An economic evaluation of two cervical screening algorithms in Belgium: HR-HPV primary compared to HR-HPV and liquid-based cytology co-testing.

OBJECTIVE: To assess the costs and benefits of two algorithms for cervical cancer screening in Belgium (1) high-risk human papillomavirus (HR-HPV) primary screening and (2) HR-HPV and liquid-based cytology (LBC) co-testing. METHODS: A decision tree was adapted from published work and parameterised using HORIZON study data and Belgian cost and population data. The theoretical model represents two different screening algorithms for a cohort of 577 846 women aged 25-64 attending routine cervical screening. Scenario analyses were used to explore the impact of including vaccinated women and alternative pricing approaches. Uncertainty analyses were conducted. RESULTS: The cost per woman screened was €113.50 for HR-HPV primary screening and €101.70 for co-testing, representing a total cost of €65 588 573 and €58 775 083, respectively, for the cohort; a 10% difference. For one screening cycle, compared to HR-HPV primary, co-testing resulted in 13 173 more colposcopies, 67 731 more HR-HPV tests and 477 020 more LBC tests. Co-testing identified 2351 more CIN2+ cases per year (27% more than HR-HPV primary) and 1602 more CIN3+ cases (24% more than HR-HPV primary) than HR-HPV primary. CONCLUSION: In Belgium, a co-testing algorithm could increase cervical pre-cancer detection rates compared to HR-HPV primary. Co-testing would cost less than HR-HPV primary if the cost of the HPV test and LBC were cost-neutral compared to the current cost of LBC screening but would cost more if the cost per HPV test and LBC were the same in both co-testing and HR-HPV primary strategies.

Comparing the Costs and Diagnostic Outcomes of Replacing Cytology with the QIAsure DNA Methylation Test as a Triage within HPV Primary Cervical Cancer Screening in The Netherlands.

Detecting hypermethylation of tumour suppressor genes could provide an alternative to liquid-based cytology (LBC) triage within HPV primary cervical screening. The impact of using the QIAsure® FAM19A4/mir124-2 DNA Methylation Test (QIAGEN, N.V, Hilden, Germany) on CIN3+ diagnoses, retention, unnecessary colposcopies, and programme costs is unknown. A decision-tree model was developed to compare LBC with the QIAsure Methylation testing to guide colposcopy referral. Incorporating clinician- and self-sampling pathways the model was informed by the Dutch cervical cancer screening programme, published studies, and manufacturer data. Clinical and cost outcomes were assessed using two scenarios for DNA methylation testing and LBC relative performance. Sensitivity analyses (deterministic and probabilistic) were performed to assess model and parameter uncertainty. A range of self-sampling uptake was assessed in scenario analyses. For the screening cohort (n = 807,269) where 22.1% self-sampled, the number of unnecessary colposcopies and CIN3+ diagnoses varied according to the relative performance of methylation testing and LBC. Irrespective of relative performance, the cost per complete screen was lower and fewer people were lost to follow-up when using DNA methylation testing. The results indicate that, within an HPV primary screening programme that incorporates self-sampling, using the QIAsure Methylation Test for triage reduces the cost per screen compared to LBC.

Estimating the Health and Economic Impact of Improved Management in Prevalent Chronic Obstructive Pulmonary Disease Populations in England, Germany, Canada, and Japan: A Modelling Study.

Introduction: COPD is a leading cause of morbidity and mortality globally. Management is complex and costly. Although international quality standards for diagnosis and management exist, opportunities remain to improve outcomes, especially in reducing avoidable hospitalisations. Objective: To estimate the potential health and economic impact of improved adherence to guideline-recommended care for prevalent, on-treatment COPD populations in four high-income settings. Methods: A disease simulation model was developed to evaluate the impact of theoretical improvements to COPD management, comparing outcomes for usual care and policy scenarios for interventions that reduce avoidable hospitalisations: 1) increased attendance (50% vs 31-38%) of early follow-up review after severe exacerbation hospitalisation; 2) increased access (30% vs 5-10%) to an integrated disease management (IDM) programme that provides guideline adherent care. Results: For cohorts of 100,000 patients, Policy 1 yielded additional life years (England: 523; Germany: 759; Canada: 1316; Japan: 512) and lifetime cost savings (-£2.89 million; -€6.58 million; -$40.08 million; -¥735.58 million). For Policy 2, additional life years (2299; 3619; 3656) and higher lifetime total costs (£38.15 million; €35.58 million; ¥1091.53 million) were estimated in England, Germany and Japan, and additional life years (4299) and cost savings (-$20.52 million) in Canada. Scenarios found that the cost impact depended on the modelled intervention effect size. Conclusion: Interventions that reduce avoidable hospitalisations are estimated to improve survival and may generate cost savings. This study provides evidence on the theoretical impact of policies to improve COPD care and highlights priority areas for further research to support evidence-based policy decisions.

An economic evaluation of two PCR-based respiratory panel assays for patients admitted to hospital with community-acquired pneumonia (CAP) in the UK, France and Spain.

BACKGROUND: On admission to hospital, patients with community-acquired pneumonia (CAP), undergo extensive diagnostic testing. Two high-throughput laboratory-based PCR panels which return a result in 5.5 hours (h) have been developed to test for pathogens commonly associated with upper (Respiratory 1 Panel) and lower (Respiratory 3 Panel) respiratory tract infections (GeneFirst, Oxford). These could replace multiple diagnostic tests currently used. METHODS: An online survey, completed by senior clinicians in the UK, France and Spain, was used to collect data on the diagnostic testing of immunocompetent and immunocompromised adults admitted to hospital with CAP, including the cost of diagnostics. Data were used to inform a cost-comparison model. For each country, the average cost of diagnostic testing per patient was calculated separately for immunocompetent and immunocompromised patients. The model compared three testing strategies with standard of care (SoC). In the Panel 1 strategy, the Respiratory 1 Panel was used for patients that would otherwise have tests which could be replaced by Respiratory 1 Panel, equivalent strategies for Respiratory 3 Panel and for both panels combined were assessed. RESULTS: In total, 48 surveys were completed (UK = 17; France = 15; Spain = 16). Compared with SoC, the Panel 1 + 3 strategy was most favourable, resulting in cost savings for immunocompetent and immunocompromised patients respectively, of €22.09 (£18.50) and €26.12 (£21.88) in the UK, €99.60 and €108.77 in France and €27.07 and €51.87 in Spain. CONCLUSION: In all three countries, the use of these respiratory panels could reduce the average cost of diagnostics used for patients admitted to hospital with CAP.

Assessment of online self-testing and self-sampling service providers for sexually transmitted infections against national standards in the UK in 2020.

OBJECTIVES: Online testing for STIs may help overcome barriers of traditional face-to-face testing, such as stigma and inconvenience. However, regulation of these online tests is lacking, and the quality of services is variable, with potential short-term and long-term personal, clinical and public health implications. This study aimed to evaluate online self-testing and self-sampling service providers in the UK against national standards. METHODS: Providers of online STI tests (self-sampling and self-testing) in the UK were identified by an internet search of Google and Amazon (June 2020). Website information on tests and associated services was collected and further information was requested from providers via an online survey, sent twice (July 2020, April 2021). The information obtained was compared with British Association for Sexual Health and HIV and Faculty of Sexual and Reproductive Healthcare guidelines and standards for diagnostics and STI management. RESULTS: 31 providers were identified: 13 self-test, 18 self-sample and 2 laboratories that serviced multiple providers. Seven responded to the online survey. Many conflicts with national guidelines were identified, including: lack of health promotion information, lack of sexual history taking, use of tests licensed for professional-use only marketed for self-testing, inappropriate infections tested for, incorrect specimen type used and lack of advice for postdiagnosis management. CONCLUSIONS: Very few online providers met the national STI management standards assessed, and there is concern that this will also be the case for service provision aspects that were not covered by this study. For-profit providers were the least compliant, with concerning implications for patient care and public health. Regulatory change is urgently needed to ensure that all online providers are compliant with national guidelines to ensure high-quality patient care, and providers are held to account if non-compliant.

Effectiveness of a behavioural intervention delivered by text messages (safetxt) on sexually transmitted reinfections in people aged 16-24 years: randomised controlled trial.

OBJECTIVE: To quantify the effects of a series of text messages (safetxt) delivered in the community on incidence of chlamydia and gonorrhoea reinfection at one year in people aged 16-24 years. DESIGN: Parallel group randomised controlled trial. SETTING: 92 sexual health clinics in the United Kingdom. PARTICIPANTS: People aged 16-24 years with a diagnosis of, or treatment for, chlamydia, gonorrhoea, or non-specific urethritis in the past two weeks who owned a mobile phone. INTERVENTIONS: 3123 participants assigned to the safetxt intervention received a series of text messages to improve sex behaviours: four texts daily for days 1-3, one or two daily for days 4-28, two or three weekly for month 2, and 2-5 monthly for months 3-12. 3125 control participants received a monthly text message for one year asking for any change to postal or email address. It was hypothesised that safetxt would reduce the risk of chlamydia and gonorrhoea reinfection at one year by improving three key safer sex behaviours: partner notification at one month, condom use, and sexually transmitted infection testing before unprotected sex with a new partner. Care providers and outcome assessors were blind to allocation. MAIN OUTCOME MEASURES: The primary outcome was the cumulative incidence of chlamydia or gonorrhoea reinfection at one year, assessed by nucleic acid amplification tests. Safety outcomes were self-reported road traffic incidents and partner violence. All analyses were by intention to treat. RESULTS: 6248 of 20 476 people assessed for eligibility between 1 April 2016 and 23 November 2018 were randomised. Primary outcome data were available for 4675/6248 (74.8%). At one year, the cumulative incidence of chlamydia or gonorrhoea reinfection was 22.2% (693/3123) in the safetxt arm versus 20.3% (633/3125) in the control arm (odds ratio 1.13, 95% confidence interval 0.98 to 1.31). The number needed to harm was 64 (95% confidence interval number needed to benefit 334 to ∞ to number needed to harm 24) The risk of road traffic incidents and partner violence was similar between the groups. CONCLUSIONS: The safetxt intervention did not reduce chlamydia and gonorrhoea reinfections at one year in people aged 16-24 years. More reinfections occurred in the safetxt group. The results highlight the need for rigorous evaluation of health communication interventions. TRIAL REGISTRATION: ISRCTN registry ISRCTN64390461.

Modelling the effect of COVID-19 mass vaccination on acute hospital admissions.

BACKGROUND: Managing high levels of acute COVID-19 bed occupancy can affect the quality of care provided to both affected patients and those requiring other hospital services. Mass vaccination has offered a route to reduce societal restrictions while protecting hospitals from being overwhelmed. Yet, early in the mass vaccination effort, the possible impact on future bed pressures remained subject to considerable uncertainty. OBJECTIVE: The aim of this study was to model the effect of vaccination on projections of acute and intensive care bed demand within a 1 million resident healthcare system located in South West England. METHODS: An age-structured epidemiological model of the susceptible-exposed-infectious-recovered type was fitted to local data up to the time of the study, in early March 2021. Model parameters and vaccination scenarios were calibrated through a system-wide multidisciplinary working group, comprising public health intelligence specialists, healthcare planners, epidemiologists and academics. Scenarios assumed incremental relaxations to societal restrictions according to the envisaged UK Government timeline, with all restrictions to be removed by 21 June 2021. RESULTS: Achieving 95% vaccine uptake in adults by 31 July 2021 would not avert the third wave in autumn 2021 but would produce a median peak bed requirement ∼6% (IQR: 1-24%) of that experienced during the second wave (January 2021). A 2-month delay in vaccine rollout would lead to significantly higher peak bed occupancy, at 66% (11-146%) of that of the second wave. If only 75% uptake was achieved (the amount typically associated with vaccination campaigns), then the second wave peak for acute and intensive care beds would be exceeded by 4% and 19%, respectively, an amount which would seriously pressure hospital capacity. CONCLUSION: Modelling influenced decision-making among senior managers in setting COVID-19 bed capacity levels, as well as highlighting the importance of public health in promoting high vaccine uptake among the population. Forecast accuracy has since been supported by actual data collected following the analysis, with observed peak bed occupancy falling comfortably within the inter-quartile range of modelled projections.

Evidence that faecal carriage of resistant Escherichia coli by 16-week-old dogs in the United Kingdom is associated with raw feeding.

We report a survey (August 2017 to March 2018) and risk factor analysis of faecal carriage of antibacterial-resistant (ABR) Escherichia coli in 223 16-week-old dogs in the United Kingdom. Raw feeding was associated with the presence of fluoroquinolone-resistant (FQ-R) E. coli and those resistant to tetracycline, amoxicillin, and streptomycin, but not to cefalexin. Whole genome sequencing of 36 FQ-R E. coli isolates showed a wide range of sequence types (STs), with almost exclusively mutational FQ-R dominated by ST744 and ST162. Comparisons between E. coli isolates from puppies known to be located within a 50 × 50 km region with those isolated from human urinary tract infections (isolated in parallel in the same region) identified an ST744 FQ-R lineage that was carried by one puppy and caused one urinary tract infection. Accordingly, we conclude that raw feeding is associated with carriage of ABR E. coli in dogs even at 16 weeks of age and that bacteria carried by puppies are shared with humans. We therefore suggest that those who feed their dogs raw meat seriously consider the potential ABR-transmission threat their pet may become as a result and deploy appropriate hygiene practices in mitigation.

Preferences for chlamydia testing and management in Hong Kong: a discrete choice experiment.

OBJECTIVES: As most chlamydia cases are asymptomatic, regular testing and timely management may be necessary for control. We aimed to determine the preferences of people living in Hong Kong for chlamydia testing and management services. METHODS: An online panel of sexually active individuals living in Hong Kong completed the survey with two discrete choice experiments (DCEs). The first DCE examined the preferred attributes of a chlamydia testing service (cost, location, appointment time, speed of results, delivery of results and availability of other STI testing). The second DCE examined the preferred attributes of a chlamydia management service (cost, access to patient-delivered partner therapy, location, travel time, type of person consulted and attitude of staff). RESULTS: In total, 520 individuals participated: average age 36.8 years (SD 9.9), 40% males and 66% had a bachelor's degree or higher. Choosing to test was most influenced by cost, followed by speed of results, delivery of results, extra STI testing, appointment available and the least important was the location of testing. Choosing to attend for management was most influenced by staff's attitude, followed by cost, who they consult, access to patient-delivered partner therapy, travel time and the least important was treatment location. CONCLUSION: To design effective chlamydia testing and management services, it is vital to respond to patient needs and preferences. For people living in Hong Kong, cost and staff attitude were the most important factors for deciding whether to test or be managed for chlamydia, respectively.

Serological Evidence of Human Infection with Coxiella burnetii after Occupational Exposure to Aborting Cattle.

Cattle are broadly deemed a source of Coxiella burnetii; however, evidence reinforcing their role in human infection is scarce. Most published human Q fever outbreaks relate to exposure to small ruminants, notably goats. Anti-phase II C. burnetii IgG and IgM were measured by indirect fluorescent antibody tests in 27 farm and veterinary diagnostic laboratory workers to ascertain whether occupational exposure to cattle aborting due to C. burnetii was the probable source of exposure. Four serological profiles were identified on the basis of anti-phase II IgG and IgM titres. Profile 1, characterised by high IgM levels and concurrent, lower IgG titres (3/27; 11.1%); Profile 2, with both isotypes with IgG titres higher than IgM (2/27; 7.4%); Profile 3 with only IgG phase II (5/27; 18.5%); and Profile 4, in which neither IgM nor IgG were detected (17/27; 63.0%). Profiles 1 and 2 are suggestive of recent C. burnetii exposure, most likely 2.5-4.5 months before testing and, hence, during the window of exposure to the bovine abortions. Profile 3 suggested C. burnetii exposure that most likely predated the window of exposure to aborting cattle, while Profile 4 represented seronegative individuals and, hence, likely uninfected. This study formally linked human Q fever to exposure to C. burnetii infected cattle as a specific occupational hazard for farm and laboratory workers handling bovine aborted material.

Limited phylogenetic overlap between fluoroquinolone-resistant Escherichia coli isolated on dairy farms and those causing bacteriuria in humans living in the same geographical region.

BACKGROUND: Our primary aim was to test whether cattle-associated fluoroquinolone-resistant (FQ-R) Escherichia coli found on dairy farms are closely phylogenetically related to those causing bacteriuria in humans living in the same 50 × 50 km geographical region suggestive of farm-human sharing. Another aim was to identify risk factors for the presence of FQ-R E. coli on dairy farms. METHODS: FQ-R E. coli were isolated during 2017-18 from 42 dairy farms and from community urine samples. Forty-two cattle and 489 human urinary isolates were subjected to WGS, allowing phylogenetic comparisons. Risk factors were identified using a Bayesian regularization approach. RESULTS: Of 489 FQ-R human isolates, 255 were also third-generation-cephalosporin-resistant, with strong genetic linkage between aac(6')Ib-cr and blaCTX-M-15. We identified possible farm-human sharing for pairs of ST744 and ST162 isolates, but minimal core genome SNP distances were larger between farm-human pairs of ST744 and ST162 isolates (71 and 63 SNPs, respectively) than between pairs of isolates from different farms (7 and 3 SNPs, respectively). Total farm fluoroquinolone use showed a positive association with the odds of isolating FQ-R E. coli, while total dry cow therapy use showed a negative association. CONCLUSIONS: This work suggests that FQ-R E. coli found on dairy farms have a limited impact on community bacteriuria within the local human population. Reducing fluoroquinolone use may reduce the on-farm prevalence of FQ-R E. coli and this reduction may be greater when dry cow therapy is targeted to the ecology of resistant E. coli on the farm.

Evidence of changing sexual behaviours and clinical attendance patterns, alongside increasing diagnoses of STIs in MSM and TPSM.

BACKGROUND: Due to rising numbers of STI diagnosis and increasing prevalence of antimicrobial resistance, we explored trends in STI testing frequency and diagnoses, alongside sexual decision making and attitudes concerning condom use and HIV pre-exposure prophylaxis (PrEP) at a large urban UK sexual health clinic. METHODS: We examined 66 528 electronic patient records covering 40 321 attendees between 2016 and 2019, 3977 of whom were men who have sex with men or trans persons who have sex with men (MSM/TPSM). We also explored responses from MSM/TPSM attendees sent an electronic questionnaire between November 2018 and 2019 (n=1975) examining behaviours/attitudes towards PrEP. We measured trends in STI diagnoses and sexual behaviours including condomless anal intercourse (CAI), using linear and logistic regression analyses. RESULTS: Tests resulting in gonorrhoea, chlamydia or syphilis diagnoses increased among MSM/TPSM from 13.5% to 18.5% between 2016 and 2019 (p<0.001). The average MSM/TPSM STI testing frequency increased from 1.5/person/year to 2.1/person/year (p=0.017). Gay MSM/TPSM had the highest proportions of attendances resulting in diagnoses, increasing from 15.1% to 19.6% between 2016 and 2019 (p<0.001) compared with bisexual/other MSM/TPSM increasing from 6.9% to 14.5% (p<0.001), alongside smaller but significant increases in non-MSM/TPSM from 5.9% to 7.7% (p<0.001).The proportion of MSM/TPSM clinic attendees reporting CAI in the previous 3 months prior to at least one appointment in a given year increased significantly from 40.6% to 45.5% between 2016 and 2019 (p<0.0001) and average number of partners from 3.8 to 4.5 (p=0.002). Of 617 eligible questionnaire responses, 339/578 (58.7%) HIV-negative and 29/39 (74.4%) HIV-positive MSM/TPSM indicated they would be more likely to have CAI with someone on PrEP versus not on PrEP. 358/578 (61.9%) HIV-negative respondents said that PrEP use would make them more likely to have CAI with HIV-negative partners. CONCLUSION: Rising numbers of STI diagnoses among MSM/TPSM are not attributable to increased testing alone. Increased CAI and number of partners may be attributable to evolving sexual decision making among PrEP users and their partners. Proportionally, bisexual/other MSM/TPSM have the steepest increase in STI diagnoses.

A hitchhiker guide to manta rays: Patterns of association between Mobula alfredi, M. birostris, their symbionts, and other fishes in the Maldives.

Despite being among the largest and most charismatic species in the marine environment, considerable gaps remain in our understanding of the behavioural ecology of manta rays (Mobula alfredi, M. birostris). Manta rays are often sighted in association with an array of smaller hitchhiker fish species, which utilise their hosts as a sanctuary for shelter, protection, and the sustenance they provide. Species interactions, rather than the species at the individual level, determine the ecological processes that drive community dynamics, support biodiversity and ecosystem health. Thus, understanding the associations within marine communities is critical to implementing effective conservation and management. However, the underlying patterns between manta rays, their symbionts, and other hitchhiker species remain elusive. Here, we explore the spatial and temporal variation in hitchhiker presence with M. alfredi and M. birostris throughout the Maldives and investigate the factors which may influence association using generalised linear mixed effects models (GLMM). For the first time, associations between M. alfredi and M. birostris with hitchhiker species other than those belonging to the family Echeneidae are described. A variation in the species of hitchhiker associated with M. alfredi and M. birostris was identified, with sharksucker remora (Echeneis naucrates) and giant remora (Remora remora) being the most common, respectively. Spatiotemporal variation in the presence of manta rays was identified as a driver for the occurrence of ephemeral hitchhiker associations. Near-term pregnant female M. alfredi, and M. alfredi at cleaning stations, had the highest likelihood of an association with adult E. naucrates. Juvenile E. naucrates were more likely to be associated with juvenile M. alfredi, and a seasonal trend in E. naucrates host association was identified. Remora were most likely to be present with female M. birostris, and a mean number of 1.5 ± 0.5 R. remora were observed per M. birostris. It is hoped these initial findings will serve as the basis for future work into the complex relationships between manta rays and their hitchhikers.

Developing a model to predict individualised treatment for gonorrhoea: a modelling study.

OBJECTIVE: To develop a tool predicting individualised treatment for gonorrhoea, enabling treatment with previously recommended antibiotics, to reduce use of last-line treatment ceftriaxone. DESIGN: A modelling study. SETTING: England and Wales. PARTICIPANTS: Individuals accessing sentinel health services. INTERVENTION: Developing an Excel model which uses participants' demographic, behavioural and clinical characteristics to predict susceptibility to legacy antibiotics. Model parameters were calculated using data for 2015-2017 from the Gonococcal Resistance to Antimicrobials Surveillance Programme. MAIN OUTCOME MEASURES: Estimated number of doses of ceftriaxone saved, and number of people delayed effective treatment, by model use in clinical practice. Model outputs are the predicted risk of resistance to ciprofloxacin, azithromycin, penicillin and cefixime, in groups of individuals with different combinations of characteristics (gender, sexual orientation, number of recent sexual partners, age, ethnicity), and a treatment recommendation. RESULTS: Between 2015 and 2017, 8013 isolates were collected: 64% from men who have sex with men, 18% from heterosexual men and 18% from women. Across participant subgroups, stratified by all predictors, resistance prevalence was high for ciprofloxacin (range: 11%-51%) and penicillin (range: 6%-33%). Resistance prevalence for azithromycin and cefixime ranged from 0% to 13% and for ceftriaxone it was 0%. Simulating model use, 88% of individuals could be given cefixime and 10% azithromycin, saving 97% of ceftriaxone doses, with 1% of individuals delayed effective treatment. CONCLUSIONS: Using demographic and behavioural characteristics, we could not reliably identify a participant subset in which ciprofloxacin or penicillin would be effective. Cefixime resistance was almost universally low; however, substituting ceftriaxone for near-uniform treatment with cefixime risks re-emergence of resistance to cefixime and ceftriaxone. Several subgroups had low azithromycin resistance, but widespread azithromycin monotherapy risks resistance at population level. However, this dataset had limitations; further exploration of individual characteristics to predict resistance to a wider range of legacy antibiotics may still be appropriate.

Molecular prevalence of Coxiella burnetii in bulk-tank milk from bovine dairy herds: Systematic review and meta-analysis.

Coxiella burnetii is an obligate intracellular zoonotic bacterium that causes Q fever. Ruminants, including cattle, are broadly known to be reservoirs for this bacterium. Since 2006, many research groups have evaluated the herd-level prevalence of C. burnetii in cattle by molecular techniques on composite milk samples. This study explored the global C. burnetii herd-level prevalence from studies done on bovine bulk-tank milk (BTM) samples using PCR-based analysis. Also, moderators were investigated to identify sources of heterogeneity. Databases (CAB Abstracts, Medline via Ovid, PubMed, Web of Science and Google Scholar) were searched for index articles on C. burnetii prevalence in BTM samples by PCR published between January-1973 and November-2018. Numerous studies (1054) were initially identified, from which seventeen original publications were included in the meta-analysis based on the pre-defined selection criteria. These studies comprised 4031 BTM samples from twelve countries. A random-effects model was used because of considerable heterogeneity (I 2 = 98%) to estimate the herd-level prevalence of C. burnetii as 37.0%(CI95%25.2-49.5%). The average herd size appeared to account for a high level of the heterogeneity. No other moderators (geographic location, gross national income or notification criteria for Q fever) seemed to be determinant. This systematic evaluation demonstrated a high molecular prevalence of C. burnetii in BTM samples both in European and non-European countries, evidencing a widespread herd-level circulation of this agent in bovine dairy farms around the world. Meta-regression showed herd size as the most relevant moderator with the odds of a BTM sample testing positive doubling with every unit increase.

Human Immunodeficiency Virus Preexposure Prophylaxis Knowledge, Attitudes and Perceptions of Sexual Health Risk in an Age of Sexually Transmitted Infection Antimicrobial Resistance.

BACKGROUND: Human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) has helped reduce new HIV infections. However, bacterial sexually transmitted infections (STIs) have increased among PrEP users. We examined PrEP knowledge, access, and risk perceptions in an age of antimicrobial resistance (AMR). METHODS: An online anonymous survey was distributed to all cisgender men/transpersons who have sex with men attending a sexual health clinic in Bristol, United Kingdom (October 2018 to November 2019). Interviews with a sample identified at increased risk of HIV were analyzed thematically and integrated with survey data. RESULTS: Five hundred and seventy-eight (95%) of 617 cisgender men/transpersons who have sex with men survey respondents were HIV-negative/unknown, of these, 202 (34.9%) had ever used PrEP. Interviewees (n = 24) reported widespread awareness of and enthusiasm for PrEP. Among nonusers, 39% (146/376) were unaware how to access PrEP, and 27% (103/376) could not access PrEP through the national "impact" trial of whom 79% (81/103) were eligible. The PrEP was described as "life-changing," but expense was the main barrier to use. Sixty-two percent (358/578) of HIV-negative/unknown respondents on PrEP were more likely to have condomless anal intercourse with someone they thought was HIV-negative. Interviewees used PrEP with other risk-reduction strategies. Sexually transmitted infections were seen as "curable" and AMR rarely influenced risk perception or sexual decision making. CONCLUSIONS: The PrEP awareness was high, but purchase cost limited access. PrEP may increase condomless anal intercourse, but interviewees used PrEP as one of many risk-reduction tools. Reduced fear of HIV transmission and testing was highly valued. Sexually transmitted infection AMR was not seen as an immediate threat and did not influence risk perception or sexual decision making.

Reduced Antibacterial Drug Resistance and blaCTX-M ß-Lactamase Gene Carriage in Cattle-Associated Escherichia coli at Low Temperatures, at Sites Dominated by Older Animals, and on Pastureland: Implications for Surveillance.

Little is known about the drivers of critically important antibacterial resistance in species with zoonotic potential present on farms (e.g., CTX-M ß-lactamase-positive Escherichia coli). We collected samples monthly between January 2017 and December 2018 on 53 dairy farms in South West England, along with data for 610 variables concerning antibacterial usage, management practices, and meteorological factors. We detected E. coli resistant to amoxicillin, ciprofloxacin, streptomycin, and tetracycline in 2,754/4,145 (66%), 263/4,145 (6%), 1,475/4,145 (36%), and 2,874/4,145 (69%), respectively, of samples from fecally contaminated on-farm and near-farm sites. E. coli positive for blaCTX-M were detected in 224/4,145 (5.4%) of samples. Multilevel, multivariable logistic regression showed antibacterial dry cow therapeutic choice (including use of cefquinome or framycetin) to be associated with higher odds of blaCTX-M positivity. Low average monthly ambient temperature was associated with lower odds of blaCTX-ME. coli positivity in samples and with lower odds of finding E. coli resistant to each of the four test antibacterials. This was in addition to the effect of temperature on total E. coli density. Furthermore, samples collected close to calves had higher odds of having E. coli resistant to each antibacterial, as well as E. coli positive for blaCTX-M Samples collected on pastureland had lower odds of having E. coli resistant to amoxicillin or tetracycline, as well as lower odds of being positive for blaCTX-MIMPORTANCE Antibacterial resistance poses a significant threat to human and animal health and global food security. Surveillance for resistance on farms is important for many reasons, including tracking impacts of interventions aimed at reducing the prevalence of resistance. In this longitudinal survey of dairy farm antibacterial resistance, we showed that local temperature-as it changes over the course of a year-was associated with the prevalence of antibacterial-resistant E. coli We also showed that prevalence of resistant E. coli was lower on pastureland and higher in environments inhabited by young animals. These findings have profound implications for routine surveillance and for surveys carried out for research. They provide important evidence that sampling at a single time point and/or single location on a farm is unlikely to be adequate to accurately determine the status of the farm regarding the presence of samples containing resistant E. coli.

Estimating the impact of disruptions due to COVID-19 on HIV transmission and control among men who have sex with men in China.

Introduction The COVID-19 pandemic is impacting HIV care globally, with gaps in HIV treatment expected to increase HIV transmission and HIV-related mortality. We estimated how COVID-19-related disruptions could impact HIV transmission and mortality among men who have sex with men (MSM) in four cities in China. Methods Regional data from China indicated that the number of MSM undergoing facility-based HIV testing reduced by 59% during the COVID-19 pandemic, alongside reductions in ART initiation (34%), numbers of sexual partners (62%) and consistency of condom use (25%). A deterministic mathematical model of HIV transmission and treatment among MSM in China was used to estimate the impact of these disruptions on the number of new HIV infections and HIV-related deaths. Disruption scenarios were assessed for their individual and combined impact over 1 and 5 years for a 3-, 4- or 6-month disruption period. Results Our China model predicted that new HIV infections and HIV-related deaths would be increased most by disruptions to viral suppression, with 25% reductions for a 3-month period increasing HIV infections by 5-14% over 1 year and deaths by 7-12%. Observed reductions in condom use increased HIV infections by 5-14% but had minimal impact (<1%) on deaths. Smaller impacts on infections and deaths (<3%) were seen for disruptions to facility testing and ART initiation, but reduced partner numbers resulted in 11-23% fewer infections and 0.4-1.0% fewer deaths. Longer disruption periods of 4 and 6 months amplified the impact of combined disruption scenarios. When all realistic disruptions were modelled simultaneously, an overall decrease in new HIV infections was always predicted over one year (3-17%), but not over 5 years (1% increase - 4% decrease), while deaths mostly increased over one year (1-2%) and 5 years (1.2 increase - 0.3 decrease). Conclusions The overall impact of COVID-19 on new HIV infections and HIV-related deaths is dependent on the nature, scale and length of the various disruptions. Resources should be directed to ensuring levels of viral suppression and condom use are maintained to mitigate any adverse effects of COVID-19 related disruption on HIV transmission and control among MSM in China.

Characterization of AmpC-hyperproducing Escherichia coli from humans and dairy farms collected in parallel in the same geographical region.

OBJECTIVES: To characterize putative AmpC-hyperproducing third-generation cephalosporin-resistant E. coli from dairy farms and their phylogenetic relationships; to identify risk factors for their presence; and to assess evidence for their zoonotic transmission into the local human population. METHODS: Proteomics was used to explain differences in antimicrobial susceptibility. WGS allowed phylogenetic analysis. Multilevel, multivariable logistic regression modelling was used to identify risk factors. RESULTS: Increased use of amoxicillin/clavulanate was associated with an increased risk of finding AmpC hyperproducers on farms. Expansion of cephalosporin resistance in AmpC hyperproducers was seen in farm isolates with marR mutations (conferring cefoperazone resistance) or when AmpC was mutated (conferring fourth-generation cephalosporin and cefoperazone resistance). Phylogenetic analysis confirmed the dominance of ST88 amongst farm AmpC hyperproducers but there was no evidence for acquisition of farm isolates by members of the local human population. CONCLUSIONS: Clear evidence was found for recent farm-to-farm transmission of AmpC-hyperproducing E. coli and of adaptive mutations to expand resistance. Whilst there was no evidence of isolates entering the local human population, efforts to reduce third-generation cephalosporin resistance on dairy farms must address the high prevalence of AmpC hyperproducers. The finding that amoxicillin/clavulanate use was associated with an increased risk of finding AmpC hyperproducers is important because this is not currently categorized as a highest-priority critically important antimicrobial and so is not currently targeted for specific usage restrictions in the UK.