C. De Gascun

Hepatitis B virus vaccine failure resulting in chronic hepatitis B infection

A 38 year old asymptomatic male presented to the sexually ransmitted infections (STI) clinic in a large teaching hospital in pril 2006 for a sexual health screen. He had no significant past edical history although he had engaged in several episodes of nprotected sexual intercourse with male partners in the precedng six months. Serological investigations indicated recent/active reponema pallidum infection for which he was treated. Addiional serological investigations for human immunodeficiency irus (HIV), hepatitis B virus (HBV) – comprising hepatitis B surace antigen (HBsAg), antibody to hepatitis B core (anti-HBc) and

Transfusion-transmitted hepatitis B virus (HBV) infection from an individual-donation nucleic acid (ID-NAT) non-reactive donor.

Lookback was initiated upon notification of an acute HBV infection in a repeat Irish donor, 108 days post‐donation. The donation screened non‐reactive by individual‐donation nucleic acid testing (ID‐NAT) using the Procleix Ultrio Elite multiplex assay and again when the archived sample was retested, but the discriminatory assay for HBV was reactive. The immunocompromised recipient of the implicated red cell component was tested 110 days post‐transfusion, revealing a HBV DNA viral load of 470 IU/ml. Genotype C2 sequences identical across two regions of the HBV genome were found in samples from the donor and recipient.

Is universal screening for hepatitis C infection prior to commencing antitumour necrosis factor-α therapy necessary?

Screening for hepatitis C virus (HCV) prior to the commencement of antitumour necrosis factor (anti‐TNF)‐α therapies for dermatological disease is recommended for all patients.

A24 Role of phylogenetic analysis in epidemiological case definitions during an outbreak of HIV-1 in people who inject drugs in Ireland

tion patterns is limited. In this study, we employed a Bayesian phylogeographic approach to reconstruct the spatio-temporal dispersion pattern of this clade in Afghanistan and Iran for the first time. We performed a secondary data analysis on eligible HIV-1 CRF35_AD (gag and pol) sequences available in the Los Alamos HIV database (432 sequences available from Iran, 16 sequences available from Afghanistan, and a single CRF35_ADlike pol sequence available from USA). Sequences were excluded prior to analysis if they showed evidence of incorrect subtype assignment, frameshift, or drug resistance mutations, and/or stop codon positions. Subtype assignment was confirmed by maximum likelihood phylogenetic analysis. In order to reconstruct the spatio-temporal history of CRF35_AD, we used discrete Bayesian phylogeographic model in BEAST v1.8.1. Between-country viral dispersion rates were tested with Bayesian Stochastic Search Variable Selection method as implemented in SPREAD v1.0.7, and were considered as significant when Bayes factor values were >3. We checked the robustness of the key parameter estimates through a sensitivity analysis, using different priors and data subsets. The findings suggested that CRF35_AD sequences were genetically similar to parental sequences from Kenya and Uganda, and to a set of subtype A1 sequences available from Afghan refugees living in Pakistan. Our results also showed that across all phylogenies, Afghan and Iranian CRF35_AD sequences formed a monophyletic cluster (posterior clade credibility> 0.9). The divergence date of this cluster was estimated to be between 1990 and 1992. Within this cluster, a bidirectional dispersal of the virus was observed across Afghanistan and Iran. We could not clearly identify if Afghanistan or Iran first established or received this epidemic, as the root location of this cluster could not be robustly estimated. Three CRF35_AD sequences from Afghan refugees living in Pakistan nested among Afghan and Iranian CRF35_AD branches. However, the CRF35_AD-like sequence available from USA diverged independently from Kenyan subtype A1 sequences, suggesting that it may not be a true CRF35_AD lineage. The CRF35_AD viruses from Afghanistan, Iran, and Afghan refugees living in Pakistan seem to constitute a single epidemic, with multiple genetic exchanges among these populations. The date of onset for this epidemic (1990–1992) coincides with the rise of heroin production in Afghanistan (1970s). This highlights the potential role of drug trafficking in epidemic ignition in this region. Mass migration of Afghan refugees and illegal workers to Iran may be other possible contributors to among-country virus transmission.

Diagnosis of rotavirus infection in a vaccinated population: Is a less sensitive immunochromatographic method more suitable for detecting wild-type rotavirus than real-time RT-PCR?

BACKGROUND Diagnosis of wild-type rotavirus disease may be complicated by the detection of vaccine-derived virus which can be detected in stool samples following immunisation. We evaluate an immunochromatographic assay and real-time RT-PCR to determine which is more suitable for the detection of wild-type rotavirus. OBJECTIVES To compare the Ct values of wild-type rotavirus and Rotarix determined by real-time RT-PCR. To establish the Ct value corresponding to the limit of detection of the immunochromatographic Combi-Strip method (Coris, BioConcept). STUDY DESIGN Retrospective review of real-time RT-PCR Ct values was performed on 100 samples tested by a pan-rotavirus assay (n = 50 wild-type, n = 50 Rotarix). Secondly the limit of detection of the Combi-Strip assay was determined by testing; wild-type rotavirus (n = 33, Ct range 6.85-34.26) samples, Rotarix (n = 9, Ct range 20.86-34.26) samples and rotavirus negative (n = 21) samples. RESULTS The median Ct of 50 wild-type rotavirus was Ct 12.43; range 6.11-32.66 compared with the median of 50 Rotarix, Ct 29.09; range 18.91-35.28, p=<0.0001. The limit of detection of the Combi-Strip method was approximately Ct 18. The 21 rotavirus negative samples were negative by real-time RT-PCR and Combi-Strip. CONCLUSIONS We found the Ct value was significantly lower, and therefore the viral load higher, for wild-type rotavirus compared to detectable Rotarix. The Combi-Strip assay detects most wild-type infections; however, it lacks sensitivity to detect low-level wild-type rotavirus and, beneficially, is unlikely to detect Rotarix. It is not a more suitable method than real-time RT-PCR when a definitive rotavirus result is required.

A12 Predictors of treatment failure among Irish individuals infected with hepatitis C virus

Currently approved neuraminidase inhibitors (NAI) for the treatment of influenza A virus infections are prone to induce viral drug resistance development due to the rapid evolutionary dynamics of the neuraminidase (NA) and hemagglutinin (HA) proteins. Both HA and NA proteins are subject to antigenic drift and the epistatic interactions within and between these proteins can lead to genetic diversity that enables the virus to easily develop resistant mutations under selective pressure in a host. To study NAI resistance and clinical outcome, the global observational Influenza Resistance Information Study (IRIS; NCT00884117) was conducted. Patients that were clinically diagnosed with influenza were enrolled in the study. Nasal and throat swabs taken at baseline and on days 3, 6, and 10 were assessed by semi-quantitative real-time reverse transcription polymerase chain reaction (RT-qPCR) to determine the influenza virus type and subtype. NAI resistance was initially determined by mutation specific RT-PCR, Sanger sequencing and phenotypic susceptibility analysis. Genetic resistance mutations to oseltamivir were detected in 61 patients (43 H1N1pdm [H275Y] and 18 H3N2 [R292K]) by mutation specific PCR. Subsequently, samples of 43 patients were subjected to deep sequencing analysis to characterize both the betweenand the within-host diversity and the evolutionary process of the HA and NA proteins of infected patients. The NAI resistance mutations (H275Y and R292K) in the NA protein of the H1N1pdm and H3N2 viruses were either detected in day 3 samples or at later time point. Additionally, viruses in several individuals had mutations that were located across the whole HA and NA proteins. Some low frequency mutations such as D114N, S200P, and D239N, that were located in the antigenic sites or near the receptor binding site of the HA protein, became fixed in the later time point viral samples. Also, some mutations in HA may have occurred in concert with the resistance mutations in NA. Further genetic analyses and phylogeny should provide further insights in the emergence of mutations in individual hosts and the larger population.

Circulating rotavirus genotypes in the Irish paediatric population prior to the introduction of the vaccination programme

BackgroundRotavirus is the leading cause of viral gastroenteritis in children, and it is anticipated that the introduction of the Rotarix™ vaccine (GlaxoSmithKline Biologicals S.A., Rixensart, Belgium) into the Irish immunisation schedule will result in a significant reduction of rotavirus-associated disease. In the pre- and post-vaccination eras, it is important to determine circulating strains of rotavirus to assess vaccine effectiveness, to monitor vaccine failures, and to detect potential emerging strains.AimThis study was a collaboration between the Temple Street Children’s University Hospital (TSCUH), Dublin, and the National Virus Reference Laboratory (NVRL), Dublin, to determine the then circulating rotavirus strains in a paediatric hospital.MethodIn the 2015/2016 period (July 2015–June 2016) 89 faecal samples from paediatric patients (53 from TSCUH, 36 from other hospitals) were characterised.ResultsThe results showed G1P[8] to be the predominant genotype (57%), followed by G9P[8] (34%), G4P[8] (6%), G2P[4] (2%), and G12P[8] (1%).ConclusionThis distribution of genotypes is comparable to those found in other European countries prior to vaccination suggesting that the vaccine should be highly efficacious in the Irish population.

Effectiveness of interferon-free therapy for the treatment of HCV-patients with compensated cirrhosis treated through the Irish early access program

ABSTRACT Background: We investigated the real-world effectiveness of interferon-free regimens for the treatment of patients with compensated cirrhosis infected with hepatitis C virus (HCV). Method: Using the Irish national HCV treatment registry, the effectiveness and safety of interferon-free regimens for HCV-infected patients treated between April 2015 and August 2016, was determined. Results: A SVR12 was achieved in 86% of subjects treated with sofosbuvir/ledipasvir ± ribavirin (SOF/LDV±RBV), 93% treated with paritaprevir, ombitasvir and ritonavir combined with dasabuvir ± ribavirin (3D±RBV) and 89% treated with sofosbuvir/daclatasvir ± ribavirin (SOF/DCV±RBV). The discontinuation rate was 5% and the on-treatment mortality rate was 1%. Conclusion: The availability of interferon-free regimens represents a significant breakthrough for the treatment of HCV infection. Treatments options, with high SVR12 rates, are now available for patients with compensated cirrhosis who were unsuitable for treatment with interferon-based regimens. Data obtained from studies conducted in real world practice provide robust information fundamental for input into future economic evaluations for agents used for the treatment of HCV infection.

Progressive Multifocal Leucoencephalopathy and psoriasis

Progressive multifocal leucoencephalopathy (PML) is a progressive demyelinating inflammatory process in which oligodendrocytes are affected by the John Cunningham polyoma virus (JCV). John Cunningham virus infection occurs in childhood and up to 70% of adults have detectable antibodies. This article is protected by copyright. All rights reserved.

Letter to the Editor: Smoking and older age associated with mumps in an outbreak in a group of highly-vaccinated individuals attending a youth club party, the Netherlands, 2012

To the Editor: In their recent article, Ladbury et al. present an investigation of an outbreak of mumps in a highly vaccinated group attending a youth club party in March 2012 [1]. The article suggested that crowded social events and smoking may facilitate spread of mumps virus among a highly vaccinated population and that waning immunity may also play a role. We would like to address a number of interesting points.