The Lancet Infectious Diseases Commission
Sexually transmitted infections: challenges ahead

https://doi.org/10.1016/S1473-3099(17)30310-9Get rights and content

Summary

WHO estimated that nearly 1 million people become infected every day with any of four curable sexually transmitted infections (STIs): chlamydia, gonorrhoea, syphilis, and trichomoniasis. Despite their high global incidence, STIs remain a neglected area of research. In this Commission, we have prioritised five areas that represent particular challenges in STI treatment and control. Chlamydia remains the most commonly diagnosed bacterial STI in high-income countries despite widespread testing recommendations, sensitive and specific non-invasive testing techniques, and cheap effective therapy. We discuss the challenges for chlamydia control and evidence to support a shift from the current focus on infection-based screening to improved management of diagnosed cases and of chlamydial morbidity, such as pelvic inflammatory disease. The emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae is globally recognised. We review current and potential future control and treatment strategies, with a focus on novel antimicrobials. Bacterial vaginosis is the most common vaginal disorder in women, but current treatments are associated with frequent recurrence. Recurrence after treatment might relate to evidence that suggests sexual transmission is integral to the pathogenesis of bacterial vaginosis, which has substantial implications for the development of effective management approaches. STIs disproportionately affect low-income and middle-income countries. We review strategies for case management, focusing on point-of-care tests that hold considerable potential for improving STI control. Lastly, STIs in men who have sex with men have increased since the late 1990s. We discuss the contribution of new biomedical HIV prevention strategies and risk compensation. Overall, this Commission aims to enhance the understanding of some of the key challenges facing the field of STIs, and outlines new approaches to improve the clinical management of STIs and public health.

Introduction

Sexually transmitted infections (STIs) are among the most common acute conditions worldwide.1 WHO estimated in 2012 that there were 357·4 million new global cases of four common curable STIs: chlamydia (130·9 million cases), gonorrhoea (78·3 million cases), syphilis (5·6 million cases), and trichomoniasis (142·6 million cases; figure 1).2 Additionally, there are alarming increases in antimicrobial resistance in Neisseria gonorrhoeae and Mycoplasma genitalium.3 Although most STIs are not usually fatal, they result in a substantial burden of disease.1 The complications of curable STIs include pelvic inflammatory disease, ectopic pregnancy, infertility, chronic pelvic pain, seronegative arthropathy, and neurological and cardiovascular diseases.4 STIs in pregnancy can cause fetal or neonatal death, premature delivery, and neonatal encephalitis, eye infections, and pneumonia.4 STIs can also increase the infectiousness of and susceptibility to HIV.5 Despite these complications, STIs remain a neglected field for clinical and public health practice and for research.6 People with STIs experience stigma, STIs disproportionately affect marginalised groups such as sex workers and men who have sex with men (MSM), and condemnatory moral attitudes toward STIs result in unwillingness to prioritise STI control policies.6, 7, 8 In this Commission of The Lancet Infectious Diseases, we have selected five key issues for STI control that face major challenges globally and for which action is imperative.

This Commission addresses current challenges for research, practice, and policy that we selected because they are common and important global health priorities, or because new evidence is emerging in the area. Partner notification is an essential part of the management of most STIs and is mentioned in several parts of the Commission. We use this term to include all processes involved in informing the sex partners or needle-sharing contacts of people with STIs of their potential exposure to an infectious disease and ensuring their evaluation or treatment, or both.4 We consider partner management, partner services, and partner information to be synonymous.

Part 1 of the Commission addresses Chlamydia trachomatis, commonly known as chlamydia. Chlamydia is the most common bacterial STI globally1 and causes serious reproductive tract complications in women.9 Despite 20 years having passed since the first randomised controlled trial (RCT)10 of an intervention to reduce its complications, the scientific and public health communities remain unsure of how to reduce chlamydia prevalence and impact on society. The most recent RCT11 of a screening intervention did not find a marked effect on prevalence despite a substantial increase in the proportion of the target population that received screening. In this part of the Commission, Hocking and Low assess the latest research about screening, treatment, and management of chlamydia, and suggest a way forward to define chlamydia control priorities for the future.

In part 2 of the Commission, Unemo addresses the globally recognised threat of the emergence and spread of antimicrobial resistance in N gonorrhoeae. This organism has become resistant to virtually all antibiotics that have been available to treat it since sulphonamides were first used in the 1930s. The first clinical failure from the use of dual therapy with ceftriaxone and azithromycin was reported in 2016.12 For this reason, we focus on current and future treatment strategies, including three novel antimicrobials that are being evaluated in phase 2 or phase 3 RCTs. We also report on novel strategies that aim to reduce the incidence and prevalence of gonorrhoea, particularly in MSM, which should also reduce the probability of antimicrobial resistance developing. Ultimately, the development of vaccines against both N gonorrhoeae and C trachomatis are likely to be the only sustainable solutions to control these infections.13

We chose to include bacterial vaginosis in this Commission for three main reasons despite it not being considered a traditional STI. First, an accumulating body of epidemiological and microbiological evidence suggests that sexual transmission is integral to its pathogenesis.14, 15 Second, bacterial vaginosis has been neglected although it is the most prevalent urogenital disorder in women of reproductive age worldwide and is associated with serious reproductive and obstetric sequelae, including preterm delivery and increased risk of STI and HIV acquisition and transmission of HIV.16, 17 Third, treatment failure is unacceptably high: more than half of women have a recurrence after recommended therapy but neither bacterial vaginosis treatment efficacy nor outcomes have improved for decades.18 In part 3 of the Commission, Bradshaw and colleagues summarise the research implicating sexual transmission and propose combination approaches to management that include antimicrobials, biofilm-disrupting agents, and partner treatment.

Part 4 of the Commission addresses STIs in low-income and middle-income countries where more than 90% of curable STIs and almost all of the global burden of STIs occur.1, 2 Francis and colleagues review key strategies for STI case management and control, including syndromic management, presumptive periodic treatment, and partner notification. But they focus on rapid diagnostic tests and point-of-care tests within a published framework—ie, being affordable, sensitive, specific, user-friendly, rapid and robust, equipment-free, and delivered to end-users (ASSURED).19 Point-of-care tests have considerable implications for STI control in high-income countries too, but their potential benefits are greatest in resource-constrained countries where health-care infrastructure is most limited.

Part 5 of the Commission discusses epidemics of STIs in MSM in high-income countries in the context of three biomedical treatment strategies that use antiretroviral therapies (ARTs) to prevent HIV infection. Two strategies are prophylactic treatments to reduce susceptibility in individuals who are not infected with HIV: post-exposure prophylaxis (PEP), given after specific high-risk exposures; and pre-exposure prophylaxis (PrEP), given to individuals who are not infected with HIV for continuous periods of high-risk exposure to prevent acquisition of HIV. The third strategy, known as treatment as prevention (TasP), reduces HIV infectiousness and involves starting ART as soon as HIV infection is diagnosed to prevent transmission to uninfected partners. These interventions have all been suggested to increase risky sexual behaviours through risk compensation and to result in increased transmission of STIs.20 As such, de Vries and colleagues review the evidence linking PEP, TasP, and PrEP strategies to risk compensation and increasing STI prevalence.

We end the Commission with a call to action, in which we ask policy makers to rise to the public health challenge of effective STI control. Our call includes a broad suite of approaches that are often shared across infections or risk groups. They involve the optimisation of surveillance for behaviours, infections, and antimicrobial resistance; access to health services, early diagnosis, appropriate treatment, and partner notification; and intensified research into rapid point-of-care tests to detect both STIs and antimicrobial resistance, novel antimicrobials or treatment approaches (or both), and the understanding of STI transmission or pathogenesis.

Of necessity, this Commission has excluded important subjects. M genitalium was not included despite the rapid emergence of resistance to both first-line and second-line treatments, but M genitalium antimicrobial resistance and clinical management options have been reviewed in recent years elsewhere,3, 21 and is addressed in an accompanying Comment.22 We also omitted herpes simplex virus, for which vaccine development is progressing rapidly;13 human papillomavirus (HPV), for which vaccination is highly effective23 but for which implementation is now the key challenge; and infections caused by Trichomonas vaginalis, because there are no new strategies for treatment or control.

Section snippets

Part 1: chlamydia control—what should we do?

20 years after the publication of the first RCT10 of an intervention to reduce the incidence of pelvic inflammatory disease in young women, policy makers, practitioners, and researchers still need to ask, what should we do about chlamydia control? Three linked factors make this question important. First, C trachomatis remains the most commonly diagnosed bacterial STI despite chlamydia testing recommendations that have been in place for years in several high-income countries.24, 25, 26, 27, 28

Part 2: Gonorrhoea—what are current and future treatment options?

Of the 78·3 million estimated new gonorrhoea cases in adults globally in 2012, the highest number was in the WHO Western Pacific Region (35·2 million cases, figure 1). Accordingly, the vast majority of the gonorrhoea burden globally is in low-income and middle-income countries.2 There is no vaccine against N gonorrhoeae, so effective, accessible, and inexpensive antimicrobial treatment is an essential part of gonorrhoea control measures together with primary prevention, diagnostics, partner

Part 3: Bacterial vaginosis: reconsidering the evidence for sexual transmission—implications for research and management

Bacterial vaginosis is one of the great conundrums in sexual and reproductive health. At the time of its discovery in the 1950s, non-specific bacterial vaginitis—as it was known—was considered likely to be sexually transmitted. Studies by Gardner and Dukes established the clinical and microbiological features of bacterial vaginosis in uninfected women following direct inoculation of vaginal secretions from infected women.229 Subsequent work, however, altered this belief. The apparent absence of

Part 4: STI case management and control in low-income and middle-income countries

In 2012, more than 90% of new estimated cases of trichomoniasis, chlamydia, gonorrhoea, and syphilis were from low-income and middle-income countries (figure 1).2 These curable STIs can lead to severe complications and long-term sequelae, burdening already over-stretched health-care systems. Primary prevention of STIs in low-income and middle-income countries has shown some success with vaccines against HPV and hepatitis B virus and with male circumcision, but less so with interventions to

Part 5: STIs in MSM in the era of biomedical interventions for HIV prevention

A historical perspective provides insights into the epidemiology of STIs in MSM in the 21st century as we enter a new era of antiretroviral-based biomedical interventions for HIV prevention in high-income countries. The first relevant trend was the increase in notification rates of gonorrhoea and syphilis in men from the 1960s onwards in countries such as England and Wales390 (figure 9A) and the USA.393, 394 The increase in infections in MSM can be inferred from the increasing ratio of

Call to action

Action is required to address the substantial challenges facing STI control globally (figure 13). Antimicrobial resistance in N gonorrhoeae is increasing relentlessly and adverse consequences of chlamydia infection remain prevalent. STIs in MSM are increasing rapidly, new sexually transmissible infections are emerging or re-emerging, and there is evidence that bacterial vaginosis—one of the most common, but often ignored, genital conditions in women—might also be sexually transmissible. These

References (485)

  • L Newman et al.

    Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting

    PLoS One

    (2015)
  • M Unemo et al.

    Antimicrobial-resistant sexually transmitted infections: gonorrhoea and Mycoplasma genitalium

    Nat Rev Urol

    (2017)
  • KK Holmes et al.

    Sexually transmitted diseases

    (2008)
  • SR Galvin et al.

    The role of sexually transmitted diseases in HIV transmission

    Nat Rev Microbiol

    (2004)
  • E Fee

    Sin versus science: venereal disease in twentieth-century Baltimore

  • CL Haggerty et al.

    Risk of sequelae after Chlamydia trachomatis genital infection in women

    J Infect Dis

    (2010)
  • D Scholes et al.

    Prevention of pelvic inflammatory disease by screening for cervical chlamydial infection

    N Engl J Med

    (1996)
  • JS Hocking

    Screening for chlamydia: does it work, results from ACCEPt

    Sex Transm Infect

    (2015)
  • H Fifer et al.

    Failure of dual antimicrobial therapy in treatment of gonorrhea

    N Engl J Med

    (2016)
  • SL Gottlieb et al.

    Future prospects for new vaccines against sexually transmitted infections

    Curr Opin Infect Dis

    (2017)
  • KA Fethers et al.

    Sexual risk factors and bacterial vaginosis: a systematic review and meta-analysis

    Clin Infect Dis

    (2008)
  • CM Liu et al.

    Penile microbiota and female partner bacterial vaginosis in Rakai, Uganda

    mBio

    (2015)
  • RM Brotman et al.

    Bacterial vaginosis assessed by gram stain and diminished colonization resistance to incident gonococcal, chlamydial, and trichomonal genital infection

    J Infect Dis

    (2010)
  • CR Cohen et al.

    Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples

    PLoS Med

    (2012)
  • CS Bradshaw et al.

    Recurrence of bacterial vaginosis is significantly associated with posttreatment sexual activities and hormonal contraceptive use

    Clin Infect Dis

    (2013)
  • RW Peeling et al.

    Rapid tests for sexually transmitted infections (STIs): the way forward

    Sex Transm Infect

    (2006)
  • LA Eaton et al.

    Risk compensation in HIV prevention: implications for vaccines, microbicides, and other biomedical HIV prevention technologies

    Curr HIV/AIDS Rep

    (2007)
  • JS Jensen et al.

    Management of Mycoplasma genitalium infections—can we hit a moving target?

    BMC Infect Dis

    (2015)
  • JS Jensen

    Mycoplasma genitalium: yet another challenging STI

    Lancet Infect Dis

    (2017)
  • Guidelines for preventive activities in general practice (The Red Book)

    (2012)
  • Canadian guidelines on sexually transmitted infections

  • National chlamydia screening programme standards

    (2014)
  • IV van den Broek et al.

    Changes in chlamydia control activities in Europe between 2007 and 2012: a cross-national survey

    Eur J Public Health

    (2016)
  • KA Workowski et al.

    Sexually transmitted diseases treatment guidelines, 2015

    MMWR Recomm Rep

    (2015)
  • TL Sutton et al.

    Prevalence and high rate of asymptomatic infection of Chlamydia trachomatis in male college Reserve Officer Training Corps cadets

    Sex Transm Dis

    (2003)
  • JF Peipert

    Clinical practice. Genital chlamydial infections

    N Engl J Med

    (2003)
  • JS Hocking et al.

    Advances in sampling and screening for chlamydia

    Future Microbiol

    (2013)
  • Guidance on chlamydia control in Europe—2015

    (2016)
  • WR Dowdle

    The principles of disease elimination and eradication

    Bull World Health Organ

    (1998)
  • Global health sector strategy on sexually transmitted infections 2016–2021

    (2016)
  • SM Redmond et al.

    Genital chlamydia prevalence in Europe and non-European high income countries: systematic review and meta-analysis

    PLoS One

    (2015)
  • MJ Mimiaga et al.

    Gonococcal, chlamydia, and syphilis infection positivity among MSM attending a large primary care clinic, Boston, 2003 to 2004

    Sex Transm Dis

    (2009)
  • GA van Liere et al.

    Evaluation of the anatomical site distribution of chlamydia and gonorrhoea in men who have sex with men and in high-risk women by routine testing: cross-sectional study revealing missed opportunities for treatment strategies

    Sex Transm Infect

    (2014)
  • D Lewis et al.

    The prevalence of Chlamydia trachomatis infection in Australia: a systematic review and meta-analysis

    BMC Infect Dis

    (2012)
  • V Goulet et al.

    Prevalence of Chlamydia trachomatis: results from the first national population-based survey in France

    Sex Transm Infect

    (2010)
  • JS Hocking et al.

    A chlamydia prevalence survey of young women living in Melbourne, Victoria

    Sex Health

    (2006)
  • I Klavs et al.

    Prevalence of genital Chlamydia trachomatis infection in the general population of Slovenia: serious gaps in control

    Sex Transm Infect

    (2004)
  • J van Bergen et al.

    Prevalence of urogenital Chlamydia trachomatis increases significantly with level of urbanisation and suggests targeted screening approaches: results from the first national population based study in the Netherlands

    Sex Transm Infect

    (2005)
  • H Kløvstad et al.

    Population based study of genital Chlamydia trachomatis prevalence and associated factors in Norway: a cross sectional study

    BMC Infect Dis

    (2012)
  • SD Datta et al.

    Chlamydia trachomatis trends in the United States among persons 14 to 39 years of age, 1999–2008

    Sex Transm Dis

    (2012)
  • Cited by (470)

    View all citing articles on Scopus
    *

    Joint first authors

    Joint last authors

    View full text