Gill Bell

A prospective social and molecular investigation of gonococcal transmission

BACKGROUND Gonorrhoea is a common infectious disease, poorly controlled despite effective treatments. Tracing chains of transmission is difficult, because sexual partners are commonly difficult or impossible to identify. We assess the use of gonococcal opa-typing in identifying transmission links not revealed through interview. METHODS Epidemiological data and gonococcal isolates were collected prospectively from patients at two UK clinics in London and Sheffield. Social and epidemiological data were combined with molecular typing of gonococcal isolates by a new methodology based on the polymorphisms of the opa gene. FINDINGS In London, interview data and opa-typing on samples from 215 cases showed a diverse population with few links. In Sheffield, interview data identified links between 51 (43%) of 120 cases, whereas opa-typing suggested a more connected population: 95 (79%) of cases had shared profiles. There was a highly significant correlation between the two distributions with epidemiological clusters appearing as a subset of the opa clusters. Two large opa clusters, of 18 and 43 cases, accounted for 50% of local cases of gonorrhoea. Discordance between epidemiological and opa-typing data was observed at highly connected points in the sexual network. INTERPRETATION Opa-typing is a more powerful tool for epidemiological investigation of gonorrhoea transmission than earlier methods. Opa-typing can link infections that would otherwise remain unlinked, and may aid interventions to control endemic disease.

Sexual partner networks in the transmission of sexually transmitted diseases. An analysis of gonorrhea cases in Sheffield, UK.

Background and Objectives: Routine contact tracing data on patients with gonorrhea are used to identify sexual partner networks. These are combined with gonococcal typing data to study patterns of transmission. The role of persons in transmission is discussed. Study Design: Contact tracing data on patients with gonorrhea attending the Royal Hallamshire Hospital in Sheffield in 1988 and 1989 are analyzed. Gonococcal strains identified by auxotype/serovar (A/S) class are combined with these data to identify transmission paths. Results: The network contained 1,272 persons, 724 (77%) of whom had gonorrhea during the study period. Four hundred two clusters of linked cases were identified. The largest cluster, containing 35 persons connected over 16 months, is discussed in greater detail to illustrate how these data may help identify patterns of transmission and the role of persons. Conclusion: Contact tracing data can be used to identify sexual partner networks and to study transmission patterns. Microbiologic data can aid interpretation. An persons risk of acquiring infection depends on indirect links as well as direct links. To understand patterns of transmission it may be important to distinguish between those involved in transmission and those only acquiring infection. Networks established through gonococcal transmission are also relevant to the transmission of other sexually transmitted diseases.

Costs and cost effectiveness of different strategies for chlamydia screening and partner notification: an economic and mathematical modelling study

Objectives To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. Design An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. Setting England. Population Individuals eligible for the National Chlamydia Screening Programme. Main outcome measures Cost effectiveness of National Chlamydia Screening Programme in 2008–9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions—(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. Results In 2008–9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. Conclusions In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely to cost less than increasing male coverage but also improve the ratio of women to men diagnosed. Further evaluation of the cost effectiveness of partner notification and screening is urgently needed. The spreadsheet tool developed in this study can be easily modified for use in other settings to evaluate chlamydia control programmes.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling

BACKGROUND Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification. OBJECTIVE To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs). DESIGN Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness. SETTING General population and genitourinary medicine clinic attenders. PARTICIPANTS Heterosexual women and men. INTERVENTIONS Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT). MAIN OUTCOME MEASURES Population prevalence; index case reinfection; and partners treated per index case. RESULTS Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, >10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage. CONCLUSIONS There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Concordance between Neisseria gonorrhoeae genotypes recovered from known sexual contacts.

ABSTRACT Neisseria gonorrhoeae multiantigen sequence typing (NG-MAST) is a highly discriminatory molecular typing procedure that provides precise and unambiguous strain characterization. Since molecular typing can complement contact tracing for reconstructing gonorrhea sexual networks, the concordance between the NG-MAST genotypes of pairs of N. gonorrhoeae isolates from recent sexual contacts was examined. Among 72 pairs of gonococci from recent sexual contacts, the genotypes of each pair were concordant in 65 cases (90.3%). In two further pairs, the isolates from sexual contacts differed by only a single nonsynonymous substitution in the porin gene, and in both of these pairs, the isolates were the same by opa typing. The other five nonconcordant pairs of isolates were clearly different strains. opa typing data were available for 51 of the pairs of isolates from sexual contacts, and concordant opa types were obtained in 38 cases (74.5%). NG-MAST should therefore be better than opa typing at identifying recent sexual contacts and has the important advantage over opa typing of being a more precise method of strain characterization.

Partner notification for sexually transmitted infections in the modern world: a practitioner perspective on challenges and opportunities

Our aim is to provide a practitioner perspective on approaches to partner notification (PN)—some old, some new—which may improve the control of sexually transmitted infections (STIs), including HIV, in a variety of settings. PN services support patients with STI/HIV in the difficult task of informing often unsuspecting partners—past or present—of their possible exposure to an STI and hence the need to seek medical care. It is an essential component of STI management and control, protecting patients from reinfection, partners from long-term tissue damage from untreated infection and the community from onward transmission. Beneficial dimensions include ethics (duty to warn), disease control (case finding) and epidemiology (identifying factors associated with STI transmission).1 Patients may inform partners themselves (patient referral) or supply details for a healthcare worker to notify the partner without disclosing their identity (provider referral). These approaches may be combined whereby a time frame is agreed for patients to inform partners before the healthcare worker notifies those who have not sought care (contract referral). Patient referral is the method used most frequently, partly because most patients prefer to notify their own partners and also because provider referral is not available in some settings.2 3 The stigma attached to STIs/HIV can, however, make informing partners traumatic: Gorbach et al 4 found that up to one third of patients failed to tell all partners because of embarrassment or fears for personal safety or reputation. Least likely to be informed are casual and ex-partners4 5 who may have moved on to infect new partners. Provider referral is therefore an important service to protect patients from adverse consequences and reach partners who would not otherwise be informed, thereby improving disease intervention. The intensity of …

The characterisation of a recent syphilis outbreak in Sheffield, UK and an evaluation of contact tracing as a method of control.

Objective: To explore the factors around and the success of contact-tracing in a recent major outbreak of infectious syphilis in Sheffield, and to evaluate the effectiveness of it, our hitherto standard strategy of control. Method: Retrospective chart review Results: Over a period of 18 months, an outbreak of 21 cases was, on closer inspection, the result of several, discrete “micro” outbreaks in different groups. Two major patterns emerged, a relatively straightforward and more accessible cluster in heterosexual persons (a “spread” network), and more sporadic, “starburst” networks in men who have sex with men. Conclusion: Our traditional method of control, contact-tracing, was seen to be most effective in the spread network in heterosexuals. In the face of an apparent outbreak, clinicians should explore the nature and parameters of their local epidemic and engage a mixture of control methods. These may include, but not excusively so, contact-tracing to interrupt transmission by case-finding and by treatment.

Repeat infection with gonorrhoea in Sheffield, UK: predictable and preventable?

Background Repeat infection with gonorrhoea may contribute significantly to infection persistence and health service workload. The authors investigated whether repeat infection is associated with particular subgroups who may benefit from tailored interventions. Methods Data on gonorrhoea diagnoses between 2004 and 2008 were obtained from Sheffield sexually transmitted infection clinic. Kaplan–Meier survival curves were used to estimate the percentage of patients with repeat diagnoses within a year, and a Cox proportional hazard model was used to investigate associated risk factors. Results Of 1650 patients diagnosed with gonorrhoea, 7.7% (95% CI 6.5% to 9.1%) had a repeat diagnosis within 1 year. Men who have sex with men under 30, teenage heterosexuals, black Caribbeans, people living in deprived areas and those diagnosed in 2004 were most likely to re-present. Of those patients (53%) providing additional behavioural data, repeat diagnosis was more common in those reporting prior history of gonorrhoea, any previous sexually transmitted infection diagnoses, two or more partners in the past 3 months and a high-risk partner in the past year. In an adjusted analysis, repeat diagnosis was independently associated with being a young man who has sex with men, living in a deprived area, a history of gonorrhoea and being diagnosed in 2004 but was most strongly associated with non-completion of behavioural data forms. Conclusions Groups most at risk of repeat infection with gonorrhoea are highly predictable but are disinclined to provide detailed information on their sexual behaviour. Care pathways including targeted and intensive one-to-one risk reduction counselling, effective partner notification and offers of re-testing could deliver considerable public health benefit.

The value of a screen and treat policy for Chlamydia trachomatis in women attending for termination of pregnancy.

We aimed to assess the efficacy of a screen and treat policy for sexually transmitted infections in women requesting termination of pregnancy, with particular reference to Chlamydia trachomatis. A retrospective review of 100 consecutive cases of Chlamydia-positive women between December 1995 and February 1998, was performed. The referral rate to genitourinary medicine (GUM), the subsequent management, contact tracing and treatment of partners were assessed. Ninety-nine women were referred to the GUM department, of whom 72 (71.4%) attended. Eighteen (25%) required further treatment. Seventy-five women identified 89 potentially infected men, of whom 62 (69%) attended for treatment. Identification of positive cases with referral to GUM enabled tests of cure to be carried out, treatment of those reinfected and re-enforcement of behaviour modification, in addition to successful contact tracing. This policy may confer greater benefit for the patient herself and make a significant impact on the reservoir of infection in the community when compared to a policy of blanket prophylactic antibiotic treatment at the time of termination. The implications for future service provision are discussed.

An effective strategy to diagnose HIV infection: findings from a national audit of HIV partner notification outcomes in sexual health and infectious disease clinics in the UK.

Objectives Partner notification (PN) is a key public health intervention in the control of STIs. Data regarding its clinical effectiveness in the context of HIV are lacking. We sought to audit HIV PN outcomes across the UK. Methods All UK sexual health and HIV services were invited to participate. Clinical audit consisted of retrospective case-note review for up to 40 individuals diagnosed with HIV per site during 2011 (index cases) and a review of PN outcomes for up to five contacts elicited by PN per index case. Results 169/221 (76%) clinical services participated (93% sexual health/HIV services, 7% infectious diseases/HIV units). Most (97%) delivered PN for HIV. Data were received regarding 2964 index cases (67% male; 50% heterosexual, 52% white). PN was attempted for 88% of index cases, and outcomes for 3211 contacts were audited (from an estimated total of 6400): 519 (16%) were found not to be at risk of undiagnosed HIV infection, 1399 (44%) were informed of their risk and had an HIV test, 310 (10%) were informed of the risk but not known to have tested and 983 (30%) were not informed of their risk of HIV infection. Of 1399 contacts tested through PN, 293 (21%) were newly diagnosed with HIV infection. Regular partners were most likely to test positive (p<0.001). Conclusions HIV PN is a highly effective diagnostic strategy. Non-completion of PN thus represents a missed opportunity to diagnose HIV in at-risk populations. Vigorous efforts should be made to pursue PN to identify people living with, and at risk of, HIV infection.