Venereal Syphilis
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Syphilis () is a
sexually transmitted infection Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are Transmission (medicine), spread by Human sexual activity, sexual activity, especi ...
caused by the bacterium '' Treponema pallidum''
subspecies In biological classification, subspecies is a rank below species, used for populations that live in different areas and vary in size, shape, or other physical characteristics (morphology), but that can successfully interbreed. Not all species ...
''pallidum''. The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary). The primary stage classically presents with a single chancre (a firm, painless, non-itchy
skin ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
usually between 1 cm and 2 cm in diameter) though there may be multiple sores. In secondary syphilis, a diffuse rash occurs, which frequently involves the palms of the hands and soles of the feet. There may also be sores in the mouth or vagina. In latent syphilis, which can last for years, there are few or no symptoms. In tertiary syphilis, there are gummas (soft, non-cancerous growths), neurological problems, or heart symptoms. Syphilis has been known as " the great imitator" as it may cause symptoms similar to many other diseases. Syphilis is most commonly spread through sexual activity. It may also be transmitted from mother to baby during pregnancy or at birth, resulting in congenital syphilis. Other diseases caused by '' Treponema'' bacteria include yaws ('' T. pallidum'' subspecies ''pertenue''), pinta ('' T. carateum''), and nonvenereal endemic syphilis (''T. pallidum'' subspecies ''endemicum''). These three diseases are not typically sexually transmitted. Diagnosis is usually made by using
blood tests A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
; the bacteria can also be detected using dark field microscopy. The Centers for Disease Control and Prevention (U.S.) recommend all pregnant women be tested. The risk of sexual transmission of syphilis can be reduced by using a latex or polyurethane
condom A condom is a sheath-shaped barrier device used during sexual intercourse to reduce the probability of pregnancy or a sexually transmitted infection (STI). There are both male and female condoms. With proper use—and use at every act of in ...
. Syphilis can be effectively treated with antibiotics. The preferred antibiotic for most cases is benzathine benzylpenicillin injected into a muscle. In those who have a severe penicillin allergy,
doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
or tetracycline may be used. In those with neurosyphilis,
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
benzylpenicillin or ceftriaxone is recommended. During treatment people may develop fever, headache, and muscle pains, a reaction known as Jarisch–Herxheimer. In 2015, about 45.4 million people had syphilis infections, of which six million were new cases. During 2015, it caused about 107,000 deaths, down from 202,000 in 1990. After decreasing dramatically with the availability of penicillin in the 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This is believed to be partly due to increased sexual activity,
prostitution Prostitution is the business or practice of engaging in Sex work, sexual activity in exchange for payment. The definition of "sexual activity" varies, and is often defined as an activity requiring physical contact (e.g., sexual intercourse, n ...
, and decreasing use of
condom A condom is a sheath-shaped barrier device used during sexual intercourse to reduce the probability of pregnancy or a sexually transmitted infection (STI). There are both male and female condoms. With proper use—and use at every act of in ...
s.


Signs and symptoms

Syphilis can
present The present (or here'' and ''now) is the time that is associated with the events perception, perceived directly and in the first time, not as a recollection (perceived more than once) or a speculation (predicted, hypothesis, uncertain). It is ...
in one of four different stages: primary, secondary, latent, and tertiary, and may also occur
congenital A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...
ly. It was referred to as "the great imitator" by Sir William Osler due to its varied presentations.


Primary

Primary syphilis is typically acquired by direct sexual contact with the infectious lesions of another person. Approximately 2–6 weeks after contact (with a range of 10–90 days) a skin lesion, called a chancre, appears at the site and this contains infectious spirochetes. This is classically (40% of the time) a single, firm, painless, non-itchy
skin ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes normal function of the affected organ. According to Robbins's pathology, "ulcer is the breach of the continuity of skin, epithelium or mucous membrane caused by sloughing o ...
with a clean base and sharp borders approximately 0.3–3.0 cm in size. The lesion may take on almost any form. In the classic form, it evolves from a macule to a papule and finally to an erosion or ulcer. Occasionally, multiple lesions may be present (~40%), with multiple lesions being more common when coinfected with HIV. Lesions may be painful or tender (30%), and they may occur in places other than the genitals (2–7%). The most common location in women is the
cervix The cervix or cervix uteri (Latin, 'neck of the uterus') is the lower part of the uterus (womb) in the human female reproductive system. The cervix is usually 2 to 3 cm long (~1 inch) and roughly cylindrical in shape, which changes during ...
(44%), the penis in heterosexual men (99%), and anally and rectally in men who have sex with men (34%). Lymph node enlargement frequently (80%) occurs around the area of infection, occurring seven to 10 days after chancre formation. The lesion may persist for three to six weeks if left untreated.


Secondary

upright=1.4, Reddish
nodules Nodule may refer to: *Nodule (geology), a small rock or mineral cluster *Manganese nodule, a metallic concretion found on the seafloor *Nodule (medicine), a small aggregation of cells *Root nodule Root nodules are found on the roots of plants, p ...
over much of the body due to secondary syphilis Secondary syphilis occurs approximately four to ten weeks after the primary infection. While secondary disease is known for the many different ways it can manifest, symptoms most commonly involve the skin, mucous membranes, and lymph nodes. There may be a symmetrical, reddish-pink, non-itchy rash on the trunk and extremities, including the palms and soles. The rash may become maculopapular or pustular. It may form flat, broad, whitish, wart-like lesions on mucous membranes, known as condyloma latum. All of these lesions harbor bacteria and are infectious. Other symptoms may include fever, sore throat,
malaise As a medical term, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. The word has existed in French since at least the 12th century. The term is often used ...
, weight loss, hair loss, and
headache Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches. Headaches can occur as a result ...
. Rare manifestations include
liver inflammation Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain ...
, kidney disease, joint inflammation, periostitis, inflammation of the optic nerve, uveitis, and interstitial keratitis. The acute symptoms usually resolve after three to six weeks; about 25% of people may present with a recurrence of secondary symptoms. Many people who present with secondary syphilis (40–85% of women, 20–65% of men) do not report previously having had the classical chancre of primary syphilis.


Latent

Latent syphilis is defined as having serologic proof of infection without symptoms of disease. It develops after secondary syphilis and is divided into early latent and late latent stages. Early latent syphilis is defined by the World Health Organization as less than 2 years after original infection. Early latent syphilis is infectious as up to 25% of people can develop a recurrent secondary infection (during which spirochetes are actively replicating and are infectious). Two years after the original infection the person will enter late latent syphilis and is not as infectious as the early phase. The latent phase of syphilis can last many years after which, without treatment, approximately 15-40% of people can develop tertiary syphilis.


Tertiary

Tertiary syphilis may occur approximately 3 to 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis (6.5%), and cardiovascular syphilis (10%). Without treatment, a third of infected people develop tertiary disease. People with tertiary syphilis are not infectious. Gummatous syphilis or late benign syphilis usually occurs 1 to 46 years after the initial infection, with an average of 15 years. This stage is characterized by the formation of chronic gummas, which are soft, tumor-like balls of inflammation which may vary considerably in size. They typically affect the skin, bone, and liver, but can occur anywhere. Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis, which may result in
aortic aneurysm An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. The prevalence of abdominal aortic ...
formation. Neurosyphilis refers to an infection involving the central nervous system. Involvement of the central nervous system in syphilis (either asymptomatic or symptomatic) can occur at any stage of the infection. It may occur early, being either asymptomatic or in the form of syphilitic
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
; or late as meningovascular syphilis, manifesting as general paresis or tabes dorsalis. Meningovascular syphilis involves inflammation of the small and medium arteries of the central nervous system. It can present between 1–10 years after the initial infection. Meningovascular syphilis is characterized by stroke, cranial nerve palsies and spinal cord inflammation. Late symptomatic neurosyphilis can develop decades after the original infection and includes 2 types; general paresis and tabes dorsalis. General paresis presents with dementia, personality changes, delusions, seizures, psychosis and depression. Tabes dorsalis is characterized by gait instability, sharp pains in the trunk and limbs, impaired positional sensation of the limbs as well as having a positive Romberg's sign. Both tabes dorsalis and general paresis may present with
Argyll Robertson pupil Argyll Robertson pupils (AR pupils) are bilateral small pupils that reduce in size on a near object (i.e., they accommodate), but do ''not'' constrict when exposed to bright light (i.e., they do not react). They are a highly specific sign of neu ...
which are pupils that constrict when the person focuses on near objects ( accommodation reflex) but do not constrict when exposed to bright light (
pupillary reflex Pupillary reflex refers to one of the reflexes associated with pupillary function. These include the pupillary light reflex and accommodation reflex. Although the pupillary response, in which the pupil dilates or constricts due to light is not ...
).


Congenital

Congenital syphilis is that which is transmitted during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that develop over the first couple of years of life include enlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), and
lung inflammation The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either si ...
(20%). If untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, Higouménakis' sign, saber shin, or
Clutton's joints Clutton's joints is a term describing the finding of symmetrical joint swelling seen in patients with congenital syphilis. It most commonly affects the knees, presenting with synovitis and joint effusions (collections of fluid within the joint c ...
among others. Infection during pregnancy is also associated with
miscarriage Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
. The three main dental defects in congenital syphilis are
Hutchinson's incisors Hutchinson's teeth is a sign of congenital syphilis. Affected people have teeth that are smaller and more widely spaced than normal and which have notches on their biting surfaces. It is named after Sir Jonathan Hutchinson, an English surgeon and ...
(screwdriver shaped incisors), Moon's molars or bud molars, and Fournier's molars or
mulberry molars Mulberry molars are a dental condition usually associated with congenital syphilis Congenital syphilis is syphilis present ''in utero'' and at birth, and occurs when a child is born to a mother with syphilis. Untreated early syphilis infections r ...
(molars with abnormal occlusal anatomy resembling a
mulberry ''Morus'', a genus of flowering plants in the family Moraceae, consists of diverse species of deciduous trees commonly known as mulberries, growing wild and under cultivation in many temperate world regions. Generally, the genus has 64 identif ...
).


Cause


Bacteriology

''Treponema pallidum'' subspecies'' pallidum'' is a spiral-shaped, Gram-negative, highly mobile bacterium. Three other human diseases are caused by related ''Treponema pallidum'' subspecies, including yaws (subspecies ''pertenue''), pinta (subspecies ''carateum'') and bejel (subspecies ''endemicum''). Unlike subspecies ''pallidum'', they do not cause neurological disease. Humans are the only known natural reservoir for subspecies ''pallidum''. It is unable to survive more than a few days without a host. This is due to its small genome (1.14 Mbp) failing to encode the metabolic pathways necessary to make most of its macronutrients. It has a slow
doubling time The doubling time is the time it takes for a population to double in size/value. It is applied to population growth, inflation, resource extraction, consumption of goods, compound interest, the volume of malignant tumours, and many other things th ...
of greater than 30 hours. The bacterium is known for its ability to evade the immune system and its invasiveness.


Transmission

Syphilis is transmitted primarily by sexual contact or during pregnancy from a mother to her baby; the spirochete is able to pass through intact mucous membranes or compromised skin. It is thus transmissible by kissing near a lesion, as well as oral, vaginal, and
anal sex Anal sex or anal intercourse is generally the insertion and thrusting of the erect penis into a person's anus, or anus and rectum, for sexual pleasure.Sepages 270–271for anal sex information, anpage 118for information about the clitoris. ...
. Approximately 30% to 60% of those exposed to primary or secondary syphilis will get the disease. Its infectivity is exemplified by the fact that an individual inoculated with only 57 organisms has a 50% chance of being infected. Most new cases in the United States (60%) occur in men who have sex with men; and in this population 20% of syphilis cases were due to oral sex alone. Syphilis can be transmitted by blood products, but the risk is low due to screening of donated blood in many countries. The risk of transmission from
sharing needles Needle sharing is the practice of intravenous drug-users by which a needle or syringe is shared by multiple individuals to administer intravenous drugs such as heroin, steroids, and hormones. This is a primary vector for blood-borne diseases whic ...
appears to be limited. It is not generally possible to contract syphilis through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing. This is mainly because the bacteria die very quickly outside of the body, making transmission by objects extremely difficult.


Diagnosis

Syphilis is difficult to diagnose clinically during early infection. Confirmation is either via
blood tests A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose test or a cholester ...
or direct visual inspection using dark field microscopy. Blood tests are more commonly used, as they are easier to perform. Diagnostic tests are unable to distinguish between the stages of the disease.


Blood tests

Blood tests are divided into nontreponemal and treponemal tests. Nontreponemal tests are used initially, and include
venereal disease research laboratory The Venereal Disease Research Laboratory test (VDRL) is a blood test for syphilis and related non-venereal treponematoses that was developed by the eponymous lab. The VDRL test is used to screen for syphilis (it has high sensitivity), whereas othe ...
(VDRL) and rapid plasma reagin (RPR) tests. False positives on the nontreponemal tests can occur with some viral infections, such as varicella (chickenpox) and
measles Measles is a highly contagious infectious disease caused by measles virus. Symptoms usually develop 10–12 days after exposure to an infected person and last 7–10 days. Initial symptoms typically include fever, often greater than , cough, ...
. False positives can also occur with lymphoma, tuberculosis, malaria, endocarditis, connective tissue disease, and pregnancy. Because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, such as
treponemal pallidum particle agglutination The ''Treponema pallidum'' particle agglutination assay (also called TPPA test) is an indirect agglutination assay used for detection and titration of antibodies against the causative agent of syphilis, ''Treponema pallidum'' subspecies ''pallid ...
(TPHA) or fluorescent treponemal antibody absorption test (FTA-Abs). Treponemal antibody tests usually become positive two to five weeks after the initial infection. Neurosyphilis is diagnosed by finding high numbers of leukocytes (predominately
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated, cytotoxic innate immunity), T cells (for cell-mediated, cytotoxic adap ...
) and high protein levels in the cerebrospinal fluid in the setting of a known syphilis infection.


Direct testing

Dark field microscopy of serous fluid from a chancre may be used to make an immediate diagnosis. Hospitals do not always have equipment or experienced staff members, and testing must be done within 10 minutes of acquiring the sample. Two other tests can be carried out on a sample from the chancre:
direct fluorescent antibody A direct fluorescent antibody (DFA or dFA), also known as "direct immunofluorescence", is an antibody that has been tagged in a direct fluorescent antibody test. Its name derives from the fact that it directly tests the presence of an antigen with ...
(DFA) and polymerase chain reaction (PCR) tests. DFA uses
antibodies An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
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

, 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 A condom is a sheath-shaped barrier device used during sexual intercourse to reduce the probability of pregnancy or a sexually transmitted infection (STI). There are both male and female condoms. With proper use—and use at every act of in ...
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 Abstinence is a self-enforced restraint from indulging in bodily activities that are widely experienced as giving pleasure. Most frequently, the term refers to sexual abstinence, but it can also mean abstinence from alcohol, drugs, food, etc. ...
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 Monogamy ( ) is a form of Dyad (sociology), dyadic Intimate relationship, relationship in which an individual has only one Significant other, partner during their lifetime. Alternately, only one partner at any one time (Monogamy#Serial monogamy, ...
relationship with a partner who has been tested and is known to be uninfected."


Congenital disease

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 Prenatal care, also known as antenatal care, is a type of preventive healthcare. It is provided in the form of medical checkups, consisting of recommendations on managing a healthy lifestyle and the provision of medical information such as materna ...
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

As a form of chemotherapy, elemental mercury was frequently used to treat syphilis in Europe very early on in the epidemic, and in this respect was rather effective. Mercury is highly anti-microbial, and in the early stages of infection was sometimes sufficient in halting development of the disease when applied to cankers or other wounds. Once the bacterium gained a strong foothold, however, the amounts and forms of mercury necessary to control its development exceeded the human ability to endure this extremely toxic metal, and the treatment became worse and more lethal than the disease. Medically directed mercury poisoning also became widespread, and thousands died in desperate attempts to rid themselves of the excruciating, disfiguring, and humiliating illness.


Early infections

The first-line treatment for uncomplicated syphilis (primary or secondary stages) remains a single dose of intramuscular benzathine benzylpenicillin.
Doxycycline Doxycycline is a broad-spectrum tetracycline class antibiotic used in the treatment of infections caused by bacteria and certain parasites. It is used to treat bacterial pneumonia, acne, chlamydia infections, Lyme disease, cholera, typhus, an ...
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 Resistance may refer to: Arts, entertainment, and media Comics * Either of two similarly named but otherwise unrelated comic book series, both published by Wildstorm: ** ''Resistance'' (comics), based on the video game of the same title ** ''T ...
to macrolides,
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
, and
clindamycin Clindamycin is an antibiotic medication used for the treatment of a number of bacterial infections, including osteomyelitis (bone) or joint infections, pelvic inflammatory disease, strep throat, pneumonia, acute otitis media (middle ear infec ...
is often present. Ceftriaxone, a third-generation
cephalosporin The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
, may be as effective as penicillin-based treatment. It is recommended that a treated person avoid sex until the sores are healed.


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 Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
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

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 Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
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

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 A developing country is a sovereign state with a lesser developed industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is also no clear agreem ...
. It affects between 700,000 and 1.6 million pregnancies a year, resulting in
spontaneous abortion Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Miscarriage before 6 weeks of gestation is defined by ESHRE as biochemical lo ...
s,
stillbirth Stillbirth is typically defined as fetal death at or after 20 or 28 weeks of pregnancy, depending on the source. It results in a baby born without signs of life. A stillbirth can result in the feeling of guilt or grief in the mother. The term ...
s, and congenital syphilis. During 2015, it caused about 107,000 deaths, down from 202,000 in 1990. In
sub-Saharan Africa Sub-Saharan Africa is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, syphilis contributes to approximately 20% of perinatal deaths. Rates are proportionally higher among intravenous drug users, those who are infected with
HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immu ...
, and men who have sex with men. In the United States about 55,400 people are newly infected each year. 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. African Americans accounted for almost half of all cases in 2010. As of 2014, syphilis infections continue to increase in the United States. 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
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s, 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

Paleopatholgists have known for decades that syphilis was present in the Americas before European contact. The situation in Europe and
Afro-Eurasia Afro-Eurasia (also Afroeurasia, Eurafrasia or the Old World) is a landmass comprising the continents of Africa, Asia, and Europe. The terms are compound words of the names of its constituent parts. Its mainland is the largest and most populou ...
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 Treponematosis is a term used to individually describe any of the diseases caused by four members of the bacterial genus ''Treponema''. The four diseases are collectively referred to as treponematoses: * Syphilis (''Treponema pallidum pallidum'') * ...
—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 viral 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 viral 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 viral 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. 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. 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. 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 the disease instead. As syphilis, bejel, and yaws vary considerably in mortality rates and the level of human disgust they elicit, it is important to know which one is under discussion in any given case, but it remains difficult for paleopathologists to distinguish among them. (The fourth of the treponemal diseases is Pinta, a skin disease and therefore unrecoverable through paleopathology.) Ancient DNA (aDNA) holds the answer, because just as only aDNA suffices to distinguish between syphilis and other diseases that produce similar symptoms in the body, it alone can differentiate spirochetes that are 99.8 percent identical with absolute accuracy. Progress on uncovering the historical extent of syndromes through aDNA remains slow, however, because the spirochete responsible for treponematosis is rare in skeletal remains and fragile, making it notoriously difficult to recover and analyze. Precise dating to the medieval period is not yet possible, but work by Kettu Majander et al. uncovering the presence of several different kinds of treponematosis at the beginning of the early modern period argues against its recent introduction from elsewhere. Therefore, they argue, treponematosis—including syphilis—almost certainly existed in medieval Europe. Despite significant progress in tracing the presence of syphilis in past historic periods, definitive findings from paleopathology and aDNA studies are still lacking for the medieval period. Evidence from art is therefore helpful in settling the issue. Research by Marylynn Salmon has demonstrated that deformities in medieval subjects can be identified by comparing them to those of modern victims of syphilis in medical drawings and photographs. One of the most typical deformities, for example, is a collapsed nasal bridge called saddle nose. Salmon discovered that it appeared often in medieval illuminations, especially among the men tormenting Christ in scenes of the crucifixion. The association of saddle nose with men perceived to be so evil they would kill the son of God indicates the artists were thinking of syphilis, which is typically transmitted through sexual intercourse with promiscuous partners, a mortal sin in medieval times. One illuminator goes so far as to show a flagellant with an exposed penis, red at the tip as though infected with a syphilitic sore. Others show the deformed teeth associated with congenital syphilis—
Hutchinson's incisors Hutchinson's teeth is a sign of congenital syphilis. Affected people have teeth that are smaller and more widely spaced than normal and which have notches on their biting surfaces. It is named after Sir Jonathan Hutchinson, an English surgeon and ...
—or the eye deformity
ptosis Ptosis (from the Greek: πτῶσις 'falling', 'a fall', 'dropped') refers to droopiness or abnormal downward displacement of a body part or organ. Particular cases include: * Ptosis (eyelid) * Ptosis (chin) * Ptosis (breasts) * Visceroptosis, ...
that often appears in victims of the disease. It remains mysterious why the authors of medieval medical treatises so uniformly refrained from describing syphilis or commenting on its existence in the population. Probably many confused it with other diseases such as leprosy ( Hansen's Disease) or elephantiasis. The great variety of symptoms of treponematosis, the different ages at which the various diseases appears, and its widely divergent outcomes depending on climate and culture, would have added greatly to the confusion of medical practitioners, as indeed they did right down to the middle of the twentieth century. In addition, evidence indicates that some writers on disease feared the political implications of discussing a condition more fatal to elites than to commoners. Historian Jon Arrizabalaga has investigated this question for Castile with startling results revealing an effort to hide its association with elites. The first written records of an outbreak of syphilis in Europe occurred in 1495 in Naples, Italy, during a French invasion ( Italian War of 1494–98). Since it was claimed to have been spread by French troops, it was initially called the "French disease" by the people of Naples. The disease reached London in 1497 and was recorded at St Batholomew's Hospital as infected 10 out of the 20 patients. In 1530, the pastoral name "syphilis" (the name of a character) was first used by the Italian physician and poet Girolamo Fracastoro as the title of his Latin poem in dactylic hexameter ''
Syphilis sive morbus gallicus Girolamo Fracastoro ( la, Hieronymus Fracastorius; c. 1476/86 August 1553) was an Italian physician, poet, and scholar in mathematics, geography and astronomy. Fracastoro subscribed to the philosophy of atomism, and rejected appeals to hidden c ...
'' (''Syphilis or The French Disease'') describing the ravages of the disease in Italy. In Great Britain it was also called the "Great Pox". In the 16th through 19th centuries, syphilis was one of the largest public health burdens in prevalence, symptoms, and disability, although records of its true prevalence were generally not kept because of the fearsome and sordid status of sexually transmitted infections in those centuries. According to a 2020 study, more than 20% of individuals in the age range 15–34 years in late 18th century London were treated for syphilis. At the time the causative agent was unknown but it was well known that it was spread sexually and also often from mother to child. Its association with sex, especially sexual promiscuity and
prostitution Prostitution is the business or practice of engaging in Sex work, sexual activity in exchange for payment. The definition of "sexual activity" varies, and is often defined as an activity requiring physical contact (e.g., sexual intercourse, n ...
, made it an object of fear and revulsion and a taboo. The magnitude of its morbidity and mortality in those centuries reflected that, unlike today, there was no adequate understanding of its pathogenesis and no truly effective treatments. Its damage was caused not so much by great sickness or death early in the course of the disease but rather by its gruesome effects decades after infection as it progressed to neurosyphilis with tabes dorsalis.
Mercury Mercury commonly refers to: * Mercury (planet), the nearest planet to the Sun * Mercury (element), a metallic chemical element with the symbol Hg * Mercury (mythology), a Roman god Mercury or The Mercury may also refer to: Companies * Merc ...
compounds and isolation were commonly used, with treatments often worse than the disease. The causative organism, ''Treponema pallidum'', was first identified by Fritz Schaudinn and Erich Hoffmann, in 1905. The first effective treatment for syphilis was arsphenamine, discovered by Sahachiro Hata in 1909, during a survey of hundreds of newly synthesized organic arsenical compounds led by Paul Ehrlich. It was manufactured and marketed from 1910 under the trade name Salvarsan by Hoechst AG. This organoarsenic compound was the first modern chemotherapeutic agent. During the 20th century, as both
microbiology Microbiology () is the scientific study of microorganisms, those being unicellular (single cell), multicellular (cell colony), or acellular (lacking cells). Microbiology encompasses numerous sub-disciplines including virology, bacteriology, prot ...
and
pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...
advanced greatly, syphilis, like many other infectious diseases, became more of a manageable burden than a scary and disfiguring mystery, at least in developed countries among those people who could afford to pay for timely diagnosis and treatment. Penicillin was discovered in 1928, and effectiveness of treatment with
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
was confirmed in trials in 1943, at which time it became the main treatment. Many famous historical figures, including Franz Schubert,
Arthur Schopenhauer Arthur Schopenhauer ( , ; 22 February 1788 â€“ 21 September 1860) was a German philosopher. He is best known for his 1818 work ''The World as Will and Representation'' (expanded in 1844), which characterizes the phenomenal world as the prod ...
, Édouard Manet,
Charles Baudelaire Charles Pierre Baudelaire (, ; ; 9 April 1821 – 31 August 1867) was a French poetry, French poet who also produced notable work as an essayist and art critic. His poems exhibit mastery in the handling of rhyme and rhythm, contain an exoticis ...
, and Guy de Maupassant are believed to have had the disease. Friedrich Nietzsche was long believed to have gone mad as a result of tertiary syphilis, but that diagnosis has recently come into question.


Arts and literature

The earliest known depiction of an individual with syphilis is
Albrecht Dürer Albrecht Dürer (; ; hu, Ajtósi Adalbert; 21 May 1471 – 6 April 1528),Müller, Peter O. (1993) ''Substantiv-Derivation in Den Schriften Albrecht Dürers'', Walter de Gruyter. . sometimes spelled in English as Durer (without an umlaut) or Due ...
's ''Syphilitic Man'', a woodcut believed to represent a Landsknecht, a Northern European mercenary. The myth of the ''
femme fatale A ''femme fatale'' ( or ; ), sometimes called a maneater or vamp, is a stock character of a mysterious, beautiful, and seductive woman whose charms ensnare her lovers, often leading them into compromising, deadly traps. She is an archetype of ...
'' or "poison women" of the 19th century is believed to be partly derived from the devastation of syphilis, with classic examples in literature including
John Keats John Keats (31 October 1795 – 23 February 1821) was an English poet of the second generation of Romantic poets, with Lord Byron and Percy Bysshe Shelley. His poems had been in publication for less than four years when he died of tuberculo ...
' " La Belle Dame sans Merci". The Flemish artist Stradanus designed a print called ''Preparation and Use of Guayaco for Treating Syphilis'', a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum sometime around 1590.


Tuskegee and Guatemala studies

The "Tuskegee Study of Untreated Syphilis in the Negro Male" was an infamous, unethical and racist clinical study conducted between 1932 and 1972 by the U.S. Public Health Service. Whereas the purpose of this study was to observe the natural history of untreated syphilis; the African-American men in the study were told they were receiving free treatment for "bad blood" from the United States government. The Public Health Service started working on this study in 1932 in collaboration with Tuskegee University, a historically black college in Alabama. Researchers enrolled 600 poor, African-American sharecroppers from Macon County, Alabama in the study. Of these men, 399 had contracted syphilis before the study began, and 201 did not have the disease. Medical care, hot meals and free burial insurance were given to those who participated. The men were told that the study would last six months, but in the end it continued for 40 years. After funding for treatment was lost, the study was continued without informing the men that they were only being studied and would not be treated. Facing insufficient participation, the Macon County Health Department nevertheless wrote to subjects to offer them a "last chance" to get a special "treatment", which was not a treatment at all, but a spinal tap administered exclusively for diagnostic purposes. None of the men infected were ever told that they had the disease, and none were treated with
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
even after the antibiotic had been proven to successfully treat syphilis. According to the Centers for Disease Control, the men were told they were being treated for "bad blood"—a colloquialism describing various conditions such as fatigue, anemia and syphilis—which was a leading cause of death among southern African-American men. The 40-year study became a textbook example of poor
medical ethics Medical ethics is an applied branch of ethics which analyzes the practice of clinical medicine and related scientific research. Medical ethics is based on a set of values that professionals can refer to in the case of any confusion or conflict. T ...
because researchers had knowingly withheld treatment with
penicillin Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by P. chrysogenum using ...
and because the subjects had been misled concerning the purposes of the study. The revelation in 1972 of these study failures by a whistleblower, Peter Buxtun, led to major changes in U.S. law and regulation on the protection of participants in clinical studies. Now studies require
informed consent Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
, communication of diagnosis, and accurate reporting of test results. Similar experiments were carried out in
Guatemala Guatemala ( ; ), officially the Republic of Guatemala ( es, República de Guatemala, links=no), is a country in Central America. It is bordered to the north and west by Mexico; to the northeast by Belize and the Caribbean; to the east by H ...
from 1946 to 1948. It was done during the administration of American President Harry S. Truman and Guatemalan President Juan José Arévalo with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prostitutes, prisoners and mental patients with syphilis and other
sexually transmitted infection Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are Transmission (medicine), spread by Human sexual activity, sexual activity, especi ...
s, without the
informed consent Informed consent is a principle in medical ethics and medical law, that a patient must have sufficient information and understanding before making decisions about their medical care. Pertinent information may include risks and benefits of treatme ...
of the subjects, and treated most subjects with
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention of ...
s. The experiment resulted in at least 83 deaths. In October 2010, the U.S. formally apologized to Guatemala for the ethical violations that took place. Secretary of State Hillary Clinton and Health and Human Services Secretary Kathleen Sebelius stated "Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health. We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices." The experiments were led by physician John Charles Cutler who also participated in the late stages of the Tuskegee syphilis experiment.


Names

It was first called ''grande verole'' or the "great pox" by the French. Other historical names have included "button scurvy", sibbens, frenga and dichuchwa, among others. Since it was a disgraceful disease, the disease was known in several countries by the name of their neighbouring country. The English, the Germans, and the Italians called it "the French disease", while the French referred to it as the "Neapolitan disease". The Dutch called it the "Spanish/Castilian disease". To the Turks it was known as the "Christian disease", whilst in India, the Hindus and Muslims named the disease after each other.


References


Further reading

* *


External links


"Syphilis - CDC Fact Sheet"
Centers for Disease Control and Prevention (CDC)
UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV

Recommendations for Public Health Surveillance of Syphilis in the United States
* {{Authority control Bacterial diseases Bacterium-related cutaneous conditions Infectious diseases Infectious diseases with eradication efforts Infections with a predominantly sexual mode of transmission Sexually transmitted diseases and infections Spirochaetes Wikipedia medicine articles ready to translate (full) Wikipedia infectious disease articles ready to translate