LGV in the UKLGV in the UKnational surveillance of a national surveillance of a

re-emerging diseasere-emerging disease

Helen WardHelen Ward1,21,2, Iona Martin, Iona Martin11, Ian Simms, Ian Simms11, , Neil MacdonaldNeil Macdonald11, Sarah Alexander, Sarah Alexander11, Kevin , Kevin

FentonFenton1,31,3, Cathy Ison, Cathy Ison11..

1. Health Protection Agency Centre for Infections, London, UK2. Department of Infectious Disease Epidemiology, Imperial College London, UK3. Centres for Disease Control, Atlanta, USA

BackgroundBackground 2003: 2003: First case report of LGV in the NetherlandsFirst case report of LGV in the Netherlands11

2004: 2004: Clusters reported from Netherlands, Belgium, Germany Clusters reported from Netherlands, Belgium, Germany 2-32-3

May 2004:May 2004: ESSTI (European network for the Surveillance of ESSTI (European network for the Surveillance of STI) meeting collated reports of LGV STI) meeting collated reports of LGV

2005: 2005: Further reports from France, Spain, Sweden, Germany, Further reports from France, Spain, Sweden, Germany, USA, Canada USA, Canada 4-74-7

1. Sex transm inf 2003;79(6):453-5; 2. Clin Inf Dis 2004;39(7):996-10033. MMWR 2004;53(42):985-84. Sex transm inf 2005;81(1):91-2

5. Emerg Infect Dis 2005;1103.046. Eurosurv Weekly 2005;10(5)7. CMAJ 2005;21;172(13):1674-6.

Characteristics of emerging LGVCharacteristics of emerging LGV

CasesCases Men who have sex with menMen who have sex with men High level of co-infection with HIVHigh level of co-infection with HIV ProctitisProctitis

ClustersClusters Links between European countriesLinks between European countries Parties, internet, sex on premises venuesParties, internet, sex on premises venues

Background in the UKBackground in the UK LGV rarely diagnosed in the UK pre-2004LGV rarely diagnosed in the UK pre-2004 Sporadic imported cases of urogenital LGVSporadic imported cases of urogenital LGV Reported together with chancroid and DonavonosisReported together with chancroid and Donavonosis

*Routine aggregate reporting of STI from genitourinary medicine clinics in the UK

Chancroid, LGV and Donovanosis KC60*

0

20

40

60

80

100

1999 2000 2001 2002 2003 2004

Males

Females

Establishing a surveillance systemEstablishing a surveillance system

Diagnostic capacityDiagnostic capacity Enhanced surveillance based on case Enhanced surveillance based on case

reportsreports Alert clinicians and microbiologistsAlert clinicians and microbiologists Alert community groupsAlert community groups

Internet informationInternet information

Referral of specimens for confirmation of LGV

“STBRL will accept rectal specimens from patients with proctitis

or urethral swabs from patients with inguinal

lymphadenopathy Urethral or rectal specimens from LGV

contacts

who have a confirmed positive CT result (using NAAT, or EIA)”

Testing algorithmTesting algorithm

Confirm presence of CT

Determine if LGV associated

Report issued

pos neg

Report issued

Genotype retrospectively for L1, L2 or L3

LGV pos

RT PCR for CT

RT PCR LGV specific

ReportingReporting

LGV confirmed by STBRL

STI section informed

Case report formsent to clinician

Basic data entered

Case report received

Linked lab and Clinical data

UK LGV Surveillance formUK LGV Surveillance form

Please return form to: Neil Macdonald, HPA HIV & Sexually Transmitted Infrections Department,61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 7546. Email: neil.macdonald@hpa.org.uk

Fax: 0208 200 7868

Please return form to: Neil Macdonald, HPA HIV & Sexually Transmitted Infrections Department,61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 7546. Email: neil.macdonald@hpa.org.uk

Fax: 0208 200 7868

LGV Enhanced Surveillance Report Form HPA:LGV6

Health Protection Agency - Centre for InfectionsTo be completed for confirmed cases of Lymphogranuloma Venereum diagnosed in the United Kingdom

Reporting clinic

Patient clinic number

Reported by

Date

CONFIDENTIAL

1. Sex Male Female

2. Date of birth (dd/mm/yy)

3. Postcode of residence(minus last digit)

4. Ethnicity

WhiteBritish Irish other

Black or black BritishCaribbean African other

Asian or Asian BritishIndian

Bangladeshi

Pakistani

other

Chinese

Other/mixed - specify

Unknown

5. Sexuality Homosexual

Bisexual

Heterosexual

Unknown

6. Date of onset of LGV symptoms

(dd/mm/yy)

7. Date of 1st presentation at the clinic for thisepisode

(dd/mm/yy)

8. Reason(s) for attendingSymptoms

Contact tracing

Routine STI screen

Referral

Unknown

Other - specify

9. Proctitis symptoms - tick all that apply

No proctitis

Rectal pain

Tenesmus

Rectal discharge

Bloody stools

Constipation

Other - specify

10. Genital symptoms - tick all that apply

No genital symptoms

Abcess/Ulcers

Swollen lymphnodes

Painful lymph nodes

Pain on urinating

Discharge(penile/vaginal)

Other - specify

11. Systemic symptoms - tick all that apply

No systemicsymptoms

Fever

Muscular pain

Weight loss

General malaise

Other - specify

12. Antibiotic treatment

Doxycyline

Dose (mg) Course (days)

Azithromycin

Erythromicin

Other - specify

Not treated

13. Had the patient seen the THT leaflet on LGVbefore the 1st presentation ?

Yes No unknown

Please return form to: Neil Macdonald, HPA HIV & Sexually Transmitted Infrections Department,61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 7546. Email: neil.macdonald@hpa.org.uk

Fax: 0208 200 7868

Please return form to: Neil Macdonald, HPA HIV & Sexually Transmitted Infrections Department,61 Colindale Avenue, London NW9 5EQ Tel: 020 8327 7546. Email: neil.macdonald@hpa.org.uk

Fax: 0208 200 7868

14. Other STI(s) diagnosed at LGV presentationNone

Gonorrhoea

Chlamydia (not LGV)

NSU

Syphilis

Genital warts

Genital herpes

Hepatitis B

Hepatitis C

HIV

Other - specify

15. Was the patient already known HIV positive?Yes

No Go to Q19

Unknown Go to Q19

16. Date of first positiveHIV test mm/yy

17. CD4 count at LGVdiagnosis

cells/mm3

18. Was the patient receiving HAART?Yes No unknown

Treatment since(mm/yy)

19. Was the patient Hepatitis C antibody positive?Yes No Unknown

20. Was the patient Hepatitis C PCR positive?Yes No Unknown

21. Where does the patient think LGV infectionwas probably acquired? - tick all that apply

UK

Elsewhere in Europe

Outside Europe

unknown

Specify if known e.g. City, name of bar/sauna etc.

22. Where did the patient meet new sexualcontacts in the 3 months prior to the onset ofLGV symptoms? - tick all that apply

No new contacts

Bar/club

Backroom

Internet

Sauna

Cruising ground

Internet

Sex party

Other

Unknown

Specify if known

23. Sexual contacts in the 3 months prior to 1stpresentation at the clinic:

Total

UK

Abroad

Untraceable

Traceable

Treated

24. Please indicate if the patient engaged in any of the following in the 3 months prior to the onset ofLGV symptoms:

Receptive anal intercourse

no yes-protected* yes -unprotected unknown

Insertive anal intercourse

Receptive oral sex

Insertive oral sex

Sharing sex toys

Receptive fisting

Insertive fisting

Vaginal intercourse

Other relevant sexual activity

* Protected refers to the use of condoms or other barrier methods.

Please use the space below to report any further information relevant to LGV surveillance

UK LGV Surveillance formUK LGV Surveillance form

LGV Enhanced Surveillance Report Form HPA:LGV6

Health Protection Agency - Centre for InfectionsTo be completed for confirmed cases of Lymphogranuloma Venereum diagnosed in the United Kingdom

Reporting clinic

Patient clinic number

Reported by

Date

CONFIDENTIAL

1. Sex Male Female

2. Date of birth (dd/mm/yy)

3. Postcode of residence(minus last digit)

4. Ethnicity

WhiteBritish Irish other

9. Proctitis symptoms - tick all that apply

No proctitis

Rectal pain

Tenesmus

Rectal discharge

Bloody stools

Constipation

Other - specify

10. Genital symptoms - tick all that apply

Available on www.hpa.org.uk/infections/topics_az/hiv_and_sti/LGV/lgv.htm

UK LGV Surveillance formUK LGV Surveillance form

14. Other STI(s) diagnosed at LGV presentationNone

Gonorrhoea

Chlamydia (not LGV)

NSU

Syphilis

Genital warts

Genital herpes

Hepatitis B

Hepatitis C

HIV

Other - specify

15. Was the patient already known HIV positive?Yes

No Go to Q19

Unknown Go to Q19

16. Date of first positiveHIV test mm/yy

17. CD4 count at LGVdiagnosis

cells/mm3

18. Was the patient receiving HAART?Yes No unknown

21. Where does the patient think LGV infectionwas probably acquired? - tick all that apply

UK

Elsewhere in Europe

Outside Europe

unknown

Specify if known e.g. City, name of bar/sauna etc.

22. Where did the patient meet new sexualcontacts in the 3 months prior to the onset ofLGV symptoms? - tick all that apply

No new contacts

Bar/club

Backroom

Internet

Sauna

Cruising ground

Internet

Sex party

Other

Unknown

Specify if known

23. Sexual contacts in the 3 months prior to 1stpresentation at the clinic:

Total

not CT equiv CT not classified LGV L2 CT D-K

Oct 04 to Mar 06Oct 04 to Mar 061334 samples received1334 samples received

216

327655

101

982

35

Map of 327 LGV casesMap of 327 LGV cases

Country or region N (%)

London 233 (71)

South East - Brighton 42 (13)

- Rest of region 5 (2)

North West 15 (5)

Scotland 11 (3)

South West 6 (2)

East of England 3 (1)

East Midlands 3 (1)

Wales 3 (1)

West Midlands 3 (1)

Yorks and Humberside 2 (1)

North East 1 (0)

Total 327

Map of 327 LGV casesMap of 327 LGV cases

Country or region N (%)

London 233 (71)

South East - Brighton 42 (13)

- Rest of region 5 (2)

North West 15 (5)

Scotland 11 (3)

South West 6 (2)

East of England 3 (1)

East Midlands 3 (1)

Wales 3 (1)

West Midlands 3 (1)

Yorks and Humberside 2 (1)

North East 1 (0)

Total 327

Map of 327 LGV casesMap of 327 LGV cases

Country or region N (%)

London 233 (71)

South East - Brighton 42 (13)

- Rest of region 5 (2)

North West 15 (5)

Scotland 11 (3)

South West 6 (2)

East of England 3 (1)

East Midlands 3 (1)

Wales 3 (1)

West Midlands 3 (1)

Yorks and Humberside 2 (1)

North East 1 (0)

Total 327

Total samples and LGV, Oct 2004 Total samples and LGV, Oct 2004 to Feb 2006to Feb 2006

0

5

10

15

20

25

30

35

40

Oct-04 Nov-04 Dec-04

Jan-05 Feb-05 Mar-05 Apr-05 May-05

Jun-05 Jul-05 Aug-05

Sep-05

Oct-05 Nov-05 Dec-05

Jan-06 Feb-06

case

s L

GV

0

20

40

60

80

100

120

140

160

sam

ple

s

LGV Samples

Epidemic curve for LGV by date of onset of symptoms, Epidemic curve for LGV by date of onset of symptoms, 2003 to end 2005 (n=2772003 to end 2005 (n=277))

0

5

10

15

20

25

30

35

40

1 13 25 37

HIV negative

HIV positive

2003 2004 2005

Co

un

t

2006

Case reportsCase reports

3 cases in heterosexual men3 cases in heterosexual men urethral syndrome urethral syndrome Contacts abroadContacts abroad Excluded from rest of this analysisExcluded from rest of this analysis

277 case reports in MSM277 case reports in MSM White 260 (95%)White 260 (95%) British 194 (70%)British 194 (70%) Age 21 to 65 (median 38)Age 21 to 65 (median 38) 9 men with repeat infection9 men with repeat infection

PresentationPresentation

Symptoms 228 (84%)Symptoms 228 (84%) Contact referral 16Contact referral 16 Clinician referral 10Clinician referral 10 Detected on routine screen 9Detected on routine screen 9 Asymptomatic 8Asymptomatic 8

4 LGV contacts4 LGV contacts 4 during routine STI screen4 during routine STI screen

SymptomsSymptoms

Proctitis 262 (93%)Proctitis 262 (93%) Plus genital symptoms 34Plus genital symptoms 34

Genital symptoms alone 12 (4%)Genital symptoms alone 12 (4%) Duration of symptomsDuration of symptoms

1 day to >18 months (median 12 days)1 day to >18 months (median 12 days)

Presentation – anorectal (n=228)Presentation – anorectal (n=228)

N (%)Rectal discharge 179 (79)

Rectal pain 157 (69)

Rectal bleeding 133 (58)

Tenesmus 65 (29)

Constipation 56 (25)

3 or more local symptoms 116 (50.9)

Systemic symptoms 68 (30)

Presentation - genitalPresentation - genital

Symptoms N=12Genital ulcer 5

Urethral discharge 2

Dysuria 1

Inguinal lymphadenopathy 6

Systemic symptoms 4

SeveritySeverity

16 cases had been investigated by 16 cases had been investigated by gastroenterologistsgastroenterologists Hospital admission documented in fiveHospital admission documented in five Several reports of misdiagnosis including Several reports of misdiagnosis including

Crohn’s and ulcerative colitisCrohn’s and ulcerative colitis11

1. See BMJ 2006;332(7533):99-1001. See BMJ 2006;332(7533):99-100

Co-infectionCo-infection

HIV 214 (76%)HIV 214 (76%) Including 9 newly diagnosed at time of LGVIncluding 9 newly diagnosed at time of LGV 38% diagnosed within previous 2 years38% diagnosed within previous 2 years 45% on ART45% on ART

Hepatitis C 41 (19%)Hepatitis C 41 (19%) Other STI 39%Other STI 39%

Associations with HIVAssociations with HIV

No difference in demographics or sexual No difference in demographics or sexual meeting placesmeeting places

Men with HIV Men with HIV more likely to have PCR positive HCV, more likely to have PCR positive HCV,

p=0.013p=0.013 More likely to report unprotected anal More likely to report unprotected anal

intercourse 77% vs 60%, p=0.031intercourse 77% vs 60%, p=0.031

Sexual behaviourSexual behaviour

Partners in the past 3 monthsPartners in the past 3 months 0 – 200, median 30 – 200, median 3

Unprotected anal intercourseUnprotected anal intercourse 188 receptive188 receptive 139 insertive139 insertive

Fisting reported by 32Fisting reported by 32 Sex toys reported by 15Sex toys reported by 15

But lots of missing data!But lots of missing data!

Sexual networksSexual networks

178 (79%) reported likely acquisition in UK178 (79%) reported likely acquisition in UK 48 (20%) reported partners overseas48 (20%) reported partners overseas

Commonly Netherlands, Spain, and EuropeCommonly Netherlands, Spain, and Europe More contact in Netherlands for early More contact in Netherlands for early

(2004) than later (2005) cases:(2004) than later (2005) cases:

7/40 (17.5%) vs 2/167 (1.2%)7/40 (17.5%) vs 2/167 (1.2%)

OR 17.5, 95%CI 4.48, 88.02OR 17.5, 95%CI 4.48, 88.02

Meeting placesMeeting places

Data were available on meeting places for Data were available on meeting places for 113 men:113 men: 80 (71%) reported sex on premises venues or 80 (71%) reported sex on premises venues or

at sex partiesat sex parties 26 (23%) via the internet26 (23%) via the internet

A few men reported sex work and travel-A few men reported sex work and travel-related workrelated work

SummarySummary

First national picture of LGV in MSMFirst national picture of LGV in MSM Significant burden of infectionSignificant burden of infection

327 cases in 17 months327 cases in 17 months Varied clinical presentation, often severeVaried clinical presentation, often severe Widespread across the UK, mostly local Widespread across the UK, mostly local

transmissiontransmission High level of co-infectionHigh level of co-infection

Underestimate of scale of infectionUnderestimate of scale of infection

Limited diagnostic serviceLimited diagnostic service symptomatic MSM/ contactssymptomatic MSM/ contacts confirmed CTconfirmed CT

Lack of awarenessLack of awareness Clinicians (outside of specialist clinics)Clinicians (outside of specialist clinics) Patients Patients

Is it an outbreak?Is it an outbreak?

Evidence for:Evidence for: geographic clusteringgeographic clustering links to Netherlands in links to Netherlands in

early cases early cases Anecdotal evidence Anecdotal evidence

from cliniciansfrom clinicians common social venues common social venues

with linked sexual with linked sexual networksnetworks

all L2all L2

Evidence against:Evidence against: No baseline dataNo baseline data Increase could be Increase could be

artefact of surveillanceartefact of surveillance Poor prevalence dataPoor prevalence data Same serovar existed Same serovar existed

in MSM in the USA in in MSM in the USA in the 1980sthe 1980s

Has there been a shift in the Has there been a shift in the epidemiology?epidemiology?

Introduced into favourable networks?Introduced into favourable networks? Sero-sorting and unsafe practices?Sero-sorting and unsafe practices? Opportunistic infection?Opportunistic infection?

But likely to overestimate HIV link due to But likely to overestimate HIV link due to selection bias in diagnosisselection bias in diagnosis

ResponseResponse

LGV incident group includingLGV incident group including Public healthPublic health MicrobiologistsMicrobiologists Community groupsCommunity groups CliniciansClinicians Communications/press officerCommunications/press officer

Awareness campaignsAwareness campaigns

Clinicians/ public healthClinicians/ public health Several articles in specialist and general Several articles in specialist and general

journalsjournals Talks at conferencesTalks at conferences Liaison with specialist societiesLiaison with specialist societies

CommunityCommunity Outreach to venuesOutreach to venues Ongoing press campaignOngoing press campaign Banner adverts for websitesBanner adverts for websites

Information for gay menInformation for gay men

Implications for practiceImplications for practice

Public healthPublic health Maintain awarenessMaintain awareness

cliniciansclinicians community organisationscommunity organisations Outreach, press coverageOutreach, press coverage

Case findingCase finding Ongoing exerciseOngoing exercise ? Recommend widespread ? Recommend widespread

screeningscreening

Maintain active Maintain active surveillancesurveillance

Clinical Clinical Alert to possible LGVAlert to possible LGV

STI clinics STI clinics HIV clinicsHIV clinics GastroenterologyGastroenterology Primary carePrimary care

Increase CT testing in Increase CT testing in MSMMSM

SymptomaticSymptomatic ContactsContacts routine?routine?

RecommendationsRecommendations

Extended testing for chlamydia in MSMExtended testing for chlamydia in MSM rectal samples for men with proctitis and others who rectal samples for men with proctitis and others who

may have been exposedmay have been exposed Presumptive treatmentPresumptive treatment

(if unable to confirm LGV)(if unable to confirm LGV) Use three weeks of therapy for rectal chlamydia and Use three weeks of therapy for rectal chlamydia and

proctitis in MSM proctitis in MSM Ensure test of cureEnsure test of cure Active partner notification and follow-upActive partner notification and follow-up Local awareness campaigns Local awareness campaigns

Members of LGV Incident Group Members of LGV Incident Group

HPA Centre for InfectionsHPA Centre for Infections Sarika Desai Sarika Desai Josephine RuwendeJosephine Ruwende Alan Smith Alan Smith Maria SolomouMaria Solomou Ucheoma Ugoji Ucheoma Ugoji

Terence Higgins TrustTerence Higgins Trust Will NutlandWill Nutland

BASHHBASHH Sandy McMillanSandy McMillan Pat MundayPat Munday

Society for Sexual Health AdvisorsSociety for Sexual Health Advisors Jamie HardyJamie Hardy

National representativesNational representatives Lesley Wallace (Scotland)Lesley Wallace (Scotland) Mary Cronin (Eire)Mary Cronin (Eire) Neil Irvine (Northern Ireland)Neil Irvine (Northern Ireland) Daniel Thomas (Wales)Daniel Thomas (Wales)

Local representativesLocal representatives Peter Trail (London)Peter Trail (London) Helen Maguire (London)Helen Maguire (London) Patrick French (London)Patrick French (London) Stephen Gillespie (London)Stephen Gillespie (London) John White (London)John White (London) Andy Winter (Glasgow) Andy Winter (Glasgow) Gillian Dean (Brighton)Gillian Dean (Brighton)