The COVID-19 pandemic has revealed the importance of virus genome sequencing to guide public health interventions to control virus transmission and understand SARS-CoV-2 evolution. As of July 20th, 2021, >2 million SARS-CoV-2 genomes have been submitted to GISAID, 94% from high income and 6% from low and middle income countries. Here, we analyse the spatial and temporal heterogeneity in SARS-CoV-2 global genomic surveillance efforts. We report a comprehensive analysis of virus lineage diversity and genomic surveillance strategies adopted globally, and investigate their impact on the detection of known SARS-CoV-2 virus lineages and variants of concern. Our study provides a perspective on the global disparities surrounding SARS-CoV-2 genomic surveillance, their causes and consequences, and possible solutions to maximize the impact of pathogen genome sequencing for efforts on public health. One-Sentence Summary The causes, consequences and possible solutions for disparities in genomic surveillance observed in the COVID-19 pandemic.

Introduction: Mycoplasma genitalium is an established cause of sexually transmitted infections in men and women. Current guidelines recommend azithromycin and moxifloxacin as first- and second-line treatment, respectively. However, azithromycin treatment failure has been increasingly reported. The aim of this study was to determine the efficacy of azithromycin and alternative antibiotic regimens in a prospective cohort of M. genitalium-positive patients, and macrolide resistance mutations associated with azithromycin failure. Materials and methods: Consecutive eligible M. genitalium-positive patients attending the National Center of Infectious and Parasitic Diseases in Sofia, Bulgaria between 1 January 2018 and 31 December 2020 were treated with azithromycin and retested by polymerase chain reaction 21-28 days after completion of the treatment. Cure was defined as M. genitalium-negative result on the test of cure. Cases failing azithromycin were treated with moxifloxacin and retested another 21-28 days after treatment. Pre- and post-treatment samples were assessed for macrolide resistance mutations by conventional DNA sequencing. Results: Of 21 patients treated with azithromycin, 11 (52.4%) were cured. Pre- and post-treatment macrolide resistance mutations were detected in 10 (47.6%) patients, and all of them failed azithromycin. Moxifloxacin was effective in all cases failing azithromycin; and all were M. genitalium-negative at the test of cure after moxifloxacin treatment. Conclusions: In this study a high azithromycin failure rate (47.6%) in an M. genitalium-positive cohort in association with high levels of pretreatment macrolide resistance was reported. Moxifloxacin was highly effective in treating macrolide-resistant infections. These findings necessitate implementation of new diagnostic and therapeutic strategies such as sequential antimicrobial therapy for M. genitalium guided by a macrolide-resistance assay.

Background/Objectives: The increasing prevalence of Mycoplasma genitalium infections with macrolide-resistance, causing high azithromycin failure rates, is a major concern internationally. In response to this challenge, diagnostics that simultaneously detect M. genitalium and genetic markers for macrolide-resistance enable the therapy to be individually tailored, i.e., to implement resistance-guided therapy (RGT). This study aimed to evaluate patient treatment outcomes of M. genitalium therapy, guided by a macrolide-resistance assay in Bulgaria. Methods: Consecutively referred M. genitalium infection cases (n = 17) were analyzed for macrolide-resistance mutations (MRMs) and specific antimicrobial treatment was recommended accordingly (MRMs-negative infections received azithromycin and MRMs-positive infections received moxifloxacin). The treatment outcome based on test-of-cure was recorded, and the treatment failure rates and time to achieve a microbiological cure were compared to treatment outcomes in patients treated before the implementation of RGT. Results: Among patients given RGT (n = 17), the overall treatment failure rate was 1/17 (5.9%). This was significantly lower than the rate (47.6%) observed in patients treated pre-RGT (p = 0.002). The time to achieve a microbiological cure was 29.4 days (CI 24.5–34.3), compared to 45.2 days (CI 36.5–53.7) pre-RGT (p = 0.001). Conclusions: The implementation of M. genitalium diagnostics with macrolide-resistance detection improved treatment outcomes in Bulgaria, with significantly lower treatment failure rates and reduced time to achieve a microbiological cure. In light of the limited treatment options and concerns about their decreasing efficacy in response to misuse and overuse, a diagnostic macrolide-resistance assay is critical to direct the appropriate first-line treatment, to maintain the efficacy of antimicrobial treatment (antibiotic stewardship) and to minimize the spread of antimicrobial resistance.

Background: N. gonorrhoeae and M. genitalium infections remain public health concern due to emerging antimicrobial resistance which compromise effective treatment and infection prevention and control. Objective: To estimate the prevalence for N. gonorrhoeae and M. genitalium infections and identify demographic and sexual behavioral risk factors in Bulgarian population of reproductive age from Sofia municipality. Material and methods: Participants were sexually active 443 men and 198 women aged 18-49 years. They answered questionnaires on sexual behavior and provided samples for N. gonorrhoeae and M. genitalium testing. Results: The prevalence of N. gonorrhoeae infection was 3.28% (21/641) and with M. genitalium infection it was 2.49% (16/641). For both infections the presence of urogenital symptoms was associated with greater risk of being infected. Among gonococcal infections an increased number of lifetime partners and partners during the last 6 months, previously diagnosed STIs and use of contraception other than condoms were associated risk factors. Conclusions: The prevalence of N. gonorrhoeae and M. genitalium infections in Bulgarian population of reproductive age from Sofia municipality was relatively low but due to significant disease burden data on prevalence and identified risk factors should help the development of future control strategies.

Background: The increasing prevalence of Mycoplasma genitalium infections with macrolide resistance causing high azithromycin failure rates is a major concern internationally. In response to this challenge, diagnostics that simultaneously detect M. genitalium and genetic markers for macrolide resistance enable the therapy to be individually tailored, i.e. to implement resistance-guided therapy (RGT). Objectives: This study aimed to evaluate patient treatment outcomes of M. genitalium therapy guided by a macrolide-resistance assay in Bulgaria; Methods: Consecutively referred M. genitalium infection cases (n=17) were analyzed for macrolide-resistance mutations (MRMs) and specific antimicrobial treatment was recommended accordingly (MRMs-negative infections received azithromycin and MRMs-positive received moxifloxacin). Treatment outcome based on test-of-cure was recorded and treatment failure rates and time to microbiological cure were compared with treatment outcomes in patients treated before the implementation of RGT; Results: Among patients given RGT (n=17), the overall treatment failure rate was 1/17 (5.9%). This was significantly lower than the rate (47.6%) observed in patients treated pre-RGT (p=0.002). The time to microbiological cure was 29.4 days (CI 24.5 – 34.3) compared to 45.2 days (CI 36.5 – 53.7) pre-RGT (p=0.001); Conclusions: Implementation of M. genitalium diagnostics with macrolide-resistance detection improved treatment outcomes in Bulgaria with significantly lower treatment failure rates and reduced time to microbiological cure. In light of limited treatment options and concerns about their decreasing efficacy in response to misuse and overuse, diagnostic macrolide-resistance assay is critical to direct appropriate first-line treatment, to maintain the efficacy of antimicrobial treatment (antibiotic stewardship) and to minimize the spread of antimicrobial resistance.