Dr Claudia Estcourt. Barts and the London School of Medicine and Dentistry THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014

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2 THIRD JOINT CONFERENCE OF BHIVA AND BASHH 2014 Dr Claudia Estcourt Barts and the London School of Medicine and Dentistry 1-4 April 2014, Arena and Convention Centre Liverpool

3 Preventing STI Re-infection Dr Claudia Estcourt Reader in Sexual Health & HIV BASHH/BHIVA Spring Conference, Liverpool 2014

4 Aims: evidence, clinical practice & policy Context for re-infection (consequences, scale, costs, rationale & potential for intervention) Evidence for different interventions / infections Policy and politics (commissioning, NICE, NCSP, standards) Debate 4

5 Plan 1. Scope 2. Context for re-infection 3. Interventions and evidence 4. Policy and politics 5. Your thoughts 5

6 Scope Re-infection: treated index patient re-tests positive for a bacterial STI within 12 weeks of initial Dx/Rx Assume as a result of UPSI with untreated sex partner Patients: heterosexuals- data on MSM limited STIs: C.trachomatis, N gonorrhoeae, T pallidum Predominately developed world health care settings Partner notification/partner services 6

7 Context Majority adverse health consequences bacterial STIs result from re-infection eg reproductive health sequelae in women Eg C trachomatis positivity at next test (UK) 10-15% Associated health care costs HIGH High proportion of STIs are asymptomatic More effective prevention of re-infection could have significant individual and health economic benefits Strategy = partner notification 7

8 Partner notification / contact tracing / partner services.process of contacting the sexual partners of an individual with an STI, including HIV, and advising them that they have been exposed to infection. By this means, people who are at high risk of STI/HIV, many of whom are unaware that they have been exposed, are contacted and encouraged to attend for counselling, testing & other prevention and treatment services (Cowan F et al 1996) Also see CDC, WHO, BASHH 8

9 Partner Notification Two broad aims: 1. Public health level: Breaking chain of onward transmission by incidence disease burden 2. Patient-level: Prevention of re-infection of index prevent complications 9

10 Which partners? Look back: guidance given eg BASHH (bashh.org.uk) on look back period for individual STIs eg 3/12, 6/12 etc We may need to rethink: (Althaus CL et al 2014: value up to 18/12, last 3 partners) Individual level: ongoing regular? sex partners pose greatest risk of re-infection will you have sex with that partner again? Public health gain may be greater for strategies which target casual partners to prevent secondary transmission (Mercer C et al 2011) 10

11 Definitions: PN approaches 1. Patient referral: index informs partner (s) a. Simple: verbal advice b. Enhanced: verbal advice enhanced by eg written information, online PN resources, APT, EPT 2. Provider referral: hcp informs partner (s) 3. Contract / conditional referral: index undertakes to inform partner but if partner fails to attend service within an agreed time frame, hcp will contact him/her directly (Manual for Sexual Health Advisers, Ferreira A et al 2013) 11

12 Definitions: PN methods & tools Expedited partner therapy (ExPT) Patient delivered partner therapy (PDP) Accelerated partner therapy (APT) (Web based / online eg inspot) Epidemiological Rx 12

13 Overview of PN Approaches & Tools APPROACHES TOOLS PARTNER CONSULT Patient referral: Simple (verbal info) Patient referral: Enhanced Provider referral Contract referral Add n verbal Written Info Web PN EPT:PDP APT Yes Yes Yes Yes No Yes

14 EPT: Patient delivered partner therapy Doctor gives index patient antibiotic or prescription to give to their sexual partner(s) ExPT: treating sex partners of persons with curable STIs without req partner to first seek medical evaluation (CDC 2006, Golden, Hogben, Schillinger, Kissinger) 14

15 Accelerated Partner Therapy (APT) Partner notification strategies which reduce time for sex partners to be treated AND include assessment by appropriately qualified health care professional Use telephone or pharmacy-led partner assessments Aimed at minimally / asymptomatic contacts & can include a partner test 15

16 APT Summary Data Estcourt et al 2011 APTHotline APTPharmacy Routine Partners treated 80/135 (59%) 29/44 (66%) 42/117 (36%) Time to treatment (median days) 1 (0-14) 2 (0-6) 3 (0-17) Partner test C.trachomatis & N. gonorrhoeae 29/49 (59%) 6/15 (40%) 12/13 (92%) Partner test HIV & Syphilis 2/49 (4%) 0/15 (0%) 12/13 (92%) Many partners achieved treatment outside the trial. Routine: 69%; Hotline41%; Pharmacy 48% 16

17 APT Conclusions APT models acceptable and feasible PN interventions, compliant with UK prescribing guidance preliminary evidence of effectiveness missed opportunity for HIV & Syphilis test time to treat may be shorter than routine many complex factors influence preference for PN method future work: trial APT in primary care (NIHR funded APTPrimary care) (Estcourt CS et al 2012, Roberts TE et al 2012) 17

18 APTPrimary care Woman tested chlamydia positive Consent obtained by GP/practice nurse Randomised by webtool Std + APTHotline Std + APTPharmacy Standard only Primary outcome: proportion of partners treated Secondary outcomes: time to treatment etc 18

19 Epidemiological treatment Treatment given to (named) contacts of patients after a history of exposure to disease but without confirmatory pathological findings..risk to the patient of unnecessary treatment is outweighed by risk of complications or probability of transmission of infection to other contacts (Carne CA 1997) window period antibiotic resistance 19

20 How to prevent re-infection Adequately treat all exposed ongoing sexpartners before next sex with treated index More effective PN More partners treated (ongoing SI) Faster partner treatment 20

21 How to measure PN effectiveness Index positivity at eg 3/12 (re-infection rate) Time to partner treatment Proportion and type of partners reached Behaviours posing risk of re-infection (eg UPSI) 21

22 Evidence: Key references Strategies for partner notification for sexually transmitted infections, including HIV (Review). Ferreira A, Young T, Mathews C, Zunza M, Low N, 2013 The Cochrane Collaboration Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling. Althaus CL et al. Health Technology Assessment 2014;18:2. DOI /hta18020 Reinfection by untreated partners of people treated for c trachomatis and N gonorrhoeae: mathematical modelling study. Low N, Heijene JCM, Herzog SA, Althaus CL. 2014, Sex Transm Infect Special Issue on re-infection and re-testing Sex Transm Infect Feb 2013, Vol 89 (1) 22

23 Effectiveness of PN (Re-infection) Ferreira A et al aimed to assess effects of different PN strategies in people with STI (inc HIV) RCTs comparing >/= 2 PN strategies Compared each main strategy with simple patient referral & then with each other (if trials available) 26 RCTs, >17,000 participants, 50% women, 5 from LEDCs, 2 in HIV+ Sensitivity analysis excluding trials with >20% attrition 23

24 Key findings: STIs causing cervicitis & urethritis (CT, GC, NGU) EPT better than Simple Pt Referral in preventing index reinfection (6 trials, moderate evidence RR 0.71, 95% CI ) attenuated for CT only and excluding >20% attrition trials o EPT not better than Enhanced Pt Referral in preventing index re-infection (3 trials, low quality evidence RR 0.96, 95% CI ) o Home sampling kits for sex partners (4 trials) did not lead to lower rates of reinfection in index than Simple Pt Referral (1 trial) o No consistent evidence for relative effects of provider/contract or other methods 24

25 Ferreira et al: Conclusions Unable to identify a single optimal strategy for PN for any particular STI / setting Insufficient evidence to determine optimal components of enhanced patient referral strategy Too few trials to draw consistent conclusions about rel effects of different PN strategies for diff STIs 25

26 Effectiveness of PN (Re-infection) Althaus et al aimed to compare effectiveness of different PN approaches to providing testing and treatment to partners of people with curable STIs by Systematic reviews and analysis of secondary data (clinical audit) to obtain outcome estimates Mathematical modelling to estimate impact (CT & GC, heterosexual) Cost-effectiveness 26

27 Key findings: Chlamydia transmission dynamics modeling 1 Static & dynamic models and new models derived new estimates of: Duration of asymptomatic chlamydia in women: 433 days (95% CI ) Heterosexual per partnership transmission probability: 55.5% (IQR ) Heterosexual per sex act transmission probability: 9.5% (IQR ) 27

28 Key findings: Chlamydia transmission dynamics modeling 1 Static & dynamic models and new models derived new estimates of: Duration of asymptomatic chlamydia in women: 433 days (95% CI ) Heterosexual per partnership transmission probability: 55.5% (IQR ) Heterosexual per sex act transmission probability: 9.5% (IQR ) 68% current partners of chlamydia positive indexes infected (baseline prevalence 3%) Look back of 18/12 would identify >10% positivity in notified partners 28

29 Key findings: Chlamydia transmission dynamics modeling 2 Individual-based model Chlamydia screening rates of 0.1% per year, at 5 yrs: prevalence reduced to 70% of baseline If PN factored in, prevalence reduced to 60% of baseline (predominately attributable to Rx of current partner) Individual-based model of chlamydia & gonorrhoea transmission APT, by reducing time to treatment of sex partners, could reduce index reinfection substantially 29

30 Althaus et al: Implications for health care What does this mean for our current look back periods? PN outcomes modest even in GUM Enhanced patient referral via GUM & extend availability to non-specialist setting Limited evidence for MSM Reducing time to Rx: APT needs further investigation in context of RCTs/modelling / health economics 30

31 Effectiveness of PN (Re-infection) Herzog et al aimed to determine the impact of delays in treatment of current partners of people with chlamydia and gonorrhoea on reinfection of index cases Mathematical modeling Without partner Rx, median reinfection probability: chlamydia: 19.4% (IQR %) gonorrhoea 12.5% (IQR %) If partner Rx within 3 days of index: chlamydia 4.2% (IQR ) gonorrhoea: 5.5% ( ) 31

32 Herzog et al: Implications for health care Quicker PN could provide significant benefits in preventing re-infection APT could be useful strategy as data to date suggests faster Rx 32

33 Evidence for web PN Online resources, ecards, SMS, MSM, or not Australia: (letthemknow.org.au) USA: inspot.org (isis-inc.org/inspot.php) UK: GMFA, MSM, UK, (gmfa.org.uk/pn) Rietmeijer CA 2012 Plant A et al 2012 inspotla: high level of use of website but no evidence of program effectiveness for PN in LA MSM Bilardi JE et al

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35 Policy National Institute for Clinical Excellence 2007: assisting patients to get partners tested & treated is essential element irrespective of health care setting appreciation of central role of PN in STI care responsibilities of PCTs in support & training innovative research into most effective methods of PN in UK ( Trelle S et al 2007) 35

36 Service specifications & Standards BASHH/MedFASH 2014 STIMS Sexual Health Service Specifications re PN provision NCSP 36

37 Politics / challenges Measures- how well are we doing? How to measure PN effectiveness? How are we measuring re-infection? Plurality of provision Who is responsible? 37

38 How well are we doing? GUM: median 0.47 partners treated for CT per index & 0.60 partners treated per index similar to RCT data, lwr in London & lwr in MSM outcomes modest (BASHH audits & GUMCAD ) GP: mainly chlamydia & PID. Poor outcomes (Cassell J et al) NCSP: CTAD does not mandate PN outcomes 38

39 How can we measure? GUMCAD V3 PHE Pilot of enhanced risk behaviour and PN data collection (for public health purposes) in addition to routine data reporting Mohammed H et al: analysis to describe the initial findings from behavioural data collection 39

40 Detecting re-infection: Routine chlamydia re-infection screen, NCSP NCSP 2013 recommendation to rescreen all people diagnosed with chlamydia around 12/52 (as part of routine care) Rationale: evidence (10-15% young adults testing positive are also positive at next test) (after a positive test, rate of subsequent positive test is 2-3x higher than in those with initial negative test) Feasibility: consultation (highlighted some unintended consequences), postal / SMS reminders Limited evidence on impact of retesting on incidence or adverse health outcomes eg PID BUT NCSP no longer req data on index Rx & PN (CTAD does not included this) (NCSP Position statement, Evidence summary on re-testing of positive chlamydia cases, 2013) 40

41 Experience with postal re-testing for Chlamydia: feasible but is it acceptable? 1. Elangasinghe M, Bell G, Bowman C. BASHH Bristol, 2013, Sheffield GUM, routine care All pts with chlamydia offered 6/52 TOC 548/633 (87%) eligible for postal (>16, uncomplicated, nonpregnant, ano-genital only) 234/548 (43%) accepted postal initially 155/548 (28%) still happy to receive postal at FU call 95/548 (17%) returned a test 6/548 (1%) positive 41

42 Experience with postal re-testing for Chlamydia: feasible but is it acceptable? 2. Estcourt et al (2014 STD Prevention Conference) London & South East Coast England, within RCT of APTPrimary Care Women diagnosed with chlamydia in primary care All women 6/52 postal re-infection screen, consent at recruitment 19% returned a test 42

43 Postal chlamydia TOC: thoughts Feasible but not very acceptable Low positivity in returned samples? Cost-effective Can it be improved? 43

44 Summary No easy answers Current PN outcomes room for improvement inc in GUM V little MSM data V little infection-specific data but what about partnership-type specific? Postal retesting beguiling but low acceptability to date Faster partner Rx APT RCT Enhanced PN 44

45 Thank you Edom Debebe Lorna Sutcliffe Laura Greaves The APT Primary Care RCT represents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Reference Number RP-PG ). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. 45

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