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Background:The scale of the 2022 global mpox (formerly known as monkeypox) outbreak has been unprecedented. In less than 6 months, non-endemic countries have reported more than 67 000 cases of a disease that had previously been rare outside of Africa. Mortality has been reported as rare but hospital admission has been relatively common. We aimed to describe the clinical and laboratory characteristics and outcomes of individuals admitted to hospital with mpox and associated complications, including tecovirimat recipients. Methods:In this cohort study, we undertook retrospective review of electronic clinical records and pathology data for all individuals admitted between May 6, and Aug 3, 2022, to 16 hospitals from the Specialist and High Consequence Infectious Diseases Network for Monkeypox. The hospitals were located in ten cities in England and Northern Ireland. Inclusion criteria were clinical signs consistent with mpox and MPXV DNA detected from at least one clinical sample by PCR testing. Patients admitted solely for isolation purposes were excluded from the study. Key outcomes included admission indication, complications (including pain, secondary infection, and mortality) and use of antibiotic and anti-viral treatments. Routine biochemistry, haematology, microbiology, and virology data were also collected. Outcomes were assessed in all patients with available data. Findings:156 individuals were admitted to hospital with complicated mpox during the study period. 153 (98%) were male and three (2%) were female, with a median age of 35 years (IQR 30–44). Gender data were collected from electronic patient records, which encompassed full formal review of clincian notes. The prespecified options for data collection for gender were male, female, trans, non-binary, or unknown. 105 (71%) of 148 participants with available ethnicity data were of White ethnicity and 47 (30%) of 155 were living with HIV with a median CD4 count of 510 cells per mm3(IQR 349–828). Rectal or perianal pain (including proctitis) was the most common indication for hospital admission (44 [28%] of 156). Severe pain was reported in 89 (57%) of 156, and secondary bacterial infection in 82 (58%) of 142 individuals with available data. Median admission duration was 5 days (IQR 2–9). Ten individuals required surgery and two cases of encephalitis were reported. 38 (24%) of the 156 individuals received tecovirimat with early cessation in four cases (two owing to hepatic transaminitis, one to rapid treatment response, and one to patient choice). No deaths occurred during the study period. Interpretation:Although life-threatening mpox appears rare in hospitalised populations during the current outbreak, severe mpox and associated complications can occur in immunocompetent individuals. Analgesia and management of superimposed bacterial infection are priorities for patients admitted to hospital.

In the United Kingdom, organ donors/recipients are screened for evidence of human T-cell leukaemia virus type-1 and type-2 (HTLV-1/2) infections. Since the United Kingdom is a low prevalence country for HTLV infections, a screening assay with high sensitivity and specificity is required. Samples with repeat reactivity on antibody testing are sent to a reference lab for confirmatory serological and molecular testing. In the case of donor screen, this leads to delays in the release of organs and can result in wastage. We aim to assess whether a signal/cut-off (S/CO) ratio higher than the manufacturer's recommendation of 1.0 in the Abbott Architect antibody assay is a reliable measure of HTLV-1/2 infection.We conducted a 5 year retrospective analysis of 7245 patients from which 11 766 samples were tested on the Abbott Architect rHTLV I/II assay. Reactive samples (S/CO 1) were referred for confirmatory serological and molecular detection (Western Blot and proviral DNA) at UK Health Security Agency, (formerly PHE, Colindale), the national reference laboratory. Electronic, protected laboratory and hospital patient databases were employed to collate data.A total of 45 patients had initially reactive samples. 42.2% (n = 19/45) had an S/CO ratio 20, with HTLV infection confirmed in n = 18/19 and indeterminate confirmatory results in n = 1/19. No samples with an S/CO ratio4 (48.9%, n = 22/45) or 4-20 (8.9%, n = 4/45) had positive confirmatory results on subsequent confirmatory testing.Samples with an S/CO20 likely represent a true HTLV-1/2 infection. Reactive samples with an S/CO 4 were unlikely to confirm for HTLV infections. Interpretation of these ratios can assist clinicians in the assessment of low reactive samples and reiterates the need for faster access to confirmatory testing.

Background Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic. Methods We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020–March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed. Results Overall, 116 of 119 cases developed COVID-19 post–first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P Conclusions Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.

BackgroundThe Alpha variant (B.1.1.7 lineage) of SARS-CoV-2 emerged and became the dominant circulating variant in the UK in late 2020. Current literature is unclear on whether the Alpha variant is associated with increased severity. We linked clinical data with viral genome sequence data to compare admitted cases between SARS-CoV-2 waves in London and to investigate the association between the Alpha variant and the severity of disease.MethodsClinical, demographic, laboratory and viral sequence data from electronic health record systems were collected for all cases with a positive SARS-CoV-2 RNA test between 13 March 2020 and 17 February 2021 in a multisite London healthcare institution. Multivariate analysis using logistic regression assessed risk factors for severity as defined by hypoxia at admission.ResultsThere were 5810 SARS-CoV-2 RNA-positive cases of which 2341 were admitted (838 in wave 1 and 1503 in wave 2). Both waves had a temporally aligned rise in nosocomial cases (96 in wave 1 and 137 in wave 2). The Alpha variant was first identified on 15 November 2020 and increased rapidly to comprise 400/472 (85%) of sequenced isolates from admitted cases in wave 2. A multivariate analysis identified risk factors for severity on admission, such as age (OR 1.02, 95% CI 1.01 to 1.03, for every year older; pConclusionsOur analysis is the first in hospitalised cohorts to show increased severity of disease associated with the Alpha variant. The number of nosocomial cases was similar in both waves despite the introduction of many infection control interventions before wave 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

BACKGROUND: Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis worldwide. Typically associated with a self-limiting illness, infection may persist in immunosuppressed populations with significant morbidity and mortality. Based on clinical data published world-wide, UK blood safety guidance recommends the universal screening for HEV RNA of blood donors and donors of tissue, organs and stem cells. OBJECTIVES: This cross-sectional study aimed to determine the point prevalence of HEV viraemia and clinical course of viraemic patients in the peri-transplant period in solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) recipients transplanted over a 3-year period (2013–2015). STUDY DESIGN: Nucleic acid extracts of whole blood from patients undergoing SOT or HSCT were tested by an in-house real-time reverse-transcriptase polymerase chain reaction assay for HEV RNA. Samples were tested at baseline (time of transplant), 30, 60 and 90 days post-transplant. RESULTS: 870 patients (259 HSCT, 262 liver and 349 kidney transplant) were included with 2554 samples meeting the inclusion criteria. No kidney transplant patients had HEV viraemia at time of testing. One HSCT and three liver transplant patients were found to be HEV RNA positive. Overall this represented 0.46% of the patients testing positive for HEV viraemia. CONCLUSION: Prevalence of HEV viraemia in SOT and HSCT patients in U.K. although higher than in the general population is low at baseline and remains low throughout the early post-transplant phase. Clearance of viraemia can be maintained despite ongoing immunosuppression. Prospective U.K. studies are necessary to inform screening policies in this population.

Background Respiratory illness contributes significantly to higher ED attendance during winter months. Polymerase chain reaction (PCR) testing of nasopharyngeal swabs (NPS) for respiratory viruses is a key investigation, with positive influenza results having both clinical and infection control implications. In response to ED colleagues requesting clear and concise guidance, we undertook a QIP to improve management of seasonal influenza. Methods A survey of 10 questions was sent to all Doctors and Advanced Care Practitioners (ACPs) working in the ED, and the results collated. Results There were 21 survey respondents, the majority were registrars. 81% correctly identified how to request influenza testing and 95% knew the symptoms. 90% identified which risk groups should be treated, which personal protective equipment (PPE) should be donned, and suggested Oseltamavir as their treatment of choice. However only 29% of respondents knew where to find the trust guidelines and only 10% correctly prescribed prophylaxis to contacts. 95% would review a discharged case found to have influenza on testing and 67% would treat this case if they were in an at risk group. Discussion and Conclusions The results show that the majority of staff surveyed correctly identified the symptoms of flu, infection control precautions and those requiring treatment. However, knowledge regarding the location of guidelines, management of contacts and the use of agents other than oseltamivir was low. Based on these results we developed a single-page influenza testing algorithm aiming to improve management in A&E, and will reassess staff knowledge following the introduction of this.

Background Hepatitis E virus (HEV) is an important infectious agent causing acute and chronic disease. Chronic hepatitis E affects immunocompromised people and serological testing is neither reliable nor sufficient to infer whether a patient has infection; therefore HEV RNA testing is the only reliable diagnostic test presently available. An HEV antigen-specific ELISA test is commercially available but is not yet in clinical use. Objectives 1) determine the prevalence of HEV infection in the Royal Free Hospital (RFH) liver transplant cohort; 2) compare the diagnostic utility of HEV antigen-detection against the current gold standard; 3) consider screening strategies for HEV infection in immunocompromised groups. Study design The serum samples of 490 post liver transplant patients visiting the outpatient clinic at the RFH over an eight-month period were tested for HEV with both an HEV antigen-specific ELISA and HEV RNA test. Results The prevalence of HEV infection was 0.20% (95% CI 0.0%–1.1%). The specificity of the ELISA was 98.2% with a positive predictive value of 10.0%. There was one true positive HEV case, which was picked up correctly by the antigen-specific ELISA. These results were improved by incorporating a neutralisation step into further ELISA tests. Conclusions The antigen-specific ELISA test gave no false negative results, supporting its utility as a screening tool. There was one true antigen positive result. Further investigation including cost analysis is indicated to determine the efficacy of HEV antigen-specific ELISA testing in a screening context and in the clinical investigation of HEV infection in immunocompromised patients.

Hepatitis E Virus (HEV) is a common cause of acute viral hepatitis worldwide. Typically associated with a self-limiting illness, infection may persist in immunosuppressed populations with significant morbidity and mortality. Based on clinical data published world-wide, UK blood safety guidance recommends the universal screening for HEV RNA of blood donors and donors of tissue, organs and stem cells.This cross-sectional study aimed to determine the point prevalence of HEV viraemia and clinical course of viraemic patients in the peri-transplant period in solid organ transplant (SOT) and haematopoietic stem cell transplant (HSCT) recipients transplanted over a 3-year period (2013-2015).Nucleic acid extracts of whole blood from patients undergoing SOT or HSCT were tested by an in-house real-time reverse-transcriptase polymerase chain reaction assay for HEV RNA. Samples were tested at baseline (time of transplant), 30, 60 and 90 days post-transplant.870 patients (259 HSCT, 262 liver and 349 kidney transplant) were included with 2554 samples meeting the inclusion criteria. No kidney transplant patients had HEV viraemia at time of testing. One HSCT and three liver transplant patients were found to be HEV RNA positive. Overall this represented 0.46% of the patients testing positive for HEV viraemia.Prevalence of HEV viraemia in SOT and HSCT patients in U.K. although higher than in the general population is low at baseline and remains low throughout the early post-transplant phase. Clearance of viraemia can be maintained despite ongoing immunosuppression. Prospective U.K. studies are necessary to inform screening policies in this population.

Background Adenovirus infection is a recognized complication following haematopoietic stem cell transplantation. We present a review of our experience of these infections in our transplant cohort over 10 years including 3 patients treated with the novel antiviral brincidofovir. Objectives We aimed to describe the presentation, response to treatment and outcomes of adult stem cell transplant patients with disseminated adenovirus infection. Study design All adult cases of disseminated adenovirus infection following haematopoietic stem cell transplant in our unit between 2005 and 2015 were identified. Transplant details and data on timing of diagnosis, course of infection, viral co-infection and treatment were collected. Results Of 733 patients transplanted, 10 patients had disseminated infection, including 4 male and 6 female patients with median age of 36.5 (range 19–59) years. 6/10 received an allograft from an unrelated donor. Median post-transplant time to detection of viraemia was 67 days (range 20–1140 days). Median peak viral load was 3133 copies/ml (352–11,000,000) in survivors received cidofovir alone, one cidofovir then brincidofovir and two brincidofovir alone. 8/10 p and 1,580,000 copies/ml (41,999–3,000.000) in those who died. Five patientsatients had a decrease in viral load following antivirals and/or reduction in immunosuppression including all on brincidofovir. Three died on treatment. Conclusions Disseminated adenovirus infection is uncommon in adult transplant patients and uncertainties remain surrounding effective treatment. In our cohort, brincidofovir has shown promise in treatment of adenoviral infection. However, randomized controlled studies are required to confirm this impression.

Acute hepatitis E is becoming increasingly recognised in Europe with up to 40% of the population in Southern France being exposed to the virus, which is harboured in pigs. Patients with known liver disease may present with acute hepatitis E and present a diagnostic challenge. For example patients with autoimmune hepatitis (AIH) who are immunosuppressed and contract hepatitis E may be at increased risk of developing chronicity due to concurrent immunosuppression. Importantly, the diagnosis may be missed with the infection misdiagnosed as an autoimmune flare, and immunosuppression increased by the attending physician, thus enhancing the risk of chronicity of infection leading to progressive liver injury in immunocompromised patients. We report a case of acute hepatitis E in a patient with AIH and discuss the features that helped us differentiating it from an autoimmune flare.

Background Hepatitis C virus (HCV) genotyping is required for tailoring the dose and duration of antiviral therapy, predicting virological response rates, and selecting future treatment options. Objective To establish whether baseline genotypes, performed by INNO-LiPA Version 1.0 (v1.0), before 2008, were valid for making treatment decisions now or whether genotypic determination should be repeated. Furthermore, to evaluate concordance between Abbott RealTime genotype II assay (RT) and genotyping by sequencing HCV C/E1, NS5A, NS5B. Study design Genotyping by RT and sequencing was performed on paired historic and current specimens from 50 patients previously baseline genotyped using INNO-LiPA. Results Of 100 samples from 50 patients, ≥2 of HCV genomic target regions yielded a sequence that was suitable for genotyping, with 100% concordance, providing no evidence of recombination events. Genotype and subtype prediction based on RT and sequencing agreed in 62.8% historic and 72.7% current specimens, with a kappa coefficient score of 0.48 and 0.76, respectively. LiPA could not subtype 46% of HCV gt1 infections, and LiPA subgenotype was only in agreement with RT and sequencing in 28.6% cases, where matched baseline and historic specimens were available. Three patients were indeterminate by RT, and five patients with HCV gt1 infections could not be subtyped by RT. However, RT revealed mixed infections in five patients where sequencing detected only single HCV infection at 20% threshold. Conclusion Genotyping by sequencing, exhibited excellent concordance, with moderate to good agreement with RT, and could resolve RT indeterminates and subtype HCV-gt1 infections not possible by LiPA.

Background: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited. Objective: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results. Methods: CSF from patients with was tested for human herpesviruses types 1–6, JC virus, enteroviruses, and Toxoplasma gondii . The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis. Results: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3–14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection. Conclusions: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

Correctly identifying Koplik’s spots is not an easy feat, as noted in Spitzer’s excellent letter.12 Koplik’s spots are still thought to be pathognomonic for measles, but oral lesions, similar in appearance to Koplik’s spots, can be found in other illnesses, such as parvovirus B12 infection.3 Zenner and Nacul’s study included reporting of “Koplik’s spots” by clinicians with variable levels of experience and did not include independent assessment …

What you need to know A 23 year old woman has fever, flu-like symptoms, diarrhoea, and a rash that has spread from her face to her body. She cannot recall being in contact with anyone unwell and has not recently travelled or taken any drugs. She reports missing vaccinations as a child because her parents were concerned about safety. On examination she has a maculopapular blanching rash on her face and chest. Measles was suspected and confirmed with serology that was positive for immunoglobulin M antibodies to the measles virus. Reverse transcription polymerase chain reaction on a throat swab detected measles virus RNA. Measles is widely perceived as a disease of early childhood, despite almost two thirds of recent cases in the United Kingdom being in those aged 15 and older.1 Patients typically present with fever, cough, coryza, and conjunctivitis, followed two to four days later by a characteristic erythematous maculopapular rash that spreads downwards from the face (figs 1⇓ and 2⇓).2 Patients are infectious from four days before to four days after the onset of rash. Koplik’s spots—whitish lesions …

The use of triple-therapy, pegylated-interferon, ribavirin and either of the first generation hepatitis C virus (HCV) protease inhibitors telaprevir or boceprevir, is the new standard of care for treating genotype 1 chronic HCV. Clinical trials have shown response rates of around 70–80%, but there is limited data from the use of this combination outside this setting. Through an expanded access programme, we treated 59 patients, treatment naive and experienced, with triple therapy. Baseline factors predicting treatment response or failure during triple therapy phase were identified in 58 patients. Thirty seven (63.8%) of 58 patients had undetectable HCV RNA 12 weeks after the end of treatment. Genotype 1a (p = 0.053), null-response to previous treatment (p = 0.034), the rate of viral load decline after 12 weeks of previous interferon-based treatment (p = 0.033) were all associated with triple-therapy failure. The most common cause of on-treatment failure for telaprevir-based regimens was the development of resistance-associated variants (RAVs) at amino acids 36 and/or 155 of HCV protease (p = 0.027) whereas in boceprevir-based regimens mutations at amino acid 54 were significant (p = 0.015). SVR12 rates approaching 64% were achieved using triple therapy outside the clinical trial setting, in a patient cohort that included cirrhotics.

Introduction: Hepatitis E Virus (HEV) is one of the leading causes of acute infectious hepatitis worldwide; while usually a self-limiting, sub-clinical illness, genotype 3 HEV infection may become chronic in immunosuppressed patients such as solid organ transplant (SOT) or haematopoietic stem cell transplant (HSCT) recipients and rapid progression to cirrhosis may occur. Recent seroprevalence from screening of English blood donors shows antibody prevalence of ~13%. RNA prevalence in donors has increased in the UK from 1:2850 to 1:1460 over the past 3 years. This study examines the point-prevalence of HEV in SOT and HSCT recipients transplanted between January 2013 - December 2015 at a major UK transplant centre. Data on HEV clearance rates and risk factors for infection were collected in the patient cohort. Methods: Stored extracts of blood from patients undergoing liver transplant (OLT), renal transplant (RT) or HSCT were tested by real-time reverse-transcriptase polymerase chain reaction for HEV RNA. Samples were tested at baseline, 30, 60 and 90 days post-transplant +/- 7 days. Time points were chosen to give good coverage of the early post-transplant period whilst avoiding a patient becoming viraemic and clearing the infection between sample time points. All positive samples were sent to the Public Health England reference laboratory for verification, viral RNA genotyping and quantification. Patients with confirmed positive samples underwent further testing and evaluation of clinical parameters to determine chronology of infection, blood product exposure, organ function and histopathology results. Results: 259 HSCT, 262 OLT and 349 RT patients met the inclusion criteria. Of the HSCTs there were 111 allogeneic stem cell transplants, 145 autologous transplants and 3 CD34 "top ups". The OLTs comprised 259 deceased donor, 2 live donor and 2 domino liver transplant patients. The RTs comprised 241 deceased donor, 38 live unrelated, 63 live related transplants and 1 live transplant where the relationship of the donor was unrecorded. In total 4 patients (1 HSCT and 3 OLT) were found to have HEV viraemiain our study period. This represents 0.39% of the HSCT and 1.15% of the OLT patients. All were positive with HEV genotype 3. Virologicaland clinical data regarding these patients are presented in tables below. Conclusion: Chronic HEV, genotype 3 in transplant patients is associated with significant morbidity. With the increasing incidence of HEV, immunosuppressed patients with high transfusion burden have an infection risk equivalent to 7-9 years' dietary exposure. Our results show that prevalence of HEV viraemia in OLT, RT and HSCT patients is higher than expectedbased on comparison from UK blood donors. Secondly, infection is not cleared as would be expected in the general population with 3 of the 4 patients requiring treatment to clear the virus. The source of infection for these patients is unclear; on a population wide basis HEV is usually a dietary acquired infection, with pork products carrying the greatest risk. In the transplant patient population, the risk of iatrogenic infection via infected blood products or an infected transplanted organ is an important consideration and UK guidance has recently changed so that transplant recipients receive dietary advice and HEV-negative blood to avoid infection (SaBTO2016). In this study 2 patients were found to be positive for HEV RNA in the baseline sample. One, the recipient of HSCT, did not acquire it through transfusion as testing of the transfused products that the patient had received were negative for the virus. It is not clear how the two OLT patients who tested positive acquired the virus. The absence of any positive results in the renal transplant recipients may reflect the lower transfusion burden in this patient group. Given the multiple routes of possible infection with HEV, a strategy if screening recipients for the virus in addition to screening blood and organ donors would be an effective way of detecting viral transmission via all routes. Table 1 Virology results for HEV positive patients Table 1. Virology results for HEV positive patients Table 2 Clinical data regarding HEV positive patients Table 2. Clinical data regarding HEV positive patients Disclosures Sekhar: Novartis: Research Funding.

Hepatitis C virus (HCV) seroconversion was detected by routine screening in a haemodialysis patient, Patient 1. Serological investigations were undertaken over the following 3 months to determine if further transmission to other patients on the unit had occurred. No additional cases were identified. Twenty-two haemodialysis patients known to have HCV infection were investigated using molecular epidemiological methods to determine if transmission between patients had occurred. HCV viraemia was demonstrated by polymerase chain reaction in 19 of 22 patients (86%). Genotyping showed that eight patients were infected with genotype 1, three with genotype 3 and eight, including Patient 1, with genotype 2. Phylogenetic analysis of viral sequences from the eight patients with genotype 2 revealed three, including Patient 1,with a novel subtype of HCV type 2, and revealed close similarity between viral sequences from patient 1 and those from one other patient, suggesting transmission. This was consistent with haemodialysis histories. Among other patients with genotype 2, there were two with subtype 2a and three others with three separate novel subtypes, as yet undesignated. With the exception of patient 1, all patients infected with novel subtypes were of Afro-Caribbean origin. The HCV prevalence among patients on the haemodialysis unit was high (14%), which may reflect the ethnicity of our haemodialysis population. This case emphasises the risk of nosocomial transmission and the importance of infection control procedures on haemodialysis units, and highlights the usefulness of molecular epidemiological techniques for the investigation of outbreaks of HCV infection.

No: 1752 Presentation at ESCV 2015: Oral 38 Salivirus Type 1 and Type 2 in patients with acute gastroenteritis, Germany S. Aldabbagh1,∗, I. Eckerle1, A. Muller2, E.L. Delwart3, A.M. Eis-Hubinger1 1 Institute of Virology, University of Bonn Medical Centre, Germany 2 Department of Neonatology and Pediatric Intensive Care, Childrens Hospital, University of Bonn Medical Centre, Germany 3 Blood Systems Research Institute, Department of Laboratory Medicine, University of California, USA Background: Salivirus (SaV-A) is a novel member of the family Picornaviridae and the only species within the novel picornaviral genus Salivirus. The virus was found in up to 9% of fecal samples from patients, mostly children, with gastroenteritis, with highest prevalences in Asian countries. Thus, the virus was suspected to cause acute gastroenteritis. Recently, a second type of SaV-A (SaVA2) was identified in a sewage sample from Thailand. Because no information is available on SaV-A infection in Western Europe, we analysed stool samples from patients with symptoms suspicious of acute viral gastroenteritis for SaV-A and evaluated the clinical course of SaV-A-positive individuals. Methods: A total of 3019 fecal samples from 1941 hospitalised patients with symptoms of acute gastroenteritis were analysed. Samples were collected during 2012–2013 at the University Hospital Bonn and were routinely screened by (RT-)PCR for human norovirus, sapovirus, astrovirus, rotavirus, and adenovirus. A SaVA real-time RT-PCR was designed targeting a conserved nucleotide sequence in the 5′-untranslated region. Positive results were verified by sequencing the viral capsid protein 1 gene allowing also typing of the virus andwhole genome sequencing. Medical records of SaV-A-infected patients were reviewed for clinical features and laboratory data. Results: SaV-A was detected in five unrelated patients, with viral concentrations ranging between 7.1×106 and 7.2×108 copies/g feces, in the absence of common gastroenteritis viruses. The viruses from four patients were classified as SaV-A1 while in one patient SaV-A2 was present. In none of the five patients SaV-A infection was considered as the major cause of the gastroenteritis symptoms. Conclusion: SaV-A infection can be detected in Germany,Western Europe, albeit at low levels. The detection of SaV-A2 in Europe suggests global spread of SaV-A2. Presence of SaV-A, even at high concentration, in a stool sample provides no conclusive evidence that SaV is the major cause of the patient’s gastroenteritis symptoms. http://dx.doi.org/10.1016/j.jcv.2015.07.048 Abstract No: 1526 Presentation at ESCV 2015: Oral 39 Disseminated adenovirus infection following allogeneic haemopoetic stem cell transplantation – A report on the use of brincidofovir and 10 year retrospective review of an adult transplant cohort I. Ramsay1,∗, C. Attwood2, D. Irish1, D. Lowe3, P.D. Griffiths1, Kyriacou Charalampia2 1 Department of Virology, Royal Free Hospital, London UK 2 Department of Haematology, Royal Free Hospital, London UK 3 Department of Immunology, Royal Free Hospital

BACKGROUND: Pregnant women with hepatitis B virus (HBV) infection can transmit the infection to their infants, screening of patients and appropriate interventions reduce vertical transmission. This audit was conducted to assess adherence to the national guidelines for management of HBV infection in pregnancy. METHODS: A retrospective audit was conducted on pregnant women diagnosed with hepatitis B on screening in antenatal clinics, across four hospitals in London over 2 years (2009-2010). Data was collected from antenatal records and discharge summaries using a standard audit form. The outcomes measured included HBV serological markers, HBV DNA, detection of other blood borne viruses and referral to hepatology services, administration of active and passive prophylaxis to infants at birth. Descriptive statistics are presented. Proportions were compared using the χ2 test and 95% confidence intervals (CI) were calculated for prevalence estimates. Analyses were conducted using STATA 12. RESULTS: HBsAg was detected in 1.05% (n = 401, 95% CI 0.95-1.16) of women attending an antenatal appointment, 12% (n = 48) of the women were at a high risk of vertical transmission (HBe Ag positive or antiHBe and HBeAg negative or HBV DNA >106 IU/ml). Only 62% (n = 248) women were referred to hepatology or specialist clinics and 29% (n = 13) of women of high infectivity were on antiviral agents. Testing for hepatitis C and delta virus was suboptimal. 75% (n = 36) of the infants at a high risk of acquisition of HBV received both active and passive prophylaxis. CONCLUSION: In certain sectors of London, implementation of the pathway for management of women with hepatitis B and their infants is suboptimal. National guidelines should be followed and improved intersectorial sharing of information is needed to reduce the risk of women of high infectivity being lost to follow up.

Pustular rash in a neonate is very common and is usually associated with staphylococcal infection. The present report describes the case of a 12-day-old neonate with a pustular rash, secondary to herpes simplex infection. A high index of suspicion is necessary in neonates presenting with suggestive signs, especially with negative bacterial cultures. Prompt initiation of aciclovir treatment after obtaining diagnostic samples may be life-saving.

A review of a large number of HIV-1 tropism test requests ( n = 1148) performed at a London tertiary referral centre was carried out. The aim was to establish whether these were being performed in line with recommendations from published guidelines and whether this represented the most cost-effective use of these tests in informing prescribing decisions of the CCR5 antagonist drug, maraviroc. The cost of these assays within the UK was covered by commercial funding until April 2013 which has subsequently been withdrawn. Furthermore, all healthcare settings are under increasing cost constraints and hence establishing the real utility and appropriate use of these tests is of vital importance.

Background and Aims: The failure of HCV-specific CD8 T-cells is linked to the development of chronic infection. However, the responsible mechanisms are only partly understood. The initial priming of CD8 T-cells is key for the induction of immune responses. Studies have shown an important role of the cytokine interleukin-10 (IL-10) in HCV-infection. Thus, we analyzed whether IL-10 affects the initial priming of HCV-specific CD8 T-cells. Methods: To address this important question, we performed in vitro priming experiments of naive HCV-specific CD8 T-cells from healthy donors by using autologous monocyte-derived dendritic cells (MD-DCs) in the presence or absence of IL-10. After 8 days of co-culture, frequency, phenotype and function of HCV-specific CD8 T-cells were analyzed. Results: The presence of IL-10 during priming significantly reduces the frequency of HCV-specific CD8 T-cells after 8 day proliferation. To identify the target cells of IL-10 action, we performed separate pre-incubations of MD-DCs and CD8 T-cells with IL-10. These results revealed that IL-10 acts directly on CD8 T-cells. Interestingly, HCV-specific CD8 T-cells primed in the presence of IL-10 also showed signs of impaired differentiation into effector cells. In contrast to the suppressive effect of IL-10 during priming, addition of IL-10 at day 4 after priming had no inhibitory but rather stimulatory activity on HCV-specific CD8 T-cell proliferation. Conclusions: In sum, we could show a suppressive effect of IL-10 on the priming of naive HCV-specific CD8 T-cells. This provides a mechanistic basis for the clinical observation, that high IL-10 levels in the acute phase of infection are associated with the progression to chronicity.

Introduction We report the impact of host and viral factors on treatment outcome in the first 53 patients who have completed therapy for CHC with either telaprevir or boceprevir, in combination with pegylated-interferon and ribavirin (PEG/R) at our centre. Methods Patients were treatment naive or experienced with F3 or F4 fibrosis, CHC genotype1 and HCV RNA > 10,000 IU/ml. Data were collected on host and viral factors including single nucleotide polymorphisms (SNPs) in the IL28B gene noncoding region at sites rs12979860 and rs8099917. Results 53 patients (42 Caucasian, 32 F4) were treated with TVR (n = 41) and BOC (n = 12). Seven patients were treatment naive. Subtyping was unattainable in 2 patients. Thus far, 18 patients (34%) have failed treatment and the remainder are being evaluated for SVR (24 patients with SVR-4 to date). HCV viral negativity at triple therapy week 4 was associated with treatment success in patients with rs12979860CC and rs8099917TT and rs12979860non-CC and rs8099917non-TT (OR 20.2 P-value Conclusion In our prospective cohort of CHC patients with advanced fibrosis treated with PIs, HCV RNA negativity at triple therapy week 4 and both IL28B genotypes were independent predictors of treatment outcome. Despite similar rates of early viral suppression, our preliminary data indicate more favourable end of treatment results for rs12979860CC and rs8099917TT versus rs12979860non-CC and rs8099917TT. Disclosure of Interest None Declared.

Introduction: We report the prevalence and characteristics of DRMs associated with virological failure (VF) in a prospective cohort of 59 patients with chronic HCV infection treated with telaprevir (TVR) or boceprevir (BOC) combined with pegylated interferon-alfa and ribavirin (PEG/R). Methods: All patients had baseline HCV RNA levels >10,000 IU/ml and evidence of at least bridging fibrosis. VF was defined as HCV RNA >1000 IU/ml at week 4 or 12 for TVR, or HCV RNA >100IU/ml at week 12 for BOC, or an increase of >1log10 VL from nadir. Genotypic resistance was detected using nested RT-PCR to amplify viral RNA and the first 181 amino acids of the NS3 protease were sequenced by population sequencing. Results: Forty seven patients (80%) were treated with TVR and 12 (20%) with BOC. Nineteen patients (32%) had VF (18 TVR, 1 BOC) of which DRMs were detected in 16 (84%). All patients who developed VF with DRMs had HCV genotype 1a and were treated with TVR. Mutations evolved at NS3 positions 155 and 36; Arginine to Lysine at 155 and/or Valine to Methionine, Leucine, Alanine or Valine/Methionine at 36, none of which were detected at baseline. Eight of fifteen DRMs were detected during TVR therapy, the remainder during PEG/R ‘tail’ of therapy (4 at week 4; 2 at week 8; 2 at week 12; 1 at week 15; 3 at week 24; 1 at week 36; 1 at week 48 and 1 at week 60). Those patients with VF without identifiable DRMs had breakthrough after week 12 with TVR (1 at week 22; 1 at week 24) and at week 8 with BOC. Of the VF/no DRM patients, all TVR patients had subtype 1b and severe fibrosis. The BOC treated patient had subtype 1a with moderate fibrosis. Conclusion: In this cohort treated with TVR, VF was associated with development of DRMs which were identified both before and during the PEG/R tail of therapy. Given the potential impact of DRMs on success of future therapy with protease inhibitors we suggest HCV protease sequencing for DRMs for all patients presenting with VF.