Syphilis

What is Syphilis?

Syphilis is an infection caused by a type of bacteria known as Treponema pallidum. It’s known as a ‘great imitator’ because its many different symptoms can look like many other diseases. There is a lot of debate over where syphilis originated, but the most widely accepted theory suggests that it came to Europe in the late 1400s when Columbus returned from America. The disease quickly spread across Europe after that.

The term “syphilis” came from a story written in 1530 by Girolamo Fracastoro, a famous poet and doctor from Italy. He told a story about a shepherd named Syphilus who angered the god Apollo and caused him to curse Syphilus and everyone else with this disease.

Syphilis is a sexually transmitted disease, and it only affects humans. Treponema bacteria can’t survive for long outside the human body because they’re sensitive to heat, cold, and oxygen. A small number of bacteria (anywhere from 500 to 1000) are enough to infect a person. Syphilis symptoms usually show up about 3 to 4 weeks after a person gets infected.

The first reliable test for syphilis was developed in 1906 and is known as the Wasserman test. Today, we have better tests which are more reliable, such as the venereal disease research laboratory (VDRL) test and the rapid plasma reagin (RPR) test.

If syphilis isn’t treated, it can go through four stages (primary, secondary, latent, and tertiary) and affect multiple organs in the body, often many years or even decades after the original infection. Syphilis cases reached its peak in 1947, just before penicillin was widely introduced. Once penicillin became available, the rates of syphilis dropped. However, recent trends have shown that the rates of syphilis are rising again.

Today, millions of people worldwide are still affected by syphilis, and the number of cases is increasing. Syphilis can be much more severe in people who have human immunodeficiency virus (HIV). Therefore, people who test positive for either HIV or syphilis are usually tested for the other disease as well. The best way to stop syphilis from spreading is by early testing and treatment.

Doctors always need to be aware that symptoms affecting almost any organ in the body could be due to syphilis, and they should order the appropriate blood tests when needed. Even though syphilis bacteria are very sensitive to penicillin, it remains a significant global health issue as the testing and treatment efforts so far have not been sufficient to stop the disease from increasing.

What Causes Syphilis?

The Treponema family of bacteria are spiral-shaped, covered by a thick layer of fats called a phospholipid membrane. They are known for their slow growth rate, usually taking around 30 hours to duplicate. Treponema pallidum is the only type within this family known to cause sexually transmitted disease.

Other types of Treponema bacteria are responsible for different diseases that are not sexually transmitted. These diseases are caught through non-sexual contact. For example, Treponema pertenue causes a skin disease called yaws; Treponema pallidum endemicum brings about a condition known as bejel or endemic syphilis; and Treponema carateum causes a skin condition called pinta. All of these bacteria have similar genetic make-up but they act differently and are found in different parts of the world.

It’s notable that humans are the only creatures that can host these bacteria, meaning there are no animals that carry them.

Syphilis, caused by the Treponema pallidum bacteria, is mainly spread through sexual activity. This includes vaginal, anal, and oral sex. However, it can occasionally be caught through non-sexual methods, like skin-to-skin contact, or direct transfer such as shared needles or blood transfusions. A pregnant woman can also pass the infection to her baby, resulting in the baby being born with the condition, known as congenital syphilis.

Risk Factors and Frequency for Syphilis

Syphilis is a global health concern with the number of cases dramatically increasing for the past couple of decades. A study done in 2019 showed a shocking 60% rise in syphilis cases worldwide from 1990 to 2019, amounting to around 50 million people infected. The World Health Organization (WHO) reported around 7.1 million new cases in 2020, mostly coming from sub-Saharan Africa, Southeast Asia, Latin America, and the Caribbean.

In the United States, the rise in syphilis cases has been quite steep as well. There has been a 38% increase from 2008 to 2012, and a staggering 80% increase from 2018 to 2022, with 207,255 new cases reported just in 2022. Similar trends have been noticed in Europe as well, where the number of confirmed syphilis cases increased by 34% in 2022.

Particularly worrying is the heavily disproportionate burden of syphilis on developing countries and impoverished communities. These areas account for over 60% of all new diagnoses, making it an endemic issue for these regions. Despite existing tests that can diagnose both HIV and Syphilis, there has been a missed opportunity to increase syphilis testing by 100% to 200% in high-risk countries, primarily due to limited healthcare resources and the fact that many people with early stages of the disease do not show symptoms.

Women have been particularly affected by this increase, with incidence rates doubling from 2013 to 2017 and then increasing by a further 147% from 2016 to 2020. Similarly, there has been a concerning rise in congenital syphilis cases (where the disease is passed from mother to child during pregnancy), with the number of cases quadrupling from 2010 to 2020. Sex workers, too, have been heavily impacted, with a reported incidence of active syphilis at 10.8% worldwide in 2019.

Every year, about 1.5 million babies are born with congenital syphilis, especially in low-income countries. Congenital syphilis cases have been on the rise even in Western nations. In the U.S., the incidence nearly quadrupled from 2015 to 2019. The spike was highest among women aged 24 and under. The disease is disproportionately high among infants born to Black and Hispanic mothers, with most cases reported from California and Texas.

Despite this alarming increase, federal funding for STD prevention has dipped by 40% in the last two decades. This is alarming, especially considering that 30% of syphilis cases went untreated despite early diagnosis, indicating a missed opportunity for public health improvement. Barriers to adequate testing and treatment include lack of prenatal care programs, inadequate syphilis testing, lack of point-of-care tests, cultural issues, poverty, homelessness, discrimination, lack of health insurance, and substance abuse.

The 1932 Tuskegee syphilis experiment, where poor Black sharecroppers were denied treatment for syphilis, is a regretful chapter in U.S. medical history, causing continuing distrust in the healthcare system. Mistrust also stems from a lesser-known study in Guatemala where individuals were deliberately infected with syphilis to test if penicillin could prevent the disease.

Risky sexual behavior and having multiple partners also greatly increase the risk of syphilis transmission. Syphilis is common among bisexuals and men who have sex with men (MSM). Young men aged 20 to 29 are particularly at risk. MSM show a higher rate of syphilis compared to heterosexual men. Syphilis has been closely linked with HIV infections, as people having syphilis are more likely to become HIV positive.

The sharp increase in syphilis cases, both in the U.S. and globally, makes this a pressing health concern that needs more attention and resources. Factors contributing to its resurgence include improved HIV treatment, increased use of online dating, rise in drug abuse, increased acceptance of homosexual behavior, increasing population, poverty, homelessness, and the general misconception that syphilis is an “old” disease no longer relevant.

Signs and Symptoms of Syphilis

Syphilis is a disease that can be divided into four stages: primary, secondary, latent, and tertiary/late.

Primary syphilis usually starts with a firm, round, painless ulcer at the site of original infection, which often happens to be the genital region. This ulcer, called a chancre, appears 10 to 90 days after you’re exposed to the disease-causing bacteria. Patients usually don’t know it’s there, especially women, because it can occur on the cervix and is not painful. Despite the localized chancre, the bacteria quickly spread throughout the body, even into the cerebrospinal fluid, without any obvious symptoms.

Secondary syphilis develops in about 25% of untreated patients. Symptoms typically appear 2 to 8 weeks after the primary chancre has gone away. The bacteria multiply and spread throughout the body, causing symptoms such as fever, muscle ache, headache, loss of appetite, sore throat, weight loss, joint pain, fatigue, and skin issues. A rash on the palms of the hands and soles of the feet, as well as in the mouth is characteristic of secondary syphilis. Enlarged lymph nodes are common at this stage.

• Fever
• Headache
• Loss of appetite
• Sore throat
• Weight loss
• Skin rash, especially on the palms and soles
• Enlarged lymph nodes

Tertiary syphilis is a late stage of the disease that can appear months, years, or even decades after the initial infection. It includes neurosyphilis (which can cause meningitis, stroke, or other neurological problems), cardiovascular syphilis (which can lead to problems with the heart and blood vessels), and gummatous syphilis (which can damage any organ in the body). A majority of patients with untreated syphilis may eventually develop tertiary syphilis, although it may take a very long time for symptoms to appear.

Congenital syphilis is passed from an infected mother to her baby during pregnancy or birth. It can result in stillbirth, infant death, or serious health issues in the baby. Worldwide, it is estimated that 7 out of every 1000 pregnant women are infected with syphilis, and over 1.5 million babies are born with congenital syphilis. With no treatment, up to 40% of pregnancies in women with syphilis end in stillbirth, and many others result in premature birth or low birth weight babies.

Testing for Syphilis

If your doctor suspects that you might have syphilis, there are several tests they could use to try and confirm this. Two common methods are dark-field microscopy and tests on samples from your body, such as blood, tissue, or cerebrospinal fluid (i.e., the fluid around your brain and spine).

Dark-field microscopy is a technique where the doctor takes some fluid from syphilis sores and looks at it under a special microscope. This is good for diagnosing early syphilis and can give immediate results, but it may miss up to 20% of cases, especially when overseen by a less experienced operator. Furthermore, it doesn’t rule out syphilis if no bacteria are seen.

Another test called Polymerase chain reaction (PCR) can also be used. This test has a high accuracy rate and can be performed on a variety of body samples. However, it’s not recommended for testing fresh samples from sores due to its insufficient sensitivity.

While dark-field microscopy and PCR testing aren’t widely available in the US, serological testing (testing on body fluids like blood) is the preferred way to diagnose syphilis. There are two types of serological tests available: nontreponemal (general) and treponemal (specific).

Nontreponemal tests like VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin) are initial screening tests that detect antibodies in your body that form in response to syphilis. While these tests could be false positive, meaning they suggest you have syphilis when you don’t, a secondary or confirmatory test is required to be sure.

Treponemal antibody tests, another form of serological testing, can detect antibodies that specifically target the bacteria causing syphilis, confirming the diagnosis. They are positive early and remain positive for life, but they do not reflect the stage or severity of the infection.

Imaging tests such as a chest X-ray or CT scan may be required to determine the involvement of other organs. These are particularly useful in detecting complications like an aortic aneurysm.

Some newer, simpler tests that can give results within 15-30 minutes, requiring only a small sample of blood from a finger stick, are now available for point-of-care testing or home testing. Furthermore, the FDA has recently approved an over-the-counter treponemal antibody test for syphilis for home use, aiming to improve early detection.

If you test positive for syphilis, it’s important to remember that it doesn’t necessarily mean you have an active infection. You’ll also need a negative test, called a nontreponemal test, to be sure. If the initial tests suggest the disease is active, your doctor may take fluid from your spine to check for any neurological complications or treat you for neurosyphilis just to be safe.

It’s also important to be aware that syphilis can cause a wide range of symptoms and may be nicknamed “the great imitator.” This makes it crucial to conduct confirmatory testing to ensure an accurate diagnosis.

Treatment Options for Syphilis

Penicillin is the go-to antibiotic for all stages of syphilis, which is a sexually transmitted infection caused by the bacterium, Treponema. The bacteria multiplies very slowly, so types of penicillin that last for a long time in the body are preferred. Penicillin works by disabling a critical enzyme the bacteria need to grow and repair and without it, the bacteria can’t survive and will burst as fluids rush into them.

If you have syphilis, the exact treatment you’ll receive will depend on the stage of the disease.

– For early stages of the disease (primary, secondary, and early latent syphilis), a doctor would usually treat you with a single dose of benzathine penicillin given as a muscle injection.

– If you have later stages of the disease (tertiary, late latent syphilis), or if you have HIV along with syphilis, the treatment is usually three weekly doses of the same type of penicillin.

– If syphilis affects your nervous system (neurosyphilis) or your eyes or ears (ocular and otosyphilis), you would usually be treated with crystalline penicillin given through an IV for around two weeks.

The exact treatment could change depending on whether certain formulations of penicillin are available and resistance patterns among the bacteria in your locality. Following treatment, you will need to attend regular check-ups at 6, 12, and 24 months, with additional checks at 3 and 9 months for high-risk patients to ensure successful outcome of treatment.

Pregnant women should be tested for syphilis at their first prenatal visit. If tested positive, they are typically treated with a single injection of benzathine penicillin. This treatment can effectively prevent harmful outcomes for the fetus if given before the 28th week of pregnancy. If the infection is discovered in the second half of pregnancy, an ultrasound of the fetus is recommended as there might be signs of congenital syphilis. If necessary, newborns can be treated for syphilis as well.

In older children diagnosed with syphilis, treatment is usually administered through IV over 10 days, followed by a single dose of benzathine penicillin.

For those who have a confirmed allergy to penicillin, doxycycline might be used as an alternative. However, tetracyclines should be avoided in the later stages of pregnancy due to limited data available on the subject. For pregnant women, if other medications can’t be used and are desperately needed, cefriaxone is suggested.

It’s important to understand that most patients who think they are allergic to penicillin aren’t actually allergic. For pregnant women who are allergic to penicillin, considering desensitization can be a potential solution, as penicillin is still the most effective antibiotic for treating syphilis, especially during pregnancy.

Please avoid azithromycin and tetracyclines for pregnant women and babies, as they do not cure the infection reliably. Other antibiotics should be used with caution and only when absolutely necessary due to lack of data on their effects in such patients.

For preventing syphilis, options include a single dose of benzathine penicillin if one has been in unprotected sexual contact with a known syphilis patient. There’s also a possibility of using doxycycline within 72 hours after direct exposure, which may reduce the risk of infections, including syphilis. This is especially significant for high-risk groups such as men who have sex with men.

What else can Syphilis be?

There are several conditions that can show similar signs and symptoms to syphilis. These include:

• Behcet syndrome
• Chancroid
• Contact or atopic dermatitis
• Dementia
• Erythema multiforme
• Genital herpes
• Granuloma inguinale
• Lymphogranuloma venereum
• Lymphoma
• Mononucleosis
• Pityriasis rosea
• Psychiatric illness
• Rocky Mountain Spotted Fever
• Uveitis
• Viral exanthema

What to expect with Syphilis

It’s essential to understand the potential progression and outcome of syphilis to make informed decisions about treatment and to accurately inform patients about possible health effects they might encounter. How syphilis affects a person can vary based on the stage of the disease and which organs are affected.

If not treated, the bacteria that causes syphilis can lead to severe health issues and even death. In most cases, the disease progresses and negatively affects the heart and central nervous system (CNS), which is essentially the brain and spinal cord. If these conditions are not treated, they can be lethal.

In pregnancy, syphilis can lead to serious complications like miscarriages, stillbirths, and the death of the baby after birth. Without treatment during pregnancy, the syphilis infection is almost always transmitted from the mother to the unborn child.

Possible Complications When Diagnosed with Syphilis

Untreated syphilis can cause permanent damage to your brain and heart. Depending on how long you’ve had syphilis, it can show up as meningitis, stroke, or damaged cranial nerves in the early stages, or cause a condition called ‘tabes dorsalis’, dementia, and generalized muscle weakness in the late stages.

Heart issues can also occur from syphilis if left untreated. These complications can show up as inflammation of the aorta (the main artery of your body), leaking aortic valve, narrowing of the root of the carotid artery, or nodular lesions known as ‘gummas’ in various body parts.

Untreated syphilis also impacts people with HIV, resulting in higher virus replication rates and lower levels of the immune cell called CD4. Also, syphilis progresses at a quicker pace in these individuals.

If a pregnant woman has syphilis and it isn’t diagnosed and treated quickly, it can cause neonatal infections leading to congenital syphilis in the baby and adverse outcomes for the pregnancy.

Possible Complications:

• Meningitis, Stroke, Damaged Cranial Nerves
• Tabes dorsalis, Dementia, Muscle Weakness
• Heart Inflammation, Leaking Heart Valve, Narrowing of Main Artery
• Nodular Lesions in Various Body Parts
• Increased HIV replication, Decreased CD4 Levels, Faster Progression
• Congenital Syphilis, Adverse Pregnancy Outcomes

Preventing Syphilis

There’s been a concerning rise in syphilis cases around the world, especially among underserved or economically disadvantaged populations. One tool that could help is self-testing, a method like the at-home tests that became widely used during the COVID-19 pandemic. Such kits can be used by people who don’t have easy access to healthcare services. They can provide fast results and are generally socially acceptable — many people and doctors even prefer them for initial screenings.

Self-testing kits are a practical and cost-efficient solution that maintains privacy, decreases the burden on healthcare facilities, and reduces unnecessary clinic visits while encouraging follow-up appointments for the people who test positive.

At-home testing kits for sexually transmitted diseases (STDs) work similarly to quick on-the-spot tests used by medical professionals. They also are associated with higher testing rates in both men and women compared to clinic testing. On average, these kits can accurately identify 90% of positive cases and correctly rule out 96% of negative cases. Specifically for syphilis, these kits have an 85% accuracy rate for picking up positive cases and a 91% accuracy rate for ruling out negative cases.

The majority of self-testing kits can detect chlamydia and gonorrhea. Most can also identify other diseases, like syphilis, trichomonas, HIV, herpes simplex virus type 2, and hepatitis C. However, the tests for herpes and syphilis may sometimes mistakenly flag past or insignificant infections. If you get a positive test result, it’s best to get further testing from a doctor to be sure.

Some of these kits can be analyzed at home, while others require you to send a sample to a laboratory for processing. Remember that the quality of the sample you provide and how it’s handled can impact the reliability of the test. For follow-up testing and treatment, you’ll still need to involve a medical professional.

Keep in mind that if you test positive, you could experience high levels of anxiety due to the lack of immediate access to a healthcare professional who you can ask questions, arrange further testing with, or seek treatment from. Insurance may cover some of these tests in the U.S., but they aren’t available in every state.

For people with typical risk levels, it’s suggested to test for syphilis once a year if you’re in a monogamous relationship. If you’re a man who has sex with men (MSM) and has multiple partners or are HIV-positive, testing is advised every 3 to 6 months. It’s also strongly recommended that all pregnant individuals get tested.

Reversing the global increase of syphilis will require better patient knowledge, early diagnosis, immediate treatment in suspected cases, and the adoption of public health guidelines. Improved on-the-spot testing and prompt treatment in high-risk areas can assist with this. In the long run, a vaccine might be necessary to fully address this issue. Progress is being made, with specific protective factors already identified in the bacterium that causes syphilis.