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Resurgence in Infectious Syphilis in Ireland

An Epidemiological Study


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Sexually Transmitted Diseases: May 2004 - Volume 31 - Issue 5 - p 317-321
doi: 10.1097/01.OLQ.0000123653.84940.59
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Syphilis is a genital ulcerative disease caused by the spirochete Treponema pallidum, which facilitates the transmission of HIV. 1 Untreated, infectious syphilis is likely to recur in 23% of cases and cause tertiary complications (cardiovascular, neurologic, and musculoskeletal) in 28% of cases. In a retrospective analysis on the natural history of syphilis, mortality from untreated syphilis was estimated to be 17.1% for men and 8% for women. 2 Untreated infectious maternal syphilis has a perinatal mortality in the order of 50%, and 50% of live newborns show evidence of symptomatic congenital syphilis. Even with later noninfectious maternal syphilis (up to 8 years postprimary infection), studies report no perinatal mortality but a 10% risk of congenital syphilis. 3,4

In the United States, low rates of syphilis throughout the 1990s led the Surgeon General to develop the National Plan to Eliminate Syphilis from the United States. 5 The rates of primary and secondary syphilis reported in 2000 were the lowest recorded since 1941 when reporting began. In 2001, a 2.1% increase in infectious syphilis was observed in men compared with 2000. This was associated with reports from many cities of syphilis outbreaks among men who have sex with men (MSM) characterized by high rates of HIV coinfection and high-risk sexual behavior. 6

In the United Kingdom, similar trends have been noted. 7 Between 1998 and 2000, reported cases of infectious syphilis more than doubled in men (from 172 to 372) and increased by 53% (from 102 to 156) in women. This correlated with a number of outbreaks in Britain occurring predominantly among MSM with similar characteristics as the U.S. outbreaks.

The emergence of an outbreak was identified by the Department of Genitourinary Medicine and Infectious Diseases, St. James’s Hospital, Dublin, in 2000. The aim of this report is to describe the changing epidemiology of syphilis that has occurred in Ireland over the last 10 years.

Materials and Methods

The Department of Genitourinary Medicine and Infectious Diseases, St. James’s Hospital is the largest center for the provision of sexually transmitted infection (STI) and HIV services in the Republic of Ireland with over 25,000 patient attendances per year. Approximately 90% of syphilis cases in the eastern region of Ireland (including Dublin) and approximately 75% of syphilis cases in the Republic of Ireland were diagnosed and treated in this center. Patients attend the hospital through a walk-in emergency service, general practitioner referral, self-referral, and linked STI clinic referrals (predominantly the Gay Man’s Health Project, the only community-based STI service for gay and bisexual men in Ireland with approximately 3000 attendances per year).

In 2000, a prospective enhanced database of all syphilis cases was established in the clinic. Data collected included demographics (age, sex, county of address, sexuality, socioeconomic class) and codiagnoses (notably HIV and other STIs). Patients were questioned on their risk factors and risk behavior (numbers of sexual partners, venues where sexual partners were encountered, and utilization of drugs).

Retrospective data (before 2000) is based on the STI clinic (KC60) returns to the regional Department of Public Health.

Crude incidence rates (new cases of infectious syphilis per population) were calculated on an annual basis per 100,000 of the general population. In this report, the incidence rates were calculated using the 2002 Census data using age-specific, gender-specific, and area-specific data. 8 Denominators used in the calculation of incidence rates for MSM is based on the U.K. Natsal Study 2000, 9 because such a study has not been performed in Ireland. This data reports that 2.6% of men living in Britain between the ages of 16 and 44 years had a homosexual partner in the previous 5 years. Assuming a similar pattern in Ireland would mean that there are 19,601 MSM between the ages of 16 and 44 living in Ireland, and they are likely to be predominantly located in the Dublin metropolitan area. Approximately 80% of all newly diagnosed HIV-1-infected MSM between January 2000 and December 2002 attended St. James’s Hospital (10 and department statistics). Denominators used in the calculation of crude incidence rates of syphilis in known HIV-1-infected individuals are based on the total HIV-1-infected MSM cohort attending St. James’s Hospital. Numerators used were based on the HIV-positive MSM attending St. James’s Hospital for follow-up care (ie, HIV-positive MSM diagnosed with syphilis whose HIV care was at another institution were excluded from this analysis).

Data were analyzed using SPPS 11.0 with chi-squared test and Fisher exact test for numbers below 100 to compare differences between sexes and sexuality.

Case Definitions

For the purpose of surveillance, the following case definitions were used to allow the collection of standardized data.

Infectious syphilis was defined as primary, secondary, or early-latent disease. 11 A diagnosis of noninfectious syphilis was recorded in all cases of late-latent or tertiary disease. Individuals under the age of 16 years (including congenital syphilis) attend the pediatric services and were therefore not captured in this report.

Primary syphilis was defined as the appearance of a chancre (single or multiple) at the inoculation point associated with regional lymphadenopathy. The diagnosis was confirmed by dark ground microscopy and/or positive serology.

Secondary syphilis was defined by a generalized mucocutaneous rash (macular, maculopapular, or maculosquamous), generalized lymphadenopathy, systemic symptoms compatible with secondary syphilis and confirmed with positive syphilis serology.

Early-latent syphilis was defined as seroconversion or a fourfold rise in nonspecific treponemal tests, a history of nontreated primary or secondary infection, or a history of contact with an individual with documented infectious syphilis and confirmed with positive serology within the previous 12 months.

All patients had standardized serology performed in St. James’s Hospital Microbiology Laboratory. All samples were screened using a nonspecific (nontreponemal) test (reactive plasma reagin [RPR]) and a specific (treponemal) test (T. pallidum particle agglutination [TPPA]). Any samples positive in one or more of these tests were confirmed positive by the specific and sensitive fluorescent treponemal antibody (FTA) absorption test (RPR: Axis-Shield; Axis-Shield Diagnostics Ltd., The Technology Park, Dundee, U.K.; TPPA: Seodia-TP-PA; Fujirebio Inc., Tokyo, Japan; FTA IgG and IgM: Trepo-Spot IF; bioMerieux sa, 69280 Marcy-l’Etolie, France)


The mean number of cases reported per year in the 1990s was 15, of which 5 were classified as infectious. The total number of cases diagnosed between January 2000 and June 2003 was 610: 56 cases in 2000, 257 cases in 2001, 226 cases in 2002, and 71 cases in the first 6 months of 2003 (Fig 1). Since January 2000, 356 infectious cases of syphilis were diagnosed (58% of all diagnosed cases). Additionally, 51 cases of syphilis were treated as reinfections or reactivations based on clinical signs and serology (37% of whom were coinfected with HIV-1) and 203 cases were classified as noninfectious syphilis. The cases of noninfectious syphilis occurred equally in men and women (100 men [49%] and 103 [51%] women) and predominantly among heterosexuals (162 cases [80%]). Of the noninfectious cases, 120 (59%) individuals were from countries with a recognized high prevalence of syphilis (Eastern Europe and Sub-Saharan Africa). Forty (19.7%) of the noninfectious cases were codiagnosed with HIV-1 infection.

Fig. 1
Fig. 1:
All cases of syphilis at St. James’s Hospital, January 1991 to June 2003. *Figures relate to the first 6 months of 2003.

The subsequent results relate exclusively to infectious syphilis (reinfections and reactivations were excluded from this analysis).


According to the case definition, there were 133 cases of primary syphilis (37%), 118 cases of secondary syphilis (33%), and 105 cases of early latent infection (29%).

Three hundred twenty-nine men and 27 women were diagnosed with infectious syphilis (male:female 12.2:1; P < 0.001). These individuals reported their sexuality as homosexual in 269 cases (males = 269), bisexual in 32 cases (males = 32), and heterosexual in 55 cases (males = 28; females = 27; 1:1) (Fig. 2).

Fig. 2
Fig. 2:
Cases of syphilis in heterosexuals and men who have sex with men, St. James’s Hospital, January 2000 through June 2003.

A diagnosis of infectious syphilis occurred at a mean age of 35 years (primary 34 years; secondary 36 years; early-latent 35 years). The mean age at diagnosis was 35 years in men (heterosexual 33 years and MSM 35 years; P = not significant) and 30 years in women (P = 0.008) (Fig. 3). The mean age of those with HIV-1 and infectious syphilis coinfection was 37 years (both for those with known HIV infection and those with newly diagnosed HIV-1 infection).

Fig. 3
Fig. 3:
Number of cases of infectious syphilis by age and sex, St. James’s Hospital, January 2000 through June 2003.

The crude incidence rates of infectious syphilis in male and female heterosexuals increased over 6-fold between 1998 and 2002; in males, this rose from 0.26 cases per 100,000 in 1998 to 1.59 cases per 100,000 in 2002 and in females from 0.26 cases per 100,000 to 1.72 cases per 100,000. However, the rate of infectious syphilis in 20- to 44-year-old MSM peaked in 2001 at 719 cases per 100,000, more than a 140-fold increase from 1998 (Table 1). This increase occurred maximally in the 30- to 34-year-old age group with a rate of 883 cases per 100,000 in 2001.

Rate of Infectious Syphilis in 20 to 44 Year Olds per 100,000 of the Population*

Two hundred ninety-six (84%) individuals with infectious syphilis were Irish nationals (P < 0.0001). Only 27 (7.5%) individuals came from countries with a recognized high prevalence of disease, ie, Eastern Europe or Sub-Saharan Africa. Three hundred one (90%) MSM were Irish.


Sixty-two cases (62 of 356; 17.4%) of syphilis occurred in HIV-infected individuals. Twenty-six patients were codiagnosed (within 3 months of each other) with HIV and syphilis infection; 36 patients with known HIV infection were diagnosed with syphilis. Seven patients tested positive for HIV-1 infection during a mean follow up of 1 year for syphilis; however, 151 (53%) syphilis cases whose HIV serology was initially negative either declined or did not attend for follow-up HIV serology. Of the 62 patients codiagnosed or coinfected with syphilis, 22 (35%) met the case definition for primary infection, 28 (45%) the case definition for secondary infection, and 12 (19%) the case definition for early-latent disease. Three patients with syphilis and HIV infection were heterosexual (male:female 2:1) from Sub-Saharan Africa. The patients with known HIV infection had been diagnosed HIV-1-positive a mean 5 years previously.

Crude incidence rates for infectious syphilis in known HIV-1-infected MSM increased from 0 per 100,000 between 1996 and 1999 to 2326 per 100,000 in 2000, 7280 per 100,000 in 2001, 1553 per 100,000 in 2002, and 1111 per 100,000 to June 2003. This incidence rate is over 10 times greater in HIV-infected versus noninfected MSM. Codiagnosis of HIV and syphilis has impacted on the incidence of HIV infection among MSM attending the department. Thirty-three cases presented with infectious syphilis, and asymptomatic HIV infection was diagnosed through routine serologic testing. Eighteen of these individuals (54.5%) had a negative HIV serology within the previous 12 months. Two percent (1 of 51) of the department’s HIV diagnoses in 2000 were codiagnosed with syphilis and HIV; 26% (16 codiagnosed with HIV and syphilis of 61 MSM diagnosed with HIV) in 2001, 29% (11 of 38) in 2002, and 23% (5 of 22) for the first 6 months of 2003.

Risk Factors

Three (1%) MSM denied either unprotected oral or anal intercourse; 270 (90%) reported unprotected oral intercourse and 123 (41%) reported unprotected anal intercourse. Similar percentages of MSM with known HIV infection reported high-risk sexual behavior (32 of 36 [89%] and 13 of 36 [36%], respectively). Thirty-two (58%) heterosexuals reported unprotected vaginal sex and 26 (47%) admitted to unprotected oral sex. The mean number of sexual partners in the previous year in MSM was over 10 times that of heterosexuals (Table 2).

Numbers of Sexual Partners in Patients With Syphilis

MSM, compared with heterosexuals, commonly used drugs in relation to sexual activity (P < 0.001; alcohol 246 [82%]:33 [66%], alkyl nitrites 93 [31%]:0, marijuana 76 [25%]:1 [2%], MDMA [ecstasy] 50 [17%]:1 [2%], cocaine 30 [12%]:0, intravenous heroin 3 [1%]:1 [2%]).

MSM, compared with heterosexuals, commonly met their sexual partners in clubs (127 [59%]:7 [15%]; P < 0.0001), followed by saunas (174 [58%]:0; P < 0.0001). MSM also met their sexual partners through Internet chat rooms (30 [10%]:0; P = 0.004), through friends (33 [11%]:8 [15%]; P = not significant), and in parks (25 [8.3%]:0; P = 0.02). Only 1 individual (MSM) admitted to commercial sex work (CSW); no other MSM or heterosexual admitted to links with CSW (purchaser or provider).

Two hundred seventy-seven (78%) of the infectious syphilis cases had sexual contact only in Ireland in the previous year. Fifty-five cases (15%) reported sexual activity abroad within the previous 3 months. Two heterosexual males and 53 MSM reported sex abroad (P = 0.15). Seven MSM had traveled to, and had sex in, more than one country in the previous 3 months. Sexual exposure was documented in the United Kingdom in 17 cases, Spain in 11, France in 6, other European countries in 8, North America in 7, Asia in 4, Africa in 2, and Australia in 1. Another 24 (8%) of patients had sex abroad within the last year.


Epidemics are described as increases in the number of cases of an illness or disease in excess of normal expectancy. Epidemics could arise from the introduction of a novel pathogen (or strain) to a previously unexposed population. Historically syphilis endemics involved individuals with higher rates of partner change (often CSW) within populations of lower socioeconomic class and low levels of education. 5,6 In the 1980s and early 1990s, after the HIV pandemic, a reduction in all STIs was observed throughout Europe and the United States. This report documents a syphilis epidemic among MSM in Ireland.

No true denominators exist for either the number of MSM or the seroprevalence of HIV among MSM in Ireland. Ireland’s geographic proximity and cultural links to the United Kingdom would predict that similar percentages of MSM live in both countries, ie, 2.6% in the Natsal study. The limitation of this report is that figures for syphilis quoted are from a single center rather than all of Ireland. The denominators for heterosexuals and MSM are for the total Irish population so that the resultant crude incidence rates could be an underestimate of the true extent of the epidemic. However, it is likely that it accurately reflects the epidemic, particularly among MSM and HIV-infected individuals given that the center at St. James’s Hospital diagnosed and treated at least 80% of syphilis cases and newly diagnosed HIV-positive MSM in Ireland between 2000 and 2002. 10,12

The possible negative impact of highly active antiretroviral therapy on sexual behavior, STIs, and subsequently on the incidence of HIV infection raised concerns as early as 1997. Published studies have demonstrated that less than 10% of respondents reported a reduced practice of safer sex with availability of these treatment moieties. 13,14 However, in San Francisco, the percentage of MSM who reported both unprotected anal intercourse and multiple sexual partners increased from 24% in 1994% to 45% in 1999. 15 Furthermore, in 1 U.K. study, there was a significant increase in unprotected anal intercourse between 1996 and 1998 (using 1996 as a baseline, the odds ratio for 1997 was 1.13 [1.03–1.33] and for 1998 it was 1.23 [1.12–1.45]). 16

In the last 4 years, discrete outbreaks of syphilis have occurred in North America, the United Kingdom, and Europe, predominantly among MSM. 6,7 As reported in those outbreaks, this outbreak occurred in MSM with high-risk sexual behavior. Eightyfive percent of cases occurred in MSM with high rates of partner change (median number of partners in previous year was 10 compared with 2 for male heterosexuals and 1 for female heterosexuals), low condom use (10% for oral sex and 59% for anal sex), and frequent use of drugs around the time of sexual activity.

Syphilis and HIV have demonstrated epidemiologic synergy, in which each infection can facilitate the transmission of the other. Symptomatic infectious syphilis disrupts the mucosal surfaces and increases the presence and activation of HIV susceptible cells, whereas HIV replication could be increased in genital ulcerative lesions with amplified viral shedding increasing the risk of HIV and syphilis acquisition to susceptible partners. 1,17 Outbreaks in the United States and Europe have reported rates of syphilis and HIV coinfection between 20% and 73% in MSM. 18 Ireland has a low prevalence of HIV-infected MSM (probably between 3% and 6%) with disproportionate numbers of HIV-infected men infected with syphilis. 19 Crude incidence rates in 2001 per 100,000 were 7280 among HIV-infected MSM compared with 591 cases per 100,000 in non-HIV-infected MSM during the same period. The estimated incidence rates per 100,000 in 2001 during an outbreak of syphilis among MSM in King County, Washington, were 683 among HIV-infected MSM compared with 141 for non-HIV-infected MSM. 20 When compared with these figures, our rates in HIV-infected individuals are alarming because it would suggest that there will be an increase in both the HIV incidence and seroprevalence among MSM in Ireland. This Irish syphilis outbreak has already had an obvious impact on HIV incidence with 29% of MSM HIV diagnoses in 2002 being codiagnosed with infective syphilis.

The syphilis epidemic in Ireland appears to be now in a declining phase (2003) having gone through a growth phase (2000) and hyperendemic phase (2001–2002). This is probably accounted for by both intervention measures that have taken place throughout the epidemic and the natural history of such an outbreak (the numbers of susceptible individuals in the population being reduced as a result of prior infection). Intervention measures such as media campaigns, community education to improve uptake of testing, contact tracing, outreach work by peer workers, and serologic syphilis screening in venues where MSM met their sexual partners contributed to active case finding and ascertainment and could have increased the incidence rates in 2001 and 2002. Continued vigilance and ongoing diseases surveillance is essential because recrudescence to a hyperendemic phase could occur as immunity to syphilis wanes in this population. Furthermore, the refusal of many MSM (53%) to undergo follow-up HIV serology signifies that cases of seroconversion secondary to syphilis could have gone unnoticed. Therefore, active HIV surveillance for links to this syphilis population should be maintained to monitor the potential long-term impact of this serious STI on HIV seroprevalence and incidence in Ireland.


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