Human cytomegalovirus (HCMV) strains may be genotyped based on polymorphisms that exist within the UL144 gene, which is one of 19 viral genes lost in attenuated laboratory strains. In the present study, UL144 genotypes in congenitally infected babies (congenital cytomegalovirus [cCMV]) were determined, and the relationship between the genotype, viral load, cytokine profile, and patient developmental outcome was investigated. All cCMV infections identified during 2006 and 2007 were included (n ‫؍‬ 29). A portion of the infants were clinically assessed at birth and at 12 to 18 months postinfection for cCMV clinical sequelae (n ‫؍‬ 18/29). The plasma viral load (PVL) was requested for 23/29 patients, and the UL144 genotype was determined (n ‫؍‬ 27/29). The cytokine profile in patient plasma or serum was assessed (n ‫؍‬ 20/29). UL144 genotypes A, B, and C were detected within the cCMV population at 33.3%, 29.6%, and 25.9%, respectively. UL144 A and C were associated with a high PVL (P < 0.04). Furthermore, a significant association between the developmental outcome and UL144 A and C was observed (P < 0.04). Only patients infected with UL144 B and A/B were described as having a normal clinical outcome. In addition, a significant correlation between interleukin 10 (IL-10) levels and the PVL was observed (P < 0.04); however, there was no association between the genotype and the cytokine profile. The present study determined that the specific detection of UL144 genotypes A and C was indicative of serious cCMV infection and more likely to lead to long-term cCMV-associated clinical manifestations. The inclusion of HCMV UL144 genotyping along with the recommended PVL monitoring following cCMV diagnosis may aid prediction of the clinical outcome.

We describe 3 cases of adolescent varicella-zoster virus reactivation, complicated by aseptic meningitis, presenting to our institution in a 3-year period. These cases highlight varicella-zoster virus reactivation as an important cause of aseptic meningitis in the differential diagnosis of healthy adolescents, even in the absence of a characteristic exanthem. Evidence-based management recommendations are needed.

TPS473 Background: Gastric Cancer (GC) is the third most common cause of cancer related deaths worldwide. The median overall survival of patients with stage 4 disease is approximately 1 year. Current accepted treatment approach with chemotherapy is applied with little consideration for known genetic or biologic heterogeneity. Whilst immune-based approaches in GC look promising it is clear that single-agent PD1/PDL1 inhibition benefit a minority. We must clarify a means of identifying prospectively those patients who may benefit from this treatment. A recent landmark paper by The Cancer Genome Atlas (TCGA) proposed a classification of GC into four subtypes: Epstein-Barr-virus (EBV)-positive, microsatellite instable (MSI), chromosomal instable (CI), and genomically stable (GS). Two of the four – EBV and MSI subtypes – are likely to be immunogenic and amenable to PD1/PDL1 inhibition. Recent advances have shown EBV-positive tumors to be infiltrated by lymphocytes and be enriched for PDL1. Methods: This single centre single-arm pilot study in gastric or junctional adenocarcinoma will explore the hypothesis that administering anti-PDL1 therapy (Avelumab) in a prospectively identified population enriched for potential responders will result in improved outcomes. The anticipated frequency of EBV associated-GC (c10%) means that approximately N = 100 patients will be screened to identify N = 10 participants. If a positive signal for efficacy is seen this will provide a basis for a larger, multicentre study. Previously treated Patients with confirmation of stage 4 EBV- positive gastric or oesophago-gastric adenocarcinoma meeting eligibility criteria will be enrolled. Avelumab will be administered at a dose of 10mg/kg IV every 14days. Primary endpoint is to determine the 6-month progression free survival (PFS) of Avelumab in EBV-associated GC. Secondary endpoints include overall response rate, overall survival, median PFS time and feasibility/accrual rate at 12 months. Exploratory endpoints will be to evaluate changes in immune parameters in the peripheral blood over time. Kaplan-Meier methods for primary efficacy endpoint with two-tailed one-sample proportion test will be used to evaluate the evidence to reject the null hypothesis. Clinical trial information: 2018-002085-39.

IntroductionNatalizumab treatment for relapsing remitting multiple sclerosis (RRMS) is associated with a risk of progressive multifocal leukoencephalopathy (PML) due to reactivation of latent JC virus (JCV). We prospectively screened for JCV DNA in urine & serum before treatment to identify those at higher risk of PML. Recently a two-step ELISA test to detect JCV antibodies (JCVAb) as a marker for prior exposure has been developed.AimTo compare rates of detection of serum JCVAb with those of JCV DNA in serum & urine by PCR in a natalizumab treated cohort.MethodsQualitative real-time PCR was prospectively used on urine & serum to identify JCV DNA. JCVAb testing by a two-step ELISA technique was undertaken in the same group and results compared.ResultsOf 81 patients treated with natalizumab, 36/81 tested positive for JCVAb. JCV DNA in urine was identified in 10/81 (12%) with no positive serum tests; all ten had positive JCVAbs. 26/36 (72%) in the higher risk category for PML had not been identified by PCR.ConclusionPCR testing detects JCV DNA in blood or urine but does not identify patients with latent JCV. Establishing JCVAb status allows clinicians to more effectively counsel patients with regard to their risk of PML.