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1.
Infect Genet Evol ; 75: 103969, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31325610

RESUMO

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.

2.
Pediatr Infect Dis J ; 38(8): 866-872, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31306399

RESUMO

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.

3.
J Infect ; 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31323249

RESUMO

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.

4.
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).

5.
J Allergy Clin Immunol Pract ; 7(6): 1970-1985.e4, 2019 Jul - Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30877075

RESUMO

BACKGROUND: Although autoimmunity and hyperinflammation secondary to recombination activating gene (RAG) deficiency have been associated with delayed diagnosis and even death, our current understanding is limited primarily to small case series. OBJECTIVE: Understand the frequency, severity, and treatment responsiveness of autoimmunity and hyperinflammation in RAG deficiency. METHODS: In reviewing the literature and our own database, we identified 85 patients with RAG deficiency, reported between 2001 and 2016, and compiled the largest case series to date of 63 patients with prominent autoimmune and/or hyperinflammatory pathology. RESULTS: Diagnosis of RAG deficiency was delayed a median of 5 years from the first clinical signs of immune dysregulation. Most patients (55.6%) presented with more than 1 autoimmune or hyperinflammatory complication, with the most common etiologies being cytopenias (84.1%), granulomas (23.8%), and inflammatory skin disorders (19.0%). Infections, including live viral vaccinations, closely preceded the onset of autoimmunity in 28.6% of cases. Autoimmune cytopenias had early onset (median, 1.9, 2.1, and 2.6 years for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively) and were refractory to intravenous immunoglobulin, steroids, and rituximab in most cases (64.7%, 73.7%, and 71.4% for autoimmune hemolytic anemia, immune thrombocytopenia, and autoimmune neutropenia, respectively). Evans syndrome specifically was associated with lack of response to first-line therapy. Treatment-refractory autoimmunity/hyperinflammation prompted hematopoietic stem cell transplantation in 20 patients. CONCLUSIONS: Autoimmunity/hyperinflammation can be a presenting sign of RAG deficiency and should prompt further evaluation. Multilineage cytopenias are often refractory to immunosuppressive treatment and may require hematopoietic cell transplantation for definitive management.

6.
Influenza Other Respir Viruses ; 13(3): 298-304, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30801995

RESUMO

The Middle-East and Africa Influenza Surveillance Network (MENA-ISN), established in 2014, includes 15 countries at present. Country representatives presented their influenza surveillance programmes, vaccine coverage and influenza control actions achieved, and provided a list of country surveillance/control objectives for the upcoming 3 years. This report details the current situation of influenza surveillance and action plans to move forward in MENA-ISN countries. Data were presented at the 8th MENA-ISN meeting, organized by the Mérieux Foundation that was held on 10-11 April 2018 in Cairo, Egypt. The meeting included MENA-ISN representatives from 12 countries (Algeria, Egypt, Jordan, Kenya, Lebanon, Libya, Morocco, Pakistan, Saudi Arabia, South Africa, Tunisia and United Arab Emirates) and experts from the Canadian Centre for Vaccinology, and the World Health Organization. Meeting participants concluded that influenza remains a significant threat especially in high-risk groups (children under-5, elderly, pregnant women and immunosuppressed individuals) in the MENA-ISN region. Additional funding and planning are required by member countries to contain this threat. Future meetings will need to focus on creative and innovative ways to inform policy and initiatives for vaccination, surveillance and management of influenza-related morbidity and mortality especially among the most vulnerable groups of the population.

7.
PLoS One ; 14(2): e0212687, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30789963

RESUMO

Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in children and immunocompromised individuals. A multi-center surveillance of the epidemiologic and molecular characteristics of RSV circulating in Lebanon was performed. The attachment (G) and fusion (F) glycoproteins were analyzed and compared to those reported regionally and globally. 16% (83/519) of the nasopharyngeal swabs collected during the 2016/17 season tested positive for RSV; 50% (27/54) were RSV-A and 50% (27/54) were RSV-B. Phylogenetic analysis of the G glycoprotein revealed predominance of the RSVA ON1 genotype, in addition to two novel Lebanese genotype variants, hereby named LBA1 and LBA2, which descended from the ON1 and NA2 RSV-A genotypes, respectively. RSV-B strains belonged to BA9 genotype except for one BA10. Deduced amino acid sequences depicted several unique substitutions, alteration of glycosylation patterns and the emergence of palivizumab resistance among the Lebanese viruses. The emergence of ON1 and other novel genotypes that are resistant to palivizumab highlights the importance of monitoring RSV globally.

8.
J Med Virol ; 91(7): 1191-1201, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30763464

RESUMO

BACKGROUND: Patients with pediatric cancer have a higher risk of morbidity and mortality because of respiratory viral infections than other patient populations. OBJECTIVES: To investigate the causative viruses of respiratory infections and their burden among patients with pediatric cancer in Lebanon. STUDY DESIGN: Nasopharyngeal swabs along with clinical and demographic data were collected from patients with pediatric cancer presenting febrile episodes with upper respiratory tract symptoms. Total nucleic acid was extracted from specimens followed by the real-time PCR analysis targeting 14 respiratory viruses to estimate the frequency of infections. RESULTS: We obtained 89 nasopharyngeal swabs from patients with pediatric cancer (mean age, 5.8 ± 4.2 years). Real-time PCR confirmed viral infection in 77 swabs (86.5%). Among these, 151 respiratory viruses were detected. Several viruses cocirculated within the same period; respiratory syncytial virus (RSV) being the most common (45.45%), followed by parainfluenza virus (PIV; 26%), influenza type B (26%), human metapneumovirus (24.6%), and human coronavirus (HCoV; 24.6%). Coinfections were detected in 55% of the subjects, and most of them involved RSV with one or more other viruses. A strong correlation was found between PIV, Flu (influenza of any type), RSV, and HCoV with the incidence of coinfections. RSV was associated with lower respiratory tract infections, nasal congestion, bronchitis, and bacteremia. HCoV was associated with bronchiolitis; rhinovirus was associated with hospital admission. CONCLUSION: Patients with pediatric cancer have a high burden of respiratory viral infections and a high incidence of coinfections. Molecular diagnostics can improve management of febrile episodes and reduce antibiotic use.

9.
Vaccine ; 37(12): 1601-1607, 2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30795940

RESUMO

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

10.
J Virol ; 93(7)2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30700605

RESUMO

Annual influenza outbreaks are associated with significant morbidity and mortality worldwide despite the availability of seasonal vaccines. Influenza pathogenesis depends on the manipulation of host cell signaling to promote virus replication. Ceramide is a sphingosine-derived lipid that regulates diverse cellular processes. Studies highlighted the differential role of ceramide de novo biosynthesis on the propagation of various viruses. Whether ceramide plays, a role in influenza virus replication is not known. In this study, we assessed the potential interplay between the influenza A (IAV) and ceramide biosynthesis pathways. The accumulation of ceramide in human lung epithelial cells infected with influenza A/H1N1 virus strains was evaluated using thin-layer chromatography and/or confocal microscopy. Virus replication was assessed upon the regulation of the de novo ceramide biosynthesis pathway. A significant increase in ceramide accumulation was observed in cells infected with IAV in a dose- and time-dependent manner. Inoculating the cells with UV-inactivated IAV did not result in ceramide accumulation in the cells, suggesting that the induction of ceramide required an active virus replication. Inhibiting de novo ceramide significantly decreased ceramide accumulation and enhanced virus replication. The addition of exogenous C6-ceramide prior to infection mediated an increase in cellular ceramide levels and significantly attenuated IAV replication and reduced viral titers (≈1 log10 PFU/ml unit). Therefore, our data demonstrate that ceramide accumulation through de novo biosynthesis pathway plays a protective and antiviral role against IAV infection. These findings propose new avenues for development of antiviral molecules and strategies.IMPORTANCE Understanding the effect of sphingolipid metabolism on viral pathogenesis provide important insights into the development of therapeutic strategies against microbial infections. In this study, we demonstrate a critical role of ceramide during influenza A virus infection. We demonstrate that ceramide produced through de novo biosynthesis possess an antiviral role. These observations unlock new opportunities for the development of novel antiviral therapies against influenza.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30446255

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.

12.
Lancet Child Adolesc Health ; 2(5): 338-349, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30169267

RESUMO

BACKGROUND: Despite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6-35 months. METHODS: In this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 µg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort. FINDINGS: Between Oct 1, 2011, and Dec 31, 2014, 12 018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52-72) against moderate-to-severe influenza and 50% (42-57) against all influenza in the per-protocol cohort, and 64% (53-73) against moderate-to-severe influenza and 50% (42-57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control. INTERPRETATION: IIV4 prevented influenza A and B in children aged 6-35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden. FUNDING: GlaxoSmithKline Biologicals SA.

13.
Oman Med J ; 33(4): 283-290, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30038727

RESUMO

Objectives: Influenza is a vaccine-preventable acute respiratory viral infection that causes epidemics annually around the globe. A regional influenza stakeholder network (MENA-ISN) comprised of experts assessed the status of influenza prevention and control using a structured survey. Methods: A survey questionnaire was used to obtain information from each participating country on surveillance system, the burden of disease, influenza vaccination programs, recommendations, funding and access for vaccine and vaccination, target rate, coverage rate monitoring, and drivers and barriers to influenza vaccination. Results: Out of the 10 countries that participated, nine had an influenza surveillance system and vaccination policy, and seven had World Health Organization (WHO) accredited reference laboratory. Three countries had burden of disease data available and eight had a reimbursement vaccine policy. Influenza vaccine was available in five countries through the Ministry of Health whereas in others, pharmacies also dispensed for the private sector. In all countries, prescribers were physicians, and vaccinators, which could be physicians, nurses, and pharmacists. Eight countries had a set vaccination target rate and only three monitored the influenza coverage rates. Drivers and barriers of vaccination were similar in all countries. Conclusions: Despite existing policies, influenza vaccination coverage remains far below the WHO recommendations. Increased awareness and effective implementation of policies with collaboration of stakeholders can help increase the rates to reach WHO targets.

14.
Vaccine ; 36(28): 4102-4111, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29784470

RESUMO

BACKGROUND: Invasive meningococcal disease has a high burden in young children, particularly during infancy. We investigated the immunogenicity and safety of a quadrivalent meningococcal conjugated vaccine (MenACWY-TT) co-administered with routine vaccines in healthy infants. METHODS: In this phase IIIb study (NCT01340898) conducted in 2 centers in Lebanon and Mexico, 750 infants were randomized (2:1:1) to receive MenACWY-TT according to 3 schedules: 3+1 (at ages 2, 4, 6 and 15-18 months; group ACWY3+1); 1+1 (at 6 and 15-18 months; group ACWY1+1) or single-dose at 15-18 months (group ACWY1). All infants received PHiD-CV and DTPa-IPV/Hib at ages 2, 4, 6, 15-18 months. Immune responses to MenACWY-TT were assessed by rSBA and hSBA at 7 months (groups ACWY3+1, ACWY1+1) and pre- and post-vaccination at 15-18 months of age (all groups). Immune responses to co-administered vaccines, reactogenicity and safety were also evaluated. RESULTS: Immunogenicity of MenACWY-TT at 1 month post-primary vaccination was demonstrated in group ACWY3+1: the lower limit of the 95% confidence interval for the percentage of infants with rSBA titers ≥8 was >80% for each serogroup. At 7 months of age, ≥93.9% of MenACWY-TT-primed infants had rSBA titers ≥8. Post-MenACWY-TT vaccination at age 15-18 months, ≥96.3% of participants in all groups had rSBA titers ≥8, regardless of the number of doses received previously. The percentage of infants with hSBA titers ≥4 were ≥87.2% and ≥89.7% at post-primary and booster/single-dose vaccination, respectively. Immune responses to PHiD-CV and DTPa-IPV/Hib did not seem impacted by co-administration with MenACWY-TT in infancy. The incidence of all adverse events was similar among groups. Serious adverse events were reported for 63/750 children in all groups; none were considered vaccine-related by investigators. CONCLUSION: Primary vaccination with 3 or 1 dose(s) of MenACWY-TT when co-administered with routine pediatric vaccines in infants is immunogenic and well-tolerated.


Assuntos
Anticorpos Antibacterianos/sangue , Meningite Meningocócica/prevenção & controle , Vacinas Meningocócicas/efeitos adversos , Vacinas Meningocócicas/imunologia , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/efeitos adversos , Vacina contra Difteria, Tétano e Coqueluche/imunologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Feminino , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/efeitos adversos , Vacinas Anti-Haemophilus/imunologia , Voluntários Saudáveis , Humanos , Esquemas de Imunização , Lactente , Líbano , Masculino , Vacinas Meningocócicas/administração & dosagem , México , Vacinas Pneumocócicas/administração & dosagem , Vacinas Pneumocócicas/efeitos adversos , Vacinas Pneumocócicas/imunologia , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/efeitos adversos , Vacina Antipólio de Vírus Inativado/imunologia , Vacinas Conjugadas/administração & dosagem , Vacinas Conjugadas/efeitos adversos , Vacinas Conjugadas/imunologia
15.
Genome Announc ; 6(16)2018 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-29674556

RESUMO

We report here the complete genome sequence of a human respiratory syncytial virus (HRSV) strain obtained from an infant who presented to the emergency room with an acute respiratory illness during the 2014/2015 HRSV season in Lebanon. Analysis revealed that this virus belongs to the ON1 genotype that has recently emerged worldwide.

16.
Artigo em Inglês | MEDLINE | ID: mdl-29521234

RESUMO

The B-cell lymphoma 2 (Bcl-2) family proteins play an important role in regulating apoptosis, or programmed cell death, in response to several extracellular and intracellular signals. These proteins are either pro-apoptotic or anti-apoptotic. The pro-apoptotic Noxa is a Bcl-2 family protein that belongs to a subclass of BH3-only proteins. Noxa induces apoptosis via p53-dependent and/or p53-independent mechanisms. While Noxa may play a limited role in apoptosis, it is a crucial player that interacts with several proteins in the apoptosis pathway, highlighting its importance in the pathogenesis and treatment of certain cancers. In this review, we will elucidate the mechanisms by which Noxa regulates apoptosis and review the roles of chemotherapeutic drugs in relation to Noxa.

17.
Hum Vaccin Immunother ; 14(5): 1084-1097, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29393729

RESUMO

Meningococcal disease continues to be a life threatening infection with high morbidity and mortality even in appropriately treated patients. Meningococcal vaccination plays a major role in the control of the disease; however, implementing vaccination remains problematic in the developing world. The objective of this review is to identify the challenges facing the use of meningococcal vaccines in the developing world in order to discuss the opportunities and available solutions to improve immunization in these countries. Inadequate epidemiologic information necessary to implement vaccination and financial challenges predominate. Multiple measures are needed to achieve the successful implementation of meningococcal conjugate vaccination programs that protect against circulating serogroups in developing countries including enhanced surveillance systems, financial support and aid through grants, product development partnerships that are the end result of effective collaboration and communication between different interdependent stakeholders to develop affordable vaccines, and demonstration of the cost-effectiveness of new meningococcal vaccines.

18.
IDCases ; 11: 36-38, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29387550

RESUMO

Guillain-Barre Syndrome, an acute flaccid paralysis known to be caused by recent Gastro-intestinal infections mainly campylobacter, and Respiratory infections mainly mycoplasma pneumoniae and influenza. One reported case of severe invasive pneumococcal disease in a 68 year old female, that presented with Austrian's triad of meningitis, pneumonia and endocarditis, and progressed to develop Guillain Barre syndrome, an association never been documented before. We present a case of 13 year old male, presented with hypoactivity and inability to bare his own weight, developed septic shock due to pneumococcus with Acute Respiratory Distress Syndrome, and was found to have neurological findings of Guillain-Barre Syndrome. A new association in pediatric age group, never been reported before.

19.
Int J Med Microbiol ; 308(3): 358-363, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29478838

RESUMO

Clostridium (Clostridioides) difficile is the main cause for nosocomial diarrhoea in industrialised nations. Epidemiologic data on the pathogen's occurrence in other world regions are still scarce. In this context we characterized with phenotypic and molecular genetic methods C. difficile isolates stemming from hospitalised patients with diarrhoea in Lebanon. From 129 stool samples of symptomatic patients at a tertiary care University hospital in Lebanon, a total of 107 C. difficile strains were cultivated and underwent ribotyping, toxin gene detection and antibiotic resistance testing. Ribotype 014 (RT014, 16.8%) predominated, followed by RT002 (9.3%), RT106 (8.4%) and RT070 (6.5%). Binary toxin gene-positive isolates (RT023, RT078 and RT126) were rarely detected and RT027 was absent. Interestingly, within one isolate only the toxin A gene (tcdA) was detected. Multiple-locus variable-number tandem repeat analysis (MLVA) revealed strong strain diversity in most RTs. The isolates were sensitive to metronidazole and vancomycin, and only a small proportion of strains displayed resistance against moxifloxacin, rifampicin, and clarithromycin (5.6%, 1.9%, and 2.8%), respectively. The data indicate that the genetic strain composition of Lebanese strains differs markedly from the situation seen in Europe and North America. Especially the epidemic RTs seen in the latter regions were almost absent in Lebanon. Interestingly, most strains showed almost no resistance to commonly used antibiotics that are suspected to play a major role in the development of C. difficile infection, despite frequent use of these antibiotics in Lebanon. Thus, the role of antimicrobial resistance as a major driving force for infection development remains uncertain in this area.


Assuntos
Antibacterianos/farmacologia , Toxinas Bacterianas/genética , Infecções por Clostridium/microbiologia , Clostridium difficile/efeitos dos fármacos , Clostridium difficile/genética , Farmacorresistência Bacteriana Múltipla , Toxinas Bacterianas/isolamento & purificação , Infecções por Clostridium/epidemiologia , Clostridium difficile/isolamento & purificação , Clostridium difficile/patogenicidade , Enterocolite Pseudomembranosa/epidemiologia , Enterocolite Pseudomembranosa/microbiologia , Enterotoxinas/genética , Fezes/microbiologia , Feminino , Fluoroquinolonas/farmacologia , Humanos , Líbano/epidemiologia , Masculino , Metronidazol/farmacologia , Testes de Sensibilidade Microbiana , Moxifloxacina , Tipagem de Sequências Multilocus/métodos , Fenótipo , Ribotipagem/métodos , Vancomicina/farmacologia
20.
PLoS One ; 12(12): e0190221, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29272311

RESUMO

Molt-4 leukemia cells undergo p53-dependent apoptosis accompanied by accumulation of de novo ceramide after 14 hours of γ-irradiation. In order to identify the potential mediators involved in ceramide accumulation and the cell death response, differentially expressed genes were identified by Affymetrix Microarray Analysis. Molt-4-LXSN cells, expressing wild type p53, and p53-deficient Molt-4-E6 cells were irradiated and harvested at 3 and 8 hours post-irradiation. Human genome U133 plus 2.0 array containing >47,000 transcripts was used for gene expression profiling. From over 10,000 probes, 281 and 12 probes were differentially expressed in Molt-4-LXSN and Molt-4-E6 cells, respectively. Data analysis revealed 63 (upregulated) and 20 (downregulated) genes (>2 fold) in Molt-4-LXSN at 3 hours and 140 (upregulated) and 21 (downregulated) at 8 hours post-irradiation. In Molt-4-E6 cells, 5 (upregulated) genes each were found at 3 hours and 8 hours, respectively. In Molt-4-LXSN cells, a significant fraction of the genes with altered expression at 3 hours were found to be involved in apoptosis signaling pathway (BCL2L11), p53 pathway (PMAIP1, CDKN1A and FAS) and oxidative stress response (FDXR, CROT and JUN). Similarly, at 8 hours the genes with altered expression were involved in the apoptosis signaling pathway (BAX, BIK and JUN), p53 pathway (BAX, CDKN1A and FAS), oxidative stress response (FDXR and CROT) and p53 pathway feedback loops 2 (MDM2 and CDKN1A). A global molecular and biological interaction map analysis showed an association of these altered genes with apoptosis, senescence, DNA damage, oxidative stress, cell cycle arrest and caspase activation. In a targeted study, activation of apoptosis correlated with changes in gene expression of some of the above genes and revealed sequential activation of both intrinsic and extrinsic apoptotic pathways that precede ceramide accumulation and subsequent execution of apoptosis. One or more of these altered genes may be involved in p53-dependent ceramide accumulation.


Assuntos
Apoptose/fisiologia , Raios gama , Leucemia/genética , Leucemia/patologia , Proteína Supressora de Tumor p53/fisiologia , Linhagem Celular Tumoral , Humanos , Família Multigênica , Biologia de Sistemas
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