Antimicrobial Resistance Surveillance for Neisseria gonorrhoeae—What Do We Really Need to Know to Guide Public Health Interventions?

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Excerpt

Antimicrobial resistant gonorrhoea is an increasing public health concern in today’s world. In 2012, the World Health Organization (WHO) published a Global Action Plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae.1 A year later, the United States' Centers for Disease Control and Prevention (CDC) listed drug-resistant N. gonorrhoeae as one of three urgent antimicrobial resistance threats, along with Clostridium difficile and carbapenem-resistant Enterobacteriaceae.2 As a recommended response, both the WHO and the CDC have emphasized the need for urgent public health attention to identify gonococcal infections and reduce transmission.
Ironically, we are arguably less able to identify and control the spread of antimicrobial-resistant gonorrhoea in 2017 than we were two decades ago. This is due to 2 major changes in the way sexually transmitted infections (STI) are now diagnosed and treated, namely, the introduction of syndromic management in many countries and a switch from culture-based to molecular-based diagnostic testing for N. gonorrhoeae in others.
The introduction of the syndromic management approach as a tool to improve the diagnosis and treatment of symptomatic STIs in many low- and middle-income countries in the late 1990s has undoubtedly made significant gains with predominantly symptomatic diseases, such as chancroid which has virtually disappeared as a cause of genital ulceration. However, it has failed to control those STIs which are frequently asymptomatic in nature and for which laboratory diagnostic testing is essential for case identification. This is particularly true for gonorrhoea. For example, in the case of women, only about half of gonococcal infections produce genital symptoms, whereas among men who have sex with men (MSM), up to 90% of oropharyngeal and anorectal infections are asymptomatic. The syndromic approach to STI control has focused on a “see-and-treat” approach using syndrome-based flowcharts and standardized antimicrobial therapy, in the absence of laboratory testing, to guide patient management.
For higher income countries, the past 10 to 15 years has seen a significant trend toward molecular testing for gonorrhoea, often in combination with testing for Chlamydia trachomatis on dual platforms. The use of more sensitive molecular tests has increased our ability to diagnose gonorrhoea in higher risk patients, such as MSM and sex workers, particularly at the oropharyngeal and anorectal sites. However, there has been a simultaneous and dramatic decline in the number of N. gonorrhoeae culture-based antimicrobial susceptibility testing requests received by laboratories. Currently, we lack commercial molecular N. gonorrhoeae assays that can both detect and predict antimicrobial susceptibility. Although development of such assays would be relatively straight forward for the detection of the various plasmids responsible for high-level penicillin and tetracycline resistance as well as for detection of the very limited and well characterized point mutations for fluoroquinolone and high-level macrolide resistance, it is technically much more challenging to develop assays for detection of resistance to those antibiotics where multiple mutations affecting several genes are involved, for example, the detection of cephalosporin resistance or low level chromosomal resistance to penicillin, tetracycline, and macrolides.
Given the global decrease in N. gonorrhoeae antimicrobial susceptibility testing data derived from routine culture-based testing of patient samples, attention must now focus on strengthening existing, or establishing new, antimicrobial surveillance programs to generate the strategic information required to inform treatment algorithms. The best examples of long-standing surveillance programs include the Gonococcal Resistance to Antimicrobials Surveillance Programme in England and Wales, the Gonorrhea Isolate Surveillance Project run by the US CDC, and the Australian Gonococcal Surveillance Programme.3–5 The WHO's Gonococcal Antimicrobial Surveillance Programme, which provides a global rather than a national picture, has highlighted important gaps in global surveillance, particularly in low and middle income countries.

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