Mitigating the Emergence and Spread of Multidrug- and Extensively Drug-Resistant Gonorrhea

Gonorrhea is a significant public health concern globally and may become untreatable because Neisseria gonorrhoeae isolates have developed resistance to all antimicrobials recommended for treatment.1–3 The World Health Organization (WHO) estimated that the global burden of gonorrhea in adults (2008) was 106 million cases. Of those cases, 21 million (20%; a 21% increase compared with 2005) were estimated to come from the WHO African region (46 countries; population of 384 million adults), which also had the highest estimated incidence rates of gonorrhea worldwide, with approximately 50 and 100 new infections per 1000 women and men, respectively.4 However, the numbers of actual reported gonorrhea cases and cases with definitive diagnosis of gonorrhea, that is, using laboratory diagnostics, in Africa are low. In general, the infrastructure, laboratory methods, and antimicrobials required to appropriately diagnose, treat, and report the disease are frequently lacking. To meet the significant global public health challenges associated with the emergence and spread of multidrug-resistant and extensively drug-resistant N. gonorrhoeae, the WHO published its “Global action plan to control the spread and impact of antimicrobial resistance (AMR) in Neisseria gonorrhoeae” in 2012.5 This action plan focuses on improving laboratory-based isolation and identification of N. gonorrhoeae. It also stresses the importance of establishment of networks of laboratories to obtain up-to-date, quality assured, national and regional information on AMR in N. gonorrhoeae isolates; this is essential for informing evidence-based revisions of preestablished empirical treatment guidelines. The WHO plan additionally aims to increase awareness on the correct use of antibiotics; improve the detection, verification, and follow-up of confirmed treatment failures, especially to extended-spectrum cephalosporins (ESCs); and, substantially intensify research efforts to identify or develop alternative therapeutic strategies and compounds for the treatment of gonorrhea.5 The WHO’s Global Gonococcal Antimicrobial Surveillance Programme (GASP), supported by the global action plan, was initially established in the early 1990s3,5,6 and revitalized in 2009.7 It is a major concern that longitudinal quality-assured GASP programs remain sporadic or completely lacking in large parts of the world including Eastern Europe, Central Asia, and Africa.8,9 These regions also suffer from a high burden of gonorrhea, creating the prerequisites for rapid emergence and spread of gonococcal AMR. However, in the WHO African region, gonococcal AMR surveillance efforts, such as the one reported from Uganda by Vandepitte et al.10 in the current issue, show the way forward and will help catalyze enhanced national and regional GASP networks essential for the whole WHO African region. This important study was performed in accordance with international recommendations for quality-assured AMR surveillance, using a method that determines the minimum inhibitory concentrations of antimicrobials, in N. gonorrhoeae.5,11 Vandepitte et al. examined AMR in N. gonorrhoeae isolates cultured from female commercial sex workers in Kampala, Uganda (2008–2009), using Etest in accordance with recommendations and quality control strains from WHO,11 and noted high resistance levels to ciprofloxacin (83.1%), penicillin (68.2%), and tetracyclines (97.3%). One (0.7%) and 4 (2.7%) isolates were resistant to cefixime and azithromycin, respectively. At the time of this study, ciprofloxacin was the recommended antimicrobial for treating gonorrhea. However, the Ugandan Ministry of Health, based on the result from the study, replaced ciprofloxacin with cefixime as the national first-line recommended therapy. This quick action is especially notable and illustrates how AMR surveillance data should be appropriately used, that is, to inform prompt revisions of treatment guidelines. Despite country-specific reports of resistance to fluoroquinolones in Africa and elsewhere,1,2,8,9,12,13 in many other countries, public health agencies have had great difficulty in updating country-specific treatment guidelines to recommend effective antimicrobials and treatment strategies in a timely fashion. The study by Vandepitte et al. is one of the very few publications on N. gonorrhoeae AMR in Uganda. Accordingly, this study describes important gonococcal AMR data from Uganda; however, it also emphasizes that continued surveillance of AMR is critical because, by 2008–2009, 1 (0.7%) isolate was resistant to cefixime and 4 (2.7%) isolates were resistant to azithromycin, an antimicrobial used in combination therapy and, although not recommended, also used in monotherapy. The first cefixime treatment failures from Africa were recently verified in South Africa.14 In March 2011, the WHO convened a 3-day international (11 African countries represented) workshop in Harare, Zimbabwe, to initiate an African GASP.9 Although the response has been slow, recent AMR data for a small number of gonococcal isolates have been reported from Cameroon, Côte d’Ivoire, Kenya, Madagascar, Zimbabwe, and South Africa (worryingly, only 13% of the WHO African countries).9,13 Only South Africa has described AMR trends annually. Resistance to penicillin and tetracycline was high in all these African countries, and the information obtained indicated that fluoroquinolones should no longer be used as first-line treatment in Africa.9,13 In conclusion, it is a pressing public health priority to establish a sustainable Africa-wide GASP. To deliver such a program, national and regional capacity for gonococcal antimicrobial surveillance must be developed and strengthened. The syndromic management of sexually transmitted infections (STIs), which has been introduced in most African countries and resulted in loss of skills in sample taking and laboratory methodologies (quality-assured gonococcal culture and AMR testing11), should be supported by laboratory-based STI surveillance and/or an STI reference laboratory in each country. This is essential for performing studies using etiologically based STI diagnostics to inform adjustments of syndromic STI management algorithms. In addition, the STI reference laboratory would support training in quality-assured sample taking and gonococcal culture, identification, and AMR testing. The redevelopment of this capacity will require substantial political advocacy and funding (internal and external) as well as national and international collaboration. To minimize costs, it would be constructive to make AMR surveillance an integral part of patient care and/or national STI surveillance; gonococcal AMR surveillance should not be regarded as “special” or unique research.