Shatter the Stigma: We Need to Talk About Syphilis

History

Syphilis is known by many names, including “great pox”, “French disease”, “Neapolitan disease”, “German disease”, “Spanish disease”, “Polish disease”, and even “Christian disease”, depending on the time period and culture involved. This is because people often have a xenophobic tendency to blame the transmission of infectious diseases on people from other countries [6].

Origins of the disease

There are few detailed records that can be used to definitively trace the origin of syphilis. However, various hypotheses have emerged over the centuries. Some of these are described below. [1,6].

• Pre-Columbian hypothesis: The pre-Columbian hypothesis maintains that the syphilis originated around 7,000 BC. According to this model, by about 3,000 BC, the bacteria that causes syphilis, which was endemic to Southwest Asia, emerged as a sexually transmissible disease due to the climate change that occurred during this time. It then spread to Europe and the remaining parts of the world. Adherents of this model believe that syphilis was once a mild disease whose virulence grew over time due to a number of deadly mutations.
• Unitarian hypothesis: The unitarian hypothesis advocates that syphilis and non-venereal treponemal diseases are different variants of the same infections. It further stresses that clinical variations are due to geographic, climatic, and cultural differences. For instance, Yaws, a non-venereal disease in Africa, is believed to have evolved into endemic syphilis in countries with cold and dry climates where personal hygiene is poor.
• Columbian hypothesis: According to the Columbian hypothesis, syphilis was brought to Europe from the Americas in 1493 by Christopher Columbus and his sailors. Documents belonging to Spanish physicians Fernandez de Oviedo and Ruy Diaz de Isla stand out as supportive evidence to back this theory. These physicians were present when Christopher Columbus returned from America. This theory has been disproved. 

Several other theories tried to establish a connection between syphilis and leprosy. For instance, a tale from 16th-century Spain speculated that syphilis originated from a sexual relationship between a Spanish prostitute and a person with leprosy [6].

How Syphilis got its name

In 1530, Giraloma Fracastoro, an Italian physician and poet, was the first to coin the word “syphilis.” The name  referred to a character in one of his books, ‘Syphilis Sive Morbus Gallicus’. 

Evolution of diagnosis

Throughout the centuries, various attempts have been made to find a cure for syphilis. The first major breakthrough occurred in 1943 with the invention of penicillin, the world’s first antibiotic [7]. 

Until the 18th century, many physicians did not differentiate between sexually transmitted diseases. This makes it difficult for historians to definitively determine how many people in the past had syphilis.  Below is a short history of the successes and failures in understanding, diagnosing, and treating syphilis. 

• Differentiating from other STIs: In 1767, John Hunter, a venereal diseases specialist, used secretions from a patient with gonorrhea to infect a healthy patient. The healthy patient soon developed syphilis, which led Hunter to believe that syphilis resulted from gonorrhea. However, the person from whom the sample was taken was concurrently infected with both syphilis and gonorrhea. Hunter’s error hindered progress in understanding syphilis. 
• Disease spread: In 1831, French venereologist Philippe Ricord made a few interesting observations regarding the spread of syphilis. He pointed out that people become infected when they came into physical contact with infected individuals. 
• Causative agent: In 1905, Schaudinn and Hoffman discovered the etiologic agent of syphilis. It was initially named Spirochaeta pallida and was subsequently changed to Treponema pallidum.
• Microscopy: In 1906, Karl Landsteiner made use of the dark-field microscopy method for detecting the spirochete of syphilis. 
• Blood test: The first serologic test to diagnose syphilis was introduced in 1910 by August Wasserman, a German bacteriologist.
• The TPI test: In 1949, Nelson and Mayer introduced the Treponema Pallidum immobilization (TPI) test, the first test explicitly used to detect the presence of T. pallidum. It has since become instrumental in confirming syphilis infections [6].   

In 2016, the World Health Organization (WHO) developed a roadmap to eradicate STIs by 2021. One of their main focuses was eliminating congenital syphilis by improving screening and treatment, especially among pregnant women. 

Their specific goals are listed here:

• Reduce the global incidence of syphilis by 90%.
• Bring the number of congenital syphilis cases worldwide to 50 (or less) per 100,000 live births in about 80% of countries by 2030 [8].

Epidemiology

The geographic distribution of syphilis varies based on a region’s socioeconomic status. The incidence is higher in lower and middle-income countries than in developed nations or high-income countries. This is mainly due to a lack of proper infrastructure for screening and testing. In high-income countries, including the US, Western Europe, and China, the incidence of syphilis is higher among men who have sex with men (MSM) [8].

People at a greater risk of getting exposed to the infection include sexual partners of people with syphilis, people with multiple sex partners, sex workers, transgender people, pregnant women, MSM, HIV-positive people who are sexually active, and those taking pre-exposure prophylaxis (PrEP) for HIV prevention [3,8].  

United States

There has been a significant increase in syphilis cases in the US since 2001. According to the Centers for Disease Control and Prevention (CDC), there were 133,945 new cases in 2020 alone. MSM accounted for 43% of all primary and secondary cases. The country has also seen an increase in the number of congenital syphilis cases. In 2021, about 2,100 cases of congenital syphilis were reported nationwide [3]. 

Asia

Syphilis cases are on the rise in many Asian countries. The prevalence of the illness has increased from 0.9% in 2009 to 30.9% in 2019 [9]. China, in particular, has seen a significant increase in syphilis cases since 1995. The incidence of illness has increased from 1.0 per 100,000 population in 1995 to 32.2 per 100,000 population in 2016. It is exceptionally high among MSM involved in condomless sex with multiple sexual partners [10]. 

In 2019, the prevalence of the disease in other Asian countries, including India, Myanmar, Indonesia, Cambodia, Nepal, Bangladesh, Taiwan, the Philippines, and Vietnam, was 17.5%, 14.1%, 9.0%, 5.5%, 4.8%, 4.46%, 2.5%, 2.3%, and 1.3%, respectively. Interestingly, over 50% of MSM infected with syphilis are HIV positive [9].

Canada

In Canada, the incidence of syphilis has increased gradually from 5.1 per 100,000 population in 2011 to 24.7 per 100,000 population in 2020. The prevalence was higher in men compared to women during this period. In 2020, about 50 congenital syphilis cases were reported in the country, much higher than in previous years [13].

Europe

In 2018, data gathered through comprehensive surveillance in the EU showed an incidence of about 7.0 syphilis cases per 100,000 population. Malta, Luxembourg, the United Kingdom, and Spain had the highest incidence rates (17.9, 17.1, 12.6, and 10.3 cases per 100,000 population, respectively). The prevalence of illness was higher in men than in women. People between the ages of 25 and 34 had the highest number of incidences, with 29 cases per 100,000 population [11].

Africa

The prevalence of syphilis is high among pregnant women in Africa. As of 2018, around 6.5% of pregnant women in South Africa, 4.6% in East Africa, and 4.0% in West Africa were infected with syphilis [8].  

Australia and the Pacific 

The number of cases reported in Australia skyrocketed by 358% between 2009 and 2019. Aboriginal and Torres Strait Islander people and MSM were the most affected populations [12].

How is it spread?

Syphilis is highly contagious and can spread from one person to another, either through direct or indirect contact. 

• Direct route – This occurs when an uninfected person comes into contact with a syphilis sore during vaginal, anal, or oral sex. Although rare, syphilis can be spread through kissing when there is direct contact with an open sore.
• Indirect route – An indirect route of transmission occurs when an uninfected person encounters objects or surfaces contaminated with syphilis, such as tubs, toilet seats, swimming pools, and door knobs. Also, sharing clothes or eating utensils can infect a person.
• Neonatal route – Pregnant women with syphilis can transmit the infection to their unborn children [3]. 

Biology of the disease

The syphilis bacteria enter the body through a person’s skin or bodily fluids when they come into contact with an infected sore called a chancre. These sores can be found on the genitals, anus, or mouth. The bacteria then spread quickly throughout the body through the blood, potentially causing fever, sore throat, muscle aches, and fatigue.

If the infection is not treated by this stage, rashes appear on the skin, especially on the palms of the hands and soles of the feet. Other symptoms may include swollen lymph nodes, fever, and weight loss.

If the disease remains untreated, it can progress to the latent stage where there are no visible symptoms, but the bacteria remain in the body and cause severe damage to the brain, nerves, eyes, heart, blood vessels, liver, bones, and joints. In severe cases, the infection can lead to death [5].

Symptoms

It might take between 10 and 90 days for symptoms to appear following exposure to the infection. However, the average time until symptoms manifest is 21 days.

The disease progresses in four phases: primary, secondary, latent, and tertiary. The clinical signs and symptoms vary from phase to phase.  

Primary Phase

Single or multiple sores appear in and around the penis, vagina, anus, rectum, lips, and mouth. These are painless sores that are round and firm. The sores last about three to six weeks, regardless of whether or not a patient receives treatment. According to the CDC, treatment is necessary to prevent the infection from progressing to the secondary stage.

Secondary Phase

Rashes will appear in and around the mouth, vagina, or anus as the sores that occurred during the primary phase begin to heal. Sometimes, they appear several weeks after the sores have healed. They appear on the palms and/or feet and are usually rough, red, or reddish-brown. Patients don’t usually experience any itching. Other symptoms that occur during this phase include:

• Fever
• Headache
• Swelling of lymph glands
• Sore throat
• Hair loss
• Weight loss
• Muscle pain
• Tiredness

Without proper treatment, the disease will progress to the latent stage.

Latent Phase

As the word suggests, the latent phase is characterized by no visible signs or symptoms. However, the disease can progress to the tertiary stage if treatment is not given.

Tertiary Phase

The disease will progress to this phase only in specific individuals who have not received proper treatment during the early stages of their illness. The tertiary phase usually manifests itself clinically 10 to 30 years after infection. During this phase, syphilis can affect various parts of the body, including the heart, blood vessels, brain, bones, joints, eyes, and liver. It can even lead to death. 

Those who do not receive treatment can develop serious complications as the infection spreads to the eyes (ocular syphilis), ears (otosyphilis), nervous system brain (neurosyphilis). These complications may develop at any of the four stages of the disease. 

Congenital syphilis (CS) could result in: 

• Neonatal deaths
• Miscarriages
• Premature births
• Intrauterine growth retardation
• Symptomatic children [4].

Diagnosis

Treponemal tests: These are performed to detect treponemal antibodies that are specific to syphilis. The tests include:

• TP-PA
• Chemiluminescence immunoassays
• Immunoblots
• Rapid treponemal assays
• EIAs [3]  

Cerebrospinal fluid (CSF) evaluation: For those who experience symptoms related to neurosyphilis, including cranial nerve dysfunction, stroke, meningitis, altered mental status (acute and chronic), or loss of vibration sense, CSF evaluation is the preferred method used for diagnosis [14]. 

Congenital syphilis diagnosis: Diagnosis for congenital syphilis should be performed on infants born to mothers with reactive nontreponemal and treponemal test results. Infants should be completely examined for congenital syphilis if quantitative nontreponemal tests are reactive. 

Lesions, bodily fluids, or tissues, including the umbilical cord and placenta, should be examined by darkfield microscopy PCR testing or special stains. Other evaluations recommended by the CDC include the following:

• CSF analysis by VDRL
• Cell count and protein
• CBC with differential and platelet count
• Long-bone radiographs [3].

Treatment

Preferably, treatment must start during the initial stages of the infection to prevent the disease from progressing. However, syphilis can cause certain types of damage that are irreversible [3]. 

Treatment for primary and secondary syphilis

For adults and adolescents, 2.4 million units of benzathine penicillin G is intramuscularly administered as a single dose [3,15].

For infants and children, 50,000 units/kg (body weight of benzathine penicillin G is intramuscularly administered as a single dose) [15].

Treatment for latent syphilis

For this stage, 2.4 million units of benzathine penicillin G is intramuscularly administered in three doses each at weekly intervals (7. 2 million units in total) [3].

Treatment for tertiary syphilis

For this stage, 2.4 million units of benzathine penicillin G is intramuscularly administered in three doses each at weekly intervals (7. 2 million units in total) [16].

Treatment for neurosyphilis, ocular syphilis, and otosyphilis

Three to four million units of aqueous crystalline penicillin G are intravenously administered continuously or every four hours a day (18-24 million units per day) for about 10-14 days [3].

Can syphilis recur?

Yes, persistence or recurrence of signs and symptoms and a continuous fourfold increase in nontreponemal test titer indicate reinfection [3].

Prevention

Currently, there are no vaccines to protect against syphilis, but attempts are underway to develop a vaccine that could reduce morbidity and mortality caused by the disease, especially with regard to congenital syphilis [8]. 

However, the following preventive measures can help prevent the spread of the disease: 

• Regular and proper use of condoms is helpful. However, some lesions may not be completely covered by condoms. In such cases, sex partners can still become susceptible to the infection.
• People in long-term, mutually monogamous relationships have fewer chances of acquiring syphilis. Another way could be to completely abstain from vaginal, anal, or oral sex [3].
• People who have had sexual relations with infected individuals 90 days before they were diagnosed with primary, secondary, or early latent syphilis should be treated presumptively for early syphilis. In such cases, people should receive treatment even if they are seronegative for the infection. 
• Those who have had sexual relations with infected people three months before the latter was diagnosed with the infection should still take presumptive treatment until the serologic tests show negative [14]. 
• The CDC recommends that pregnant women should take a blood test to detect the presence of syphilis. This helps to prevent the spread of the infection from the mother to the baby [3].

Outbreaks of sexually transmitted infections (STIs) are a serious health concern with a long-lasting impact on individuals, communities, and entire regions. While STIs can be prevented through safe sex practices, many people are at risk for contracting STIs. 

Hopefully, with sustained community-based public health initiatives, we can lower the incidence of syphilis.

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