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In July 2022, a genetically linked and geographically dispersed cluster of 12 cases of Shiga toxin-producing Escherichia coli (STEC) O103:H2 was detected by the UK Health Security Agency using whole genome sequencing. Review of food history questionnaires identified cheese (particularly an unpasteurized brie-style cheese) and mixed salad leaves as potential vehicles. A case-control study was conducted to investigate exposure to these products. Case food history information was collected by telephone. Controls were recruited using a market research panel and self-completed an online questionnaire. Univariable and multivariable analyses were undertaken using Firth Logistic Regression. Eleven cases and 24 controls were included in the analysis. Consumption of the brie-style cheese of interest was associated with illness (OR 57.5, 95% confidence interval: 3.10-1,060). Concurrently, the production of the brie-style cheese was investigated. Microbiological sample results for the cheese products and implicated dairy herd did not identify the outbreak strain, but did identify the presence of stx genes and STEC, respectively. Together, epidemiological, microbiological, and environmental investigations provided evidence that the brie-style cheese was the vehicle for this outbreak. Production of unpasteurized dairy products was suspended by the business operator, and a review of practices was performed.

Aims: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe., Design, Setting and Participants: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months)., Measurements: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID., Findings: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity., Conclusions: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration., (© 2023 Society for the Study of Addiction.)

We investigated an outbreak of SARS-CoV-2 variant BA.2.86 in an East of England care home. We identified 45 infections (33 residents, 12 staff), among 38 residents and 66 staff. Twenty-nine of 43 PCR swabs were sequenced, all of which were variant BA.2.86. The attack rate among residents was 87%, 19 were symptomatic, and one was hospitalised. Twenty-four days after the outbreak started, no cases were still unwell. Among the 33 resident cases, 29 had been vaccinated 4 months earlier.

We report a 5-single nucleotide polymorphism cluster of Salmonella Enteriditis in England, part of a global cluster of S. Enteritidis ST11. Forty-seven confirmed cases have been investigated of whom 25 were linked to a restaurant. In addition, there were 18 probable cases with restaurant exposure. Epidemiological investigations suggested eggs or chicken as the most likely cause of the outbreak but were unable to distinguish between those two food vehicles. Ongoing food chain investigations indicated links to imported eggs from Poland.

Background: Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of Streptococcus pneumoniae is a necessary step in the development of pneumococcal pneumonia. We aimed to assess the association between exposure to household air pollution and the prevalence and density of S pneumoniae carriage among children., Methods: The Malawi Streptococcus pneumoniae Carriage and Air Pollution Exposure study was a nested, prospective, observational study of children participating in the cluster randomised controlled Cooking and Pneumonia Study (CAPS) in the Karonga Health and Demographic Surveillance System (HDSS) area in northern Malawi. CAPS compared the effects of a cleaner burning biomass-fuelled cookstove (intervention group) with traditional open-fire cooking (control group) on the incidence of pneumonia in children. Eligible children aged 6 weeks or 6 months (those recruited a 6 weeks were also followed up at age 6 months) were identified by the Karonga HDSS centre. Nasopharyngeal swabs were taken to detect S pneumoniae, and infant exposure to particulate matter with a diameter of ≤2·5 μm (PM 2·5 ) exposure was assessed by use of a MicroPEM device. The primary outcome was the prevalence of nasopharyngeal S pneumoniae carriage in all children aged 6 months, assessed in all children with valid data on PM 2·5 . The effects of the intervention stoves (intention-to-treat analysis) and PM 2·5 (adjusted exposure-response analysis) on the prevalence of S pneumoniae carriage were also assessed in the study children., Findings: Between Nov 15, 2015, and Nov 2, 2017, 485 children were recruited (240 from the intervention group and 245 from the control group). Of all 450 children with available data at age 6 months, 387 (86% [95% CI 82-89]) were positive for S pneumoniae. Geometric mean PM 2·5 exposure was 60·3 μg/m 3 (95% CI 55·8-65·3) in S pneumoniae-positive children and 47·0 μg/m 3 (38·3-57·7) in S pneumoniae-negative children (p=0·044). In the intention-to-treat analysis, a non-significant increase in the risk of S pneumoniae carriage was observed in intervention group children compared with control group children (odds ratio 1·36 [95% CI 0·95-1·94]; p=0·093). In the exposure-response analysis, a significant association between PM 2·5 exposure and S pneumoniae carriage was observed; a one unit increase in decile of PM 2·5 was found to significantly increase the risk of S pneumoniae carriage by 10% (1·10 [1·01-1·20]; p=0·035), after adjustment for age, sex, 13-valent pneumococcal conjugate vaccination status, season, current use of antibiotics, and MicroPEM run-time., Interpretation: Despite the absence of effect from the intervention cookstove, household air pollution exposure was significantly associated with the prevalence of nasopharyngeal S pneumoniae carriage. These results provide empirical evidence for the potential mechanistic association between exposure to household air pollution and childhood pneumonia., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: To date, evidence on whether sexualized drug use (SDU) and chemsex occur less frequently in rural compared to urban areas in Britain has been conflicting. This study aimed to better measure and understand whether attending urban versus rural sexual health clinics in the United Kingdom was associated with a difference in men who have sex with men's (MSM) experience of SDU or their access to SDU support. Methods: Men from 29 sexual health services across England and Scotland were recruited by self-completing a waiting room survey. Results: A total of 2655 men (864 MSM) took part. There was no statistically significant difference in recent SDU or chemsex identified in MSM attending rural compared to urban clinics. Gamma-Hydroxybutyrate/Gamma-Butyrolactone (GHB/GBL) was the most commonly reported chemsex drug used in a sexual setting, with equal prevalence of use in urban and rural MSM attendees. Distance travelled for SDU was not significantly different for rural compared to urban MSM. Rural MSM reported a higher rate of unmet need for SDU specific services, although this difference was not statistically significant. Conclusion: Within this sample of MSM, there were no significant differences in sexualized drug use behaviours between those attending rural compared to urban sexual health settings.

Direct-acting antiviral (DAA) therapy for anybody with viraemic HCV infection has been scaled-up in England since 2017. To assess early impacts, we investigated trends in, and factors associated with, HCV viraemia among people who inject drugs (PWID). We also examined trends in self-reported treatment access. Bio-behavioural data from an annual, national surveillance survey of PWID (2011-2018) estimated trends in viraemic prevalence among HCV antibody-positive PWID. Multivariable logistic regression identified characteristics independently associated with viraemia. Trends in treatment access were examined for PWID with known infection. Between 2011 and 2016, viraemic prevalence among antibody-positive PWID remained stable (2011, 57.7%; 2016, 55.8%) but decreased in 2017 (49.4%) and 2018 (50.4%) (both p < 0.001). After adjustment for demographic and behavioural characteristics, there remained significant reduction in viraemia in 2017 (adjusted odds ratio [aOR] 0.79, 95% CI 0.65-0.94) and 2018 (aOR 0.79, 95% CI 0.66-0.93) compared to 2016. Other factors associated with viraemia were male gender (aOR 1.68, 95% CI 1.53-1.86), geographical region, injecting in past year (aOR 1.26, 95% CI 1.13-1.41), imprisonment (aOR 1.14, 95% CI 1.04-1.31) and homelessness (aOR 1.17, 95% CI 1.04-1.31). Among non-viraemic PWID with known infection, the proportion reporting ever receiving treatment increased in 2017 (28.7%, p < 0.001) and 2018 (38.9%, p < 0.001) compared to 2016 (14.5%). In conclusion, there has been a small reduction in HCV viraemia among antibody-positive PWID in England since 2016, alongside DAA scale-up, and some indication that treatment access has improved in the same period. Population-level monitoring and focus on harm reduction is critical for achieving and evaluating elimination., (© 2021 Crown copyright. Journal of Viral Hepatitis published by John Wiley & Sons Ltd. This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.)

Background: A target to eliminate HIV transmission in England by 2030 was set in early 2019. This study aimed to estimate trends from 2013 to 2019 in HIV prevalence, particularly the number of people living with undiagnosed HIV, by exposure group, ethnicity, gender, age group, and region. These estimates are essential to monitor progress towards elimination., Methods: A Bayesian synthesis of evidence from multiple surveillance, demographic, and survey datasets relevant to HIV in England was used to estimate trends in the number of people living with HIV, the proportion of people unaware of their HIV infection, and the corresponding prevalence of undiagnosed HIV. All estimates were stratified by exposure group, ethnicity, gender, age group (15-34, 35-44, 45-59, or 60-74 years), region (London, or outside of London) and year (2013-19)., Findings: The total number of people living with HIV aged 15-74 years in England increased from 83 500 (95% credible interval 80 200-89 600) in 2013 to 92 800 (91 000-95 600) in 2019. The proportion diagnosed steadily increased from 86% (80-90%) to 94% (91-95%) during the same time period, corresponding to a halving in the number of undiagnosed infections from 11 600 (8300-17 700) to 5900 (4400-8700) and in undiagnosed prevalence from 0·29 (0·21-0·44) to 0·14 (0·11-0·21) per 1000 population. Similar steep declines were estimated in all subgroups of gay, bisexual, and other men who have sex with men and in most subgroups of Black African heterosexuals. The pace of reduction was less pronounced for heterosexuals in other ethnic groups and people who inject drugs, particularly outside London; however, undiagnosed prevalence in these groups has remained very low., Interpretation: The UNAIDS target of diagnosing 90% of people living with HIV by 2020 was reached by 2016 in England, with the country on track to achieve the new target of 95% diagnosed by 2025. Reductions in transmission and undiagnosed prevalence have corresponded to large scale-up of testing in key populations and early diagnosis and treatment. Additional and intensified prevention measures are required to eliminate transmission of HIV among the communities that have experienced slower declines than other subgroups, despite having very low prevalences of HIV., Funding: UK Medical Research Council and Public Health England., Competing Interests: Declaration of interests HM was a PHE technical advisor on the UK National Institute for Health and Care Excellence pending guideline on Reducing sexually transmitted infections (GID-NG10142). All other authors declare no competing interests., (This is an open access article under the CC BY-NC-ND license.)

Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas.

Introduction and Aims: Historically, people who inject image and performance enhancing drugs (IPED) were not perceived as being at high risk of HIV or hepatitis C virus (HCV) infection. However, recent studies indicate HCV and HIV prevalences are elevated, with many HCV infections undiagnosed., Design and Methods: Men who inject IPEDs recruited from community settings and specialist services, including needle-syringe programs, across UK during 2016 self-completed a questionnaire. Multivariate analyses examined factors associated with HCV/HIV testing., Results: The participants' (n=562; 24% service recruited) median age was 31 years, 4% identified as gay or bisexual, 18% had ever been imprisoned and 6% had ever injected a psychoactive drug. Those community recruited more often reported sharing drugs vials (16% vs. 8%, P=0.021) and, among those with 2+ sexual partners, poor condom use (50% vs. 36%, P=0.063), than those service recruited. Overall, one-third had ever been tested for HCV (31%) and/or HIV (34%). Testing uptake was associated with other risk factors for HCV/HIV, being recruited through services and having received metabolic tests. Participants' motivations for using IPEDs were associated with recruitment setting and HIV/HCV testing uptake., Discussion and Conclusions: The majority were untested for HCV/HIV. HCV/HIV testing and risks were associated with recruitment through services. Previous needle and syringe program-based studies have potentially overestimated testing uptake and underestimated risk. Targeted interventions are needed, particularly for those not accessing services. The association between HCV/HIV testing uptake and receipt of metabolic tests suggests that developing a combined offer of these tests as part of health monitoring could improve uptake., (© 2020 Australasian Professional Society on Alcohol and other Drugs.)

Background: Pneumococcal conjugate vaccine (PCV) and rotavirus vaccine (RV) are key tools for reducing common causes of infant mortality. However, measurement of population-level mortality impact is lacking from sub-Saharan Africa. We evaluated mortality impact and vaccine effectiveness (VE) of PCV13 introduced in November 2011, with subsequent RV1 roll-out in October 2012, in Malawi., Methods: We conducted two independent community-based birth cohort studies. Study 1, in northern Malawi (40000population), evaluated population impact using change-point analysis and negative-binomial regression of non-traumatic 14-51-week infant mortality preintroduction (1 January 2004 to 31 September 2011) and postintroduction (1 October 2011 to 1 July 2019), and against three-dose coverage. Study 2, in central Malawi (465 000 population), was recruited from 24 November 2011 to 1 June 2015. In the absence of preintroduction data, individual three-dose versus zero-dose VE was estimated using individual-level Cox survival models. In both cohorts, infants were followed with household visits to ascertain vaccination, socioeconomic and survival status. Verbal autopsies were conducted for deaths., Results: Study 1 included 20 291 live births and 216 infant deaths. Mortality decreased by 28.6% (95% CI: 15.3 to 39.8) post-PCV13 introduction. A change point was identified in November 2012. Study 2 registered 50 731 live births, with 454 deaths. Infant mortality decreased from 17 to 10/1000 live births during the study period. Adjusted VE was 44.6% overall (95% CI: 23.0 to 59.1) and 48.3% (95% CI: -5.9 to 74.1) against combined acute respiratory infection, meningitis and sepsis-associated mortality., Conclusion: These data provide population-level evidence of infant mortality reduction following sequential PCV13 and RV1 introduction into an established immunisation programme in Malawi. These data support increasing coverage of vaccine programmes in high-burden settings., Competing Interests: Competing interests: NC, NB-Z and NF received an investigator initiated grant by GlaxoSmithKline Biologicals to support data collection. NC has received research grant support and honoraria for participation in rotavirus vaccine advisory board meetings from GlaxoSmithKline Biologicals. DH has received research grant support on the topic of rotavirus vaccines from GlaxoSmithKline Biologicals, Sanofi Pasteur and Merck and Co (Kenilworth, New Jersey, US) after the closure of Sanofi Pasteur-MSD in December 2016., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: People who inject drugs (PWID) are at high risk of injection-related skin and soft tissue infections (SSTI). If not treated promptly, these can lead to serious health complications, which are a considerable healthcare burden. Data from two community surveys, with different approaches, were used to assess SSTI prevalence and associated factors among PWID to inform intervention implementation., Methods: Data were analysed from two surveys, a national surveillance survey (n=2,874; 2017-18) of infections among PWID in the United Kingdom (UK) and an in-depth survey (n=455; 2018-19) of SSTI among PWID based in London, UK. Multivariable logistic regression models were constructed to ascertain the factors associated with self-reported SSTI., Results: High prevalence of SSTI were reported in both samples: 52 % of participants from the national surveillance survey reported having SSTI within the preceding 12 months and 65 % of the London sample reported a lifetime history of SSTI. The factors associated with SSTI in both surveys were similar, including older age; number of years injecting; number of attempts required to inject into the vein; injecting into the hands, feet, groin or neck and re-using or sharing needles/syringes., Conclusions: The number of PWID reporting SSTI in the UK is concerningly high. The two surveys used different recruitment approaches but found similar associations. We provide strong evidence of a relationship between venous access difficulty and SSTI. To stem the increase of SSTI and related complications in the UK, it is crucial that interventions attend to the underlying causes of venous damage among PWID., Competing Interests: Declaration of Competing Interest No conflict declared., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Pneumococcal conjugate vaccines (PCVs) have reduced pneumococcal diseases globally. Pneumococcal genomic surveys elucidate PCV effects on population structure but are rarely conducted in low-income settings despite the high disease burden., Methods: We undertook whole-genome sequencing (WGS) of 660 pneumococcal isolates collected through surveys from healthy carriers 2 years from 13-valent PCV (PCV13) introduction and 1 year after rollout in northern Malawi. We investigated changes in population structure, within-lineage serotype dynamics, serotype diversity, and frequency of antibiotic resistance (ABR) and accessory genes., Results: In children <5 years of age, frequency and diversity of vaccine serotypes (VTs) decreased significantly post-PCV, but no significant changes occurred in persons ≥5 years of age. Clearance of VT serotypes was consistent across different genetic backgrounds (lineages). There was an increase of nonvaccine serotypes (NVTs)-namely 7C, 15B/C, and 23A-in children <5 years of age, but 28F increased in both age groups. While carriage rates have been recently shown to remain stable post-PCV due to replacement serotypes, there was no change in diversity of NVTs. Additionally, frequency of intermediate-penicillin-resistant lineages decreased post-PCV. Although frequency of ABR genes remained stable, other accessory genes, especially those associated with mobile genetic element and bacteriocins, showed changes in frequency post-PCV., Conclusions: We demonstrate evidence of significant population restructuring post-PCV driven by decreasing frequency of vaccine serotypes and increasing frequency of few NVTs mainly in children under 5. Continued surveillance with WGS remains crucial to fully understand dynamics of the residual VTs and replacement NVT serotypes post-PCV., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Introduction: Hepatitis C virus (HCV) is the second largest contributor to liver disease in the UK, with injecting drug use as the main risk factor among the estimated 200 000 people currently infected. Despite effective prevention interventions, chronic HCV prevalence remains around 40% among people who inject drugs (PWID). New direct-acting antiviral (DAA) HCV therapies combine high cure rates (>90%) and short treatment duration (8 to 12 weeks). Theoretical mathematical modelling evidence suggests HCV treatment scale-up can prevent transmission and substantially reduce HCV prevalence/incidence among PWID. Our primary aim is to generate empirical evidence on the effectiveness of HCV 'Treatment as Prevention' (TasP) in PWID., Methods and Analysis: We plan to establish a natural experiment with Tayside, Scotland, as a single intervention site where HCV care pathways are being expanded (including specialist drug treatment clinics, needle and syringe programmes (NSPs), pharmacies and prison) and HCV treatment for PWID is being rapidly scaled-up. Other sites in Scotland and England will act as potential controls. Over 2 years from 2017/2018, at least 500 PWID will be treated in Tayside, which simulation studies project will reduce chronic HCV prevalence among PWID by 62% (from 26% to 10%) and HCV incidence will fall by approximately 2/3 (from 4.2 per 100 person-years (p100py) to 1.4 p100py). Treatment response and re-infection rates will be monitored. We will conduct focus groups and interviews with service providers and patients that accept and decline treatment to identify barriers and facilitators in implementing TasP. We will conduct longitudinal interviews with up to 40 PWID to assess whether successful HCV treatment alters their perspectives on and engagement with drug treatment and recovery. Trained peer researchers will be involved in data collection and dissemination. The primary outcome - chronic HCV prevalence in PWID - is measured using information from the Needle Exchange Surveillance Initiative survey in Scotland and the Unlinked Anonymous Monitoring Programme in England, conducted at least four times before and three times during and after the intervention. We will adapt Bayesian synthetic control methods (specifically the Causal Impact Method) to generate the cumulative impact of the intervention on chronic HCV prevalence and incidence. We will use a dynamic HCV transmission and economic model to evaluate the cost-effectiveness of the HCV TasP intervention, and to estimate the contribution of the scale-up in HCV treatment to observe changes in HCV prevalence. Through the qualitative data we will systematically explore key mechanisms of TasP real world implementation from provider and patient perspectives to develop a manual for scaling up HCV treatment in other settings. We will compare qualitative accounts of drug treatment and recovery with a 'virtual cohort' of PWID linking information on HCV treatment with Scottish Drug treatment databases to test whether DAA treatment improves drug treatment outcomes., Ethics and Dissemination: Extending HCV community care pathways is covered by ethics (ERADICATE C, ISRCTN27564683, Super DOT C Trial clinicaltrials.gov: NCT02706223). Ethical approval for extra data collection from patients including health utilities and qualitative interviews has been granted (REC ref: 18/ES/0128) and ISCRCTN registration has been completed (ISRCTN72038467). Our findings will have direct National Health Service and patient relevance; informing prioritisation given to early HCV treatment for PWID. We will present findings to practitioners and policymakers, and support design of an evaluation of HCV TasP in England., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Objective: Hospitals in the UK are under increasing clinical and financial pressures. Following introduction of childhood rotavirus vaccination in the UK in 2013, rotavirus gastroenteritis (RVGE) hospitalisations reduced significantly. We evaluated changes in 'hospital pressures' (demand on healthcare resources and staff) following rotavirus vaccine introduction in a paediatric setting in the UK., Design: Retrospective hospital database analysis between July 2007 and June 2015., Setting: A large paediatric hospital providing primary, secondary and tertiary care in Merseyside, UK., Participants: Hospital admissions aged <15 years. Outcomes were calculated for four different patient groups identified through diagnosis coding (International Classification of Disease, 10th edition) and/or laboratory confirmation: all admissions; any infection, acute gastroenteritis and RVGE., Methods: Hospital pressures were compared before and after rotavirus vaccine introduction: these included bed occupancy, hospital-acquired infection rate, unplanned readmission rate and outlier rate (medical patients admitted to surgical wards due to lack of medical beds). Interrupted time-series analysis was used to evaluate changes in bed occupancy., Results: There were 116 871 admissions during the study period. Lower bed occupancy in the rotavirus season in the postvaccination period was observed for RVGE (-89%, 95% CI 73% to 95%), acute gastroenteritis (-63%, 95% CI 39% to 78%) and any infection (-23%, 95% CI 15% to 31%). No significant overall reduction in bed occupancy was observed (-4%, 95% CI -1% to 9%). No changes were observed for the other outcomes., Conclusions: Rotavirus vaccine introduction was not associated with reduced hospital pressures. A reduction in RVGE hospitalisation without change in overall bed occupancy suggests that beds available were used for a different patient population, possibly reflecting a previously unmet need., Trials Registration Number: NCT03271593., Competing Interests: Competing interests: Rotarix is a trademark of the GSK group of companies. NAC, NF and DH are in receipt of research grant support from the GSK group of companies for the conduct of the present study. NAC has received honoraria for participation in GSK Rotavirus Vaccine Advisory Board Meetings from the GSK group of companies and from Watermark Research Partners for participation in independent data monitoring committee of GSK-sponsored clinical trials of Rotavirus vaccine. The institution of NAC and NF received grant from the GSK group of companies for the conduct of other analysis, not related to the present work. DH received grants from the GSK group of companies and Sanofi Pasteur, and Merck & Co (Kenilworth, New Jersey, USA) outside the submitted work. NB-Z reports grants from the GSK group of companies and from Takeda Pharmaceuticals outside the submitted work. BS and ET are employees of the GSK group of companies. EH, RC, MC and JC have nothing to disclose., (© Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In 2015, Bristol (South West England) experienced a large increase in cases of meticillin-resistant Staphylococcus aureus (MRSA) infection in people who inject drugs (PWID)., Aim: We aimed to characterise and estimate the prevalence of MRSA colonisation among PWID in Bristol and test evidence of a clonal outbreak., Methods: PWID recruited through an unlinked-anonymous community survey during 2016 completed behavioural questionnaires and were screened for MRSA. Univariable logistic regression examined associations with MRSA colonisation. Whole-genome sequencing used lineage-matched MRSA isolates, comparing PWID (screening and retrospective bacteraemia samples from 2012-2017) with non-PWID (Bristol screening) in Bristol and national reference laboratory database samples., Results: The MRSA colonisation prevalence was 8.7% (13/149) and was associated with frequently injecting in public places (odds ratio (OR): 5.5; 95% confidence interval (CI):1.34-22.70), recent healthcare contact (OR: 4.3; 95% CI: 1.34-13.80) and injecting in groups of three or more (OR: 15.8; 95% CI: 2.51-99.28). People reporting any one of: injecting in public places, injection site skin and soft tissue infection or hospital contact accounted for 12/13 MRSA positive cases (sensitivity 92.3%; specificity 51.5%). Phylogenetic analysis identified a dominant clade associated with infection and colonisation among PWID in Bristol belonging to ST5-SCCmecIVg., Conclusions: MRSA colonisation in Bristol PWID is substantially elevated compared with general population estimates and there is evidence of clonal expansion, community-based transmission and increased infection risk related to the colonising strain. Targeted interventions, including community screening and suppression therapy, education and basic infection control are needed to reduce MRSA infections in PWID.

Background: People who inject drugs (PWID) experience a high prevalence of incarceration and might be at high risk of HIV and hepatitis C virus (HCV) infection during or after incarceration. We aimed to assess whether incarceration history elevates HIV or HCV acquisition risk among PWID., Methods: In this systematic review and meta-analysis, we searched MEDLINE, Embase, and PsycINFO databases for studies in any language published from Jan 1, 2000 until June 13, 2017 assessing HIV or HCV incidence among PWID. We included studies that measured HIV or HCV incidence among community-recruited PWID. We included only studies reporting original results and excluded studies that evaluated incident infections by self-report. We contacted authors of cohort studies that met the inclusion or exclusion criteria, but that did not report on the outcomes of interest, to request data. We extracted and pooled data from the included studies using random-effects meta-analyses to quantify the associations between recent (past 3, 6, or 12 months or since last follow-up) or past incarceration and HIV or HCV acquisition (primary infection or reinfection) risk among PWID. We assessed the risk of bias of included studies using the Newcastle-Ottawa Scale. Between-study heterogeneity was evaluated using the I 2 statistic and the P-value for heterogeneity., Findings: We included published results from 20 studies and unpublished results from 21 studies. These studies originated from Australasia, western and eastern Europe, North and Latin America, and east and southeast Asia. Recent incarceration was associated with an 81% (relative risk [RR] 1·81, 95% CI 1·40-2·34) increase in HIV acquisition risk, with moderate heterogeneity between studies (I 2 =63·5%; p=0·001), and a 62% (RR 1·62, 95% CI 1·28-2·05) increase in HCV acquisition risk, also with moderate heterogeneity between studies (I 2 =57·3%; p=0·002). Past incarceration was associated with a 25% increase in HIV (RR 1·25, 95% CI 0·94-1·65) and a 21% increase in HCV (1·21, 1·02-1·43) acquisition risk., Interpretation: Incarceration is associated with substantial short-term increases in HIV and HCV acquisition risk among PWID and could be a significant driver of HCV and HIV transmission among PWID. These findings support the need for developing novel interventions to minimise the risk of HCV and HIV acquisition, including addressing structural risks associated with drug laws and excessive incarceration of PWID., Funding: Engineering and Physical Sciences Research Council, National Institute for Health Research, National Institutes of Health., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Thirteen-valent pneumococcal conjugate vaccine (PCV13) was introduced in Malawi in November 2011 and is offered to infants at 6, 10 and 14 weeks of age as part of routine immunisation. PCV13 is expected to reduce vaccine type (VT) nasopharyngeal carriage, leading to reduced transmission and herd protection., Methods: We compared pneumococcal carriage in rural Karonga District, Malawi, pre-vaccine in 2009-2011 and post-vaccine in 2014 using a combination of cross-sectional and longitudinal analyses. Nasopharyngeal swabs were collected from a cohort of mother-infant pairs and household members <16 years. Pneumococci from 2009 to 2011 were serogrouped using latex agglutination and serotyped by Quellung reaction. In 2014, latex agglutination was used for both steps. Carriage prevalence ratios using prevalence data from before and after vaccine introduction were calculated by log-binomial regression, adjusted for age, seasonality and household composition. Participating infants in 2014 received PCV13 as part of routine immunisation., Results: VT carriage prior to PCV-13 introduction was 11.4%, 45.1%, 28.2%, 21.2% and 6.6% for 6-week old infants, 18-week old infants, children 1-4 years, children 5-15 years and mothers, respectively. After vaccine introduction, VT carriage decreased among vaccinated 18-week old infants (adjusted prevalence ratio 0.24 (95%CI 0.08-0.75)), vaccinated children 1-4 years (0.54 (0.33-0.88)), unvaccinated children 5-15 years (0.37 (0.17-0.78)) and mothers (0.34 (0.15-0.79)). No decrease in VT carriage was observed for 6-week old infants too young to be vaccinated (1.07 (0.38-3.02)) and PCV-13 ineligible children 1-4 years (0.84 (0.53-1.33)). Non-VT carriage increased only among vaccinated children 1-4 years (1.58 (1.21-2.06))., Conclusions: There is evidence of reduced VT pneumococcal carriage three years after vaccine introduction in this rural Malawian population with good vaccine coverage using a 3 + 0 schedule. However carriage was sustained among 6-week-old infants and PCV13 ineligible 1-4 year olds, and there was some indication of serotype replacement in vaccinated 1-4 year olds., (Copyright © 2018 Univerity of Liverpool. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Syringes with attached needles (low dead space syringes [LDSS]) retain far less blood following injection than syringes with detachable needles (high dead space syringes [HDSS]). People who inject drugs (PWID) who share needles/syringes may be less likely to acquire Hepatitis C virus (HCV) infection using LDSS, compared with HDSS, but data are limited., Methods: Utilizing drug behavior and HCV antibody testing data from the UK 2014/2015 Unlinked Anonymous Monitoring Survey of PWID, we calculated the percentage of syringes used in the past month that were LDSS. We investigated which injecting characteristics and demographic factors were associated with 100% LDSS (against 0-99%) usage, and whether 100% LDSS use was associated with antibody HCV-status, after adjusting for confounders., Result: Of 2174 participants, 55% always used LDSS, 27% always used HDSS, and 17% used both LDSS and HDSS. PWID that had injected into their groin during the past month were unlikely to use LDSS, adjusted odds ratio (aOR) 0.14 (95% confidence interval 0.11-0.17), compared to those not using the groin. Those injecting crack were less likely to use LDSS than those not, aOR 0.79 (0.63-0.98). Polydrug use was negatively associated with LDSS use, aOR 0.88 (0.79-0.98) per additional drug. LDSS use was associated with lower prevalent HCV among all PWID (aOR 0.77, [0.64-0.93]), which was stronger among recent initiates (aOR 0.53 [0.30-0.94]) than among experienced PWID (aOR 0.81 [0.66-0.99])., Discussion: People who inject into their groin were less likely to use LDSS. Exclusive LDSS use was associated with lower prevalence of HCV amongst PWID that started injecting recently, suggesting LDSS use is protective against HCV., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Rotavirus is a major contributor to child mortality. The effect of rotavirus vaccine on diarrhoea mortality has been estimated in middle-income but not low-income settings, where mortality is high and vaccine effectiveness in reducing admissions to hospital is lower. Empirical population-based mortality studies have not been done in any setting. Malawi introduced monovalent rotavirus vaccine (RV1) in October, 2012. We aimed to investigate the impact and effectiveness of the RV1 vaccine in reducing diarrhoea-associated mortality in infants aged 10-51 weeks., Methods: In this population-based cohort study, we included infants born between Jan 1, 2012, and June 1, 2015, in Mchinji, Central Malawi and analysed data on those surviving 10 weeks. Individual vaccination status was extracted from caregiver-held records or report at home visits at 4 months and 1 year of age. Survival to 1 year was confirmed at home visit, or cause of death ascertained by verbal autopsy. We assessed impact (1 minus mortality rate ratio following vs before vaccine introduction) using Poisson regression. Among vaccine-eligible infants (born from Sept 17, 2012), we assessed effectiveness (1 minus hazard ratio) using Cox regression., Findings: Between Jan 1, 2012, and June 1, 2015, we recruited 48 672 livebirths in Mchinji, among whom 38 518 were vaccine-eligible and 37 570 survived to age 10 weeks. Two-dose versus zero-dose effectiveness analysis included 28 141 infants, of whom 101 had diarrhoea-associated death before 1 year of age. Diarrhoea-associated mortality declined by 31% (95% CI 1-52; p=0·04) after RV1 introduction. Effectiveness against diarrhoea-mortality was 34% (95% CI -28 to 66; p=0·22)., Interpretation: RV1 was associated with substantial reduction in diarrhoea-associated deaths among infants in this rural sub-Saharan African setting. These data add considerable weight to evidence showing the impact of rotavirus vaccine programmes., Funding: Wellcome Trust and GlaxoSmithKline Biologicals., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

We report a national Pseudomonas aeruginosa outbreak from a common source following piercings between July and September 2016 in England. The multi-agency outbreak investigation included active case finding, microbiological testing of environmental samples and case specimens including Variable Number Tandem Repeat (VNTR) typing and a retrospective cohort study. Overall, 162 outbreak cases (29 confirmed, 14 probable and 119 possible) and 14 non-outbreak cases were identified; all confirmed cases had ear piercings (93% cartilage). Outbreak cases were predominantly female (95%) and had a median age of 18 years (interquartile range: 13-56 years). Nineteen outbreak cases required surgery under general anaesthetic The same outbreak VNTR type (11,3,5,3,3,3,6,4,7) was isolated from bottles of an aftercare solution from a single manufacturer and in specimens from confirmed cases who attended eight different piercing studios supplied with this product. In the cohort study, use of aftercare solution was associated with becoming a case (aOR: 4.60, 95% confidence interval: 1.65-12.90). Environmental, microbiological and epidemiological investigations confirmed that contamination during production of aftercare solution was the source of this national outbreak; highlighting challenges in the regulation of a cosmetic products used in the piercing industry and that guidance on piercing aftercare may need to be reviewed.

Background: Higher levels of drug use have been reported in lesbian, gay, bisexual and transgender (LGBT) communities, some of which can be explained by sexualised drug use, including 'chemsex'; the use of drugs before or during planned sexual activity to sustain, enhance, disinhibit or facilitate sex. We explored injecting and non-injecting drug use by sexual behaviour among people who inject drugs (PWID) in England, Wales and Northern Ireland., Methods: Data were used from an unlinked-anonymous survey of PWID (2013-2016), where participants recruited through services self-completed a questionnaire. We included sexually active participants who had injected in the previous year, and compared injecting and non-injecting drug use between men reporting sex with men (MSM) and heterosexual men, and between women reporting sex with women (WSW) and heterosexual women. The questionnaire did not include GHB/GBL and methamphetamine use., Results: There were 299 MSM, 3215 heterosexual male, 122 WSW and 1336 heterosexual female participants. MSM were more likely than heterosexual men to use drugs associated with chemsex: injected or non-injected mephedrone (adjusted OR (AOR) 2.22, 95%CI 1.54-3.22; AOR 2.15, 95%CI 1.48-3.11) and injected or non-injected ketamine (AOR 1.98, 95%CI 1.29-3.05; AOR 2.57, 95%CI 1.59-4.15). MSM were also more likely to inject methadone, inhale solvents, take ecstasy, cocaine or speed. WSW were more likely than heterosexual women to use non-injected mephedrone (AOR 2.19, 95%CI 1.20-3.99) and use injected or non-injected ketamine (AOR 5.58, 95%CI 2.74-11.4; AOR 3.05, 95%CI 1.30-7.19). WSW were also more likely to inject methadone, inject cocaine, use non-injected cocaine, crack, benzodiazepines or ecstasy, inhale solvents, or smoke cannabis., Conclusion: Injecting and non-injecting drug use differed between MSM/WSW and heterosexual men and women. The use of drugs that have been associated with chemsex and sexualised drug use is more common among both MSM and WSW than heterosexual men and women., (Copyright © 2018. Published by Elsevier B.V.)

Background: Sexualised drug use (SDU) refers to the use of drugs in a sexual context. This includes 'Chemsex'- the use of drugs (specifically crystal methamphetamine, GHB/GBL and mephedrone) before or during planned sexual activity to sustain, enhance, disinhibit or facilitate the experience. Here we aimed to synthesise available UK prevalence data for Chemsex, SDU and the use of Chemsex drugs in an undefined context (CDU) in men who have sex with men (MSM)., Methods: Papers published between January 2007 and August 2017 reporting Chemsex, SDU and/or Chemsex drug use (CDU) prevalence in MSM were identified through PubMed. Citations were searched for further eligible publications. We also conducted a review of national surveillance data, extracting prevalence data for Chemsex, SDU or CDU. Synthesized data were then assessed to determine the time at which these drugs were taken, in this case just prior to or during sexual activity (event-level)., Results: Our search identified 136 publications, of which 28 were included in the final data synthesis. Three of the four surveillance systems assessed provided SDU or CDU data in MSM. Few publications included event-level data for Chemsex (n = 4), with prevalence estimates ranging from 17% among MSM attending sexual health clinics (SHC) to 31% in HIV-positive MSM inpatients. Prevalence estimates for SDU (n = 7 publications) also varied considerably between 4% in MSM receiving HIV care to 41% among MSM attending SHC for HIV post-exposure prophylaxis (PEP). Eighteen publications provided data for CDU., Conclusion: Prevalence estimates varied considerably due to differences in the definition used and population assessed. Standardised definitions and studies with representative national samples of MSM are required to improve our understanding of the extent of Chemsex and its associated risks. Longitudinal event-level data for SDU and Chemsex are needed to monitor impact of interventions., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Accurate estimates of rotavirus incidence in infants are crucial given disparities in rotavirus vaccine effectiveness from low-income settings. Sero-surveys are a pragmatic means of estimating incidence however serological data is prone to misclassification. This study used mixture models to estimate incidence of rotavirus infection from anti-rotavirus immunoglobulin A (IgA) titres in infants from Vellore, India, and Karonga, Malawi. IgA titres were measured using serum samples collected at 6 month intervals for 36 months from 373 infants from Vellore and 12 months from 66 infants from Karonga. Mixture models (two component Gaussian mixture distributions) were fit to the difference in titres between time points to estimate risk of sero-positivity and derive incidence estimates. A peak incidence of 1.05(95% confidence interval [CI]: 0.64, 1.64) infections per child-year was observed in the first 6 months of life in Vellore. This declined incrementally with each subsequent time interval. Contrastingly in Karonga incidence was greatest in the second 6 months of life (1.41 infections per child year [95% CI: 0.79, 2.29]). This study demonstrates that infants from Vellore experience peak rotavirus incidence earlier than those from Karonga. Identifying such differences in transmission patterns is important in informing vaccine strategy, particularly where vaccine effectiveness is modest.

Between July 2016 and January 2017, 37 confirmed cases of hepatitis A with two unique IA genotype strains primarily among men who have sex with men, were reported across eight areas in England and Northern Ireland. Epidemiological and laboratory investigations indicate that these strains may have been imported several times from Spain, with secondary sexual transmission in the United Kingdom. Local and national public health services are collaborating to control this ongoing outbreak., (This article is copyright of The Authors, 2017.)

Background: Malawi introduced pneumococcal conjugate vaccine (PCV13) and monovalent rotavirus vaccine (RV1) in 2011 and 2012 respectively, and is planning the introduction of a second-dose measles vaccine (MV). We assessed predictors of availability, uptake and timeliness of these vaccines in a rural Malawian setting., Methods: Commencing on the first date of PCV13 eligibility we conducted a prospective population-based birth cohort study of 2,616 children under demographic surveillance in Karonga District, northern Malawi who were eligible for PCV13, or from the date of RV1 introduction both PCV13 and RV1. Potential predictors of vaccine uptake and timeliness for PCV13, RV1 and MV were analysed respectively using robust Poisson and Cox regression., Results: Vaccine coverage was high for all vaccines, ranging from 86.9% for RV1 dose 2 to 95.4% for PCV13 dose 1. Median time delay for PCV13 dose 1 was 17 days (IQR 7-36), 19 days (IQR 8-36) for RV1 dose 1 and 20 days (IQR 3-46) for MV. Infants born to lower educated or farming mothers and those living further away from the road or clinic were at greater risk of being not fully vaccinated and being vaccinated late. Delays in vaccination were also associated with non-facility birth. Vaccine stock-outs resulted in both a delay in vaccine timeliness and in a decrease in completion of schedule., Conclusion: Despite high vaccination coverage in this setting, delays in vaccination were common. We identified programmatic and socio-demographic risk factors for uptake and timeliness of vaccination. Understanding who remains most vulnerable to be unvaccinated allows for focussed delivery thereby increasing population coverage and maximising the equitable benefits of universal vaccination programmes.

The prevalence of Streptococcus pneumoniae (pneumococcus) carriage is higher in adults who are infected with human immunodeficiency virus (HIV) than in adults who are not. We hypothesized that infants exposed to HIV become carriers of nasopharyngeal pneumococcus earlier and more frequently than infants who are not exposed to HIV. We compared infant pneumococcal acquisition by maternal HIV status and household exposure in Karonga District, Malawi, in 2009-2011, before the introduction of pneumococcal conjugate vaccine. Nasopharyngeal swabs were collected every 4-6 weeks in the first year of life from infants with known HIV-exposure status, their mothers, and other household members. We studied infant pneumococcal acquisition by maternal HIV status, serotype-specific household exposure, and other risk factors, including seasonality. We recruited 54 infants who were exposed to HIV and 131 infants who were not. There was no significant difference in pneumococcal acquisition by maternal HIV status (adjusted rate ratio (aRR) = 1.00, 95% confidence interval (CI): 0.87, 1.15). Carriage by the mother was associated with greater acquisition of the same serotype (aRR = 3.09, 95% CI: 1.47, 6.50), but the adjusted population attributable fraction was negligible (1.9%, 95% CI: 0.0, 4.3). Serotype-specific exposure to children under 5 years of age was associated with higher acquisition (aRR = 4.30, 95% CI: 2.80, 6.60; adjusted population attributable fraction = 8.8%, 95% CI: 4.0, 13.4). We found no evidence to suggest that maternal HIV infection would affect the impact of pneumococcal vaccination on colonization in this population., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Objective: HIV-infected adults have high rates of pneumococcal carriage and invasive disease. We investigated the effect of antiretroviral therapy (ART) on pneumococcal carriage in HIV-infected adults prior to infant pneumococcal conjugate vaccine (PCV) rollout., Design: Observational cohort study., Methods: We recruited HIV-infected adults newly attending a rural HIV clinic in northern Malawi between 2008 and 2010. Nasopharyngeal samples were taken at baseline and after 6, 12, 18 and 24 months. We compared pneumococcal carriage by ART status using generalized estimated equation models adjusted for CD4 cell count, sex, seasonality, and other potential confounders., Results: In total, 336 individuals were included, of which 223 individuals started ART during follow-up. Individuals receiving ART had higher pneumococcal carriage than individuals not receiving ART (25.9 vs. 19.8%, P = 0.03) particularly for serotypes not included in PCV13 (16.1 vs. 9.6% P = 0.003). Following adjustment, increased carriage of non-PCV13 serotypes was still observed for individuals on ART, but results for all serotypes were nonsignificant [all serotypes: adjusted risk ratio (aRR) 1.22 (0.95-1.56); non-PCV13 serotypes: aRR 1.72, 95% CI 1.13-2.62]., Conclusion: Pneumococcal carriage in HIV-infected adults in Malawi remained high despite use of ART, consistent with failure of mucosal immune reconstitution in the upper respiratory tract. There was evidence of increased carriage of non-PCV13 serotypes. HIV-infected adults on ART could remain an important reservoir for pneumococcal diversity post infant pneumococcal vaccine introduction. Control of pneumococcal disease in African HIV remains a priority.

Objectives: In England, national guidance recommends that all patients with suspected invasive meningococcal disease (IMD) should be investigated by blood culture and polymerase chain reaction (PCR) testing. The Meningococcal Reference Unit (MRU) provides a national service for meningococcal species confirmation and PCR-testing of clinical samples. We performed a population-level assessment of the added value of PCR-testing for IMD to augment traditional culture confirmation., Methods: We analysed all PCR-samples and invasive meningococcal isolates received by MRU in 2009 and 2010. We assumed that all patients with PCR-samples submitted to MRU also had blood cultures performed and that positive blood cultures were referred to MRU. We confirmed this assertion by case ascertainment., Results: In total, 25,379 specimens from 22,039 patients were submitted for PCR-testing and 1492 (6.8%) tested PCR-positive. MRU received 825 invasive meningococcal isolates; 393 confirmed by PCR and culture, 405 without a PCR-specimen submitted and 27 with a PCR-negative result. Thus, of 1924 reported IMD cases, 1099 (57.1%) were confirmed by PCR only, 432 (22.5%) by culture only and 393 (20.4%) by both tests., Conclusion: More than half of all confirmed IMD cases were confirmed by PCR only, indicating this service ensures high case ascertainment for national surveillance., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

This literature review identifies the factors that influence the decision to introduce inactivated polio vaccine (IPV) in developing countries as opposed to the policy of vaccine cessation. Attenuated viruses in the oral polio vaccine (OPV) can replicate, revert to neurovirulence and become transmissible circulating vaccine-derived polioviruses (cVDPVs), preventing use of the vaccine in the post-eradication era. This literature review identifies (1) risks of complete cessation of vaccination, (2) barriers and (3) solutions for the introduction of IPV in developing countries. The reviewed literature favours to circumvent the so-called "OPV paradox" by global introduction of IPV., (Copyright 2010 Elsevier Ltd. All rights reserved.)