Postexposure Prophylaxis With rVSV-ZEBOV Following Exposure to a Patient With Ebola Virus Disease Relapse in the United Kingdom: An Operational, Safety, and Immunogenicity Report.

BACKGROUND: In October 2015, 65 people came into direct contact with a healthcare worker presenting with a late reactivation of Ebola virus disease (EVD) in the United Kingdom. Vaccination was offered to 45 individuals with an initial assessment of high exposure risk. METHODS: Approval for rapid expanded access to the recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine as an unlicensed emergency medicine was obtained from the relevant authorities. An observational follow-up study was carried out for 1 year following vaccination. RESULTS: Twenty-six of 45 individuals elected to receive vaccination between 10 and 11 October 2015 following written informed consent. By day 14, 39% had seroconverted, increasing to 87% by day 28 and 100% by 3 months, although these responses were not always sustained. Neutralizing antibody responses were detectable in 36% by day 14 and 73% at 12 months. Common side effects included fatigue, myalgia, headache, arthralgia, and fever. These were positively associated with glycoprotein-specific T-cell but not immunoglobulin (Ig) M or IgG antibody responses. No severe vaccine-related adverse events were reported. No one exposed to the virus became infected. CONCLUSIONS: This paper reports the use of the rVSV-ZEBOV vaccine given as an emergency intervention to individuals exposed to a patient presenting with a late reactivation of EVD. The vaccine was relatively well tolerated, but a high percentage developed a fever ≥37.5°C, necessitating urgent screening for Ebola virus, and a small number developed persistent arthralgia.

The burden of hepatitis E among patients with haematological malignancies: A retrospective European cohort study.

BACKGROUND & AIMS: The burden of hepatitis E virus (HEV) infection among patients with haematological malignancy has only been scarcely reported. Therefore, we aimed to describe this burden in patients with haematological malignancies, including those receiving allogeneic haematopoietic stem cell transplantation. METHODS: We conducted a retrospective, multicentre cohort study across 11 European centres and collected clinical characteristics of 50 patients with haematological malignancy and RNA-positive, clinically overt hepatitis E between April 2014 and March 2017. The primary endpoint was HEV-associated mortality; the secondary endpoint was HEV-associated liver-related morbidity. RESULTS: The most frequent underlying haematological malignancies were aggressive non-Hodgkin lymphoma (NHL) (34%), indolent NHL (iNHL) (24%), and acute leukaemia (36%). Twenty-one (42%) patients had received allogeneic haematopoietic stem cell transplantation (alloHSCT). Death with ongoing hepatitis E occurred in 8 (16%) patients, including 1 patient with iNHL and 1 patient >100 days after alloHSCT in complete remission, and was associated with male sex (p = 0.040), cirrhosis (p = 0.006) and alloHSCT (p = 0.056). Blood-borne transmission of hepatitis E was demonstrated in 5 (10%) patients, and associated with liver-related mortality in 2 patients. Hepatitis E progressed to chronic hepatitis in 17 (34%) patients overall, and in 10 (47.6%) and 6 (50%) alloHSCT and iNHL patients, respectively. Hepatitis E was associated with acute or acute-on-chronic liver failure in 4 (8%) patients with 75% mortality. Ribavirin was administered to 24 (48%) patients, with an HEV clearance rate of 79.2%. Ribavirin treatment was associated with lower mortality (p = 0.037) and by trend with lower rates of chronicity (p = 0.407) when initiated <24 and <12 weeks after diagnosis of hepatitis E, respectively. Immunosuppressive treatment reductions were associated with mortality in 2 patients (28.6%). CONCLUSION: Hepatitis E is associated with mortality and liver-related morbidity in patients with haematological malignancy. Blood-borne transmission contributes to the burden. Ribavirin should be initiated early, whereas reduction of immunosuppressive treatment requires caution. LAY SUMMARY: Little is known about the burden of hepatitis E among patients with haematological malignancy. We conducted a retrospective European cohort study among 50 patients with haematological malignancy, including haematopoietic stem cell transplant recipients, with clinically significant HEV infection and found that hepatitis E is associated with hepatic and extrahepatic mortality, including among patients with indolent disease or among stem cell transplant recipients in complete remission. Hepatitis E virus infection evolved to chronic hepatitis in 5 (45.5%) patients exposed to a rituximab-containing regimen and 10 (47.6%) stem cell transplant recipients. Reducing immunosuppressive therapy because of hepatitis E was associated with mortality, while early ribavirin treatment was safe and effective.

Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis.

Background: Harm reduction has dramatically reduced HIV incidence among people who inject drugs (PWID). In Glasgow, Scotland, <10 infections/year have been diagnosed among PWID since the mid-1990s. However, in 2015 a sharp rise in diagnoses was noted among PWID; many were subtype C with 2 identical drug-resistant mutations and some displayed low avidity, suggesting the infections were linked and recent. Methods: We collected Scottish pol sequences and identified closely related sequences from public databases. Genetic linkage was ascertained among 228 Scottish, 1820 UK, and 524 global sequences. The outbreak cluster was extracted to estimate epidemic parameters. Results: All 104 outbreak sequences originated from Scotland and contained E138A and V179E. Mean genetic distance was <1% and mean time between transmissions was 6.7 months. The average number of onward transmissions consistently exceeded 1, indicating that spread was ongoing. Conclusions: In contrast to other recent HIV outbreaks among PWID, harm reduction services were not clearly reduced in Scotland. Nonetheless, the high proportion of individuals with a history of homelessness (45%) suggests that services were inadequate for those in precarious living situations. The high prevalence of hepatitis C (>90%) is indicative of sharing of injecting equipment. Monitoring the epidemic phylogenetically in real time may accelerate public health action.

HCV avidity as a tool for detection of recent HCV infection: Sensitivity depends on HCV genotype.

Accurate detection of incident hepatitis C virus (HCV) infection is required to target and evaluate public health interventions, but acute infection is largely asymptomatic and difficult to detect using traditional methods. Our aim was to evaluate a previously developed HCV avidity assay to distinguish acute from chronic HCV infection. Plasma samples collected from recent seroconversion subjects in two large Australian cohorts were tested using the avidity assay, and the avidity index (AI) was calculated. Demographic and clinical characteristics of patients with low/high AI were compared via logistic regression. Sensitivity and specificity of the assay for recent infection and the mean duration of recent infection (MDRI) were estimated stratified by HCV genotype. Avidity was assessed in 567 samples (from 215 participants), including 304 with viraemia (defined as ≥250 IU/mL). An inverse relationship between AI and infection duration was found in viraemic samples only. The adjusted odds of a low AI (<30%) decreased with infection duration (odds ratio [OR] per week of 0.93; 95% CI:0.89-0.97), and were lower for G1 compared with G3 samples (OR = 0.14; 95% CI:0.05-0.39). Defining recent infection as <26 weeks, sensitivity (at AI cut-off of 20%) was estimated at 48% (95% CI:39-56%), 36% (95% CI:20-52%), and 65% (95% CI:54-75%) and MDRI was 116, 83, and 152 days for all genotypes, G1, and G3, respectively. Specificity (≥52 weeks infection duration, all genotypes) was 96% (95% CI:90-98%). HCV avidity testing has utility for detecting recent HCV infection in patients, and for assessing progress in reaching incidence targets for eliminating transmission, but variation in assay performance across genotype should be recognized.

Factors associated with spontaneous clearance of chronic hepatitis C virus infection.

BACKGROUND & AIMS: Spontaneous clearance of chronic hepatitis C virus (HCV) infection (CHC) is rare. We conducted a retrospective case-control study to identify rates and factors associated with spontaneous clearance of CHC. METHODS: We defined cases as individuals who spontaneously resolved CHC, and controls as individuals who remained chronically infected. We used data obtained on HCV testing between 1994 and 2013 in the West of Scotland to infer case/control status. Specifically, untreated patients with ⩾2 sequential samples positive for HCV RNA ⩾6months apart followed by ⩾1 negative test, and those with ⩾2 positive samples ⩾6months apart with no subsequent negative samples were identified. Control patients were randomly selected from the second group (4/patient of interest). Case notes were reviewed and patient characteristics obtained. RESULTS: 25,113 samples were positive for HCV RNA, relating to 10,318 patients. 50 cases of late spontaneous clearance were identified, contributing 241 person-years follow-up. 2,518 untreated, chronically infected controls were identified, contributing 13,766 person-years follow-up, from whom 200 controls were randomly selected. The incidence rate of spontaneous clearance was 0.36/100 person-years follow-up, occurring after a median 50months' infection. Spontaneous clearance was positively associated with female gender, younger age at infection, lower HCV RNA load and co-infection with hepatitis B virus. It was negatively associated with current intravenous drug use. CONCLUSIONS: Spontaneous clearance of CHC occurs infrequently but is associated with identifiable host and viral factors. More frequent HCV RNA monitoring may be appropriate in selected patient groups. LAY SUMMARY: Clearance of hepatitis C virus infection without treatment occurs rarely once chronic infection has been established. We interrogated a large Scottish patient cohort and found that it was more common in females, patients infected at a younger age or with lower levels of HCV in the blood, and patients co-infected with hepatitis B virus. Patients who injected drugs were less likely to spontaneously clear chronic infection.

BCSH/BSBMT/UK clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation.

A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.

Metagenomic next-generation sequencing aids the diagnosis of viral infections in febrile returning travellers.

OBJECTIVES: Travel-associated infections are challenging to diagnose because of the broad spectrum of potential aetiologies. As a proof-of-principle study, we used MNGS to identify viral pathogens in clinical samples from returning travellers in a single center to explore its suitability as a diagnostic tool. METHODS: Plasma samples from 40 returning travellers presenting with a fever of ≥38°C were sequenced using MNGS on the Illumina MiSeq platform and compared with standard-of-care diagnostic assays. RESULTS: In total, 11/40 patients were diagnosed with a viral infection. Standard of care diagnostics revealed 5 viral infections using plasma samples; dengue virus 1 (n = 2), hepatitis E (n = 1), Ebola virus (n = 1) and hepatitis A (n = 1), all of which were detected by MNGS. Three additional patients with Chikungunya virus (n = 2) and mumps virus were diagnosed by MNGS only. Respiratory infections detected by nasal/throat swabs only were not detected by MNGS of plasma. One patient had infection with malaria and mumps virus during the same admission. CONCLUSIONS: MNGS analysis of plasma samples improves the sensitivity of diagnosis of viral infections and has potential as an all-in-one diagnostic test. It can be used to identify infections that have not been considered by the treating physician, co-infections and new or emerging pathogens. SUMMARY: Next generation sequencing (NGS) has potential as an all-in-one diagnostic test. In this study we used NGS to diagnose returning travellers with acute febrile illness in the UK, highlighting cases where the diagnosis was missed using standard methods.

Association between universal hepatitis B prison vaccination, vaccine uptake and hepatitis B infection among people who inject drugs.

BACKGROUND AND AIMS: In Scotland, hepatitis B virus (HBV) vaccination for all prisoners was introduced in 1999; here, we examine the impact of this programme among people who inject drugs (PWID) in the community. This study aimed to compare rates of HBV vaccine uptake before and after implementation of the prison programme and to estimate the determinants of vaccine uptake, the levels of ever/current HBV infection and the associations between vaccine uptake and ever/current HBV infection. DESIGN: Data collected via serial cross-sectional surveys were used to compare the proportion who reported being vaccinated over time. For the 2013-14 survey, rates of ever/current HBV infection were calculated and the associations between vaccine uptake and ever/current HBV infection were examined using logistic regression. SETTING: Services providing injecting equipment and drug treatment and street sites in Glasgow (1993-2002) and throughout Scotland (2008-14). PARTICIPANTS: More than 10 000 PWID in total were recruited in the surveys. MEASUREMENTS: Participants completed a questionnaire (all years) to ascertain self-reported vaccine uptake and provided a blood spot (in 2013-14), tested for HBV core antibodies (anti-HBc) and surface antigen (HBsAg). FINDINGS: Among recent-onset PWID in Glasgow, vaccine uptake increased from 16% in 1993 to 59% in 2008-14 (P < 0.001). Among all PWID in Scotland, uptake increased further from 71% in 2008-09 to 77% in 2013-14 (P < 0.001) and was associated with incarceration [adjusted odds ratio (aOR) = 2.91, 95% confidence interval (CI) = 2.23-3.79]. The prevalence of anti-HBc and HBsAg in Scotland was 2.6 and 0.3%, respectively, among PWID who had commenced injecting in the decade since the programme's introduction. Vaccination was associated with reduced odds of ever (aOR = 0.60, CI = 0.37-0.97) and current (aOR = 0.40, CI = 0.16-0.97) HBV infection. CONCLUSIONS: In Scotland, uptake of hepatitis B virus (HBV) vaccination among people who inject drugs (PWID) in the community has increased since the 1999 introduction of universal prison vaccination, and current levels of HBV infection among PWID are low compared with other European countries.

Transmission of influenza A in families.

We conducted a prospective, nested study using nucleotide sequencing to examine influenza positive respiratory samples in families for genetic homology in the hemagglutinin and neuraminidase genes. Influenza A H3N2 viruses from 3 families had identical, family specific, HA1 nucleotide sequences. Sequences among these families were genetically heterogeneous. A 4th family was distinguished by sequencing of the influenza neuraminidase gene.

Hepatitis C reinfection following treatment induced viral clearance among people who have injected drugs.

BACKGROUND: Although people who inject drugs (PWID) are an important group to receive Hepatitis C Virus (HCV) antiviral therapy, initiation onto treatment remains low. Concerns over reinfection may make clinicians reluctant to treat this group. We examined the risk of HCV reinfection among a cohort of PWID (encompassing all those reporting a history of injecting drug use) from Scotland who achieved a sustained virological response (SVR). METHODS: Clinical and laboratory data were used to monitor RNA testing among PWID who attained SVR following therapy between 2000 and 2009. Data were linked to morbidity and mortality records. Follow-up began one year after completion of therapy, ending on 31st December, 2012. Frequency of RNA testing during follow-up was calculated and the incidence of HCV reinfection estimated. Cox proportional hazards regression was used to examine factors associated with HCV reinfection. RESULTS: Among 448 PWID with a SVR, 277 (61.8%) were tested during follow-up, median 4.5 years; 191 (69%) received one RNA test and 86 (31%) received at least two RNA tests. There were seven reinfections over 410 person years generating a reinfection rate of 1.7/100py (95% CI 0.7-3.5). For PWID who have been hospitalised for an opiate or injection related cause post SVR (11%), the risk of HCV reinfection was greater [AHR=12.9, 95% CI 2.2-76.0, p=0.002] and the reinfection rate was 5.7/100py (95% CI 1.8-13.3). CONCLUSION: PWID who have been tested, following SVR, for HCV in Scotland appear to be at a low risk of reinfection. Follow-up and monitoring of this population are warranted as treatment is offered more widely.

Long term stability of HBsAg, anti-HBc and anti-HCV in dried blood spot samples and eluates.

BACKGROUND: Dried blood spots (DBS) are a useful specimen collection tool in situations where venous access is problematic, however, detection of biomarkers from this specimen type is subject to variation depending on storage conditions and storage time. OBJECTIVES: The objective of this study is to assess the detection of HBsAg, anti-HBc and anti-HCV from DBS after storage. STUDY DESIGN: DBS specimens were stored at -70°C, -20°C, 4°C, 22 to 28°C and 37°C either with or without desiccant. Eluates were also prepared from DBS specimens and stored at -20°C and -70°C. DBS cards and eluates were tested for HBsAg, anti-HBc and anti-HCV at baseline on day 0 and thereafter at intervals of 14, 70 and 200 days. RESULTS: Loss of detection of both HBsAg and anti-HBc was evident by the first time point (14 days) in all storage conditions except for the samples (DBS and eluates) stored at -20°C or -70°C. Both HBsAg and anti-HBc stored under these conditions showed minimal variation up to the final time point (200 days) of storage. The detection of anti-HCV did not differ between the 22 to 28°C, 4°C, -20°C and -70°C DBS nor the -20°C or the -70°C stored eluates over the 200 day time period. CONCLUSION: We suggest that extended storage of DBS intended for downstream testing is best carried out by freezing either the DBS, or eluate, at -20°C or -70°C as soon as possible following collection for optimal detection of HBsAg, anti-HBc and anti-HCV.

Prevalence of HCV NS3 pre-treatment resistance associated amino acid variants within a Scottish cohort.

BACKGROUND: Protease inhibitors (PI) including boceprevir, telaprevir and simeprevir have revolutionised HCV genotype 1 treatment since their introduction. A number of pre-treatment resistance associated amino acid variants (RAVs) and polymorphisms have been associated with reduced response to treatment. OBJECTIVES: We measured the prevalence of RAVs/polymorphisms in a PI treatment-naïve HCV genotype 1 Scottish cohort using Sanger sequencing. STUDY DESIGN: Chronically infected, treatment-naïve, HCV genotype 1 patients (n = 146) attending NHS Greater Glasgow and Clyde clinics were investigated for RAVs/polymorphisms to the PIs boceprevir, telaprevir and simeprevir. The NS3/4A region was amplified by nested polymerase chain reaction. The 1.4 kb amplified product was sequenced using an ABI 3710XL DNA sequencer. Sequence analysis was performed using web-based ReCall (beta 2.10). Amino acid positions 36, 41, 43, 54, 55, 80, 109, 122, 155, 156, 168 and 170 were analysed for RAVs/polymorphisms. RESULTS: Overall, 23.29% (34/146) of patients had an RAV or polymorphism detected. Overall, 13.69% (20/146) of patients had HCV virus that contained the Q8 K polymorphism. Other RAVs detected were: V36 M 0.70% (1/146), V36L 0.70% (1/146), T54S 6.85% (10/146), V55A 3.42% (5/146) and V/I170A 0.68% (1/146). Four patients had dual combinations of mutations (T54S+V36L; T54S+V55A and 2 patients with T54S+Q80K). CONCLUSIONS: Q80K was the most prevalent baseline polymorphism detected in the Scottish cohort. Simeprevir treatment is not recommended in patients infected with the Q80K genotype 1a variant. This highlights the need for baseline sequencing prior to administration of this drug in this population.

Development of an avidity assay for detection of recent HIV infections.

HIV avidity can measure the incidence of recent infections within the population. The aim of this study was to evaluate an HIV avidity assay, initially from a clinically defined group of patients and then apply the assay to a prospective study to determine the false recency rate and mean duration of recency for the assay. The assay is a commercial ELISA modified with 7 M urea. The validation of the assay used plasma from patients split into Group 1 (recently infected N=25) and group 2 (established infection N=301). The prospective study tested 178 newly diagnosed HIV patients for avidity. A total of 326 retrospective samples of known HIV status were collected and tested. The initial evaluation gave a sensitivity 100% (CI 86.16-100%) and specificity of 98.65% (95% CI 97.05-99.78%). The prospective study incorporating 178 newly diagnosed patients found 22 patients with low avidity. Follow-up samples obtained from low avidity patients determined the estimated mean duration of recency to be between 3 and 4 months with a false recency rate of 0.89% (CI: 0.24-2.3%). The assay described here compares well in sensitivity, specificity and false recency rate with that of other published avidity assays.

Influenza A community-acquired pneumonia in East London infants and young children.

BACKGROUND: Community-acquired pneumonia (CAP) is common in young children, but there are few data in Europe on influenza A virus as a cause of childhood CAP. The aim of this study was to determine the relative contributions of different etiologic agents to CAP in children. METHODS: This was a 6-month prospective study of pediatric accident and emergency and general practice consultations with a diagnosis of CAP. Nasopharyngeal aspirates for viral immunofluorescence and PCR studies and blood cultures for bacterial studies were taken from 51 children with symptoms, signs and chest radiographic features that satisfied a diagnosis of pneumonia. RESULTS: An etiologic agent was isolated from 25 patients (49%). A viral cause was identified in 22 patients (43%), and influenza A virus and respiratory syncytial virus (RSV) were detected in 16 and 18% of all cases, respectively. Only four patients (8%) had a positive bacterial blood culture; three had Streptococcus pneumoniae and one had Neisseria meningitidis W135. Mycoplasma pneumoniae was detected in 2 children, and mixed infections were detected in 5 (10%). The use of viral PCR increased the detection rate of influenza A virus by 100%. CONCLUSION: Influenza A virus caused more than one-third of all viral CAP cases, a rate comparable with that of RSV CAP. Viral PCR doubled the diagnostic yield of influenza A virus. The clinical burden of influenza A CAP was comparable with that of RSV CAP, as measured by the duration of fever, hospital stay and total duration of illness.

Ethnicity and discordance in plasma HIV-1 RNA viral load and CD4+ lymphocyte count in a cohort of HIV-1-infected individuals.

BACKGROUND: Guidelines for commencing therapy for HIV infection have been based upon HIV-1 RNA and CD4 lymphocyte thresholds. The influence of confounding factors such as gender, ethnicity and co-infections is unproven. OBJECTIVES: To analyse ethnic discordance in plasma HIV-1 viral load (VL) and CD4+ count and its potential clinical significance in Black and Caucasian groups. STUDY DESIGN: Retrospective, cross-sectional, observational study of 537 antiretroviral nai;ve HIV-1-positive individuals attending two East London clinics. Baseline data were obtained from individuals who registered at the clinic from November 1996 to August 1999. An analysis was performed comparing ethnic differences in plasma HIV-1 VL, CD4+ count, CD8+ count, co-infections, CDC disease category, AIDS-defining illnesses and mode of transmission. RESULTS: Plasma HIV-1 VL was significantly lower in Blacks (4.5 copies/ml versus 4.7 copies/ml; P<0.05) despite lower baseline CD4+ counts and similar rates of disease progression to Caucasian groups. This association remained for patients with less advanced disease after stratification for CD4+ count (CD4+ 200-500, VL 4.5 copies/ml versus 4.7 copies/ml, P<0.01; CD4+ >500, VL 3.4 copies/ml versus 4.3 copies/ml, P<0.001) and disease category (non-AIDS, 4.4 copies/ml versus 4.7 copies/ml; P<0.005). On multivariate analysis, the association persisted following adjustment for gender, age, co-infections, CD4+ count and mode of transmission. CONCLUSIONS: These results suggest that plasma HIV-1 VL is discordantly low in Black compared with Caucasian groups stratified for CD4+ count, in this cohort of antiretroviral nai;ve HIV-1-positive individuals living in London. Although there are a number of possible explanations for this finding, it has considerable clinical relevance for the management of Black HIV-1-infected patients within UK, with significant implications for the decision about when to commence antiretroviral or immune-based therapies.

Rapid decline in HCV incidence among people who inject drugs associated with national scale-up in coverage of a combination of harm reduction interventions.

BACKGROUND: Government policy has precipitated recent changes in the provision of harm reduction interventions - injecting equipment provision (IEP) and opiate substitution therapy (OST) - for people who inject drugs (PWID) in Scotland. We sought to examine the potential impact of these changes on hepatitis C virus (HCV) transmission among PWID. METHODS AND FINDINGS: We used a framework to triangulate different types of evidence: 'group-level/ecological' and 'individual-level'. Evidence was primarily generated from bio-behavioural cross-sectional surveys of PWID, undertaken during 2008-2012. Individuals in the window period (1-2 months) where the virus is present, but antibodies have not yet been formed, were considered to have recent infection. The survey data were supplemented with service data on the provision of injecting equipment and OST. Ecological analyses examined changes in intervention provision, self-reported intervention uptake, self-reported risk behaviour and HCV incidence; individual-level analyses investigated relationships within the pooled survey data. Nearly 8,000 PWID were recruited in the surveys. We observed a decline in HCV incidence, per 100 person-years, from 13.6 (95% CI: 8.1-20.1) in 2008-09 to 7.3 (3.0-12.9) in 2011-12; a period during which increases in the coverage of OST and IEP, and decreases in the frequency of injecting and sharing of injecting equipment, were observed. Individual-level evidence demonstrated that combined high coverage of needles/syringes and OST were associated with reduced risk of recent HCV in analyses that were unweighted (AOR 0.29, 95%CI 0.11-0.74) and weighted for frequency of injecting (AORw 0.05, 95%CI 0.01-0.18). We estimate the combination of harm reduction interventions may have averted 1400 new HCV infections during 2008-2012. CONCLUSIONS: This is the first study to demonstrate that impressive reductions in HCV incidence can be achieved among PWID over a relatively short time period through high coverage of a combination of interventions.

Rise in testing and diagnosis associated with Scotland's Action Plan on Hepatitis C and introduction of dried blood spot testing.

BACKGROUND: A key aim of the Hepatitis C Action Plan for Scotland was to reduce the undiagnosed population through awareness-raising activities, for general practitioners and those at risk, and the introduction of dried blood spot (DBS) sampling in community drug services to overcome barriers to testing. This study evaluates the impact of these activities on testing and diagnosis. METHODS: Data on hepatitis C virus (HCV) testing undertaken between January 1999 and December 2011 in Scotland's four largest health boards were analysed. Segmented regression analysis was used to examine changes in testing following the (1) launch of the Action Plan and (2) introduction of DBS testing. RESULTS: Between the pre-Action Plan and Action Plan periods, increases were observed in the average number of HCV tests (19 058-29 045), positive tests (1993-2405) and new diagnoses (1221-1367). Since July 2009, 26% of new diagnoses were made in drug services. The trend in the number of positive tests was raised during the Action Plan, compared to pre-Action Plan, particularly in drug services (rate ratio (RR)=1.4, p<0.001) and prisons (RR=1.2, p<0.001); no change was observed in general practice. Following introduction of DBS testing, there was a 3-fold increase in testing (RR=3.5, p<0.001) and 12-fold increase in positives (RR=12.1, p<0.001) in drug services. CONCLUSIONS: The introduction of DBS sampling in community drug services has made an appreciable contribution to efforts to diagnose the HCV-infected population in Scotland. These findings are important to other countries, with injecting-related HCV epidemics, needing to scale-up testing/case-finding initiatives.