A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1.

A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a ß-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.

Epidemiology of Escherichia coli bloodstream infection antimicrobial resistance trends across South West England during the first 2 years of the coronavirus disease 2019 pandemic response.

OBJECTIVES: Between 2016 and 2019, the proportion of Escherichia coli bloodstream infection (BSI) with resistance to at least one antibiotic increased nationally. Public health interventions implemented in response to the COVID-19 pandemic changed population contact patterns and healthcare systems, with consequent effects on epidemiological trends of numerous pathogens. We investigated the impact of COVID-19 restrictions on epidemiological trends of E. coli BSI antimicrobial resistance (AMR) across South West England. METHODS: We undertook a retrospective ecological analysis utilizing routine surveillance data of E. coli BSI cases reported to the UK Health Security Agency between 2016 and 2021. We analysed AMR trends for antimicrobial agents including amoxicillin-clavulanate, ciprofloxacin, piperacillin-tazobactam, gentamicin, third-generation cephalosporins and carbapenems before and after the implementation of COVID-19 restrictions (23 March 2020) using Bayesian segmented regression. RESULTS: We identified 19 055 cases. A total of 50.2% were male. Median age was 76 (interquartile range, 65-85 years). Piperacillin-tazobactam (-2.90% [95% highest density interval {HDI} -4.51%, -0.48%]) and ciprofloxacin (-2.40% [95% HDI -4.35%, 0.48%]) resistance demonstrated immediate step changes at the implementation of COVID-19 restrictions. Gentamicin (odds ratio [OR] 0.92 [95% HDI 0.76, 1.12]) and third-generation cephalosporins (OR 0.95 [95% HDI 0.80, 1.14]) exhibited decreasing annual resistance trends after the implementation of COVID-19 restrictions, with moderate evidence for a lower OR after restrictions as compared to the period before (gentamicin Bayes Factor = 5.10, third-generation cephalosporins Bayes Factor = 6.67). DISCUSSION: COVID-19 restrictions led to abrupt and longer term changes to E.coli BSI AMR. The immediate effects suggest altered transmission, whereas changes to resistant E. coli reservoirs may explain trend effects.

Dissolved arsenic and lead concentrations in rooftop harvested rainwater: Community generated dataset.

Here, we detail arsenic (As) and lead (Pb) concentrations in community science generated rooftop harvested rainwater data from Project Harvest (PH), a co-created community science study, and National Atmospheric Deposition Program (NADP) National Trends Network wet-deposition AZ samples as analyzed by Palawat et al. [1]. 577 field samples were collected in PH and 78 field samples were collected by NADP. All samples were analyzed via inductively coupled plasma mass spectrometry (ICP-MS) for dissolved metal(loid)s including As and Pb by the Arizona Laboratory for Emerging Contaminants after 0.45 um filtration and acidification. Method limits of detection (MLOD) were assessed and sample concentrations above MLODs were considered detects. Summary statistics and box and whisker plots were generated to assess variables of interest such as community and sampling window. Finally, As and Pb data is provided for potential reuse; the data can be used to assess contamination of harvested rainwater in AZ and to inform community use of natural resources.

Foodborne Outbreak of Extended Spectrum Beta-lactamase Producing Shigella sonnei Associated with Contaminated Spring Onions in the United Kingdom.

Globalization of the food supply chain has created conditions favorable for emergence and spread of multidrug-resistant (MDR) foodborne pathogens. In November 2021, the UK Health Security Agency detected an outbreak of 17 cases infected with the same strain of MDR extended spectrum beta-lactamase (ESBL)-producing Shigella sonnei. Phylogenetic analysis of whole-genome sequencing data revealed the outbreak was closely related to strains of S. sonnei isolated from travelers returning to the UK from Egypt. None of the outbreak cases reported travel and all 17 cases reported eating food from a restaurant/food outlet in the week prior to symptom onset, of which 11/17 (64.7%) ate at branches of the same national restaurant franchise. All 17 cases were adults and 14/17 (82.4%) were female. Ingredient-level analyses of the meals consumed by the cases identified spring onions as the common ingredient. Food chain investigations revealed that the spring onions served at the implicated restaurants could be traced back to a single Egyptian producer. The foodborne transmission of ESBL-producing bacteria is an emerging global health concern, and concerted action from all stakeholders is required to ensure an effective response to mitigate the risks to public health.

Patterns of contamination and burden of lead and arsenic in rooftop harvested rainwater collected in Arizona environmental justice communities.

As climate change exacerbates water scarcity, rainwater harvesting for household irrigation and gardening becomes an increasingly common practice. However, the use and quality of harvested rainwater are not well studied, and the potential pollutant exposures associated with its use are generally unknown. There are currently no federal standards in the United States to assess metal(loid)s in harvested rainwater. Project Harvest, a community science research project, was created to address this knowledge gap and study the quality of harvested rainwater, primarily used for irrigation, in four environmental justice communities in Arizona, USA. Community scientists collected 577 unique rooftop harvested rainwater samples from 2017 to 2020, which were analyzed for metal(loid)s, where arsenic (As) concentrations ranged from 0.108 to 120 µg L-1 and lead (Pb) concentrations ranged from 0.013 to 350 µg L-1 and compared to relevant federal/state standards/recommendations. Community As and Pb concentrations decreased as: Hayden/Winkelman > Tucson > Globe/Miami > Dewey-Humboldt. Linear mixed models were used to analyze rooftop harvested rainwater data and results indicated that concentrations of As and Pb in the summer monsoon were significantly greater than winter; and contamination was significantly greater closer to extractive industrial sites in three of the four study communities (ASARCO Hayden Plant Superfund Alternative site in Hayden/Winkelman, Davis-Monthan United States Air Force Base in Tucson - Pb only, and Freeport McMoRan Copper and Gold Mine in Globe/Miami). Based on models, infrastructure such as proximity to roadway, roof material, presence of a cistern screen, and first-flush systems were not significant with respect to As and Pb when controlling for relevant spatiotemporal variables; whereas, cistern age was associated with Pb concentrations. These results however, indicate that concentrations vary seasonally and by proximity to industrial activity, not by decisions made regarding collection system infrastructures at the individual home level. This study shows that generally, individuals are not responsible for environmental contamination of rooftop harvested rainwater, rather activities and decisions of government and corporate industries control contaminant release.

Epidemiology of respiratory syncytial virus in children younger than 5 years in England during the COVID-19 pandemic, measured by laboratory, clinical, and syndromic surveillance: a retrospective observational study.

BACKGROUND: Seasonal epidemics of respiratory syncytial virus (RSV) cause a clinically significant burden of disease among young children. Non-pharmaceutical interventions targeted at SARS-CoV-2 have affected the activity of other respiratory pathogens. We describe changes in the epidemiology of RSV among children younger than 5 years in England since 2020. METHODS: Surveillance data on RSV infections, comprising laboratory-confirmed cases, proportion of positive tests, hospital admissions for RSV-attributable illness, and syndromic indicators for RSV-associated disease (emergency department attendances for acute bronchitis or bronchiolitis, non-emergency health advice telephone service [NHS 111] calls for cough, general practitioner [GP] in-hours consultations for respiratory tract infections, and GP out-of-hours contacts for acute bronchitis or bronchiolitis) were analysed from Dec 29, 2014 to March 13, 2022, for children younger than 5 years. Data were extracted from national laboratory, clinical, and syndromic surveillance systems. Time-series analyses using generalised linear models were used to estimate the effect of non-pharmaceutical interventions targeting SARS-CoV-2 on RSV indicators, with absolute and relative changes calculated by comparing observed and predicted values. FINDINGS: RSV-associated activity was reduced for all RSV indicators during winter 2020-21 in England, with 10 280 (relative change -99·5% [95% prediction interval -100·0 to -99·1]) fewer laboratory-confirmed cases, 22·2 (-99·6%) percentage points lower test positivity, 92 530 (-80·8% [-80·9 to -80·8]) fewer hospital admissions, 96 672 (-73·7% [-73·7 to -73·7]) fewer NHS 111 calls, 2924 (-88·8% [-90·4 to -87·2]) fewer out-of-hours GP contacts, 91 304 (-89·9% [-90·0 to -89·9]) in-hours GP consultations, and 27 486 (-85·3% [-85·4 to -85·2]) fewer emergency department attendances for children younger than 5 years compared with predicted values based on winter seasons before the COVID-19 pandemic. An unprecedented summer surge of RSV activity occurred in 2021, including 11 255 (1258·3% [1178·3 to 1345·8]) extra laboratory-confirmed cases, 11·6 percentage points (527·3%) higher test positivity, 7604 (10·7% [10·7 to 10·8]) additional hospital admissions, 84 425 (124·8% [124·7 to 124·9]) more calls to NHS 111, 409 (39·0% [36·6 to 41·8]) more out-of-hours GP contacts, and 9789 (84·9% [84·5 to 85·4]) more emergency department attendances compared with the predicted values, although there were 21 805 (-34·1% [-34·1 to -34·0]) fewer in-hours GP consultations than expected. Most indicators were also lower than expected in winter 2021-22, although to a lesser extent than in winter 2020-21. INTERPRETATION: The extraordinary absence of RSV during winter 2020-21 probably resulted in a cohort of young children without natural immunity to RSV, thereby raising the potential for increased RSV incidence, out-of-season activity, and health-service pressures when measures to restrict SARS-CoV-2 transmission were relaxed. FUNDING: None.

Prospective Study of the Performance of Parent-Collected Nasal and Saliva Swab Samples, Compared with Nurse-Collected Swab Samples, for the Molecular Detection of Respiratory Microorganisms.

Respiratory tract infections (RTIs) are ubiquitous among children in the community. A prospective observational study was performed to evaluate the diagnostic performance and quality of at-home parent-collected (PC) nasal and saliva swab samples, compared to nurse-collected (NC) swab samples, from children with RTI symptoms. Children with RTI symptoms were swabbed at home on the same day by a parent and a nurse. We compared the performance of PC swab samples as the test with NC swab samples as the reference for the detection of respiratory pathogen gene targets by reverse transcriptase PCR, with quality assessment using a human gene. PC and NC paired nasal and saliva swab samples were collected from 91 and 92 children, respectively. Performance and interrater agreement (Cohen's κ) of PC versus NC nasal swab samples for viruses combined showed sensitivity of 91.6% (95% confidence interval [CI], 85.47 to 95.73%) and κ of 0.84 (95% CI, 0.79 to 0.88), respectively; the respective values for bacteria combined were 91.4% (95% CI, 86.85 to 94.87%) and κ of 0.85 (95% CI, 0.80 to 0.89). In saliva samples, viral and bacterial sensitivities were lower at 69.0% (95% CI, 57.47 to 79.76%) and 78.1% (95% CI, 71.60 to 83.76%), as were κ values at 0.64 (95% CI, 0.53 to 0.72) and 0.70 (95% CI, 0.65 to 0.76), respectively. Quality assessment for human biological material (18S rRNA) indicated perfect interrater agreement. At-home PC nasal swab samples performed comparably to NC swab samples, whereas PC saliva swab samples lacked sensitivity for the detection of respiratory microbes. IMPORTANCE RTIs are ubiquitous among children. Diagnosis involves a swab sample being taken by a health professional, which places a considerable burden on community health care systems, given the number of cases involved. The coronavirus disease 2019 (COVID-19) pandemic has seen an increase in the at-home self-collection of upper respiratory tract swab samples without the involvement of health professionals. It is advised that parents conduct or supervise swabbing of children. Surprisingly, few studies have addressed the quality of PC swab samples for subsequent identification of respiratory pathogens. We compared NC and PC nasal and saliva swab samples taken from the same child with RTI symptoms, for detection of respiratory pathogens. The PC nasal swab samples performed comparably to NC samples, whereas saliva swab samples lacked sensitivity for the detection of respiratory microbes. Collection of swab samples by parents would greatly reduce the burden on community nurses without reducing the effectiveness of diagnoses.

Impact of flooding on health-related quality of life in England: results from the National Study of Flooding and Health.

BACKGROUND: Flooding can have extensive effects on the health and wellbeing of affected communities. The impact of flooding on psychological morbidity has been established; however, the wider impacts of flooding exposure, including on health-related quality of life (HRQoL), have not been described. METHODS: Using data from the English National Study of Flooding and Health cohort, HRQoL 2 and 3 years post-flooding was assessed with the EuroQol Group EQ-5D-5L tool. Associations between exposure groups (flooding and disruption from flooding) and HRQoL were assessed, using ordinal and linear regression, adjusting for a priori confounders. RESULTS: For both 2 and 3 years post-flooding, the median HRQoL scores were lower in the flooded and disrupted groups, compared with unaffected respondents. A higher proportion of flooded and disrupted respondents reported HRQoL problems in most dimensions of the EQ-5D-5L, compared with unaffected respondents. In year 2, independent associations between exposure to flooding and experiencing anxiety/depression [adjusted odds ratio (aOR) 7.7; 95% CI 4.6-13.5], problems with usual activities (aOR 5.3; 95% CI 2.5-11.9) and pain/discomfort (aOR 2.4; 95% CI 1.5-3.9) were identified. These problems persisted 3 years post-flooding; associations between exposure to flooding and experiencing anxiety/depression (aOR 4.3; 95% CI 2.5-7.7), problems with usual activities (aOR 2.9; 95% CI 1.5-6.1) and pain/discomfort (aOR 2.5; 95% CI 1.5-4.2) were identified. CONCLUSIONS: Exposure to flooding and disruption from flooding significantly reduces HRQoL. These findings extend our knowledge of the impacts of flooding on health, with implications for multi-agency emergency response and recovery plans.

The English National Cohort Study of Flooding & Health: psychological morbidity at three years of follow up.

BACKGROUND: Flooding is expected to increase due to climate change, population growth and urban development. The longer-term mental health impacts of flooding are not well understood. In 2015, the English National Study of Flooding and Health was established to improve understanding of the impact of flooding on health and inform future public health action. METHODS: We used 3 years of data from the English National Study of Flooding and Health. Participants who had consented to follow up were sent a questionnaire. Participants were classified into either "unaffected", "disrupted" or "flooded" according to their exposure. Logistic regression models were used to calculate adjusted odds ratios for probable depression, anxiety and post-traumatic stress disorder (PTSD) in each exposure group. The Wald test was used to assess the difference in probable mental health outcomes for those who did and did not experience "persistent damage" to their home. Conditional logistic regression was conducted to assess change in prevalence over the 3 years and to identify possible determinants of recovery. RESULTS: Eight hundred nineteen individuals were included in the final analysis - 119 were classified as unaffected, 421 disrupted and 279 flooded. Overall, 5.7% had probable depression, 8.1% had probable anxiety and 11.8% had probable PTSD, with higher prevalence in the flooded group compared with the unaffected group. After adjustment for potential confounders, probable mental health outcomes were higher in the flooded group compared to the unaffected group, significantly for probable depression (aOR 8.48, 95% CI 1.04-68.97) and PTSD (aOR 7.74, 95% CI 2.24-26.79). Seventy-seven (9.4%) participants reported experiencing persistent damage to their home, most commonly damp (n = 40) and visible mould (n = 26) in liveable rooms. Of the 569 participants who responded at all 3 years, a significant reduction in prevalence for all probable mental health outcomes was observed in the flooded group. CONCLUSIONS: Flooding can have severe long-lasting consequences on mental health in affected populations. If these problems are not identified and treated early, they may persist for years. Further research is necessary to develop and evaluate interventions to increase resilience in at risk populations and to ensure timely access to support services following flooding.

HIV vaccine delayed boosting increases Env variable region 2-specific antibody effector functions.

In the RV144 HIV-1 phase III trial, vaccine efficacy directly correlated with the magnitude of the variable region 2-specific (V2-specific) IgG antibody response, and in the presence of low plasma IgA levels, with the magnitude of plasma antibody-dependent cellular cytotoxicity. Reenrollment of RV144 vaccinees in the RV305 trial offered the opportunity to define the function, maturation, and persistence of vaccine-induced V2-specific and other mAb responses after boosting. We show that the RV144 vaccine regimen induced persistent V2 and other HIV-1 envelope-specific memory B cell clonal lineages that could be identified throughout the approximately 11-year vaccination period. Subsequent boosts increased somatic hypermutation, a critical requirement for antibody affinity maturation. Characterization of 22 vaccine-induced V2-specific mAbs with epitope specificities distinct from previously characterized RV144 V2-specific mAbs CH58 and CH59 found increased in vitro antibody-mediated effector functions. Thus, when inducing non-neutralizing antibodies, one method by which to improve HIV-1 vaccine efficacy may be through late boosting to diversify the V2-specific response to increase the breadth of antibody-mediated anti-HIV-1 effector functions.

In vivo delivery of synthetic DNA-encoded antibodies induces broad HIV-1-neutralizing activity.

Interventions to prevent HIV-1 infection and alternative tools in HIV cure therapy remain pressing goals. Recently, numerous broadly neutralizing HIV-1 monoclonal antibodies (bNAbs) have been developed that possess the characteristics necessary for potential prophylactic or therapeutic approaches. However, formulation complexities, especially for multiantibody deliveries, long infusion times, and production issues could limit the use of these bNAbs when deployed, globally affecting their potential application. Here, we describe an approach utilizing synthetic DNA-encoded monoclonal antibodies (dmAbs) for direct in vivo production of prespecified neutralizing activity. We designed 16 different bNAbs as dmAb cassettes and studied their activity in small and large animals. Sera from animals administered dmAbs neutralized multiple HIV-1 isolates with activity similar to that of their parental recombinant mAbs. Delivery of multiple dmAbs to a single animal led to increased neutralization breadth. Two dmAbs, PGDM1400 and PGT121, were advanced into nonhuman primates for study. High peak-circulating levels (between 6 and 34 µg/ml) of these dmAbs were measured, and the sera of all animals displayed broad neutralizing activity. The dmAb approach provides an important local delivery platform for the in vivo generation of HIV-1 bNAbs and for other infectious disease antibodies.

Impact of repeat flooding on mental health and health-related quality of life: a cross-sectional analysis of the English National Study of Flooding and Health.

OBJECTIVE: To assess the association between flooding/repeat flooding and: (1) psychological morbidity (anxiety, depression, post-traumatic stress disorder (PTSD)) and (2) health-related quality of life (HRQoL) at 6 months post-flooding. DESIGN: Cross-sectional analysis of data from the English National Study of Flooding and Health. SETTING: Cumbria, England. PARTICIPANTS: Questionnaires were sent to 2500 residential addresses at 6 months post-flooding; 590 people responded. OUTCOMES: Probable depression was assessed using the Patient Health Questionnaire, probable anxiety using the Generalised Anxiety Disorder scale and probable PTSD using the short-form PTSD checklist (PCL-6). HRQoL was assessed using the EQ-5D-5L. Mental health outcomes were analysed using logistic regression; HRQoL dimensions using ordinal regression; and summary index/Visual Analogue Scale scores using linear regression. RESULTS: One hundred and nineteen participants had been flooded, over half of whom were experiencing a repeat flooding event (54%; n=64). Mental health outcomes were elevated among flooded compared with unaffected participants (adjusted OR for probable depression: 7.77, 95% CI: 1.51 to 40.13; anxiety: 4.16, 95% CI: 1.18 to 14.70; PTSD: 14.41, 95% CI: 3.91 to 53.13). The prevalence of depression was higher among repeat compared with single flooded participants, but this was not significant after adjustment. There was no difference in levels of anxiety or PTSD. Compared with unaffected participants, those flooded had lower EQ-5D-5L index scores (adjusted coefficient: -0.06, 95% CI: -0.12 to -0.01) and lower self-rated health scores (adjusted coefficient: -6.99, 95% CI: -11.96 to -2.02). There was, however, little difference in HRQoL overall between repeat and single flooded participants. CONCLUSIONS: Interventions are needed to help minimise the impact of flooding on people's mental health and HRQoL.

Outbreak of diarrhetic shellfish poisoning associated with consumption of mussels, United Kingdom, May to June 2019.

We report on six cases of diarrhetic shellfish poisoning following consumption of mussels harvested in the United Kingdom. Dinophysis spp. in the water column was found to have increased rapidly at the production site resulting in high levels of okadaic acid-group lipophilic toxins in the flesh of consumed mussels. Clinicians and public health professionals should remain aware of algal-derived toxins being a potential cause of illness following seafood consumption.

Cannabis use and the risk of tuberculosis: a systematic review.

BACKGROUND: Cannabis has been identified as a possible risk factor in some tuberculosis (TB) outbreaks. As the most widely used (largely) illegal substance in Western countries this may be an important public health concern. We aim to systematically review the evidence on the association between cannabis use and TB (latent infection and active disease) to inform ongoing and future TB prevention and control strategies. METHODS: We conducted a systematic review. We searched Ovid Medline, Embase and PsycInfo, together with the World Health Organization website and Google Scholar, for all years to January 2018. Reference lists and conference abstracts were hand-searched, a forward citation search was conducted on the Web of Science, and experts were contacted. Two authors independently screened studies for inclusion, extracted data and assessed risk of bias using an adapted version of ROBINS-I ("Risk of Bias in Non-randomised Studies - of Interventions"). Data were narratively synthesised. RESULTS: Of 377 records identified, 11 studies were eligible. Study designs were heterogeneous. Six studies utilised a relevant comparator group. Four of these investigated the association between cannabis use and latent TB infection; all provided some evidence of an association, although only two of these had adjusted for confounders. The remaining two comparator studies investigated the association between cannabis use and active TB disease; neither found evidence of an association after adjusting for confounding. All six studies were at "Serious" risk of bias. The five studies which did not utilise a relevant comparator group were all indicative of TB outbreaks occurring among cannabis users, but the quality of the evidence was very weak. CONCLUSIONS: Evidence for an association between cannabis use and TB acquisition is weak. The topic warrants further robust primary research including the collection of consistent and accurate exposure information, including cannabis use practices, dose and frequency, and adjustment for confounders.

Antibody Fab-Fc properties outperform titer in predictive models of SIV vaccine-induced protection.

Characterizing the antigen-binding and innate immune-recruiting properties of the humoral response offers the chance to obtain deeper insights into mechanisms of protection than revealed by measuring only overall antibody titer. Here, a high-throughput, multiplexed Fab-Fc Array was employed to profile rhesus macaques vaccinated with a gp120-CD4 fusion protein in combination with different genetically encoded adjuvants, and subsequently subjected to multiple heterologous simian immunodeficiency virus (SIV) challenges. Systems analyses modeling protection and adjuvant differences using Fab-Fc Array measurements revealed a set of correlates yielding strong and robust predictive performance, while models based on measurements of response magnitude alone exhibited significantly inferior performance. At the same time, rendering Fab-Fc measurements mathematically independent of titer had relatively little impact on predictive performance. Similar analyses for a distinct SIV vaccine study also showed that Fab-Fc measurements performed significantly better than titer. These results suggest that predictive modeling with measurements of antibody properties can provide detailed correlates with robust predictive power, suggest directions for vaccine improvement, and potentially enable discovery of mechanistic associations.

Reducing Primary Care Attendance Intentions for Pediatric Respiratory Tract Infections.

PURPOSE: The aim of this study was to evaluate a theory and evidence-based, parent-targeted online intervention, combining microbiological local syndromic surveillance data, symptom information, and home-care advice, to reduce primary care attendance for self-limiting, low-risk pediatric respiratory tract infections (RTIs). METHODS: The effect of this novel intervention on primary care attendance intentions was evaluated in an online experimental study. A representative sample of mothers (n = 806) was randomly assigned to receive the intervention material before (intervention) or after (control) answering questions concerning attendance intentions for an RTI illness scenario and mediating factors. Both groups provided feedback on the material. Group comparisons, linear regression, and path analyses were conducted. RESULTS: Intervention participants reported lower attendance intentions compared with control participants (d = 0.69, 95% CI, 0.55-0.83), an effect that remained when controlling for demographic and clinical characteristics (B = -1.62, 95% CI, -1.97 to -1.30). The path model highlighted that the intervention effect (B = -0.33, 95% CI, -0.40 to -0.26) was mostly indirect and mediated by infection and antibiotic knowledge, symptom severity concerns, and social norm perceptions concerning attendance. Information on when to attend was rated as the most important intervention component 227 times, followed by symptoms rated 186 times. Information on circulating viruses was rated as least important 274 times. CONCLUSIONS: The intervention was effective in reducing primary care attendance intentions by increasing knowledge, lowering attendance motivation, and reducing the need for additional resources. The contribution of individual intervention components and effects on behavioral outcomes requires further testing.

Effect of Insurance-Related Factors on the Association between Flooding and Mental Health Outcomes.

Floods are a significant public health problem linked with increased psychological morbidity. We aimed to investigate the effect of insurance-related factors on the association between flooding and probable mental health outcomes. We performed a secondary analysis of cross-sectional survey data from the English National Study of Flooding and Health (NSFH) collected two years after an initial flooding event in 2013-14. Our analysis focused on 851 respondents who experienced flooding or disruption. Multivariable logistic regression models were run for each exposure group. Among those whose homes had been flooded, not having household insurance was associated with increased odds of all outcomes compared to those with household insurance, significantly so for post-traumatic stress disorder (PTSD) (aOR 4.31, 95% CI 1.31-14.20). Those who reported severe stress due to insurance issues had increased odds of probable depression (aOR 11.08, 95% CI 1.11-110.30), anxiety (aOR 4.48, 95% CI 1.02-19.70) and PTSD (aOR 7.95, 95% CI 2.10-30.1) compared to those reporting no/mild stress. The study suggests there is increased psychological morbidity amongst the uninsured and those who report feeling severe stress as a result of insurance issues associated with flooding. Services should be prepared to support communities through insurance processes, to reduce probable mental health morbidity following a flood event.

Detection in the United Kingdom of the Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate resistance to azithromycin, October to December 2018.

We describe detection in the United Kingdom (UK) of the drug-resistant Neisseria gonorrhoeae FC428 clone, with ceftriaxone resistance and intermediate azithromycin resistance. Two female patients developed infection following contact with UK-resident men from the same sexual network linked to travel to Ibiza, Spain. One case failed treatment with ceftriaxone, and azithromycin and gentamicin, before successful treatment with ertapenem. Both isolates had indistinguishable whole-genome sequences. Urgent action is essential to contain this drug-resistant strain.

Social network analysis and whole genome sequencing in a cohort study to investigate TB transmission in an educational setting.

BACKGROUND: TB outbreaks in educational institutions can result in significant transmission and pose a considerable threat to TB control. Investigation using traditional microbiological and epidemiological tools can lead to imprecise screening strategies due to difficulties characterising complex transmission networks. Application of whole genome sequencing (WGS) and social network analysis can provide additional information that may facilitate rapid directed public health action. We report the utility of these methods in combination with traditional approaches for the first time to investigate a TB outbreak in an educational setting. METHODS: Latent tuberculosis infection (LTBI) cases were screenees with a positive T-SPOT®.TB test. Active TB cases were defined through laboratory confirmation of M. tuberculosis on culture or through clinical or radiological findings consistent with infection. Epidemiological data were collected from institutional records and screenees. Samples were cultured and analysed using traditional M. tuberculosis typing and WGS. We undertook multivariable multinomial regression and social network analysis to identify exposures associated with case status and risk communities. RESULTS: We identified 189 LTBI cases (13.7% positivity rate) and nine active TB cases from 1377 persons screened. The LTBI positivity rate was 39.1% (99/253) among persons who shared a course with an infectious case (odds ratio 7.3, 95% confidence interval [CI] 5.2 to 10.3). The community structure analysis divided the students into five communities based on connectivity, as opposed to the 11 shared courses. Social network analysis identified that the community including the suspected index case was at significantly elevated risk of active disease (odds ratio 7.5, 95% CI 1.3 to 44.0) and contained eight persons who were lost to follow-up. Five sputum samples underwent WGS, four had zero single nucleotide polymorphism (SNP) differences and one had a single SNP difference. CONCLUSION: This study demonstrates the public health impact an undiagnosed case of active TB disease can have in an educational setting within a low incidence area. Social network analysis and whole genome sequencing provided greater insight to evolution of the transmission network and identification of communities of risk. These tools provide further information over traditional epidemiological and microbiological approaches to direct public health action in this setting.