Abstract
Background:
Syphilis is a bacterial infection caused by Treponema pallidum. In recent years, there has been a rising trend of syphilis noted worldwide, including in India. The aim of this study was to analyze the changing epidemiological patterns, demographic attributes, high-risk behavior, clinical presentations, and stages of syphilis among patients attending the sexually transmitted infections (STI) clinic at a tertiary healthcare facility in eastern Uttar Pradesh over the last 7 years.
Patients and Methods:
We conducted a retrospective study spanning 7 years (2017–2023) at a tertiary care center. Demographics and clinical data of all confirmed cases were recorded and analyzed.
Results:
Over 7 years, 8,325 patients who attended the STI clinic were included in this study. Among STI clinic attendees, 2.78% tested positive for syphilis, confirmed by either a positive venereal disease research laboratory (VDRL) test along with a positive Treponema pallidum hemagglutination assay (TPHA) test or by TPHA positivity alone, with males representing the majority at 87%. The mean age of patients was 34.80 ± 8.01 years, with most patients falling into the 25–34 years age group. The prevalence of syphilis among STI clinic attendees showed a rising trend from 1.55% in 2017 to 4.05% in 2023, which was statistically significant. High-risk behaviors such as multiple sexual partners (62%) and contact with commercial sex workers (35%) were frequently reported. In our study, 73% of patients were diagnosed in the late latent stage of syphilis, whereas 13% were in the secondary stage, 9% in the early latent phase, and 5% in the primary stage. Additionally, concurrent STIs were observed in 24% of syphilis-positive patients, with genital warts being the most common.
Limitations:
The retrospective nature of the study, and this being a single-center study, are the major limitations of this study.
Conclusion:
This study shows that syphilis is becoming more common. Risky behaviors, such as engaging in sex with multiple partners or with sex workers, were identified as major contributing factors. There is a need for enhanced educational campaigns on safe sex practices.
Keywords: HIV, latent syphilis, sexually transmitted diseases, syphilis
Introduction
Syphilis is caused by the bacterium Treponema pallidum and is often referred to as “The Great Pretender” due to its ability to mimic various other diseases. It is primarily transmitted through sexual contact and progresses through four stages: primary, secondary, latent, and tertiary.
The clinical and epidemiological trends of syphilis exhibit cycles of resurgence and decline. Despite advancements in prevention and treatment, syphilis continues to pose a significant public health challenge globally. Many countries, including India, have observed an increasing trend in syphilis cases.[1,2,3,4,5,6,7] In 2020, the World Health Organization estimated 11 million new cases of syphilis globally.[1]
In the United States, there was a notable increase in syphilis cases, with 203,500 new cases diagnosed in 2022, marking a 17% rise from the previous year. Furthermore, there was a 78% increase in syphilis cases from 2018 to 2022 in the United States.[2] The United Kingdom (UK) Health Security Agency also reported a 15.2% increase in syphilis cases in 2022 compared to 2021.[3]
Therefore, this study was conducted to analyze the clinical and epidemiological trends of syphilis among patients attending the sexually transmitted infections (STIs) clinic at our tertiary center in eastern Uttar Pradesh over a 7-year period. Understanding these clinico-epidemiological trends is crucial for developing prevention and treatment strategies to control the spread of syphilis.
Patients and Methods
A retrospective study was conducted at our tertiary care center for 7 years, from January 2017 to December 2023. Approval of the Ethics Committee was obtained (BRD Medical College, approval number 24/IHEC/2024, approval date 11/1/2024).
Our study included all patients attending STI clinics during the study period, except for pregnant women, cases with biological false-positive venereal disease research laboratory (VDRL) results (i.e.. a reactive VDRL but a nonreactive specific treponemal test), patients who did not follow up with VDRL or Treponema pallidum hemagglutination assay (TPHA) reports, and those with incomplete data regarding their medical history, clinical features, treatments, and laboratory tests.
Demographic data such as age, sex, and marital status were extracted from the patient’s medical records. Sexual behavior history, including details on unprotected sex, multiple sexual partners, history of sexual contact with commercial sex workers (CSWs), sexual orientation such as heterosexuality, homosexuality, and bisexuality, as well as premarital and extramarital sexual history, was documented for all included patients.
Clinical data at the time of diagnosis, including the presentation and stage of the disease, laboratory test results (VDRL, TPHA, human immunodeficiency virus [HIV], and Hepatitis B and C), treatment regimens, follow-up information, and any associations with other STIs, along with a history and clinical examination findings, such as the presence of genital ulcers, lymphadenopathy, skin and mucosal lesions, eye involvement, arthritis, and any involvement of the central nervous system and cardiovascular system, were collected and analyzed. Patients with a reactive VDRL test were subjected to confirmatory testing using the TPHA. Patients with positive results on both VDRL and TPHA or those who tested positive on TPHA alone were confirmed as syphilis-positive.
All collected data were summarized, tabulated, and analyzed using Epi Info 7.2.2. All categorical variables were represented as percentages or proportions, and continuous variables were presented as mean ± standard deviation (SD). All associations were tested using Chi-square statistics. A significant level was accepted at P < 0.05.
Results
A total of 8,809 patients attended the STI clinic during the 7-year study period, of which 8,325 patients who met the inclusion criteria were included in our study. Among the 8,325 patients, 2.78% (n = 232) tested positive for syphilis [Figure 1]. Among these 232 patients, 61% (n = 142) were married and 39% (n = 90) were unmarried. The majority, 87% (n = 202), were male, 12.5% (n = 29) were female, and 0.5% (n = 1) was transgender; the male-to-female ratio was 7:1. The mean age of the patients was 34.80 ± 8.01 years. The patients were divided into five age groups. The ≤24 years age group comprised 25 individuals (10.7%). The 25–34 years age group had the highest representation with 110 individuals (47.2%). The 35–44 years age group included 61 individuals (26.2%), while the 45–54 age group consisted of 35 individuals (15%). The lowest representation was in the 55–64 age category, with only one patient (0.4%).
Figure 1.
Flow diagram of the study
The distribution of syphilis cases by gender and year is presented in Table 1. Out of 232 syphilis-positive cases, 224 tested positive for both VDRL and TPHA, while 8 were positive for TPHA only. Among the only TPHA patients, two had primary syphilis and six had secondary syphilis. These patients were VDRL negative. Their clinical features, along with a history of multiple sexual partners, raised a strong suspicion of syphilis. Based on this, TPHA testing was conducted, which confirmed the diagnosis of syphilis in all eight cases. Patients with latent syphilis were VDRL positive, and their diagnosis was confirmed through TPHA testing.
Table 1.
Year-wise and gender-wise distribution of syphilis cases with seropositivity
| Year | Number of samples tested | Syphilis cases detected (n) | Seropositivity (%) | Males n (%) | Females n (%) | Transgender n (%) |
|---|---|---|---|---|---|---|
| 2017 | 1350 | 21 | 1.55 | 20 (95.24%) | 1 (4.76%) | – |
| 2018 | 1214 | 43 | 3.54 | 37 (86.05%) | 6 (13.95%) | – |
| 2019 | 1321 | 41 | 3.10 | 34 (82.93%) | 7 (17.07%) | – |
| 2020 | 1173 | 24 | 2.04 | 19 (79.17%) | 5 (20.83%) | – |
| 2021 | 1188 | 27 | 2.27 | 25 (92.59%) | 2 (7.41%) | – |
| 2022 | 995 | 32 | 3.21 | 28 (87.50%) | 3 (9.38%) | 1 (3.13%) |
| 2023 | 1084 | 44 | 4.05 | 39 (88.64%) | 5 (11.36%) | – |
Initially, there was a rise in syphilis cases from 1.55% in 2017 to 3.10% in 2019, which was statistically significant (χ2 = 7.058, P = 0.007). There was a decline in syphilis seropositivity from 3.10% in 2019 to 2.04% in 2020, coinciding with the onset of the coronavirus disease 2019 (COVID-19) pandemic, though this decrease in seropositivity was not significant (χ2 = 2.73, P = 0.097). Following a decline in syphilis seropositivity from 2019 to 2020, there was a sustained increase in seropositivity from 2.04% in 2020 to 4.05% in 2023, which was statistically significant (χ2 = 7.812, P = 0.005). Overall, seropositivity increased from 1.55% in 2017 to 4.05% in 2023, showing a statistically significant upward trend (χ2 =21.25, P = 0.001) [Figure 2].
Figure 2.
Seropositivity trends of syphilis
Among the 232 positive patients, 62% (n = 144) reported a history of sexual contact with multiple partners, and 35% (n = 81) had a history of sexual contact with CSWs. Additionally, 9% (n = 20) of patients were men who have sex with men (MSM), with five patients identifying as bisexual. Premarital sexual exposure was reported by 52.1% (n = 120) of patients.
Concurrent STIs were observed in 24% (n = 56) of syphilis-positive patients, with genital wart (7%, n = 17) being the most common followed by HIV (6.5%, n = 15), herpes genitalis (5.5%, n = 13), molluscum contagiosum (genital) (4.5%, n = 10), and chancroid (0.5%, n = 1). Additionally, five patients tested positive for hepatitis B along with syphilis.
In our study, 73% (n = 169) of patients were diagnosed in the late latent stage, while 13% (n = 30), 9% (n = 21), and 5% (n = 12) were diagnosed in the secondary stage, early latent phase, and primary stage of syphilis, respectively. Figure 3 illustrates the distribution of syphilis cases according to the stages throughout the study period, from 2017 to 2023. No cases of tertiary syphilis were observed during the study period.
Figure 3.
Trend of clinical stages of syphilis from 2017 to 2023
In cases of primary syphilis, among the 12 patients, a single chancre was noted in 10 patients (83.33%), while two patients (16.67%) had multiple chancres. Eight out of the 12 patients with primary syphilis presented with lymphadenopathy (66.67%), while the remaining 4 (33.33%) did not have any lymphadenopathy.
A total of 30 patients had secondary syphilis. Among them, 9 patients (30%) had a maculopapular rash, while palmoplantar syphilides were observed in 15 patients (50%). Furthermore, four patients (13.33%) showed condyloma lata, and two patients (6.67%) presented with annular syphilides. Out of 30 patients with secondary syphilis, 10 patients (33.33%) had inguinal lymphadenopathy, while 18 patients (60%) did not exhibit any lymphadenopathy. Additionally, two patients (6.67%) displayed generalized lymphadenopathy.
All patients who were not allergic to penicillin received benzathine penicillin G 2.4 million units intramuscularly once a week for three consecutive weeks.
Two patients had a documented history of penicillin allergy and were therefore treated with doxycycline 100 mg twice daily for 14 days instead of benzathine penicillin. No additional information regarding their allergic reactions was provided in the records.
A four-fold reduction in VDRL titre between the initial and subsequent tests was considered a serological response to treatment. Among the 232 patients, 153 (65.95%) showed a response within 6 months, and 79 (34.05%) responded within 1 year. Follow-up visits were as follows: 53 patients (22.8%) had follow-up visits till 3 months, 44 patients (19%) till 6 months, 58 patients (25%) till 12 months, 47 patients (20.3%) till 18 months, and 30 patients (12.9%) had follow-up visits till ≥24 months. A positive response was seen in all patients, and no reinfections occurred during the follow-up period.
Discussion
In recent years, studies from India and other countries have shown a rise in syphilis cases.[1,2,3,4,5,6] Our research confirms this trend, with syphilis seropositivity increasing from 1.55% in 2017 to 4.05% in 2023. Solaimalai et al.[6] also reported a significant jump from 0.52% to 2.1%. Sambyal et al.[5] and Baskaran et al.[7] also observed a similar upward trend. In our study, there was a decrease in cases in 2020 when COVID-19 emerged. The decline in syphilis cases in 2020, also noted by Sambyal et al.[5] and Baskaran et al.,[7] likely resulted from overwhelmed healthcare systems diverting resources from STI screenings, reduced STI clinic services, and staff reassignments to COVID-19 tasks. Additionally, fear of COVID-19 exposure deterred healthcare visits, and social distancing, lockdowns, and travel restrictions reduced high-risk sexual activities, leading to an actual reduction in cases. Our study found no decrease in samples tested in 2020, suggesting testing access was likely unaffected. However, factors like fear of seeking medical care or reduced risky sexual behavior probably led to fewer reported syphilis cases during COVID-19 in our study.
A significant post-COVID rise in syphilis cases was observed in our study, aligning with other published studies.[5,7,8]
Our findings demonstrate a male predominance, consistent with studies conducted by Thokchom et al.,[4] Sambyal et al.,[5] Solaimalai et al.,[6] Baskaran et al.,[7] Ahuja et al.,[8] Jain et al.,[9] Shah et al.,[10] and Sethi et al.[11] The lower number of syphilis cases among females may result from fewer STI clinic visits due to social stigma and fear of judgment or discrimination.[12,13] Addressing taboos around syphilis and STIs is essential to curb their spread, and healthcare providers can help by fostering a supportive, nonjudgmental environment for patients to discuss their concerns.
Our study highlights the vulnerability of young adults to STIs, with most patients falling within the 25–34 age group, similar to findings by Solaimalai et al.[6] In our study, 39% (n = 90) were unmarried, most of whom were young. Young individuals are more likely to engage in high-risk behaviors, such as unprotected sex with multiple partners, MSM, or CSW contact, due to sexual exploration during adolescence.[14,15] Educating young people about STIs and the proper use of barrier methods during sexual activity can significantly reduce the risk of syphilis transmission.[16]
High-risk sexual behaviors, including unprotected sex with multiple partners, MSM, and contact with CSWs, were the primary risk factors for syphilis in our study. Multiple sex partners were the most common risk factor for syphilis in our study, reported by 62% (n = 144) of patients. Similarly, Baskaran et al.[7] found this in 56.8% of cases. In the United States, there was a 4% increase in syphilis cases from 2021 to 2022 among MSM.[17] This may be attributed to condomless anal sex, casual sex with unknown and multiple partners.[18] A study conducted by Tsuboi et al.[19] reported that the global syphilis prevalence among MSM was 7.5% over 20 years. In this study, we reported that 9% (n = 20) of patients were MSM. This is comparable to a study[6] that observed 7.5% of patients were MSM. In our study, 35% (n = 81) of patients had a history of visiting CSWs. CSWs and their clients constitute a high-risk population for the transmission of syphilis and other STIs.[20] Awareness campaigns targeting high-risk populations, including CSWs and their clients, are crucial for STI prevention.
In our study, 6.5% (n = 15) of patients with syphilis were HIV-positive. Coinfection of syphilis and HIV presents a very dangerous situation, as both conditions can alter each other’s clinical features.[6,21,22] The incidence of neurosyphilis is particularly high in HIV and syphilis-coinfected patients, leading to a heightened risk of treatment failure for syphilis even after appropriate treatment.[4,23,24] Additionally, syphilis coinfection may increase HIV viral load in plasma and decrease CD4 cell count, contributing to antiretroviral therapy failure.[21] Therefore, it is imperative that all patients with syphilis be screened for HIV infection, and vice versa.[22]
The increased infectivity of HIV among MSM can be attributed to factors such as injectable drug abuse and engaging in high-risk sexual behavior.[17] MSM can serve as a bridging population in the transmission of HIV and syphilis.[4]
Table 2 shows a comparison of the stage of syphilis at the time of diagnosis among different studies. Our study, like some other previous studies,[5,6,7] reported a high prevalence of latent syphilis (82%, 92%, 79%, and 66.7%, respectively). In contrast, Thokchom et al.,[4] Kamat et al.,[25] and Gupta et al.[26] observed lower rates of latent syphilis (37%, 30.5%, and 38.7%, respectively). Our study, Sambyal et al.,[5] and Solaimalai et al.[6] had lower percentages of primary and secondary syphilis. In contrast, Thokchom et al.,[4] Kamat et al.,[25] Gupta et al.,[26] and Sivayadevi and Anandan[27] observed higher rates of primary and secondary syphilis.
Table 2.
A comparison of the stage of syphilis at the time of diagnosis among different Indian studies
| Study | Study period | Nature of study | Total cases | Primary syphilis | Secondary syphilis | Latent syphilis | Tertiary syphilis | Congenital syphilis | Both primary and secondary syphilis |
|---|---|---|---|---|---|---|---|---|---|
| This Study | 2017–2023 | Retrospective | 232 | 12 (5%) | 30 (13%) | 190(82%) | – | – | – |
| Thokchom et al.[4] | 2013–2019 | Retrospective | 43 | 16 (37%) | 11 (26%) | 16 (37%) | – | – | – |
| Sambyal et al.[5] | 2016–2022 | Retrospective | 216 | 7 (3%) | 10 (5%) | 199 (92%) | – | – | – |
| Solaimalai et al.[6] | 2015–2020 | Retrospective | 265 | 8 (3%) | 27 (10%) | 210 (79%) | 20 (8%) | – | – |
| Baskaran et al.[7] | 2011–2023 | Retrospective | 324 | 29 (8.9%) | 61 (18.8%) | 229 (66.7%) | 5 (1.54%) | – | – |
| Kamat et al.[25] | Aug 2019–Jul 2021 | Observational, cross-sectional | 200 | 49 (24.5%) | 89 (44.5%) | 61 (30.5%) | – | 1 (0.5%) | – |
| Gupta et al.[26] | 2012–2022 | Retrospective | 31 | 6 (19.35%) | 12 (38.7%) | 12 (38.7%) | – | – | 1 (3%) |
| Sivayadevi and Anandan[27] | 2013–2017 | Retrospective | 140 | 18 (12.85%) | 38 (27.15%) | 84 (60%) | – | – | – |
Our study shows a high number of latent syphilis cases, with late latent syphilis accounting for 73% and early latent syphilis making up 9% of the total 232 cases. All latent syphilis cases in our study were identified through routine or mandatory screenings conducted in various settings, including STI clinics, preoperative evaluations, blood donation drives, military recruitment, and partner notification programs.
The high number of latent cases may be attributed to several factors such as fear of judgment, social stigma, and self-medication discouraging individuals from seeking timely care; limited awareness of syphilis progression and its asymptomatic nature in the latent stage can lead to a false sense of being disease-free allowing individuals to spread the infection unknowingly. In rural areas, poor access to healthcare and delayed contact tracing further contribute to untreated cases and the spread of infection.
Secondary syphilis presents with varied symptoms, from rashes to rare conditions like lupus erythematosus.[28] This diversity leads to low clinical suspicion by dermatologists and other clinicians, resulting in missed diagnoses and progression to latent syphilis. This could be an additional factor contributing to a greater number of latent syphilis cases.[4] Like the visible tip of an iceberg, detected latent syphilis cases likely represent only a fraction of the actual number of cases in the population. This underscores the need for screening programs to identify asymptomatic cases and prevent further spread.
Contact tracing and partner management are essential components of STI prevention and control. However, many challenges arise in effectively implementing these processes. Table 3 highlights these challenges and provides strategies to address them.[29]
Table 3.
Challenges faced in contact tracing and partner management and ways to tackle them
| Problem area | Challenges | Ways to tackle |
|---|---|---|
| Stigma and social perception | Social stigma and fear of judgment by partner and family Social boycott and relationship estrangement Fear of identity disclosure and recall bias in partner info | Launch social awareness campaigns to reduce stigma and encourage testing. Promote education on safe sexual practices and public acceptance. Ensure patient confidentiality and provide counseling for patients and contacts. |
| Healthcare system limitations | Lack of funding for proper sexually transmitted infection care Shortage of resources, staff, and equipment Limited access to testing facilities | Streamline funding allocation to enhance access to care and resources. Improve resource management and expand staff training in sexual health care. Upgrade testing infrastructure and increase the availability of testing sites. |
| Technological barriers | Network availability issues for remote consultations Database and record-keeping problems Digital safety concerns, including data leaks | Ensure stable and reliable network connectivity for telemedicine and online health services. Implement efficient data storage systems and better management protocols. Enhance cybersecurity and encrypt patient data to ensure privacy. |
| Patient–provider interaction | Hesitancy of patients and providers in seeking treatment Unmotivated healthcare providers Patients seeking care from the private sector, complicating contact tracing | Build strong doctor–patient relationships through trust and counseling. Improve healthcare provider motivation through training and recognition. Encourage collaboration between public and private sectors for better care coordination. |
Limitations
Our study has certain limitations, such as inadequate available information because of it’s retrospective nature and for including patients from our tertiary center. Therefore, our findings may not fully represent the true epidemiological trends in the community. Larger population-based studies are necessary to provide a more comprehensive understanding of the clinico-epidemiological trends of syphilis. Another important limitation is the use of the VDRL test as the sole screening tool, which may have resulted in missed cases of latent syphilis, especially among individuals in early or later stages of the disease. Furthermore, the exclusion of pregnant women, a crucial demographic group in syphilis surveillance, restricts the scope of our conclusions. This is particularly relevant given the alarming global rise in congenital syphilis, as reported in recent studies from the United States and Europe. Despite its limitations, this study offers a valuable understanding of the epidemiology of syphilis and improves our understanding of the clinical characteristics and risk factors associated with the disease.
Conclusion
Our study sheds light on the escalating prevalence of syphilis, with a greater number of cases in the latent phase. We have identified important risk factors such as sex with CSW, multiple sexual partnerships, and the increased vulnerability of young adults and MSM. To address this, a comprehensive approach is needed, including strengthening prevention programs, promoting awareness through sexual health education, improving laboratory testing and surveillance, and combating stigma. Further population-based research is crucial to understand the clinico-epidemiological trends of syphilis and guide targeted intervention strategies.
Conflicts of interest
There are no conflicts of interest.
Use of artificial intelligence (AI)
The authors confirm that there was no use of artificial intelligence (AI) for assisting in the writing or editing of the manuscript.
Funding Statement
Nil.
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