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 Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...

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 chancre ( )chancres
thefreedictionary is a painless

(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 A rash is a change of the human skin which affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cr ...

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 A gumma (plural gummata or gummas) is a soft, non-cancerous growth resulting from the tertiary stage of syphilis (and yaws). It is a form of granuloma. Gummas are most commonly found in the liver (''gumma hepatis''), but can also be found in br ...

(soft, non-cancerous growths), neurological problems, or heart symptoms. Syphilis has been known as "

the great imitator The Great Imitator (also the Great Masquerader) is a phrase used for medical conditions that feature nonspecific symptoms and may be confused with a number of other diseases.J.C. Segen. The Dictionary of Modern Medicine'. CRC Press; 1992. . p. 265. ...

" as it may cause symptoms similar to many other diseases. Syphilis is most commonly spread through

sexual activity Human sexual activity, human sexual practice or human sexual behaviour is the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts, ranging from activities done alone (e.g., masturbation) ...

. It may also be transmitted from mother to baby during pregnancy or at birth, resulting in

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 results in a high risk of poor pregnancy outcomes, including saddle nose, lower ext ...

. Other diseases caused by ''

Treponema ''Treponema'' is a genus of spiral-shaped bacteria. The major treponeme species of human pathogens is ''Treponema pallidum'', whose subspecies are responsible for diseases such as syphilis, bejel, and yaws. ''Treponema carateum'' is the cause o ...

'' bacteria include

yaws Yaws is a tropical infection of the skin, bones, and joints caused by the spirochete bacterium ''Treponema pallidum pertenue''. The disease begins with a round, hard swelling of the skin, in diameter. The center may break open and form an ulce ...

(''

T. pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacterium with various subspecies that cause the diseases syphilis, bejel (also known as endemic syphilis), and yaws. It is transmitted only among humans. It is ...

'' subspecies ''pertenue''), pinta ('' T. carateum''), and

nonvenereal endemic syphilis Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the ''endemicum'' subspecies of the spirochete ''Treponema pallidum''. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped ...

(''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 Dark-field microscopy (also called dark-ground microscopy) describes microscopy methods, in both light and electron microscopy, which exclude the unscattered beam from the image. As a result, the field around the specimen (i.e., where there is ...

. The

Centers for Disease Control and Prevention The Centers for Disease Control and Prevention (CDC) is the national public health agency of the United States. It is a United States federal agency, under the Department of Health and Human Services, and is headquartered in Atlanta, Georgi ...

(U.S.) recommend all pregnant women be tested. The risk of sexual transmission of syphilis can be reduced by using a

latex Latex is an emulsion (stable dispersion) of polymer microparticles in water. Latexes are found in nature, but synthetic latexes are common as well. In nature, latex is found as a milky fluid found in 10% of all flowering plants (angiosperms ...

polyurethane Polyurethane (; often abbreviated PUR and PU) refers to a class of polymers composed of organic chemistry, organic units joined by carbamate (urethane) links. In contrast to other common polymers such as polyethylene and polystyrene, polyurethan ...

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 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 o ...

. The preferred antibiotic for most cases is

benzathine benzylpenicillin Benzathine benzylpenicillin, also known as benzathine penicillin G, is an antibiotic medication useful for the treatment of a number of bacterial infections. Specifically it is used to treat strep throat, diphtheria, syphilis, and yaws. It is a ...

injected into a muscle. In those who have a severe

penicillin allergy The side effects of penicillin are bodily responses to penicillin and closely related antibiotics that do not relate directly to its effect on bacteria. A side effect is an effect that is not intended with normal dosing. Some of these reactions are ...

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 ...

tetracycline Tetracycline, sold under various brand names, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including Acne vulgaris, acne, cholera, brucellosis, plague (disease), plague, malaria, and sy ...

may be used. In those with

neurosyphilis Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurologic ...

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 Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...

ceftriaxone Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint ...

is recommended. During treatment people may develop fever, headache, and

muscle pains Myalgia (also called muscle pain and muscle ache in layman's terms) is the medical term for muscle pain. Myalgia is a symptom of many diseases. The most common cause of acute myalgia is the overuse of a muscle or group of muscles; another likel ...

, 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 The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause AIDS, acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the ...

(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

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 Sir William Osler, 1st Baronet, (; July 12, 1849 – December 29, 1919) was a Canadian physician and one of the "Big Four" founding professors of Johns Hopkins Hospital. Osler created the first residency program for specialty training of phys ...

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 A chancre ( )chancres
thefreedictionary is a painless

, appears at the site and this contains infectious

spirochete A spirochaete () or spirochete is a member of the phylum Spirochaetota (), (synonym Spirochaetes) which contains distinctive diderm (double-membrane) gram-negative bacteria, most of which have long, helically coiled (corkscrew-shaped or s ...

s. This is classically (40% of the time) a single, firm, painless, non-itchy

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 A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this sy ...

to a

papule A papule is a small, well-defined bump in the skin. It may have a rounded, pointed or flat top, and may have a dip. It can appear with a stalk, be thread-like or look warty. It can be soft or firm and its surface may be rough or smooth. Some h ...

and finally to an

erosion Erosion is the action of surface processes (such as water flow or wind) that removes soil, rock, or dissolved material from one location on the Earth's crust, and then transports it to another location where it is deposited. Erosion is distin ...

ulcer 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 ...

. 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 A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males do n ...

in heterosexual men (99%), and anally and

rectal The rectum is the final straight portion of the large intestine in humans and some other mammals, and the gut in others. The adult human rectum is about long, and begins at the rectosigmoid junction (the end of the sigmoid colon) at the le ...

ly in

men who have sex with men Men who have sex with men (MSM) are male persons who engage in sexual activity with members of the same sex. The term was created in the 1990s by epidemiology, epidemiologists to study the spread of disease among all men who have sex with men, r ...

(34%).

Lymph node enlargement Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cli ...

frequently (80%) occurs around the area of infection, occurring seven to 10 days after chancre formation. The

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

may persist for three to six weeks if left untreated.

Secondary

upright=1.4, Reddish nodules_over_much_of_the_body_due_to_secondary_syphilis.html" ;"title="nodule (dermatology)#Primary lesions">nodules over much of the body due to secondary syphilis">nodule (dermatology)#Primary lesions">nodules 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 Skin is the layer of usually soft, flexible outer tissue covering the body of a vertebrate animal, with three main functions: protection, regulation, and sensation. Other cuticle, animal coverings, such as the arthropod exoskeleton, have diffe ...

mucous membranes A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

, and

lymph nodes A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

. There may be a symmetrical, reddish-pink, non-itchy

on the trunk and extremities, including the palms and soles. The rash may become

maculopapular A maculopapular rash is a type of rash characterized by a flat, red area on the skin that is covered with small confluent bumps. It may only appear red in lighter-skinned people. The term "maculopapular" is a compound: ''macules'' are small, flat ...

pustular An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends b ...

. It may form flat, broad, whitish, wart-like lesions on mucous membranes, known as

condyloma latum Condylomata lata or condyloma latum, is a cutaneous condition characterized by wart-like lesions on the genitals. They are generally symptoms of the secondary phase of syphilis, caused by the spirochete, ''Treponema pallidum''. Condylomata lata oc ...

. All of these lesions harbor bacteria and are infectious. Other symptoms may include

fever Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...

sore throat Sore throat, also known as throat pain, is pain or irritation of the throat. Usually, causes of sore throat include * viral infections * group A streptococcal infection (GAS) bacterial infection * pharyngitis (inflammation of the throat) * tonsi ...

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 Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

hair loss Hair loss, also known as alopecia or baldness, refers to a loss of hair from part of the head or body. Typically at least the head is involved. The severity of hair loss can vary from a small area to the entire body. Inflammation or scarri ...

, 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,

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...

disease, joint inflammation,

periostitis Periostitis, also known as periostalgia, is a medical condition caused by inflammation of the periosteum, a layer of connective tissue that surrounds bone. The condition is generally chronic, and is marked by tenderness and swelling of the bone an ...

, inflammation of the optic nerve,

uveitis Uveitis () is inflammation of the uvea, the pigmented layer of the eye between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and ...

, and

interstitial keratitis Interstitial keratitis (IK) is corneal scarring due to chronic inflammation of the corneal stroma. Interstitial means space between cells i.e. corneal stroma which lies between the epithelium and the endothelium. Keratitis means corneal inflammat ...

. 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 Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mic ...

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 The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...

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

(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 Malignancy () is the tendency of a medical condition to become progressively worse. Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous benign tumor, ''benign'' tumor in that a malign ...

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

, 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 Syphilitic aortitis is inflammation of the aorta associated with the Tertiary syphilis, tertiary stage of syphilis infection. SA begins as inflammation of the adventitia, outermost layer of the blood vessel, including the blood vessels that suppl ...

, 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 Neurosyphilis refers to infection of the central nervous system in a patient with syphilis. In the era of modern antibiotics the majority of neurosyphilis cases have been reported in HIV-infected patients. Meningitis is the most common neurologic ...

refers to an infection involving the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

. 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 General paresis, also known as general paralysis of the insane (GPI), paralytic dementia, or syphilitic paresis is a severe neuropsychiatry, neuropsychiatric disorder, classified as an organic mental disorders, organic mental disorder and is c ...

tabes dorsalis Tabes dorsalis is a late consequence of neurosyphilis, characterized by the slow degeneration (specifically, demyelination) of the neural tracts primarily in the dorsal root ganglia of the spinal cord (nerve root). These patients have lancinating n ...

. 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 Romberg's test, Romberg's sign, or the Romberg maneuver is a test used in an exam of neurological function for balance, and also as a test for driving under the influence of an intoxicant. The exam is based on the premise that a person requires ...

. 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 Accommodation may refer to: * A dwelling * A place for temporary lodging * The technique of adaptation to local cultures that the Jesuits used in their missions to spread Christianity among non-Christian peoples. * Reasonable accommodation, a l ...

) 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 us ...

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 (20%). If untreated,

late 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 results in a high risk of poor pregnancy outcomes, including saddle nose, lower extr ...

may occur in 40%, including

saddle nose Saddle nose is a condition associated with nasal trauma, congenital syphilis, relapsing polychondritis, granulomatosis with polyangiitis, cocaine abuse, and leprosy, among other conditions. The most common cause is nasal trauma. It is characteri ...

deformation,

Higouménakis' sign Higouménakis' sign is a unilateral enlargement of the sternoclavicular portion of the clavicle, seen in congenital syphilis. It is an end result of neonatal periostitis. The sign was named for George Higoumenakis, who first described it in 1927 ...

saber shin Saber shin is a malformation of the tibia. It presents as a sharp anterior bowing, or convexity, of the tibia. __TOC__ Causes Periosteal reaction along the shaft of the tibia. It can result from congenital syphilis, yaws, Paget's disease of bo ...

, 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 cap ...

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 an ...

(screwdriver shaped incisors), Moon's molars or bud molars, and Fournier's molars or mulberry molars (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 Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...

, highly mobile bacterium. Three other human diseases are caused by related ''Treponema pallidum'' subspecies, including

(subspecies ''pertenue''), pinta (subspecies ''carateum'') and

bejel Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by the ''endemicum'' subspecies of the spirochete ''Treponema pallidum''. Bejel is one of the "endemic treponematoses" (endemic infections caused by spiral-shaped ...

(subspecies ''endemicum''). Unlike subspecies ''pallidum'', they do not cause neurological disease. Humans are the only known

natural reservoir In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and rep ...

for subspecies ''pallidum''. It is unable to survive more than a few days without a

host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places * Host, Pennsylvania, a village in Berks County People *Jim Host (born 1937), American businessman * Michel 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 Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

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 A kiss is the touch or pressing of one's lips against another person or an object. Cultural connotations of kissing vary widely. Depending on the culture and context, a kiss can express sentiments of love, passion, romance, sexual attraction, ...

near a lesion, as well as

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or oral ...

vaginal In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hyme ...

, 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 In epidemiology, infectivity is the ability of a pathogen to establish an infection. More specifically, infectivity is a pathogen's capacity for horizontal transmission — that is, how frequently it spreads among hosts that are not in a parent� ...

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 product A blood product is any therapeutic substance prepared from human blood. This includes whole blood; blood components; and plasma derivatives. Whole blood is not commonly used in transfusion medicine. Blood components include: red blood cell concen ...

s, but the risk is low due to screening of donated blood in many countries. The risk of transmission from sharing needles 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 Object may refer to: General meanings * Object (philosophy), a thing, being, or concept ** Object (abstract), an object which does not exist at any particular time or place ** Physical object, an identifiable collection of matter * Goal, an ...

extremely difficult.

Diagnosis

Syphilis false shame and fear may destroy your future

Syphilis is difficult to diagnose clinically during early infection. Confirmation is either via

or direct visual inspection using

. 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 A nontreponemal test (NTT) is a blood test for diagnosis of infection with syphilis. Nontreponemal tests are an indirect method in that they detect biomarkers that are released during cellular damage that occurs from the syphilis spirochete. In ...

and treponemal tests. Nontreponemal tests are used initially, and include venereal disease research laboratory (VDRL) and

rapid plasma reagin The rapid plasma reagin test (RPR test or RPR titer) is a type of rapid diagnostic test that looks for non-specific antibodies in the blood of the patient that may indicate an infection by syphilis or related non-venereal treponematoses. It is on ...

(RPR) tests.

False positives A false positive is an error in binary classification in which a test result incorrectly indicates the presence of a condition (such as a disease when the disease is not present), while a false negative is the opposite error, where the test result ...

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 Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

tuberculosis Tuberculosis (TB) is an infectious disease usually caused by '' Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...

malaria Malaria is a mosquito-borne infectious disease that affects humans and other animals. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases, it can cause jaundice, seizures, coma, or death. S ...

endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...

connective tissue disease A connective tissue disease (collagenosis) is any disease that has the connective tissues of the body as a target of pathology. Connective tissue is any type of biological tissue with an extensive extracellular matrix that supports, binds togeth ...

, and

. Because of the possibility of false positives with nontreponemal tests, confirmation is required with a treponemal test, such as treponemal pallidum particle agglutination (TPHA) or

fluorescent treponemal antibody absorption test The fluorescent treponemal antibody absorption (FTA-ABS) test is a diagnostic test for syphilis. Using antibodies specific for the ''Treponema pallidum ''Treponema pallidum'', formerly known as ''Spirochaeta pallida'', is a spirochaete bacter ...

(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 White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

(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 Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the bra ...

in the setting of a known syphilis infection.

Direct testing

Dark field microscopy Dark-field microscopy (also called dark-ground microscopy) describes microscopy methods, in both light and electron microscopy, which exclude the unscattered beam from the image. As a result, the field around the specimen (i.e., where there is ...

serous fluid In physiology, serous fluid or serosal fluid (originating from the Medieval Latin word ''serosus'', from Latin ''serum'') is any of various body fluids resembling Serum (blood), serum, that are typically pale yellow or transparent and of a benign ...

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 The polymerase chain reaction (PCR) is a method widely used to rapidly make millions to billions of copies (complete or partial) of a specific DNA sample, allowing scientists to take a very small sample of DNA and amplify it (or a part of it) t ...

(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 Fluorescein is an organic compound and dye based on the xanthene tricyclic structural motif, formally belonging to triarylmethine dyes family. It is available as a dark orange/red powder slightly soluble in water and alcohol. It is widely used ...

, which attach to specific syphilis proteins, while PCR uses techniques to detect the presence of specific syphilis

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

s. These tests are not as time-sensitive, as they do not require living bacteria to make the diagnosis.

Prevention

Vaccine

, there is no

vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...

effective for prevention. Several vaccines based on treponemal proteins reduce lesion development in an

animal model An animal model (short for animal disease model) is a living, non-human, often genetic-engineered animal used during the research and investigation of human disease, for the purpose of better understanding the disease process without the risk of ha ...

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

(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 The United States Preventive Services Task Force (USPSTF) is "an independent panel of experts in primary care and prevention that systematically reviews the evidence of effectiveness and develops recommendations for clinical preventive services". ...

(USPSTF) strongly recommends universal screening of all pregnant women, while the

(WHO) recommends all women be tested at their first antenatal visit and again in the

third trimester Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but can ...

. If they are positive, it is recommended their partners also be treated. Congenital syphilis is still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others receive does not include screening. It still occasionally occurs in the developed world, as those most likely to acquire syphilis are least likely to receive care during pregnancy. Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries.

Point-of-care testing Point-of-care testing (POCT or bedside testing) is defined as medical diagnostic testing at or near the point of care—that is, at the time and place of patient care. This contrasts with the historical pattern in which testing was wholly or most ...

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 A notifiable disease is any disease that is required by law to be reported to government authorities. The collation of information allows the authorities to monitor the disease, and provides early warning of possible outbreaks. In the case of live ...

in many countries, including Canada, the

European Union The European Union (EU) is a supranational political and economic union of member states that are located primarily in Europe. The union has a total area of and an estimated total population of about 447million. The EU has often been des ...

, and the United States. This means health care providers are required to notify

public health Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...

authorities, which will then ideally provide

partner notification Partner notification is the practice of notifying the sexual partners of a person, known as the "index case", who has been newly diagnosed with a sexually transmitted infection that they may have been exposed to the infection. It is a kind of conta ...

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 Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

, 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 Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...

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

are alternative choices for those allergic to penicillin; due to the risk of

birth defect 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 ...

s, these are not recommended for pregnant women. Resistance to

macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Macrol ...

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 Ceftriaxone, sold under the brand name Rocephin, is a third-generation cephalosporin antibiotic used for the treatment of a number of bacterial infections. These include middle ear infections, endocarditis, meningitis, pneumonia, bone and joint ...

, 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

, those affected are given large doses of

penicillin G Benzylpenicillin, also known as penicillin G (PenG) or BENPEN, and in military slang "Peanut Butter Shot" is an antibiotic used to treat a number of bacterial infections. This includes pneumonia, strep throat, syphilis, necrotizing enterocolitis ...

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 A Jarisch–Herxheimer reaction is a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. Efficacious antimicrobial therapy results in lysis (destruction) of bacterial ce ...

. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscle pains, headache, and a

fast heart rate Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...

. 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

lipoprotein A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat) molecules in water, as in blood plasma or other extracellular fluids. They consist of a triglyceride and cholesterol center, sur ...

s 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

Syphilis world map-Deaths per million persons-WHO2012

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 ...

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 death Perinatal mortality (PNM) refers to the death of a fetus or neonate and is the basis to calculate the perinatal mortality rate. Variations in the precise definition of the perinatal mortality exist, specifically concerning the issue of inclusion o ...

s. Rates are proportionally higher among

intravenous drug users Recreational drug use indicates the use of one or more psychoactive drugs to induce an altered state of consciousness either for pleasure or for some other casual purpose or pastime by modifying the perceptions and emotions of the user. When a ...

, 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 immune ...

, 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 American African Americans (also referred to as Black Americans and Afro-Americans) are an ethnic group consisting of Americans with partial or total ancestry from sub-Saharan Africa. The term "African American" generally denotes descendants of ens ...

s 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 Gustave Flaubert ( , , ; 12 December 1821 – 8 May 1880) was a French novelist. Highly influential, he has been considered the leading exponent of literary realism in his country. According to the literary theorist Kornelije Kvas, "in Flauber ...

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

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 Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...

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 Cuba ( , ), officially the Republic of Cuba ( es, República de Cuba, links=no ), is an island country comprising the island of Cuba, as well as Isla de la Juventud and several minor archipelagos. Cuba is located where the northern Caribbea ...

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 Christopher Columbus * lij, Cristoffa C(or)ombo * es, link=no, Cristóbal Colón * pt, Cristóvão Colombo * ca, Cristòfor (or ) * la, Christophorus Columbus. (; born between 25 August and 31 October 1451, died 20 May 1506) was a ...

in 1492 and spread from there, with a serious epidemic in

Naples Naples (; it, Napoli ; nap, Napule ), from grc, Νεάπολις, Neápolis, lit=new city. is the regional capital of Campania and the third-largest city of Italy, after Rome and Milan, with a population of 909,048 within the city's adminis ...

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,

, and

—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. Medieval illumination of Christ being tortured

Medieval illumination of Christ being tortured

Four men torture Christ before his crucifixion

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

. 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

—

—or the eye deformity ptosis 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 Monster Beverage Corporation is an American beverage company that manufactures energy drinks including Monster Energy, Relentless and Burn. The company was originally founded as Hansen's in 1935 in Southern California, originally selling juice ...

) or

elephantiasis Elephantiasis is the enlargement and hardening of limbs or body parts due to tissue swelling. It is characterised by edema, hypertrophy, and fibrosis of skin and subcutaneous tissues, due to obstruction of lymphatic vessels. It may affect the genit ...

. 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 Naples (; it, Napoli ; nap, Napule ), from grc, Νεάπολις, Neápolis, lit=new city. is the regional capital of Campania and the third-largest city of Italy, after Rome and Milan, with a population of 909,048 within the city's adminis ...

, during a French invasion (

Italian War of 1494–98 Italian(s) may refer to: * Anything of, from, or related to the people of Italy over the centuries ** Italians, an ethnic group or simply a citizen of the Italian Republic or Italian Kingdom ** Italian language, a Romance language *** Regional Ita ...

). 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 London is the capital and largest city of England and the United Kingdom, with a population of just under 9 million. It stands on the River Thames in south-east England at the head of a estuary down to the North Sea, and has been a majo ...

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 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 ...

as the title of his

Latin Latin (, or , ) is a classical language belonging to the Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) around present-day Rome, but through the power of the ...

poem in

dactylic hexameter Dactylic hexameter (also known as heroic hexameter and the meter of epic) is a form of meter or rhythmic scheme frequently used in Ancient Greek and Latin poetry. The scheme of the hexameter is usually as follows (writing – for a long syllable, ...

'' Syphilis sive morbus gallicus'' (''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 In epidemiology, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...

, symptoms, and disability, although records of its true prevalence were generally not kept because of the fearsome and sordid status of

sexually transmitted infections Sexually transmitted infections (STIs), also referred to as sexually transmitted diseases (STDs) and the older term venereal diseases, are infections that are spread by sexual activity, especially vaginal intercourse, anal sex, and oral se ...

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 In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...

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 Promiscuity is the practice of engaging in sexual activity frequently with different partners or being indiscriminate in the choice of sexual partners. The term can carry a moral judgment. A common example of behavior viewed as promiscuous by ma ...

and

, 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 Pathogenesis is the process by which a disease or disorder develops. It can include factors which contribute not only to the onset of the disease or disorder, but also to its progression and maintenance. The word comes from Greek πάθος ''pat ...

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

with

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 Fritz Richard Schaudinn (19 September 1871 – 22 June 1906) was a German zoologist. Born in Röseningken, East Prussia, he co-discovered, with Erich Hoffmann in 1905, the causative agent of syphilis, ''Spirochaeta pallida'' (also known as ''Trep ...

and

Erich Hoffmann Erich Hoffmann (25 April 1868 – 8 May 1959) was a German dermatologist who was a native of Witzmitz, Pomerania. He studied medicine at the Berlin Military Academy, and was later a professor at the Universities of Halle and Bonn. Hoffmann ...

, in 1905. The first effective treatment for syphilis was

arsphenamine Arsphenamine, also known as Salvarsan or compound 606, is a drug that was introduced at the beginning of the 1910s as the first effective treatment for syphilis, relapsing fever, and African trypanosomiasis. This organoarsenic compound was the f ...

, discovered by

Sahachiro Hata was a prominent Japanese bacteriologist who researched the bubonic plague under Kitasato Shibasaburō and assisted in developing the Arsphenamine drug in 1909 in the laboratory of Paul Ehrlich. Hata received three unsuccessful nominations for ...

in 1909, during a survey of hundreds of newly synthesized organic

arsenic Arsenic is a chemical element with the symbol As and atomic number 33. Arsenic occurs in many minerals, usually in combination with sulfur and metals, but also as a pure elemental crystal. Arsenic is a metalloid. It has various allotropes, but ...

al compounds led by

Paul Ehrlich Paul Ehrlich (; 14 March 1854 – 20 August 1915) was a Nobel Prize-winning German physician and scientist who worked in the fields of hematology, immunology, and antimicrobial chemotherapy. Among his foremost achievements were finding a cure ...

. It was manufactured and marketed from 1910 under the trade name

Salvarsan Arsphenamine, also known as Salvarsan or compound 606, is a drug that was introduced at the beginning of the 1910s as the first effective treatment for syphilis, relapsing fever, and African trypanosomiasis. This organoarsenic compound was the fi ...

Hoechst AG Hoechst AG () was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999. With the new company's 2004 merger with Sanofi-Synthélabo, it became a subsidiary of the ...

. This

organoarsenic compound Organoarsenic chemistry is the chemistry of compounds containing a chemical bond between arsenic and carbon. A few organoarsenic compounds, also called "organoarsenicals," are produced industrially with uses as insecticides, herbicides, and fungic ...

was the first modern

chemotherapeutic agent This is a list of chemotherapeutic agents, also known as cytotoxic agents or cytostatic drugs, that are known to be of use in chemotherapy for cancer. This list is organized by type of agent, although the subsections are not necessarily definitive ...

. 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 A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastruct ...

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 Franz Peter Schubert (; 31 January 179719 November 1828) was an Austrian composer of the late Classical and early Romantic eras. Despite his short lifetime, Schubert left behind a vast ''oeuvre'', including more than 600 secular vocal wor ...

Arthur Schopenhauer Arthur Schopenhauer ( , ; 22 February 1788 – 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 Édouard Manet (, ; ; 23 January 1832 – 30 April 1883) was a French modernist painter. He was one of the first 19th-century artists to paint modern life, as well as a pivotal figure in the transition from Realism to Impressionism. Born ...

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 Henri René Albert Guy de Maupassant (, ; ; 5 August 1850 – 6 July 1893) was a 19th-century French author, remembered as a master of the short story form, as well as a representative of the Naturalist school, who depicted human lives, destin ...

are believed to have had the disease.

Friedrich Nietzsche Friedrich Wilhelm Nietzsche (; or ; 15 October 1844 – 25 August 1900) was a German philosopher, prose poet, cultural critic, philologist, and composer whose work has exerted a profound influence on contemporary philosophy. He began his ...

was long believed to have gone mad as a result of

tertiary syphilis Tertiary ( ) is a widely used but obsolete term for the geologic period from 66 million to 2.6 million years ago. The period began with the demise of the non-avian dinosaurs in the Cretaceous–Paleogene extinction event, at the start ...

, 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 The (singular: , ), also rendered as Landsknechts or Lansquenets, were Germanic mercenaries used in pike and shot formations during the early modern period. Consisting predominantly of pikemen and supporting foot soldiers, their front line wa ...

, a Northern European

mercenary A mercenary, sometimes also known as a soldier of fortune or hired gun, is a private individual, particularly a soldier, that joins a military conflict for personal profit, is otherwise an outsider to the conflict, and is not a member of any o ...

. 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 "La Belle Dame sans Merci" ("The Beautiful Lady Without Mercy") is a ballad produced by the England, English poet John Keats in 1819. The title was derived from the title of a 15th-century poem by Alain Chartier called ''La Belle Dame sans ...

". The Flemish artist

Stradanus Stradanus, Johannes Stradanus, Jan van der Straet or Giovanni StradanoMore name variations: Johannes Stradanus, Giovanni della Strada, Johannes della Strada, Giovanni Stradano, Johannes Stradano, Giovanni Stradanus, Johannes Stradanus, Jan van St ...

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 ''Guaiacum'' (''OED'' 2nd edition, 1989.Entry "guaiacum"
in
The "Tuskegee Study of Untreated Syphilis in the Negro Male" was an infamous, unethical and racist

clinical study Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

conducted between 1932 and 1972 by the

U.S. Public Health Service The United States Public Health Service (USPHS or PHS) is a collection of agencies of the Department of Health and Human Services concerned with public health, containing nine out of the department's twelve operating divisions. The Assistant ...

. Whereas the purpose of this study was to observe the Natural history of disease, 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, 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

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 because researchers had knowingly withheld treatment with

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, communication of diagnosis, and accurate reporting of test results. Similar experiments were carried out in Guatemala 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

s, without the informed consent of the subjects, and treated most subjects with

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

External links

"Syphilis - CDC Fact Sheet"

(CDC)
UCSF HIV InSite Knowledge Base Chapter: Syphilis and HIV

Recommendations for Public Health Surveillance of Syphilis in the United States
* {{Authority control Syphilis, 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

Signs and symptoms

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