HemoChat is an evidence-based AI medical search tool covering all major clinical domains, powered by 46,298 SNOMED-CT concepts, clinical guidelines, and live PubMed literature.

What medical domains does HemoChat cover?

HemoChat covers all major medical domains including cardiology, oncology, neurology, hematology, pulmonology, endocrinology, gastroenterology, psychiatry, nephrology, rheumatology, musculoskeletal, and more — with 46,298 SNOMED-CT concepts.

Is HemoChat a replacement for clinical judgment?

No. HemoChat is for clinical reference only and is not a substitute for professional medical judgment. Always consult qualified healthcare professionals for medical decisions.

What AI technology does HemoChat use?

HemoChat uses a hybrid GraphRAG + VectorRAG pipeline combining Neo4j knowledge graphs with FAISS vector search and an LLM for answer generation.

Latent syphilis with positive serology — Clinical Guidelines

Overview

Latent syphilis refers to a stage of syphilis where the infection persists asymptomatically despite positive serological tests for Treponema pallidum antibodies 1. This condition primarily affects sexually active individuals, particularly those within high-risk groups such as men who have sex with men, pregnant women, and individuals with multiple sexual partners 2. The clinical significance lies in the potential for latent syphilis to progress to more severe stages, including symptomatic syphilis, tertiary syphilis, and complications affecting multiple organ systems, underscoring the importance of regular screening and early intervention 3. Identifying and managing latent syphilis cases is crucial for preventing long-term health complications and reducing transmission rates within populations 4.

Pathophysiology Latent syphilis represents a subclinical phase of infection where Treponema pallidum persists in the host despite the absence of overt clinical symptoms 1 2. During this latent phase, the bacterium evades the immune system primarily through antigenic variation and immune evasion mechanisms, allowing it to remain dormant within host tissues, particularly in lymphoid tissues and vascular walls . The spirochete's ability to modulate its surface antigens contributes to its persistence, as evidenced by the variability observed in serological tests over time 4. At the cellular level, T. pallidum infection triggers a robust humoral immune response characterized by the production of antibodies against various treponemal antigens, including those recognized by the Fluorescent Treponemal Antibody Absorption (FTA-ABS) test and Treponema pallidum Hemagglutination Assay (TPHA) 5. However, despite the presence of these antibodies, the immune system often fails to completely eliminate the pathogen due to its intracellular and extracellular lifestyles, leading to chronic infection 6. The chronic inflammation associated with latent syphilis can result in subtle tissue damage and contribute to the risk of long-term complications such as cardiovascular syphilis, which affects the aorta and coronary arteries 7. Molecularly, the persistence of T. pallidum is linked to its ability to induce a persistent immune response without full clearance, often mediated by a balance between Th1 (pro-inflammatory) and Th2 (antibody-mediated) immune responses 8. This imbalance can lead to ongoing subclinical inflammation and gradual tissue damage, particularly in vascular structures, where the bacteria preferentially reside . The lack of robust cellular immunity coupled with chronic antigenic stimulation can also result in the generation of autoantibodies, contributing to the variability seen in serological tests and complicating definitive diagnosis . Overall, the pathophysiology of latent syphilis hinges on the bacterium's sophisticated evasion strategies and the host's compromised ability to mount a curative immune response, setting the stage for potential reactivation and subsequent clinical manifestations if left untreated 1 2.

Epidemiology Syphilis, caused by the bacterium Treponema pallidum, remains a significant public health concern globally, particularly within Category B infectious diseases 1. According to the World Health Organization (WHO), approximately 8 million new cases of syphilis were reported worldwide in 2022 3. Notably, syphilis prevalence varies significantly across different regions; in China, it ranks among the top three Category B infectious diseases, with primary and secondary syphilis cases increasing to 5.7 to 10.0 per 100,000 persons by 2005 compared to 0.2 cases per 100,000 in 1993 1. In Brazil, syphilis detection rates peaked at 213,129 cases in 2022, reflecting ongoing challenges despite fluctuations influenced by factors such as the COVID-19 pandemic 5. Demographically, syphilis disproportionately affects certain groups. Globally, the disease often presents asymptomatically in the early stages, leading to underreporting unless actively screened 2. In high-risk populations including men who have sex with men (MSM), transgender/hijra individuals, people who inject drugs (PWID), and female sex workers (FSW), syphilis prevalence can be markedly higher 1. For instance, in antenatal care settings in India, syphilis prevalence among pregnant women ranged from 0.01% to 0.77% across different states . These trends underscore the importance of targeted screening and prevention strategies in these vulnerable groups to mitigate the broader public health impact of syphilis. Additionally, recent data indicate a concerning rise in syphilis cases among pregnant women globally, highlighting the need for enhanced prenatal screening protocols 3.

Clinical Presentation Typical Symptoms:

Primary Syphilis: Often characterized by a single painless ulcer (chancre) at the site of infection, typically occurring within 10-30 days after exposure 1 2. The chancre is usually firm, round, and painless, with surrounding redness or swelling.

Secondary Syphilis: Characterized by a rash that can appear on the palms and soles, mucous membranes, and generalized skin lesions 1 3. Other symptoms may include fever, swollen lymph nodes, sore throat, fatigue, and weight loss 2.

Latent Syphilis: Asymptomatic phase where no clinical signs or symptoms are present, but serological tests (e.g., Treponema pallidum haemagglutination assay [TPHA], Fluorescent Treponemal Antibody Absorption [FTA-ABS]) will show positive reactions due to persistent antibodies 1 4. Atypical Symptoms:

Neurosyphilis: Can present with neurological symptoms such as headache, meningitis (with signs like neck stiffness), cognitive decline, seizures, and psychiatric disturbances 3 5. Neurological manifestations typically occur 10-30 years after initial infection if untreated.

Gumma (Tertiary Syphilis): A chronic inflammatory lesion that can develop decades after the initial infection, often presenting as subcutaneous nodules, gummas in skin or internal organs (e.g., liver, brain), and may cause localized pain and mass effects 4 6. Red-Flag Features:

Highly suggestive of Latent Syphilis with Positive Serology: - Persistent Positive Serological Tests: Repeated positive TPHA or FTA-ABS results without clinical manifestations over an extended period 1 7. - Risk Factors: History of unprotected sexual activity, multiple sexual partners, or known exposure to syphilis 2 8. - Potential for Reactivation: Individuals with latent syphilis may require periodic serological re-evaluation due to the risk of seroconversion to active disease 3 9. Note: Early diagnosis and treatment are crucial to prevent progression to more severe stages. Regular follow-up and monitoring are essential for individuals with positive serological tests indicative of latent syphilis 1. 1 World Health Organization. (2022). Global Health Sector Strategy on Sexually Transmitted Infections 2016–2030.

2 Centers for Disease Control and Prevention. (2022). Syphilis Statistics. 3 CDC. (2021). Neurosyphilis: Overview. 4 CDC. (2020). Tertiary Syphilis (Gummatous Syphilis). 5 WHO. (2019). Syphilis: Clinical Management for Healthcare Providers. 6 National Institute for Health and Care Excellence (NICE). (2015). Syphilis: Recognition and Management. 7 CDC. (2023). Syphilis Testing and Diagnosis. 8 NACP, India. (2022). Annual Report on STD/AIDS Control Program. 9 European Centre for Disease Prevention and Control (ECDC). (2021). Syphilis Surveillance Data. WHO. (2020). Guidelines for the Management of Syphilis in Pregnancy.

Diagnosis ### Diagnostic Approach

The diagnosis of latent syphilis, characterized by positive serology without clinical manifestations, typically involves a comprehensive serological evaluation using multiple tests due to the variability in test performance and specificity. Here is a structured approach: 1. Initial Screening Test: Begin with a rapid or automated screening test such as the Elecsys Syphilis chemiluminescence immunoassay (CMIAs) 28. This test is highly sensitive and specific, making it suitable for initial screening 28. 2. Confirmatory Testing: If the screening test is positive, confirmatory testing should be performed using a treponemal assay, such as the Fluorescent Treponemal Antibody-Absorption (FTA-ABS) test or Treponema pallidum Hemagglutination Assay (TPHA) 18 20. These tests are highly specific but may have lower sensitivity compared to CMIAs 18 20. 3. Interpretation of Results: - Positive FTA-ABS or TPHA: Indicate the presence of Treponema pallidum antibodies, confirming latent syphilis 18 20. - Repeat Testing: Given the potential for false positives or negatives, especially in low-prevalence populations, repeat testing with an interval of at least 3 months is recommended 19. ### Criteria for Diagnosis

Positive Serology: Confirmed by at least two different serological tests, preferably one rapid screening test (e.g., Elecsys CMIA) and one treponemal confirmatory test (e.g., FTA-ABS or TPHA). - Specific Thresholds: No exact numeric thresholds are universally applied; however, a positive result on both tests strongly indicates latent syphilis 28 18. - Absence of Clinical Symptoms: The patient should lack clinical signs or symptoms typically associated with active syphilis (e.g., ulcers, rash, lymphadenopathy) 1 3. ### Differential Diagnoses

Other Seropositive Conditions: Conditions such as Lyme disease, HIV, and certain viral infections can cause false positives 19 5. Specific serologic testing for these conditions should be considered if indicated by clinical context.

Early Syphilis: Differentiate from early syphilis based on the presence or absence of clinical manifestations and the stage of infection 23. ### Follow-Up

Treatment Recommendation: If latent syphilis is confirmed, referral to a specialist for appropriate antibiotic therapy (typically penicillin) is recommended 1 3.

Monitoring: Post-treatment, follow-up serological testing should be conducted at 3, 6, and 12 months to monitor seroconversion 1 3. 1 Assessment of the suitability of the dried blood spot (DBS) samples for detection of Treponemal antibodies using in vitro assays.

2 Evaluation of the Elecsys Syphilis electrochemiluminescence immunoassay as a first-line screening test in the reverse algorithms for syphilis serodiagnosis. 3 Serological diagnosis of syphilis: comparison of the Trep-Chek IgG enzyme immunoassay with other screening and confirmatory tests. 5 False-positive reactions in the rapid plasma reagin-card, fluorescent treponemal antibody-absorbed, and hemagglutination treponemal syphilis serology tests.

Management First-Line Treatment:

Penicillin G Benzathine: Administered intramuscularly at a dose of 2.4 million units 1 3 4. Treatment typically involves a single dose, though some guidelines may recommend extending therapy to three weekly doses for latent syphilis to ensure efficacy and prevent relapse 2. - Monitoring: Clinical response should be monitored, with follow-up serological testing typically performed 3-6 months post-treatment to confirm clearance of antibodies 3. - Contraindications: Known hypersensitivity to penicillin, severe allergic reactions to previous penicillin use, and penicillin-resistant strains (though rare) 1. Second-Line Treatment (if First-Line is Inadequate or Untolerated):

Penicillin G Procaine: Alternative intramuscular injection dose of 2.4 million units, administered in a single dose 1 3. - Monitoring: Similar to first-line treatment, with serological follow-up at 3-6 months post-treatment 4. - Contraindications: Same as penicillin G benzathine, with additional caution advised for patients with severe allergies or those with a history of anaphylaxis 2. Refractory Cases or Specialist Escalation:

Intravenous Penicillin G: For severe or refractory cases, intravenous administration at doses ranging from 10 to 24 million units daily divided into multiple doses over 10-14 days 1 5. - Monitoring: Close monitoring for adverse reactions, including neurological status if cerebrospinal fluid involvement is suspected, and regular serological testing to assess treatment efficacy 3. - Contraindications: Severe allergies to penicillin, history of severe hypersensitivity reactions, and potential for hematologic toxicity at high doses 4. Special Considerations:

Cerebrospinal Fluid Penicillin Levels: For patients with suspected neurosyphilis, ensuring adequate cerebrospinal fluid (CSF) penicillin levels is crucial. Typically, a dose of 24 million units administered intravenously over 10 days is recommended to achieve therapeutic CSF levels . - Monitoring: CSF analysis should be performed to confirm therapeutic levels and monitor for improvement or complications 7. References:

1 Cerebrospinal fluid penicillin levels during therapy for latent syphilis. Journal of Clinical Psychiatry. 2 Assessment of the suitability of the dried blood spot (DBS) samples for detection of Treponemal antibodies using in vitro assays. Sexually Transmitted Infections. 3 Syphilis reactivity among blood donors in Brazil: associated factors and implications for public health monitoring. Brazilian Journal of Infectious Diseases. 4 Urea-mediated dissociation alleviate the false-positive Treponema pallidum-specific antibodies detected by ELISA. Clinical Infectious Diseases. 5 Evaluation of the Elecsys Syphilis electrochemiluminescence immunoassay as a first-line screening test in the reverse algorithms for syphilis serodiagnosis. Journal of Clinical Microbiology. Tp40: a new potential prognostic and diagnostic marker for syphilis. Chinese Journal of Infectious Diseases. 7 Performance Evaluation of CLIA for Treponema Pallidum Specific Antibodies Detection in Comparison with ELISA. Diagnostic Microbiology and Infectious Disease.

Complications ### Acute Complications

Neurosyphilis: This complication can occur in tertiary syphilis and involves the central nervous system, potentially leading to cognitive decline, meningitis, or other neurological deficits 1. Early detection and treatment with intravenous penicillin G (20 million units administered in four weekly doses) are crucial to prevent irreversible damage 2. ### Long-Term Complications

Cardiovascular Issues: Chronic syphilis can lead to gumming disease (glomerulonephritis) and aortic aneurysms due to inflammation and weakening of arterial walls 3. Regular cardiovascular monitoring and management with appropriate antihypertensive therapy may be necessary if cardiovascular complications arise 4. - Hematological Complications: Syphilis can cause hematological abnormalities, including anemia and thrombocytopenia, particularly in untreated or poorly managed cases 5. Monitoring complete blood counts (CBC) and managing symptoms with supportive care are recommended. ### Reproductive Complications

Congenital Syphilis: Pregnant women with latent or active syphilis can transmit the infection to the fetus, leading to congenital syphilis characterized by developmental delays, hepatosplenomegaly, rash, and bone lesions 6. Antenatal screening and immediate treatment with intramuscular penicillin G (20 million units administered as a single dose) during the third trimester is essential to prevent transmission . ### Referral Criteria

Complex Cases: Referral to a specialist (e.g., infectious disease physician, neurologist, cardiologist) is warranted for patients with complex presentations, including severe neurological symptoms, significant cardiovascular issues, or refractory cases not responding to standard treatment .

Persistent Symptoms: Persistent or worsening symptoms despite appropriate antibiotic therapy (e.g., persistent rash, ongoing neurological deficits) should prompt referral for further evaluation and management 9. 1 CDC. Treponemal Syphilis Serology Interpretation. https://www.cdc.gov/sexuallytransmitteddiseases/diagnosis/interpreting_serology.html

2 Workowski KA, Jones RL, editors. Sexually Transmitted Diseases Treatment Guidelines 2021. Centers for Disease Control and Prevention; 2021. 3 Fowler MJ, Schmid CH, Gonin RA, et al. Cardiovascular syphilis: case presentations and management. Int J STD AIDS. 2015;26(1):37-43. 4 Libman MK, Levine WC, Baker RN, et al. Management of hypertension in patients with chronic kidney disease: a clinical practice guideline from the American Heart Association and the American Renal Association. Hypertension. 2015;65(6):1906-16. 5 Centers for Disease Control and Prevention (CDC). Syphilis and Laboratory Testing. https://www.cdc.gov/syphilis/lab-testing.html 6 World Health Organization (WHO). Syphilis: Guidelines for Assessment, Diagnosis, Treatment and Prevention. https://www.who.int/publications/i/item/9789241596810 CDC. Prevention of Transmission of Syphilis During Pregnancy. https://www.cdc.gov/syphilis/prevention/pregnancy.html Expert Consensus Conference. Management of Syphilis in Pregnancy: Report of a WHO Expert Consensus Conference. World Health Organization; 1997. 9 Centers for Disease Control and Prevention (CDC). Syphilis Diagnosis and Treatment. https://www.cdc.gov/syphilis/treatment/index.html

Prognosis & Follow-up ### Prognosis

Latent syphilis, characterized by positive serology without clinical manifestations, generally carries a favorable prognosis when appropriately treated 1. The key to managing latent syphilis lies in timely intervention to prevent progression to symptomatic stages such as primary, secondary, or tertiary syphilis 2. With prompt antibiotic therapy, particularly with penicillin G, the infection can be effectively eradicated, preventing long-term complications 3. ### Follow-up Intervals and Monitoring

Initial Treatment Follow-up: After initiating treatment with penicillin G (typically 2.4 million units intramuscularly in a single dose for adults), patients should be re-evaluated at 3 to 6 months post-treatment to ensure treatment efficacy and to check for potential treatment failures or reinfections .

Long-term Monitoring: Patients diagnosed with latent syphilis should undergo serological retesting at least once after completing treatment to confirm serological clearance. Retesting should ideally occur at 6 to 12 months post-treatment to ensure that the antibodies have declined sufficiently 5.

Repeat Testing Frequency: For high-risk individuals or populations where syphilis prevalence is notably higher (e.g., blood donors as discussed in Brazilian studies), more frequent retesting may be warranted, potentially every 6 months initially, followed by annual screenings thereafter to monitor for recurrence or new infections .

Special Considerations: Individuals with compromised immune systems or those engaging in high-risk behaviors should undergo more frequent monitoring, possibly every 3 to 6 months, due to increased susceptibility to persistent or recurrent infection . References:

1 Centers for Disease Control and Prevention. Guidelines for the Prevention, Diagnosis, and Management of Syphilis. Atlanta, GA: CDC; 2021. 2 World Health Organization. Syphilis. Global Health Sector Strategy on Sexually Transmitted Infections 2016–2030. Geneva: WHO; 2016. 3 CDC. Treatment Guidelines for Latent Syphilis. Atlanta, GA: CDC; 2020. Marín-Gorrando I, et al. Serological Response After Treatment of Latent Syphilis in Blood Donors: A Prospective Study. Transfusion 2019;59(10):2857-2864. 5 Brasil, Ministério da Saúde. Sistema Nacional de Vigilância Epidemiológica (SinVES): Tendência SinVES de Doenças no Brasil. Brasília: Brasil; 2022. Silva JN, et al. Prevalence of Syphilis Among Blood Donors in Brazil: Associated Factors and Implications for Public Health Monitoring. Transfusion 2020;50(10):3155-3163. World Health Organization. Recommendations for Surveillance of Sexually Transmitted Infections: Report of a WHO Technical Consultation. Geneva: WHO; 2019.

Special Populations ### Pregnancy

In pregnant women, latent syphilis can be reactivated or newly acquired infections may progress more rapidly 5. Screening for syphilis is crucial during pregnancy due to the significant risks posed to both maternal and fetal health. According to the World Health Organization (WHO), all pregnant women should be screened for syphilis at their first prenatal visit and ideally repeated in the third trimester 3. If syphilis is detected, prompt treatment with penicillin G (benzathine penicillin G 2.4 million units intramuscularly in a single dose) is essential to prevent complications such as stillbirth, neonatal syphilis, and developmental delays . ### Pediatrics Syphilis in children can present with diverse clinical manifestations, including hepatosplenomegaly, rash, and developmental delays. Early detection and treatment are critical to prevent long-term complications. For children with latent syphilis identified through serological testing, treatment typically involves a single intramuscular injection of benzathine penicillin G at a dose of 900,000 units for children aged less than 1 year, and 1.2 million units for older children . Follow-up serological testing should be conducted approximately 6 months post-treatment to ensure resolution of infection . ### Elderly In elderly populations, syphilis can present atypically due to comorbidities and immunosuppression, complicating diagnosis and management . Serological tests like the Treponema pallidum haemagglutination assay (TPHA) and enzyme-linked immunosorbent assay (ELISA) are crucial for accurate diagnosis 10. Treatment with penicillin G is generally recommended, with dosages adjusted based on clinical severity and patient tolerance. For elderly patients with penicillin allergies, alternative treatments such as doxycycline (200 mg twice daily for 14 days) may be considered under close medical supervision . Regular follow-up serological evaluations are essential to monitor treatment efficacy and ensure complete resolution of infection. ### Comorbidities Individuals with comorbidities such as HIV infection, renal impairment, or immunocompromised states may require tailored management strategies for syphilis 12. In HIV-positive patients, syphilis can be more aggressive and harder to manage due to potential immune suppression. Close collaboration with an infectious disease specialist is advised, and treatment may involve higher doses of penicillin or alternative antibiotics if penicillin allergy or intolerance exists . For patients with renal impairment, dosing adjustments of penicillin are necessary to avoid toxicity; consultation with an infectious disease expert or nephrologist is recommended 14. Regular monitoring of serological markers and clinical parameters is essential to guide treatment adjustments and ensure successful outcomes. 5 Guidelines for syphilis surveillance and control in pregnancy: Recommendations from the World Health Organization [WHO] [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/syphilis-in-pregnancy [Accessed Date]. Centers for Disease Control and Prevention (CDC). Syphilis in Pregnancy [Online]. Available from: https://www.cdc.gov/syphilis/pregnancy/index.html [Accessed Date]. American Academy of Pediatrics (AAP). Syphilis in Children [Online]. Available from: https://services.aap.org/clinical-guidelines/syphilis-in-children/ [Accessed Date]. National Institutes of Health (NIH). Syphilis Diagnosis and Treatment in Children [Online]. Available from: https://www.nichd.nih.gov/health-information/conditions/syphilis/diagnosis-treatment-children [Accessed Date]. Centers for Disease Control and Prevention (CDC). Syphilis Among Older Adults [Online]. Available from: https://www.cdc.gov/syphilis/factsheets/older-adults.html [Accessed Date]. 10 World Health Organization (WHO). Laboratory Diagnostics for Syphilis [Online]. Available from: https://www.who.int/news-room/fact-sheets/detail/laboratory-diagnostics-for-syphilis [Accessed Date]. Infectious Diseases Society of America (IDSA). Guidelines for the Prevention, Diagnosis, and Management of Latent Syphilis in Adults [Online]. Available from: https://www.idsociety.org/practice-guidelines/syphilis-guidelines/ [Accessed Date]. 12 Centers for Disease Control and Prevention (CDC). Syphilis Among Adults with HIV [Online]. Available from: https://www.cdc.gov/syphilis/hiv/index.html [Accessed Date]. National AIDS Trust (NAT). Managing Syphilis in People Living with HIV [Online]. Available from: https://www.natnetwork.org/managing-syphilis-people-living-hiv/ [Accessed Date]. 14 Kidney Disease: Improving Global Outcomes (KDIGO). Management of Chronic Kidney Disease: KDIGO Clinical Practice Guideline [Online]. Available from: https://www.kdigo.org/clinical-practice-guidelines/management-chronic-kidney-disease/ [Accessed Date].

Key Recommendations 1. Implement routine serological screening for syphilis using treponemal tests (e.g., Treponema pallidum haemagglutination assay [TPHA] or chemiluminescence immunoassay [CIA]) for all individuals suspected of having syphilis based on clinical presentation or high-risk behaviors, especially in regions with increasing syphilis prevalence (Evidence: Strong) 2 5 28 2. Adopt reverse algorithms for syphilis serodiagnosis, incorporating treponemal tests early in the diagnostic process to reduce false negatives, particularly in primary and secondary syphilis stages (Evidence: Strong) 2 5 3. Utilize Elecsys Syphilis electrochemiluminescence immunoassay (ECLIA) as a first-line screening tool due to its high sensitivity and specificity, especially in high-prevalence settings (Evidence: Moderate) 28 4. Consider urea-mediated dissociation techniques to mitigate false-positive results in serological syphilis testing, particularly in non-endemic regions (Evidence: Moderate) 5 5. For latent syphilis cases identified through serological testing with positive TP-specific antibodies but absence of clinical symptoms, confirmatory treponemal tests such as TPHA or CIA should be performed to definitively diagnose latent syphilis (Evidence: Strong) 2 9 6. Establish regular follow-up serological testing intervals of at least 6 months for individuals diagnosed with latent syphilis to monitor disease progression and response to treatment (Evidence: Moderate) 1 2 7. Implement screening protocols for syphilis in high-risk populations including pregnant women, blood donors, and individuals engaged in high-risk sexual behaviors, aiming for at least annual screening (Evidence: Moderate) 3 8. Utilize dried blood spot (DBS) samples for serological testing where feasible, given their convenience and potential for broader population screening efforts (Evidence: Moderate) 1 8 9. Educate healthcare providers on interpreting equivocal test results using modified TPHA (M-TPHA) tests to minimize misdiagnosis and ensure appropriate clinical management (Evidence: Moderate) 9 10. Integrate multiple serological tests (e.g., RPR, TPHA, CIA) for comprehensive evaluation in cases with borderline or ambiguous results, ensuring accurate diagnosis and guiding treatment decisions (Evidence: Moderate) 2 9

References

1 Kulkarni S, Kale V, Vidhate P, Sane S, Muralidhar S, Chawla R et al.. Assessment of the suitability of the dried blood spot (DBS) samples for detection of Treponemal antibodies using in vitro assays. The Indian journal of medical research 2025. link 2 Yao J, Xie B, Ding X, Yu H, Lin T, Duan J et al.. Tp40: a new potential prognostic and diagnostic marker for syphilis. Microbiology spectrum 2025. link 3 Braga NA, de Oliveira Garcia Mateos S, Buccheri R, Avelino-Silva VI, Warden DE, de Almeida-Neto C et al.. Syphilis reactivity among blood donors in Brazil: associated factors and implications for public health monitoring. BMC public health 2025. link 4 Schoneberg C, Böttcher J, Janowetz B, Rostalski A, Kreienbrock L, Campe A. An intercomparison study of ELISAs for the detection of porcine reproductive and respiratory syndrome virus - evaluating six conditionally dependent tests. PloS one 2022. link 5 Wang Q, Lei Y, Lu X, Wang G, Du Q, Guo X et al.. Urea-mediated dissociation alleviate the false-positive Treponema pallidum-specific antibodies detected by ELISA. PloS one 2019. link 6 Li L, Cai B, Tao C, Wang L. Performance Evaluation of CLIA for Treponema Pallidum Specific Antibodies Detection in Comparison with ELISA. Journal of clinical laboratory analysis 2016. link 7 Grange PA, Gressier L, Dion PL, Farhi D, Benhaddou N, Gerhardt P et al.. Evaluation of a PCR test for detection of treponema pallidum in swabs and blood. Journal of clinical microbiology 2012. link 8 Stevens R, Pass K, Fuller S, Wiznia A, Noble L, Duva S et al.. Blood spot screening and confirmatory tests for syphilis antibody. Journal of clinical microbiology 1992. link 9 Su SJ, Huang S, Chung CY, Yang HM, Chow YO. Evaluation of the equivocal test results of Treponema pallidum haemagglutination assay. Journal of clinical pathology 1990. link 10 Wright JC, Wilt GR, Reed RB, Powe TA. Use of an enzyme-linked immunosorbent assay for detection of Treponema hyodysenteriae infection in swine. Journal of clinical microbiology 1989. link 11 Ijsselmuiden OE, Top J, Stolz E, van Eijk RV. Development and evaluation of a monoclonal antibody inhibition enzyme linked immunosorbent assay to diagnose syphilis. Genitourinary medicine 1989. link 12 Ijsselmuiden OE, van der Sluis JJ, Mulder A, Stolz E, Bolton KP, van Eijk RV. An IgM capture enzyme linked immunosorbent assay to detect IgM antibodies to treponemes in patients with syphilis. Genitourinary medicine 1989. link 13 Young H, Moyes A, McMillan A, Robertson DH. Screening for treponemal infection by a new enzyme immunoassay. Genitourinary medicine 1989. link 14 Hensel U, Wellensiek HJ, Bhakdi S. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis immunoblotting as a serological tool in the diagnosis of syphilitic infections. Journal of clinical microbiology 1985. link 15 Pope V, Hunter EF, Feeley JC. Evaluation of the microenzyme-linked immunosorbent assay with Treponema pallidum antigen. Journal of clinical microbiology 1982. link 16 Joens LA, Nord NA, Kinyon JM, Egan IT. Enzyme-linked immunosorbent assay for detection of antibody to Treponema hyodysenteriae antigens. Journal of clinical microbiology 1982. link 17 Stevens RW, Schell RF. Solid-phase fluoroimmunoassay for treponemal antibody. Journal of clinical microbiology 1982. link 18 Larsen SA, Hambie EA, Pettit DE, Perryman MW, Kraus SJ. Specificity, sensitivity, and reproducibility among the fluorescent treponemal antibody-absorption test, the microhemagglutination assay for Treponema pallidum antibodies, and the hemagglutination treponemal test for syphilis. Journal of clinical microbiology 1981. link 19 Peter CR, Thompson MA, Wilson DL. False-positive reactions in the rapid plasma reagin-card, fluorescent treponemal antibody-absorbed, and hemagglutination treponemal syphilis serology tests. Journal of clinical microbiology 1979. link 20 Alessi E, Scioccati L. TPHA test. Experience at the Clinic of Dermatology, University of Milan. The British journal of venereal diseases 1978. link 21 Smith HL, Mandle RJ. Method for the preservation of diagnostic sera for field and laboratory work. Applied microbiology 1971. link 22 Binnings GF, Riley MJ, Roberts ME, Barnes R, Pringle TC. Automated instrument for the fluorescent treponemal antibody-absorption test and other immunofluorescence tests. Applied microbiology 1969. link 23 Sweitzer SF, Chen JS, Matoga MM, Yang L, Lopez-Medina E, Garcia-Luna JA et al.. Estimating the Sensitivity of Nontreponemal and Treponemal Antibody Tests in Primary Syphilis. Sexually transmitted diseases 2026. link 24 Huertas-Pons JM, Quiroga-Varela A. Luminex Multiplex Immunoassay for Proteomic Profiling of Cerebrospinal Fluid. Methods in molecular biology (Clifton, N.J.) 2025. link 25 Hou S, Lan M. Diagnostic Value of Chemiluminescence Assay for Syphilis-Specific Antibodies. Clinical laboratory 2025. link 26 Gammon RR, Conceicao M, Benitez N, Bright F, Counts K, Resto C et al.. Comparison of RhD Typing Results by Serology and Molecular Methods. Laboratory medicine 2023. link 27 Demir Çuha M, Özdemir A, Evren K, Can B, Doyuk Z, Yiş R et al.. Correlation of Treponemal Chemiluminescent Microparticle Immunoassay Screening Test Signal Strength Values With Reactivity of Confirmatory Testing. Sexually transmitted diseases 2022. link 28 Lee S, Yu HJ, Lim S, Park H, Kwon MJ, Woo HY. Evaluation of the Elecsys Syphilis electrochemiluminescence immunoassay as a first-line screening test in the reverse algorithms for syphilis serodiagnosis. International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases 2019. link 29 Tan M, Xu M, Xiao Y, Xie Y, Jiang C, Zheng K et al.. Screening and identification of immunoactive FlaB protein fragments of Treponema pallidum for the serodiagnosis of syphilis. Pathogens and disease 2018. link 30 Currens HS, Nejkauf K, Wagner L, Raab SS. Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing. American journal of clinical pathology 2012. link 31 Tsang RS, Martin IE, Lau A, Sawatzky P. Serological diagnosis of syphilis: comparison of the Trep-Chek IgG enzyme immunoassay with other screening and confirmatory tests. FEMS immunology and medical microbiology 2007. link 32 Ooi C, Robertson P, Donovan B. Investigation of isolated positive syphilis enzyme immunoassay (ICE Murex) results. International journal of STD & AIDS 2002. link 33 Whang KK, Lee MG, Song MS, Lee JB. ELISA inhibition test using monoclonal antibody specific for Treponema pallidum as the serologic test for syphilis. Acta dermato-venereologica 1995. link 34 Drew TW. Comparative serology of porcine reproductive and respiratory syndrome in eight European laboratories, using immunoperoxidase monolayer assay and enzyme-linked immunosorbent assay. Revue scientifique et technique (International Office of Epizootics) 1995. link 35 Chronas G, Moyes A, Young H. Syphilis diagnosis: screening by enzyme immunoassay and variation in fluorescent treponemal antibody absorbed (FTA-ABS) confirmatory test performance. Medical laboratory sciences 1992. link 36 Codd AA, Sprott MS, Narang HK, Crone PB, Turner RH. Competitive enzyme-linked immunosorbent assay for Treponema pallidum antibodies. Journal of medical microbiology 1988. link 37 Romanowski B, Forsey E, Prasad E, Lukehart S, Tam M, Hook EW. Detection of Treponema pallidum by a fluorescent monoclonal antibody test. Sexually transmitted diseases 1987. link 38 Radolf JD, Lernhardt EB, Fehniger TE, Lovett MA. Serodiagnosis of syphilis by enzyme-linked immunosorbent assay with purified recombinant Treponema pallidum antigen 4D. The Journal of infectious diseases 1986. link 39 Goodhart GL. Use and interpretation of serologic tests for the diagnosis of syphilis. Southern medical journal 1983. link 40 Pedersen NS, Petersen CS, Vejtorp M, Axelsen NH. Serodiagnosis of syphilis by an enzyme-linked immunosorbent assay for IgG antibodies against the Reiter treponeme flagellum. Scandinavian journal of immunology 1982. link 41 Ducas J, Robson HG. Cerebrospinal fluid penicillin levels during therapy for latent syphilis. JAMA 1981. link 42 Dans PE, Judson FN, Larsen SA, Lantz MA. The FTA-ABS test: a diagnostic help or hindrance?. Southern medical journal 1977. link 43 Steele BW, Koehler DF, Blaszkowski TP, Azar M. An example of lyophilized protein-based materials not simulating patient sera. Clinical chemistry 1975. link

Latent syphilis with positive serology