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1.
World J Pediatr Congenit Heart Surg ; 12(1): 55-60, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33407033

RESUMO

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 International Classification of Diseases, Ninth Revision, Clinical Modification 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 (P value < .001) and a longer duration of pacing wires (P 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.

2.
Neuroscientist ; : 1073858420984106, 2021 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-33393420

RESUMO

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.

3.
J Clin Immunol ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464451

RESUMO

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.

4.
Pediatr Blood Cancer ; 68(1): e28784, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33128443

RESUMO

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.

5.
J Gen Virol ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33331815

RESUMO

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.

6.
Biosci Rep ; 40(10)2020 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-33048123

RESUMO

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.

7.
iScience ; : 101697, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33103068

RESUMO

The beginning of the twenty-first 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 COVID-19 patients.

8.
PLoS One ; 15(9): e0239258, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32961548

RESUMO

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.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Influenza Humana/epidemiologia , Neoplasias/epidemiologia , Infecções Respiratórias/epidemiologia , Adolescente , Criança , Criança Hospitalizada , Pré-Escolar , Coinfecção/complicações , Coinfecção/diagnóstico , Coinfecção/virologia , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/virologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Hospitais , Humanos , Lactente , Influenza Humana/complicações , Influenza Humana/diagnóstico , Influenza Humana/virologia , Líbano/epidemiologia , Reação em Cadeia da Polimerase Multiplex/métodos , Neoplasias/complicações , Neoplasias/diagnóstico , Neoplasias/virologia , Pediatria , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Vírus Sincicial Respiratório Humano/patogenicidade , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/virologia , Estudos Retrospectivos , Infecções por Rotavirus/complicações , Infecções por Rotavirus/diagnóstico , Infecções por Rotavirus/epidemiologia , Infecções por Rotavirus/patologia
9.
J Infect Dev Ctries ; 14(8): 878-885, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32903232

RESUMO

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.

10.
Can J Infect Dis Med Microbiol ; 2020: 9598210, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733623

RESUMO

Bacterial pericarditis is a critical diagnosis caused by a wide range of organisms including Streptococcus pneumoniae and other anaerobic organisms like Cutibacterium acnes 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, Cutibacterium acnes can cause pericarditis with serious complications. In this paper, we present a comprehensive review of the literature regarding pericarditis caused by Cutibacterium acnes 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 Cutibacterium acnes 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 Cutibacterium acnes 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.

11.
Mol Cell Biochem ; 475(1-2): 215-226, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32767230

RESUMO

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.

12.
Clin Immunol ; 219: 108573, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32814211

RESUMO

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.

13.
Front Microbiol ; 11: 612, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32425895

RESUMO

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.

14.
Clin Immunol ; 215: 108453, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32360517

RESUMO

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.

15.
BMC Infect Dis ; 20(1): 339, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32397965

RESUMO

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.


Assuntos
Coinfecção/diagnóstico , Coinfecção/epidemiologia , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza B/genética , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Pandemias , Adolescente , Adulto , Idoso , Antivirais/uso terapêutico , Criança , Pré-Escolar , Coinfecção/complicações , Coinfecção/tratamento farmacológico , Feminino , Hospitalização , Humanos , Lactente , Recém-Nascido , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza B/imunologia , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Líbano/epidemiologia , Masculino , Pessoa de Meia-Idade , Morbidade , Pneumonia/etiologia , Estudos Retrospectivos , Centros de Atenção Terciária , Adulto Jovem
16.
J Allergy Clin Immunol ; 146(5): 1165-1179.e11, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32311393

RESUMO

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 Rag2R229Q/R229Q (Rag2R229Q) 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 Rag2R229Q 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 Th1/Th2/Th17 inflammatory signature is detected in the periphery and in the skin. Increased Tlr4 expression in the skin of Rag2R229Q mice is associated with enhanced cutaneous inflammation on local and systemic administration of LPS. Likewise, boosting colitis in Rag2R229Q 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 Th1 effector T cells. CONCLUSIONS: These results support the existence of an interplay between gut and skin that can sustain skin inflammation in OS.

17.
Front Immunol ; 11: 317, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174920

RESUMO

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.

18.
J Infect Public Health ; 13(3): 377-384, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32146138

RESUMO

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.


Assuntos
Política de Saúde , Vacinas contra Influenza/uso terapêutico , Influenza Humana/prevenção & controle , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Pessoal de Saúde/psicologia , Humanos , Programas de Imunização , Influenza Humana/epidemiologia , Irã (Geográfico)/epidemiologia , Masculino , Região do Mediterrâneo/epidemiologia , Pessoa de Meia-Idade , Oriente Médio/epidemiologia , Arábia Saudita/epidemiologia , Estações do Ano , Adulto Jovem
19.
J Infect Public Health ; 13(12): 2092-2100, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30948221

RESUMO

This is a retrospective medical file review of adult inpatients with Streptococcus pneumoniae infections admitted to a Lebanese hospital between 2006 and 2015. We revisited the clinical scenarios of these infections in view of increasing antibiotic resistance in Lebanon. One hundred and three patients were included; 92% were eligible for pneumococcal vaccination, yet none were vaccinated. Non-invasive pneumococcal disease (non-IPD) represented 64% of these infections. Superinfections caused by antibiotic-resistant bacteria were documented in 17.5% of the patients, with the predominance of ventilator-associated pneumonia (12.6%). Kidney disease and septic shock were positive predictors for mortality [adjusted odds ratio (OR) = 14.96, 95% confidence interval (CI) 2.34-95.45, P = 0.004; OR = 5.09, 95% CI 1.33-19.51, P = 0.02, respectively]. Herein, the differences in clinical success, S. pneumoniae infection-related death, and total mortality were not statistically significant between invasive pneumococcal disease (IPD) and non-IPD subgroups (59.5% vs. 77.3%, P = 0.056; 21.6% vs. 9.1%, P = 0.08; and 35.1% vs. 22.7%, P = 0.174; respectively). Upon comparing antibiotic susceptibility of S. pneumoniae during the first two years of the study (2006-2007) (n = 32 isolates) and the last two (2014-2015) (n = 14 isolates), there was an increasing non-susceptibility to penicillin (34.4%-50.0%, P = 0.25), and a decreasing susceptibility to erythromycin and clindamycin (81.3%-78.6%, P = 0.67 and 90.6%-85.7%, P = 0.65; respectively).

20.
Infect Genet Evol ; 78: 104133, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31812761

RESUMO

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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