Marco De Ambrogi

Turning the spotlight on sexually transmitted infections

Sexually transmitted infections (STIs) represent a heterogeneous group of infections that affect millions of people, including key populations such as sex workers, men who have sex with men, and people who inject drugs. Among them, chlamydia infection and bacterial vaginosis are very common problems, especially in women; it is estimated that one of 12 people in the world has genital infection with herpes simplex virus; the number of cases of syphilis and gonorrhoea is increasing worldwide; and there is an intense debate on how interventions to prevent HIV infection, such as pre-exposure prophylaxis and post-exposure prophylaxis, might have a negative effect on risk taking when it comes to sexual behaviour. Moreover, besides the immediate effect on the health of the infected person, STIs can also lead to infertility, miscarriage, stillbirth, and transmission from mother to child. Overall, WHO estimated that one million new cases of STIs (chlamydia, gonorrhoea, syphilis, and trichomoniasis) occur every day. Although this number should be hard to ignore, these infections remain a neglected issue in both the public health agenda and the research community. This situation is in part due to the fact that in the past 30 years, the spotlight in media coverage, prevention campaigns, and education on STIs has focused largely on HIV infection whereas other infections such as chlamydia, gonorrhoea, and syphilis have been sidelined in the public debate. Furthermore, despite the advances made in increasing awareness of HIV infection and the implications of risk taking in sexual behaviour, inadequate public awareness and widespread stigma about STIs still exist. At present, specific public health policies that should address such challenges, such as improved training of health-care workers, availability of diagnostic tests, and platforms to educate the general public about STIs, are insufficient. At the same time, diagnosis remains difficult, especially in low-income and middle-income countries where syndromic management is the standard for STIs. This method is simple, rapid, and cheap but it misses asymptomatic infections, which constitute the majority of STIs globally. With this background, The Lancet Infectious Diseases is publishing a Commission on STIs to discuss the most recent advances in the field and promote the debate on education, control, treatment, and diagnosis of these infections. In recent years, new challenges have emerged with the rise of antimicrobial resistance (especially for strains of Neisseria gonorrhoeae resistant to the last line treatment option, oral and injectable cephalosporins), introduction of prophylactic strategies for HIV infection with direct effect on possible changes in risk taking of sexual behaviour, and changes in incidence and prevalence of some STIs in different parts of the world. The Commission was created under the guidance of Christopher Fairley who has gathered a very motivated group of international experts with deep knowledge of different areas of STIs. The authors have identified five areas in clinical practice and research for which there have been particularly relevant advances in recent years, new problems have emerged, or the epidemiology of the infections has changed: these five areas are future directions of the control of chlamydia, treatment of gonorrhoea in times of increasing antimicrobial resistance, cause of bacterial vaginosis and implications for treatment, challenges in the diagnosis and control of STIs in low-income and middle-income countries, and how the medical interventions to curb HIV infection might affect other STIs. Because some topics could not be included in the Commission, we have included them in three other Comments that briefly discuss challenges in the control of Mycoplasma genitalium, the burden of syphilis (with a special focus on China), and what improvements in the management of STIs at the health system level should be implemented. We hope that this Commission will help to increase visibility and discussion of STIs in the public arena and favour the development of new solutions and strategies for a group of infections that are more widespread than is popularly acknowledged.

International Forum on Gonococcal Infections and Resistance

Experts in gonococcal infections and antimicrobial resistance from all over the world gathered for the 2017 International Forum on Gonococcal Infections and Resistance in Shenzhen, China, to discuss knowledge and challenges in the control of gonorrhoea. Recent years have seen an increase in reports of gonorrhoea (there were 78 million news cases in 2012) and, in particular, a rise in Neisseria gonorrhoeae strains resistant to the antibiotics used for therapy. Thus, there is widespread concern that gonorrhoea will soon become untreatable unless new solutions are found. As highlighted by Teodora Wi (WHO, Geneva, Switzerland), WHO recommends a dual therapy for gonorrhoea, consisting of the combination of extended-spectrum cephalosporins (ceftriaxone) and azithromycin. Some countries, including China, have not yet adopted dual therapy but instead use monotherapy with ceftriaxone to treat gonorrhoea. However, resistance to azithromycin and more recently to ceftriaxone has been reported all over the world and in the absence of alternative new antibiotics, the future looks dim. Under the coordination of XiangSheng Chen (National Center for AIDS/STD Control, Beijing, China), the International Forum in Shenzhen was thus a useful occasion for experts in the field to discuss and identify areas for research and investment in basic science, epidemiology, better diagnostic tests, and new therapeutic options before the treatment of gonorrhoea reaches the point of no return. In some regions, including most of Africa and the Middle East, epidemiological data regarding antimicrobial resistance in N gonorrhoeae are very limited. The WHO Gonococcal Antimicrobial Surveillance Programme (GASP) was created to fill these gaps with the engagement of partner countries. Even within countries, extensive work is needed to gather essential information on minimum inhibitory concentrations and prevalence of resistance in gonococcal isolates. Yue-Ping Yin (National Center for AIDS/STD Control, Beijing, China) described the work done by the China Gonococcal Resistance Surveillance Programme in the past 30 years and highlighted how further work to increase coverage, quality assessment, and standardisation of the collection of information will be essential for an adequate response to the spread of resistant gonococcal strains in China. As indicated by Caroline Genco (Tufts University, Medford, MA, USA), a correct understanding of how gonorrhoea spreads across networks within a population is also impaired by a basic lack of knowledge about how N gonorrhoeae affects men and women differently. The focus of research on men who have sex with men has created uncertainty about the role of women in maintaining N gonorrhoeae in a population. As for diagnostics, the absence of point-of-care tests for gonorrhoea hampers the collection of data to inform surveillance and strategies to curb gonococcal resistance. In terms of treatment, the lack of development of new classes of antibiotics in recent decades is a major concern as much for gonorrhoea as for any other bacterial disease. One solution highlighted by David Lewis (University of Sidney, Sidney, Australia) could be the repurposing of old antimicrobials, s u c h a s s p e c t i n o m y c i n o r ciprofloxacin. However, this option might be insufficient because resistance to these drugs can emerge very rapidly in N gonorrhoeae. Carolyn Deal (National Institutes of Health, Rockville, MD, USA) talked instead about the only two new drugs in the pipeline that recently completed phase 2 studies and could be considered for treating gonorrhoea: gepotidacin (for which the primary indication for licensure is biodefense, which might impair future market strategies) and zoliflodacin. However, the introduction of these drugs into clinical use will take time, as they will not be licensed until successful phase 3 trials are completed. The experts agreed that when discussing antibiotic-resistant gonorrhoea, it is important to consider the issue as part of the broader problem of antimicrobial resistance. Makoto Ohnishi (National Institute of Infectious Diseases, Tokyo, Japan) used data on gonococcal strains from his laboratory in Tokyo to show that the emergence of resistance to cephalosporins in gonococcal isolates is strongly associated with the widespread use of these antibiotics in the general population. Thus, any strategy to reduce the incidence of antibiotic-resistant gonorrhoea will need to be part of a broader plan to implement antimicrobial stewardship and reduce the inappropriate use of antibiotics in the general population. It is clear that reducing the incidence of gonorrhoea should be the main target for the future. Meetings like the International Forum on Gonococcal Infections and Resistance will help such efforts to be effective.

“John”—Searching for you in the darkness

The highly innovative DV8 Physical Theatre Company has never refrained from touching controversial topics, such as homophobia, freedom of speech, and religious fundamentalism. Now they are back on tour around Europe with John, a piece of physically-fuelled verbatim theatre that is based on a series of interviews about love and sex done with more than 50 men in gay saunas. The show mainly focuses on the poignant story of John, a man whose life has been marked by abuse, losses, and drug addiction. Even the budding love for the HIV positive Bianca turns into tragedy: her decision to stop antiretroviral treatment because she cannot bear the side-eff ects leads to her rapid death and John is left alone again. Only after being jailed for arson, John manages to break the vicious circle of drug addiction and insecurity, and can tentatively start to hope for a better future, this time by seeking some kind of love unencumbered by the past in gay saunas. It is at this point that with its unique combination of movement and words, the play broadens its focus by representing the diff erent attitudes of patrons of gay saunas towards the risk of contracting HIV and other sexually transmitted diseases (STDs). Most men interviewed are aware of the risk, but worryingly some still prefer having unprotected sex and are unaff ected by the possibility of infecting others, all as part of a search for escape, satisfaction, and intimacy at any cost. One man even expresses relief at the idea of contracting HIV so that he could stop worrying and just enjoy sex. These voices show that despite extensive health information available on STDs, even in the same gay saunas where the risk of contracting STDs might be higher, personal choice unavoidably has a major role in their occurrence. It is also possible that the availability of antiretroviral drugs and antibiotics might have generated complacency on the subject, as shown by the recent increase of syphilis cases in Canada. In the play, in his matter-of-fact approach to life, John points out that in the end it is important to take responsibility for one’s personal choices. At the same time, it is impossible not to wonder how much solitude and social marginalisation can help poor judgement and acceptance of a high risk of STDs, just for the sake of some human connection. In the tradition of best thought-provoking theatre, John leaves us with questions, not answers.