International Journal of STD & AIDS >
Volume 19, Number 12 >
Pp. 838-842
Original research articles |
* National STD Reference Laboratory and;
** Department of STD Epidemiology, National Center for STD Control, Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Dermatology, Nanjing, China;
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA;
Department of STD Control of Guangxi Autonomous Region Institute of Dermatology, Nanjing;
Family Health International Country Office in China, Beijing, China;
Division of Clinical Infectious Disease, University of North Carolina Chapel Hill School of Medicine, Chapel Hill, NC, USA
Correspondence to: Dr Xiang-Sheng Chen, National Center for STD Control, China CDC, 12 Jiangwangmiao Road, Nanjing, Jiangsu, China 210042 Email: chenxs{at}vip.163.com
 | Summary |
|---|
 Top Summary INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
Key Words: syphilis • screening • STD patients • China
| INTRODUCTION |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
Case detection is a cornerstone of syphilis control. China's primary means (excluding voluntary antenatal testing and partner notification) of case identification at STD clinics relies mainly on symptomatic criteria.9 Guidelines for syphilis testing are based on the manifestation of hallmark signs of infection, such as painless genital ulcer, palmar/plantar rash, lymphadenopathy and orthopaedic, neurological or cardiovascular findings. Risk assessment and asymptomatic screening are not routine and no definitive screening guidelines are available.10,11 A significant proportion of syphilis infections fall outside the scope of China's methods of surveillance.
Fifty years ago in China, mass screening was carried out using a survey of eight simple questions inquiring about risk factors and symptoms consistent with STD (Box 1).12 While the survey items are somewhat outdated for the current epidemic, their rationale and the motivation behind the survey are not. In this report, we describe our search for an improved screening method that could help bridge the gap on missed opportunities for syphilis case detection and control of the rising STD population in China.
| Box 1 Eight questions for mass syphilis screening The Eight Questions – Have you had...
|
| MATERIALS AND METHODS |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
Our cross-sectional study was conducted at 14 community- and hospital-based dermatovenereal clinics (‘STD clinics’) in eight cities across Guangxi Autonomous Region. Between December 2004 and February 2006, patients 18 years of age or older who required only outpatient examination and treatment were consecutively recruited to participate. Participating patients provided verbal consent to respond to an anonymous survey on their clinical presentation, socioeconomic background and risk behaviours and to have blood drawn for syphilis and HIV testing. Recruitment and survey interviews were conducted by STD clinic staff who were visited and trained by investigators.
Socioeconomic characteristics investigated included sex, age, marital status, ethnicity, employment, education and residence. Behavioural information gathered were number of sexual partners, condom use, having received money for sex, having offered money for sex, any drug use (type and method not questioned), having a sexual partner who uses any drugs and being a man who has sex with men (MSM). Results of targeted physical exams, including detailed skin, lymph node and genital exam were also documented.
Patients' blood specimens were centrifuged and the sera were separated, on-site syphilis tests were performed with toluidine red unheated serum test (TRUST, Rongsheng Biotech Inc., Shanghai, China) and a rapid treponemal test (SD-TP, SD BIOLINE syphilis 3.0, Standard Diagnostics Inc., Kyunggi-do, Korea) at each local STD clinic for guiding the treatment, and the remaining sera were frozen and stored until it could be shipped to the National STD Reference Laboratory at the China CDC National Center for STD Control (NCSTD) for unlinked and anonymous syphilis and HIV serological testing. The TRUST and confirmation using Treponema pallidum particle agglutination test (TPPA, Serodia TP-PA, Fujirebio Inc., Japan) were conducted on each sample at the reference laboratory.
Survey and serological test results were concurrently double-entered into a computer database by independent research assistants and reviewed for congruency using Epi Info Software (version 6.04, Centers for Disease Control and Prevention, Atlanta, GA, USA). When database entries conflicted, the original test results and surveys for these cases were retrieved to correct entered data.
The study protocol was approved by the Institutional Review Board at the University of North Carolina Chapel Hill, USA and the Medical Ethics Committee at NCSTD, Nanjing, China.
Cases with positive TRUST and TPPA results were defined as serologically positive for syphilis.
Patients presenting with cardinal signs of syphilis, namely genital ulcer, lymphadenopathy or palmar/plantar rash that would have indicated syphilis testing based on China's current clinical guidelines were defined as ‘triaged patients’. Patients presenting without any of the aforementioned symptoms and who would not have been consulted syphilis testing were defined as ‘non-triaged patients’.
We devised a hypothetical screening survey on behavioural and health risk for syphilis that could potentially be used by health-care providers in determining which non-triaged STD patients should receive syphilis testing. Questions in our screening tool were drawn directly from items screened in the behavioural risk survey: (i) in the last three months, have you had more than one partner? (ii) In the last three months, did you never use condoms? (iii) In the last three months, did you or your partner use drugs (type not specified)? (iv) In the last three months, have you ever given or received money for sex? (v) Are you a man who has sex with men? A sixth item accounted for the patient's HIV status as determined by the serological test conducted as a part of this study and was posed, ‘Are the patient's serological test results positive for HIV infection?’
We initially undertook Pearson correlation analysis of potential risk factors surveyed by each screening item with syphilis among non-triaged patients. Analysis was performed using Statistical Program for Social Sciences (SPSS, version 13.0, Chicago, IL, USA) software. Results of our correlation analysis (Table 1) demonstrated statistically significant positive correlations between infection and being MSM (r = 0.039, P = 0.023) and lack of condom use among women (r = 0.067, P = 0.011), however, given their low r values, these correlations would not be considered clinically significant.
|
| RESULTS |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
Twenty-nine percent (3096/10,695) of subjects presented with genital ulcer, lymphadenopathy and/or palmar/plantar rash and would have been triaged for syphilis testing under the current testing guidelines. Among these triaged patients, 24.3% (751/3096) were indeed infected with Treponema pallidum. Seventy-one percent (7599/10,695) of STD patients did not present with the aforementioned signs or symptoms and would have been not been triaged for testing. Conversely, 40.9% (519/1270) of seropositive patients did not show hallmark signs of syphilis and would have been missed under the current screening guidelines. Among non-triaged patients, infection was more common in female than in male patients (8.7% vs. 5.4%, 
2 = 1.67, 95% CI 1.40–2.00, P < 0.001). No association (P > 0.5) could be found between infection and age or ethnicity when both sexes were examined together and separately in this cohort.
The results of validity testing of our screening tool (Table 1) demonstrate that our screening survey was more effective in detecting infection in male non-triaged patients than in female non-triaged patients; 90% of infection in male non-triaged patients was detected when the screening tool was applied with a total risk-score cut off = 1, while a mere 55.0% of infection was detected in female non-triaged patients using the same cut-off for testing. Furthermore, 85.0% (130/153) of infected non-triaged patients who lacked any indication (answering ‘no’ to all screening items) for testing were women. Graphed ROC curves presented in Figure 1 indicate that a lower optimal threshold cut-off to necessitate syphilis testing should be used in female non-triaged patients (optimal total risk score cut-off = 1) versus in male non-triaged patients (cut-off = 2). If the screening tool with a risk-score cut-off = 1 was applied in addition to China's current screening measures (testing triaged patients) to all STD patients, 88.0% (1117/1270) of syphilis infection would have been detected while testing 80.5% (8610/10,695) of STD patients (Table 2).
|
|
| DISCUSSION |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
Given the previously reported associations of these behavioural and health risk factors with syphilis, that in our study these risk factors lacked significant correlation with syphilis in non-triaged patients was surprising. The lack of correlation, however, should not be understood as suggesting that high-risk behaviours are irrelevant to syphilis; the nominally high rates of infection for each group reporting a behavioural risk (2.2–18.8%) reiterate that syphilis is a major health problem for individuals engaging in high-risk behaviours. The lack of correlation may be due to the masking effect of generally high rates of infection or to considerable under-reporting of risk by patients. It may also reflect broad high risk-taking behaviour in the STD clinic population and the urgent need for counselling and behavioural interventions in this group.
Should our risk assessment survey be used at the optimal total risk score cut-off = 1 to supplement current testing guidelines, risk assessment would greatly improve case detection in the STD clinic population. Behavioural risk assessment has also been shown to be beneficial in case detection of other STDs that can also have asymptomatic presentations and grave outcomes, such as chlamydial and HIV infections.17–21 Syphilis should not be excluded from such rigorous assessment practices.
It is important to emphasize that the screening tool performs better in male non-triaged patients than in female non-triaged patients, which may be due to several factors. Men may be more willing to disclose risk. This is reassuring as it suggests that counselling men on STD and risk may be feasible if not successful. Women may be more hesitant to reveal risk behaviours. China is a patriarchal society and women suffer a greater risk of disdain and reprisal for engaging in more liberal sexual behaviour. On the other hand, the low endorsement rate of risk factors in women could also be accurate. A national representative study on chlamydial infection in China found that increased risk for disease in women was in fact conferred by their male partners6 and was less attributed to her personal risk-taking. Women may still be at a disadvantage even with enhanced screening practices. As our study results show, women represent the great majority of infected patients whose infection is missed despite the use of current clinical guidelines for testing and risk factor assessment.
This is of paramount concern as it raises uncertainty as to whether such behavioural surveys can be effectively administered in China, or at least among women in China. Such surveys are only feasible if doctors are willing to ask about risk and patients are willing to respond truthfully to such questions. Heavy patient loads, embarrassment about asking and responding to personal questions, and fear of stigma and discrimination all compound to preclude proper risk assessment. Furthermore, such surveys are unable to detect risk conferred by partners and can wrongfully conclude that a patient, who does not suspect her partner of having syphilis and has no apparent personal indicators for syphilis, does not require testing.
To achieve enhanced syphilis surveillance, an alternative is to implement universal serological testing of all patients. Universal testing can ensure that all susceptible persons are offered testing. Universal testing for syphilis is not radical or unprecedented in China or in other countries.22 Cost versus benefit is a major consideration, particularly for developing nations such as China, where resources are limited and multiple public needs must be addressed. Benefit (high case yield) of universal testing correlates with disease prevalence, and limited benefit is gained when mass testing is misdirected to low prevalence groups.23–25 The prevalence of syphilis to warrant universal testing among antenatal women in China is 0.45%.13 A 6% prevalence rate among USA servicemen after the First World War invoked the surgeon general to fiercely advocate and institute universal testing.22 These rates pale when compared with that found in China's STD population.
The World Health Organization has recognized the STD population as a golden opportunity for syphilis control and firmly recommends syphilis serologic testing to patients presenting with any STD syndrome, not just exclusively to patients with genital ulcer.29 Moreover, with advancements made in inexpensive syphilis rapid diagnostic tests and their ease of use, high performance and favourable acceptance in China,26,27 universal testing of China's STD population is a realistic option. Furthermore, universal screening may serve as a good entry point for introduction of voluntary counselling and testing or provider-initiated testing and counselling for other STD including HIV in this population.
There are several important limitations to our study. First, our study population may not reflect Guangxi's or the nation's STD population. The syphilis infection rate documented in our study exceeds that of other similar studies in China reporting prevalences below 8%.28–30 In addition, the lack of data on the proportion of patients who refused participation in our study undermines our study's representation of this population. Secondly, while our study results may allude to the potential outcomes and weaknesses of risk assessment, the performance of such a screening tool can only be decisively known through designing a study specifically to test it. Finally, our screening tool may not have encompassed the full range of risk factors for syphilis and its questions may not have been sufficiently focused or appropriately composed to ascertain a patient's risk.
Our study confirms that the mounting syphilis epidemic in China demands urgent action. More than one in 10 STD patients were infected with syphilis, and more than one in three syphilis patients may have gone undiagnosed if the current clinical guidelines for testing were followed. Current syphilis surveillance practices in China are weak, the repercussions of which can impact the HIV epidemic and family planning in China. Our study demonstrates that selective testing using risk assessment surveys, while able to assist health-care providers in improving case detection, will not be successful in communities where there is considerable fear of disclosure and where risk is conferred by partners such as with women in China. We support universal syphilis testing in China's STD population as an appropriate and necessary means to achieve comprehensive surveillance of syphilis and timely detection and treatment of infection.
| ACKNOWLEDGEMENTS |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
| REFERENCES |
|---|
|
TopSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONACKNOWLEDGEMENTSREFERENCES |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
