Gonorrhoea is a non-ulcerative bacterial STI caused by Neisseria gonorrhoeae (NG). Untreated or inappropriately treated gonorrhoea can lead to serious complications and sequelae particularly in women including infertility, chronic pelvic pain, first-trimester abortion and ectopic pregnancy. Furthermore, gonorrhoea increases the risk of HIV transmission.^1–3 In 2016, the WHO estimated 87 million new NG infections among adults globally, with 21.8 million cases occurring in the WHO African Region (an increase of 91% since 2012) and the highest incidence worldwide, with 41 cases per 1000 women and 50 per 1000 men.^{4 5} However, estimation of the true burden of gonorrhoea in many sub-Saharan African (SSA) countries, including Uganda, remains extremely challenging due to the use of syndromic patient management algorithms and lack of surveillance and diagnostic capacity.^6–8

Increasing international reports of NG strains with high levels of antimicrobial resistance (AMR) and multidrug resistance complicate efforts towards effective management and control of gonorrhoea.^{4 6 7 9} In the WHO Global Gonococcal Antimicrobial Surveillance Programme, among the countries reporting on susceptibility to ceftriaxone (n=63), azithromycin (n=62) and ciprofloxacin (n=67) in 2015–2016, 23.8%, 80.6% and 100%, respectively, reported isolates showing decreased susceptibility or resistance.⁹ Worryingly, only two (4.3%) of the 47 WHO African countries reported data on all these key antimicrobials in the WHO Global GASP in 2015–2016.⁹ Increasing levels of decreased susceptibility or resistance to extended-spectrum cephalosporins (ESCs) such as ceftriaxone and cefixime have been reported in most regions globally, including in SSA countries.^{7 9–12} In most SSA countries, the high burden of STIs, suboptimal antimicrobial stewardship (AMS) and absence of NG and AMR surveillance programmes contribute to an underestimation of the burden of gonorrhoea and NG AMR.^{6 7 9 13} The implementation of the WHO’s Enhanced Gonococcal Surveillance Programme (EGASP) protocol,¹³ which includes standardised collection of quality-assured AMR and epidemiological data of corresponding participants, remains low internationally.^{7 9}

Calls for concerted efforts to combat AMR are the subject of World Health Assembly resolutions and WHO global action plans.^{12 14 15} Objective 2 of the 2015 WHO Global Action Plan to combat AMR aims to strengthen knowledge and evidence bases through surveillance and research.¹⁵ Increased surveillance is also a key strategy in the WHO Global Health Sector Strategy on STI, 2016–2021, and the WHO Global Action Plan to control the spread and impact of NG-AMR.^{12 14}

The present paper aims to describe the establishment and design of a standardised and quality-assured EGASP in Kampala, Uganda, which adheres to WHO EGASP protocols,¹³ and report the main AMR results from 2018 to 2019.

AMR in NG is a global public health concern and enhanced, standardised and quality-assured national and international NG AMR surveillance is crucial for control and treatment efforts. However, despite having the highest gonorrhoea incidence globally,^{4–7 17} there is limited recent NG AMR surveillance data in the WHO African region.^{6–9 16 18} Consequently, in Africa, AMR NG strains may emerge and/or rapidly spread unnoticed. The present paper describes the steps involved and logistics required in the establishment and implementation of a standardised and quality-assured WHO EGASP¹³ in Kampala, Uganda, that could be easily instituted in other similar resource-limited countries in SSA. The examined population was diverse and included high-risk and vulnerable populations such as HIV-positive and HIV-negative males who have sex with men, commercial sex workers, people using narcotic drugs, inmates and teenagers.

The establishment of Kampala EGASP demonstrated the feasibility of implementing the WHO EGASP protocol in a resource-limited setting,¹³ through collaboration and partnerships between government, WHO and academic partners. National NG AMR surveillance programmes are critical in SSA countries for collecting local data on AMR in order to inform treatment guidelines and contribute to international efforts to combat AMR. As well as local use, Kampala EGASP can add to the international gonorrhoea and NG AMR data, that is, in the WHO African Region but also globally. In Kampala EGASP, the surveillance is systematic and based on WHO standardised laboratory methodologies and surveillance protocols,^{12 13} within the largest city, which is a strategic sentinel site for emerging NG AMR given national and international travelling and the frequency and poorly regulated access to empiric antimicrobial treatment. The Kampala EGASP is also informing the national STI management guidelines in Uganda and strengthened AMS.

The Kampala EGASP used Etest for 458 NG isolates and reported associated epidemiological data over 1.5 years. This exceeds the minimum 100 NG isolates per year and country requested in the WHO Global GASP to detect AMR levels with confidence.^{7 9 12 14} In contrast, only approximately 50% of the WHO Global GASP countries in 2009–2016 collected the requested number of NG isolates per year.^{7 9} Furthermore, the Kampala EGASP being led by the National STI Control Programme at MoH presents an opportunity of a long-term sustainability since the surveillance activities have been integrated into the daily routine patient care at the health facilities. Obtaining epidemiological data provides further opportunities for developing population level interventions including targeting key populations in order to combat the spread of AMR NG strains in Uganda and internationally. Inability to collect epidemiological data has been a major limitation for many of the GASPs worldwide.^{7 9 13} The use of the WHONET system for data collection, collation and analysis has also bridged gaps in data management while achieving WHO targets for AMR surveillance.¹⁹

An extremely high level of gonococcal resistance to ciprofloxacin (99.6%) was identified, which is in line with a previous study conducted in Uganda.²⁰ Despite the recommended treatment of cefixime 400 mg single oral dose plus doxycycline 100 mg twice daily for 7 days as first-line treatment for urethritis since 2012,²¹ complete ciprofloxacin resistance is maintained in NG strains. This suggests that in NG ciprofloxacin resistance does not exert a fitness cost and/or that there is ongoing selection pressure from fluoroquinolone use in the community. However, only 0.7% (n=7) of the 1013 males presenting with urethritis in the present surveillance received the recommended treatment of cefixime and doxycycline. It is imperative to substantially increase the adherence to the recommended treatment in the national clinical guidelines. In the present surveillance, all isolates were susceptible to cefixime and ceftriaxone, which is consistent with studies from other African countries such as Kenya,²² Cote d’Ivoire,²³ Zimbabwe¹⁷ and South Africa in 2016.⁹ Nevertheless, decreased susceptibility or resistance to ceftriaxone and cefixime has earlier been identified in, for example, South Africa.^{7 11} The susceptibility to azithromycin was also high; however, 0.2% of isolates were non-susceptible to this antimicrobial in this surveillance, and this may represent emerging resistance. Azithromycin non-susceptible/resistant NG strains have earlier been reported in Uganda,⁷ as well as in other African countries such as Cote d’Ivoire,²³ Malawi, South Africa and Kenya.^{7 9} Kampala EGASP is a vital tool to track changing patterns in MICs of azithromycin and ESCs in particular.

The main limitations of the present surveillance included that only male urethral samples were collected and no samples from other anatomical sites and/or from women, relatively low culture positivity rate of Gram-stained positive samples due to for example long transport times and suboptimal sampling swabs in some time periods, lack of recommended WHO NG reference strains for quality assurance and control (will be included in future surveillance)^{7 9 24} and lack of follow-up of participants to determine treatment outcomes.

An EGASP to monitor existing and emerging AMR strains of NG, a WHO priority pathogen for AMR surveillance,²⁵ has been established in Kampala, Uganda, and contributes to the WHO global action plan to control NG AMR.^{7 9 12 13} Through public–private partnerships, we show the feasibility of setting up a structured, standardised and quality-assured EGASP based on a WHO protocols in a resource-limited setting. Continued and strengthened NG AMR surveillance, including test of cure, in Kampala and nationally in Uganda is critical. Whole-genome sequencing of selected NG isolates will be considered to provide further understanding regarding NG AMR determinants and the transmission of NG and NG resistance in different populations and risk groups in Uganda.