1. Background
One of the most urgent threats to sexual health globally is the progressive development and spread of
Neisseria gonorrhoeae antimicrobial resistance (NG AMR) [
1,
2]. NG can develop resistance in two main ways: through plasmid-mediated resistance (PMR), and, to a greater extent, through chromosomally mediated resistance (CMR), with the latter bolstered by frequent genetic material exchange with commensal
Neisseria species [
3]. Some public health commentators have predicted that NG infection may be becoming untreatable [
1,
2,
4]. In response to this threat, the World Health Organization (WHO), the United States of America Centers for Disease Control and Prevention (USA-CDC), and other regulators have developed global action plans for improving the management of NG AMR [
5]. Prominent within these documents are recommendations for developing rapid molecular assays to enhance the testing and surveillance of NG AMR [
5,
6].
The “gold standard” for NG AMR testing is the culture method [
7]. However, it can be unreliable and particularly challenging to maintain in settings with limited resources [
8,
9]. For this reason, the WHO and others have called for developing molecular assays for NG AMR testing. Several in-house genotyping methods have been established and validated to test the presence of genes and gene mutations in NG that are associated with causing resistance towards the main class of antibiotics in treating it [
2,
10]. The advantages of NG AMR testing by molecular assays are that it does not require live bacteria for testing, and requires less stringent conditions for sample storage and transportation [
8,
9]. In addition, the samples can be self-collected by non-invasive techniques, such as urine or anorectal swabs, for molecular testing. The privacy and ease in sample collection for molecular testing thus increases sampling numbers, which improves surveillance of NG AMR by increasing sample size accuracy of prevalence estimates [
10]. Though molecular testing methods are not as definitive as the culture method for determining NG AMR, they can effectively complement and supplement culture-based NG AMR surveillance.
The WHO recommended that national NG AMR surveillance be done at regular intervals to inform treatment. If observed resistance prevalence is above 5% for any antibiotics, a change in treatment is required [
2,
5]. Despite this, many low-to-middle-income countries (LMIC) with a high prevalence rate of NG infection cannot afford to do so. Typically, many LMIC lack local testing capacity, such as Papua New Guinea (PNG). Almost all countries in the WHO Western Pacific Region (WPR) and Southeast Asian Region (SEAR) have abolished the use of penicillin and ciprofloxacin treatment option due to the high prevalence of resistance, estimated at 70–100% for the two antibiotics [
11]. Most are using cephalosporins (ceftriaxone and cefixime) and azithromycin drug combinations. However, cephalosporin (ceftriaxone) resistance is on the rise. Resistance in the range of 30–70% has been reported in Cambodia; 5–30% in China, Japan, and Taiwan; and 1–5% in Australia [
12]. Elsewhere, the United States of America and Canada have reported a cephalosporin (ceftriaxone) resistance prevalence of 1–5%. Several European countries reported resistance prevalence to cephalosporins (cefixime) at 5–30% [
12]. Interestingly, some countries in WPR and SEAR, such as China, Cambodia, Thailand, and Australia, reported an azithromycin resistance prevalence of 5–30% [
12].
Papua New Guinea (PNG) has some of the highest rates of sexually transmitted infections (STI) in the WPR [
13]. The recent gonorrhea prevalence estimate for PNG is 11% (95% CI: 4.5–16.1) [
13]. However, this may still be an underestimation, as a relatively higher prevalence was previously reported, with a disproportionately higher prevalence among female sex workers (23–44% in 2010, and 15–33% in 2017) [
14,
15], men who have sex with men, transgender women (3–15% in 2017) [
14], and people attending STI clinics (60–88% among males, and 13–41% among females in 2010) [
15]. The high prevalence of NG infection alone in PNG is a concern, and more concerning is the lack of NG AMR data in the last decade. The existing NG AMR data is not sufficient or representative because of the small sample size from only several sampling sites across PNG. Therefore, up-to-date NG AMR data are crucially needed for PNG [
16].
The standard treatment for gonorrhea in PNG is a single-dose cocktail of the following antibiotics: amoxicillin (penicillin), probenecid (uricosurics), augmentin (penicillinase/beta-lactamase inhibitor), and azithromycin (macrolide) [
17]. Occasionally, doxycycline (tetracycline) or erythromycin (macrolide) are administered as a substitute for azithromycin [
17], but this may change to a cephalosporin (cefixime and ceftriaxone) and azithromycin combination treatment for PNG [
18]. However, there is insufficient NG AMR surveillance to inform such change [
18].
2. Antimicrobial Resistant Neisseria gonorrhoeae in Papua New Guinea
There is an increase in PPNG prevalence from 1989 to 2009. PNG has reported some of the highest prevalence of PPNG in the WHO WPR and SEAR. The pooled PPNG prevalence estimate (37.9%, 95% CI: 29.3–47.2) in this meta-analysis is similar to that observed in other countries in the WHO WPR and SEAR, such as Hong Kong (32.4%), Malaysia (30%), and Vietnam (32.5%) [
41]. Despite high PPNG prevalence in PNG, treatment with augmentin (amoxicillin-clavulanic acid, a penicillinase inhibitor) is used effectively in treating PPNG-positive NG strains. However, it is important to note is that a resistance prevalence of 6.1% towards amoxicillin-clavulanic acid was recently reported [
40].
Japan has reported the highest prevalence of CMR to penicillin (39%), whereas other countries in the WPR and SEAR reported CMR to penicillin in the range of 10–20% [
41].
Tetracycline is not the recommended antibiotic for treating gonorrhea, but is sporadically used. There is an increase in tetracycline resistance prevalence between 1989 and 2000, followed by a decline between 2001 and 2004 in PNG. Surprisingly, a spike in prevalence was reported in 2016 in PNG, estimated at 37.6% (95% CI: 26.2–49.6). The recently reported tetracycline resistance prevalence in PNG in 2016 [
40] is much higher when compared to that of Australia in 2017 (12–21%) [
42].
Several studies in PNG have reported a high prevalence of ciprofloxacin resistance in the mid to late 1990s, followed by a decline. A similar trend was seen for spectinomycin resistance. The declining resistance prevalence may be due to the strict use of amoxicillin and azithromycin. With the rise of ciprofloxacin resistance in the WPR (6–15% in New Caledonia; 16–30% in urban Australia; and 71–100% in China, Philippines, and Vietnam), PNG needs research and surveillance to ascertain the observed decline [
43].
The only three countries in the WHO WPR that are still using penicillin and azithromycin for treating gonorrhea are PNG, Fiji, and the Solomon Islands. The rest of the countries in this region use cephalosporins (ceftriaxone or cefixime) and azithromycin [
41,
44]. However, PNG has a new treatment guideline that recommended the change of treatment to cephalosporin (ceftriaxone and cefixime) and azithromycin [
18]. Though this change in treatment represents an important step towards consistency in treatment strategies for gonorrhea in the WPR and SEAR, there were insufficient NG AMR data in PNG to inform this change [
18].
The estimated pooled resistance prevalence for most antibiotics is below the 5% threshold. This suggested the possibility to use other drug combinations, then to quickly use the last line of treatment. At the same time, it must be noted that most of the studies included in this meta-analysis were conducted a decade ago. Thus, this could mean that the estimates reported here may be outdated due to the lack of recent NG AMR surveillance in PNG.
The lack of representative and updated NG AMR data in PNG emphasizes the need to explore methods other than the culture method, including molecular methods, to complement and support culture for NG AMR surveillance. Molecular testing has increasingly been used for NG and NG AMR testing in many countries, and is proving to be an invaluable tool for NG AMR surveillance [10]. Given its advantages discussed above, its adoption for use in PNG would be of great value to enhance NG AMR surveillance.
In Papua New Guinea (PNG), penicillin and azithromycin remain the standard treatment for gonorrhea. That may soon change as per the newly drafted National STI Treatment Guidelines. Cephalosporins (cefixime and ceftriaxone) and azithromycin are now the recommended treatment for NG in PNG. However, PNG does not have sufficient NG AMR data to inform this change, which was acknowledged in the new treatment guidelines. This highlights the need for evidence-based research and surveillance of NG AMR in PNG.
Though the culture method remains the “gold standard” for NG AMR testing, it requires viable NG bacteria. Maintaining viable bacteria for culture is often challenging in PNG because of the logistical difficulties and costs associated with the storage and transportation, which severely limits NG AMR testing. Thus, it is appropriate to consider molecular testing methods for NG AMR testing and surveillance in PNG. Considering the advantages discussed above, molecular methods could be established easily, and used to enhance NG AMR surveillance quickly and efficiently in PNG.