Threat Of Untreatable Gonorrhoea Research Articles

Experimental Urethral Infection with Neisseria gonorrhoeae.

Gonorrhea rates and antibiotic resistance are both increasing. Neisseria gonorrhoeae (Ng) is an exclusively human pathogen and is exquisitely adapted to its natural host. Ng can subvert immune responses and undergoes frequent antigenic variation, resulting in limited immunity and protection from reinfection. Previous gonococcal vaccine efforts have been largely unsuccessful, and the last vaccine to be tested in humans was more than 35years ago. Advancing technologies and the threat of untreatable gonorrhea have fueled renewed pursuit of a vaccine as a long-term sustainable solution for gonorrhea control. Despite the development of a female mouse model of genital gonococcal infection two decades ago, correlates of immunity or protection remain largely unknown, making the gonococcus a challenging vaccine target. The controlled human urethral infection model of gonorrhea (Ng CHIM) has been used to study gonococcal pathogenesis and the basis of anti-gonococcal immunity. Over 200 participants have been inoculated without serious adverse events. The Ng CHIM replicates the early natural course of urethral infection. We are now at an inflexion point to pivot the use of the model for vaccine testing to address the urgency of improved gonorrhea control. Herein we discuss the need for gonorrhea vaccines, and the advantages and limitations of the Ng CHIM in accelerating the development of gonorrhea vaccines.

New treatment options for Neisseria gonorrhoeae in the era of emerging antimicrobial resistance

Neisseria gonorrhoeae, the causative agent of gonorrhoea, has rapidly evolved from an exquisitely susceptible pathogen into a 'superbug' with the capacity to exhibit an extensively drug resistant (XDR) phenotype. The threat of untreatable gonorrhoea now looms on the horizon while the arsenal of effective antimicrobial agents diminishes with time. Ceftriaxone remains the mainstay of first-line therapy as a single agent or as the backbone of a dual therapy regimen. The implementation of new assays to facilitate 'precision' treatment, based on the prediction of N. gonorrhoeae susceptibility to old anti-gonococcal drugs, may enable sparing use of ceftriaxone in those countries that can afford this technology. A few existing drugs, such as ertapenem, can be repositioned to help manage multi-drug resistant and XDR gonorrhoea. Recent clinical trials involving solithromycin and delafloxacin have generated disappointing results in that both agents failed to show non-inferiority to conventional ceftriaxone-based regimens. At present, zoliflodacin and gepotidacin appear to be the most promising antimicrobial agents in clinical development. Both drugs performed well in eradicating urogenital gonorrhoea in recent Phase 2 trials; however, treatment failures were reported at the oropharyngeal site, which is an important site of infection in men who have sex with men and sex workers. Given this observation, it is unlikely that either of these new agents could be promoted for monotherapy of gonorrhoea. The pre-clinical pipeline remains relatively empty of agents likely to progress to clinical development for gonorrhoea treatment and increased investment into gonorrhoea-specific drug discovery is recommended.

Molecular diagnostics for gonorrhoea: implications for antimicrobial resistance and the threat of untreatable gonorrhoea.

This Essay from Nicola Low and colleagues discusses the importance of the nucleic acid amplification tests for rapid detection of N. gonorrhoeae and its resistance determinants, as well as the importance of ensuring their rational use, as priorities for controlling both gonorrhoea and antimicrobial resistance. Please see later in the article for the Editors' Summary

The threat of untreatable gonorrhoea: implications and consequences for reproductive and sexual morbidity

Gonorrhoea (caused by the organism Neisseria gonorrhoeae) is one of the most commonly reported sexually transmitted infections (STIs), with 106 million new cases per year globally, according to 2008 estimates by the World Health Organization (WHO). There is growing global concern about antimicrobial resistance in N. gonorrhoeae. Only third-generation cephalosporins, the last available class of antibiotics to treat this condition, currently remain as the recommended first line treatment. If gonococcal infections become untreatable, they will cause a wide range of reproductive morbidities, including pelvic inflammatory disease, infertility and neonatal blindness. Furthermore, infection with N. gonorrhoeae facilitates the transmission of HIV. Thus, there is an urgent need to contain the threat of untreatable gonorrhoea within the framework of WHO's policy package to combat antimicrobial resistance, launched in April 2011. Interventions should take cognisance of sexual networks, international travel and reproductive commodity supplies, e.g. male and female condoms. There is also an urgent need for the identification of alternative effective treatment regimens for gonococcal infections; concerted efforts to prescribe antibiotics appropriately and ensure treatment compliance; strengthened programmes for primary prevention of STIs, including the importance of protected oral sex (fellatio); enhanced screening; development of affordable and accurate screening tests; and better surveillance and monitoring of resistance.