New tools for old bugs – the fight against STIs

Starting my career as a technician working in the laboratory of the Brisbane Sexual Health Clinic in the late 1990s, I was around to witness the initial implementation of nucleic acid amplification tests (NAATs), including polymerase chain reaction (PCR), for detection of sexually transmitted infections (STIs). Noting that circulating strains of Neisseria gonorrhoeae and certainly Chlamydia trachomatis at the time were highly treatable (at least compared to modern day N. gonorrhoeae), one may have expected these highly sensitive, high-throughput NAATs to have had tremendous effects upon infection rates by ensuring optimal screening and treatment of individuals. Sadly, the reality was much different, and it could be cynically argued that the introduction of NAATs was simply perfectly timed to watch STIs once again surge in the Australian population, and elsewhere.

In Australia, C. trachomatis and N. gonorrhoeae infection rates have continued to skyrocket since the late 1990s, as has syphilis since 2011. New problems have continued to emerge, including a recent surge in Mpox virus, classified in August 2024 by the World Health Organization (WHO) as a ‘public health emergency of international concern’. So, what are we doing wrong? It is now well understood that just having excellent screening tests is not enough, particularly if you are unable to access and test many infected individuals. But it’s also increasingly clear that testing and treatment strategies will fail if we don’t consider the population dynamics that help sustain infections in populations.

Adding to the above issues, are emerging concerns of antimicrobial resistance (AMR). These concerns over AMR are epitomised by Mycoplasma genitalium. Although much has been done to improve treatments outcomes for M. genitalium infection (as detailed in this issue), there are increasing numbers of patients facing the prospect of untreatable infection. Antibiotic-resistant N. gonorrhoeae is now considered a ‘high priority’ by the WHO¹ due to emerging resistance to ceftriaxone, the mainstay of treatment in most regions globally. The particular concerns here are that there are no obvious alternative first-line N. gonorrhoeae treatments, and we have already struggled to control gonorrhoea in an era of treatable infection.

In this issue, we highlight the amazing depth of STI research and development being conducted in Australia by leaders in the field.

Ei Aung and Eric Chow highlight the need for patient-centred detection methods and tailored interventions to manage syphilis in difficult-to-access populations in Australia, including a multidisciplinary approach combining health promotion, ensuring the availability of condoms and appropriate diagnostics, including in key populations.² Gladymar Pérez Chacón, Amit Saha, Emily Phillips, Rebecca Guy, Tanya Applegate, Louise Causer, Skye McGregor and Belinda Hengel provide a snapshot of where we are at with syphilis point-of-care (POC) tests, Australia’s syphilis POC programmes and the attributes of the ideal POC test.³ Similarly, Chuan Kok Lim, Shivani Parischa and Soo Jen Low pave the way forward for an integrated approach to Mpox control, including Mpox POC diagnostics and genomics to target public health strategies.⁴

Means of addressing AMR also feature prominently; Monica Lahra, Rob George and Sebastiaan van Hal detail the problems of emerging N. gonorrhoeae AMR,⁵ including the exemplary work of the National Neisseria Network (NNN) and associated Australian Gonococcal Surveillance Programme (AGSP), gaps in AMR surveillance globally and the need to enhance AMR surveillance internationally and the urgent need to develop new N. gonorrhoeae treatments. Amy Jennison, Shivani Pasricha and Francesca showcase the potential for new direct sequencing tools to aid in the public health space for N. gonorrhoeae, syphilis, M. genitalium and C. trachomatis, including improved understanding of epidemiological trends, enhanced AMR surveillance and the obstacles associated with implementation of such methods.⁶ Gerald Murray, Emma Sweeney and Catriona Bradshaw highlight how we can make the best use of currently available antibiotics in an era of AMR by the use of rapid molecular AMR assays and individualised treatment.⁷ Focusing on M. genitalium, they show how an understanding of AMR markers and development of associated rapid AMR PCR tests has led to significant improvements in M. genitalium treatment outcomes and antimicrobial stewardship.

Todd Pryce reminds us of the fact that NAAT technology can still have its own inherent issues.⁸ He discusses the ongoing challenges of NAAT-based detection of N. gonorrhoeae and ways forward, including the potential for cross-reaction with non-gonococcal Neisseria species and the use of supplementary tests for both confirmatory testing and AMR prediction.

As the late Prof. John Tapsall once said to me, ‘the best way to control AMR is to eliminate the disease’. And in that context, Bing Wang, Kate Seib and Helen Marshall detail where we are at in the search for the N. gonorrhoeae holy grail – a vaccine!⁹ They detail the various vaccine candidates that are currently in development as well as evidence to date showing the potential for meningococcal vaccines to protect against N. gonorrhoeae infection.

Overall, these articles showcase much promise in the fight against STIs. Unfortunately, there is still much more work to do given STIs continue spread, and that they remain disproportionately and unacceptably high for Aboriginal and Torres Strait Islander peoples.