DIAGNOSES OF SYPHILIS MADE at genitourinary medicine (GUM) clinics have fluctuated throughout the 20th century, influenced by social change, conflict, changing sexual behavior, and developments in health care (Fig. 1).1 The second peak in syphilis diagnoses that started in the early 1960s declined during the 1980s in the face of behavioral changes brought about by the emergence of the HIV pandemic. By the early 1990s, diagnoses had stabilized, and syphilis had a low prevalence and low incidence but had not been eliminated. In 1997, an outbreak (a greater than expected number of cases over a defined time period) of infectious syphilis was reported in Bristol.2 A subsequent increase in incidence has challenged established public health intervention strategies and the way in which syphilis cases are diagnosed and managed.3 It has also highlighted the need for targeted education and healthcare resources, and detailed surveillance data. We describe the outbreaks that have occurred and explore the reasons for the re-emergence of infectious syphilis within the context of the phase-specific epidemiologic model (Table 1).4–6.
Materials and Methods
Data used in this report were derived from 3 sources: diagnoses made in GUM clinics reported on form KC60 and ISD(D)5; outbreak reports published in the medical literature; and information collected through the enhanced surveillance initiatives coordinated by Health Protection Agency North West (Manchester outbreak), Health Protection Agency North East (Newcastle-upon-Tyne outbreak), the Scottish Centre for Infection and Environmental Health (SCIEH), and Health Protection Agency Communicable Disease Surveillance Centre (CDSC) (London outbreak), CDSC Northern Ireland, and the National Public Health Service for Wales, together with their associated partners.
In England and Wales, the KC60 return collects quarterly aggregate data on the total number of episodes of sexually transmitted infections or sexual health services provided in GUM clinics.1 Data from the KC60 return are reported by quarter in arrears and consequently cannot be used to respond to rapidly developing epidemics. The enhanced surveillance initiatives, which rely on voluntary reporting from GUM clinics, were specifically designed to create an evidence base to guide health service planning and intervention strategies. The initiatives were tailored to collect timely, detailed information about the syphilis epidemic. Demographic, behavioral, and clinical data are collected, including gender, age, ethnic background, sexual orientation, stage of infection, HIV status, location where the infection was likely to have been acquired, and connections with networks such as saunas and bars. The role of oral sex in the transmission of syphilis was considered during each patient consultation. Oral transmission was only recorded as the most likely route of transmission if both the clinician and patient considered this to be appropriate.
The first enhanced surveillance initiative started in Manchester in 1999 and was extended to cover the whole of the northwest region in January 2003. The London Enhanced Laboratory Surveillance for Infectious Syphilis, which was established in April 2001, is health advisor-led and was extended to include the whole of England and Wales in 2002.
SCIEH established an enhanced syphilis surveillance system in January 2003 that was based on that developed by the English Health Protection Agency. Data were collected retrospectively in Glasgow to 2000.
Before 1997, the last syphilis epidemic in the United Kingdom had peaked in the late 1970s (Fig. 2). Phase IV of that epidemic occurred between 1988 and 1996. Between 1997 and 2002, diagnoses of primary, secondary, and early latent syphilis made at GUM clinics (KC60 data) increased by 213% in heterosexual males, 1412% in men who have sex with men (MSM) and 22% in females (Fig. 2). In 2002, 1232 cases were reported in England, Wales, and Northern Ireland, 460 in heterosexual males, 635 in MSM, and 137 in heterosexual women. The outbreaks that have accompanied these overall increases are summarized in Table 2.
Up to the end of October 2003, the 2 largest outbreaks were seen in Manchester (528) and London (1222) (Fig. 3)3,7–9. Enhanced surveillance started in Manchester in 1999 (Fig. 3). In Manchester, from the baseline at the beginning of the outbreak (KC60 returns), the number of diagnoses doubled in the first 7 months and doubled again in the next 12 months. A similar pattern was seen in the London outbreak in 2001–2002.
In Manchester, 84% (443 of 518; sexual orientation unknown in 10 cases) of the cases were seen in MSM. Of the MSM, the median age was 33 years (range, 16–67 years); 92% (385 of 419) were white; 56% (236 of 424) had previously had a sexually transmitted infection; and 36% (126 of 354) had an HIV coinfection. Oral sex was a key transmission route; 88% (226 of 256) of the MSM did not use a condom for oral sex, whereas 28% (69 of 250) did not use a condom for anal sex. Only 3 cases of MSM syphilis were acquired abroad. In the same outbreak, 75 cases reported to have been acquired by heterosexuals, 41 in males (median age, 32 years; range, 17–46 years) and 34 in females (median age, 24 years; range, 17–36 years). Forty-five percent (34 of 68; ethnicity not recorded in 7 cases), and 32% were either black Caribbean or black African. Nearly one fourth (17 of 70) of the syphilis cases had previously had a sexually transmitted infection. Six of 42 heterosexual syphilis cases were also HIV-positive (14%, with HIV status not known in an additional 33 cases).
The geographic origin of cases in Manchester was diverse: 38% (205) originated from Central Manchester, 36% (195) from Greater Manchester, and 18% (97) from outside Manchester. Social venues including pubs, clubs, and saunas in central Manchester were important for the spread of the infection, and there was some evidence of an increase in partners meeting through the Internet. Forty-seven percent (210 of 447) of cases were diagnosed as a result of a routine sexually transmitted infection health check; few were identified through contact tracing or antenatal screening.7 In keeping with observations from other outbreak sites, partner notification had a success rate of 4% (that is, 1 or more partners were traced in 4% of cases).
In London, enhanced surveillance started in 2001 in response to the detection of a cluster 24 cases diagnosed in MSM (Fig. 4). By the end of October 2003, 1222 cases had been reported and 2 epidemics had emerged: 1 in MSM (829) and a second in heterosexuals (256 cases in males, 137 in females). The divergence between heterosexual male and female cases may reflect increased case finding among males or genuine differences in risk behavior. In MSM, diagnoses made at the GUM clinic took less than 12 months to double. The median age of MSM was 35 years (range, 18–75 years). There were a high proportion of coinfections with HIV; a high proportion of cases reported oral sex; cases were predominantly of white ethnic origin and had been born in the United Kingdom. Thirty-five percent of MSM diagnosed with syphilis were reported to have acquired the infection at social venues; specifically, cruising grounds, saunas, bars, and the Internet were important to the spread of infection. HIV-positive MSM were older than those who were HIV-negative and more likely to present with secondary syphilis rather than primary or early latent. A high proportion of HIV-positive MSM who were infected with syphilis reported using venues that facilitate sexual partner acquisition such as saunas and cruising grounds and greater numbers of sexual partnerships in the last 3 months than HIV-negative MSM with syphilis. Most cases had been identified through routine health service screening or because the patient was symptomatic.
In London, the median age for heterosexual males was 35 years (range, 17–92 years) and 30 years (range, 16–64 years) for heterosexual females. Few cases were identified through contact tracing or antenatal screening. Twenty-one percent (66 of 314) of heterosexual cases were acquired outside the United Kingdom. Most heterosexuals were either white or black British. Contact with a commercial sex worker was reported by 27 of the heterosexual cases. There was little reported contact with other U.K. outbreak sites and no connection with Eastern Europe.
The Brighton outbreak was identified in 1999 and has mainly been focused on MSM; HIV coinfections are commonly reported, and oral sex was reported as the likely route of transmission in 37% of cases.10,11 Between July 1999 and the end of 2001, 44 cases were identified and a further 140 cases of primary, secondary, and early latent syphilis were reported between the beginning of 2002 and the end of October 2003. In MSM, more than 90% of sexual contacts were either anonymous or untraceable. In addition, 38% of the MSM with syphilis not previously known to be HIV-positive were diagnosed with HIV.
Smaller epidemic foci have been associated with the principal outbreak areas. For example, the cases seen in Walsall were probably associated with the Manchester outbreak.12 In contrast, other foci such as those seen in Peterborough and Bournemouth were associated with infections acquired in Eastern Europe.13 A cluster of cases in MSM in South Wales has been attributed to local transmission through sexual networks, including a gay sauna, in Southeast Wales.
The Scottish outbreak started in mid-2001 and since then, 103 (75%) cases in MSM, 18 in heterosexual males, and 10 in heterosexual females.14 Although most cases were seen in Glasgow (63) and Edinburgh (21), a further 19 cases were reported from 8 other clinics. Among MSM, 38% of the cases were likely to have acquired the infection through oral sex; 19% were HIV-positive; 20% had attended health services; and 6% reported meeting partners through the Internet. Seventy-two MSM reported 470 sexual contacts in the preceding 3 months but only 19% were traceable. Most cases were likely to have been acquired in Scotland, but 16% probably acquired their infection in England (mostly in Manchester) and 9% outside the United Kingdom. Heterosexual female cases were more likely to present with early latent syphilis. Around half the cases seen in heterosexual females were linked to high syphilis prevalence countries.
The Northern Ireland outbreak started in 2001.15 To September 30, 2003, 75 cases had been reported, 6 in females and 69 in males; 88% (61 of 69) of the male cases were in MSM. Oral sex was considered the most likely route of infection in 46% of cases in MSM, few of whom reported regularly using a condom for oral sex. In contrast to other outbreaks, the median number of sexual partners was low, 76% of cases reporting fewer than 3 anonymous partners in the past 3 months. The cases identified in 2001 had strong links with the Dublin outbreak, but since the beginning of 2002, the majority of cases had acquired their infections had been acquired in Northern Ireland.16
The year 1997 was a crucial time in the evolution of the U.K. syphilis epidemic. Phase IV of the previous epidemic, which occurred between 1985 and 1996, had seen incidence decline rapidly to a very low level and was sustained by infection acquired both within the United Kingdom and in high-prevalence countries. In phase I of the new epidemic, incidence increased rapidly and 2 areas of high endemicity emerged (London and Manchester), together with a number of microepidemics. The enhanced surveillance initiatives proved to be crucial to our understanding of the contextual issues that surrounded the reemergence of syphilis at phase I. Outbreaks were characterized quickly and completeness of reporting has been improved by crossreferencing diagnoses made in the GUM against laboratory reports made to CDSC and SCIEH.
The main feature of the re-emergence of syphilis has been the rapid increase in cases seen in MSM. The high number of cases coinfected with HIV suggests that the epidemiology of syphilis has been influenced by developments in the HIV epidemic and behavioral change in MSM. The availability of effective antiretroviral therapies in 1996 has been associated with a change in sexual behavior among HIV-positive MSM and an increase in HIV prevalence.17,18 The availability of Viagra (sildenafil citrate) may also have increased sexual activity in HIV-positive MSM. Reports of unsafe sex among MSM, particularly with a partner of unknown HIV status, have increased in London since 1996.19 There has also been an increase in traditional “sexual marketplaces” such as saunas and cruising grounds, together with a rapid growth in internet chat rooms.20–22 The Internet has allowed rapid and easy acquisition of sexual partners to be negotiated and increased the opportunity to contact new sexual partners. The effect has been to join previously isolated sexual networks, reducing the time taken for the epidemic to evolve and increasing the effective size of the sexual network.
Although the burden of diagnoses has fallen on MSM, the first outbreak to be identified (Bristol, 1997) was among heterosexuals, and there has been a steady stream of heterosexual cases over the past 8 years. Factors including travel abroad, commercial sex work (CSW), and illicit drug use have been associated with syphilis infection. A cluster was seen in a “swingers” club, that is, a heterosexual sex club and the source of infection, was considered to have been a CSW in Warsaw, Poland.13 The influence of the syphilis epidemic that emerged in Eastern Europe with the collapse of the Soviet Union in 1990 has been seen in other U.K. outbreaks; however, the number of cases associated with Eastern Europe has been small. Infection acquired abroad has always been a feature of syphilis epidemiology in the United Kingdom, even in phase IV (mid to late 1980s) of the previous epidemic. However, the overall number of heterosexual cases is low, most transmission has occurred in the United Kingdom, and the proportion of all heterosexual cases acquired abroad is similar to that seen in the mid-1990s when incidence was low.23 In phase I of the new epidemic, most transmission has occurred within the United Kingdom. Increased incidence of syphilis among heterosexuals is also an important dimension in the development of the epidemic in London.24 Cases of congenital syphilis have been reported and this could present an emerging public health problem.
“Crack” cocaine use has been associated with a number of heterosexual diagnoses of syphilis, as well as outbreaks of other infectious agents such as hepatitis A and drug-resistant tuberculosis.25–27 In the United Kingdom, the use of “crack” was first described in 1986, and increased use was reported in 2000.28 The association between “crack” and infectious disease probably reflects the chaotic lifestyle related to the use of this short-acting drug that encourages a high frequency of injection. Cases of infectious syphilis have also occurred among people who have had unprotected oral or vaginal sex with casual partners/strangers, or who have bought or sold sex.24
The increase in diagnoses seen in phase I may have been influenced by the factors outlined here, although development through the stages of the phase-specific model may have been stunted by the intervention strategies. This has been followed by the oscillating plateau of phase II, a “boom and bust” in incidence characterized by a steady slow supply of susceptible individuals balanced against the number of detected infections. This suggests that infection has saturated at a low prevalence in high-risk groups. In the smaller outbreaks, infection could die out by chance.5 However, where syphilis, HIV, and Neisseria gonorrhoeae have reset at a new endemic level, as has been the case in Manchester and London, it is unlikely that the epidemic can be eradicated through established case-finding methods.1
Although the enhanced surveillance initiatives have proved an invaluable source of information, they do not collect information on the provision of diagnostic services. The timely detection and management of symptomatic and asymptomatic cases are central to the control of infection. However, over the past 5 years, waiting times to access GUM services have increased substantially.29 These problems have been caused by large increases in attendance at already overstretched clinical services. For example, in 2000–2001 patients attending clinics in Manchester waited between 6 to 12 weeks for an appointment, although waiting times were shorter for symptomatic cases. This is likely to have contributed to an increase in the duration of infectiousness. GUM services have responded to these problems by using less time-consuming diagnostic and treatment strategies and have incorporated prevention work into consultations with patients with syphilis. Nevertheless, improvements in access to GUM services are urgently needed. This problem has been recognized by the Department of Health (England), and investment in sexual health is a government priority.
Traditional models of partner management have been largely unsuccessful because many partners are anonymous and untraceable. The best models of health promotion within healthcare settings are unclear at the national level, but local initiatives have provided new approaches to health promotion and control that have been tailored to local needs and developments. These have included defining and intervening in sexual networks as well as health advisors working in venues where syphilis transmission is known to occur.30 Other sources of care such as primary care have been closely involved in case management.
Syphilis awareness has been raised through targeted information campaigns such as “Look what’s back!,” “Sex Pigs” (Terrance Higgins Trust), and “Spreads Easily” (Manchester). These have promoted knowledge about syphilis with the objectives of informing decision-making and choice in sexual relationships. Evaluation of the 2002 Glasgow syphilis awareness campaign demonstrated rises in requests for voluntary confidential testing: 18% had used sexual health services as a result of the initiative. Whereas the information campaigns have been well received, screening initiatives in social venues within outbreak areas have identified few cases. Rapid diagnostic tests based on salivary assays have been used, but the sensitivity and specificity of the salivary tests need to be characterized further.31 Pinprick blood tests could be used to screen for infection within risk groups to encourage treatment compliance using single- dose azithromycin therapy.32 However, after the failure of the mass treatment intervention initiative in Vancouver and growing evidence of antimicrobial resistance, the use of azithromycin in outbreak situations needs further investigation.33,34
Although the United Kingdom has not experienced a syphilis epidemic on the scale seen in Eastern Europe, a dramatic change in incidence has been observed over the past 7 years. Similar outbreaks have been seen in major cities in Europe, North America, and Australia and there are striking similarities between these outbreaks.35–42 Nevertheless, syphilis is curable. It is unlikely that the epidemics of syphilis and other sexually transmitted infections will bring about sexual behavior modification on the scale that coincided with the emergence of HIV in the mid-1980s. Experience from phase I suggests that incidence will be reduced by a combination of: increased education and awareness to infection within at-risk groups; the development of novel approaches to intervention; and linking syphilis awareness and targeted screening campaigns to rapid access to GUM services. As the epidemic matures into phase II, it appears that incidence continues to be centered within high-risk groups with limited spread into the wider population. However, the epidemic’s future course is difficult to predict, and control remains elusive.
1. Health Protection Agency, SCIEH, ISD, National Public Health Service for Wales, CDSC Northern Ireland and the UASSG. Renewing the Focus. HIV and Other Sexually Transmitted Infections in the United Kingdom in 2002. London, UK: Health Protection Agency, 2003.
2. CDSC. Syphilis in Bristol 1997–8: an update CDR Wkly Health Protection Agency web site. November 28, 1998. Available at: http://www.hpa.org.uk/cdr/CDR98/cdr4798.pdf
. Accessed July 31, 2003.
3. Fenton K, Nicoll A, Kinghorn G. Resurgence of syphilis in England: Time for more radical and nationally co-ordinated approaches. Sex Transm Infect 2001; 77:309–310.
4. Aral SO. Determinants of STD epidemics: Implications for phase appropriate intervention strategies. Sex Transm Infect 2003; 78:i3–i13.
5. Garnett GP. The geographical and temporal evolution of sexually transmitted disease epidemics. Sex Transm Infect 2003; 78:i14–i19.
6. Wasserheit JN, Aral SO. The dynamic topology of sexually transmitted disease epidemiology for prevention strategies. J Infect Dis 1996; 174:S201–213.
7. Clark P, Cook PA, Syed Q, Ashton J, Bellis M. Re-emerging syphilis in the North West: Lessons from the Manchester outbreak. Liverpool: Public Health Sector, Liverpool John Moore University, 2001.
8. Ashton M, Sopwith W, Clark P, McKelvey D, Lighton L, Mandal D. An outbreak no longer: Factors contributing to the return of syphilis in Greater Manchester. Sex Transm Infect 2003; 79:291–293.
9. Crook PD, Paine TC, Davis M, Fenton KA. London—The next battleground for syphilis? Commun Dis Public Health 2002; 5:163–164.
10. Poulton M, Dean GL, Williams DI, Carter P, Iversen A, Fisher M. Surfing with spirochetes: An ongoing syphilis outbreak in Brighton. Sex Transm Infect 2001; 77:319–321.
11. CDSC. Increased transmission of syphilis in Brighton and Greater Manchester among men who have sex with men. CDR Weekly Health Protection Agency web site. October 27, 2000. Available at: http://www.hpa.org.uk/cdr/CDR00/cdr4300.pdf
. Accessed June 11, 2004.
12. Pugh RN, Laverty S, Simms I, et al. Syphilis outbreak in Walsall: Case profiles and public health implications. Commun Dis Public Health 2004; 7:27–29.
13. CDSC. Outbreak of heterosexually acquired syphilis in Cambridgeshire. CDR Weekly Health Protection Agency web site. November 10, 2000. Available at: http://www.hpa.org.uk/cdr/CDR00/cdr4500.pdf
. Accessed June 11, 2004.
14. Redman C, Winter A, Sharma S, et al. Infectious syphilis in Scotland: the implementation of a new surveillance system. SCIEH Weekly Report 2003; 37:6–7.
15. Lynch A, Smyth B. Syphilis outbreak in Northern Ireland. Eurosurveillance Weekly Health Protection Agency web site. June 12, 2003. Available at: http://www.eurosurveillance.org/ew/2003/030612.asp
. Accessed June 11, 2004.
16. Hopkins S, Lyons F, Mulcahy F, Bergin C. The great pretender returns to Dublin, Ireland. Sex Transm Infect 2001; 77:316–318.
17. Ho T, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowi M. Rapid turnover of plasma virions and CD4 lymphocytes in HIV infection. Nature 1995; 373:123–126.
18. Rice B, McHenry A, Sinka K, et al. Prevalent diagnosed HIV in England, Wales and Northern Ireland—Adjusted totals 1996 to 2001 and extrapolation to 2004. AIDS 2004; 18:927–932.
19. Dodds JP, Nardone A, Mercey DE, Johnson AM. Increasing high risk sexual behaviour amongst homosexual men in London 1996–8: A repeated cross sectional questionnaire study. BMJ 2000; 320:1510–1511.
20. Centers for Disease Control and Prevention. Internet use and early syphilis infection among men who have sex with men—San Francisco, California. MMWR Morb Mortal Wkly Rep 2003; 52:1229–1232.
21. Mettey A, Crosby R, DiClemente RJ, Holtgrave DR. Associations between Internet sex seeking and STI associated risk behaviours among men who have sex with men. Sex Transm Infect 2003; 79:466–468.
22. Klausner J, Wolf W, Fischer-Ponce L, Zolt I, Katz M. Tracing a syphilis epidemic through cyberspace. JAMA 2000; 284:447–449.
23. CDSC. Sexually transmitted diseases quarterly report: Syphilis—National and international epidemiology. CDR Wkly 1999; 9:38–39.
24. Crawley-Boevey E, Simms I. Rise in heterosexually transmitted cases of syphilis in south London, England. Eurosurveillance Weekly Health Protection Agency web site. July 31, 2003. Available at: http://www.eurosurveillance.org/ew/2003/030731.asp
. Accessed June 11, 2004.
25. CDSC. Hepatitis A outbreak in Weymouth, Dorset. CDR Wkly Health Protection Agency web site. July 31, 2003. Available at: http://www.hpa.org.uk/cdr/PDFfiles/2003/cdr3103.pdf
. Accessed June 11, 2004.
26. CDSC. Cluster of wound botulism cases in injecting drug users. CDR Wkly Health Protection Agency web site. October 31, 2002. Available at: http://www.hpa.org.uk/cdr/PDFfiles/2002/cdr4402.pdf
. Accessed June 11, 2004.
27. CDSC. Drug resistant tuberculosis outbreak in north London—update. CDR Wkly Health Protection Agency web site. August 1, 2002. Available at: http://www.hpa.co.uk/cdr/PDFfiles/2002/cdr3102.pdf
. Accessed June 11, 2004.
28. Ramsay M, Baker P, Goulden C, Sharp C, Sondhi A. Drug misuse declared in 2000: Results from the British Crime Survey. London: The Home Office, 2001.
29. House of Commons Health Committee. Sexual Health. Third report of session 2002–03. London: The Stationary Office Limited, 2003.
30. Pendrey J, McDonald T, Parry JV, et al. The development of an oral fluid assay for syphilis surveillance. Presented at the Health Protection Agency First Scientific Conference; Warwick, UK; September 15–17, 2003.
31. The Sexually Transmitted Disease Diagnostic Initiative. Laboratory-based evaluation of rapid syphilis diagnostics. Geneva: World Health Organization; 2003. Available at: http://www.who.int/stddiagnostics
. Accessed October 10, 2004.
32. Rothenberg RB, Sterk C, Toomey KE, et al. Using social network and ethnographic tools to evaluate syphilis transmission. Sex Transm Dis 1998; 25:154–160.
33. Rekart ML, Patrick DM, Chakraborty B, et al. Targeted mass treatment for syphilis with oral azithromycin. Lancet 2003; 361:313–314.
34. Simms I, French P, Fenton KA. Azithromycin failures in the treatment of syphilis. Eurosurveillance Weekly Health Protection Agency web site. April 1, 2004. Available at: http://www.eurosurveillance.org/ew/2004/040401.asp
. Accessed June 11, 2004.
35. Smacchia C, Parolin A, Di Perri G, Vento S, Concia E. Syphilis in prostitutes from Eastern Europe. Lancet 1998; 351:572.
36. Hiltunen-Back E, Haikala O, Koskela P, Vaalasti A, Reunala T. Epidemics due to imported syphilis in Finland. Sex Transm Dis 2002; 29:746–751.
37. Couturier E, Dupin N, Janier M, et al. Syphilis: Increasing trends in Paris, France 1998–2001. Abstract AIDS 2002 Barcelona XVI International AIDS Conference; July 7–12, 2002.
38. van der Meijden W, van der Snoek E, Haks K, van de Laar M. Outbreak of syphilis in Rotterdam, The Netherlands. Eurosurveillance Weekly Health Protection Agency web site. March 28, 2002. Available at: http://www.eurosurveillance.org/ew/2002/020328.asp
. Accessed June 11, 2004.
39. Halsos AM, Edgardh K. An outbreak of syphilis in Oslo. Int J STD AIDS 2002; 13:370–372.
40. De Schrijver K. Syphilis outbreak in Antwerp, Belgium. Eurosurveillance Weekly Health Protection Agency web site. May 10, 2001. Available at: http://www.eurosurveillance.org/ew/2001/010510.asp
. Accessed June 11, 2004.
41. Blystad H, Nilsen Ø, Aavitsland P. An outbreak of syphilis among homosexual men in Oslo, Norway. Eurosurveillance Weekly Health Protection Agency web site. November 18, 9993. Available at: http://www.eurosurveillance.org/ew/1999/991118.asp
. Accessed June 11, 2004.
42. Axelsen N, Smith E, Koch-Hansen GH. Syphilis cases increasing in Denmark, 2000–01. Eurosurveillance Weekly Health Protection Agency web site. August 29, 2002. Available at: http://www.eurosurveillance.org/ew/2002/020829.asp
. Accessed June 11, 2004.