The CDC recommends that sexually active men who have sex with men be tested at least yearly. The USPSTF also recommends screening among those at high risk.

Syphilis is a notifiable disease in many countries, including Canada the European Union, and the United States. This means health care providers are required to notify public health authorities, which will then ideally provide partner notification to the person's partners. Physicians may also encourage patients to send their partners to seek care. Several strategies have been found to improve follow-up for STI testing, including email and text messaging as reminders of appointments.

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 recommends all women be tested at their first antenatal visit and again in the third trimester. If they are positive, it is recommend 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 (through drug use, etc.) are least likely to receive care during pregnancy. Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries. Point-of-care testing to detect syphilis appeared to be good although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies.

There are many different forms on prevention of syphilis and other sexually transmitted diseases in general. Prevention of syphilis includes avoiding contact of bodily fluids with an infected person. This can be particularly difficult because syphilis is usually transmitted by people who are unaware that they have the disease because they do not have any visible sores or rashes that may denote having an infection in general. Being abstinent or having mutually monogamous sex with a person who is uninfected with any type of sexually transmitted disease is the greatest guarantee of not becoming infected with syphilis or any form of a sexually transmitted disease. Using latex condoms can however reduce the risk of obtaining syphilis. In order to prevent further contamination to other individuals, benzathine penicillin is given to any contacts. Washing, douching, or urinating cannot prevent the transmission of a sexually transmitted disease in general.

Individuals obtain syphilis through a variety of circumstances. In general, syphilis can be transmitted from individual to individual through direct contact with sores that are present on the external genitals, vagina, rectum, anus, lips, or mouth. Transmission can occur through any form of sexual contact, including vaginal, anal, and oral sex. In addition, women who are pregnant and infected with syphilis can transmit the disease onto their child as well. If transmission has occurred, it is important to check up immediately with a physician to avoid further damage.

Specific age groups, persons who participate in risky sexual behavior, or those have certain health conditions may require screening. The CDC recommends that sexually active women under the age of 25 and those over 25 at risk should be screened for chlamydia and gonorrhea yearly. Appropriate times for screening are during regular pelvic examinations and preconception evaluations. Nucleic acid amplification tests are the recommended method of diagnosis for gonorrhea and chlamydia. This can be done on either urine in both men and women, vaginal or cervical swabs in women, or urethral swabs in men. Screening can be performed:

- to assess the presence of infection and prevent tubal infertility in women

- during the initial evaluation before infertility treatment

- to identify HIV infection

- for men who have sex with men

- for those who may have been exposed to hepatitis C

- for HCV

The Jarisch-Herxheimer reaction, which is the response to the body after endotoxins are released by the death of harmful organisms in the human body, starts usually during the first day of antibiotic treatment. The reaction increases the person's body temperature, decreases the overall blood pressure (both systolic and diastolic levels), and results in leukopenia and rigors in the body. This reaction can occur during any treatment of spirochete diseases.

It is important to realize that syphilis can recur. An individual who has had the disease once, even if it has been treated, does not prevent the person from experiencing recurrence of syphilis. Individuals can be re-infected, and because syphilis sores can be hidden, it may not be obvious that the individual is infected with syphilis. In these cases, it is vital to become tested and treated immediately to reduce spread of the infection.

Researchers had hoped that nonoxynol-9, a vaginal microbicide would help decrease STI risk. Trials, however, have found it ineffective and it may put women at a higher risk of HIV infection.

Babies can also become infected by their mothers during birth. Some infectious agents may be transmitted to the embryo or fetus in the uterus, while passing through the birth canal, or even shortly after birth. The distinction is important because when transmission is primarily during or after birth, medical intervention can help prevent infections in the infant.

During birth, babies are exposed to maternal blood, body fluids, and to the maternal genital tract without the placental barrier intervening. Because of this, blood-borne microorganisms (hepatitis B, HIV), organisms associated with sexually transmitted disease (e.g., "Neisseria gonorrhoeae" and "Chlamydia trachomatis"), and normal fauna of the genitourinary tract (e.g., "Candida albicans") are among those commonly seen in infection of newborns.

If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the fetus, especially if he or she is treated before the sixteenth week of pregnancy. The fetus is at greatest risk of contracting syphilis when the mother is in the early stages of infection, but the disease can be passed at any point during pregnancy, even during delivery (if the child had not already contracted it). A woman in the secondary stage of syphilis decreases her fetus's risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy. An afflicted child can be treated using antibiotics much like an adult; however, any developmental symptoms are likely to be permanent.

Kassowitz’s law is an empirical observation used in context of congenital syphilis stating that the greater the duration between the infection of the mother and conception, the better is the outcome for the infant. Features of a better outcome include less chance of stillbirth and of developing congenital syphilis.

The Centers for Disease Control and Prevention recommends treating symptomatic or babies born to infected mother with unknown treatment status with procaine penicillin G, 50,000 U/kg dose IM a day in a single dose for 10 days. Treatment for these babies can vary on a case by case basis. Treatment cannot reverse any deformities, brain, or permanent tissue damage that has already occurred.

Chancroid is a bacterial infection caused by the fastidious Gram-negative streptobacillus "Haemophilus ducreyi". It is a disease found primarily in developing countries, most prevalent in low socioeconomic groups, associated with commercial sex workers. In the United States socioeconomic status has not been found to be a factor in the spread of sexually transmitted diseases.

Chancroid, caused by H. ducreyi has infrequently been associated with cases of Genital Ulcer Disease in the US, but has been isolated in up to 10% of genital ulcers diagnosed from STD clinics in Memphis and Chicago.

Infection levels are very low in the Western world, typically around one case per two million of the population (Canada, France, Australia, UK and US). Most individuals diagnosed with chancroid have visited countries or areas where the disease is known to occur frequently, although outbreaks have been observed in association with crack cocaine use and prostitution.

Chancroid is a risk factor for contracting HIV, due to their ecological association or shared risk of exposure, and biologically facilitated transmission of one infection by the other.

Death from congenital syphilis is usually due to bleeding into the lungs.

The embryo and fetus have little or no immune function. They depend on the immune function of their mother. Several pathogens can cross the placenta and cause (perinatal) infection. Often, microorganisms that produce minor illness in the mother are very dangerous for the developing embryo or fetus. This can result in spontaneous abortion or major developmental disorders. For many infections, the baby is more at risk at particular stages of pregnancy. Problems related to perinatal infection are not always directly noticeable.

Penicillin is used to treat neurosyphilis; however, early diagnosis and treatment is critical. Two examples of penicillin therapies include:

- Aqueous penicillin G 3–4 million units every four hours for 10 to 14 days.

- One daily intramuscular injection and oral probenecid four times daily, both for 10 to 14 days.

Follow-up blood tests are generally performed at 3, 6, 12, 24, and 36 months to make sure the infection is gone. Lumbar punctures for CSF fluid analysis are generally performed every 6 months.

Neurosyphilis was almost at the point being unheard of in the United States after penicillin therapy was introduced. However, concurrent infection of "T. pallidum" with human immunodeficiency virus (HIV) has been found to affect the course of syphilis. Syphilis can lie dormant for 10 to 20 years before progressing to neurosyphilis, but HIV may accelerate the rate of the progress. Also, infection with HIV has been found to cause penicillin therapy to fail more often. Therefore, neurosyphilis has once again been prevalent in societies with high HIV rates and limited access to penicillin. Blood testing for syphilis was once required in order to obtain a marriage license in most U.S. states, but that requirement has been discontinued by all 50 states over recent years, also contributing to the spread of the disease.

An individual may only develop signs of an infection after a period of subclinical infection, a duration that is called the incubation period. This is the case, for example, for subclinical sexually transmitted diseases such as AIDS and genital warts. Individuals with such subclinical infections, and those that never develop overt illness, creates a reserve of individuals that can transmit an infectious agent to infect other individuals. Because such cases of infections do not come to clinical attention, health statistics can often fail to measure the true prevalence of an infection in a population, and this prevents the accurate modeling of its infectious transmission.

"H. ducreyi" enters skin through microabrasions incurred during sexual intercourse. A local tissue reaction leads to development of erythomatous papule, which progresses to pustule in 4–7 days. It then undergoes central necrosis to ulcerate.

It is treatable with penicillin or other antibiotics, resulting in a complete recovery.

Fever and sickness behavior and other signs of infection are often taken to be due to them. However, they are evolved physiological and behavioral responses of the host to clear itself of the infection. Instead of incurring the costs of deploying these evolved responses to infections, the body opts to tolerate an infection as an alternative to seeking to control or remove the infecting pathogen.

Subclinical infections are important since they allow infections to spread from a reserve of carriers. They also can cause clinical problems unrelated to the direct issue of infection. For example, in the case of urinary tract infections in women, this infection may cause preterm delivery if the person becomes pregnant without proper treatment.

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 also known by a variety of other names, including belesh, dichuchwa, endemic syphilis, nonvenereal syphilis, frenga, njovera, skerljevo, siti, or treponematosis-bejel type.

A chancre ( ) is a painless ulceration (sore) most commonly 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 syphilis through direct physical contact. These ulcers usually form on or around the anus, mouth, penis, and vagina. Chancres may diminish between four and eight weeks without the application of medication.

Chancres, as well as being painless ulcerations formed during the primary stage of syphilis, are associated with the African trypanosomiasis sleeping sickness, surrounding the area of the tsetse fly bite.

Human immunodeficiency virus type I (HIV) infection can occur during labor and delivery, in utero through mother-to-child transmission or postnatally by way of breastfeeding. Transmission can occur during pregnancy, delivery or breastfeeding. Most transmission occurs during delivery. In women with low detectable levels of the virus, the incidence of transmission is lower. Transmission risk can be reduced by:

- providing antiretroviral therapy during pregnancy and immediately after birth

- delivery by caesarean section

- not breastfeeding

- antiretroviral prophylaxis in infants born to mothers with HIV.

A low number of women whose HIV status are unknown until after the birth, do not benefit from interventions that could help lower the risk of mother-to-child HIV transmission.

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. Most great imitators are systemic in nature. Diseases sometimes referred to with this name include:

- Various cancers

- Intravascular large B-cell lymphoma

- Various rheumatic conditions, including:

- Fibromyalgia

- Psoriatic arthritis

- Lupus erythematosus

- Systemic lupus erythematosus

- Sarcoidosis

- Multiple sclerosis

- Celiac disease

- Addison's Disease

- Pulmonary embolism

- Various infectious diseases, including:

- Syphilis

- Lyme disease

- Nocardiosis

- Tuberculosis

- Brucellosis

- Malaria

- Breathing-related sleep disorders (chiefly sleep apnea/hypopnea and upper-airway resistance syndrome).

Pinta (also known as Azul, Carate, Empeines, Lota, Mal del Pinto and Tina) is a human skin disease endemic to Mexico, Central America, and South America caused by infection with a spirochete, "Treponema pallidum carateum", which is morphologically and serologically indistinguishable from the bacterium that causes syphilis.

Sixty percent of mothers of preterm infants are infected with cytomegalovirus (CMV). Infection is asymptomatic in most instances but 9% to 12% of postnatally infected low birth weight, preterm infants have severe, sepsis-like infection. CMV infection duration can be long and result in pneumonitis in association with fibrosis. CMV infection in infants has an unexpected effect on the white blood cells of the immune system causing them to prematurely age. This leads to a reduced immune response similar to that found in the elderly.

In addition to evaluation of any symptoms and signs, various blood tests can be done:

- Venereal Disease Research Laboratory test (VDRL)

- Fluorescent treponemal antibody absorption (FTA-ABS)

- Rapid plasma reagin (RPR)

- Treponema pallidum particle agglutination assay (TPPA)

Also, it is important to test the cerebrospinal fluid for signs of syphilis.

Additional tests to look for problems with the nervous system may include the following:

- Cerebral angiogram

- Head CT scan

- Lumbar puncture ("spinal tap") to acquire a sample for cerebrospinal fluid analysis

- MRI scan of the brain, brainstem, or spinal cord

Differences between the conditions chancre and chancroid:

- Chancre is a lesion typical of infection with the bacterium that causes syphilis, Treponema pallidum

- Chancroid is a lesion typical of infection with the bacterium Haemophilus ducreyi

- Chancres are typically painless, whereas chancroid are typically painful

- Chancres are typically single, whereas chancroid are typically multiple

- Chancres cause regional bilateral lymph node enlargement, whereas chancroid cause regional unilateral lymph node enlargement

- Chancres typically exude serum, whereas chancroid typically have a grey or yellow purulent exudate

- Chancres have a hard (indurated) base with sloping edges, whereas chancroid have a soft base with undermined edges

- Chancres heal spontaneously within three to six weeks, even in the absence of treatment

- Chancres can occur in the pharynx as well as on the genitals. Not to be confused with condyloma lata, which is seen in secondary syphilis

Treponematosis is a term used to collectively or individually describe any of the diseases caused by the bacterial species "Treponema". There are four subspecies described which cause the following diseases:

- Syphilis ("Treponema pallidum pallidum")

- Yaws ("Treponema pallidum pertenue")

- Bejel ("Treponema pallidum endemicum")

- Pinta ("Treponema carateum")