London School of Hygiene & Tropical Medicine

Collaborations

WHO Collaborating Centre for Sexually Transmitted Infections

LSHTM is one of eight WHO Sexually Transmitted Infection (STI) Collaborating Centres worldwide. The Centre works with the WHO Global HIV, Hepatitis and STIs Programme (HHS), the UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), and a network of international collaborators on activities to improve the prevention, control and management of STIs worldwide.

The key objectives of the Centre are to

1. Support the development, implementation and evaluation of STI diagnostic strategies, including point-of-care tests (POCTs); training; health systems research; laboratory capacity building; and advise on research/validation, test performance, process and impact evaluations.
2. Assist WHO in activities that aim to improve STI prevention and control and sexual and reproductive health (SRH) services in key and vulnerable populations for STIs including HIV (support normative work [e.g. guidelines]; generate evidence to inform policy and programmes including STI prevalence and surveillance, sexual behaviour, SRH service access and use; and training).
3. Provide support to WHO in activities related to elimination of STIs and their sequelae, including cervical cancer, and mother-to-child-transmission of STIs including HIV, hepatitis and syphilis.

Health Protection Research Unit in Blood Borne and Sexually Transmitted Infections

The National Institute for Health Research (NIHR) Health Protection Research Unit in Blood Borne and Sexually Transmitted Infections is led by University College London in partnership with Public Health England and LSHTM. The unit aims to conduct state-of-the-art research to improve the health of the population, and to help develop practical policy guidelines for those working in health protection.

The NIHR HPRU has received almost £3.7 million to undertake collaborative research that addresses the key health protection priorities for the prevention and control of STIs and BBVs, notably understanding risk and risk reduction, reducing the burden of under-diagnosis, and improving care and management of those diagnosed with infections.

There are three research themes

• Theme A: Understanding risk and risk reduction for STIs and BBVs
   
• Theme B: Reducing the burden of undiagnosed STIs and BBVs
   
• Theme C: Improving the care and management of people with STIs and BBVs

LSHTM investigators

Tim Rhodes; Peter Wetherburn

SHIP (Sexual Health Improvement Programme)

The Sexual Health Improvement Programme (SHIP) was set up as a Bristol Health Partners Health Integration Team in 2013. It brings together experts from across disciplines to improve the sexual health of people in the region and reduce STIs, supporting the commissioning of evidence-based sexual health services. Our priorities are: increasing uptake of HIV testing; improving STI testing and responding to antimicrobial resistant (AMR) infections; increasing patient and public involvement in sexual health and ending stigma; ending domestic violence; reducing health inequalities; implementing informatics and digital transformation; developing a national network for sexual health improvement. A major focus for the next three years will be evaluating and developing strategies, including vaccination, for combating the development of antimicrobial resistance (AMR) in STIs.

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LSHTM investigator

Emma Harding-Esch

The Applied Diagnostic Research and Evaluation Unit (ADREU)

The Applied Diagnostic Research and Evaluation Unit (ADREU) based at St George’s, University of London (SGUL) is a proven multi-institutional and multi-disciplinary group including experts in clinical medicine, diagnostic evaluations, epidemiology, public health, social science, basic and translational science. ADREU provides a comprehensive service to facilitate the development and evaluation of rapid diagnostics for STIs, other infectious diseases and antimicrobial resistance for both academic institutions and industry. ADREU offers bespoke diagnostic accuracy evaluations, from proof-of-concept projects to late-stage evaluations, providing data for regulatory approval for our collaborating partners in academia and industry. With close links to Public Health England and LSHTM, ADREU combines real word situations with leading academic insight to evaluate novel commercial technologies, providing feedback on the clinical and social impact that STIs and rapid STI diagnostics can have on all aspects of the healthcare system, from patients to healthcare professionals.

LSHTM investigator

Emma Harding-Esch

Staff-led research projects

safetxt: A randomised controlled trial of an intervention delivered by mobile phone messaging to reduce STI in young people

The NIHR-funded safetxt Trial is a single blind randomised controlled trial to evaluate the effect of a safer sex intervention delivered by text message on chlamydia and gonorrhoea infection at 12 months. The intervention targets partner notification, condom use and getting tested before unprotected sex with a new partner (1).
Over 5900 participants aged 16-24 have been recruited from 50 GU and Sexual and Reproductive Health services across the UK.

Full recruitment is crucial to provide trials with sufficient power to detect intervention effects, yet only 56% of publicly funded trials in the UK achieve their target sample size.

Mixed methods supported by evidence from behavioural science were used to maximise recruitment including meetings with site staff to enable new services to learn from experienced recruiters, monthly newsletters to highlight major achievements, competitions to develop engagement and motivation and certificates for staff who achieve recruitment milestones.

The questionnaire follow-up of participants is closely monitored and is currently 88.2% at 4 weeks and 77.1% at 1 year. The return of test kits at 1 year is 71.8%. Steps taken to improve follow up rates include: simplified test kit instructions, clear postage instructions, and a prize draw entry for participants who return test kits (2).

The safetxt collaboration between 50 GU and Sexual and Reproductive Health services and the trial management team is on target to recruit 6250 participants on time by December 2018. The trial is due to report in 2020.

LSHTM investigators

Caroline Free, Ona McCartney, Rebecca French, Kaye Wellings

References

Free C, McCarthy O, French RS, Wellings K, Michie S, Roberts I, et al. Can text messages increase safer sex behaviours in young people? Intervention development and pilot randomised controlled trial. Health Technol Assess 2016;20(57)
McCarthy O, French RS, Roberts I, Free C. Simple steps to develop trial follow-up procedures. Trials. 2016;17:28. doi:10.1186/s13063-016-1155-1

TracVac: A phase I adjuvant Chlamydia trachomatis vaccine

TracVac builds on the results of a phase I clinical trial (NCT02787109) of an adjuvanted Chlamydia trachomatis vaccine (CTH522; Olsen et al 2015, JID PMID2578320) developed by Statens Serum Institut (SSI), Copenhagen. TracVac (www.trachoma-vaccine.org) is a 4 partner (LSHTM, Imperial College London, Commissariat à l’Energie Atomique et aux Energies Alternatives, Paris and SSI) EU sponsored consortium that will expand the C. trachomatis serotype coverage of CTH522 and investigate the immunization regimen required for the optimal induction of protective responses at mucosal surfaces that include the eye. C. trachomatis infection of the eye causing trachoma remains the leading cause of blindness due to any infection. The immunological routes of C. trachomatis protection and pathogenesis in both the eye and urogenital tract are believed to share common features. There are currently no chlamydial vaccines licenced for human use. We expect that study of trachoma can serve as a useful and translatable model for C. trachomatis vaccine development in addition to the delivery of vaccine that protects against ocular infection. We are using novel Human B cell cloning technologies to select neutralizing and protective epitopes from trachoma ‘resistant’ individuals. We have identified 'resistant' individuals from longitudinal cohort studies. The selected epitopes will be incorporated into the next generation recombinant vaccine. Antibody neutralization and cellular responses to the vaccine constituents are being further tested on a wider scale in longitudinal trachoma cohort studies established LSHTM from The Gambia and Tanzania. By the end of the study we aim to deliver a vaccine that covers both urogenital and ocular C. trachomatis infection for further clinical development in 2020.

LSHTM investigators

Martin Holland; Harry Pickering

iGugu: Prevalence of STIs among young people in South Africa: A nested survey in a health and demographic surveillance site

iGugu means precious, and is short for Ukuvikela impilo yetho yokuzalana eyigugu, Zulu for "protecting our precious reproductive health."

Adolescents and young adults are particularly vulnerable to sexually transmitted infections (STIs). The first strategic direction of the WHO Global Health Sector Strategy on Sexually Transmitted Infections 2016-2021 is to collect information on STI prevalence and incidence across representative populations. There is also evidence that bacterial vaginosis (BV) is a risk factor for poor birth outcomes and STIs including HIV. The collection of BV prevalence may therefore also be important. However, developing new cohorts for dedicated STI/BV prevalence studies may not be realistic, particularly in sub-Saharan Africa, where the impact of STIs/BV and their consequences may be greatest. Therefore, nesting STI/BV surveys within networks of health and demographic surveillance sites (HDSSs) could be an efficient way of providing data to better understand STI epidemiology among adolescents and young people in high HIV prevalence settings.

We carried out a nested STI/BV survey among 1,342 adolescent and young people in an HDSS in KwaZulu-Natal, South Africa, between October 2016 and January 2017. Potential participants were contacted at home and invited to participate. Participants were interviewed, and samples were collected for STI/BV testing.

We showed that this study was feasible within the 3.5-month time period: 1,171/1,342 (87%) individuals had ≥1 attempted home visit, of whom 790 (67%) were successfully contacted (1).

The study was acceptable: among those contacted and eligible, 447/645 (69%) enrolled. Both men and women reported few problems with sample collection. We report a high burden of STIs/BV in this population, particularly of chlamydia (5% in men and 11% in women), herpes simplex virus type 2 (17% in men and 29% in women), and BV (42% in women).

Nested STI/BV surveys in HDSSs can be feasible and acceptable; however, more survey time is needed to ensure that all potential participants are visited and contacted. These studies should be carried out in conjunction with studies to measure STI/BV prevalence in high-risk populations (e.g. female sex workers) to provide robust prevalence estimates.

These data are essential to advocate, fund, plan, implement, and evaluate interventions for STI prevention and control among adolescents and young people. Strategies for the prevention and control of chlamydia, herpes simplex virus type 2, and BV are needed in this population.

LSHTM Investigators

Suzanna Francis; Kathy Baisley

References

Francis SC, Mthiyane TN, Baisley K, Mchunu SL, Ferguson J, Smit T, Gareta D, Dlamini S, Mutevedzi T, Seeley J, Pillay D, McGrath N, Shahmanesh M. Prevalence of Sexually Transmitted Infections among Young People in South Africa: A Nested Survey in a Health and Demographic Surveillance Site. PLOS Medicine, 2018; 15(2):e1002512

Systematic Review: Novel testing technologies, strategies and approaches for testing populations at high risk of STIs in EU/EEA countries

In 2012, the European Centre for Disease Prevention and Control (ECDC) published the technical report “Novel approaches to testing for sexually transmitted infections, including HIV and hepatitis B and C in Europe”. This report was a comprehensive review of testing technologies and strategies across Europe. Almost six years later, there have been a number of developments in the field, and an updated review is required.

We are carrying out a critical appraisal via a systematic literature review of novel STI testing technologies, strategies and approaches for detecting Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, Mycoplasma genitalium, and Trichomonas vaginalis, in at-risk populations. The objectives are to: describe novel (since 2011) STI testing strategies and approaches and determine how they impact on access to testing, testing coverage, and linkage to care; describe what testing technologies are used in these novel strategies and approaches; describe the impact of novel testing technologies, approaches and strategies on reporting to public health surveillance programmes; highlight quality assurance needs and risks; and highlight their feasibility and acceptability. Gaps in knowledge and data availability will also be identified to highlight future research needs.

LSHTM investigators: Emma Harding-Esch; Suzanna Francis

Research degree student projects

Factors associated with sexual behaviour and sexually transmitted infections among adolescents in Comarca Ngäbe-Buglé, Panama

PhD Student: Amanda Gabster

PhD supervisors: Philippe Mayaud and Beniamino Cislaghi

The aim of Amanda’s PhD is to describe the factors that contribute to sexual behaviour and sexually transmitted infections (STI) outcome among adolescents (14-19 years) of the indigenous region called the Comarca Ngäbe-Buglé (CNB), Panama, in collaboration with the Gorgas Memorial Institute for Health Studies in Panama. The PhD employs mixed methods. In the first stage, qualitative methods were used to describe gender norms, other social norms, and parenting styles of adolescent and parents of adolescents of CNB.  Results from this stage informed the study tools for the second stage. In the second stage was a cross-sectional study with two-stage cluster sampling. It was carried out with 700 adolescents to investigate the association of social norms, parenting styles, and sexual behaviours, with STIs. The prevalence of the following STIs and reproductive tract infections were measured: HIV, syphilis, hepatitis B virus, human T-lymphotrophic virus, herpes simplex virus type 2, chlamydia, gonorrhea, high-risk human papillomavirus (women only) and bacterial vaginosis (women only). This study is the first to explore the factors related to adolescent sexual health in CNB. Based on the results of this research, governmental and non-governmental agencies will work towards targeted, culturally competent, sexual health interventions for indigenous adolescents of the Comarca Ngäbe-Buglé. Funding for this project was obtained from Panama's National HIV/STI/Viral Hepatitis Program and support from the Gorgas Memorial Institute for Health Studies.

Inflammation and the vaginal microbiota in Zambian Women with Female Genital Schistosomiasis and their potential role in HIV acquisition

PhD Student: Amy Sturt

PhD Supervisors: Amaya Bustinduy, Emily Webb and Suzanna Francis

The overall aim of Amy’s PhD research is to explore the potential role of female genital schistosomiasis (FGS), sexually transmitted infections (STI), and the vaginal microenvironment in HIV acquisition. Female genital schistosomiasis (FGS) affects over 45 million women worldwide, mostly in sub-Saharan Africa. FGS is caused by an infectious agent, the waterborne parasite Schistosoma haematobium. Genital tract morbidity is caused by inflammation from egg-deposition that leads to mucosal erosion and granulomatous reaction. There is cross-sectional evidence of increased HIV prevalence in S. haematobium infected women. Amy’s research takes place in Livingstone, Zambia where eligible women were recruited from communities within HPTN071 (PopART) that are also endemic for infection with S. haematobium. The vaginal microbiota in FGS have not yet been evaluated and literature evaluating the association of FGS and STI is limited. As non-optimal cervicovaginal microbiota and STI have both previously been associated with HIV acquisition, Amy is evaluating the association between FGS and vaginal dysbiosis or STI (including chlamydia, gonorrhea, trichomoniasis, infections with Mycoplasma genitalium and Herpes simplex virus types 1 and 2). This may provide further evidence to strengthen the understanding of the mechanism of the association of FGS with HIV acquisition. Amy also plans to evaluate HIV incidence rates in women with and without FGS.

The epidemiology of, and risk factors for, oro-genital and anal human papillomavirus infections among sexually active Nigerians: A mixed methods study

PhD Student: Imran Morhason-Bello

PhD Supervisors: Deborah Watson-Jones and Suzanna Francis

Imran’s PhD aims to describe risk factors for genital, oral and anal sexual intercourse, and association of these behaviours with the prevalence of genital, oral and anal human papillomavirus (HPV) infections among different heterosexual populations in Ibadan, Nigeria. The first part of the PhD was a systematic review of reported oral and anal sex among heterosexual adolescents and adults in sub-Saharan Africa. This review informed the mixed methods study which enrolled adolescent girls and young women from the general populations and brothel-based female sex workers (FSW). Stage 1 of the study included formative research to explore the knowledge, socio-cultural interpretations, local terminologies, and personal experiences with different sexual behaviours within the community. Results from this stage informed the tools for Stage 2. Stage 2 was a cross-sectional survey using household sampling of adolescents/young adult females, and brothel sampling of FSWs. During the cross-sectional survey, face-to-face interviews, clinical examination and collection of samples were carried out. A blood sample was collected for HIV testing. Samples from the oral cavity, the genital area (vulva, cervix and penis) and anal canal was collected for HPV DNA genotyping in the laboratory. The research was support by University of Ibadan, Ibadan, Nigeria.

Detecting sexual bridges: rapid genome-mapping of sexually transmitted infections among female sex worker and non sex worker populations in Ecuador

PhD Student: Claire Broad

PhD Supervisors: Phil Cooper (SGUL/LSHTM), Tariq Sadiq (SGUL), Ken Laing (SGUL)

Claire’s PhD is a part of the MRC London Intercollegiate Doctoral Training Partnership (MRC LID) between St George’s University of London (SGUL) and LSHTM. The aim of this project is to estimate the prevalence of sexually transmitted infections (STIs) among female sex workers in Quininde and Las Golondrinas, Ecuador, and to demonstrate a system of surveillance that identifies sexual transmission clusters and potential sexual transmission ‘bridges’ within the general population. In Latin America, like many low- and middle-income countries, control of STIs is limited to syndromic management and there are a lack of reliable testing platforms, lack of knowledge surrounding STIs and unregulated antibiotic usage, e.g. self-medication. In Ecuador, surveillance strategies are limited and rely on disease case reporting of STI syndromes; few laboratory diagnosed STI prevalence data are available for common infections such as chlamydia and gonorrhoea. It is important when implementing public health interventions to understand whether an outbreak in a high risk population, such as female sex workers, will lead to infection ‘bridging’ and affect the wider population. Surveillance systems that incorporate methods such as whole genome sequencing (WGS) can be used to identify strain types, geographical clustering and antimicrobial resistance patterns within a population. WGS enables targeted capture of specific bacterial genomes; however, culture is usually required to provide sufficient pathogenic material and reduce interference from other bacterial or human DNA. For STIs such as chlamydia and infection with Mycoplasma genitalium, culture techniques are specialised, expensive and have varying success rates. Enrichment methods (e.g. using hybridization or ‘bait’ capture, bypassing culture and amplifying bacterial genomes directly from clinical samples) are an attractive resource for field settings and LMICs. The main output from the thesis will be to optimise enrichment and amplification methods to allow direct sequencing from clinical samples which have been collected from sex worker and non-sex worker populations in rural regions of Ecuador.

Epidemiology of sexually transmitted infections (STIs) in a cohort of transgender women in São Paulo, Brazil

DrPH Student: Daniel McCartney

DrPH Supervisor: Philippe Mayaud

Daniel’s DrPH project aims to assess the prevalence and incidence of sexually transmitted infections (STIs) among transgender women in São Paulo, Brazil, including chlamydia, gonorrhoeae, trichomoniasis, Lymphogranuloma venereum (LGV) and infection with Mycoplasma genitalium through laboratory diagnosis of self-collected samples from anorectal, oropharyngeal and neovaginal sites. This project is nested within an ongoing cohort study of transgender women by the Santa Casa de São Paulo School of Medicine, and a preliminary study was conducted to assess the acceptability of providing self-collected samples among a sample of transgender women enrolled in the cohort study.

While recommendations for serologic screening (for HIV, syphilis and hepatitis) and management of confirmed STIs do not differ from those for non-transgender people, specific considerations are required when screening for other STIs, as transgender people differ in hormone use, history of gender-affirming surgical procedures, and patterns of sexual behaviours and practices. Often conflated with men who have sex with men (MSM), transgender women have been underrepresented in epidemiological studies of STIs.

Research findings will have important policy and public health implications in Brazil and internationally for improving STI screening of this often over-looked and underserved population and inform specific STI-related recommendations for transgender women including screening and syndromic management for anorectal, oropharyngeal and neovaginal infections and syndromes.

Assessing the effect of economic shocks on HIV, STIs and Risky Sexual Behaviours

PhD Student: Henry Cust

PhD Supervisors: Dr Tim Powell-Jackson (LSHTM), Dr Aurélia Lépine (University College London) and Dr Rosalba Radice (City, University of London)

Henry’s PhD aims to better understand the circumstances in which FSWs have unprotected (condomless) by modelling the decision to have unprotected sex as a rational economic decision to earn additional money in times of need among female sex workers (FSWs). Economic shocks, where the finances of a household dramatically changes due to a change in income or a change in expenditures is one explanation as to why FSWs choose to have unprotected sex. Additional money earned from unprotected sex is used to make up the difference between regular earning and their income after a shock. This “risk premium” for unprotected sex can be as high as 81% in low and middle income countries.

Henry’s PhD will contribute to this area of research by providing new evidence from two unique settings, one in urban Senegal with a dataset of FSWs collected in Dakar over a two-year period. Sex work is legal in Senegal on the condition FSWs attend and pass a monthly health check for STIs. He will explore the evidence that economic shocks lead to risky sexual behaviours and STIs. Second, Henry is using a dataset from Karnataka state in southern India, which collected information from a group of sex workers predominantly from the devadasi background where sex work is culturally accepted. He will study the effects of economic shocks in both of these settings, including the different responses when the shocks are anticipated and unanticipated to see how risky sexual behaviours differ. He will also evaluate the effectiveness of interventions designed to protect against economic shocks such as personalised savings accounts.

Pharyngeal gonorrhoea as a driver of antimicrobial resistance; how can we better control it?

PhD Student: Victoria Miari

PhD Supervisors: Richard Stabler and David Mabey

Vicky is a clinical scientist at LSHTM and carrying out a staff PhD. Her PhD has several strands, all relating back to pharyngeal gonorrhoea. She first looked at patients with multi-site gonorrhoea and found that 15% of those patients carried different gonococcal strains in different anatomical sites which has an impact on detection of antimicrobial resistant (AMR) gonococcal strains and surveillance of those strains. She is also in the process of evaluating antimicrobial compounds that could potentially treat gonorrhoea – some compounds are novel and some are existing ones used in a new way.

Antimicrobial resistant gonorrhoea has been on the public health radar for some time now. More recently, ‘super gonorrhoea’ has crossed into mainstream news, especially with the recent multi-drug resistant (MDR) case. These MDR gonococcal strains have been surfacing spontaneously since 2011 and since then, no new antimicrobials have been approved to reliably treat gonorrhoea. She has evaluated the activity of closthioamide (CTA), a new antimicrobial class, against several strains of N. gonorrhoeae, and although very effective in vitro, CTA is at the early stages of development and could be years before it is available as a treatment. This research was published in Antimicrobial Agents and Chemotherapy. She is also evaluating chlorehexidine, readily available within dental mouthwashes, to be used topically as a gargle.

This is particularly important; pharyngeal gonorrhoea is difficult to treat. She has found that chlorhexidine has high efficacy against gonorrhoea; the median minimum bactericidal concentration is approximately 65 fold less than the concentration in commercial mouthwashes. Chlorhexidine also appears to be rapidly bactericidal against gonorrhoea, taking less than a minute to kill 10 million bacteria. Vicky is continuing to research chlorhexidine and the next stages will be to perform a randomised controlled trial of a gargle to treat pharyngeal gonorrhoea.

She has written an editorial for Sexually Transmitted Infections about the role of topical antiseptics. As a clinical scientist she is also developing a diagnostic molecular test, able to detect live bacteria in human specimens. She hopes that this test will enable clinicians to detect AMR strains much faster, by reducing the test of cure time period. Lastly, she is further interested in genetic exchange between N. gonorrhoeae and commensal Neisseria species in the pharynx and is preparing  cross sectional study to measure the carriage of resistant commensals in MSM.