The Roles of Unrecognized Mpox Cases, Contact Isolation and Vaccination in Determining Epidemic Size in Belgium: A Modeling Study.

We used a network model to simulate a mpox epidemic among men who have sex with men. Our findings suggest that unrecognized infections have an important impact on the epidemic, and that vaccination of individuals at highest risk of infection reduces epidemic size more than post-exposure vaccination of sexual partners.

Presymptomatic viral shedding in high-risk mpox contacts: A prospective cohort study.

The risk of infection after exposure to clade IIb mpox virus (MPXV) is unknown, and potential presymptomatic shedding of MPXV remains to be demonstrated. High-risk contacts of mpox patients were followed-up in a prospective longitudinal cohort study. Individuals reporting sexual contact, >15 min skin-to-skin contact, or living in the same household with an mpox patient were recruited in a sexual health clinic in Antwerp, Belgium. Participants kept a symptom diary, performed daily self-sampling (anorectal, genital, and saliva), and presented for weekly clinic visits for physical examination and sampling (blood and oropharyngeal). Samples were tested for MPXV by PCR. Between June 24 and July 31, 2022, 25 contacts were included, of which 12/18 (66.0%) sexual and 1/7 (14.0%) nonsexual contacts showed evidence of infection by MPXV-PCR. Six cases had typical mpox symptoms. Viral DNA was detected as early as 4 days before symptom onset in 5 of them. In 3 of these cases, replication-competent virus was demonstrated in the presymptomatic phase. These findings confirm the existence of presymptomatic shedding of replication-competent MPXV and emphasize the high risk of transmission during sexual contact. Sexual contacts of mpox cases should abstain from sex during the incubation period, irrespective of symptoms.

Persistent morbidity in Clade IIb mpox patients: interim results of a long-term follow-up study, Belgium, June to November 2022.

While mpox was well characterised during the 2022 global Clade IIb outbreak, little is known about persistent morbidity. We present interim results of a prospective cohort study of 95 mpox patients assessed 3-20 weeks post-symptom onset. Two-thirds of participants had residual morbidity, including 25 with persistent anorectal and 18 with genital symptoms. Loss of physical fitness, new-onset/worsened fatigue and mental health problems were reported in 36, 19 and 11 patients, respectively. These findings require attention by healthcare providers.

Global epidemiology of antimicrobial resistance in commensal Neisseria species: A systematic review.

BACKGROUND: Commensal Neisseria species (spp). represent an important reservoir of antimicrobial resistance genes for pathogenic Neisseria spp. In this systematic review, we aimed to assess the antimicrobial susceptibility of commensal Neisseria spp. and how this has evolved over time. We also aimed to assess if commensal Neisseria spp. showed intrinsic resistance to four antimicrobials - penicillin, azithromycin, ceftriaxone and ciprofloxacin. METHODS: Pubmed and Google Scholar were searched following the PRISMA guidelines. Articles reporting MICs of commensal Neisseria spp. were included according to inclusion/exclusion criteria, and the quality of the articles was assessed using a pre-designed tool. Individual and summary measures of penicillin, azithromycin, ceftriaxone and ciprofloxacin MICs were collected. Additional data was sought to perform a comparison between the MICs of pathogenic and commensal Neisseria spp. RESULTS: A total of 15 studies met our criteria.We found no evidence of intrinsic AMR in commensal Neisseria spp. We did find evidence of an increasing trend in MICs of commensal Neisseria spp. over time for all antimicrobials assessed. These findings were similar in various countries. Eight additional studies were included to compare pathogenic and commensal Neisseria spp. CONCLUSION: The MICs of commensal Neisseria spp. appear to be increasing in multiple countries. Surveillance of MICs in commensals could be used as an early warning system for antimicrobial resistance emergence in pathogens. Our findings underline the need for antibiotic stewardship interventions, particularly in populations with high antimicrobial consumption.

Chlorhexidine Mouthwash Fails to Eradicate Oropharyngeal Gonorrhea in a Clinical Pilot Trial (MoNg).

ABSTRACT: This single-arm open-label pilot trial in Antwerp, Belgium, was ended early in accordance with the protocol because twice-daily gargling with chlorhexidine 0.2% for 6 days failed to eradicate Neisseria gonorrhoeae from the oropharynx of asymptomatic men who have sex with men (n = 3; efficacy of 0%; 95% confidence interval, 0%-56.1%).

Facing increased sexually transmitted infection incidence in HIV preexposure prophylaxis cohorts: what are the underlying determinants and what can be done?

PURPOSE OF REVIEW: The combined incidence of chlamydia, gonorrhoea and syphilis in MSM PrEP (preexposure prophylaxis) cohorts now frequently exceeds 100 per 100 person years. The efficacy of antiretroviral PrEP in reducing HIV transmission has led to efforts to find similar biomedical ways reduce sexually transmitted infection (STI) incidence. We review the recent evidence for these and other strategies. RECENT FINDINGS: Doxycycline PrEP/postexposure prophylaxis has been shown to reduce the incidence of syphilis and chlamydia but not gonorrhoea. A meningococcal vaccine has been found to result in a lower incidence of gonorrhoea. Novel insights into the role of the pharynx in the transmission of gonorrhoea have led to clinical trials of oral antiseptics to reduce the spread of gonorrhoea. Intensified STI screening has been introduced in a number of clinics. Serious concerns have however been raised about the emergence of resistance to each of these strategies. This is particularly true for doxycycline PrEP which is not advocated by any guidelines we reviewed. SUMMARY: Randomized controlled trials are urgently required to ascertain the benefits and risks of interventions to reduce STIs in MSM PrEP cohorts.

Association between STI screening intensity in men who have sex with men and gonococcal susceptibility in 21 States in the USA: an ecological study.

OBJECTIVES: Antimicrobial resistance is generally linked to antimicrobial selection pressure. Antimicrobial-resistant Neisseria gonorrhoeae infections frequently emerge in core groups. We hypothesised that these groups are more often exposed to antimicrobials as a consequence of the repeated treatment of both symptomatic and asymptomatic sexually transmitted infections (STIs) and that frequent STI screening in asymptomatic patients may contribute indirectly to antimicrobial exposure. In this study, we explored the ecological association between screening intensity in men who have sex with men and antimicrobial susceptibility in N. gonorrhoeae in the USA. METHODS: Data on STI screening intensity came from the American Men's Internet Survey between October 2014 and March 2015. Data on gonococcal susceptibility to azithromycin, ceftriaxone and cefixime were used from the Gonococcal Isolate Surveillance Project in 2015. Spearman's correlation was used to determine the association between these two variables. RESULTS: A positive ecological association was found between STI screening intensity and geometric mean gonococcal minimum inhibitory concentration for ceftriaxone (rho=0.42, p=0.031) and cefixime (rho=0.42, p=0.029), but not for azithromycin (rho=0.31, p=0.11). The above results must be interpreted with caution as many limitations apply. CONCLUSIONS: Variation in STI screening intensity may contribute to differences in gonococcal resistance between States in the USA.

Could Intensive Screening for Gonorrhea/Chlamydia in Preexposure Prophylaxis Cohorts Select for Resistance? Historical Lessons From a Mass Treatment Campaign in Greenland.

INTRODUCTION: Neisseria gonorrhoeae has developed resistance to all classes of antimicrobials used against it. Current strategies to prevent the emergence of pan-resistance include increased gonorrhea screening in high-prevalence populations such as men who have sex with men taking HIV preexposure prophylaxis. By increasing antimicrobial exposure, others have argued that intensive screening may inadvertently promote the emergence of antimicrobial resistance. AIM/METHODOLOGY: To contribute to this discussion, we conducted a historical review of the effect of a mass gonorrhea treatment campaign in Greenland from 1965 to 1968 on the incidence of gonorrhea and antimicrobial resistance. We conducted a literature review using PubMed and Google Scholar to find relevant studies. Data on the incidence of gonorrhea, antimicrobial susceptibility, and antimicrobials dispensed were extracted and analyzed. RESULTS: Eight articles were found with relevant information. The cornerstone of the campaign involved the repeated treatment for all persons with a diagnosis of gonorrhea in the past 6 months as well as all remaining unmarried persons between 15 and 30 years of age. There was a small and temporary decline in the incidence of gonorrhea during the campaign. The campaign was, however, associated with an increase in the proportion of gonococci that were not susceptible to penicillin. Gonococcal incidence continued to climb after the campaign ended but did decline dramatically after reductions in risk behavior after the global AIDS epidemic. DISCUSSIONS: The mass gonorrhea treatment campaign in Greenland was associated with only a temporary decline in the incidence of gonorrhea. It was, however, followed by an increase in penicillin nonsusceptibility. Intense gonorrhea screening and treatment strategies should be aware of the risk of inducing antimicrobial resistance.

Automated quantification of glenoid bone defects using 3-dimensional measurements.

BACKGROUND: Assessment of glenoid bone defects is important to select the optimal glenoid component design during shoulder arthroplasty planning and implantation. This study presents a fully automated method to describe glenoid bone loss using 3-dimensional measurements without the need for a healthy contralateral reference scapula. METHODS: The native shape of the glenoid is reconstructed by fitting a statistical shape model (SSM) of the scapula. The total vault loss percentage, local vault loss percentages, defect depth, defect area percentage, and subluxation distance and region are computed based on a comparison of the reconstructed and eroded glenoids. The method is evaluated by comparing its results with a contralateral bone-based reconstruction approach in a data set of 34 scapula and humerus pairs with unilateral glenoid bone defects. RESULTS: The SSM-based defect measurements deviated from the contralateral bone-based measurements with mean absolute differences of 5.5% in the total vault loss percentage, 4.5% to 8.0% in the local vault loss percentages, 1.9 mm in the defect depth, 14.8% in the defect area percentage, and 1.6 mm in the subluxation distance. The SSM-based method was statistically equivalent to the contralateral bone-based method for all parameters except the defect area percentage. CONCLUSION: The presented method is able to automatically analyze glenoid bone defects using 3-dimensional measurements without the need for a healthy contralateral bone.

Where have all the susceptible gonococci gone? A historical review of changes in MIC distribution over the past 75 years.

BACKGROUND: Does the emergence of antimicrobial resistance in Neisseria gonorrhoeae include the erasure of highly susceptible strains or does it merely involve a stretching of the MIC distribution? If it was the former this would be important to know as it would increase the probability that the loss of susceptibility is irreversible. METHODS: We conducted a historical analysis based on a literature review of changes of N. gonorrhoeae MIC distribution over the past 75 years for 3 antimicrobials (benzylpenicillin, ceftriaxone and azithromycin) in five countries (Denmark, Japan, South Africa, the United Kingdom and the United States). RESULTS: Changes in MIC distribution were most marked for benzylpenicillin and showed evidence of a right shifting of MIC distribution that was associated with a reduction/elimination of susceptible strains in all countries. In the case of ceftriaxone and azithromycin, where only more recent data was available, right shifting was also found in all countries but the extent of right shifting varied and the evidence for the elimination of susceptible strains was more mixed. CONCLUSIONS: The finding of right shifting of MIC distribution combined with reduction/elimination of susceptible strains is of concern since it suggests that this shifting may not be reversible. Since excess antimicrobial consumption is likely to be responsible for this right shifting, this insight provides additional impetus to promote antimicrobial stewardship.

Antibiotic stewardship interventions in hospitals in low-and middle-income countries: a systematic review.

OBJECTIVE: To review the effectiveness of antibiotic stewardship interventions in hospitals in low- and middle-income countries. METHODS: We searched MEDLINE®, Embase®, Cochrane Central Register of Controlled Trials and regional indexes for studies of interventions to improve appropriate prescribing and use of antibiotics for hospitalized patients in low- and middle-income countries. We included controlled trials, controlled before-and-after studies and interrupted time-series studies published up to December 2017. We report prescribing, clinical and microbiological outcomes using a narrative approach. FINDINGS: We screened 7342 original titles and abstracts, assessed 241 full-text articles and included 27 studies from 2 low-income and 11 middle-income countries. We found a medium (11 studies) or high risk (13 studies) of bias. Generally, all types of interventions (structural, persuasive and enabling) and intervention bundles were reported to improve prescribing and clinical outcomes. However, the studied interventions and reported outcomes varied widely. The most frequent intervention was procalcitonin-guided antibiotic treatment (8 of 27 studies, all randomized controlled trials). The intervention was associated with a relative risk for patients receiving antibiotics ranging between 0.40 and 0.87. CONCLUSION: The majority of studies reported a positive effect of hospital antibiotic stewardship interventions. However, we cannot draw general conclusions about the effectiveness of such interventions in low- and middle-income countries because of low study quality, heterogeneity of interventions and outcomes, and under-representation of certain settings. To strengthen the evidence base, action needs to be taken to address these shortcomings.

Virtual reconstruction of glenoid bone defects using a statistical shape model.

BACKGROUND: Description of the native shape of a glenoid helps surgeons to preoperatively plan the position of a shoulder implant. A statistical shape model (SSM) can be used to virtually reconstruct a glenoid bone defect and to predict the inclination, version, and center position of the native glenoid. An SSM-based reconstruction method has already been developed for acetabular bone reconstruction. The goal of this study was to evaluate the SSM-based method for the reconstruction of glenoid bone defects and the prediction of native anatomic parameters. METHODS: First, an SSM was created on the basis of 66 healthy scapulae. Then, artificial bone defects were created in all scapulae and reconstructed using the SSM-based reconstruction method. For each bone defect, the reconstructed surface was compared with the original surface. Furthermore, the inclination, version, and glenoid center point of the reconstructed surface were compared with the original parameters of each scapula. RESULTS: For small glenoid bone defects, the healthy surface of the glenoid was reconstructed with a root mean square error of 1.2 ± 0.4 mm. Inclination, version, and glenoid center point were predicted with an accuracy of 2.4° ± 2.1°, 2.9° ± 2.2°, and 1.8 ± 0.8 mm, respectively. DISCUSSION AND CONCLUSION: The SSM-based reconstruction method is able to accurately reconstruct the native glenoid surface and to predict the native anatomic parameters. Based on this outcome, statistical shape modeling can be considered a successful technique for use in the preoperative planning of shoulder arthroplasty.

Estimating Partnership Duration among MSM in Belgium-A Modeling Study.

Mathematical modeling is widely used for describing infection transmission and evaluating interventions. The lack of reliable social parameters in the literature has been mentioned by many modeling studies, leading to limitations in the validity and interpretation of the results. Using data from the European MSM Internet survey 2017, we developed a network model to describe sex acts among MSM in Belgium. The model simulates daily sex acts among steady, persistent casual and one-off partners in a population of 10,000 MSM, grouped as low- or high-activity by using three different definitions. Model calibration was used to estimate partnership duration and homophily rates to match the distribution of cumulative sex partners over 12 months. We estimated an average duration between 1065 and 1409 days for steady partnerships, 4-6 and 251-299 days for assortative high- and low-activity individuals and 8-13 days for disassortative persistent casual partnerships, respectively, varying across the three definitions. High-quality data on social network and behavioral parameters are scarce in the literature. Our study addresses this lack of information by providing a method to estimate crucial parameters for network specification.

Lack of Association between Antimicrobial Consumption and Antimicrobial Resistance in a HIV Preexposure Prophylaxis Population: A Cross-Sectional Study.

BACKGROUND: In antibiotic naïve populations, there is a strong association between the use of an antimicrobial and resistance to this antimicrobial. Less evidence is available as to whether this relationship is weakened in populations highly exposed to antimicrobials. Individuals taking HIV preexposure prophylaxis (PrEP) have a high intake of antimicrobials. We previously found that there was no difference in the prevalence of pheno- and genotypic antimicrobial resistance between two groups of PrEP clients who had, and had not, taken antimicrobials in the prior 6 months. Both groups did, however, have a higher prevalence of resistance than a sample of the general population. METHODS: In the current study, we used zero-inflated negative binomial regression models to evaluate if there was an individual level association between the consumption of antimicrobials and 1. the minimum inhibitory susceptibilities of oral Neisseria subflava and 2. the abundance of antimicrobial resistance genes in the oropharynges of these individuals. RESULTS: We found no evidence of an association between the consumption of antimicrobials and the minimum inhibitory susceptibilities of oral Neisseria subflava or the abundance of antimicrobial resistance genes in these individuals. CONCLUSIONS: We conclude that in high-antimicrobial-consumption populations, the association between antimicrobial consumption and resistance may be attenuated. This conclusion would not apply to lower-consumption populations.

Gonococcal resistance to zoliflodacin could emerge via transformation from commensal Neisseria species. An in-vitro transformation study.

One of the most promising new treatments for gonorrhoea currently in phase 3 clinical trials is zoliflodacin. Studies have found very little resistance to zoliflodacin in currently circulating N. gonorrhoeae strains, and in-vitro experiments demonstrated that it is difficult to induce resistance. However, zoliflodacin resistance may emerge in commensal Neisseria spp., which could then be transferred to N. gonorrhoeae via transformation. In this study, we investigated this commensal-resistance-pathway hypothesis for zoliflodacin. To induce zoliflodacin resistance, ten wild-type susceptible isolates belonging to 5 Neisseria species were serially passaged for up to 48 h on gonococcal agar plates containing increasing zoliflodacin concentrations. Within 7 to 10 days, all strains except N. lactamica, exhibited MICs of ≥ 4 µg/mL, resulting in MIC increase ranging from 8- to 64-fold. The last passaged strains and their baseline were sequenced. We detected mutations previously reported to cause zoliflodacin resistance in GyrB (D429N and S467N), novel mutations in the quinolone resistance determining region (QRDR) (M464R and T472P) and mutations outside the QRDR at amino acid positions 28 and 29 associated with low level resistance (MIC 2 µg/mL). Genomic DNA from the laboratory evolved zoliflodacin-resistant strains was transformed into the respective baseline wild-type strain, resulting in MICs of ≥ 8 µg/mL in most cases. WGS of transformants with decreased zoliflodacin susceptibility revealed presence of the same zoliflodacin resistance determinants as observed in the donor strains. Two inter-species transformation experiments were conducted to investigate whether zoliflodacin resistance determinants of commensal Neisseria spp. could be acquired by N. gonorrhoeae. N. gonorrhoeae strain WHO P was exposed to (i) pooled genomic DNA from the two resistant N. mucosa strains and (ii) a gyrB amplicon of the resistant N. subflava strain 45/1_8. Transformants of both experiments exhibited an MIC of 2 µg/mL and whole genome analysis revealed uptake of the mutations detected in the donor strains. This is the first in-vitro study to report that zoliflodacin resistance can be induced in commensal Neisseria spp. and subsequently transformed into N. gonorrhoeae.

Effect of screening for Neisseria gonorrhoeae and Chlamydia trachomatis on incidence of these infections in men who have sex with men and transgender women taking HIV pre-exposure prophylaxis (the Gonoscreen study): results from a randomised, multicentre, controlled trial.

BACKGROUND: Guidelines recommend screening for Neisseria gonorrhoeae and Chlamydia trachomatis at three anatomical sites (urethra, anus, and pharynx) every 3 months (3 × 3) in men who have sex with men (MSM) and transgender women taking HIV pre-exposure prophylaxis (PrEP). We present the first randomised controlled trial to compare the effect of screening versus non-screening for N gonorrhoeae and C trachomatis on the incidence of these infections in MSM and transgender women taking PrEP. METHODS: A multicentre, randomised, controlled trial of 3 × 3 screening for N gonorrhoeae and C trachomatis versus non-screening was done among MSM and transgender women taking PrEP in five HIV reference centers in Belgium. Participants attended the PrEP clinics quarterly for 12 months. N gonorrhoeae and C trachomatis was tested at each visit in both arms, but results were not provided to the non-screening arm, if asymptomatic. The primary outcome was incidence rate of N gonorrhoeae and C trachomatis infections in each arm, assessed in the per-protocol population. Non-inferiority of the non-screening arm was proven if the upper limit of the 95% CI of the incidence rate ratio (IRR) was lower than 1·25. This trial is registered with ClinicalTrials.gov, NCT04269434, and is completed. FINDINGS: Between Sept 21, 2020, and June 4, 2021, 506 participants were randomly assigned to the 3 × 3 screening arm and 508 to the non-screening arm. The overall incidence rate of N gonorrhoeae and C trachomatis was 0·155 cases per 100 person-days (95% CI 0·128-0·186) in the 3 × 3 screening arm and 0·205 (95% CI 0·171-0·246) in the non-screening arm. The incidence rate was significantly higher in the non-screening arm (IRR 1·318, 95% CI 1·068-1·627). Participants in the non-screening arm had a higher incidence of C trachomatis infections and symptomatic C trachomatis infections. There were no significant differences in N gonorrhoeae infections. Participants in the non-screening arm consumed significantly fewer antimicrobial drugs. No serious adverse events were reported. INTERPRETATION: We failed to show that non-screening for N gonorrhoeae and C trachomatis is non-inferior to 3 × 3 screening in MSM and transgender women taking PrEP in Belgium. However, screening was associated with higher antibiotic consumption and had no effect on the incidence of N gonorrhoeae. Further research is needed to assess the benefits and harms of N gonorrhoeae and C trachomatis screening in this population. FUNDING: Belgian Health Care Knowledge Centre.