardiovascular syphilis - usually happens 10 to 30 years after the person first got infected with syphilis. The most common symptom caused by cardiovascular syphilis is syphilitic aortitis, which can make the aorta - an important part of the heart - become dilated, or too big.[6]

Congenital[change | change source]

If a woman has syphilis, she can pass on the infection to her baby while she is pregnant, or to her baby when it is born. When a fetus or baby gets syphilis this way, it is called congenital syphilis. Two-thirds of infants with syphilis (or two out of every three) are born without any symptoms.

Cause[change | change source]

Bacteria[change | change source]

Histopathology of Treponema pallidum spirochetes using a modified Steiner silver stain

Treponema pallidum is a species of bacterium which is shaped like a spiral: a spirochaete.[11] There are different types of Treponema pallidum bacteria, which are subspecies.[12]

As far as scientists know, Treponema pallidum cannot live inside any animal other than humans.[13] This bacterium also cannot survive outside a human for more than a few days.

Transmission: how syphilis is spread[change | change source]

Syphilis is transmitted (or spread) mostly by sexual contact or during pregnancy from a mother to her fetus. Syphilis can pass through intact (whole and undamaged) mucous membranes, or through damaged skin.[6][13] Because of this, syphilis can be spread by kissing, and also through oral, vaginal, and anal sex.[6]

A person only needs to be exposed to a very small amount of the bacteria that causes syphilis in order to get infected. However, not everybody who is exposed to primary or secondary syphilis will get the disease.[10]

Most new cases of syphilis in the United States happen in men who have sex with men (who, specifically, get 60% of new cases, or 6 out of every 10). Syphilis can be spread through blood products (for example, if a person gets a blood donation). However, blood products are tested for syphilis in many countries, so in those countries there is only a low risk of getting syphilis this way. Scientists think that there is also a fairly low risk of getting syphilis by sharing needles.[6] Syphilis cannot be spread through toilet seats, daily activities, hot tubs, or sharing eating utensils (like forks or spoons) or clothing.[14]

Diagnosis[change | change source]

Rapid point-of-care syphilis test.
Syphlis is curable
Syphilis is curable if treated in time.

It is hard for doctors to diagnose syphilis (or to figure out that syphilis is what is causing a person's symptoms) based on the signs and symptoms that happen early on.[7] A medical professional can confirm that a person has syphilis by testing the person's blood, or by looking at the blood under a microscope. Blood tests are used more often, because they are easier to do. However, blood tests cannot tell which stage of syphilis a person has.

Prevention[change | change source]

As of 2010, there is no vaccine that works to prevent syphilis.[13] One of the best ways to prevent getting infected with syphilis is to abstain from (or stay away from) having sexual contact with someone who has syphilis. Using a latex condom the right way makes it less likely that a person will get syphilis if he has sexual contact with an infected person. However, even if a person uses a condom, it is still possible for him to get syphilis.[14][15] Because of this, the Centers for Disease Control and Prevention (CDC) says that the best ways to prevent syphilis are to be in a long-term relationship with a partner who does not have syphilis; for both partners to be loyal in their long-term relationship and not have sexual contact with anyone else; and to avoid using alcohol or other drugs that make it more likely for a person to have the type of sexual contact which is risky and can spread syphilis.[14]

Congenital syphilis in newborn babies can be prevented by screening mothers during early pregnancy (finding out whether they have syphilis) and treating women who are infected.[16] The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening, meaning that all pregnant women would be tested for syphilis.[17] The World Health Organization says that all women should be tested at their first antenatal (prenatal) visit, and again in the third trimester (the last of the three stages of pregnancy).[18] If a woman tests positive, her sexual partners should also be treated.[18] However, congenital syphilis is still common in the developing world, because many women do not get healthcare during pregnancy, and others get healthcare that does not include screening for syphilis.[16] Congenital syphilis still occurs once in a while in the developed world, because the people who are most likely to get syphilis (for example, through drug use) are also the least likely to get healthcare during pregnancy.[16] Different programs have been tried in low- and middle-income countries to make testing easier to get, and when these programs are happening and testing is easier to get, rates of congenital syphilis drop in those countries (meaning that not as many babies get the disease).[18]

Syphilis is a notifiable disease in many countries, including Canada,[19] the European Union,[20] and the United States.[21] This means that if a healthcare provider (like a doctor or nurse) knows that a person has syphilis, the provider has to tell public health authorities that the person is infected. This is done so that the public health authorities can talk to all of the people who the infected person has had sexual contact with, to let them know that they have been exposed to syphilis.[22] Doctors might also try to get patients to send their partners to get treatment.[23]

Medical professionals say that people who behave in ways that make it more likely to get syphilis should get tested regularly. For example, the CDC says that men who have sex with men should be tested at least every year.[24] Getting tested regularly helps prevent syphilis from being spread, because if a person is tested and finds out that they have syphilis, they are more likely to then get treatment and may be more careful to avoid spreading the disease to other people.

Treatment[change | change source]

Early infections[change | change source]

Syphilis that is not complicated can usually be treated and cured by antibiotic medications. Usually, the first treatment that is used is either a single dose of penicillin G, given intramuscularly (given with a needle as a shot into the muscle), or a single dose of oral azithromycin.[25] There are also other medications which can be used if penicillin G or azithromycin cannot be used (for example, if a person is allergic to them). Doxycycline and tetracycline are two other possible choices; however, they cannot be used in pregnant women. Antibiotic resistance has developed to a number of agents, including macrolides, clindamycin, and rifampin.[13] Ceftriaxone, a third-generation cephalosporin antibiotic, might be as effective as penicillin-based treatment.[6]

Late infections[change | change source]

Once syphilis progresses (or gets worse) into the late stages of the disease, it is harder to treat. For example, penicillin G does not travel very well into the central nervous system - the brain and major nerves, the areas which neurosyphilis affect. Because it is hard for penicillin G to get into these areas of the body, a single shot of penicillin - which will usually cure early syphilis - is not enough to cure neurosyphilis. Instead, people with neurosyphilis usually need to be given large doses of penicillin for at least 10 days, with the medicine given intravenously (given with a needle as a shot into a vein; this makes the medicine travel more directly into the central nervous system than a shot given into a muscle).[6][13] If a person is allergic to penicillin, other antibiotics like ceftriaxone, doxycycline, or tetracycline can be used, but they have to be given over longer periods of time[6]. Doctors may also try penicillin desensitization - meaning that they start by giving the person a very small dose of penicillin, and bit by bit they increase the amount of penicillin they give; sometimes this can keep the person from having an allergic reaction to the penicillin. Sometimes, late syphilis can also be treated with intramuscular penicillin G (given as a shot into the muscle), but the medication has to be given once a week for three weeks. Once a person has late-stage syphilis, treatment will keep their syphilis from getting any worse, but if the disease has already damaged the person's body, the treatment really does not help to reverse those damages. At best, treatment can only have a very small effect on the damage that has already happened.[6]

Jarisch-Herxheimer reaction[change | change source]

Sometimes, people who are getting treatment for syphilis can have a side effect - a symptom or problem that the medication is not designed to cause - called the Jarisch-Herxheimer reaction. This reaction usually starts within one hour after treatment begins and lasts for 24 hours. Some symptoms of the Jarisch-Herxheimer reaction are fever, muscle pains, headache, and tachycardia (meaning that the heart beats faster than usual)[6] This reaction is caused by proteins that are released from syphilis bacteria as they get broken open by antibiotic medication.[26]

Epidemiology[change | change source]

Age-standardized death from syphilis per 100,000 inhabitants in 2004[27]
     no data      <35      35-70      70-105      105-140      140-175      175-210
     210-245      245-280      280-315      315-350      350-500      >500

By 1999, syphilis was thought to have infected 12 million people, with more than 90% of cases (or 9 out of 10) happening to people in the developing world.[13] Syphilis affects between 700,000 and 1.6 million pregnancies a year. This can cause spontaneous abortions (the fetus dying before being born); stillbirths (the fetus being born dead); and congenital syphilis (where a fetus gets syphilis from its mother while she is pregnant, or a baby gets syphilis from its mother whike being born). In sub-Saharan Africa (the area below the Sahara Desert), syphilis plays a role in about 20% of perinatal deaths - deaths that happen soon after a baby is born.[12]

Rates of syphilis are higher among intravenous drug users (people who inject drugs into their veins using needles); among people who are infected with HIV; and among men who have sex with men.[2][3][4] In the United States, rates of syphilis (which measure how common the disease is within a certain group) have increased a lot among men. In 1997, men and women were equally as likely to have the disease; however, by 2007, rates of syphilis were six times greater in men than women.[28] Rates of syphilis are also different among different racial groups in the United States. In 2010, almost half of all people who had syphilis were African American.[29]

Syphilis used to be very common, and it caused many cases of illness and death all over the world. It was especially was very common in Europe during the 18th and 19th centuries (the 1700s and 1800s). During the early 20th century (the early 1900s), cases of syphilis decreased very quickly in the developed world, because antibiotics were being used more and more. However, rates of syphilis stopped decreasing in the 1980s and 1990s.[11] Since the year 2000, rates of syphilis have been increasing in the USA, United Kingdom, Australia, and Europe, mostly among men who have sex with men.[13] Rates of syphilis are not increasing as much for other specific groups of people in these countries. For example, among American women, rates of syphilis have stayed the same since the year 2000. Rates among women in the United Kingdom have increased, but not as much as among men in the United Kingdom.[30] In China and Russia, rates of syphilis have increased since the 1990s among heterosexual ("straight") people.[13] This is thought to be because of unsafe sexual practices, such as sexual promiscuity (having sex with many different people), prostitution (getting paid to have sex), and people not using things like condoms to protect themselves from getting sexually transmitted infections like syphilis.[13][30][31]

If they do not get treatment, 8% to 58% of people with syphilis (or 8 to 58 people out of 100) will die from the disease. Men die more often than women from syphilis.[6] Over the 19th and 20th centuries (the 1800s and 1900s), the symptoms of syphilis have become less severe (or not quite as bad), partly because treatments that work well have become much more available, and partly because the bacteria that causes syphilis has become weaker.[8] If a person gets treatment early on, he usually can be cured without the disease causing damage that cannot be fixed.[7] However, syphilis is still very dangerous and still causes serious problems, and sometimes death, if it is not treated. Also, if a person has syphilis, they are two to five times more likely to get HIV. Coinfection (being infected with both syphilis and HIV) is common; it happens in as many as 30% to 60% of people with syphilis (or 30 to 60 out of every 100) of people in some big cities.[6][13]

History[change | change source]

Portrait of Gerard de Lairesse by Rembrandt van Rijn, ca. 1665–67, oil on canvas. De Lairesse, himself a painter and art theorist, suffered from congenital syphilis that severely deformed his face and eventually blinded him.[32]

Nobody knows exactly where syphilis originated (meaning where and how it started)[6] There are two major ideas about where the disease came from. The first idea is called the "Columbian hypothesis" (a hypothesis is an educated guess about how something happened). This hypothesis says that when Christopher Columbus's crew came back to Europe after exploring the Americas, they brought syphilis back to Europe and spread the disease there. The other idea is called the "pre-Columbian" (meaning 'before Columbus') hypothesis. This hypothesis says that syphilis was already in Europe before this, and people just did not realize that the disease existed.[33] While there is evidence that can be used to back up both of these ideas, there is more evidence for the Columbian hypothesis.[34]

The first written records that talk about an outbreak of syphilis (where many people got the disease) in Europe are from 1494-1495. The outbreak happened in Naples, Italy, during a French invasion (meaning that France's military was coming into Italy).[11][33] Because the disease was spread by French troops (or soldiers) who were coming back from Italy, at first syphilis was called the "French disease". The name "syphilis" was first used in 1530 by an Italian doctor and poet named Girolamo Fracastoro; he used the word "syphilis" as the title of a Latin poem that talked about the damage the disease was causing in Italy.[35] At other times in history, syphilis was also known as the "Great Pox".[36][37]

In 1905, two men named Fritz Schaudinn and Erich Hoffmann first figured out that syphilis is caused by the Treponema pallidum bacteria.[11] The first treatment that was helpful in treating syphilis (called Salvarsan) was created in 1910 by Paul Ehrlich. Penicillin was then studied, and in 1943 penicillin was officially labeled as effective (or helpful) for syphilis.[11][36] This was a major breakthrough in the treatment of syphilis. Before there were good treatments for syphilis, the treatments that were used were often even worse than the disease. For example, people were treated with mercury (which is poisonous and causes serious health problems), or people were isolated (kept away from everyone else).[36]

Many famous people in history are thought to have had syphilis. For example, some people think that Franz Schubert, Arthur Schopenhauer, Édouard Manet[11], and Adolf Hitler had the disease[38].

References[change | change source]

  1. not using condoms to protect themselves from sexually transmitted infections
  2. 2.0 2.1 Coffin, LS; Newberry A et al (2010). "Syphilis in drug users in low and middle income countries". The International journal on drug policy 21 (1): 20–7. doi:10.1016/j.drugpo.2009.02.008. PMC 2790553. PMID 19361976.
  3. 3.0 3.1 Gao, L; Zhang L, Jin Q (2009). "Meta-analysis: prevalence of HIV infection and syphilis among MSM in China". Sexually transmitted infections 85 (5): 354–8. doi:10.1136/sti.2008.034702. PMID 19351623.
  4. 4.0 4.1 Karp, G; Schlaeffer F, Jotkowitz A, Riesenberg K (2009 Jan). "Syphilis and HIV co-infection". European journal of internal medicine 20 (1): 9–13. doi:10.1016/j.ejim.2008.04.002. PMID 19237085.
  5. 5.0 5.1 Committee on Infectious Diseases (2006). Larry K. Pickering. ed. Red book 2006 Report of the Committee on Infectious Diseases (27th ed.). Elk Grove Village, IL: American Academy of Pediatrics. pp. 631–44. ISBN 9781581102079.
  6. 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 Kent M.E. & Romanelli F. 2008. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother 42 (2): 226–36. [1]
  7. 7.0 7.1 7.2 7.3 7.4 Eccleston, K; Collins L, Higgins SP (2008 Mar). "Primary syphilis". International journal of STD & AIDS 19 (3): 145–51. doi:10.1258/ijsa.2007.007258. PMID 18397550.
  8. 8.0 8.1 8.2 Mullooly, C; Higgins, SP (2010 Aug). "Secondary syphilis: the classical triad of skin rash, mucosal ulceration and lymphadenopathy". International journal of STD & AIDS 21 (8): 537–45. doi:10.1258/ijsa.2010.010243. PMID 20975084.
  9. Dylewski J, Duong M (2 January 2007). "The rash of secondary syphilis". Canadian Medical Association Journal 176 (1): 33–5. doi:10.1503/cmaj.060665. PMC 1764588. PMID 17200385.
  10. 10.0 10.1 10.2 10.3 10.4 Bhatti MT (2007). "Optic neuropathy from viruses and spirochetes". Int Ophthalmol Clin 47 (4): 37–66, ix. doi:10.1097/IIO.0b013e318157202d. PMID 18049280.
  11. 11.0 11.1 11.2 11.3 11.4 11.5 Franzen, C (2008 Dec). "Syphilis in composers and musicians--Mozart, Beethoven, Paganini, Schubert, Schumann, Smetana". European Journal of Clinical Microbiology and Infectious Diseases 27 (12): 1151–7. doi:10.1007/s10096-008-0571-x. PMID 18592279.
  12. 12.0 12.1 Woods CR (June 2009). "Congenital syphilis-persisting pestilence". Pediatr. Infect. Dis. J. 28 (6): 536–7. doi:10.1097/INF.0b013e3181ac8a69. PMID 19483520.
  13. 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 Stamm LV (February 2010). "Global Challenge of Antibiotic-Resistant Treponema pallidum". Antimicrob. Agents Chemother. 54 (2): 583–9. doi:10.1128/AAC.01095-09. PMC 2812177. PMID 19805553. http://aac.asm.org/content/54/2/583.full.pdf.
  14. 14.0 14.1 14.2 "Syphilis - CDC Fact Sheet". Centers for Disease Control and Prevention (CDC). 16 September 2010. http://www.cdc.gov/std/syphilis/STDFact-Syphilis.htm. Retrieved 2007-05-30.
  15. Koss CA, Dunne EF, Warner L (July 2009). "A systematic review of epidemiologic studies assessing condom use and risk of syphilis". Sex Transm Dis 36 (7): 401–5. doi:10.1097/OLQ.0b013e3181a396eb. PMID 19455075.
  16. 16.0 16.1 16.2 Schmid, G (2004 Jun). "Economic and programmatic aspects of congenital syphilis prevention". Bulletin of the World Health Organization 82 (6): 402–9. PMC 2622861. PMID 15356931.
  17. U.S. Preventive Services Task, Force (2009 May 19). "Screening for syphilis infection in pregnancy: U.S. Preventive Services Task Force reaffirmation recommendation statement". Annals of internal medicine 150 (10): 705–9. PMID 19451577.
  18. 18.0 18.1 18.2 Hawkes, S; Matin, N, Broutet, N, Low, N (2011 Jun 15). "Effectiveness of interventions to improve screening for syphilis in pregnancy: a systematic review and meta-analysis". The Lancet infectious diseases 11 (9): 684–91. doi:10.1016/S1473-3099(11)70104-9. PMID 21683653.
  19. "National Notifiable Diseases". Public Health Agency of Canada. 2005-04-05. http://dsol-smed.phac-aspc.gc.ca/dsol-smed/ndis/list-eng.php. Retrieved 2 August 2011.
  20. Viñals-Iglesias, H; Chimenos-Küstner, E (2009 Sep 1). "The reappearance of a forgotten disease in the oral cavity: syphilis". Medicina oral, patologia oral y cirugia bucal 14 (9): e416–20. PMID 19415060.
  21. "Table 6.5. Infectious Diseases Designated as Notifiable at the National Level-United States, 2009 [a"]. Red Book. http://www.unboundmedicine.com/redbook/ub/view/RedBook/187389/all/Table_6_5__Infectious_Diseases_Designated_as_Notifiable_at_the_National_Level_United_States__2009_%5Ba%5D. Retrieved 2 August 2011.
  22. Brunner & Suddarth's textbook of medical-surgical nursing. (12th ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. 2010. p. 2144. ISBN 9780781785891. http://books.google.com/books?id=SmtjSD1x688C&pg=PA2144.
  23. Hogben, M (2007 Apr 1). "Partner notification for sexually transmitted diseases". Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 44 Suppl 3: S160–74. doi:10.1086/511429. PMID 17342669.
  24. "Trends in Sexually Transmitted Diseases in the United States: 2009 National Data for Gonorrhea, Chlamydia and Syphilis". Centers for Disease Control and Prevention (CDC). 22 November 2010. http://www.cdc.gov/std/stats09/tables/trends-table.htm. Retrieved 3 August 2011.
  25. David N. Gilbert, Robert C. Moellering, George M. Eliopoulos, et al.. The Sanford guide to antimicrobial therapy 2011 (41st ed.). Sperryville, VA: Antimicrobial Therapy. p. 22. ISBN 9781930808652.
  26. Radolf, JD; Lukehart SA (editors) (2006). Pathogenic Treponema: Molecular and Cellular Biology. Caister Academic Press. ISBN 1-904455-10-7.
  27. "Disease and injury country estimates". World Health Organization (WHO). 2004. http://www.who.int/healthinfo/global_burden_disease/estimates_country/en/index.html. Retrieved 11 November 2009.
  28. "Trends in Reportable Sexually Transmitted Diseases in the United States, 2007". Centers for Disease Control and Prevention(CDC). 13 January 2009. http://www.cdc.gov/std/stats07/trends.htm. Retrieved 2 August 2011.
  29. "STD Trends in the United States: 2010 National Data for Gonorrhea, Chlamydia, and Syphilis". Centers for Disease Control and Prevention (CDC). 22 November 2010. http://www.cdc.gov/std/stats10/tables/trends-table.htm. Retrieved 20 November 2011.
  30. 30.0 30.1 Kent, ME; Romanelli, F (2008 Feb). "Reexamining syphilis: an update on epidemiology, clinical manifestations, and management". The Annals of pharmacotherapy 42 (2): 226–36. doi:10.1345/aph.1K086. PMID 18212261.
  31. Ficarra, G; Carlos, R (2009 Sep). "Syphilis: The Renaissance of an Old Disease with Oral Implications". Head and neck pathology 3 (3): 195–206. doi:10.1007/s12105-009-0127-0. PMC 2811633. PMID 20596972.
  32. The Metropolitan Museum of Art Bulletin, Summer 2007, pp. 55–56.
  33. 33.0 33.1 Farhi, D; Dupin, N (2010 Sep-Oct). "Origins of syphilis and management in the immunocompetent patient: facts and controversies". Clinics in dermatology 28 (5): 533–8. doi:10.1016/j.clindermatol.2010.03.011. PMID 20797514.
  34. Rothschild, BM (2005-05-15). "History of syphilis". Clinical infectious diseases: an official publication of the Infectious Diseases Society of America 40 (10): 1454–63. doi:10.1086/429626. PMID 15844068.
  35. Nancy G. "Siraisi, Drugs and Diseases: New World Biology and Old World Learning," in Anthony Grafton, Nancy G. Siraisi, with April Shelton, eds., New World, Ancient Texts (Cambridge MA: Belknap Press/Harvard University Press, 1992), 159-94
  36. 36.0 36.1 36.2 Dayan, L; Ooi, C (2005 Oct). "Syphilis treatment: old and new". Expert opinion on pharmacotherapy 6 (13): 2271–80. doi:10.1517/14656566.6.13.2271. PMID 16218887.
  37. Knell, RJ (2004-05-07). "Syphilis in renaissance Europe: rapid evolution of an introduced sexually transmitted disease?". Proceedings. Biological sciences / the Royal Society 271 Suppl 4 (Suppl 4): S174–6. doi:10.1098/rsbl.2003.0131. PMC 1810019. PMID 15252975. http://rspb.royalsocietypublishing.org/content/271/Suppl_4/S174.full.pdf.
  38. "Hitler syphilis theory revived". BBC News. 12 March 2003. http://news.bbc.co.uk/2/hi/health/2842819.stm.