Publications by authors named "Ghassan Dbaibo"

133 Publications

The unfolding role of ceramide in coordinating retinoid-based cancer therapy.

Biochem J 2021 10;478(19):3621-3642

Department of Biochemistry and Molecular Genetics, American University of Beirut, Beirut, Lebanon.

Sphingolipid-mediated regulation in cancer development and treatment is largely ceramide-centered with the complex sphingolipid metabolic pathways unfolding as attractive targets for anticancer drug discovery. The dynamic interconversion of sphingolipids is tightly controlled at the level of enzymes and cellular compartments in response to endogenous or exogenous stimuli, such as anticancer drugs, including retinoids. Over the past two decades, evidence emerged that retinoids owe part of their potency in cancer therapy to modulation of sphingolipid metabolism and ceramide generation. Ceramide has been proposed as a 'tumor-suppressor lipid' that orchestrates cell growth, cell cycle arrest, cell death, senescence, autophagy, and metastasis. There is accumulating evidence that cancer development is promoted by the dysregulation of tumor-promoting sphingolipids whereas cancer treatments can kill tumor cells by inducing the accumulation of endogenous ceramide levels. Resistance to cancer therapy may develop due to a disrupted equilibrium between the opposing roles of tumor-suppressor and tumor-promoter sphingolipids. Despite the undulating effect and complexity of sphingolipid pathways, there are emerging opportunities for a plethora of enzyme-targeted therapeutic interventions that overcome resistance resulting from perturbed sphingolipid pathways. Here, we have revisited the interconnectivity of sphingolipid metabolism and the instrumental role of ceramide-biosynthetic and degradative enzymes, including bioactive sphingolipid products, how they closely relate to cancer treatment and pathogenesis, and the interplay with retinoid signaling in cancer. We focused on retinoid targeting, alone or in combination, of sphingolipid metabolism nodes in cancer to enhance ceramide-based therapeutics. Retinoid and ceramide-based cancer therapy using novel strategies such as combination treatments, synthetic retinoids, ceramide modulators, and delivery formulations hold promise in the battle against cancer.
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http://dx.doi.org/10.1042/BCJ20210368DOI Listing
October 2021

Therapeutic applications and biological activities of bacterial bioactive extracts.

Arch Microbiol 2021 Oct 9;203(8):4755-4776. Epub 2021 Aug 9.

Department of Biology, Faculty of Sciences, Lebanese University, Hadath, Lebanon.

Bacteria are rich in a wide variety of secondary metabolites, such as pigments, alkaloids, antibiotics, and others. These bioactive microbial products serve a great application in human and animal health. Their molecular diversity allows these natural products to possess several therapeutic attributes and biological functions. That's why the current natural drug industry focuses on uncovering all the possible ailments and diseases that could be combated by bacterial extracts and their secondary metabolites. In this paper, we review the major utilizations of bacterial natural products for the treatment of cancer, inflammatory diseases, allergies, autoimmune diseases, infections and other diseases that threaten public health. We also elaborate on the identified biological activities of bacterial secondary metabolites including antibacterial, antifungal, antiviral and antioxidant activities all of which are essential nowadays with the emergence of drug-resistant microbial pathogens. Throughout this review, we discuss the possible mechanisms of actions in which bacterial-derived biologically active molecular entities could possess healing properties to inspire the development of new therapeutic agents in academia and industry.
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http://dx.doi.org/10.1007/s00203-021-02505-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349711PMC
October 2021

The burden of Respiratory Syncytial Virus (RSV) infection in the Middle East and North Africa (MENA) region across age groups: A systematic review.

Vaccine 2021 06 4;39(29):3803-3813. Epub 2021 Jun 4.

Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon; Division of Pediatric Infectious Diseases, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon. Electronic address:

Respiratory Syncytial Virus (RSV) is a common respiratory virus that generally causes a mild illness in children and adults or severe symptoms with complications in infants and the elderly, particularly in the presence of underlying comorbidities. While epidemiological data about this virus are available globally, data from the Middle East and North Africa (MENA) region are still scarce. For this reason, we conducted a systematic review to determine the burden of RSV disease in the MENA region by searching the available literature up until September 2018. A total of 1242 studies were retrieved of which 90 were included in the review. Most of the included studies were conducted in subjects aged 0-18 years with the majority being in children below 3 years of age, while only 2 studies included exclusively adults above 18 years of age. RSV infection rates varied greatly between different studies on hospitalized subjects and ranged between 4% and 82%, while the range was smaller in studies on outpatient subjects (between 6% and 36%). When calculating the RSV infection rates in the hospitalized subjects with different inclusion criteria, we found that it was 19%, 70%, and 33% among subjects admitted with Acute Respiratory Infections (ARIs), Acute Lower Respiratory Infections (ALRIs), and bronchiolitis, respectively. RSV infections were most common during the winter season. With regards to complications, intensive care unit admissions ranged between 1% and 15%, while the need for mechanical ventilation ranged between 1% and 10%. The overall RSV related mortality rate across all age groups in studies included in our review was 1.9%. This review identifies several limitations in the existing data and under-representation of the adult population. Future studies should be providing more evidence on the RSV burden in adults and children with comorbidities in order to better assess the potential impact of future preventive strategies in the MENA region.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.076DOI Listing
June 2021

The Emergence of Invasive Serotype 24F in Lebanon: Complete Genome Sequencing Reveals High Virulence and Antimicrobial Resistance Characteristics.

Front Microbiol 2021 19;12:637813. Epub 2021 Feb 19.

Center for Infectious Diseases Research (CIDR) and WHO Collaborating Center for Reference and Research on Bacterial Pathogens, American University of Beirut, Beirut, Lebanon.

Background: Invasive pneumococcal disease (IPD) remains a global health problem. IPD incidence has significantly decreased by the use of pneumococcal conjugate vaccines (PCV). Nevertheless, non-PCV serotypes remain a matter of concern. Eight serotype 24F isolates, belonging to a non-PCV serotype, were detected through the Lebanese Inter-Hospital Pneumococcal Surveillance Program. The aim of the study is to characterize phenotypic and genomic features of the 24F isolates in Lebanon.

Methods: WGS using long reads sequencing (PacBio) was performed to produce complete circular genomes and to determine clonality, antimicrobial resistance and virulence determinants.

Results: The sequencing results yielded eight closed circular genomes. Three multilocus sequence typing (MLST) types were identified (ST11618, ST14184, ST15253). Both MLST and WGS analyses revealed that these isolates from Lebanon were genetically homogenous belonging to clonal complex CC230 and clustered closely with isolates originating from Canada, United States of America, United Kingdom and Iceland. Their penicillin binding protein profiles correlated with both β-lactam susceptibility patterns and MLST types. Moreover, the isolates harbored the macrolide and tetracycline resistance genes and showed a similar virulence gene profile. To our knowledge, this study represents the first report of complete phenotypic and genomic characterization of the emerging , serotype 24F, in the Middle East and North Africa region.
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http://dx.doi.org/10.3389/fmicb.2021.637813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967862PMC
February 2021

First Outbreak during a COVID-19 Pandemic in a Tertiary-Care Center in Lebanon.

Pathogens 2021 Feb 3;10(2). Epub 2021 Feb 3.

Division of Infectious Diseases, Internal Medicine Department, American University of Beirut Medical Center, Beirut 1107 2020, Lebanon.

is an emerging fungal pathogen considered as a global health threat. Recently there has been growing concern regarding drug resistance, difficulty in identification, as well as problems with eradication. Although outbreaks have been reported throughout the globe including from several Arab countries, there were no previous reports from Lebanon. We herein report the first cases of infection from the American University of Beirut Medical Center, a tertiary care center in Lebanon describing the clinical features of the affected patients in addition to the infection control investigation and applied interventions to control the outbreak. Fourteen patients with infection/colonization identified using MALDI-TOF and VITEK 2- Compact system were reported over a period of 13 weeks. Patients were admitted to four separate critical care units. All of them came through the emergency room and had comorbid conditions. Half of the patients were infected with COVID-19 prior to isolation of the was isolated from blood (two isolates), urine (three isolates), respiratory tract (10 isolates) and skin (one isolate). All the patients had received broad spectrum antibiotics prior to isolation of . Six patients received antifungal treatment, while the remaining eight patients were considered colonized. Environmental cultures were taken from all four units and failed to isolate the organism from any cultured surfaces. A series of interventions were initiated by the Infection Prevention and Control team to contain the outbreak. Rapid detection and reporting of cases are essential to prevent further hospital transmission. A national standardized infection control registry needs to be established to identify widespread colonization.
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http://dx.doi.org/10.3390/pathogens10020157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913166PMC
February 2021

Expanding the Nude SCID/CID Phenotype Associated with FOXN1 Homozygous, Compound Heterozygous, or Heterozygous Mutations.

J Clin Immunol 2021 05 19;41(4):756-768. Epub 2021 Jan 19.

Department of Translational Medical Sciences, Pediatrics Section, Federico II University of Naples, via S. Pansini 5, 80131, Naples, Italy.

Human nude SCID is a rare autosomal recessive inborn error of immunity (IEI) characterized by congenital athymia, alopecia, and nail dystrophy. Few cases have been reported to date. However, the recent introduction of newborn screening for IEIs and high-throughput sequencing has led to the identification of novel and atypical cases. Moreover, immunological alterations have been recently described in patients carrying heterozygous mutations. The aim of this paper is to describe the extended phenotype associated with FOXN1 homozygous, compound heterozygous, or heterozygous mutations. We collected clinical and laboratory information of a cohort of 11 homozygous, 2 compound heterozygous, and 5 heterozygous patients with recurrent severe infections. All, except one heterozygous patient, had signs of CID or SCID. Nail dystrophy and alopecia, that represent the hallmarks of the syndrome, were not always present, while almost 50% of the patients developed Omenn syndrome. One patient with hypomorphic compound heterozygous mutations had a late-onset atypical phenotype. A SCID-like phenotype was observed in 4 heterozygous patients coming from the same family. A spectrum of clinical manifestations may be associated with different mutations. The severity of the clinical phenotype likely depends on the amount of residual activity of the gene product, as previously observed for other SCID-related genes. The severity of the manifestations in this heterozygous family may suggest a mechanism of negative dominance of the specific mutation or the presence of additional mutations in noncoding regions.
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http://dx.doi.org/10.1007/s10875-021-00967-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8068652PMC
May 2021

Placement of Labcor Pulmonary Conduit Results in a High Incidence of Postoperative Fever.

World J Pediatr Congenit Heart Surg 2021 Jan;12(1):55-60

Department of Pediatrics and Adolescent Medicine, 66984American University of Beirut Medical Center, Beirut, Lebanon.

Background: Fever in the postoperative period in cardiac patients is common. The purpose of this study is to recognize the risk factors for prolonged postoperative fever in cardiac patients with pulmonary conduit insertion.

Methods: Patients were identified retrospectively by looking at the procedure code for pulmonary conduit insertion between June 2009 and December 2015 at the American University of Beirut Medical Center. Data about preoperative, perioperative, and postoperative variables were collected. Data entry and analysis were performed using SPSS version 22.

Results: The study identified 59 patients. The most common type of pulmonary conduit used was the Contegra type (57.6%) (n = 34), followed by the Labcor type (20.3%; n = 12). Postoperative fever occurred in 61% of patients (n = 36). Fourteen patients (38.8%) had a prolonged fever that lasted for more than seven days. Prolonged postoperative fever was significantly associated with the Labcor pulmonary conduit ( value < .001) and a longer duration of pacing wires ( value: .039). Significantly prolonged fever that lasted for more than 21 days occurred in five patients who all had inserted the Labcor pulmonary conduit.

Conclusions: The Labcor pulmonary conduit type is a risk factor for prolonged postoperative fever. The protracted use of pacing wires could be a consequence of the prolonged fever rather than a cause. In the absence of a demonstrable infectious etiology for prolonged postoperative fever in cardiac patients with pulmonary conduit insertion, the Labcor pulmonary conduit could be the underlying cause. Alternative management of such cases may lead to decreased antibiotic use and morbidity.
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http://dx.doi.org/10.1177/2150135120956995DOI Listing
January 2021

Neurological and Neuropsychological Changes Associated with SARS-CoV-2 Infection: New Observations, New Mechanisms.

Neuroscientist 2021 Jan 3:1073858420984106. Epub 2021 Jan 3.

Department of Biochemistry & Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

SARS-CoV-2 infects cells through angiotensin-converting enzyme 2 (ACE2), a ubiquitous receptor that interacts with the virus' surface S glycoprotein. Recent reports show that the virus affects the central nervous system (CNS) with symptoms and complications that include dizziness, altered consciousness, encephalitis, and even stroke. These can immerge as indirect immune effects due to increased cytokine production or via direct viral entry into brain tissue. The latter is possible through neuronal access via the olfactory bulb, hematogenous access through immune cells or directly across the blood-brain barrier (BBB), and through the brain's circumventricular organs characterized by their extensive and highly permeable capillaries. Last, the COVID-19 pandemic increases stress, depression, and anxiety within infected individuals, those in isolation, and high-risk populations like children, the elderly, and health workers. This review surveys the recent updates of CNS manifestations post SARS-CoV-2 infection along with possible mechanisms that lead to them.
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http://dx.doi.org/10.1177/1073858420984106DOI Listing
January 2021

The origins of G12P[6] rotavirus strains detected in Lebanon.

J Gen Virol 2021 03 17;102(3). Epub 2020 Dec 17.

Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, Beirut, Lebanon.

The G12 rotaviruses are an increasingly important cause of severe diarrhoea in infants and young children worldwide. Seven human G12P[6] rotavirus strains were detected in stool samples from children hospitalized with gastroenteritis in Lebanon during a 2011-2013 surveillance study. Complete genomes of these strains were sequenced using VirCapSeq-VERT, a capture-based high-throughput viral-sequencing method, and further characterized based on phylogenetic analyses with global RVA and vaccine strains. Based on the complete genomic analysis, all Lebanese G12 strains were found to have Wa-like genetic backbone G12-P[6]-I1-R1-C1-M1-A1-N1-T1-E1-H1. Phylogenetically, these strains fell into two clusters where one of them might have emerged from Southeast Asian strains and the second one seems to have a mixed backbone between North American and Southeast Asian strains. Further analysis of these strains revealed high antigenic variability compared to available vaccine strains. To our knowledge, this is the first report on the complete genome-based characterization of G12P[6] emerging in Lebanon. Additional studies will provide important insights into the evolutionary dynamics of G12 rotaviruses spreading in Asia.
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http://dx.doi.org/10.1099/jgv.0.001535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515856PMC
March 2021

Emergence of gram-negative organisms as the cause of infections in patients with sickle cell disease.

Pediatr Blood Cancer 2021 01 31;68(1):e28784. Epub 2020 Oct 31.

Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Background: Patients with sickle cell disease are at higher risk of infections with encapsulated bacteria due to immature immune responses and functional asplenia. We aimed to study our patient population for the emergence of gram-negative organisms other than Salmonella as the cause of osteomyelitis and document a vast decrease in Streptococcus pneumoniae bacteremia rates.

Methods: We conducted a retrospective chart review of 158 patients with sickle cell disease registered at our hospital. Over a period of 13 years, every patient presenting to the emergency department (ED) with fever had their medical record reviewed for blood cultures, wound cultures, and magnetic resonance imaging results for osteomyelitis.

Results: The number of patients presenting to the ED with fever was 105, with 581 febrile episodes and 893 blood cultures. Among those, no culture grew Streptococcus pneumoniae, 14 grew coagulase-negative staphylococci (1.5%), one grew Salmonella enterica Paratyphi B, and three grew Salmonella enterica group C (in the same patient). The total number of osteomyelitis episodes in patients with sickle cell disease presenting with fever and documented by imaging was nine (1.5%). In patients with osteomyelitis, organisms were isolated in four patients (44%), including Enterobacter cloacae, Bacteroides, Pseudomonas aeruginosa, and Salmonella enterica group C.

Conclusions: Immunization against Streptococcus pneumoniae and the use of prophylactic penicillin has virtually eliminated pneumococcal bacteremia among our patients. We observed the emergence of gram-negative organisms other than Salmonella as the cause of osteomyelitis in patients with sickle cell disease.
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http://dx.doi.org/10.1002/pbc.28784DOI Listing
January 2021

Integrative Transcriptome Analyses Empower the Anti-COVID-19 Drug Arsenal.

iScience 2020 Nov 19;23(11):101697. Epub 2020 Oct 19.

Department of Pharmacology and Physiology, Université de Montréal, Montreal, QC, Canada.

The beginning of the 21st century has been marked by three distinct waves of zoonotic coronavirus outbreaks into the human population. The COVID-19 (coronavirus disease 2019) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and emerged as a global threat endangering the livelihoods of millions worldwide. Currently, and despite collaborative efforts, diverse therapeutic strategies from ongoing clinical trials are still debated. To address the need for such an immediate call of action, we leveraged the largest dataset of drug-induced transcriptomic perturbations, public SARS-CoV-2 transcriptomic datasets, and expression profiles from normal lung transcriptomes. Most importantly, our unbiased systems biology approach prioritized more than 50 repurposable drug candidates (e.g., corticosteroids, Janus kinase and Bruton kinase inhibitors). Further clinical investigation of these FDA-approved candidates as monotherapy or in combination with an antiviral regimen (e.g., remdesivir) could lead to promising outcomes in patients with COVID-19.
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http://dx.doi.org/10.1016/j.isci.2020.101697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571421PMC
November 2020

Restoration of ceramide de novo synthesis by the synthetic retinoid ST1926 as it induces adult T-cell leukemia cell death.

Biosci Rep 2020 10;40(10)

Department of Biochemistry and Molecular Genetics, American University of Beirut, Lebanon.

Ceramide (Cer) is a bioactive cellular lipid with compartmentalized and tightly regulated levels. Distinct metabolic pathways lead to the generation of Cer species with distinguishable roles in oncogenesis. Deregulation of Cer pathways has emerged as an important mechanism for acquired chemotherapeutic resistance. Adult T-cell leukemia (ATL) cells are defective in Cer synthesis. ATL is an aggressive neoplasm that develops following infection with human T-cell lymphotropic virus-1 (HTLV-1) where the viral oncogene Tax contributes to the pathogenesis of the disease. ATL cells, resistant to all-trans-retinoic acid, are sensitive to pharmacologically achievable concentrations of the synthetic retinoid ST1926. We studied the effects of ST1926 on Cer pathways in ATL cells. ST1926 treatment resulted in early Tax oncoprotein degradation in HTLV-1-treated cells. ST1926 induced cell death and a dose- and time-dependent accumulation of Cer in malignant T cells. The kinetics and degree of Cer production showed an early response upon ST1926 treatment. ST1926 enhanced de novo Cer synthesis via activation of ceramide synthase CerS(s) without inhibiting dihydroceramide desaturase, thereby accumulating Cer rather than the less bioactive dihydroceramide. Using labeling experiments with the unnatural 17-carbon sphinganine and measuring the generated Cer species, we showed that ST1926 preferentially induces the activities of a distinct set of CerS(s). We detected a delay in cell death response and interruption of Cer generation in response to ST1926 in Molt-4 cells overexpressing Bcl-2. These results highlight the potential role of ST1926 in inducing Cer levels, thus lowering the threshold for cell death in ATL cells.
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http://dx.doi.org/10.1042/BSR20200050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593536PMC
October 2020

Epidemiology and clinical characteristics of viral infections in hospitalized children and adolescents with cancer in Lebanon.

PLoS One 2020 22;15(9):e0239258. Epub 2020 Sep 22.

Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon.

Background: Viral infections in children and adolescents with malignancy are commonly encountered and have a significant impact on morbidity and mortality. Studies and epidemiological data regarding viral infections in children with cancer in developing countries are lacking. This retrospective cohort study aims to assess the burden of viral infections in children and adolescents with cancer, by assessing prevalence, risk factors, as well as morbidity and mortality of common viruses over a period of 8 years.

Methods And Findings: Medical records of cancer patients treated at the Children Cancer Center of Lebanon were reviewed and 155 participants under the age of 21 were identified with at least one documented viral infection during the period from July 2009 to November 2017. This subset included 136 participants with active malignancy and 19 participants with a history of cancer who underwent hematopoietic stem cell transplantation [HSCT] and were in remission; the latter group was analyzed separately. Information regarding participant characteristics, hospital course, and complications were obtained. Associations between viral infections and certain factors were assessed. In the cohort, 64% were male, 81% were Lebanese. In participants with active malignancy, 90% received chemotherapy in the 6 months preceding the viral infection episode, 11% received radiotherapy. 51% of participants were neutropenic at the time of viral detection, and 77% were lymphopenic. 17% experienced a bacterial co-infection, and 3 experienced a viral co-infection. Among 162 viral infection episodes, clinically diagnosed skin infections, mainly herpes simplex virus type 1 and varicella-zoster virus, were the most common [44% of cases]. These were followed by laboratory-proven systemic herpes infections: cytomegalovirus [14%] and Epstein-Barr virus [6%]. Respiratory viruses: influenza and respiratory syncytial virus, accounted for 9% and 4%, respectively, whereas rotavirus represented 11% and BK virus represented 3% of cases. Acute lymphocytic leukemia was the most prevalent neoplasia [57%]. Fever was the most common presenting symptom [55%] and febrile neutropenia was the reason for admission in 24% of cases. The mean length of stay was significantly longer in participants with cytomegalovirus infections and significantly lower in rotavirus infection. Admission to the ICU occurred in 9%, complications in 8%, and mortality in 5%. Participants with viral infections post-HSCT were noted to have a significantly longer length of hospital stay compared to non-HSCT participants, with no other significant differences in clinical course and outcome. The study was limited by its retrospective nature and by the late introduction and underuse of multiplex PCR panels, which may have led to underdiagnosis of viral infections.

Conclusions: Viral infections were prevalent in our sample of cancer patients and may have contributed to morbidity and mortality. Newly available viral diagnostics are likely to vastly increase the number and scope of detectable viral infections in this population. Prospective studies using multiplex PCR technology with systematic testing of patients will be more helpful in defining the burden of viral infections. Furthermore, efforts at antimicrobial stewardship would benefit from the identification of viral causes of infection and limit the unnecessary use of antibiotics in the pediatric cancer population.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0239258PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508634PMC
November 2020

Spoligotyping of Mycobacterium tuberculosis isolates using Luminex®-based method in Lebanon.

J Infect Dev Ctries 2020 08 31;14(8):878-885. Epub 2020 Aug 31.

WHO Collaborating Center for Reference and Research on Bacterial Pathogens, Center for Infectious Diseases Research (CIDR), Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Introduction: Data about the genotypes of circulating Mycobacterium tuberculosis isolates (MTB) in Lebanon are scarce. This study was undertaken to reveal the spoligotypes of MTB isolates recovered from patients in Lebanon.

Methodology: MTB isolates from 49 patients living in Lebanon were recovered and identified. The samples were heat killed and subjected to DNA extraction. Spoligotyping was performed using microbeads from TB-SPOL Kit and the fluorescence intensity was measured using Luminex 200®. Generated patterns were assigned to families using the SITVIT2 international database of the Pasteur Institute of Guadeloupe and compared.

Results: The spoligotyping of the 49 MTB isolates revealed that 31 isolates belonged to Lineage 4 (Euro-American, 63.3%), 12 to Lineage 3 (East- African Indian, 24.5%), 3 to Lineage 2 (East Asian, 6%) and 2 were unknown. Over half of the genotypes (16 of 30) harbored SIT127 supposed to belong to the L4.5 sublineage. One isolate belonging to the rare Manu-Ancestor SIT523 was recovered for the first time in Lebanon, being associated with highly virulent extensively drug-resistant (XDR) MTB phenotype.

Conclusion: The application of the Spoligotyping Multiplex Luminex® method is an efficient, discriminatory and rapid method to use for first-lane genotyping of MTB isolates. Though humble numbers were tested, this study is one of the first to describe the genomic diversity and epidemiology of MTB isolates of Lebanon, and suggests an increasing prevalence of SIT127 in the country.
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http://dx.doi.org/10.3855/jidc.12072DOI Listing
August 2020

Wiskott-Aldrich Syndrome in four male siblings from a consanguineous family from Lebanon.

Clin Immunol 2020 10 16;219:108573. Epub 2020 Aug 16.

Department of Experimental Pathology, Immunology, and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Division of Pediatric Infectious Diseases, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon; Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon. Electronic address:

Background: Wiskott-Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency disorder (PID) characterized by microthrombocytopenia, bloody diarrhea, eczema, recurrent infections, and a high incidence of autoimmunity and malignancy.

Objective: To investigate the mechanism of thrombocytopenia and infections in four boys of consanguineous parents from Lebanon.

Methods: Patient gDNA was studied using Next Generation Sequencing and Sanger Sequencing. Protein expression was determined by immunoblotting, and mRNA expression by semi-quantitative RT-PCR. F-actin polymerization and cellular proliferation were assayed by flow cytometry.

Results: We identified a threonine to a methionine change at position 45 (T45M) of the WAS protein (WASp) that abolished protein expression and disturbed F-actin polymerization and T cell proliferation, but not B cell proliferation. In addition, the levels of the WAS-interacting protein (WIP) were significantly decreased in the patients.

Conclusion: The mutation identified severely destabilizes WASp and affects the downstream signaling events important for T cell function, but not B cell function. It was previously known that the stability of WASp depends on WIP. In this manuscript, we report that the stability of WIP also depends on WASp. Finally, it is important to suspect X-linked PIDs even in consanguineous families.

Clinical Implications: The patients are above the optimal age for transplant in WAS, and it is difficult to identify one or more donors for four patients, therefore, they represent ideal candidates for gene therapy or interleukin-2 therapy.
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http://dx.doi.org/10.1016/j.clim.2020.108573DOI Listing
October 2020

Crosstalk between Noxa, Bcl-2, and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.

Mol Cell Biochem 2020 Dec 7;475(1-2):215-226. Epub 2020 Aug 7.

Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Ionizing radiation induces apoptosis in human Molt-4 leukemia cells in a p53-dependent manner. The tumor suppressor p53 stimulates various downstream targets that presumably trigger, individually or in concert, de novo ceramide synthesis and intrinsic apoptosis via mitochondrial outer membrane permeabilization (MOMP). Among these targets, BH3-only protein Noxa was found to be promptly activated by p53 prior to ceramide accumulation and apoptosis in response to irradiation. To evaluate the relation between Noxa and ceramide in irradiation-induced apoptosis, Noxa was silenced in Molt-4 cells and apoptosis, p53 expression, and ceramide accumulation were assessed in response to irradiation. In the absence of Noxa, irradiation of Molt-4 cells still induced apoptosis in a p53-dependent manner however ceramide levels decreased significantly although they remained higher than untreated control. Upon irradiation, Noxa was found to translocate to the mitochondria where endogenous ceramide accumulation was observed. In contrast, overexpression of Bcl-2, another mitochondrial protein, in Molt-4 cells abolished the endogenous ceramide accumulation and apoptosis. In irradiation-induced, p53-dependent pathways of apoptosis, the pro-apoptotic Noxa represents one of several, yet to be identified, pathways simultaneously triggered by p53 to produce mitochondrial ceramide accumulation and apoptosis. In contrast, Bcl-2 functions as a broader inhibitor of both ceramide accumulation and apoptosis. Altogether, these results indicate that members of the Bcl-2 family differentially regulate ceramide accumulation and reveal the existence of crosstalk between Bcl-2 family members and ceramide in mediating p53-dependent apoptosis in Molt-4 human T-cell leukemia.
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http://dx.doi.org/10.1007/s11010-020-03874-9DOI Listing
December 2020

Cardiac Tamponade Caused by : An Updated and Comprehensive Review of the Literature.

Can J Infect Dis Med Microbiol 2020 14;2020:9598210. Epub 2020 Jul 14.

Division of Cardiology, Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center, Beirut, Lebanon.

Bacterial pericarditis is a critical diagnosis caused by a wide range of organisms including and other anaerobic organisms like which has been gaining more importance as a causative organism. Cutibacterium species are Gram-positive microaerophilic rods that constitute part of the normal flora of skin and mucosal membranes. The incidence of pericarditis caused by this organism is underreported as it is often dismissed as a skin flora contaminant. However, if left untreated, can cause pericarditis with serious complications. In this paper, we present a comprehensive review of the literature regarding pericarditis caused by along with a case presentation from our institution. In our institution, a 20-year-old man with history of atrial septal defect presented with chest pain radiating to the back along with symptoms of upper respiratory tract infection including headaches and myalgia. Electrocardiogram was remarkable for diffuse low-voltage waves. Echocardiography revealed a large pericardial effusion with tamponade features. Pericardiocentesis drained 1.2 L of milky fluid. Pericardial fluid analysis grew after being cultured for 8 days. The patient received 3 weeks of IV penicillin followed by 3 weeks of oral amoxicillin along with nonsteroidal anti-inflammatory agents and colchicine with no recurrence. Pericarditis caused by requires a high clinical suspicion since isolation of this organism can be dismissed as a skin flora contaminant. Literature review reveals that this infection may be underdiagnosed and underreported. Prompt diagnosis may lead to timely initiation of antibiotics which can help prevent devastating complications like constrictive pericarditis. Prospective studies are needed to evaluate the true incidence and prevalence of this disease.
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http://dx.doi.org/10.1155/2020/9598210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7378628PMC
July 2020

Depletion of Host and Viral Sphingomyelin Impairs Influenza Virus Infection.

Front Microbiol 2020 30;11:612. Epub 2020 Apr 30.

Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Influenza A virus (IAV) is a major human respiratory pathogen causing annual epidemics as well as periodic pandemics. A complete understanding of the virus pathogenesis and host factors involved in the viral lifecycle is crucial for developing novel therapeutic approaches. Sphingomyelin (SM) is the most abundant membrane sphingolipid. It preferentially associates with cholesterol to form distinct domains named lipid rafts. Sphingomyelinases, including acid sphingomyelinase (ASMase), catalyzes the hydrolysis of membrane SM and consequently transform lipid rafts into ceramide-enriched membrane platforms. In this study, we investigated the effect of SM hydrolysis on IAV propagation. Depleting plasma membrane SM by exogenous bacterial SMase (bSMase) impaired virus infection and reduced virus entry, whereas exogenous SM enhanced infection. Moreover, the depletion of virus envelope SM also reduced virus infectivity and impaired its attachment and internalization. Nonetheless, inhibition of ASMase by desipramine did not affect IAV infection. Similarly, virus replication was not impaired in Niemann-Pick disease type A (NPA) cells, which lack functional ASMase. IAV infection in A549 cells was associated with suppression of ASMase activity starting at 6 h post-infection. Our data reveals that intact cellular and viral envelope SM is required for efficient IAV infection. Therefore, SM metabolism can be a potential target for therapeutic intervention against influenza virus infection.
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http://dx.doi.org/10.3389/fmicb.2020.00612DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203554PMC
April 2020

The burden of laboratory-confirmed influenza infection in Lebanon between 2008 and 2016: a single tertiary care center experience.

BMC Infect Dis 2020 May 12;20(1):339. Epub 2020 May 12.

Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, PO Box: 11-0236, Riad El-Solh, Beirut, 1107 2020, Lebanon.

Background: Influenza is a major cause of morbidity and mortality worldwide. Following the 2009 pandemic, there was widened interest in studying influenza burden in all regions. However, since data from the World Health Organization (WHO) Middle East and North Africa (MENA) region remain limited, we aimed to contribute to the understanding of influenza burden in Lebanon.

Methods: A retrospective chart review extending over a period of 8 seasons from Jan 1st, 2008 till June 30th, 2016 at a tertiary care center in Beirut was performed. All cases confirmed to have influenza based on rapid antigen detection or/and polymerase chain reaction on a respiratory sample were included for analysis. Data on epidemiology, clinical presentation, complications, antiviral use and mortality were collected for analysis.

Results: A total of 1829 cases of laboratory-confirmed influenza were identified. Average annual positivity rate was 14% (positive tests over total requested). Both influenza A and B co-circulated in each season with predominance of influenza A. Influenza virus started circulating in December and peaked in January and February. The age group of 19-50 years accounted for the largest proportion of cases (22.5%) followed by the age group of 5-19 years (18%). Pneumonia was the most common complication reported in 33% of cases. Mortality reached 3.8%. The two extremes of age (< 2 years and ≥ 65 years) were associated with a more severe course of disease, hospitalization, intensive care unit (ICU) admission, complications, and mortality rate. Of all the identified cases, 26% were hospitalized. Moderate-to-severe disease was more likely in influenza B cases but no difference in mortality was reported between the two types. Antivirals were prescribed in 68.8% and antibiotics in 41% of cases. There seemed to be an increasing trend in the number of diagnosed and hospitalized cases over the years of the study.

Conclusion: Patients with laboratory-confirmed influenza at our center had a high rate of hospitalization and mortality. A population based prospective surveillance study is needed to better estimate the burden of Influenza in Lebanon that would help formulate a policy on influenza control.
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http://dx.doi.org/10.1186/s12879-020-05013-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7216128PMC
May 2020

DNMT3B deficiency presenting as severe combined immune deficiency: A case report.

Clin Immunol 2020 06 30;215:108453. Epub 2020 Apr 30.

Medical Genetics Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon; Department of Medical Genetics, Hotel Dieu de France, Beirut, Lebanon.

Immunodeficiency, Centromeric instability and Facial anomalies (ICF) syndrome is a group of rare autosomal recessive disorders. The immune disease in the ICF syndrome consists mainly of humoral immunodeficiency. T-cell dysfunction has previously been suspected to be part of the syndrome's spectrum. However, patients with ICF display, at a young age, a normal number of T cells that tend to decline throughout disease progression due to apoptosis. Biallelic mutations in the DNMT3B gene account for around 50% of ICF cases (ICF type 1). The remaining half may be linked to ZBTB24, CDCA7 or HELLS. Here we report a novel homozygous DNMT3B mutation (NM_ 006892; p.R826H) in a Lebanese family presenting in early infancy with severe combined immune deficiency (SCID). This work expands the clinical spectrum of the ICF syndrome and confirms the importance of tailoring therapeutic approaches for each patient with ICF syndrome, according to the clinical manifestations of his disease.
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http://dx.doi.org/10.1016/j.clim.2020.108453DOI Listing
June 2020

Cutaneous barrier leakage and gut inflammation drive skin disease in Omenn syndrome.

J Allergy Clin Immunol 2020 11 18;146(5):1165-1179.e11. Epub 2020 Apr 18.

Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Md.

Background: Severe early-onset erythroderma and gut inflammation, with massive tissue infiltration of oligoclonal activated T cells are the hallmark of Omenn syndrome (OS).

Objective: The impact of altered gut homeostasis in the cutaneous manifestations of OS remains to be clarified.

Methods: We analyzed a cohort of 15 patients with OS and the 129Sv/C57BL/6 knock-in Rag2 (Rag2) mouse model. Homing phenotypes of circulating lymphocytes were analyzed by flow cytometry. Inflammatory cytokines and chemokines were examined in the sera by ELISA and in skin biopsies by immunohistochemistry and in situ RNA hybridization. Experimental colitis was induced in mice by dextran sulfate sodium salt.

Results: We show that memory/activated T cells from patients with OS and from the Rag2 mouse model of OS abundantly express the skin homing receptors cutaneous lymphocyte associated antigen and CCR4 (Ccr4), associated with high levels of chemokine C-C motif ligands 17 and 22. Serum levels of LPS are also elevated. A broad T1/T2/T17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2 mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2 mice results in increased frequency of Ccr4 splenic T cells and worsening of skin inflammation, as indicated by epidermal thickening, enhanced epithelial cell activation, and dermal infiltration by T1 effector T cells.

Conclusions: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.
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http://dx.doi.org/10.1016/j.jaci.2020.04.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7649331PMC
November 2020

Genetic Diversity of Human Rotavirus A Among Hospitalized Children Under-5 Years in Lebanon.

Front Immunol 2020 26;11:317. Epub 2020 Feb 26.

Faculty of Medicine, Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon.

Human rotavirus remains a major cause of gastroenteritis worldwide despite the availability of effective vaccines. In this study, we investigated the genetic diversity of rotaviruses circulating in Lebanon. We genetically characterized the VP4 and VP7 genes encoding the outer capsid proteins of 132 rotavirus-associated gastroenteritis specimens, previously identified in hospitalized children (<5 years) from 2011 to 2013 in Lebanon. These included 43 vaccine-breakthrough specimens and the remainder were from non-vaccinated subjects. Phylogenetic analysis of VP4 and VP7 genes revealed distinct clustering compared to the vaccine strains, and several substitutions were identified in the antigenic epitopes of Lebanese specimens. No unique changes were identified in the breakthrough specimens compared to non-breakthroughs that could explain the occurrence of infection in vaccinated children. Further, we report the emergence of a rare P[8] OP354-like strain with a G9 VP7 in Lebanon, possessing high genetic variability in their VP4 compared to vaccine strains. Therefore, human rotavirus strains circulating in Lebanon and globally have accumulated numerous substitutions in their antigenic sites compared to those currently used in the licensed vaccines. The successful spread and continued genetic drift of these strains over time might undermine the effectiveness of the vaccines. The effect of such changes in the antigenic sites on vaccine efficacy remains to be assessed.
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http://dx.doi.org/10.3389/fimmu.2020.00317DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054381PMC
March 2021

Review of seasonal influenza vaccination in the Eastern Mediterranean Region: Policies, use and barriers.

J Infect Public Health 2020 Mar 4;13(3):377-384. Epub 2020 Mar 4.

World Health Organization Regional Office for the Eastern Mediterranean, Monazamet El Seha El Alamia Street, Extension of Abdel Razak El Sanhouri Street, P.O. Box 7608, Nasr City, Cairo 11371, Egypt. Electronic address:

Vaccination is the main control measure for influenza and its severe complications. To better understand the influenza vaccination situation in the Eastern Mediterranean Region, we conducted an extensive review of literature published between 2006 and 2016 in the region on influenza vaccine policies, use, recommendations and coverage. Forty-eight articles met the inclusion criteria. These originated from 11 of the 22 countries of the region, with most being from Saudi Arabia and Iran. The review revealed knowledge gaps and misconceptions about influenza and its vaccines even among healthcare workers. Most of the papers reviewed reported low coverage in the target populations. Limited literature on the number of countries with concrete national influenza vaccination policies was available, which may not accurately represent the situation in the Region. In conclusion, lack of awareness and knowledge are the main barriers to influenza vaccination, which remains very low in the Eastern Mediterranean Region. Countries of the region need to promote and invest in research on influenza vaccination, which is critical to inform evidence-based programmes and policies to improve vaccination rates and control influenza.
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http://dx.doi.org/10.1016/j.jiph.2020.02.029DOI Listing
March 2020

Hypomorphic variants in AK2 reveal the contribution of mitochondrial function to B-cell activation.

J Allergy Clin Immunol 2020 07 17;146(1):192-202. Epub 2019 Dec 17.

Pediatrics Department, Hotel Dieu de France University Hospital, Saint Joseph University, Beirut, Lebanon.

Background: The gene AK2 encodes the phosphotransferase adenylate kinase 2 (AK2). Human variants in AK2 cause reticular dysgenesis, a severe combined immunodeficiency with agranulocytosis, lymphopenia, and sensorineural deafness that requires hematopoietic stem cell transplantation for survival.

Objective: We investigated the mechanisms underlying recurrent sinopulmonary infections and hypogammaglobulinemia in 15 patients, ranging from 3 to 34 years of age, from 9 kindreds. Only 2 patients, both of whom had mildly impaired T-cell proliferation, each had a single clinically significant opportunistic infection.

Methods: Patient cells were studied with next-generation DNA sequencing, tandem mass spectrometry, and assays of lymphocyte and mitochondrial function.

Results: We identified 2 different homozygous variants in AK2. AK2 and AK2 permit residual protein expression, enzymatic activity, and normal numbers of neutrophils and lymphocytes. All but 1 patient had intact hearing. The patients' B cells had severely impaired proliferation and in vitro immunoglobulin secretion. With activation, the patients' B cells exhibited defective mitochondrial respiration and impaired regulation of mitochondrial membrane potential and quality. Although activated T cells from the patients with opportunistic infections demonstrated impaired mitochondrial function, the mitochondrial quality in T cells was preserved. Consistent with the capacity of activated T cells to utilize nonmitochondrial metabolism, these findings revealed a less strict cellular dependence of T-cell function on AK2 activity. Chemical inhibition of ATP synthesis in control T and B cells similarly demonstrated the greater dependency of B cells on mitochondrial function.

Conclusions: Our patients demonstrate the in vivo sequelae of the cell-specific requirements for the functions of AK2 and mitochondria, particularly in B-cell activation and antibody production.
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http://dx.doi.org/10.1016/j.jaci.2019.12.004DOI Listing
July 2020

Full genome characterization of human G3P[6] and G3P[9] rotavirus strains in Lebanon.

Infect Genet Evol 2020 03 5;78:104133. Epub 2019 Dec 5.

Center for Infectious Diseases Research, American University of Beirut, Faculty of Medicine, Beirut, Lebanon; Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, Beirut, Lebanon. Electronic address:

Rotaviruses are the most common infectious agents causing severe diarrheal diseases in young children globally. Three rare human rotavirus strains, two G3P[9] and one G3P[6], were detected in stool samples of children under 5 years of age hospitalized for gastroenteritis in Lebanon during the course of a surveillance study. Complete genomes of these strains were sequenced using VirCapSeq-VERT, a capture based high-throughput sequencing method. Genomic sequences were further characterized by using phylogenetic analyses with global RVA G3P[6]/P[9] strains, other vaccine and reference strains. Genetic analysis revealed that the G3P[6] strain emerged as a DS-1/Wa-like mono-reassortant strain with a potential Ethiopian origin. The two G3P[9] strains possessed a mixed DS-1/Wa/AU-1-like origin indicating that these may have evolved via multiple reassortment events involving feline, human and bovine rotaviruses. Furthermore, analysis of these strains revealed high antigenic variability compared to the vaccine strains. Additional studies are essential to fully understand the evolutionary dynamics of G3P[6]/P[9] strains spreading worldwide and their implications on vaccine effectiveness.
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http://dx.doi.org/10.1016/j.meegid.2019.104133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999726PMC
March 2020

Quadrivalent Influenza Vaccine Prevents Illness and Reduces Healthcare Utilization Across Diverse Geographic Regions During Five Influenza Seasons: A Randomized Clinical Trial.

Pediatr Infect Dis J 2020 01;39(1):e1-e10

Institut Pediàtric Marès-Riera, Blanes, Spain.

Background: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6-35 months of age in a phase III, observer-blind trial.

Methods: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011-2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains.

Results: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1-5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1-5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America.

Conclusions: IIV4 prevented influenza in children 6-35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.
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http://dx.doi.org/10.1097/INF.0000000000002504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004464PMC
January 2020

Viral Etiology of Acute Respiratory Infections in Pediatric Patients in Lebanon.

Mediterr J Hematol Infect Dis 2019 1;11(1):e2019059. Epub 2019 Nov 1.

The Center for Infectious Diseases Research, American University of Beirut, Beirut, Lebanon.

Background: Acute respiratory infections (ARI) are the leading cause of death worldwide, especially among children. The majority of these infections in children are of viral etiology. In this study, we evaluated the incidence of viral ARI among children in Lebanon.

Patients And Methods: Children presenting with symptoms of ARI were prospectively recruited between September 2009 to February 2012. Nasopharyngeal aspirates were obtained from patients and screened for 11 respiratory viruses using a multiplex Luminex-based PCR assay.

Results: Two hundred twenty-one patients were recruited with a median age of 1 year (IQR: 0 - 5). Out of 221 patients, 116 (52.5%) were positive for at least one virus, the majority (103/116; 88.8%) of which were in children under 6-year of age. Overall, 188 viruses were detected. Rhinovirus (RhV) was the most common virus detected in 81 (69.8%) patients followed by coxsackie virus and echovirus (CVEV) which were detected as one target in the panel in 45 (38.8%), and parainfluenza viruses (PIV types: 1, 2, 3, 4) in 24 (20.7%) patients. Coinfection with more than one virus was detected in 49 (42.9%) patients. RhV and CVEV were the most common viruses associated with co-infections and higher risk of rhinorrhea.

Conclusions: Viral pathogens account for at least half of the ARIs in Lebanon, with a high frequency of co-infections being detected.
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http://dx.doi.org/10.4084/MJHID.2019.059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6827722PMC
November 2019

Molecular epidemiology and genetic characterization of influenza B virus in Lebanon during 2016-2018.

Infect Genet Evol 2019 11 17;75:103969. Epub 2019 Jul 17.

Department of Experimental Pathology, Immunology & Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon; Center for Infectious Diseases Research, Faculty of Medicine, American University of Beirut, Beirut, Lebanon. Electronic address:

Background: Influenza B viruses are a major cause of serious acute respiratory infections in humans.

Methods: Nasopharyngeal swabs were collected from subjects with influenza-like illness during October 2016-June 2018 and screened for influenza A and B. The hemagglutinin (HA) and neuraminidase (NA) genes of the Lebanese influenza B specimens were sequenced and phylogenetically compared with the vaccine strains and specimens from the Eastern Mediterranean Region and Europe.

Results: Influenza A and B viruses co-circulated between October and May and peaked between January and March. During the 2016-2017 season, A/H3N2 (33.4%) and B/Yamagata (29.7%) were the predominantly circulating viruses followed by B/Victoria and A/H1N1pdm09 viruses. During the 2017-2018 season, A/H3N2 (31.5%) and A/H1Npdm09 (29.3%) were most prevalent with co-circulation of B/Yamagata and to a lesser extent B/Victoria viruses. The B/Yamagata specimens belonged to clade-3 while the B/Victoria belonged to clade-1A. None of the analyzed specimens had a mutation known to confer resistance to NA inhibitors (NAIs).

Conclusion: Multiple subtypes of influenza co-circulate each year in Lebanon with a peak between January and March. The trivalent vaccine included a B/Victoria strain which mismatched the B/Yamagata lineage that predominated during the study period, highlighting the importance of quadrivalent vaccines.
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http://dx.doi.org/10.1016/j.meegid.2019.103969DOI Listing
November 2019

Comparative global epidemiology of influenza, respiratory syncytial and parainfluenza viruses, 2010-2015.

J Infect 2019 10 16;79(4):373-382. Epub 2019 Jul 16.

ViroScience, Erasmus Medical Centre, Rotterdam, Netherlands.

Objectives: To improve our understanding of the global epidemiology of common respiratory viruses by analysing their contemporaneous incidence at multiple sites.

Methods: 2010-2015 incidence data for influenza A (IAV), influenza B (IBV), respiratory syncytial (RSV) and parainfluenza (PIV) virus infections were collected from 18 sites (14 countries), consisting of local (n = 6), regional (n = 9) and national (n = 3) laboratories using molecular diagnostic methods. Each site submitted monthly virus incidence data, together with details of their patient populations tested and diagnostic assays used.

Results: For the Northern Hemisphere temperate countries, the IAV, IBV and RSV incidence peaks were 2-6 months out of phase with those in the Southern Hemisphere, with IAV having a sharp out-of-phase difference at 6 months, whereas IBV and RSV showed more variable out-of-phase differences of 2-6 months. The tropical sites Singapore and Kuala Lumpur showed fluctuating incidence of these viruses throughout the year, whereas subtropical sites such as Hong Kong, Brisbane and Sydney showed distinctive biannual peaks for IAV but not for RSV and PIV.

Conclusions: There was a notable pattern of synchrony of IAV, IBV and RSV incidence peaks globally, and within countries with multiple sampling sites (Canada, UK, Australia), despite significant distances between these sites.
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http://dx.doi.org/10.1016/j.jinf.2019.07.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7112594PMC
October 2019

Clinical Presentation of Influenza in Children 6 to 35 Months of Age: Findings From a Randomized Clinical Trial of Inactivated Quadrivalent Influenza Vaccine.

Pediatr Infect Dis J 2019 08;38(8):866-872

Paediatric Institute Mares-Riera, Blanes, Spain.

Background: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6-35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes.

Methods: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011-2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018).

Results: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44-0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39-0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case.

Conclusions: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.
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http://dx.doi.org/10.1097/INF.0000000000002387DOI Listing
August 2019
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