Syphilis
Overview
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum
Treponema pallidum
Treponema pallidum is a species of spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis, bejel, pinta and yaws. The treponemes have a cytoplasmic and outer membrane...

subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis
Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary syphilis. Untreated syphilis results in a high risk of a bad outcome of pregnancy, including mulberry molars in the fetus. Syphilis can cause miscarriages, premature births,...

. Other human diseases caused by related Treponema pallidum include yaws
Yaws
Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...

 (subspecies pertenue), pinta
Pinta (disease)
Pinta is a human skin disease endemic to Mexico, Central America, and South America. It is caused by infection with a spirochete, Treponema pallidum carateum, which is morphologically and serologically indistinguishable from the organism that causes syphilis.-Presentation:Pinta is thought to be...

 (subspecies carateum) and bejel
Bejel
Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by a subspecies of the spirochete Treponema pallidum....

 (subspecies endemicum).

The signs and symptoms of syphilis vary depending in which of the four stages it presents (primary, secondary, latent, and tertiary).
Encyclopedia
Syphilis is a sexually transmitted infection caused by the spirochete bacterium Treponema pallidum
Treponema pallidum
Treponema pallidum is a species of spirochaete bacterium with subspecies that cause treponemal diseases such as syphilis, bejel, pinta and yaws. The treponemes have a cytoplasmic and outer membrane...

subspecies pallidum. The primary route of transmission is through sexual contact; however, it may also be transmitted from mother to fetus during pregnancy or at birth, resulting in congenital syphilis
Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary syphilis. Untreated syphilis results in a high risk of a bad outcome of pregnancy, including mulberry molars in the fetus. Syphilis can cause miscarriages, premature births,...

. Other human diseases caused by related Treponema pallidum include yaws
Yaws
Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...

 (subspecies pertenue), pinta
Pinta (disease)
Pinta is a human skin disease endemic to Mexico, Central America, and South America. It is caused by infection with a spirochete, Treponema pallidum carateum, which is morphologically and serologically indistinguishable from the organism that causes syphilis.-Presentation:Pinta is thought to be...

 (subspecies carateum) and bejel
Bejel
Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by a subspecies of the spirochete Treponema pallidum....

 (subspecies endemicum).

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
Chancre
A chancre is a painless ulceration formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum, the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit the sexually transmissible disease of...

 (a firm, painless, non-itchy skin ulceration), secondary syphilis with a diffuse rash which frequently involves the palms of the hands and soles of the feet, latent syphilis with little to no symptoms, and tertiary syphilis with gummas
Gumma (pathology)
A gumma is a soft, non-cancerous growth resulting from the tertiary stage of syphilis. It is a form of granuloma. Gummas are most commonly found in the liver , but can also be found in brain, heart, skin, bone, testis, and other tissues, leading to a variety of potential problems including...

, neurological, or cardiac symptoms. It has, however, been known as "the great imitator" due to its frequent atypical presentations. Diagnosis is usually via blood tests; however, the bacteria can also be visualized under a microscope. Syphilis can be effectively treated with antibiotics, specifically intramuscular penicillin G, and in those who are allergic, ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

 is recommended.

Syphilis is believed to have infected 12 million people worldwide in 1999, with greater than 90% of cases in the developing world. After decreasing dramatically since the widespread availability of penicillin in 1940s, rates of infection have increased since the turn of the millennium in many countries, often in combination with human immunodeficiency virus (HIV). This has been attributed partly to unsafe sexual practices among men who have sex with men
Men who have sex with men
Men who have sex with men are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many men choose not to accept sexual identities of homosexual or bisexual...

, increased promiscuity, prostitution and decreasing use of barrier protection.

Signs and symptoms

Syphilis can present in one of four different stages: primary, secondary, latent, and tertiary, and may also occur congenitally. 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 three to 90 days after the initial exposure (average 21 days) a skin lesion, called a chancre
Chancre
A chancre is a painless ulceration formed during the primary stage of syphilis. This infectious lesion forms approximately 21 days after the initial exposure to Treponema pallidum, the gram-negative spirochaete bacterium yielding syphilis. Chancres transmit the sexually transmissible disease of...

, appears at the point of contact. This is classically (40% of the time) a single, firm, painless, non-itchy skin ulceration with a clean base and sharp borders between 0.3 and 3.0 cm in size. The lesion, however, may take on almost any form. In the classic form, it evolves from a macule to a papule
Papule
A papule is a circumscribed, solid elevation of skin with no visible fluid, varying in size from a pinhead to 1 cm.With regard to the quote "...varying in size from a pinhead to 1cm," depending on which text is referenced, some authors state the cutoff between a papule and a plaque as 0.5cm,...

 and finally to an erosion or ulcer. Occasionally, multiple lesions may be present (~40%), with multiple lesions more common when coinfected with HIV. Lesions may be painful or tender (30%), and they may occur outside of the genitals (2–7%). The most common location in women is the cervix
Cervix
The cervix is the lower, narrow portion of the uterus where it joins with the top end of the vagina. It is cylindrical or conical in shape and protrudes through the upper anterior vaginal wall...

 (44%), the penis
Penis
The penis is a biological feature of male animals including both vertebrates and invertebrates...

 in heterosexual men (99%), and anally
Anus
The anus is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, unwanted semi-solid matter produced during digestion, which, depending on the type of animal, may be one or more of: matter which the animal cannot digest,...

 and rectally relatively commonly in men who have sex with men
Men who have sex with men
Men who have sex with men are male persons who engage in sexual activity with members of the same sex, regardless of how they identify themselves; many men choose not to accept sexual identities of homosexual or bisexual...

 (34%). Lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

 enlargement frequently (80%) occurs around the area of infection, occurring 7–10 days after chancre formation. The lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...

 may persist for three to six weeks without treatment.

Secondary

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, mucus 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
Abscess
An abscess is a collection of pus that has accumulated in a cavity formed by the tissue in which the pus resides due to an infectious process or other foreign materials...

. It may form flat, broad, whitish, wart-like lesions known as condyloma latum on mucous membrane
Mucous membrane
The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

s. All of these lesions are infectious harboring bacteria. Other symptoms may include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, sore throat
Sore throat
A sore throat or throat pain is a common physical symptom usually caused by acute pharyngitis, or throat inflammation, though it also occurs in a number of other situations, such as post trauma and in diphtheria. It can cause mild to extreme pain....

, malaise
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...

, weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, hair loss, and headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

. Rare manifestations include hepatitis
Hepatitis
Hepatitis is a medical condition defined by the inflammation of the liver and characterized by the presence of inflammatory cells in the tissue of the organ. The name is from the Greek hepar , the root being hepat- , meaning liver, and suffix -itis, meaning "inflammation"...

, kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...

 disease, arthritis
Arthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....

, periostitis
Periostitis
Periostitis, also known as periostalgia, is a medical condition caused by inflammation of the periosteum, a layer of connective tissue that surrounds bone...

, optic neuritis
Optic neuritis
Optic neuritis is the inflammation of the optic nerve that may cause a complete or partial loss of vision.-Causes:The optic nerve comprises axons that emerge from the retina of the eye and carry visual information to the primary visual nuclei, most of which is relayed to the occipital cortex of the...

, uveitis
Uveitis
Uveitis specifically refers to inflammation of the middle layer of the eye, termed the "uvea" but in common usage may refer to any inflammatory process involving the interior of the eye....

, and interstitial keratitis
Interstitial keratitis
Interstitial Keratitis basically means 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...

. The acute symptoms usually resolve after three to six weeks; however, about 25% 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 the classic chancre of primary syphilis.

Latent

Latent syphilis is defined as having serologic
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

 proof of infection without symptoms of disease. It is further described as either early (less than 1 year after secondary syphilis) or late (more than 1 year after secondary syphilis) in the United States. The United Kingdom uses a cut-off of two years for early and late latent syphilis. Early latent syphilis may have a relapse of symptoms. Late latent syphilis is asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

, and not as contagious as early latent syphilis.

Tertiary

Tertiary syphilis may occur approximately three to 15 years after the initial infection, and may be divided into three different forms: gummatous syphilis (15%), late neurosyphilis
Neurosyphilis
Neurosyphilis is an infection of the brain or spinal cord caused by the bacterium Treponema pallidum. It usually occurs in people who have had untreated syphilis for many years, usually about 10 - 20 years after first infection.-Symptoms and signs:...

 (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
Benignity
Benignity [from Latin benignus , from bonus + genus ] is a medical term used to describe a condition that is harmless...

 syphilis usually occurs one 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.

Neurosyphilis
Neurosyphilis
Neurosyphilis is an infection of the brain or spinal cord caused by the bacterium Treponema pallidum. It usually occurs in people who have had untreated syphilis for many years, usually about 10 - 20 years after first infection.-Symptoms and signs:...

 refers to an infection involving the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

. It may occur early, being either asymptomatic or in the form of syphilitic meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

, or late as meningovascular syphilis, general paresis, or tabes dorsalis
Tabes dorsalis
Tabes dorsalis is a slow degeneration of the sensory neurons that carry afferent information. The degenerating nerves are in the dorsal columns of the spinal cord and carry information that help maintain a person's sense of position , vibration, and discriminative touch.-Cause:Tabes dorsalis is...

, which is associated with poor balance and lightning pains in the lower extremities. Late neurosyphilis typically occurs four to 25 years after the initial infection. Meningovascular syphilis typically presents with apathy and seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

, and general paresis with dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...

 and tabes dorsalis
Tabes dorsalis
Tabes dorsalis is a slow degeneration of the sensory neurons that carry afferent information. The degenerating nerves are in the dorsal columns of the spinal cord and carry information that help maintain a person's sense of position , vibration, and discriminative touch.-Cause:Tabes dorsalis is...

. Also, there may be Argyll Robertson pupil
Argyll Robertson pupil
Argyll Robertson pupils are bilateral small pupils that constrict when the patient focuses on a near object , but do not constrict when exposed to bright light . They are a highly specific sign of neurosyphilis. In general, pupils that “accommodate but do not react” are said to show light-near...

s, which are bilateral small pupils that constrict when the person focuses on near objects, but do not constrict when exposed to bright light.

Cardiovascular syphilis usually occurs 10–30 years after the initial infection. The most common complication is syphilitic aortitis
Syphilitic aortitis
Syphilitic aortitis is a disease of the aorta associated with the tertiary stage of syphilis infection. SA begins as inflammation of the adventia, including the vessels that supply the aorta itself with blood, the vasa vasorum...

, which may result in aneurysm
Aortic aneurysm
An aortic aneurysm is a general term for any swelling of the aorta to greater than 1.5 times normal, usually representing an underlying weakness in the wall of the aorta at that location...

 formation.

Congenital

Congenital syphilis
Congenital syphilis
Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with secondary syphilis. Untreated syphilis results in a high risk of a bad outcome of pregnancy, including mulberry molars in the fetus. Syphilis can cause miscarriages, premature births,...

 may occur during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that then develop over the first couple years of life include: hepatosplenomegaly
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...

 (70%), rash (70%), fever (40%), neurosyphylis (20%), and pneumonitis
Pneumonitis
Pneumonitis or pulmonitis is a general term that refers to inflammation of lung tissue.Pneumonia is pneumonitis combined with consolidation and exudation...

 (20%). If untreated, late congenital syphilis may occur in 40%, including: saddle nose
Saddle nose
Saddle nose is a condition associated with congenital syphilis, relapsing Polychondritis, Wegener's granulomatosis, cocaine abuse, and Leprosy, among other conditions. It is characterized by a loss of height of the nose, because of the collapse of the bridge....

 deformation, Higoumenakis sign
Higoumenakis sign
Higouménakis' sign is a unilateral enlargement of the sternoclavicular portion of the clavicle, seen in congenital syphilis. It's an end result of neonatal periostitis....

, saber shin
Saber shin
Saber shin is a malformation of the tibia. It presents as a sharp anterior bowing of the tibia.Saber shin is a sharp-edged anteriorly convex tibia.-Causes:It can result from syphilis and yaws....

, or Clutton's joints
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 lasting up to a year. It has also been reported affecting the ankles, elbows, wrists and...

 among others.

Bacteriology


Treponema pallidum subspecies pallidum is a spiral-shaped, Gram-negative
Gram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...

, highly mobile bacterium. Three other human diseases are caused by related Treponema pallidum, including yaws
Yaws
Yaws is a tropical infection of the skin, bones and joints caused by the spirochete bacterium Treponema pallidum pertenue...

 (subspecies pertenue), pinta
Pinta (disease)
Pinta is a human skin disease endemic to Mexico, Central America, and South America. It is caused by infection with a spirochete, Treponema pallidum carateum, which is morphologically and serologically indistinguishable from the organism that causes syphilis.-Presentation:Pinta is thought to be...

 (subspecies carateum) and bejel
Bejel
Bejel, or endemic syphilis, is a chronic skin and tissue disease caused by infection by a subspecies of the spirochete Treponema pallidum....

 (subspecies endemicum). Unlike subtype pallidum they do not cause neurological disease. Humans are the only known natural reservoir
Natural reservoir
Natural reservoir or nidus, refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so asymptomatic and non-lethal...

 for subspecies pallidum. It is unable to survive without a host for more than a few days. This is due to its small genome (1.14 MDa
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...

) and thus its inability to make most of its macronutrients. It has a slow doubling time of greater than 30 hours.

Transmission

Syphilis is transmitted primarily by sexual contact or during pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 from a mother to her fetus
Fetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...

; the spirochaete is able to pass through intact mucous membranes or compromised skin. It is thus transmissible by kissing, oral, vaginal, and anal sex. 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 (60%) of new cases in the United States occur in men who have sex with men. It can be transmitted via blood product
Blood product
A blood product is any component of the blood which is collected from a donor for use in a blood transfusion. Whole blood is uncommonly used in transfusion medicine at present; most blood products consist of specific processed components such as red blood cells, blood plasma, or platelets.-Relation...

s. However, it is tested for in many countries and thus the risk is low. The risk of transmission from sharing needles appears limited. Syphilis cannot be contracted through toilet seats, daily activities, hot tubs, or sharing eating utensils or clothing.

Diagnosis

Syphilis is difficult to diagnose clinically early in its presentation. Confirmation is either via blood tests or direct visual inspection using microscopy
Microscopy
Microscopy is the technical field of using microscopes to view samples and objects that cannot be seen with the unaided eye...

. Blood tests are more commonly used, as they are easier to perform. Diagnostic tests are, however, 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 (VDRL) and rapid plasma reagin
Rapid Plasma Reagin
Rapid Plasma Reagin refers to a type of test that looks for non-specific antibodies in the blood of the patient that may indicate that the organism that causes syphilis is present...

 tests. However, as these tests are occasionally false positives, confirmation is required with a treponemal test, such as treponemal pallidum particle agglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-Abs). False positives on the nontreponemal tests can occur with some viral infections such as varicella and measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...

, as well as with lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...

, tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

, malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...

, endocarditis
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 even on intracardiac devices...

, connective tissue disease
Connective tissue disease
A connective tissue disease 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 together, and protects organs...

, and pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

. 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) and high protein levels in the cerebrospinal fluid
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...

 in the setting of a known syphilis infection.

Direct testing

Dark ground microscopy
Dark field microscopy
Dark field 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 Dark field microscopy (dark ground microscopy) describes microscopy methods, in both light and electron...

 of serous fluid
Serous fluid
In physiology, the term serous fluid is used for various bodily fluids that are typically pale yellow and transparent, and of a benign nature, that fill the inside of body cavities. Serous fluid originates from serous glands, with secretions enriched with proteins and water. Serous fluid may also...

 from a chancre may be used to make an immediate diagnosis. However, hospitals do not always have equipment or experienced staff members, whereas testing must be done within 10 minutes of acquiring the sample. Sensitivity
Sensitivity and specificity
Sensitivity and specificity are statistical measures of the performance of a binary classification test, also known in statistics as classification function. Sensitivity measures the proportion of actual positives which are correctly identified as such Sensitivity and specificity are statistical...

 has been reported to be nearly 80%, thus can only be used to confirm a diagnosis but not rule one out. Two other tests that can be carried out on a sample from the chancre are direct fluorescent antibody
Direct fluorescent antibody
Direct fluorescent antibody is a laboratory test that uses antibodies tagged with fluorescent dye that can be used to detect the presence of microorganisms. This method offers straightforward detection of antigens using fluorescently labeled antigen-specific antibodies...

 testing and nucleic acid amplification
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 tests. Direct fluorescent testing uses antibodies tagged with fluorescein
Fluorescein
Fluorescein is a synthetic organic compound available as a dark orange/red powder soluble in water and alcohol. It is widely used as a fluorescent tracer for many applications....

, which attach to specific syphilis proteins, while nucleic acid amplification uses techniques, such as the polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

, 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

, there is no vaccine effective for prevention. Abstinence from intimate physical contact with an infected person is effective at reducing the transmission of syphilis, as is the proper use of a latex condom. Condom use, however, does not completely eliminate the risk. Thus, the Center for Disease Control and Prevention recommends a long-term, mutually monogamous relationship with an uninfected partner and the avoidance of substances such as alcohol and other drugs that increase risky sexual behavior.

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
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 recommends all women be tested at their first antenatal visit and again in the third trimester. If they are positive, they recommend their partners also be treated. Congenital syphilis is, however, still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others do receive does not include screening, and it still occasionally occurs in the developed world, as those most likely to acquire syphilis (through drug use, etc.) are least likely to receive care during pregnancy. A number of measures to increase access to testing appear effective at reducing rates of congenital syphilis in low to middle income countries.

Syphilis is a notifiable disease
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. Many governments have enacted regulations for reporting of both human...

 in many countries, including Canada, the European Union, and United States. This means health care providers are required to notify public health
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" . It is concerned with threats to health based on population 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. The Center for Disease Control and Prevention recommends sexually active men who have sex with men are tested at least yearly.

Early infections

The first-choice treatment for uncomplicated syphilis remains a single dose of intramuscular penicillin G
Benzylpenicillin
Benzylpenicillin, commonly known as penicillin G, is the gold standard type of penicillin. 'G' in the name 'Penicillin G' refers to 'Gold Standard'. Penicillin G is typically given by a parenteral route of administration because it is unstable in the hydrochloric acid of the stomach...

 or a single dose of oral azithromycin
Azithromycin
Azithromycin is an azalide, a subclass of macrolide antibiotics. Azithromycin is one of the world's best-selling antibiotics...

. Doxycycline
Doxycycline
Doxycycline INN is a member of the tetracycline antibiotics group, and is commonly used to treat a variety of infections. Doxycycline is a semisynthetic tetracycline invented and clinically developed in the early 1960s by Pfizer Inc. and marketed under the brand name Vibramycin. Vibramycin...

 and tetracycline are alternative choices; however, they cannot be used in pregnant women. Antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 has developed to a number of agents, including macrolide
Macrolide
The macrolides are a group of drugs whose activity stems from the presence of a macrolide ring, 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...

s, clindamycin
Clindamycin
Clindamycin rINN is a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria...

, and rifampin. Ceftriaxone
Ceftriaxone
Ceftriaxone is a third-generation cephalosporin antibiotic. Like other third-generation cephalosporins, it has broad spectrum activity against Gram-positive and Gram-negative bacteria. In most cases, it is considered to be equivalent to cefotaxime in terms of safety and efficacy...

, a third-generation cephalosporin
Cephalosporin
The cephalosporins are a class of β-lactam antibiotics originally derived from Acremonium, which was previously known as "Cephalosporium".Together with cephamycins they constitute a subgroup of β-lactam antibiotics called cephems.-Medical use:...

 antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

, may be as effective as penicillin-based treatment.

Late infections

For neurosyphilis due to the poor penetration of penicillin G into the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

, those affected are recommended to be given large doses of intravenous penicillin for a minimum of 10 days. If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular penicillin G for three weeks. If allergic, as in the case of early disease, doxycycline or tetracycline may be used, but for a longer duration. Treatment at this point will limit further progression, but has only slight effect on damage which has already occurred.

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, muscles pains, headache, and tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

. It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.

Epidemiology

Syphilis is believed to have infected 12 million people in 1999, with greater than 90% of cases in the developing world. It affects between 700,000 and 1.6 million pregnacies a year, resulting in spontaneous abortions, stillbirth
Stillbirth
A stillbirth occurs when a fetus has died in the uterus. The Australian definition specifies that fetal death is termed a stillbirth after 20 weeks gestation or the fetus weighs more than . Once the fetus has died the mother still has contractions and remains undelivered. The term is often used in...

s, and congenital syphilis. In sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...

, syphilis contributes to approximately 20% of perinatal deaths. Rates are proportionally higher among intravenous drug users
Recreational drug use
Recreational drug use is the use of a drug, usually psychoactive, with the intention of creating or enhancing recreational experience. Such use is controversial, however, often being considered to be also drug abuse, and it is often illegal...

, those who are infected with HIV, and men who have sex with men. In the United States, rates of syphilis as of 2007 were six times greater in men than women, while they were nearly equal in 1997. African American
African American
African Americans are citizens or residents of the United States who have at least partial ancestry from any of the native populations of Sub-Saharan Africa and are the direct descendants of enslaved Africans within the boundaries of the present United States...

s accounted for almost half of all cases in 2010.

Syphilis was very common is Europe during the 18th and 19th centuries. In the developed world during the early 20th century, infections declined rapidly with the widespread use of antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s, until the 1980s and 1990s. Since the year 2000, rates of syphilis have been increasing in the USA, UK, Australia and Europe, primarily among men who have sex with men. Rates of syphilis among American women have, however, remained stable during this time, and 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.

Untreated, it has a mortality of 8% to 58%, with a greater death rate in 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 decreasing virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 of the spirochaete. 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 a number of urban centers).

History

The exact origin of syphilis is unknown. Of two primary hypotheses, one proposes syphilis was carried to Europe by the returning crewmen from Christopher Columbus
Christopher Columbus
Christopher Columbus was an explorer, colonizer, and navigator, born in the Republic of Genoa, in northwestern Italy. Under the auspices of the Catholic Monarchs of Spain, he completed four voyages across the Atlantic Ocean that led to general European awareness of the American continents in the...

's voyage to the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...

, the other proposes syphilis existed in Europe previously, but went unrecognized. These are referred to as the "Columbian" and "pre-Columbian" hypotheses respectively. The Columbian hypothesis is best supported by the available evidence. The first written records of an outbreak of syphilis in Europe occurred in 1494/1495 in Naples, Italy
Naples
Naples is a city in Southern Italy, situated on the country's west coast by the Gulf of Naples. Lying between two notable volcanic regions, Mount Vesuvius and the Phlegraean Fields, it is the capital of the region of Campania and of the province of Naples...

, during a French invasion. Due to it being spread by returning French troops, it was initially known as the “French disease”. It is only in 1530 that the name "syphilis" was first used by the Italian physician and poet Girolamo Fracastoro
Girolamo Fracastoro
Girolamo Fracastoro was an Italian physician, poet, and scholar in mathematics, geography and astronomy. Fracastoro subscribed to the philosophy of atomism, and rejected appeals to hidden causes in scientific investigation....

 as the title of his Latin
Latin
Latin is an Italic language originally spoken in Latium and Ancient Rome. It, along with most European languages, is a descendant of the ancient Proto-Indo-European language. Although it is considered a dead language, a number of scholars and members of the Christian clergy speak it fluently, and...

 poem in dactylic hexameter describing the ravages of the disease in Italy. It was also known historically as the "Great Pox".

The causative organism, Treponema pallidum, was first identified by Fritz Schaudinn
Fritz Schaudinn
Fritz Richard Schaudinn was a German zoologistBorn in Röseningken, East Prussia, he co-discovered, with Erich Hoffmann in 1905, the causative agent of syphilis, Spirochaeta pallida...

 and Erich Hoffmann
Erich Hoffmann
Erich Hoffmann 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....

 in 1905. The first effective treatment (Salvarsan) was developed in 1910 by Paul Ehrlich
Paul Ehrlich
Paul Ehrlich was a German scientist in the fields of hematology, immunology, and chemotherapy, and Nobel laureate. He is noted for curing syphilis and for his research in autoimmunity, calling it "horror autotoxicus"...

, which was followed by trials of penicillin
Penicillin
Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

 and confirmation of its effectiveness in 1943. Before the advent of effective treatment, mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...

 and isolation were commonly used, with treatments often worse than the disease. Many famous historical figures, including Franz Schubert
Franz Schubert
Franz Peter Schubert was an Austrian composer.Although he died at an early age, Schubert was tremendously prolific. He wrote some 600 Lieder, nine symphonies , liturgical music, operas, some incidental music, and a large body of chamber and solo piano music...

, Arthur Schopenhauer
Arthur Schopenhauer
Arthur Schopenhauer was a German philosopher known for his pessimism and philosophical clarity. At age 25, he published his doctoral dissertation, On the Fourfold Root of the Principle of Sufficient Reason, which examined the four separate manifestations of reason in the phenomenal...

, Édouard Manet
Édouard Manet
Édouard Manet was a French painter. One of the first 19th-century artists to approach modern-life subjects, he was a pivotal figure in the transition from Realism to Impressionism....

 and Adolf Hitler
Adolf Hitler
Adolf Hitler was an Austrian-born German politician and the leader of the National Socialist German Workers Party , commonly referred to as the Nazi Party). He was Chancellor of Germany from 1933 to 1945, and head of state from 1934 to 1945...

, are believed to have had the disease.

Arts and literature

The earliest Europe work of art to depict syphilis is Albrecht Dürer
Albrecht Dürer
Albrecht Dürer was a German painter, printmaker, engraver, mathematician, and theorist from Nuremberg. His prints established his reputation across Europe when he was still in his twenties, and he has been conventionally regarded as the greatest artist of the Northern Renaissance ever since...

's Syphilitic Man, a wood cutting believed to represent a Landsknecht
Landsknecht
Landsknechte were European, predominantly German mercenary pikemen and supporting foot soldiers from the late 15th to the late 16th century, and achieved the reputation for being the universal mercenary of Early modern Europe.-Etymology:The term is from German, Land "land, country" + Knecht...

, a Northern European mercenary
Mercenary
A mercenary, is a person who takes part in an armed conflict based on the promise of material compensation rather than having a direct interest in, or a legal obligation to, the conflict itself. A non-conscript professional member of a regular army is not considered to be a mercenary although he...

. The myth of the femme fatale
Femme fatale
A femme fatale is a mysterious and seductive woman whose charms ensnare her lovers in bonds of irresistible desire, often leading them into compromising, dangerous, and deadly situations. She is an archetype of literature and art...

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
John Keats was an English Romantic poet. Along with Lord Byron and Percy Bysshe Shelley, he was one of the key figures in the second generation of the Romantic movement, despite the fact that his work had been in publication for only four years before his death.Although his poems were not...

' La Belle Dame sans Merci.

The artist Jan van der Straet painted a scene of a wealthy man receiving treatment for syphilis with the tropical wood guaiacum
Guaiacum
Guaiacum, sometimes spelled Guajacum, is a genus of flowering plants in the caltrop family Zygophyllaceae. It contains five species of slow-growing shrubs and trees, reaching a height of approximately but are usually less than half of that...

 sometime around 1580. The title of the work is "Preparation and Use of Guayaco for Treating Syphilis". That the artist chose to include this image in a series of works celebrating the New World indicates how important a treatment, however ineffective, for syphilis was to the European elite at that time. The richly colored and detailed work depicts four servants preparing the concoction while a physician looks on, hiding something behind his back while the hapless patient drinks.

Tuskegee and Guatemala studies

One of the most infamous United States cases of questionable medical ethics
Medical ethics
Medical ethics is a system of moral principles that apply values and judgments to the practice of medicine. As a scholarly discipline, medical ethics encompasses its practical application in clinical settings as well as work on its history, philosophy, theology, and sociology.-History:Historically,...

 in the 20th century was the Tuskegee syphilis study
Tuskegee Syphilis Study
The Tuskegee syphilis experiment was an infamous clinical study conducted between 1932 and 1972 in Tuskegee, Alabama by the U.S. Public Health Service to study the natural progression of untreated syphilis in poor, rural black men who thought they were receiving free health care from the U.S...

. The study took place in Tuskegee, Alabama
Tuskegee, Alabama
Tuskegee is a city in Macon County, Alabama, United States. At the 2000 census the population was 11,846 and is designated a Micropolitan Statistical Area. Tuskegee has been an important site in various stages of African American history....

, and was supported by the U.S. Public Health Service (PHS) in partnership with the Tuskegee Institute. The study began in 1932, when syphilis was a widespread problem and there was no safe and effective treatment. The study was designed to measure the progression of untreated syphilis. By 1947, penicillin had been validated as an effective cure for syphilis and was becoming widely used to treat the disease. Study directors, however, continued the study and did not offer the participants treatment with penicillin. This is debated, and some have found that penicillin was given to many of the subjects. The study did not end until 1972.

Syphilis experiments were also carried out in Guatemala
Guatemala
Guatemala is a country in Central America bordered by Mexico to the north and west, the Pacific Ocean to the southwest, Belize to the northeast, the Caribbean to the east, and Honduras and El Salvador to the southeast...

 from 1946 to 1948. They were United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

-sponsored human experiments, conducted during the government of Juan José Arévalo
Juan José Arévalo
Juan José Arévalo Bermejo was the first of the reformist presidents of Guatemala. Preceded by military junta interregnum after a definitive pro-democracy revolt in 1944...

 with the cooperation of some Guatemalan health ministries and officials. Doctors infected soldiers, prisoners, and mental patients with syphilis and other sexually transmitted diseases, without the informed consent
Informed consent
Informed consent is a phrase often used in law to indicate that the consent a person gives meets certain minimum standards. As a literal matter, in the absence of fraud, it is redundant. An informed consent can be said to have been given based upon a clear appreciation and understanding of the...

 of the subjects, and then treated them with antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s. In October 2010, the U.S. formally apologized to Guatemala for conducting these experiments.

Further reading

  • Parascandola, John. Sex, Sin, and Science: A History of Syphilis in America (Praeger, 2008) 195 pp. ISBN 978-0-275-99430-3 excerpt and text search
  • Shmaefsky, Brian, Hilary Babcock and David L. Heymann. Syphilis (Deadly Diseases & Epidemics) (2009)
  • Stein, Claudia. Negotiating the French Pox in Early Modern Germany (2009)

External links

The source of this article is wikipedia, the free encyclopedia.  The text of this article is licensed under the GFDL.
 
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