This link opens your blog's RSS feed in XML format.
To subscribe, copy and paste this link into your RSS reader:
https://jay-alam.quarto.pub/javaid-alam/blog.xml
You can use free apps like Feedly, Inoreader, or NetNewsWire.
Javaid Alam
October 25, 2025
Cite this article:
Javaid Alam. Syphilis: The Great Imitator That Refuses to Disappear – Javaid Alam.
Available at: javaidalam.com
the great imitator.
Beyond the biology lies a tangled interplay of stigma, inequality, and scientific challenge — reminding us that no infection is purely microbial.2
Despite being curable, syphilis remains an urgent global health threat. According to the World Health Organization (WHO), an estimated 8 million people aged 15–49 acquired syphilis in 2022, and nearly 700,000 infants were born with congenital syphilis.3 This tragic burden resulted in approximately 220,000 stillbirths and neonatal deaths — a toll higher than that of many tropical diseases combined.4
Globally, syphilis shows a disturbing comeback:
In high-income countries, infection rates have risen sharply among men who have sex with men (MSM) and individuals with HIV co-infection.5
In low- and middle-income nations, congenital syphilis continues to reflect gaps in antenatal screening and treatment access.6
Among pregnant women, WHO data from 2024 indicate that only 67% received syphilis screening during pregnancy.7
In the United States, syphilis cases rose by 80% between 2018 and 2023, reaching the highest level since 1950. CDC surveillance highlights a tripling of congenital syphilis cases in the past five years — preventable tragedies tied to missed screening or inadequate prenatal care.8
In Australia, where data are more granular, 5,809 infectious syphilis cases were reported between September 2023 and September 2024, with a worrying increase among women of child-bearing age and First Nations communities.9 This resurgence underscores an essential truth: biomedical cures cannot alone conquer social diseases. Stigma, underdiagnosis, and healthcare inequities still allow syphilis to slip through the cracks.
Syphilis unfolds in distinct but deceptive stages, often separated by years of silence.
The curtain rises 3–4 weeks after infection. A small, painless ulcer (chancre) appears at the site of sexual contact — genital, anal, or oral. Its clean edges and firm base make it distinctive, yet it heals spontaneously within weeks, leaving behind no trace — and often, no diagnosis.10
Weeks later, as T. pallidum infiltrates the bloodstream, the infection announces itself dramatically: a widespread rash (often on palms and soles), fever, swollen lymph nodes, patchy hair loss, and malaise. The rash may masquerade as an allergic reaction or viral exanthem — the hallmark of “the great imitator.” Symptoms fade, but the pathogen does not.11,12
In this silent interval, syphilis hides deep within tissues, undetectable except through blood tests. Early latent disease (within two years) remains infectious; late latent disease (beyond two years) is typically not. Without treatment, one-third of cases progress further.13,14
Years — sometimes decades — later, syphilis re-emerges with devastating vengeance. Gummatous lesions eat into skin and bone; cardiovascular syphilis damages the aorta; and neurosyphilis warps the brain and spinal cord, manifesting as paralysis, blindness, or psychosis.10,15 The organism’s ability to evade the immune system stems from its unique outer membrane, which expresses few antigens and continuously alters its surface proteins — a microbial cloak of invisibility that frustrates both immunity and vaccine development.16
Did You Know? In the 16th and 17th centuries, syphilis was treated with mercury ointments and vapor baths, giving rise to the saying,“A night with Venus, a lifetime with Mercury.” The toxic therapy often harmed more than it healed. Penicillin, introduced in the 1940s, changed that story forever.
Diagnosing syphilis requires both clinical suspicion and laboratory confirmation, as its symptoms mimic countless disorders.
Early lesions can be examined using dark-field microscopy or polymerase chain reaction (PCR) to visualize or detect T. pallidum DNA directly.17
Two categories of blood tests complement each other:
Treponemal tests (e.g., FTA-ABS, TPPA, TPHA) detect antibodies specific to T. pallidum and usually remain positive for life.18
Non-treponemal tests (e.g., VDRL, RPR) measure antibodies to cellular damage caused by infection. Titres correlate with disease activity and decline after treatment.19
Diagnosis is typically confirmed when both tests are reactive. False positives can occur with autoimmune diseases, viral infections, or pregnancy; false negatives may appear in early primary disease before antibody development.
In neurosyphilis, cerebrospinal fluid analysis via lumbar puncture may reveal elevated protein or reactive VDRL. Point-of-care rapid tests, increasingly deployed in low-resource settings, now enable same-day diagnosis and treatment, a crucial advance toward elimination goals.20,21
| Test | Full Name | Type | Purpose | Persistence After Cure |
|---|---|---|---|---|
| FTA-ABS | Fluorescent Treponemal Antibody Absorption | Treponemal | Confirmatory | Usually lifelong |
| TPPA | Treponema pallidum Particle Agglutination | Treponemal | Confirmatory | Lifelong |
| TPHA | Treponema pallidum Hemagglutination Assay | Treponemal | Confirmatory | Lifelong |
| VDRL | Venereal Disease Research Laboratory | Non-treponemal | Screening / Monitoring | Titers decline with treatment |
| RPR | Rapid Plasma Reagin | Non-treponemal | Screening / Monitoring | Titers decline with treatment |
Note: Treponemal tests (FTA-ABS, TPPA, TPHA) usually remain reactive for life, while non-treponemal tests (VDRL, RPR) are used to assess treatment response and monitor for reinfection.
The gold-standard therapy for all stages (check the treatment option below) is benzathine benzylpenicillin, given as a single intramuscular injection (2.4 million units) for early syphilis, or three weekly doses for late latent and tertiary stages.22
Syphilis remains fully curable — a rare blessing in infectious disease
Benzathine benzylpenicillin and benzylpenicillin
Both benzathine benzylpenicillin and benzylpenicillin belong to the β-lactam antibiotics, specifically the penicillin class. They are further classified as:
Benzylpenicillin (also called penicillin G) – a natural penicillin.
Benzathine benzylpenicillin – a long-acting depot form of benzylpenicillin, formulated as a benzathine salt to allow slow release and prolonged action.
Mechanism of Action
They both exert their bactericidal effect by inhibiting bacterial cell wall synthesis.
They bind to penicillin-binding proteins (PBPs) located on the inner membrane of the bacterial cell wall.
This inhibits the transpeptidation reaction, a critical step in the synthesis of peptidoglycan – the structural component of the bacterial cell wall.
Inhibition leads to a weakened cell wall, resulting in cell lysis and death, particularly in actively dividing bacteria.
| Situation | Recommended | Alternative (specialist oversight recommended) |
|---|---|---|
| Early syphilis (primary, secondary, early latent) * | Benzathine benzylpenicillin 2.4 MU (1.8 g) IMI, stat, given as 2 injections containing 1.2 MU (900 mg) | Doxycycline 100 mg 12-hourly for 14 days |
| Late syphilis or syphilis of unknown duration (late latent >2 years) | Benzathine benzylpenicillin 2.4 MU (1.8 g) IMI, given as 2 injections containing 1.2 MU (900 mg) once weekly for 3 weeks | Doxycycline 100 mg 12-hourly for 28 days |
| Tertiary syphilis | Benzathine benzylpenicillin 2.4 MU (1.8 g) IMI, given as 2 injections containing 1.2 MU (900 mg) once weekly for 3 weeks | — |
| Sexual contacts of syphilis | Presumptive treatment: Benzathine benzylpenicillin 2.4 MU (1.8 g) IMI, stat, given as 2 injections containing 1.2 MU (900 mg) | — |
| Neurosyphilis (specialist advice must be sought) | Benzylpenicillin 1.8 g intravenously, 4-hourly for 14 days (initiated in hospital; hospital-in-the-home program for suitable patients may be utilised) | — |
*Early syphilis includes primary, secondary, and early latent stages diagnosed within the previous two years.
For neurosyphilis, Benzylpenicillin 1.8 g intravenously, 4-hourly for 14 days.23
No documented resistance to penicillin has been observed in T. pallidum to date.24
For penicillin-allergic patients, doxycycline (100 mg twice daily for 14–28 days) is an accepted alternative, though less studied.
In pregnancy, desensitization to penicillin remains mandatory since no effective substitute prevents congenital transmission.25
Jarisch–Herxheimer Reaction Within hours of initiating therapy, patients — especially those with early syphilis — may develop fever, chills, headache, and myalgia. This transient inflammatory response, known as the Jarisch–Herxheimer reaction, results from the sudden release of bacterial components as the spirochetes die. It usually resolves within 24 hours and can be managed with rest and antipyretics.26
Treatment does not end with the injection.
Patients should abstain from sexual contact for 7 days after treatment and until partners are tested and treated.27
Partner notification — whether direct or via anonymous digital tools — is crucial to prevent reinfection and community spread.
Clinicians must report cases to public health authorities according to national guidelines.
Follow-up serologic testing at 3, 6, and 12 months assesses treatment success: a four-fold decline in non-treponemal titre signals cure.28
For HIV-positive individuals, close follow-up is essential, as treatment failure and neurosyphilis are more frequent.29
Recent studies have demonstrated that doxycycline post-exposure prophylaxis (Doxy-PEP) — a 200 mg dose taken within 72 hours after sexual activity — can reduce syphilis incidence among MSM by up to 70-80%.30,31 Yet, experts caution that widespread use may accelerate antimicrobial resistance and disrupt the microbiome, necessitating case-by-case consideration.32,33 Public health agencies, including WHO, now recommend routine syphilis screening during pregnancy, expanded testing in high-risk populations, and integrated STI services to combat the epidemic holistically.34,35
From its medieval shadow to the microscopes of modern laboratories, syphilis embodies the fragile alliance between human behavior, science, and social justice. It is a disease that hides in plain sight — imitating, evading, and reminding us of medicine’s moral imperative: vigilance. In 2025, we have every tool to end syphilis — diagnostics, antibiotics, and public health knowledge — yet the infection persists where inequity thrives. The challenge is no longer microbiological; it is societal. Eradication will demand not only injections, but empathy — ensuring that every pregnant woman, every marginalized community, and every person at risk has access to testing, treatment, and trust. Because in the story of syphilis, the final act has yet to be written.