Introduction

Syphilis, a centuries-old Sexually Transmitted Infection (STI), remains a significant global health challenge despite advances in medical science. The causative agent, Treponema pallidum, is a Spirochete bacterium known for its stealthy pathogenesis and capacity to evade immune detection. This article describes the biology and transmission of T. pallidum, the clinical manifestations of syphilis and the ongoing challenges in diagnosis, treatment and control. Treponema pallidum is a slender, helical bacterium measuring approximately 6 to 20 micrometers in length and 0.1 to 0.2 micrometers in diameter. Its spiral shape and unique motility, driven by periplasmic flagella, enable it to penetrate mucosal barriers and disseminate throughout the body. This pathogen is highly adapted to the human host, with humans serving as its only natural reservoir. Transmission of Treponema pallidum occurs primarily through direct sexual contact, when the bacterium is present in infectious lesions such as chancres or mucous patches. Vertical transmission from mother to fetus, known as congenital syphilis, can also occur during pregnancy, leading to severe complications including stillbirth, neonatal death, or congenital abnormalities. Rarely, syphilis can be transmitted through nonsexual routes such as blood transfusion or contact with infectious lesions. The bacterium’s genome is highly reduced, with limited biosynthetic capabilities, making it dependent on the human host for survival. This reliance on host factors, combined with its ability to evade immune responses through antigenic variation of surface proteins, makes T. pallidum a uniquely challenging pathogen to study and combat.

Clinical manifestations and challenges in diagnosis

Syphilis progresses through distinct stages if left untreated, each with characteristic clinical features:

Primary syphilis the attribute of this stage is a painless ulcer known as a chancre, which develops at the site of infection. Chancres heal spontaneously within weeks, but the bacterium continues to spread systemically. Secondary syphilis weeks to months after the initial infection, untreated individuals may develop systemic symptoms, including a widespread rash, mucosal lesions, lymphadenopathy, fever and malaise. These symptoms also resolve spontaneously, leading to a latent phase.

Latent syphilis in this stage, the infection is asymptomatic, but the bacterium persists in the body. Latent syphilis can last for years and is divided into early and late phases based on the duration of infection. Tertiary Syphilis decades after the initial infection, a subset of untreated individuals develops severe complications involving the cardiovascular system, central nervous system (neurosyphilis) and other organs. Gummas, granulomatous lesions, may also occur in late-stage syphilis. Congenital syphilis, resulting from vertical transmission, can cause miscarriage, stillbirth, or multisystem involvement in neonates. Early recognition and treatment during pregnancy are important to preventing these outcomes.

Treatment, resistance and prevention strategies

The fundamental of syphilis treatment remains penicillin, which has proven highly effective in eradicating Treponema pallidum. Benzathine penicillin G is the drug of choice for all stages of syphilis, while aqueous penicillin G is used for neurosyphilis and congenital syphilis. Alternative antibiotics, such as doxycycline or ceftriaxone, may be used for individuals allergic to penicillin, although desensitization to penicillin is preferred in critical cases. Despite the effectiveness of penicillin, challenges in controlling syphilis persist. Delays in diagnosis, stigma associated with STIs and limited access to healthcare contribute to ongoing transmission. Moreover, although resistance to macrolides like azithromycin has been documented, Treponema pallidum has not yet developed significant resistance to penicillin, underscoring the importance of continued surveillance and judicious use of antibiotics. Prevention strategies focus on reducing transmission through education, routine STI screening and the use of barrier methods such as condoms. Prenatal screening and treatment are critical to preventing congenital syphilis. Public health initiatives, including contact tracing and partner notification, play a vital role in controlling outbreaks. Research into a vaccine against Treponema pallidum is ongoing, but the bacterium’s complex immune evasion strategies pose significant challenges. Advances in genomics and proteomics may eventually pave the way for effective vaccines and novel therapeutic approaches. Treponema pallidum exemplifies the resilience of microbial pathogens and the ongoing challenges in infectious disease control. Despite the availability of effective treatment, syphilis remains a global public health concern due to barriers in access to care, stigma and diagnostic difficulties.

Continued investment in research, public health infrastructure and education is in need to combat the enduring threat of syphilis via ensure that the battle against Treponema pallidum does not falter.