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Herpes simplex virus (HSV) and cytomegalovirus (CMV) are DNA viruses that are common among humans. Severely immunocompromised patients are at increased risk of developing HSV or CMV disease due to a weakened immune system. Antiviral therapy can be challenging because these drugs have a narrow therapeutic window and show significant pharmacokinetic variability. Above that, immunocompromised patients have various comorbidities like impaired renal function and are exposed to polypharmacy. This scoping review discusses the current pharmacokinetic (PK) and pharmacodynamic (PD) knowledge of antiviral drugs for HSV and CMV treatment in immunocompromised patients. HSV and CMV treatment guidelines are discussed, and multiple treatment interventions are proposed: early detection of drug resistance; optimization of dose to target concentration by therapeutic drug monitoring (TDM) of nucleoside analogs; the introduction of new antiviral drugs; alternation between compounds with different toxicity profiles; and combinations of synergistic antiviral drugs. This research will also serve as guidance for future research, which should focus on prospective evaluation of the benefit of each of these interventions in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background and Objectives: A great diversity of factors including viruses such as human herpes virus 1&2 (HHV-1&2), human herpes virus 5 (HHV-5), and hepatitis B virus (HBV) play key roles in sterility and it is worth noting that male infertility accounts for nearly 50% of barrenness, globally. In this regard, we evaluated the prevalence of the aforementioned viruses in semen specimens of two distinct groups of men referred to Novin Infertility Center in Mashhad, Iran. Materials and Methods: In this cross-sectional study, 300 semen samples were collected from 150 infertile and 150 fertile men. Subsequently, genomic DNA was extracted before performing multiplex polymerase chain reaction (PCR). Eventually, the results were analyzed via SPSS Statistics V.16.0. Results: Out of 300 specimens, 183 (61.1%) were positive at least for one of the forenamed viruses; genome detection of HHV-1&2, HHV-5, and HBV were 27%, 18%, 36.66%, and 4%, respectively. Conclusion: The current study found no correlation between infertility and HBV, HHV-5, and HHV-1&2, which may have to do with factors like sample size, the geographical distribution of the viruses, and the lifestyle (sexual behavior) of the participants. These results emphasize the implementation of such studies on a broader scale to determine the exact factors involved in infertility. [ABSTRACT FROM AUTHOR]

Feline calicivirus (FCV), feline alphaherpesvirus 1 (FHV-1) and feline panleukopenia virus (FPLV) as well as retroviral agents such as feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) are important viral pathogens of cats. The aim of this study was to detect and characterise FHV-1, FPLV, FeLV, FIV and feline foamy virus (FFV) in oropharyngeal, nasal and conjunctival swabs from 93 cats that had been screened for FCV previously. We wanted to determine the possible risk factors for infection with these viruses. The prevalence was found to be 12.9% for FHV-1 and 9.7% for FPLV. FIV was detected only in two samples and FeLV in one sample, whereas the presence of FFV was not demonstrated in any of the clinical samples. The statistical analysis of the results showed that breed, age, health status, and lifestyle are important predisposing factors to FHV-1 (P < 0.05). For FPLV, only clinically unhealthy animals were found to be at risk (P < 0.001). Sequence analysis revealed that the two FIV-positive samples in this study contained different (A and B) subtypes of the virus. This is the first report on the occurrence of subtype A FIV in Turkey. [ABSTRACT FROM AUTHOR]

Introduction: Differences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV‐1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated. Methods: PBMCs were collected from persons positive for IgG against HSV‐1 and having frequent, infrequent, or no herpes labialis outbreaks. The PBMCs were tested for proliferation against HSV‐1 and a fungal antigen (Candida) and immune gene expression in the presence of HSV‐1 and Candida. On day 1 after blood collection the subjects with frequent outbreaks were dosed topically on the arm once with SADBE, and their PBMCs were collected and tested 8 weeks later. Results: Those with good immune control of their HSV‐1 infection (fewer outbreaks) differ from those with poorer immune control in these ways: (1) Greater PBMC proliferation in vitro to HSV‐1, HSV‐1‐infected cell extracts, and Candida considered together (P < 0.01). (2) Higher expression of IFNG and five other immune‐related genes (P < 0.05 for each) and lower expression of IL5 and two other immune‐related genes (P < 0.05 for each) in PBMCs in vitro stimulated with HSV‐1 virus. The subjects with frequent outbreaks were treated once with SADBE, and 56 days later the PBMCs of these subjects differed from PBMCs from the same subjects taken on day 1 before treatment in exactly the same ways listed above as differences between those with good and poor immune control of HSV‐1, and at the same levels of significance. Conclusions: Higher IFNG and lower IL5 expression by PBMCs in the presence of HSV‐1 correlate with fewer herpes labialis outbreaks, and a single topical dose of SADBE to the arm of subjects with frequent herpes labialis episodes improves immune response to HSV‐1. [ABSTRACT FROM AUTHOR]

Acute respiratory distress syndrome (ARDS) is today a leading cause of hospitalization in intensive care unit (ICU). ARDS and pneumonia are closely related to critically ill patients; however, the etiologic agent is not always identified. The presence of human herpes simplex virus 1, human cytomegalovirus and Epstein-Barr virus in respiratory samples of critically ill patients is increasingly reported even without canonical immunosuppression. The main aim of this study was to better understand the significance of herpesviruses finding in lower respiratory tract of ARDS patients hospitalized in ICU. The presence of this group of herpesviruses, in addition to the research of influenza viruses and other common respiratory viruses, was investigated in respiratory samples from 54 patients hospitalized in ICU, without a known microbiological causative agent. Moreover, the immunophenotype of each patient was analyzed. Herpesviruses DNA presence in the lower respiratory tract seemed not attributable to an impaired immunophenotype, whereas a significant correlation was observed between herpesviruses positivity and influenza virus infection. A higher ICU mortality was significantly related to the presence of herpesvirus infection in the lower respiratory tract as well as to impaired immunophenotype, as patients with poor outcome showed severe lymphopenia, affecting in particular T (CD3+) cells, since the first days of ICU hospitalization. In conclusion, these results indicate that herpesviruses lower respiratory tract infection, which occurs more frequently following influenza virus infection, can be a negative prognostic marker. An independent risk factor for ICU patients with ARDS is an impaired immunophenotype. [ABSTRACT FROM AUTHOR]

Background Seasonal influenza is a prevalent respiratory infection for children and adults in Mexico. Influenza A and B viruses co-circulate and there is a need to better understand local epidemiology to inform vaccination recommendations (tri- vs. quadrivalent vaccines). We describe the 2018–2019 influenza season to estimate influenza burden, virus co-circulation and understand the vaccine match in Mexico. Methods We reviewed preliminary sentinel surveillance data for the influenza season (October 2018–May 2019) from the Mexican Health Secretariat and World Health Organization's (WHO) FluNet databases. We performed a descriptive analysis of cases and deaths due to influenza-like illness (ILI), severe acute respiratory infections (SARI) and lab-confirmed influenza to estimate the prevalence of influenza A and B circulating strains, per state and age group, and determine B strain vaccine match. Results During the 2018–2019 season in Mexico, there were 52,525 reported cases of ILI/SARI with 6,997 lab-confirmed influenza cases (28% positivity rate among ILI/SARI) and 787 (11%) deaths (Figures 1 and 2). The states with 36% of cases were Mexico City, State of Mexico, Hidalgo, Tlaxcala, and Guanajuato. More than half of the Mexican states had a high (10–14.9%) to intense (≥15%) accumulated case positivity rate of confirmed influenza in relation to ILI/SARI cases (Figure 3). Most cases were reported among the 1–9 and > 60-year-old groups. 45% of deaths occurred in State of Mexico, Hidalgo, Mexico City, Puebla, and Guanajuato. The seasonal viral profile was dominated by A/H1N1 (68%), followed by B (16%) and A/H3N2 (12%), with 90% of deaths attributed to A/H1N1. FluNet's influenza B data show Yamagata (55%) and Victoria (27%) co-circulation (Figure 1). Conclusion The 2018–2019 seasonal co-circulation of influenza A and B viruses in Mexico showed significant nation-wide morbi-mortality burden, with A/H1N1 and B/Yamagata dominance. Stronger B lineage determination is needed in Mexico to understand associated burden and prevent vaccine mismatch, considering the trivalent vaccine does not contain both B strains. Given the circulation of both influenza B lineages and the recommendation of the WHO, Mexico could enhance quadrivalent vaccine use in coming seasons to optimize protection. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Annual national estimates of influenza vaccine effectiveness (VE) typically measure protection against outpatient medically attended influenza illness. We assessed influenza VE in preventing laboratory-confirmed influenza hospitalization in children across two influenza A(H3N2)-predominant seasons. Methods Children < 18 years hospitalized with acute respiratory illness were enrolled at 7 pediatric hospitals in the New Vaccine Surveillance Network. We included subjects ≥6 months with ≤10 days of symptoms enrolled during the 2016–2017 and 2017–2018 seasons (date of first through last influenza-positive case for each site). Combined mid-turbinate and throat swabs were tested using molecular assays. We estimated age-stratified VE from a test-negative design using logistic regression to compare the odds of vaccination among cases positive for influenza with controls testing negative, adjusting for age, enrollment month, site, underlying comorbidities, and race/ethnicity. Full/partial vaccination was defined using ACIP criteria. We verified vaccine receipt from state immunization registries and/or provider records. Results Among 3441 children with complete preliminary data, in 2016–2017, 156/1,710 (9%) tested positive for influenza: 91 (58%) with influenza A(H3N2), 5 (3%) with A(H1N1), and 60 (38%) with B viruses. In 2017–2018, 193/1,731 (11%) tested positive: 87 (45%) with influenza A(H3N2), 47 (24%) with A(H1N1), and 58 (30%) with B. VE for all vaccinated children (full and partial) against any influenza was 48% (95% confidence interval, 26%–63%) in 2016–2017 and 45% (24%–60%) in 2017–2018. Combining seasons, VE for fully and partially vaccinated children against any influenza type was 46% (32%–58%); by virus, VE was 30% (4%–49%) for influenza A(H3N2), 71% (46%–85%) for A(H1N1), and 57% (36%–70%) for B viruses. There was no statistically significant difference in VE by age or full/partial vaccination status for any virus (table). Conclusion Vaccination in the 2016–2017 and 2017–2018 seasons nearly halved the risk of children being hospitalized with influenza. These findings support the use of vaccination to prevent severe illness in children. Our study highlights the need for a better understanding of the lower VE against influenza A(H3N2) viruses. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]

Background Seroprevalence and surveillance studies indicate that influenza C virus (ICV) infection is common among humans, and initial exposure occurs early in life. ICV often causes milder disease than influenza A and B viruses, but the mechanisms underlying differences in pathogenicity remain poorly understood. Methods To compare early events of infection in natural target sites, we cultured primary human tracheal/bronchial epithelial cells under air-liquid interface conditions to allow differentiation. We-infected these cells with human strains of influenza A, B or C virus. Cells were infected at low MOI (0.1) to ensure populations of directly infected cells and uninfected neighboring cells. To compare the early immune response and cell tropism among these viruses, we performed single-cell RNA sequencing of mock- and influenza-infected cells. In parallel, we infected cells pretreated with interferon to mimic later rounds of infection after an early immune response is initiated. Results Infection of primary cells by all three viruses was confirmed by RT-qPCR of bulk cell lysates. As expected, prior exposure to interferon β results resulted in reduced levels of viral transcripts. At the single-cell level, we identified expression of genes associated with specific cell types, including basal, ciliated and secretory cells. We also identified expression of interferon stimulated genes, but these genes were not homogeneously expressed among all cell subpopulations and varied among cultures infected with different influenza viruses. We also found different patterns in gene expression in cells previously exposed to interferon, suggesting that host environment varies over subsequent rounds of infection. Conclusion Single-cell sequencing is an important tool for studying the host response to influenza infection in complex cellular environments such as the respiratory tract, in which cells vary in their susceptibility to infection and antiviral response. Further analysis will characterize differences among directly infected vs. neighboring cells and correlate responses with pathogenicity. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background Studies have demonstrated that optimal protection against childhood influenza requires two "priming" doses of influenza vaccine in the first season of vaccination. Two doses of influenza vaccine are recommended for US children aged 6 months-8 years who received ≤1 dose in prior seasons. We examined risk of influenza among children fully or partially vaccinated during study seasons and vaccine effectiveness (VE) by the number of priming doses. Methods Analyses included children aged 6 months-17 years enrolled during outpatient visits for acute illness for ≤7 days with cough in the US Influenza Vaccine Effectiveness Network during 2014–2015 through 2017–2018. Participants' respiratory specimens were tested for influenza by rRT-PCR. Vaccination histories back to birth year were obtained from electronic immunization records. VE was calculated by comparing vaccination odds among influenza-positive cases to test-negative controls, as 100 × (1 − odds ratio) adjusted for season, site, age, high-risk status, and calendar time. Results Of 7,583 children, 6,362 (84%) had received ≥1 dose in their lifetime. Among vaccinated children, 90% were primed prior to the enrollment season, and 80% were primed prior to age 2 years. Most (55%) received two priming doses in their first season. Among children recommended to receive two priming doses in the enrollment season, receipt of two doses vs. one was associated with a lower risk of influenza illness (aOR: 0.60; 95% CL: 0.36, 1.00). VE of ≥1 dose in the enrollment season against any influenza among unprimed children was 53% (95% CL: 36, 66). VE of ≥1 dose in the enrollment season was similar among children primed with one dose in their first season (46%; 95% CL: 34, 55) and among those primed with two doses (46%; 95% CL: 35, 55). Overall results were similar when stratified by age and for A/H3N2 viruses, which predominated during study years. Conclusion Among the US children recommended to receive two priming doses of vaccine in the enrollment season, receipt of two doses provided optimal protection. VE in seasons after the priming did not differ by the number of priming doses. Results were driven by predominance of A/H3N2 viruses and may not be similar for A/H1N1pdm09 or B viruses. Current US influenza vaccine recommendations for children are effective and appropriate. Disclosures All Authors: No reported Disclosures. [ABSTRACT FROM AUTHOR]