HCV treatment rates and sustained viral response among people who inject drugs in seven UK sites: real world results and modelling of treatment impact.

Hepatitis C virus (HCV) antiviral treatment for people who inject drugs (PWID) could prevent onwards transmission and reduce chronic prevalence. We assessed current PWID treatment rates in seven UK settings and projected the potential impact of current and scaled-up treatment on HCV chronic prevalence. Data on number of PWID treated and sustained viral response rates (SVR) were collected from seven UK settings: Bristol (37-48% HCV chronic prevalence among PWID), East London (37-48%), Manchester (48-56%), Nottingham (37-44%), Plymouth (30-37%), Dundee (20-27%) and North Wales (27-33%). A model of HCV transmission among PWID projected the 10-year impact of (i) current treatment rates and SVR (ii) scale-up with interferon-free direct acting antivirals (IFN-free DAAs) with 90% SVR. Treatment rates varied from <5 to over 25 per 1000 PWID. Pooled intention-to-treat SVR for PWID were 45% genotypes 1/4 [95%CI 33-57%] and 61% genotypes 2/3 [95%CI 47-76%]. Projections of chronic HCV prevalence among PWID after 10 years of current levels of treatment overlapped substantially with current HCV prevalence estimates. Scaling-up treatment to 26/1000 PWID annually (achieved already in two sites) with IFN-free DAAs could achieve an observable absolute reduction in HCV chronic prevalence of at least 15% among PWID in all sites and greater than a halving in chronic HCV in Plymouth, Dundee and North Wales within a decade. Current treatment rates among PWID are unlikely to achieve observable reductions in HCV chronic prevalence over the next 10 years. Achievable scale-up, however, could lead to substantial reductions in HCV chronic prevalence.

Transferring inpatients between wards drives large nosocomial COVID-19 outbreaks, Wales, 2020-22: a matched case-control study using routine and enhanced surveillance data.

BACKGROUND: The role of the hospital environment in the spread of COVID-19 is unclear. AIM: To measure associations between ward characteristics and outbreak size to inform mitigations. METHODS: Wards with large (case wards) and small (control wards) outbreaks in three acute hospitals were compared. Cases were healthcare-associated COVID-19 inpatients (positive polymerase chain reaction test ≥8 days post admission). Case wards were adult medical/surgical wards with ≥10 cases within rolling 14-day periods, between April 1st, 2020 and April 30th, 2022. Control wards were equivalents with 2-9 cases. Demographic and laboratory data were extracted from routine surveillance systems. Continuous data were aggregated fortnightly and analysed as binary variables according to median values. Each case ward was compared with two control wards matched on outbreak start date (±14 days) to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) using univariable and conditional multivariable logistic regression. FINDINGS: From 170 outbreaks (median: 5 cases; interquartile range: 2-9), 35 case wards were identified. Community admissions were lower in case wards vs control wards (5 vs 10 median admissions; P<0.01, respectively), whereas transfers between wards within the same hospital were higher (58 vs 29 median transfers; P<0.01, respectively). Wards with more transfers in the preceding fortnight were significantly more likely to experience a large outbreak (≥35 vs <35 transfers; adjusted OR: 9.08; 95% CI: 2.5-33). CONCLUSION: We recommend safely minimizing patient movements, such as by asking clinicians to record the rationale for transfer, to reduce the likelihood of disease transmission.

Characteristics of injecting drug users accessing different types of needle and syringe programme or using secondary distribution.

BACKGROUND: In the UK, needle and syringe programmes (NSP) are delivered via community pharmacies or substance misuse services (SMSNSP). Understanding the profile of drug injectors primarily using different sources of injecting equipment can help service design. METHODS: Blood spot samples and behavioural data were collected from drug injectors and tested for antibodies to hepatitis C and hepatitis B. Data were analysed in relation to NSP use by multivariate logistic regression. RESULTS: Of 700 eligible individuals interviewed, 657 provided information on their main source of equipment; 26% reported pharmacy NSP, 56% SMSNSP and 18% secondary distribution. In the adjusted analysis, individuals whose main source was SMSNSP were more likely to report markers of increased risk (homelessness, groin injection, having injected >16 days/month) and had a higher hepatitis B antibody prevalence than individuals primarily using pharmacy NSP. Individuals whose main source was secondary distribution had a different profile (e.g. they were younger, more likely to be recent onset injectors than main source SMSNSP users and less likely to report being in drug treatment). CONCLUSION: Differences exist in the populations primarily accessing different NSP and commissioning of services must reflect these differences. Injecting drug users relying on secondary exchange should be targeted to improve health service contact.

Improving blood-borne viral diagnosis; clinical audit of the uptake of dried blood spot testing offered by a substance misuse service.

SUMMARY: The diagnosis of blood-borne viral infection amongst drug injectors in Wales is limited by a poor uptake of diagnostic testing; recent research suggests that dried blood spot (DBS) sample collection, rather than venepuncture, may improve diagnostic rates. We carried out an audit of the uptake of DBS testing for hepatitis C, hepatitis B and HIV amongst drug injectors attending a substance misuse service (SMS) in the first year of DBS testing being routinely offered to clients (1 May 2007 to 30 April 2008) and compared the uptake to venepuncture testing of SMS clients in the previous year. Uptake of DBS testing for hepatitis C, hepatitis B and HIV was almost six times greater than the uptake of venepuncture testing amongst clients of the SMS in the previous year. The data are consistent with the hypothesis that DBS testing can increase the uptake of blood-borne viral testing amongst current and ex-drug injectors. We accept that part of the almost sixfold increase in diagnostic testing observed in the first year of DBS testing may be due to an increase in awareness amongst drug injectors of testing opportunities and a prioritization of testing by the SMS. Nonetheless the dramatic increase in uptake demonstrates that DBS testing is acceptable to drug injectors and should be subject to more rigorous trials to evaluate its potential impact on diagnosis.

The dynamics of heroin use; implications for intervention.

STUDY OBJECTIVE: To use a readily available dataset to detect periods of epidemic change and to examine the progression of heroin epidemics in different geographical areas. To consider the implications of epidemic change for strategies to tackle drug misuse. DESIGN: Comparison of trends in new treatment demand, observed incidence, and age specific population rates for treated heroin users in two geographical areas. PARTICIPANTS: Heroin users recorded to have sought treatment. MAIN RESULTS: The areas studied seem to show differences with respect to trends in new treatment demand, incidence of heroin use and distribution of age specific population rates; indicating that they may be at different epidemic stages. CONCLUSIONS: These analyses show how areas may differ with respect to epidemic progression of heroin use. It is essential that government strategies, and local responses to these, should be cognisant of these dynamics.

General framework for comparative quantitative studies on transmission of tick-borne diseases using Lyme borreliosis in Europe as an example.

Models of tick-borne diseases must take account of the particular biological features of ticks that contrast with those of insect vectors. A general framework is proposed that identifies the parameters of the transmission dynamics of tick-borne diseases to allow a quantitative assessment of the relative contributions of different host species and alternative transmission routes to the basic reproductive number, Ro, of such diseases. Taking the particular case of the transmission of the Lyme borreliosis spirochaete, Borrelia burgdorferi, by Ixodes ticks in Europe, and using the best, albeit still inadequate, estimates of the parameter values and a set of empirical data from Thetford Forest, England, we show that squirrels and the transovarial transmission route make quantitatively very significant contributions to Ro. This approach highlights the urgent need for more robust estimates of certain crucial parameter values, particularly the coefficients of transmission between ticks and vertebrates, before we can progress to full models that incorporate seasonality and heterogeneity among host populations for the natural dynamics of transmission of borreliosis and other tick-borne diseases.

Seasonal variation in the role of grey squirrels as hosts of Ixodes ricinus, the tick vector of the Lyme disease spirochaete, in a British woodland.

Data are presented on the variable patterns of the seasonal dynamics of Ixodes ricinus L. ticks seen questing on the vegetation and feeding on small rodents (mice and voles) and squirrels within a British woodland focus of Lyme borreliosis. Information on tick infestation levels on pheasants is also presented. The results show a prolonged, unimodal pattern of tick activity, with ticks feeding throughout the year in this sheltered habitat. If host density is taken into account, squirrels are quantitatively more important than small mammals as hosts for larval ticks from April until July, and overwhelmingly so for nymphal ticks throughout the year. The observed inter- and intraspecific differences in tick infestation levels are related to the behaviour of both hosts and ticks. Squirrels, as competent hosts for Borrelia burgdorferi and frequent occupants of habitats closely associated with man, will contribute significantly to the risk of Lyme disease.

Role of grey squirrels and pheasants in the transmission of Borrelia burgdorferi sensu lato, the Lyme disease spirochaete, in the U.K.

In Britain, grey squirrels (Sciurus carolinensis Gmelin) and pheasants (Phasianus colchicus Linnaeus) are important hosts of larvae and nymphs of Ixodes ricinus L., the principal European vector of the Lyme disease spirochaete, Borrelia burgdorferi sensu lato. To test whether squirrels are competent hosts of B. burgdorferi s.l., three females were trapped in the wild and then held in captivity. Following treatment, each animal was exposed to uninfected xenodiagnostic I. ricinus ticks. Squirrel A (an adult) which was inoculated experimentally with B. burgdorferi s.l., transmitted the infection to xenodiagnostic ticks. In contrast, squirrel B (a juvenile that was not inoculated)-showed no evidence of infection. Xenodiagnostic ticks that fed on control squirrel C (an adult) became infected and subsequently transmitted the infection experimentally to an uninfected hamster. The results indicated that squirrel C had a disseminated infection acquired in the wild and which persisted for at least 11 weeks. These data clearly demonstrate that grey squirrels are amplifying and reservoir hosts of B. burgdorferi s.l. The strain associated with squirrels was related to the B. afzelii genotype. Two observations implicated pheasants in a similar role: (i) a high prevalence of infection in engorged larvae collected from trapped pheasants, and (ii) the detection of B. burgdorferi s.l. (B. garinii genotype) in the wattle of 1/10 pheasants using PCR. Xenodiagnostic experiments similar to those undertaken with the squirrels are needed to confirm the role of pheasants in the transmission cycle of Lyme disease spirochaetes.

Intervention Now To Eliminate Repeat Unintended Pregnancy in Teenagers (INTERUPT): a systematic review of intervention effectiveness and cost-effectiveness, qualitative and realist synthesis of implementation factors and user engagement.

BACKGROUND: The UK has the highest rate of teenage pregnancies in Western Europe, a fifth are repeat pregnancies. Unintended conceptions can result in emotional, psychological and educational harm to teenage girls, often with enduring implications for their life chances. Babies of teenage mothers have increased mortality in their first year and increased risk of poverty, educational underachievement and unemployment later in life, with associated societal costs. METHODS AND ANALYSIS: We will conduct a streamed, mixed-methods systematic review to find and evaluate interventions designed to reduce repeat unintended teen pregnancies. OUR AIMS ARE TO IDENTIFY:  Who is at greater risk of repeat unintended pregnancies? Which interventions are effective, cost-effective, how they work, in what setting and for whom? What are the barriers and facilitators to intervention uptake? Traditional electronic database searches will be augmented by targeted searches for evidence 'clusters' and guided by an advisory group of experts and stakeholders. To address the topic's inherent complexities, we will use a highly structured, innovative and iterative approach combining methodological techniques tailored to each stream of evidence. Quantitative data will be synthesised with reference to Cochrane guidelines for public health interventions. Qualitative evidence addressing facilitators and barriers to the uptake of interventions, experience and acceptability of interventions will be synthesised thematically. We will apply the principles of realist synthesis to uncover theories and mechanisms underpinning interventions. We will conduct an integration and overarching narrative of findings authenticated by client group feedback. ETHICS AND DISSEMINATION: We will publish the complete review in 'Health Technology Assessment' and sections in specialist peer-reviewed journals. We will present at national and international conferences in the fields of public health, reproductive medicine and review methodology. Findings will be fed back to service users and practitioners via workshops run by the partner collaborators. TRAIL REGISTRATION NUMBER: PROSPERO CRD42012003168. COCHRANE REGISTRATION NUMBER: i=fertility/0068.

Incidence of hepatitis C in drug injectors: the role of homelessness, opiate substitution treatment, equipment sharing, and community size.

A prospective cohort study estimated the incidence of hepatitis C virus (HCV) in drug injectors in South Wales (UK). In total, 286/481 eligible seronegative individuals were followed up after approximately 12 months. Dried blood spot samples were collected and tested for anti-HCV antibody and behavioural data were collected at baseline and follow-up. HCV incidence was 5.9/100 person-years [95% confidence interval (CI) 3.4-9.5]. HCV incidence was predicted by community size [incident rate ratio (IRR) 6.6, 95% CI 2.11-20.51, P = 0.001], homelessness (IRR 2.9, 95% CI 1.02-8.28, P = 0.047) and sharing injecting equipment (IRR 12.7, 95% CI 1.62-99.6, P = 0.015). HCV incidence was reduced in individuals in opiate substitution treatment (IRR 0.34, 95% CI 0.12-0.99, P = 0.047). In order to reduce follow-up bias we used multiple imputation of missing data using switching regression; after imputation estimated HCV incidence was 8.5/100 person-years (95% CI 5.4-12.7). HCV incidence varies with community size, equipment sharing and homelessness are associated with increased HCV incidence and opiate substitution treatment may be protective against HCV.

Hepatitis B and hepatitis C seroprevalence and risk behaviour among community-recruited drug injectors in North West Wales.

We estimated the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, and injecting risk behaviour, among community-recruited injecting drug users (IDUs) in North West Wales in 2001 and 2002. Sample collection was undertaken by trained current and former IDUs. Oral fluid samples (n = 153) were tested as part of the Unlinked Anonymous Prevalence Monitoring Programme ongoing survey of IDUs. Approximately 12% of the sample reported that they were currently in a drug treatment programme. Of the 153 samples screened 27% (95% CI 20%-34%, 41/153) were anti-HBc positive, and 23% (95% CI 16%-30%, 35/153) were anti-HCV positive. Sixteen per cent (95% CI 10%-22%, 25/ 153) of the samples were positive for both anti-HBc and anti-HCV. Of the subjects 15% (95% CI 9%-20%) knew they had been vaccinated against hepatitis B. Direct sharing of needles and syringes in the 28 days prior to interview was reported by 44% (95% CI 35%-54%), and sharing of any equipment including that used for drug preparation prior to injection was reported by 66% (95% CI 57%-76%). In North West Wales, syringe sharing is a common practice, and a high proportion of IDUs have been exposed to bloodborne viruses. Hepatitis B vaccination coverage within this population appears to be low and needs to be increased. Further efforts are needed to improve the availability of clean injecting equipment.