Seasonal influenza vaccination policies in the Eastern Mediterranean Region:Current status and the way forward

Background: The World Health Organization recommends annual influenza vaccination, especially in high-risk groups. Little is known about the adoption and implementation of influenza vaccination policies in the Eastern Mediterranean Region. Methods: A survey was distributed to country representatives at the ministries of health of the 22 countries of the Region between December 2016 and February 2017 to capture data on influenza immunization policies, recommendations, and practices in place. Results: Of the 20 countries that responded to the survey, 14 reported having influenza immunization policies during the 2015/2016 influenza season. All countries with an influenza immunization policy recommended vaccination for people with chronic medical conditions, healthcare workers and pilgrims. Two of the 20 countries did not target pregnant women. Eight countries used the northern hemisphere formulation, one used the southern hemisphere formulation and nine used both. Vaccination coverage was not monitored by all countries and for all target groups. Where reported, coverage of a number of target groups (healthcare workers, children) was generally low. Data on the burden of influenza and vaccine protection are scarce in the Region. Conclusions: Despite widespread policy recommendations on influenza vaccination, attaining high coverage rates remains a challenge in the Eastern Mediterranean Region. Tackling disparities in influenza vaccine accessibility and strengthening surveillance systems may increase influenza vaccine introduction and use.</p

IL-1 stimulates ceramide accumulation without inducing apoptosis in intestinal epithelial cells.

BACKGROUND: In inflammatory bowel disease (IBD), cytokine levels (such as interleukin-1 (IL-1)) are elevated. We have shown previously that IL-1 activates phospholipid signaling pathways in intestinal epithelial cells (EEC), leading to increased ceramide levels. AIM: To determine whether ceramide induces apoptosis in IEC. METHODS: Apoptosis was evaluated by annexin-V binding or Hoechst nuclear staining. Levels of bcl-2, bcl-x, bax, p53 and p21 were determined by Western blotting, and celi cycle analysis was determined by flow cytometry. RESULTS: IL-1 increased ceramide accumulation in a time-dependent and concentration-dependent manner with a peak response at 4 h, with [IL-1] = 30 ng/ml. Neither IL-1 nor ceramide induced apoptosis in EEC, but they increased bcl-2 levels and decreased bax and p21 levels without affecting bcl-x and p53 levels. They also caused a slight but significant increase in the G2/M phase. These data suggest a role for ceramide in IBD and suggest a possible mechanism for the enhanced tumorigenic activity in IBD patients

Bronchiolitis Admissions in a Lebanese Tertiary Medical Center: A 10 Years' Experience

Bronchiolitis and more specifically respiratory syncytial virus (RSV) bronchiolitis is a leading cause of global childhood morbidity and mortality. Despite the previous identification of possible risk factors associated with the severity of bronchiolitis, the data from Lebanon remains limited. We described the burden of bronchiolitis hospitalizations in children under 5 years of age in a tertiary care center in Lebanon from October 2004 to October 2014 and identified the risk factors associated with severe bronchiolitis. This was a retrospective cohort study conducted at the American University of Beirut Medical Center. Records of children younger than 5 years of age admitted with a diagnosis of bronchiolitis were reviewed. More than half the patients were RSV positive. RSV bronchiolitis was found to be significantly associated with longer hospital stay compared to children with non-RSV bronchiolitis (P = 0.007). Children exposed to smoking had an increased risk for longer hospital stay (P = 0.002) and were more likely to require ICU admission (P &lt; 0.001) and supplemental oxygen (P = 0.045). Congenital heart disease was found to be a significant risk factor for severe bronchiolitis (P &lt; 0.005).Conclusion: Patients with RSV bronchiolitis had a longer hospital stay compared to patients with non-RSV bronchiolitis. Exposure to smoking was associated with a more severe and complicated RSV infection. Congenital heart disease was the only risk factor significantly associated with all markers of bronchiolitis disease severity

Apoptosis and the activity of ceramide, Bax and Bcl-2 in the lungs of neonatal rats exposed to limited and prolonged hyperoxia

BACKGROUND: The aim of the study is to examine the effect of limited and prolonged hyperoxia on neonatal rat lung. This is done by examining the morphologic changes of apoptosis, the expression of ceramide, an important mediator of apoptosis, the expression of inflammatory mediators represented by IL-1β and the expression of 2 proto-oncogenes that appear to modulate apoptosis (Bax and Bcl-2). METHODS: Newborn rats were placed in chambers containing room air or oxygen above 90% for 7 days. The rats were sacrificed at 3, 7 or 14 days and their lungs removed. Sections were fixed, subjected to TUNEL, Hoechst, and E-Cadherin Staining. Sections were also incubated with anti-Bcl-2 and anti-Bax antisera. Bcl-2 and Bax were quantitated by immunohistochemistry. Lipids were extracted, and ceramide measured through a modified diacylglycerol kinase assay. RT-PCR was utilized to assess IL-1β expression. RESULTS: TUNEL staining showed significant apoptosis in the hyperoxia-exposed lungs at 3 days only. Co-staining of the apoptotic cells with Hoechst, and E-Cadherin indicated that apoptotic cells were mainly epithelial cells. The expression of Bax and ceramide was significantly higher in the hyperoxia-exposed lungs at 3 and 14 days of age, but not at 7 days. Bcl-2 was significantly elevated in the hyperoxia-exposed lungs at 3 and 14 days. IL-1β expression was significantly increased at 14 days. CONCLUSION: Exposure of neonatal rat lung to hyperoxia results in early apoptosis documented by TUNEL assay. The early rise in Bax and ceramide appears to overcome the anti-apoptotic activity of Bcl-2. Further exposure did not result in late apoptotic changes. This suggests that apoptotic response to hyperoxia is time sensitive. Prolonged hyperoxia results in acute lung injury and the shifting balance of ceramide, Bax and Bcl-2 may be related to the evolution of the inflammatory process

Hospital-based surveillance study of rotavirus gastroenteritis in children under 5 years of age in Lebanon

AbstractBackgroundRotavirus (RV) is a major cause of gastroenteritis (GE) in infants and young children globally, with rotavirus gastroenteritis (RVGE) causing dehydration due to diarrhea and frequently leading to hospitalization. Epidemiological data on RVGE in Lebanon are lacking, therefore this study aims to collect such baseline data.MethodsWe conducted multicenter, hospital-based surveillance across Lebanon to estimate the proportion of diarrheal hospitalizations attributable to RV in children under 5 years of age. Medical history, GE symptoms, treatment prior to hospitalization and demographics were obtained from medical records and parent/guardian interviews. The severity of GE episodes was determined using the 20-point Vesikari scale (score ⩾11 was considered severe). Stool samples were analyzed for RV using an enzyme immunoassay and for strain prevalence using reverse transcriptase polymerase chain reaction.ResultsBetween April 2007 and September 2008, a total of 534 subjects were enrolled, of whom 491 were included in the final analysis. GE attributable to RV was 27.7% and nearly 75% of the RVGE cases occurred in children under 2 years of age. No differences were observed between the severity of signs and symptoms in RV positive and negative subjects. Hospitalization occurred mainly between December–March and lasted for a median of 3 days. Treatment primarily consisted of intravenous rehydration and almost all subjects (96.1%) had recovered by the time of discharge. Prevalent circulating G and P types were G4 (36.9%), G1WT (29.2%), P[8]WT (77.7%) and P[4] (17.7%); the most common circulating RV strain was G4P[8]WT (36.9%).ConclusionRVGE hospitalizations are prevalent in children under 5 years of age in Lebanon. This baseline data might be useful for decision makers when initiating measures, such as vaccination, to prevent the disease

Ceramide Activates the Stress-activated Protein Kinases

Tumor necrosis factor alpha (TNF alpha) activates the stress-activated protein kinases (SAPKs, also known as Jun nuclear kinases or JNKs) resulting in the stimulation of AP-1-dependent gene transcription and induces the translocation of NF kappa B to the nucleus resulting in the stimulation of NF kappa B-dependent gene transcription. A potential second messenger for these signaling pathways is ceramide, which is generated when TNF alpha activates sphingomyelinases. We show that treatment of HL-60 human promyelocytic cells with exogenous sphingomyelinase leads to rapid stimulation of JNK/SAPK activity, an effect not mimicked by treatment with phospholipase A2, C, or D. Further, JNK/SAPK activity is stimulated 2.7- and 2.8-fold, respectively, in cells exposed to C2-ceramide (5 microM) or TNF alpha (10 ng/ml). The prolonged stimulation of this kinase activity by C2-ceramide is similar to that previously reported for TNF alpha. In contrast, the related mitogen-activated protein kinases ERK1 and ERK2 are weakly stimulated following TNF alpha treatment (1.5-fold) and are inhibited by C2-ceramide treatment. TNF alpha also potently stimulates NF-kappa B DNA binding activity and transcriptional activity, but these effects are not mimicked by addition of C2-ceramide or sphingomyelinase to intact cells. Furthermore, TNF alpha, sphingomyelinase, and C2-ceramide induce c-jun, a gene that is stimulated by the ATF-2 and c-Jun transcription factors. These data suggest that ceramide may act as a second messenger for a subset of TNF alpha's biochemical and biological effects

Genotypes and serotype distribution of macrolide resistant invasive and non- invasive Streptococcus pneumoniae isolates from Lebanon

<p>Abstract</p> <p>Background</p> <p>This study determined macrolide resistance genotypes in clinical isolates of <it>Streptococcus pneumoniae </it>from multiple medical centers in Lebanon and assessed the serotype distribution in relation to these mechanism(s) of resistance and the source of isolate recovery.</p> <p>Methods</p> <p>Forty four macrolide resistant and 21 macrolide susceptible <it>S. pneumoniae </it>clinical isolates were tested for antimicrobial susceptibility according to CLSI guidelines (2008) and underwent molecular characterization. Serotyping of these isolates was performed by Multiplex PCR-based serotype deduction using CDC protocols. PCR amplification of macrolide resistant <it>erm </it>(encoding methylase) and <it>mef </it>(encoding macrolide efflux pump protein) genes was carried out.</p> <p>Results</p> <p>Among 44 isolates resistant to erythromycin, 35 were resistant to penicillin and 18 to ceftriaxone. Examination of 44 macrolide resistant isolates by PCR showed that 16 isolates harbored the <it>erm</it>(B) gene, 8 isolates harbored the <it>mef </it>gene, and 14 isolates harbored both the <it>erm</it>(B) and <it>mef </it>genes. There was no amplification by PCR of the <it>erm</it>(B) or <it>mef </it>genes in 6 isolates. Seven different capsular serotypes 2, 9V/9A,12F, 14,19A, 19F, and 23, were detected by multiplex PCR serotype deduction in 35 of 44 macrolide resistant isolates, with 19F being the most prevalent serotype. With the exception of serotype 2, all serotypes were invasive. Isolates belonging to the invasive serotypes 14 and 19F harbored both <it>erm</it>(B) and <it>mef </it>genes. Nine of the 44 macrolide resistant isolates were non-serotypable by our protocols.</p> <p>Conclusion</p> <p>Macrolide resistance in <it>S. pneumoniae </it>in Lebanon is mainly through target site modification but is also mediated through efflux pumps, with serotype 19F having dual resistance and being the most prevalent and invasive.</p