The public health response to increasing syphilis trends in Europe

The public health response to increasing
syphilis trends in Europe
Otilia Mårdh, Gianfranco Spiteri, Aitana Morano-Vazquez, Andrew Amato
ECDC
IUSTI 2019, Tallinn
S18 - ECDC Symposium: Responding to two of the main STI threats of our time: syphilis and antimicrobial resistant
Neisseria gonorrhoeae

Background
• Since 2010, substantial increases in syphilis notifications
rates in EU, mainly MSM;
• Increasing trends and outbreaks also in other high-income
countries (e.g. US, Japan, Canada, Australia)
• September 2018 – request of Member States to ECDC
(update on epidemiology, options for response)
• July 2019 – ECDC technical report
2

Methods
Update on syphilis
epidemiology
Non-systematic literature
review *
2007-2018
PubMed, Embase, Scopus
Identify trends, describe recent
outbreaks,
identify drivers of syphilis
epidemic
Surveillance data analysis
2007-2017
ECDC TESSy
Member States survey
2019
Changes in surveillance,
recent data
3
*EU/EEA, EU candidate countries, high-income countries (Australia, Canada, Japan, New Zealand and the USA)
Options for response
Systematic literature review*
2007-2018
PubMed, Embase, Scopus,
Cochrane, Google-, hand-
searches
Member States survey
2019
Models of practice
Collect the evidence-base and
formulate options for response
Source: ECDC Syphilis and congenital syphilis in Europe - A review of epidemiological trends (2007–2018) and options for response. 2019
Objectives Outcomes

Syphilis epidemiology, 2007-2018
EU/EEA and high income countries
4

Syphilis EU/EEA, 2007-2017
5
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Men
Total
Women
*not from Liechtenstein
Rates of syphilis infections per 100,000 population by year of
notification, EU/EEA countries
Note: includes reports from countries with comprehensive surveillance systems and consistent reporting over the period:
Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, Germany, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.
Source: ECDC Surveillance Atlas https://atlas.ecdc.europa.eu/public/index.aspx
• 260,505 syphilis cases, 30/31
Member States*
• EU/EEA rate from 4.6 in 2007 to
7.1 in 2017

• 260,505 syphilis cases, 30/31
Member States*
• EU/EEA rate from 4.6 in 2007 to
7.1 in 2017
• M:F 3 in 2007 to 8.5 in 2017
6
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Men
Total
Women
*not from Liechtenstein
Rates of syphilis infections per 100,000 population by year of
notification, EU/EEA countries
Note: includes reports from countries with comprehensive surveillance systems and consistent reporting over the period:
Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Finland, Germany, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.

0
2000
4000
6000
8000
10000
12000
14000
16000
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Numberofcases
MSM
Heterosexual men
Women
7
Number of syphilis infections by route of transmission*
Note: includes reports from Cyprus, the Czech Republic, Denmark, France, Germany, Iceland, Ireland, Latvia, Lithuania, Malta, the
Netherlands, Norway, Romania, Slovenia, Sweden and the United Kingdom.
*Reported for 152,233 (58%) cases
Overall, 2007-2017
MSM 62% 94,015
Heterosexual men 23% 35,633
Women 15% 22,242

Syphilis EU/EEA, 2014- 2017
2014 2015 2016 2017
Women 2.6% 2.1% 3.1% 1.8%
Heterosexual men 12% 12% 10% 10%
MSM 45% 44% 41% 39%
8
HIV co-infection
*includes 39,340 cases with known HIV status reported as MSM, heterosexual men
and heterosexual women between 2014-2017.
Percentage HIV-positive syphilis cases*
0
1000
2000
3000
4000
5000
6000
2014 2015 2016 2017
Numberofcases
MSM HIV-
MSM HIV+
Number of syphilis infections by HIV-status among MSM

9
0%
10%
20%
30%
40%
50%
60%
Women (n=3,986) Heterosexual men
(n=6,136)
MSM (n=24,278)
Percentage
Primary
Secondary
Early latent
Late latent
Latent (unknown duration)
Stage of syphilis infection at diagnosis
Note: includes reports from the Czech Republic, France, Hungary,
Iceland, Ireland, Latvia, Lithuania, Luxembourg, Malta, the
Netherlands, Norway, Portugal, Romania, Slovakia, Slovenia,
Sweden, the United Kingdom
• Most cases reported as early latent infection
• 49% of women as early latent infections
• Primary stage: 35% MSM, 31% MSW, 15%
WSM

10
Literature review on syphilis epidemiology
Studies reporting increasing trends and outbreaks by country and year of publication
Note: search conducted in PubMed, Embase, Scopus 2007-2018; studies
from the EU/EEA, EU candidate countries, high-income countries:
Australia, Canada, Japan, New Zealand and the USA. Five studies with
multi-country coverage not represented.
Trends Outbreaks
Australia 3 3
Canada 3 2
Switzerland 1
Czech Republic 1
Germany 2
Spain 7
Finland 1
France 2
Greece 1 2
Ireland 1
Japan 1
Netherlands 1 1
New Zeeland 3
Poland 1
Portugal 1
Romania 2
Serbia 1
UK 8 13
USA 20 7
Total 59 29
• 19 countries, 14 European

11
Literature review on syphilis epidemiology
Studies reporting increasing trends/outbreaks by risk group, country and year of publication
Note: search conducted in PubMed, Embase, Scopus 2007-2018; studies from the
EU/EEA, EU candidate countries, high-income countries: Australia, Canada, Japan,
New Zealand and the USA.
* Other includes: sex workers, military, blood donors, prisoners, PWID
Heterosexuals
HIV-positive
Migrants
MSM,bisexuals
Other*
Pregnantwomen
Albania 2
Belgium 1
Canada 2 1
France 1 1
Germany 2 2
Greece 1
Ireland 1
Italy 1 1 2
Poland 2 2
Romania 1
Serbia 1
Spain 3 2 2 1
Sweden 1
Switzerland 2 1
Netherlands 2
UK 1 3
USA 6 8 7 4 3
Total 6 21 5 17 13 8
• 68 studies, 17 countries

Factors driving syphilis increases in EU/EEA and high income
countries, 2007-2018, literature review results
• high rates of condomless sex
• increased number of sex partners (HIV-
negative MSM)
• serosorting (HIV-positive MSM)
• impact of PrEP for HIV
• use of social networking sites or mobile
device application
12
• condomless sex
• multiple sex partners
• substance use (drug or alcohol)
• young age
• history of incarceration
• sex work
• previous STI
• social vulnerabilities (e.g. poverty,
homelessness, ethnic minority, migrant or
refugee status)
MSM Heterosexual men and women

Katsushika Hokusai. The Great Wave off Kanagawa
Options for response
How can we turn the tide?
13
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017

14
0
2
4
6
8
10
12
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018
No.ofstudies
Year of publication
Biomedical interventions
Interventions using social media
Education
Partner notification
Outreach venues testing
Screening
Screening
Outreachvenuestesting
Partnernotification
Education
Socialmedia
Biomedical
Australia 5 3 1
France 1
Ireland 1
Netherlands 1
New Zeeland 1
UK 1 4 1
USA 8 1 6 11 4 1
Total 15 5 6 15 6 3
Systematic literature review on response interventions
Studies reporting single interventions with a documented impact among adult populations
Note: search conducted in PubMed, Embase,
Scopus, CDSR, Google, hand searches; studies from
the EU/EEA, EU candidate countries, high-income
countries: Australia, Canada, Japan, New Zealand
and the USA. Nine other studies reporting
multiple interventions for outbreak response
summarised in the report.
• 50 studies, 7 countries

Public health responses to increases in syphilis should aim to identify and treat
syphilis cases and prevent new infections.
Combining,
15
Case finding
Screening/testing
Partner notification and
management
Surveillance
Case management
Appropriate treatment
Risk reduction counseling
Education
General population
Populations at higher risk
Healthcare providers





1. Enhanced screening of populations at risk
Testing of other risk groups e.g. ethnic minorities, marginalised populations, sex workers, PWID - to be
informed by local epidemiology
16
Population Intervention Outcome
HIV-positive MSM Include syphilis testing in routine HIV
clinical monitoring, 3- or 6-monthly, opt-
out vs risk based Increase detection of
early/asymptomatic syphilis
infections
HIV-negative MSM
• with high no. of sex partners
• PrEP users
• with prior syphilis diagnosis
Quarterly testing vs. bi-annual or
symptom based
STI clinics attendees Routine testing as per clinical guidelines Increase detection of syphilis
infections
Reminders for clinicians (system
generated alerts) to include syphilis in
routine STI testing
Optimise screening rates and
increase testing frequency
Reminders for patients (e.g. SMS text,
telephone) to get screened or rescreened

2. Expanded testing in outreach venues
• Important to ensure links to healthcare services for the verification of positive screening tests,
reporting, treatment, and follow-up.
• Important to involve community organisations!
17
MSM (especially during outbreaks) Outreach testing
Increase syphilis detection among
individuals at risk that do not
regularly attend traditional healthcare
settings
Populations with inadequate access
to healthcare (e.g. ethnic minority
or marginalised populations)
Outreach testing
ECDC & EMCDDA guidance, 2018 - STI testing in prison settings recommended based on risk profile,
age-based and/or universal testing approaches

3. Partner management services
18
Settings that do not usually
provide partner services (e.g.
community based clinics)
Settings with high number of
syphilis cases
Placing staff trained in partner
management
OR
improving skills of existing staff
Improve performance of partner
identification and management
Setting quality standards and indicators
(e.g. no. of partners elicited/index patients,
no. of partners tested/index patients, no. of
partners treated)
Measure performance of partner
services
Using alternative tools for notifying and
locating contacts (e.g. internet-locating
information, online tools, smartphone
applications, Facebook)
Improve performance of partner
identification and management
Detailed technical guidelines: European guidelines for management of partners of persons with STI,
IUSTI; 2014 European Guideline on the Management of Syphilis

Populations at high risk Educational, health-promotion
and awareness-raising activities Improve knowledge of syphilis,
recognition of symptoms,
increase testing uptakeAdolescents, young adults and
MSM
Social media platforms (e.g.
Facebook, Twitter, YouTube,
Instagram and dating apps)
Healthcare providers Education to maintain a suitable
level of knowledge and
awareness
Facilitate early recognition of
symptoms and atypical
presentations
Increase syphilis testing and
case detection
4. Education, health-promotion, awareness-raising
19
Important! Evaluation of education campaigns outcomes is recommended due to
mixed impact reported.
Check Yourself: A Social Marketing Campaign to Increase
Syphilis Screening in Los Angeles County 2007-2009

Use of social media
20
To improve knowledge on syphilis and increase access to
testing.
As alternatives to traditional patient care pathways and
partner services.

Biomedical interventions
More evidence is needed on the long-term consequences of this strategy for syphilis and other
infections before considering widespread implementation.
21
High-risk HIV-positive MSM (with ≥ 2
syphilis episodes since HIV diagnosis)
Bolan et al. 2015 US
Daily doxycycline (100 mg) vs
contingency management, 48 weeks
Reduction in STI incidence (OR = 0.27,
95% CI 0.09-0.83, p = 0.02) at week
48 for doxycycline group. Reduction in
syphilis (2 vs 6 cases).
High risk HIV-negative MSM under PrEP
Molina et al. 2018 France
Post-exposure doxycycline (200 mg,
single dose, oral) <24 h after
condomless sex (anal or oral), 10
months
Syphilis occurrence significantly
reduced in intervention group (HR
0.27; 95% CI 0.07-0.98, p=0.047).
More GI adverse events in intervention
group (53% vs 41%, p=0.05).

Interventions reported by 13/28 Member States -
2019 survey
• Implementation of a national STI strategy (stand-alone strategy or
integrated in sexual health or HIV/STI strategy), will ensure
commitment of stakeholders and resources.
• Development of national syphilis action plans and enhanced
surveillance activities.
• Sexual education in schools, shifting from an HIV focus to HIV and
STI.
• Increasing number of ‘checkpoints’ for low-threshold testing in
major cities, mostly targeting MSM.
• Communication on increases in syphilis infections in epidemiological
bulletins.
22
ECDC report published on 4 Sept 2019

Congenital syphilis, EU/EEA, 2007–2017
23
0
5
10
15
20
25
30
0
0.5
1
1.5
2
2.5
3
3.5
2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017
Numberofcountries
Numberofcasesper100000livebirths
Year
Countries reporting zero cases Countries reporting cases
Congenital syphilis rate
Sources: Bulgaria, Cyprus, the Czech Republic, Denmark, Estonia, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania,
Luxembourg, Malta, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden and the United Kingdom
Congenital syphilis levels in the
EU/EEA have been consistently
low.
To sustain these low rates:
• effective national antenatal
screening programmes
• interventions to control
syphilis transmission among
heterosexual populations.

24
“Categories of interventions have not changed much since Parran
described his approach to identifying, treating, and preventing
cases in the 1930s, but the specifics of how they are done will vary
depending on the goal, who is targeted, and opportunities.”
Peterman T. & Cha S. Context-Appropriate Interventions to Prevent Syphilis.
A Narrative Review. STD. 2018
The Battle Against Syphilis; Dr. Parran's "Shadow on
the Land" The New York Times Archives
What is new?

Acknowledgements
External reviewers of draft ECDC report: Raj Patel (IUSTI Europe), Magnus
Unemo (Sweden), Ian Simms (UK), Tom Peterman (USA), Melanie Taylor (WHO)
The EU/EEA STI network
ECDC colleagues: Ana-Belen Escriva, Anastasia Pharris, Caroline Daamen
Contact: Otilia.Mardh@ecdc.europa.eu; STIHIVHEP@ecdc.europa.eu
25

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