CYP450 2D6 Genotype and Flecainide Efficacy in the Treatment of Patients with Lone Atrial Fibrillation

Background: CYP2D6 has been linked to one of four phenotypes: a) ultra-rapid metabolizers (UM), with multiple gene copies; b) extensive metabolizers (EM), with a single wild type gene copy, considered normal; c) intermediate (IM) metabolizer, with decreased enzymatic activity; and d) poor metabolizers (PM) with no detectable enzymatic activity.  By altering the drug dose-plasma concentration relationship, these differences may lead to severe toxicity and or therapeutic failure.Objectives: The aim of this study was to determine the correlation between CYP2D6 polymorphisms and both efficacy and magnitude of adverse reactions of flecainide, a class IC antiarrhythmic agent.Methods: Patients with Lone Atrial fibrillation (AF) were enrolled in a 2-arm prospective study: patients started on flecainide at the initial visit, then were followed up at 3 and 6 months intervals (arm 1) or exhibited AF recurrences on flecainide, defined as treatment failure (arm 2).  Data about recurrence of AF, side effects, and demographics were collected. Genotyping was performed using AmpliChipTM CYP450.Results: A total of 26 lone AF patients were enrolled (12 in arm 1, and 14 in arm 2).  The mean age was 47± 10.8 years and 56.2 ± 10.8 years respectively.  Among the analyzed phenotypes the following distribution was found: 1/26 (3.8%) UM, 19/26 (73%) EM, 5/26 (19%) IM, 1/26 (3.8%) PM.Conclusions: In this small series of patients with lone atrial fibrillation, most patients were found to be extensive metabolizers of flecainide.  There was no statistically significant correlation between the patients' genotype, and flecainide efficacy / side effects

The seroprevalence of West Nile Virus in Israel: A nationwide cross sectional study.

West Nile Virus (WNV) is endemic in Israel, affecting yearly 40-160 individuals. Israel is located on a central migratory path between Africa and Eurasia and most West Nile Fever (WNF) cases reported in recent years were among residents of the coastal plain. The aim of the study was to evaluate the seroprevalence of WNV among the Israeli population and to assess correlates for WNV infection. A cross-sectional nationwide serologic survey was conducted using 3,145 serum samples collected by the national Israeli serum bank during 2011-2014, representing all age and population groups in Israel. Prevalence rates of WNV IgG antibodies were determined. Logistic regressions models were applied to assess the associations between demographic characteristics and WNV seropositivity. 350 samples were positive to WNV (11.1%; 95%CI: 10.0-12.3%). In the multivariable analysis, there was a significant association between seropositivity and the Arab population group vs. Jews and others (OR = 1.86, 95%CI: 1.37-2.52), the time lived in Israel [50-59 years vs. 0-9 years; OR = 10.80 (95%CI: 1.03-113.46) and ≥60 years vs. 0-9 years; OR = 14.00 (1.32-148.31)] residence area] Coastal Plain, Inland Plain (Shfela) and Great Rift Valley vs. Upper Galilee; OR = 2.24 (95%CI: 1.37-3.65), OR = 2.18 (95%CI: 1.18-4.03), OR = 1.90 (95%CI: 1.10-3.30), respectively [and rural vs. urban settlement (OR = 1.65, 95%CI: 1.26-2.16). People, who reside in the Coastal Plain, Inland Plain and Great Rift Valley, should be aware of the risk of contracting WNV and reduce exposure to mosquito bites, using insect repellents, and wearing protective clothing. The Ministry of Environmental Protection should be active in reducing the mosquito population by eliminating sources of standing water, a breeding ground for mosquitoes

Seropositivity of measles antibodies in the Israeli population prior to the nationwide 2018 – 2019 outbreak

Measles vaccine is administered in Israel as part of the routine childhood immunization program, at ages 1 and 6 years. In this study, we assessed seropositivity of the Israeli population against measles before the onset and propagation of the 2018–2019 measles outbreak. From the Israel Center for Disease Control National Serum Bank, 3,164 samples collected during 2015 were tested for measles antibodies. All the tests were performed using Enzyme-Linked Immunosorbent Assay (ELISA) commercial kit (Enzygnost, Anti-Measles Virus/IgG: Behring, Marburg, Germany). The overall seropositivity rate for measles was 90.7%. The seropositivity rate at 6 months and younger was 48.9%, and decreased to 3.8% among infants aged 6–11 months. Seropositivity increased to 90.7% in the 1-4-year age group, and reached 96.1% for 5–9 year-old children. Our results suggest high immunity in the Israeli population against measles virus, but not high enough to prevent outbreaks because of pockets of specific population groups with low immunization coverage. Infants between ages 6 and 11 months and children younger than 2 years had the lowest seropositivity rates being the age groups with the highest attack rates of measles during the epidemic of 2018. Efforts should be aimed at avoiding any delay in vaccination once a child reaches the age of 1 year and improving immunity levels in children aged 1–4 years

The Concordance between Mumps and Rubella Sero-Positivity among the Israeli Population in 2015

Mumps and rubella are vaccine-preventable viral diseases through the measles-mumps-rubella-varicella (MMRV) vaccine, administered at 12 months and again at 6 years. We assessed the sero-prevalence of mumps and rubella, identified factors associated with sero-negativity, and evaluated concordance between mumps and rubella sero-positivity. A national cross-sectional sero-survey was conducted on samples collected in 2015 by the Israel National Sera Bank. Samples were tested for mumps and rubella IgG antibodies using an enzyme-linked immunosorbent assay. Of 3131 samples tested for mumps IgG, 84.8% (95%CI: 83.5–86.0%) were sero-positive. Sero-negativity for mumps was significantly associated with age (high odds ratios observed in infants younger than 4 years and 20–29 years old subjects). Of 3169 samples tested for rubella IgG antibodies, 95.2% (95%CI: 94.4–95.9%) were sero-positive. Rubella sero-negativity was significantly associated with age (high odds ratios observed in children younger than 4 years old and adults older than 30 years), males, Jews, and others. Concordant sero-positivity for both mumps and rubella viruses was observed in 83.9% of the tested samples. The Israeli population was sufficiently protected against rubella but not against mumps. Since both components are administered in the MMRV vaccine simultaneously, the mumps component has a lower uptake than rubella and quicker waning

Seroposivity of IgG antibodies against WNV in Jews and others and in Arabs by age group.

<p>Seroposivity of IgG antibodies against WNV in Jews and others and in Arabs by age group.</p

Multivariate logistic regression analysis of associated possible correlates for West Nile virus in subjects in Israel.

<p>Multivariate logistic regression analysis of associated possible correlates for West Nile virus in subjects in Israel.</p

Demographic characteristics of the study participants (N = 3,145).

<p>Demographic characteristics of the study participants (N = 3,145).</p

Seroprevalence and univariate logistic regression analysis of associated possible correlates for West Nile virus in subjects in Israel.

<p>Seroprevalence and univariate logistic regression analysis of associated possible correlates for West Nile virus in subjects in Israel.</p