Syphilis overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]
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Overview
Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. The signs and symptoms of syphilis are numerous; before the advent of serological testing, precise diagnosis was very difficult. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Syphilis (unless antibiotic-resistant) can be easily treated with antibiotics including penicillin. The oldest and still most effective method is an intramuscular injection of benzathine penicillin. If not treated, syphilis can cause serious effects such as damage to the heart, aorta, brain, eyes, and bones. In some cases these effects can be fatal. In 1998, the complete genetic sequence of T. pallidum was published which may aid understanding of the pathogenesis of syphilis.
Historical Perspective
The name "syphilis" was coined by the Italian physician and poet Girolamo Fracastoro in his epic noted poem, written in Latin, entitled Syphilis sive morbus gallicus (Latin for "Syphilis or The French Disease") in 1530. The protagonist of the poem is a shepherd named Syphilus (perhaps a variant spelling of Sipylus, a character in Ovid's Metamorphoses). Syphilus is presented as the first man to contract the disease, sent by the god Apollo as punishment for the defiance that Syphilus and his followers had shown him. From this character Fracastoro derived a new name for the disease, which he also used in his medical text De Contagionibus ("On Contagious Diseases"). Until that time, as Fracastoro notes, syphilis had been called the "French disease" in Italy and Germany, and the "Italian disease" in France. In addition, the Dutch called it the "Spanish disease", the Russians called it the "Polish disease", the Turks called it the "Christian disease" or "Frank disease" (frengi) and the Tahitians called it the "British disease". These 'national' names are due to the disease often being present among invading armies or sea crews, due to their high amount of unprotected sexual contacts with prostitutes. It's interesting to notice how the invaders named it after the invaded country and vice versa. It was also called "Great pox" in the 16th century to distinguish it from smallpox. In its early stages, the Great pox produced a rash similar to smallpox (also known as variola). However, the name is misleading, as smallpox was a far more deadly disease. The terms "Lues" (or Lues venerea, Latin for "venereal plague") and "Cupid's disease" have also been used to refer to syphilis. In Scotland, Syphilis was referred to as the Grandgore. It was also called The Black Lion.
Classification
Syphilis may be classified according to the development of disease into 2 groups: congenital and acquired. Acquired syphilis may be classified further into 4 subtypes: primary, secondary, latent and tertiary syphilis.[1][2][3]
Pathophysiology
Syphilis is caused by the spirochete, Treponema pallidum. It has an incubation period of 3 - 12 weeks. The spirochete penetrates intact mucous membrane or microscopic dermal abrasions and rapidly enters systemic circulation with the central nervous system being invaded during the early phase of infection. The meninges and blood vessels are initially involved with the brain parenchyma and spinal cord being involved in the later stages of the disease. The histopathological hallmark findings are endarteritis and plasma cell-rich infiltrates reflecting a delayed-type of hypersensitivity to the spirochete.[4][5][6]
Causes
Syphilis is caused by a spirochete, Treponema pallidum. The spirochete rapidly penetrates via intact mucosal membranes or microscopic dermal abrasions. It is spread through intimate sexual contact, blood transfusion or vertical transmission from infected mother to fetus.[7]
Differentiating Syphilis from other Diseases
Syphilis is a curable sexually transmitted disease caused by the Treponema pallidum spirochete. The route of transmission of syphilis is almost always by sexual contact, although there are examples of congenital syphilis via transmission from mother to child in utero. In fact, the disease was dubbed the "Great Imitator" because it was often confused with other diseases, particularly in its tertiary stage. Hence, patients with tertiary syphilis should also be tested for other sexually transmitted diseases such as chlamydia, gonorrhea, trichomoniasis, bacterial vaginosis and HIV infection.[4][8][9][10][11]
Epidemiology and Demographics
In 2012, the incidence of syphilis was estimated to be 6 million cases worldwide. From year 2005 to 2014, the incidence of syphilis in the United States increased from 2.9 to 6.3 cases/100,000/year. The rate of reported cases increased by 15.1% between 2013 and 2014 in the United States.[12] Syphilis incidence increased in every region of the Untied States in 2014, with the highest rate in the West and lowest rate in the Midwest. In 2012, the prevalence of syphilis was estimated to be approximately 18 million cases in men and women aged 15-29 worldwide.[13] The incidence and prevalence of syphilis may be affected by age, gender, race, sexual behavior and geographical distribution.[12][14][15][16][17][18]
Risk Factors
The risk factors of syphilis include unprotected sex, IV drug abuse and occupational risk for health care professionals.[19][20][21][22][23]
Screening
Screening guidelines for syphilis include all high risk non pregnant individuals aged 15-65, all pregnant females, men who have sex with men, women who have sex with women, HIV positive individuals.[24] Routine screening of adolescents who are asymptomatic for syphilis is not recommended [25][26]
Natural History, Complications and Prognosis
Initial presentation of syphilis is appearance of painless chancre after 3-4 weeks of exposure. If left untreated, chancre self resolves and may progress to develop constitutional symptoms and generalized symmetric rash in four to eight weeks. In less than 10% of individuals, complications such as hepatitis, iritis, nephritis, and neurological problems may develop at this stage. However, it resolves in four to eight weeks without treatment and patient enters into asymptomatic latent phase. About a quarter of patients may develop recurrence of similar symptoms in one year. If left untreated, 35% of patients may develop tertiary syphilis which include complications such as cardiovascular involvement, neurologic infection and gummatous lesions involving skin, bone and joints which is associated with significant morbidity and mortality.[6][1][27][28] The prognosis of syphilis varies by stage of disease.Prognosis of primary and secondary syphilis is good with treatment. For tertiary syphilis, prognosis varies by site of involvememnt and duration of disease. 90% of patients with neurosyphilis respond to treatment. However, mortality rates are high with cardiovascular complications.[27][28]
Treatment
Medical Therapy
Penicillin G, administered parenterally, is the preferred drug for treating all stages of syphilis. If allergic, then tetracycline or doxycycline may also be used. During pregnancy, parenteral penicillin G is the only therapy with documented efficacy for syphilis.[29]
Management of Primary and Secondary Stages
Parenteral penicillin G has been used effectively for more than 50 years to achieve clinical resolution (i.e., the healing of lesions and prevention of sexual transmission) and to prevent late sequelae. However, no comparative trials have been adequately conducted to guide the selection of an optimal penicillin regimen (i.e., the dose, duration, and preparation). Substantially fewer data are available for non-penicillin regimens.[30]
Tertiary Syphilis
Tertiary syphilis refers to gumma and cardiovascular syphilis but not to all neurosyphilis. Patients who are not allergic to penicillin and have no evidence of neurosyphilis should be treated with the following regimen.[31][32]
Neurosyphilis
CNS involvement can occur during any stage of syphilis. However, CSF laboratory abnormalities are common in persons with early syphilis, even in the absence of clinical neurological findings. No evidence exists to support variation from recommended treatment for early syphilis for patients found to have such abnormalities. If clinical evidence of neurologic involvement is observed (e.g., cognitive dysfunction, motor or sensory deficits, ophthalmic or auditory symptoms, cranial nerve palsies, and symptoms or signs of meningitis), a CSF examination should be performed. Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis. Patients who have neurosyphilis or syphilitic eye disease (e.g., uveitis, neuroretinitis, and optic neuritis) should be treated with the recommended regimen for neurosyphilis; those with eye disease should be managed in collaboration with an ophthalmologist. A CSF examination should be performed for all patients with syphilitic eye disease to identify those with abnormalities; patients found to have abnormal CSF test results should be provided follow-up CSF examinations to assess treatment response.[32]
Primary Prevention
As of 2010, there is no vaccine effective for prevention.[33]
Secondary Prevention
While abstinence from intimate physical contact with an infected person is very effective at reducing the transmission of syphilis, it should be noted that T. pallidum readily crosses intact mucosa and cut skin, including areas not covered by a condom. Proper and consistent use of a latex condom can reduce, but not eliminate, the spread of syphilis.[3]
References
- ↑ 1.0 1.1 French P (2007). "Syphilis". BMJ. 334 (7585): 143–7. doi:10.1136/bmj.39085.518148.BE. PMC 1779891. PMID 17235095.
- ↑ Chakraborty R, Luck S (2008). "Syphilis is on the increase: the implications for child health". Arch Dis Child. 93 (2): 105–9. doi:10.1136/adc.2006.103515. PMID [uid 18208988[uid]] Check
|pmid=value (help). - ↑ http://www.cdc.gov/std/stats10/app-casedef.htm Accessed on September 19, 2016
- ↑ 4.0 4.1 Carlson JA, Dabiri G, Cribier B, Sell S (2011). "The immunopathobiology of syphilis: the manifestations and course of syphilis are determined by the level of delayed-type hypersensitivity". Am J Dermatopathol. 33 (5): 433–60. doi:10.1097/DAD.0b013e3181e8b587. PMC 3690623. PMID 21694502.
- ↑ Fitzgerald TJ (1992). "The Th1/Th2-like switch in syphilitic infection: is it detrimental?". Infect Immun. 60 (9): 3475–9. PMC 257347. PMID 1386838.
- ↑ 6.0 6.1 Singh AE, Romanowski B (1999). "Syphilis: review with emphasis on clinical, epidemiologic, and some biologic features". Clin Microbiol Rev. 12 (2): 187–209. PMC 88914. PMID 10194456.
- ↑ Antal GM, Lukehart SA, Meheus AZ (January 2002). "The endemic treponematoses". Microbes Infect. 4 (1): 83–94. doi:10.1016/S1286-4579(01)01513-1. PMID 11825779.
- ↑ Fatahzadeh M, Schwartz RA (2007). "Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management". J. Am. Acad. Dermatol. 57 (5): 737–63, quiz 764–6. doi:10.1016/j.jaad.2007.06.027. PMID 17939933.
- ↑ O'Farrell N (2002). "Donovanosis". Sexually Transmitted Infections. 78 (6): 452–7. PMC 1758360. PMID 12473810.
- ↑ Coovadia YM, Kharsany A, Hoosen A (1985). "The microbial aetiology of genital ulcers in black men in Durban, South Africa". Genitourin Med. 61 (4): 266–9. PMC 1011828. PMID 2991120.
- ↑ Mabey D, Peeling RW (2002). "Lymphogranuloma venereum". Sexually Transmitted Infections. 78 (2): 90–2. PMC 1744436. PMID 12081191.
- ↑ 12.0 12.1 https://www.cdc.gov/std/stats14/surv-2014-print.pdf Accessed on September 16, 2016
- ↑ Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N; et al. (2015). "Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting". PLoS One. 10 (12): e0143304. doi:10.1371/journal.pone.0143304. PMC 4672879. PMID 26646541.
- ↑ Satterwhite CL, Torrone E, Meites E, Dunne EF, Mahajan R, Ocfemia MC; et al. (2013). "Sexually transmitted infections among US women and men: prevalence and incidence estimates, 2008". Sex Transm Dis. 40 (3): 187–93. doi:10.1097/OLQ.0b013e318286bb53. PMID 23403598.
- ↑ http://apps.who.int/iris/bitstream/10665/85376/1/9789241505895_eng.pdf?=1 Accessed on September 16, 2016
- ↑ Purcell DW, Johnson CH, Lansky A, Prejean J, Stein R, Denning P; et al. (2012). "Estimating the population size of men who have sex with men in the United States to obtain HIV and syphilis rates". Open AIDS J. 6: 98–107. doi:10.2174/1874613601206010098. PMC 3462414. PMID 23049658.
- ↑ Heffelfinger JD, Swint EB, Berman SM, Weinstock HS (2007). "Trends in primary and secondary syphilis among men who have sex with men in the United States". Am J Public Health. 97 (6): 1076–83. doi:10.2105/AJPH.2005.070417. PMC 1874206. PMID 17463387.
- ↑ Judson FN, Penley KA, Robinson ME, Smith JK (1980). "Comparative prevalence rates of sexually transmitted diseases in heterosexual and homosexual men". Am J Epidemiol. 112 (6): 836–43. PMID 6893897.
- ↑ Rolfs RT, Goldberg M, Sharrar RG (1990). "Risk factors for syphilis: cocaine use and prostitution". Am J Public Health. 80 (7): 853–7. PMC 1404975. PMID 2356911.
- ↑ Zhou H, Chen XS, Hong FC, Pan P, Yang F, Cai YM; et al. (2007). "Risk factors for syphilis infection among pregnant women: results of a case-control study in Shenzhen, China". Sex Transm Infect. 83 (6): 476–80. doi:10.1136/sti.2007.026187. PMC 2598725. PMID 17675391.
- ↑ Newell, J., et al. "A population-based study of syphilis and sexually transmitted disease syndromes in north-western Tanzania. 2. Risk factors and health seeking behaviour." Genitourinary medicine 69.6 (1993): 421-426.
- ↑ Hook EW, Peeling RW (2004). "Syphilis control--a continuing challenge". N Engl J Med. 351 (2): 122–4. doi:10.1056/NEJMp048126. PMID 15247352.
- ↑ Buchacz K, Greenberg A, Onorato I, Janssen R (2005). "Syphilis epidemics and human immunodeficiency virus (HIV) incidence among men who have sex with men in the United States: implications for HIV prevention". Sex Transm Dis. 32 (10 Suppl): S73–9. PMID 16205297.
- ↑ https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-nonpregnant-adults-and-adolescents?ds=1&s=syphilis Accessed on September 19, 2016
- ↑ http://www.cdc.gov/std/treatment/2010/specialpops.htm Accessed on September 19, 2016
- ↑ https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/syphilis-infection-in-pregnancy-screening?ds=1&s=syphilis Accessed on September 19, 2016
- ↑ 27.0 27.1 Thomas SB, Quinn SC (1991). "The Tuskegee Syphilis Study, 1932 to 1972: implications for HIV education and AIDS risk education programs in the black community". Am J Public Health. 81 (11): 1498–505. PMC 1405662. PMID 1951814.
- ↑ 28.0 28.1 GJESTLAND T (1955). "The Oslo study of untreated syphilis; an epidemiologic investigation of the natural course of the syphilitic infection based upon a re-study of the Boeck-Bruusgaard material". Acta Derm Venereol Suppl (Stockh). 35 (Suppl 34): 3–368, Annex I-LVI. PMID 13301322.
- ↑ http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 26, 2016
- ↑ Ghanem KG, Erbelding EJ, Cheng WW, Rompalo AM (2006) Doxycycline compared with benzathine penicillin for the treatment of early syphilis. Clin Infect Dis 42 (6):e45-9. DOI:10.1086/500406 PMID: 16477545
- ↑ "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
- ↑ 32.0 32.1 http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016
- ↑ Stamm LV (2010). "Global challenge of antibiotic-resistant Treponema pallidum". Antimicrobial Agents and Chemotherapy. 54 (2): 583–9. doi:10.1128/AAC.01095-09. PMC 2812177. PMID 19805553. Retrieved 2012-02-21. Unknown parameter
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