Neisseria gonorrhea is a Gram-negative diplococcus bacterium that causes one of the most prominent (STIs called gonorrhea; Whittles et al., 2018; Yakobi and Pooe, 2022). Worldwide, about 87 million incident gonorrhea cases happened among persons aged 15–49 years with an incidence rate of 26/1,000 men. The same evidence spotlighted that, in 2016, roughly more than 1 million STIs were acquired daily globally with 30 million documented cases of N. gonorrhea (Rowley et al., 2019). Besides, N. gonorrhea is known to cause male urethritis, female endocervicitis, and fatal reproductive complications such as infertility, miscarriage, ectopic pregnancy, pelvic inflammatory disease, and epididymitis that will eventually lead to substantial morbidity and mortality (Cohen, 2012).

In most of the developing countries, including Ethiopia, STI treatment is based on a syndromic management approach. This is mainly due to the shortage of laboratory equipment and resources in primary health care facilities which serves as an initial point of contact for entertaining STI cases (Feglo and Opoku, 2014). Empirical antibiotic therapy remains the gold standard treatment for N. gonorrhea infections owing to the lack of appropriate laboratory facilities for undergoing advanced microbiological tests like culture and sensitivity testing, and the higher cost of laboratory services (Acheampong et al., 2018). Although the syndromic approach has well-established financial merits, it is also questioned for its enormous contribution to the emergence of AMR (Ventola, 2015).

Recently, the progressive development and spread of N. gonorrhea AMR pose a significant sexual health threat across the globe (Whiley et al., 2012; Unemo and Shafer, 2014). Because of the widespread resistance to potent antibiotics such as sulfonamides, penicillin, tetracycline, and quinolones, the recent therapeutic alternatives for N. gonorrhea infections have been severely hampered (Olsen et al., 2013; Lebedzeu et al., 2015). A nascent study reported a prodigious degree of N. gonorrhea resistance to commonly used antibiotics in Sub-Saharan countries (Tadesse et al., 2017), while globally, new and untreated cases of N. gonorrhea infections are astoundingly rising due to treatment failures and the disease’s asymptomatic nature (Lovett and Duncan, 2019; Springer and Salen, 2023). Consequently, to stem down infection rate, various concerned stakeholders including the World Health Organization (WHO), the United States of America Centers for Disease Control and Prevention (USA-CDC), and other regulatory bodies have designed global action plans (World Health Organization, 2012). The WHO advocated that national N. gonorrhea AMR surveillance should be conducted at regular intervals and treatment modification must be implemented if the observed resistance prevalence is above 5% for any antibiotics (World Health Organization, 2012; Unemo and Shafer, 2014). However, this stringent recommendation is not affordable to many developing countries.

Therefore, this systematic review and meta-analysis aim to synthesize the available evidence on the prevalence of N. gonorrhea among STI suspected patients in Ethiopia and assess its antimicrobial susceptibility profile. By consolidating this information, we seek to provide insights that can inform policy-makers, healthcare providers, and researchers in Ethiopia and beyond, toward the development of effective strategies for N. gonorrhea control and management in resource-limited settings.

The objective of this systematic review and meta-analysis was to assess the national pooled prevalence of N. gonorrhea among suspected STI patients and evaluate the resistance profile of common antimicrobial agents used against N. gonorrhea in Ethiopia. The estimated pooled prevalence of N. gonorrhea among STI suspected patients in Ethiopia was found to be 20% (95% CI 8–30, I² = 99.0%; p < 0.001). This prevalence diverges significantly from global meta-analyzed reports in 2016, which indicated an N. gonorrhea prevalence of 0.9% in adult males and 0.7% in adult females in the general population (Rowley et al., 2019). Recent studies in 2022 revealed lower prevalence rates in developed regions, such as Europe (<0.1%), North America (0.27%), and higher rates in the Western Pacific (7.06%) and Africa (14%) [Benin: 0.9%, Malawi: 9.8%, South Africa: 3.3%] (Whelan et al., 2021). Similarly, a study in Latin America reported a pooled N. gonorrhea prevalence of 2.9% in young people (Vallejo-Ortega et al., 2023). While another study found gonorrhea prevalence at 1.46% in Latin America and the Caribbean, rising to 5.68% in high-risk populations (Bardach et al., 2023). In contrast, studies in China, sub-Saharan Africa, and South Africa reported N. gonorrhea prevalence rates of 6, 5.46, and 10.1%, respectively (Su et al., 2015; Kularatne et al., 2018; Kassa et al., 2020).

This variation might be due to differences in the study population, as this study focused on STI suspected patients, which might result in an inflation of prevalence compared to the general population, alongside cultural and geographical variations.

Unlike developed nations, there is a lack of proactive response toward monitoring N. gonorrhea AMR in Africa. A recent systematic review and meta-analysis across 11 Sub-Saharan countries, including Ethiopia, highlighted substantial resistance to ciprofloxacin, benzylpenicillin, and tetracycline (Whiley et al., 2012). For instance, in Cameroon, approximately 80.1, 64.4, and 58.4% of N. gonorrhea strains showed resistance to benzylpenicillin, ciprofloxacin, and tetracycline, respectively (Crucitti et al., 2020). Our study mirrored these findings, indicating the highest prevalence of resistance to tetracycline (97%), penicillin (79%), and ciprofloxacin (37%). The consistency across studies underscores the commonality of N. gonorrhea AMR patterns associated with specific antimicrobial classes, emphasizing the urgent need for routine AMR monitoring, antimicrobial consumption surveillance, and improved etiologic diagnostics. It also highlights the necessity for well-organized training for healthcare practitioners, quality assurance for laboratories, and the establishment of centers for regular AMR monitoring.

In contrast to a study conducted in Cameroon, which revealed a modest prevalence of resistance to ceftriaxone (1.8%) and azithromycin (2.1%), our study reported a moderate level of resistance to ceftriaxone (9%) and azithromycin (10%). Noteworthy is our unique finding of macrolide resistance, supported by a study from South Africa in the province of KwaZulu-Natal, which identified azithromycin resistance in 68% of N. gonorrhea bacteria, of which 71% exhibited multidrug resistance (Rambaran et al., 2019). Interestingly, a recent systematic and meta-analysis study in Papua New Guinea in 2022 indicated a pooled prevalence estimate of 37.3% for penicillin, 10.3% for tetracycline, and 1.7% for ciprofloxacin resistance (Willie et al., 2022). This finding is notably lower compared to our study. Spectinomycin emerged as the least resistant drug in systematic and meta-analysis studies conducted in sub-Saharan Africa (Yakobi and Pooe, 2022), Cameroon (Crucitti et al., 2020), and Papua New Guinea (Willie et al., 2022) spectinomycin is the least resistant drug reported. The discrepancies observed could potentially be attributed to differences in sample sizes of isolates tested for N. gonorrhea surveillance and monitoring,

AMR surveillance, laboratory setups, rapid point-of-care tests for the detection of N. gonorrhea, and the technical capabilities of laboratory technicians.

The subgroup analysis based on different regions of Ethiopia provided valuable insights into the varied prevalence of N. gonorrhea among STI suspected patients. Notably, the highest pooled prevalence of 55% in Addis Ababa and the subsequent prevalence of 16% in the Amhara region underscore the regional disparities in the burden of N. gonorrhea. Conversely, the notably lower prevalence of 4% in the Southern Nations, Nationalities, and Peoples’ Region (SNNPR) highlights potential regional variations in STI prevalence and emphasizes the need for targeted interventions.

Interestingly, the subgroup analysis conducted based on the study periods did not reveal a significant difference in the pooled prevalence of N. gonorrhea. This suggests a relatively consistent prevalence over time, highlighting the persistent nature of the issue and the need for continuous monitoring and intervention efforts.

The trim and fill analysis addressed the potential impact of overlooked studies on the prevalence estimate. The inclusion of five additional studies resulted in a substantial shift in the pooled prevalence from 19.9 to 6.2%, emphasizing the significance of considering potential publication bias and the importance of a more nuanced interpretation of the prevalence estimate.

Our sensitivity analysis using a random effects model demonstrated the robustness of the prevalence estimate, as the exclusion of each study did not significantly alter the overall prevalence. This lends credibility to our findings and reinforces the stability of the estimated prevalence of N. gonorrhea among STI suspected patients in Ethiopia.

The assessment of publication bias through a subjective examination of the funnel plot and Egger’s regression test revealed a significant presence of bias (p-value of 0.001). The subsequent trim and fill analysis, which added five studies, further supported the indication of potentially overlooked small studies contributing to this bias. This underscores the importance of interpreting the prevalence estimate cautiously and considering potential sources of bias in the analysis.

The observed substantial heterogeneity among the included studies, as indicated by I² = 98.1%, remained a challenge. Despite attempts with a weighted inverse variance random-effects model, the heterogeneity persisted. The subjective assessment through a forest plot and subgroup analysis provided insights, but the ultimate meta-regression using sample size revealed the absence of significant heterogeneity. This finding suggests that other unexplored factors may contribute to the observed variability between studies.

Our exhaustive systematic review and meta-analysis focused on N. gonorrhea in Ethiopia, specifically examining its prevalence among STI suspected patients and its antimicrobial susceptibility. The findings provide valuable insights, indicating a pooled prevalence of 20% for N. gonorrhea among STI suspected patients. Notably, the bacterium exhibited significant resistance to penicillin and tetracycline, with a particularly alarming high resistance rate to ciprofloxacin. However, ceftriaxone, azithromycin, and spectinomycin emerged as effective alternative treatments in the face of antimicrobial resistance.

While our study on the prevalence of N. gonorrhea among STI suspected patients and its antimicrobial resistance in Ethiopia provides valuable insights, it is essential to acknowledge certain limitations for a nuanced interpretation. Notably, there is significant heterogeneity among the included studies, attributed to variations in sample size and study designs. This diversity necessitates caution when generalizing the pooled prevalence estimate, as potential biases may exist. Another notable limitation is the prevalent use of the disk diffusion method over the recommended minimum inhibitory concentration (MIC) method in primary studies. Despite these limitations, our study holds notable strengths. It offers a comprehensive analysis of N. gonorrhea prevalence and antimicrobial resistance in Ethiopia, providing valuable insights into the current landscape. The inclusion of a diverse range of studies enhances the robustness of our findings, and the meta-analysis approach allows for a comprehensive overview of the available data. These strengths contribute to the overall significance and reliability of our study’s findings.

The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.

MG: Conceptualization, Formal analysis, Methodology, Writing – original draft, Writing – review & editing. NT: Conceptualization, Data curation, Formal analysis, Writing – original draft, Writing – review & editing. TS: Investigation, Methodology, Writing – original draft, Writing – review & editing. MD: Investigation, Validation, Writing – original draft, Writing – review & editing. TK: Conceptualization, Methodology, Writing – original draft, Writing – review & editing. TW: Investigation, Methodology, Writing – original draft, Writing – review & editing. EA: Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review & editing. MH: Conceptualization, Formal analysis, Methodology, Writing – original draft, Writing – review & editing.