To Örebro University

Sexually transmitted Chlamydia trachomatis infections remain common globally and most frequently are asymptomatic. The 2025 European C. trachomatis guideline provides up-to-date guidance regarding indications for testing and treatment of C. trachomatis infections. It includes advice on urogenital and extragenital C. trachomatis testing including the use of self-collected specimens; recommendation to use only validated NAATs for diagnosis; and recommendation to treat all C. trachomatis infections with doxycycline as first line in preference to single-dose azithromycin regimens. The absence of evidence and limited value of broad screening in asymptomatic populations for C. trachomatis infections is also discussed.

Background: Since 2009, the European Centre for Disease Prevention and Control (ECDC) has coordinated the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) to monitor antimicrobial resistance (AMR) in Neisseria gonorrhoeae across the European Union and European Economic Area (EU/EEA). The aims of this study were to report Euro-GASP 2022 data and to compare with the most recently published Euro-GASP data (from 2016 to 2019), to identify changes in AMR and in risk groups for AMR.

Methods: In this observational study, 23 EU/EEA countries submitted AMR data for gonococcal isolates from 2022, linked to patient epidemiological data, to The European Surveillance System (TESSy). Statistical analyses (Z-test) were used to determine the significance of the differences between the epidemiological data and proportion of AMR isolates in 2022 versus 2019 and 2016. The risk factors associated with AMR isolates were assessed using univariate and multivariable logistic regression analyses of odds ratios.

Findings: Ceftriaxone resistance in 2022 (0.03%, 1/3008) remained low (0.06% (2/3239) in 2019), and cefixime resistance (0.3%, 10/3008) had decreased (0.8% (26/3239) in 2019). Azithromycin resistance (24.9%, 749/3008) and ciprofloxacin resistance (65.8%, 1980/3008) had increased (9.0% (284/3159) and 57.4% (1665/2884), respectively, in 2019). A marked increase in the number (575; 502 in 2019) and proportion (19.2%; 15.8% in 2019) of female gonorrhoea cases was also identified in 2022. In the univariate analysis, azithromycin resistance was associated with oropharyngeal (OR 1.67, CI 1.28-2.18; p < 0.0001) and anorectal infections (OR 1.38, CI 1.08-1.76; p = 0.0094), men-who-have-sex-with-men (MSM) (OR 3.88, CI 2.80-5.37; p < 0.0001), and females (1.71, CI 1.21-2.41; p = 0.0022). In the multivariable logistic regression model, only azithromycin resistance and MSM remained associated (OR 2.85, CI 1.33-4.73; p = 0.0040).

Interpretation: While ceftriaxone resistance remains sporadically detected in Euro-GASP, the increase in reports of occasional ceftriaxone resistance in EU/EEA countries and substantial increase in azithromycin resistance underscore the urgent need for enhanced AMR surveillance. The Euro-GASP data is crucial for refining treatment guidelines and mitigating the spread of AMR gonococcal strains. Novel effective antimicrobials for gonorrhoea treatment remain imperative.

BACKGROUND: The global spread of antimicrobial resistance (AMR) in Neisseria gonorrhoeae threatens empiric single-dose gonorrhoea treatment. Enhanced global AMR surveillance is imperative. We report i) gonococcal antimicrobial susceptibility and resistance data from 2023 in the World Health Organization Enhanced Gonococcal Antimicrobial Surveillance Programme (WHO EGASP) in the WHO Western Pacific Region (Cambodia, the Philippines, Viet Nam), Southeast Asian Region (Indonesia, Thailand), and African Region (Malawi, South Africa, Uganda, Zimbabwe), and ii) metadata of the gonorrhoea patients.

METHODS: In 2023, WHO EGASP included men with urethral discharge (n = 3498) and gonococcal isolates (n = 2491). Minimum inhibitory concentrations (MICs, mg/L) values were determined for ceftriaxone, cefixime, azithromycin, gentamicin, and ciprofloxacin using Etest (bioMérieux). Breakpoints from the European Committee on Antimicrobial Susceptibility Testing (EUCAST) were applied. Clinical and epidemiological variables associated with AMR isolates were assessed using univariable and multivariable logistic regression analyses of odds ratios.

FINDINGS: Overall, 3.8% (95% confidence interval (95% CI) 3.1-4.6%; 95/2487), 8.9% (95% CI 7.9-10.1%; 222/2484), 3.6% (95% CI 2.9-4.4%; 89/2487), and 95.3% (95% CI 93.2-97.5%; 1801/1890) of isolates were resistant to ceftriaxone, cefixime, azithromycin, and ciprofloxacin, respectively. All the ceftriaxone-resistant isolates were from Cambodia (15.3% (95% CI 11.5-20.1%), 42/274) and Viet Nam (20.4% (95% CI 15.9-25.7%), 53/260). In univariable analysis, ceftriaxone resistance was associated with travelling within the country during previous 30 days (OR 4.66, 95% CI 3.06-7.16; p < 0.001), and this association remained in multivariable analysis (aOR 4.12, 95% CI 2.65-6.65; p < 0.001).

INTERPRETATION: Resistance to ceftriaxone, cefixime, and azithromycin is a major global concern, and expanded and improved resistance surveillance is essential. The WHO EGASP has been substantially expanded in the recent years. Additionally, resistance breakpoints have been harmonised and test-of-cure, whole-genome sequencing, and extragenital sampling implemented, where feasible. Novel antimicrobials for gonorrhoea treatment are critical; zoliflodacin and gepotidacin are promising.

With over 374 million new curable bacterial STI cases annually, we are far from meeting global health targets. Despite their serious consequences for sexual, reproductive, and mental health, control efforts often focus on individual-level interventions like condom promotion and behavior change, which are insufficient. A scientific framework for STI control emphasizes reducing infectiousness, decreasing the number of susceptible individuals, and lowering transmission probability. Effective strategies should focus on environmental modifications, including expanding access to quality sexual health care, rapid testing with same-visit treatment, and AI-enhanced diagnostics. Equally critical are protecting susceptible communities through vaccination and chemoprophylaxis (e.g., doxycycline post exposure prophylaxis). While individual behavioural interventions like condom promotion remain relevant, declining usage trends challenge their impact. Surveillance of STIs and antimicrobial resistance is essential, influ-encing all key drivers of transmission. To control STIs more effectively, we must shift from individual behaviour change to systems-level public health strategies. Prioritising accessible, stigma-free health services, leveraging technological advances, and investing in comprehensive public health policies will improve STI prevention and help meet global health goals.

OBJECTIVES: Cefixime is a promising oral treatment alternative for early syphilis but only very limited efficacy data exist. We evaluated the efficacy and safety of cefixime for the treatment of early syphilis.

METHODS: A randomized controlled, open label trial in patients with confirmed early syphilis who were randomized to treatment with cefixime 400 mg orally twice a day for 14 consecutive days or to a single dose of benzathine penicillin G (BPG) 2.4 MIU intramuscular. The outcome was a 4-fold or more (≥2 dilution steps) decrease in Venereal Disease Research Laboratory test (VDRL) titre from baseline to 3 months (primary outcome) or 12 months (secondary outcome) after the treatment.

RESULTS: Of 61 randomized patients, 58 (95.1%) completed the study (28 patients in the cefixime arm and 30 in the BPG arm). In the intention to treat analysis, the primary endpoint was achieved after 3 months in 22 of 30 (73.3%) of patients in the cefixime arm and 27 of 31 (87.1%) in the BPG arm, and after 12 months in 28 of 30 (93.3%) of patients in the cefixime arm and 30 of 31 (96.8%) of patients in the BPG arm. Both treatments were well tolerated and no serious adverse events or adverse events with severe intensity were reported.

CONCLUSIONS: The results from our study are consistent with current limited knowledge and suggest that oral cefixime can be an effective and safe therapy for the treatment of early syphilis. However, additional efficacy data from larger treatment studies are imperative.

BACKGROUND: Infection with Trichomonas vaginalis (TV) is the most prevalent curable sexually transmitted infection (STI) globally and is associated with prelabour rupture of membranes, preterm delivery, and low birthweight. Point-of-care (POC) testing for TV during pregnancy may facilitate rapid antenatal case detection and treatment. This study, part of the World Health Organization's global ProSPeRo study, aimed to evaluate the performance of OSOM® Trichomonas Rapid Test, an antigen-based POC test, against a reference nucleic acid amplification test (NAAT) among pregnant women in Zambia. We also assessed the operational characteristics and patient acceptability of the POC test, within the context of WHO's target product profiles for STI POC tests.

METHODS: We enrolled pregnant women attending four health centres in Nchelenge, Zambia, for antenatal care between 15 February and 26 May 2023. Vaginal swabs for the TV POC test and a reference NAAT (Aptima® Trichomonas vaginalis assay) were obtained. POC test results were read independently by two study staff members. Study staff filled a questionnaire on the operational characteristics of the POC test, and participants were asked about their willingness to wait for results.

RESULTS: Paired POC and reference test samples were collected from 1,015 participants. Overall, 23.0% (233/1015) tested positive for TV by NAAT, and 15.3% (155/1015) tested positive by the POC test, with three inconclusive results. The overall sensitivity and specificity of the POC test were 66.4% (95% confidence intervals [CI] 57.7-74.1%) and 99.6% (95% CI: 98.8-99.9%), respectively. Sensitivity was higher among those with TV-associated symptoms compared to those without (83.6% versus 60.4%, relative ratio 1.39, 95% CI 1.14-1.68). Inter-rater agreement was 99.7% (Cohen's Kappa 0.989). The study staff (n = 14) found the test easy to use and interpret, with most staff (12/14) reporting results were available within 25 min.

CONCLUSION: Overall, the TV POC test showed lower sensitivity than WHO's 85% target, but exceeded the 99% specificity target. Among symptomatic pregnant women, sensitivity nearly reached the WHO target. The assay was user-friendly, required minimal training, and delivered results quickly. Further studies are needed to determine the optimal antenatal settings for this technology.

TRIAL REGISTRATION: PACTR202302766902029.

Resistance to the last treatment option for gonorrhoea, ceftriaxone is a major public health concern globally, which poses a serious threat to the currently recommended ceftriaxone monotherapy. We elucidate the emergence, evolution and temporal spread of ceftriaxone-resistant gonococcal strains in China, using whole-genome sequencing of 357 ceftriaxone-resistant isolates from eight provinces during 2002-2022. We describe distinct differences between ceftriaxone-resistant gonococcal strains in China and global isolates. The resistance levels for the 357 isolates for cefixime, azithromycin, ciprofloxacin, benzylpenicillin, tetracycline, and spectinomycin were 92.4%, 17.0%, 100%, 84.9%, 92.7%, and 0.8%, respectively. Before 2019, ceftriaxone-resistant isolates in China mainly harboured non-mosaic penA alleles like penA-13, penA-12, penA-18 or mosaic penA-10. From 2019, ceftriaxone-resistant isolates with mosaic penA-60.001 increased rapidly, becoming the dominant penA allele. Meanwhile, penA-60.001 was horizontally transferred from MLST ST1903 strains to strains of other MLST STs that were prevalent in China. Notably, the MLST ST7365 isolates with penA-60.001 allele had higher ceftriaxone MICs than isolates of the typical ST1903 FC428 clone. This may be attributed to a main clade of MLST ST7365 strains in China exhibiting elevated ceftriaxone MICs, and the temporal phylogeny showed this clade emerged around 1994. In summary, we reveal the unique genomic and evolutionary patterns of ceftriaxone-resistant gonococcal strains in China, and the 357 not previously reported isolates substantially increase the number of global ceftriaxone-resistant isolates. Our results suggest potential evolutionary pathways and directions of ceftriaxone-resistant strains, and provide valuable data for examining genomic epidemiology, antimicrobial resistance determinants and formulating strategies for surveillance and interventions.

BACKGROUND: Over the past 5 years, since publication of the initial review, studies have provided additional data on macrolide and fluoroquinolone resistance in Mycoplasma genitalium, including data from regions previously lacking this information. We aimed to provide contemporary estimates of macrolide and fluoroquinolone resistance in M genitalium to inform national, regional, and global treatment guidelines.

METHODS: This is an update of a previous systematic review and meta-analysis, which was performed up to Jan 7, 2019. In this update, we searched PubMed, Embase, and MEDLINE from Jan 1, 2018, to April 18, 2023, for published studies reporting macrolide, fluoroquinolone, or dual-class (macrolide and fluoroquinolone) resistance in M genitalium. Data were combined with the previous meta-analysis to examine resistance prevalence in M genitalium samples collected up to and including 2021. Random-effects meta-analyses were used to calculate summary estimates of prevalence. Subgroup analyses by WHO region and four time periods (before 2012 to 2018-21) were performed. This study was registered with PROSPERO, number CRD42021273340.

FINDINGS: 166 studies (59 from the previous search period reporting data from M genitalium samples collected between 2003 and 2017, and 107 from the updated search period reporting data from M genitalium samples collected between 2005 and 2021) were included: 157 reporting macrolide resistance (41 countries; 22 974 samples), 89 reporting fluoroquinolone resistance (35 countries; 14 165 samples), and 74 reporting dual-class resistance (34 countries; 11 070 samples). In 2018-21, the overall prevalence of macrolide, fluoroquinolone, and dual-class resistance were 33·3% (95% CI 27·2-39·7), 13·3% (10·0-17·0), and 6·5% (4·0-9·4), respectively. Over time, there was a slight, although not statistically significant, decline in macrolide resistance in the Western Pacific and the Americas, but there was an increase in macrolide resistance in the European region. Fluoroquinolone resistance was highest in the Western Pacific and increased in the European non-Nordic region. ParC S83I was the most common variant associated with fluoroquinolone resistance, increasing from 0% (95% CI <0·0001-0·30) before 2012 to 7·3% (4·7-10·3) in 2018-21; ptrend=0·055.

INTERPRETATION: Macrolide and fluoroquinolone resistance in M genitalium requires ongoing international surveillance, use of resistance assays for optimal antibiotic stewardship, and novel treatment options.

OBJECTIVES: Doxycycline post-exposure prophylaxis (doxycycline-PEP) can reduce incident cases of syphilis, chlamydia and possibly gonorrhoea especially among men who have sex with men with recent bacterial sexually transmitted infections (STIs). Owing to potential implementation of doxycycline-PEP internationally, global tetracycline/doxycycline resistance data for contemporary Neisseria gonorrhoeae isolates has become imperative. We report tetracycline resistance data for gonococcal isolates (n = 2993) from eight WHO Enhanced Gonococcal Antimicrobial Surveillance Programme (EGASP) countries in three WHO regions in 2021-2024, i.e. to estimate potential impact of doxycycline-PEP on the incident gonorrhoea cases in these WHO EGASP countries.

METHODS: WHO EGASP isolates cultured from men with urethral discharge in Cambodia (n = 482), Indonesia (n = 101), Malawi (n = 121), The Philippines (n = 843), South Africa (n = 597), Thailand (n = 250), Uganda (n = 350) and Vietnam (n = 249) in 2021-2024 were examined. MICs (mg/L) of tetracycline were determined using Etest.

RESULTS: The tetracycline resistance (range) using the current EUCAST (MIC > 0.5 mg/L) and CLSI (MIC > 1 mg/L) clinical resistance breakpoints in the eight WHO EGASP countries was 92.2% (83.5%-99.6%) and 80.6% (66.3%-98.6%), respectively. Using a previous minocycline-PEP resistance breakpoint (MIC > 2 mg/L) and breakpoint for high-level plasmid (tetM)-mediated tetracycline resistance (MIC > 8 mg/L), the tetracycline resistance (range) was 77.3% (47.4%-98.6%) and 74.3% (31.3%-98.6%), respectively.

CONCLUSIONS: The exceedingly high levels of gonococcal tetracycline resistance (independent of resistance breakpoint used) in the eight WHO EGASP countries elucidate that doxycycline-PEP will unlikely significantly reduce the gonorrhoea cases in these countries. Furthermore, doxycycline-PEP might rapidly select for additional gonococcal strains with tetracycline resistance (low- and high-level) and MDR/XDR strains, i.e. because these strains are mostly resistant to tetracycline.