The laboratory parameters-derived CoLab score as an indicator of the host response in ICU COVID-19 patients decreases over time: a prospective cohort study.

The CoLab score was developed and externally validated to rule out COVID-19 among suspected patients presenting at the emergency department. We hypothesized a within-patient decrease in the CoLab score over time in an intensive care unit (ICU) cohort. Such a decrease would create the opportunity to potentially rule out the need for isolation when the infection is overcome. Using linear mixed-effects models, data from the Maastricht Intensive Care COVID (MaastrICCht) cohort were used to investigate the association between time and the CoLab score. Models were adjusted for sex, APACHE II score, ICU mortality, and daily SOFA score. The CoLab score decreased by 0.30 points per day (95% CI - 0.33 to - 0.27), independent of sex, APACHE II, and Mortality. With increasing SOFA score over time, the CoLab score decreased more strongly (- 0.01 (95% CI - 0.01 to - 0.01) additional decrease per one-point increase in SOFA score.) The CoLab score decreased in ICU patients on mechanical ventilation for COVID-19, with a one-point reduction per three days, independent of sex, APACHE II, and ICU mortality, and somewhat stronger with increasing multi-organ failure over time. This suggests that the CoLab score would decrease below a threshold where COVID-19 can be excluded.

The CoLab score is associated with SARS-CoV-2 viral load during admission in individuals admitted to the intensive care unit: the CoLaIC cohort study.

OBJECTIVES: The present study examines the temporal association between the changes in SARS-CoV-2 viral load during infection and whether the CoLab-score can facilitate de-isolation. METHODS: Nasal swabs and blood samples were collected from ICU-admitted SARS-CoV-2 positive patients at Maastricht UMC+ from March 25, 2020 to October 1, 2021. The CoLab-score was calculated based on 10 blood parameters and age and can range from -43 to 6. Three mixed effects analyses compared patient categories based on initial PCR Ct values (low; Ct≤20, mid; 20>Ct≤30, high; Ct>30), serial PCR Ct values to CoLab-scores over time, and the association between within-patient delta Ct values and CoLab-scores. RESULTS: In 324 patients, the median Ct was 33, and the median CoLab-score was -1.78. Mid (n=110) and low (n=41) Ct-categories had higher CoLab-scores over time (+0.60 points, 95 % CI; 0.04-1.17, and +0.28 points, 95 % CI -0.49 to 1.04) compared to the high Ct (n=87) category. Over time, higher serial Ct values were associated with lower serial CoLab-scores, decreasing by -0.07 points (95 % CI; -0.11 to -0.02) per day. Increasing delta Ct values were associated with a decreasing delta CoLab-score of -0.12 (95 % CI; -0.23; -0.01). CONCLUSIONS: The study found an association between lower viral load on admission and reduced CoLab-score. Additionally, a decrease in viral load over time was associated with a decrease in CoLab-score. Therefore, the CoLab-score may make patient de-isolation an option based on the CoLab-score.

Corneal Transplantation for Infectious Keratitis: A Prospective Dutch Registry Study.

PURPOSE: The aim of this study was to analyze real-world practice patterns and graft survival after corneal transplantation for infectious keratitis in the Netherlands. METHODS: All consecutive keratoplasties for infectious keratitis registered in the Netherlands Organ Transplant Registry were included. Graft survival was analyzed using Kaplan-Meier survival curves with Cox regression to compare the 3 most common pathogens with subgroup analysis for type and reason of transplantation, sex, and graft size. Multivariable analysis was performed using the same explanatory factors. RESULTS: Between 2007 and 2017, 1111 keratoplasties for infectious keratitis were registered in the Netherlands Organ Transplant Registry. The most common pathogens were viruses (n = 437), bacteria (n = 271), and Acanthamoeba (n = 121). Human leukocyte antigen (HLA) matching did not provide a significant survival benefit, whereas emergency procedures showed worse graft survival [hazard ratio (HR) = 0.40, P = 0.120; HR = 2.73, P < 0.001, respectively]. Graft size >8.5 mm was significantly worse than graft size 8.5 mm (HR = 2.062, P = 0.010). In therapeutic keratoplasty, graft survival was significantly worse for Acanthamoeba than viral keratitis (HR = 2.36, P = 0.008). In the multivariable model, adjusting for graft size, type, and reason for transplantation, viral and bacterial keratitis did not differ significantly in graft survival, and Acanthamoeba showed a significantly worse prognosis (vs. viral keratitis, HR = 2.30, P < 0.001; bacterial keratitis, HR = 2.65, P < 0.001). CONCLUSIONS: Viral keratitis was the most common indication for transplantation, followed by bacterial and Acanthamoeba keratitis. HLA matching did not offer protection over elective non-HLA-matched procedures, whereas emergency procedures and grafts sized >8.5 mm showed poor survival. In optical keratoplasty, survival is high for all pathogens, whereas in therapeutic keratoplasty Acanthamoeba shows poor outcome.

Chlamydia trachomatis Coinfection Does Not Influence Mycoplasma genitalium Bacterial Load in Urogenital Samples.

BACKGROUND: Mycoplasma genitalium (MG) is associated with urethritis in men and weakly associated with pelvic inflammatory disease in women. Mycoplasma genitalium coinfections with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) are commonly reported; however, little is known about their interaction. One study suggested that MG/NG coinfections might increase the bacterial load of NG, which has been shown to have a higher transmission potential. As even less is known about the impact of a simultaneous MG/CT infection, we assessed whether patients with urogenital MG/CT coinfections have a higher bacterial load than patients with a single infection. METHODS: There were 1673 urogenital samples from patients from a population-based chlamydia study, and our sexually transmitted infection clinic tested for both CT and MG. When positive, the load was quantified. Nonparametric tests compared the CT and MG load, and linear regression analyses tested the association of the CT and MG load within a patient. RESULTS: In 60 MG-positive patients, MG load ranged from 1.7 to 6.0 log10 copies/ml, similar to the CT load distribution. Only 6 patients were MG-positive and CT-negative, but the MG load distribution was similar to that of CT-positive patients (n.s.). The MG and CT load was unrelated in coinfected persons (n.s.). CONCLUSIONS: We found no correlation between the CT and MG load in urogenital samples, and the MG load distribution was similar in CT-positive and CT-negative patients. These results could have implications for the transmission risk of these infections.

Validating a clinical laboratory parameter-based deisolation algorithm for patients with COVID-19 in the intensive care unit using viability PCR: the CoLaIC multicentre cohort study protocol.

INTRODUCTION: To investigate whether biochemical and haematological changes due to the patient's host response (CoLab algorithm) in combination with a SARS-CoV-2 viability PCR (v-PCR) can be used to determine when a patient with COVID-19 is no longer infectious.We hypothesise that the CoLab algorithm in combination with v-PCR can be used to determine whether or not a patient with COVID-19 is infectious to facilitate the safe release of patients with COVID-19 from isolation. METHODS AND ANALYSIS: This study consists of three parts using three different cohorts of patients. All three cohorts contain clinical, vital and laboratory parameters, as well as logistic data related to isolated patients with COVID-19, with a focus on intensive care unit (ICU) stay. The first cohort will be used to develop an algorithm for the course of the biochemical and haematological changes of the host response of the COVID-19 patient. Simultaneously, a second prospective cohort will be used to investigate the algorithm derived in the first cohort, with daily measured laboratory parameters, next to conventional SARS-CoV-2 reverse transcriptase PCRs, as well as v-PCR, to confirm the presence of intact SARS-CoV-2 particles in the patient. Finally, a third multicentre cohort, consisting of retrospectively collected data from patients with COVID-19 admitted to the ICU, will be used to validate the algorithm. ETHICS AND DISSEMINATION: This study was approved by the Medical Ethics Committee from Maastricht University Medical Centre+ (cohort I: 2020-1565/300523) and Zuyderland MC (cohorts II and III: METCZ20200057). All patients will be required to provide informed consent. Results from this study will be disseminated via peer-reviewed journals and congress/consortium presentations.

Longitudinal fluctuations of common antimicrobial resistance genes in the gut microbiomes of healthy Dutch individuals.

The human gut microbiome is an important reservoir of antimicrobial resistance genes (ARGs), collectively termed the 'resistome'. To date, few studies have examined the dynamics of the human gut resistome in healthy individuals. Previously, the authors observed high rates of ARG acquisition and significant abundance shifts during international travel. In order to provide insight into commonly occurring dynamics, this study investigated longitudinal fluctuations in prevalent ARGs (cfxA, tetM and ermB) in the resistomes of non-travelling healthy volunteers. In addition, this study assessed the prevalence of acquirable ARGs (blaCTX-M, qnrB, qnrS, vanA and vanB) over time. Faecal samples from 23 participants were collected at baseline and after 2 and 4 weeks. DNA was isolated, and ARG quantification was performed by quantitative polymerase chain reaction adjusting for the total amount of bacterial 16S rDNA. vanA and qnrS were not detected in any of the samples, while the prevalence rates of vanB of non-enterococcal origin and qnrB were 73.9% and 5.7%, respectively. The ß-lactamase encoding blaCTX-M was detected in 17.4% of healthy participants. The results were compared with previous data from 122 travellers. ARG acquisitions observed in travellers were rare in non-travelling individuals during 4 weeks of follow-up, supporting the hypothesis of ARG acquisition during international travel. However, median -1.04- to 1.04-fold abundance changes were observed for 100% of cfxA, tetM and ermB, which did not differ from those found in travellers. Thus, common abundance shifts in prevalent ARGs of the gut resistome were found to occur independent of travel behaviour.

Culture-Independent Genotyping Improves Surveillance of Neisseria gonorrhoeae, Especially in Oropharyngeal Samples, the Netherlands, 2017 to 2018.

It is important i to monitor the transmission and antimicrobial resistance of Neisseria gonorrhoeae (NG). Current surveillance relies on culturing, which frequently fails. Previously, a culture-independent genotyping method was developed based on NG multi-antigen sequence typing (NG-MAST). To determine whether crucial sequence types (STs) are missed during culture-dependent surveillance, NG-positive NAAT samples were genotyped, and the results of the culture-positive and culture-negative samples were compared. In total, 196 NG-positive NAAT samples, from January 2017 until August 2018, which were also routinely cultured, were retrospectively included. Genotyping was successful in 152 NAAT samples (77.0%), 33 NAAT samples failed, and 11 NAAT samples showed possible mixed strain infections. Oropharyngeal samples (n = 16) showed the largest increase in typing rate from 6.3% (1/16) success in culture-dependent genotyping to 81.3% (13/16) in culture-independent genotyping. Nine genogroups (n ≥ 5 samples) were found; all included both culture-positive and culture-negative NG. However, culture-independent surveillance revealed 14 additional STs in the culture-negative samples. Overall, culture-dependent surveillance could detect all genogroups, indicating that major trends could be identified with culture-dependent surveillance. However, culture-independent surveillance provides more STs, mixed infections and more oropharyngeal samples, giving a more detailed view and could result in an earlier detection of outbreaks and transmission.

Evaluation of symptomatology and viral load among residents and healthcare staff in long-term care facilities: A coronavirus disease 2019 retrospective case-cohort study.

OBJECTIVES: We evaluated COVID-19 symptoms, case fatality rate (CFR), and viral load among all Long-Term Care Facility (LTCF) residents and staff in South Limburg, the Netherlands (February 2020-June 2020, wildtype SARS-CoV-2 Wuhan strain). METHODS: Patient information was gathered via regular channels used to notify the public health services. Ct-values were obtained from the Maastricht University Medical Centre laboratory. Logistic regression analyses were performed to assess associations between COVID-19, symptoms, CFR, and viral load. RESULTS: Of 1,457 staff and 1,540 residents, 35.1% and 45.2% tested positive for COVID-19. Symptoms associated with COVID-19 for female staff were fever, cough, muscle ache and loss of taste and smell. Associated symptoms for men were cough, and loss of taste and smell. Associated symptoms for residents were subfebrility, fatigue, and fever for male residents only. LTCF residents had a higher mean viral load compared to staff. Male residents had a higher CFR (35.8%) compared to women (22.5%). Female residents with Ct-values 31 or less had increased odds of mortality. CONCLUSIONS: Subfebrility and fatigue seem to be associated with COVID-19 in LTCF residents. Therefore, physicians should also consider testing residents who (only) show aspecific symptoms whenever available resources prohibit testing of all residents. Viral load was higher in residents compared to staff, and higher in male residents compared to female residents. All COVID-19 positive male residents, as well as female residents with a medium to high viral load (Ct-values 31 or lower) should be monitored closely, as these groups have an overall increased risk of mortality.

Infections with the SARS-CoV-2 Delta variant exhibit fourfold increased viral loads in the upper airways compared to Alpha or non-variants of concern.

There has been a growing body of evidence that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant (B.1.617.2) shows enhanced transmissibility and increased viral loads compared to other variants. A recent study has even suggested that respiratory samples from people infected with the Delta variant can harbor up to 1000 times higher viral loads compared to samples with variants that are more closely related to the original Wuhan strain, although the sample size of this study (n = 125) was very limited. Here, we have compared the viral load in 16,185 samples that were obtained in periods during which non-VOC, the Alpha (B.1.1.7) or Delta variant (B.1.617.2) were dominant as evidenced by genomic surveillance. We found that the Delta variant contained about fourfold higher viral loads across all age groups compared to the non-VOC or Alpha variants, which is significantly lower than reported earlier. Interestingly, the increased viral load for the Delta variant seemed to be age-dependent, regardless of sex, as the viral load was about 14-fold higher for Delta compared to the non-VOC or Alpha variant in age group 0-20 years and fourfold higher in age group 21-40 years, while there was no difference in viral load between variants in age groups 41-60 and 61+ years, most likely as a consequence of a higher degree of vaccination in the older age groups.

Effectiveness of Commonly Used Contact Lens Disinfectants Against SARS-CoV-2.

OBJECTIVE: To assess the effect of commonly used contact lens disinfectants against severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). METHODS: The efficacy of five disinfectant solutions against SARS-CoV-2 was tested in the presence and absence of contact lenses (CLs). Three types of unused CLs (hard gas permeable, soft hydrogel, and soft silicone hydrogel) and worn silicone hydrogel CLs were tested. Contact lenses were infected with SARS-CoV-2 and disinfected at various times, with and without rubbing and rinsing, as per manufacturer's instructions. Reverse-transcriptase polymerase chain reaction (RT-PCR) and viability polymerase chain reaction (PCR) were applied to detect SARS-CoV-2 RNA and viral infectivity of SARS-CoV-2, respectively. RESULTS: In the presence of SARS-CoV-2-infected CLs, no SARS-CoV-2 RNA could be detected when disinfectant solutions were used according to the manufacturer's instructions. When SARS-Co-V2-infected CLs were disinfected without the rub-and-rinse step, SARS-CoV-2 RNA was detected at almost each time interval with each disinfecting solution tested for both new and worn CLs. In the absence of CLs, viable SARS-CoV-2 was detected with all disinfectant solutions except Menicon Progent at all time points. CONCLUSIONS: Disinfectant solutions effectively disinfect CLs from SARS-CoV-2 if manufacturer's instructions are followed. The rub-and-rinse regimen is mainly responsible for disinfection. The viability PCR may be useful to indicate potential infectiousness.

Controversies and evidence on Chlamydia testing and treatment in asymptomatic women and men who have sex with men: a narrative review.

BACKGROUND: Chlamydia trachomatis (CT) is the most common bacterial sexually transmitted infection (STI) worldwide. CT is mainly asymptomatic. Test-and-treat strategies are widely implemented to prevent transmission and complications. Strategies are not without controversy in asymptomatic women and men who have sex with men (MSM). Concerns are emerging to test and treat asymptomatic persons for urogenital CT ('Controversy 1') and pharyngeal or rectal CT ('Controversy 2'), whereby testing symptomatic persons is not under debate. Opposed views in CT treatment involve using azithromycin versus doxycycline ('Controversy 3'). The objective of this review is to provide coverage of these public health and clinical controversies by reviewing the current scientific evidence. METHODS: A literature search was performed using PubMed for relevant publications between 2018 and September 2021, and iterative retrieval of additional relevant publications. RESULTS: Controversy 1. In women, the majority of asymptomatic CT are at the urogenital site, and detections mostly include viable CT. CT easily transmits to a partner and potentially also between the vaginal and rectal areas; the clinical impact of urogenital CT is established, although risks for adverse outcomes are uncertain. Wide-scale testing in asymptomatic women has not resulted in reduced prevalence. In MSM, evidence for the clinical impact of asymptomatic urogenital CT is lacking. Controversy 2. Rectal CT is common in women diagnosed with urogenital CT, but the clinical impact of asymptomatic rectal CT is uncertain. In MSM, rectal CT is common, and most CT infections are at the rectal site, yet the risk of longer term complications is unknown. In both sexes, pharyngeal CT is uncommon and has no documented clinical impact. Controversy 3. In the treatment of rectal CT, doxycycline has superior effectiveness to azithromycin. Evidence has also accumulated on the harms of test-and-treat strategies. CONCLUSIONS: Current practices vary widely, from widescale test-and-treat approaches to more individual patient- and partner-level case management. Choosing which asymptomatic people to test at what anatomic site, and whether to test or not, requires an urgent (re-)definition of the goals of testing and treating asymptomatic persons. Treatment guidelines are shifting toward universal doxycycline use, and clinical practice now faces the challenge of implementation.

Improving diagnosis and risk stratification across the ejection fraction spectrum: the Maastricht Cardiomyopathy registry.

AIMS: Heart failure (HF) represents a clinical syndrome resulting from different aetiologies and degrees of heart diseases. Among these, a key role is played by primary heart muscle disease (cardiomyopathies), which are the combination of multifactorial environmental insults in the presence or absence of a known genetic predisposition. The aim of the Maastricht Cardiomyopathy registry (mCMP-registry; NCT04976348) is to improve (early) diagnosis, risk stratification, and management of cardiomyopathy phenotypes beyond the limits of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: The mCMP-registry is an investigator-initiated prospective registry including patient characteristics, diagnostic measurements performed as part of routine clinical care, treatment information, sequential biobanking, quality of life and economic impact assessment, and regular follow-up. All subjects aged ≥16 years referred to the cardiology department of the Maastricht University Medical Center (MUMC+) for HF-like symptoms or cardiac screening for cardiomyopathies are eligible for inclusion, irrespective of phenotype or underlying causes. Informed consented subjects will be followed up for 15 years. Two central approaches will be used to answer the research questions related to the aims of this registry: (i) a data-driven approach to predict clinical outcome and response to therapy and to identify clusters of patients who share underlying pathophysiological processes; and (ii) a hypothesis-driven approach in which clinical parameters are tested for their (incremental) diagnostic, prognostic, or therapeutic value. The study allows other centres to easily join this initiative, which will further boost research within this field. CONCLUSIONS: The broad inclusion criteria, systematic routine clinical care data-collection, extensive study-related data-collection, sequential biobanking, and multi-disciplinary approach gives the mCMP-registry a unique opportunity to improve diagnosis, risk stratification, and management of HF and (early) cardiomyopathy phenotypes beyond the LVEF limits.

Determinants associated with viable genital or rectal Chlamydia trachomatis bacterial load (FemCure).

BACKGROUND: Chlamydia trachomatis (CT) is routinely diagnosed by nucleic acid amplification tests (NAATs), which are unable to distinguish between nucleic acids from viable and non-viable CT organisms. OBJECTIVES: We applied our recently developed sensitive PCR (viability PCR) technique to measure viable bacterial CT load and explore associated determinants in 524 women attending Dutch sexual health centres (STI clinics), and who had genital or rectal CT. METHODS: We included women participating in the FemCure study (Netherlands, 2016-2017). At the enrolment visit (pre-treatment), 524 were NAAT positive (n=411 had genital and rectal CT, n=88 had genital CT only and n=25 had rectal CT only). We assessed viable rectal and viable genital load using V-PCR. We presented mean load (range 0 (non-viable) to 6.5 log10 CT/mL) and explored potential associations with urogenital symptoms (coital lower abdominal pain, coital blood loss, intermenstrual bleeding, altered vaginal discharge, painful or frequent micturition), rectal symptoms (discharge, pain, blood loss), other anatomical site infection and sociodemographics using multivariable regression analyses. RESULTS: In genital (n=499) CT NAAT-positive women, the mean viable load was 3.5 log10 CT/mL (SD 1.6). Genital viable load was independently associated with urogenital symptoms-especially altered vaginal discharge (Beta=0.35, p=0.012) and with concurrent rectal CT (aBeta=1.79; p<0.001). Urogenital symptoms were reported by 50.3% of women; their mean genital viable load was 3.6 log10 CT/mL (vs 3.3 in women without symptoms). Of 436 rectal CT NAAT-positive women, the mean rectal viable load was 2.2 log10 CT/mL (SD 2.0); rectal symptoms were reported by 2.5% (n=11) and not associated with rectal viable load. CONCLUSION: Among women diagnosed with CT in an outpatient clinical setting, viable genital CT load was higher in those reporting urogenital symptoms, but the difference was small. Viable genital load was substantially higher when women also had a concurrent rectal CT. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT02694497.

In-Depth Investigation of Conjunctival Swabs and Tear Fluid of Symptomatic COVID-19 Patients, an Observational Cohort Study.

Purpose: The putative presence of SARS-CoV-2 in ocular specimen puts healthcare workers at risk. We thoroughly examined conjunctival swabs and tear fluid in a large cohort of COVID-19 patients. Methods: A total of 243 symptomatic laboratory-confirmed COVID-19 patients were included in this observational multicenter study. Conjunctival swabs were analyzed by reverse transcription polymerase chain reaction for detection of SARS-CoV-2 RNA. Next-generation sequencing and phylogenetic analysis were performed to identify viral strains and to determine tissue tropism. Schirmer tear samples from 43 hospitalized COVID-19 patients and 25 healthy controls were analyzed by multiplex cytokine immunoassays. Results: Viral SARS-CoV-2 RNA was detected in conjunctival swabs from 17 (7.0%) of 243 COVID-19 patients. Conjunctival samples were positive for viral SARS-CoV-2 RNA as long as 12 days after disease onset. Cycle threshold (Ct) values for conjunctival swabs (mean 34.5 ± 5.1) were significantly higher than nasopharyngeal swabs (mean 16.7 ± 3.6). No correlation between Ct values of conjunctival and nasopharyngeal swabs was observed. The majority of positive conjunctival samples were detected only once and primarily during the first visit. Next-generation sequencing analysis revealed that the virus strain found in the conjunctiva was most often identical to the one found in the nasopharynx. Tear cytokine levels IL-1ß and IL-6 were elevated in COVID-19 patients compared to healthy controls. Conclusions: Conjunctival samples that were positive for SARS-CoV-2 RNA contained the same viral strain as the nasopharynx. Translational Relevance: The presence of SARS-CoV-2 viral RNA and elevated cytokines in tear fluid confirm the involvement of the ocular surface in COVID-19 disease.

Combining stool and stories: exploring antimicrobial resistance among a longitudinal cohort of international health students.

BACKGROUND: Antimicrobial resistance (AMR) is a global public health concern that requires transdisciplinary and bio-social approaches. Despite the continuous calls for a transdisciplinary understanding of this problem, there is still a lack of such studies. While microbiology generates knowledge about the biomedical nature of bacteria, social science explores various social practices related to the acquisition and spread of these bacteria. However, the two fields remain disconnected in both methodological and conceptual levels. Focusing on the acquisition of multidrug resistance genes, encoding extended-spectrum betalactamases (CTX-M) and carbapenemases (NDM-1) among a travelling population of health students, this article proposes a methodology of 'stool and stories' that combines methods of microbiology and sociology, thus proposing a way forward to a collaborative understanding of AMR. METHODS: A longitudinal study with 64 health students travelling to India was conducted in 2017. The study included multiple-choice questionnaires (n = 64); a collection of faecal swabs before travel (T0, n = 45), in the first week in India (T1, n = 44), the second week in India (T2, n = 41); and semi-structured interviews (n = 11). Stool samples were analysed by a targeted metagenomic approach. Data from semi-structured interviews were analysed using the method of thematic analysis. RESULTS: The incidence of ESBL- and carbapenemase resistance genes significantly increased during travel indicating it as a potential risk; for CTX-M from 11% before travel to 78% during travel and for NDM-1 from 2% before travel to 11% during travel. The data from semi-structured interviews showed that participants considered AMR mainly in relation to individual antibiotic use or its presence in a clinical environment but not to travelling. CONCLUSION: The microbiological analysis confirmed previous research showing that international human mobility is a risk factor for AMR acquisition. However, sociological methods demonstrated that travellers understand AMR primarily as a clinical problem and do not connect it to travelling. These findings indicate an important gap in understanding AMR as a bio-social problem raising a question about the potential effectiveness of biologically driven AMR stewardship programs among travellers. Further development of the 'stool and stories' approach is important for a transdisciplinary basis of AMR stewardship.

Culture-Independent Genotyping Revealed 3 Strain Clusters in a Potential Neisseria gonorrhoeae Outbreak in Young Heterosexuals (<25 Years), the Netherlands, October 2017 to March 2019.

BACKGROUND: Investigation was undertaken to determine the genetic relatedness of Neisseria gonorrhoeae (NG) isolates of young (<25 years) heterosexuals of a potential outbreak from October 2017 to March 2019 in South-Limburg, the Netherlands. METHODS: Data and residual sample material of routine diagnostics were retrieved for outbreak cases (78/81), young heterosexuals at baseline (January 2016 to September 2017, n = 30), and men who have sex with men (2018, n = 47). Total DNA was isolated, and NG was genotyped using culture-free NG multiantigen sequence typing. Sanger sequence data were used to construct a phylogenetic tree. Cases of outbreak clusters were geographically mapped, and descriptive analyses were performed on patient characteristics, comparing these clusters. RESULTS: Outbreak investigation showed 81 cases of young heterosexuals between October 2017 and March 2019 (4.5 per month) compared with 30 between January 2016 and September 2017 (1.4 per month), which was considered as baseline. Culture-independent genotyping of NG was performed to assess the genetic relatedness, as only 21 outbreak cases were culture confirmed. This revealed 3 independent outbreak clusters G2 (n = 18), G13113 (n = 11), and GNewST (n = 24). None of the clusters were geographically linked or introduced by bridging with men who have sex with men networks. Number of sex partners reported by men and Chlamydia trachomatis coinfection were associated with clusters G2 and GNewST, respectively. CONCLUSIONS: Culture-independent typing proved to be essential to identify the 3 outbreak clusters. However, targeted interventions were difficult because information on sex partners was limited. Therefore, prospective culture-independent typing could be used for early outbreak detection and aid in transmission prevention.

Obligatory medical prescription of antibiotics in Russia: Navigating formal and informal health-care infrastructures.

Antimicrobial resistance control programmes often aim to "fix" the behaviour of antibiotic users and prescribers. Such behavioural interventions have been widely criticised in social science literature for being inefficient and too narrow in scope. Drawing on these criticisms, this article analyses how political programmes for fixing antibiotic behaviours were adapted into the practices of health-care professionals and patients in Russia. In 2018, we conducted interviews with medical doctors, pharmacists and patients in a Russian city; focusing on their practices around the policy requirement introduced in 2017 which obligated medical prescriptions of antibiotics. We conceptualised the obligatory medical prescription as a political technique which sought to change practices of self-treatment and over-the-counter sales of medications by establishing doctors as an obligatory passage point to access antibiotics. Our analysis shows that the requirement for medical prescriptions does not fulfil the infrastructural gaps that influence antibiotic practices. By navigating the antibiotic prescriptions, doctors, pharmacists and patients informally compensate for the gaps in the existing infrastructure creating informal networks of antibiotic care parallel to the requirement of obligatory prescriptions. Following these informal practices, we could map the inconsistencies in the current policy approaches to tackle AMR as a behavioural rather than infrastructural problem.

Routine universal testing versus selective or incidental testing for oropharyngeal Neisseria gonorrhoeae in women in the Netherlands: a retrospective cohort study.

BACKGROUND: Women are not routinely tested for oropharyngeal Neisseria gonorrhoeae. At present, selective testing based on sexual behaviour or risk groups is advocated by international guidelines. Many oropharyngeal infections are asymptomatic and thus remain undetected, establishing a reservoir for ongoing transmission. Data on effectiveness of routine testing are scarce, thus we aimed to assess the optimal testing strategy for oropharyngeal N gonorrhoeae in women. METHODS: In this retrospective cohort study, we used surveillance data obtained from all sexually transmitted infection (STI) clinics in the Netherlands between Jan 1, 2008, and Dec 31, 2017. We collected consultation-level data, and individual-level patient data from 2016 onwards, on sociodemographic characteristics, sexual behaviour in the past 6 months, self-reported symptoms, and STI diagnoses. We compared the prevalence of oropharyngeal N gonorrhoeae between women who attended clinics that offered routine universal testing (defined as >85% of women tested per clinic-year) and women who attended clinics that offered selective testing (defined as 5-85% of women tested per clinic-year) or incidental testing (<5% of women tested per clinic-year). We calculated the number of infections missed by selective testing by extrapolating prevalence for the routine universal testing group to that of weighted and unweighted samples of all selectively tested women. We used multivariable generalised estimating equations to identify independent risk factors for oropharyngeal N gonorrhoeae to identify the optimal selective testing strategy. FINDINGS: 554 266 consultations with at least one N gonorrhoeae test were recorded, of which 545 750 consultations (including repeat visits) were included in the analyses. Of 545 750 consultations, routine universal testing was used in 57 359 (10·5%), selective testing in 444 283 (81·4%), and incidental testing in 44 108 (8·1%). The prevalence of oropharyngeal N gonorrhoeae was 1·4% (95% CI 1·3-1·5; 703 of 50 962 consultations) in the routine testing group compared with 1·4% (1·3-1·5; 1858 of 132 276) in the selective testing group (p=0·68) and 2·8% (1·9-3·9; 30 of 1088) in the incidental testing group (p<0·0001). The prevalence of oropharyngeal-only infections was 47·7% (335 of 703 women) in the routine testing group, 53·3% (991 of 1858) in the selective testing group, and 60·0% (18 of 30) in the incidental testing group. Selective testing would have missed an estimated 4363 (70%; 95% CI 69-71) of all 6221 oropharyngeal N gonorrhoeae infections. Independent risk factors for oropharyngeal N gonorrhoeae were being notified for any STI (adjusted odds ratio 2·1, 95% CI 1·5-3·0), reporting sex work (4·0, 2·3-6·7), and having concurrent genital (51·5, 34·1-77·7) or anorectal (2·6, 1·4-4·8) N gonorrhoeae. Selective testing of women notified for any STI, or who reported sex work, would have led to 5418 (27·8%) of 19 455 women being tested and would have identified 119 (55·6%) of 214 oropharyngeal N gonorrhoeae infections. INTERPRETATION: Selective testing potentially misses more than two-thirds of oropharyngeal N gonorrhoeae infections in women, of whom half have oropharyngeal infections without concurrent genital or anorectal infections. Using independent risk factors for oropharyngeal infection to guide testing is a minimal testing strategy. Routine universal testing is the optimum scenario to detect the majority of infections. However, future studies are needed to assess the cost-effectiveness of routine testing and its effect on antimicrobial resistance. FUNDING: Public Health Service South Limburg.

Men and Women Have an Equal Oropharyngeal and Anorectal Chlamydia trachomatis Bacterial Load: A Comparison of 3 Anatomic Sites.

BACKGROUND: The Chlamydia trachomatis bacterial load could have impact on transmission and sequelae. This is the first study providing comparison of C. trachomatis load at 3 anatomic sites estimated by cycle quantification (Cq) values. METHODS: Data from 7900 C. trachomatis-positive samples were included (2012-2018). Cq value was used as an inversely proportional measure for C. trachomatis load. Multivariable linear regression analyses assessed differences in mean Cq values. RESULTS: Vaginal swabs had the lowest Cq values (31.0) followed by urine (32.5), anorectal swabs (34.0), and oropharyngeal swabs (36.8) (P < .001). Men and women had similar oropharyngeal (36.4 vs 37.3; P = .13) and anorectal (34.2 vs 33.9; P = .19) Cq values. Men (32.2) and women (30.7) aged <25 years had lower urogenital Cq values than men (32.8) and women (31.9) aged ≥25 years (P < .001). HIV-positive patients had higher urogenital Cq values than HIV-negative patients (33.8 vs 32.6; P < .03). CONCLUSIONS: Men and women have a similar C. trachomatis load at extragenital locations arguing for similar transmission potential and clinical relevance. Older patients and HIV-coinfected patients had lower C. trachomatis load, suggesting exposure to previous C. trachomatis infections potentially leading to partial immunity reducing load.