CITROBACTER KOSERI SKIN AND SOFT TISSUE INFECTION COMPLICATED BY ABSCESS FORMATION: A CASE REPORT AND A REVIEW OF LITERATURE.

Citrobacter koseri (C. koseri) can lead to severe infections in the neonates, elderly and immunocompromised patients. We describe the first reported case of an axillary abscess due to C. koseri in a healthy adolescent, and review the clinical aspects and associated risk factors of this rare condition.

Characteristics of medically attended influenza infection across age groups before the COVID-19 pandemic in Lebanon.

BACKGROUND: Influenza represents a significant global health burden for individuals and society. This study assessed the burden of medically attended influenza at a tertiary medical center in Lebanon to describe the demographics, risk factors, and outcomes prior to the COVID-19 pandemic. METHODS: This was a retrospective review of patients who tested positive for the influenza virus during three seasons between July 1, 2016 to June 30, 2019, at the American University of Beirut Medical Center. RESULTS: A total of 2049 patients who tested positive for influenza were analyzed. Influenza A accounted for 79.6 % of cases, and influenza B for 19.7 %, with influenza activity starting in October/November and peaking in December/January. Older age above 65 years (AOR=3.584), obesity (AOR=2.183), and chronic conditions such as chronic lung diseases (AOR=1.832), and bacterial co-infection (AOR= 2.834) were found to be independent risk factors for developing complications. Viral co-infection increased the likelihood of death tenfold. Vaccinated patients had a shorter mean hospital stay duration and a lower intensive care unit admission rate. CONCLUSION: The burden of medically attended influenza at our tertiary medical center in Lebanon prior to the COVID-19 pandemic was high. Vaccination decreased the likelihood of complications leading to intensive care unit admission in patients at risk.

Workplace wellness across the lifespan: A pilot program for health promotion in a low- and middle-income country.

Considering that a sizable segment of the population spends significant amount of time at work, workplaces have been identified as practical platforms for health educational programs. Although employee wellness programs in high-income countries have shown measurable benefits in productivity and physical and mental health, evidence-based programs in low- and middle-income countries, such as Lebanon, are unavailable. The aim is to develop and implement a pilot workplace wellness program focusing on health-related areas to improve health knowledge and behavior among working men and women of reproductive age. In collaboration with March of Dimes, the National Collaborative Perinatal Neonatal Network developed a culturally sensitive health education program focusing on lifestyle, infection, nutrition and family planning. Sessions were delivered by a multidisciplinary team of specialists at a local bank in Lebanon. To assess the impact of the program, participants completed Knowledge and Behavior Assessment Questionnaire (KBAQ) before and after implementation. KBAQ was conducted 6 months after implementation to measure retention and continuing impact. Forty-seven participants completed the program, of whom 44.7% are male, 98% have university degree and 56.5% are married. Total knowledge score improved significantly from 64.2 to 74.3 and remained significant at 6 months post-implementation with a score of 71.7 (p < 0.001). At 6-month follow-up, emotional score improved (p = 0.028), while smoking decreased (p = 0.008). Also, employees' health knowledge and behavior showed sustained and significant improvement. We plan to implement our program at other sites and among employees from different backgrounds to understand the impact of the wellness program on employees' knowledge and behaviors at a larger scale.

A novel homozygous mutation in RASGRP1 that predisposes to immune dysregulation and immunodeficiency associated with uncontrolled Epstein-Barr virus-induced B cell proliferation.

BACKGROUND: RASGRP1-deficiency results in an immune dysregulation and immunodeficiency that manifest as autoimmunity, lymphoproliferation, lymphopenia, defective T cell function, and increased incidence of Epstein-Bar Virus infections and lymphomas. OBJECTIVE: To investigate the mechanism of autoimmune hemolytic anemia and infections in a male patient of consanguineous parents from Lebanon. METHODS: Genetic diagnosis was obtained using next generation and Sanger sequencing. Protein expression and phosphorylation were determined by immunoblotting. T and B cell development and function were studied by flow cytometry. Cytokine and immunoglobulin secretions were quantified by enzyme-linked immunosorbent assay. RESULTS: The patient suffered from severe lymphopenia especially affecting the T cell compartment. Genetic analysis revealed a homozygous insertion of adenine at position 1396_1397 in RASGRP1 that abolished protein expression and downstream Ras signaling. T cells from the patient showed severe activation defects resulting in uncontrolled Epstein-Bar Virus-induced B cell proliferation. B cells from the patient were normal. CONCLUSION: This report expands the spectrum of mutations in patients with RasGRP1 deficiency, and provides evidence for the important role RasGRP1 plays in the ability of T cells to control Epstein-Bar Virus-induced B cell proliferation. CLINICAL IMPLICATIONS: Following diagnosis, the patient will be maintained on oral valganciclovir and monitored regularly for Epstein-Bar Virus infections to avoid the development of Epstein-Bar Virus- induced B cell lymphoma. He is also candidate for hematopoietic stem cell transplantation.

The opposing effects of two gene defects in STX11 and SLP76 on the disease in a patient with an inborn error of immunity.

BACKGROUND: Inborn errors of immunity are mostly monogenic. However, disease phenotype and outcome may be modified by the coexistence of a second gene defect. OBJECTIVE: We sought to identify the genetic basis of the disease in a patient who experienced bleeding episodes, pancytopenia, hepatosplenomegaly, and recurrent pneumonia that resulted in death. METHODS: Genetic analysis was done using next-generation sequencing. Protein expression and phosphorylation were determined by immunoblotting. T-cell proliferation and F-actin levels were studied by flow cytometry. RESULTS: The patient harbored 2 homozygous deletions in STX11 (c.369_370del, c.374_376del; p.V124fs60∗) previously associated with familial hemophagocytic lymphohistiocytosis and a novel homozygous missense variant in SLP76 (c.767C>T; p.T256I) that resulted in an approximately 85% decrease in SLP76 levels and absent T-cell proliferation. The patient's heterozygous family members showed an approximately 50% decrease in SLP76 levels but normal immune function. SLP76-deficient J14 Jurkat cells did not express SLP76 and had decreased extracellular signal-regulated kinase signaling, basal F-actin levels, and polymerization following T-cell receptor stimulation. Reconstitution of J14 cells with T256I mutant SLP76 resulted in low protein expression and abnormal extracellular signal-regulated kinase phosphorylation and F-actin polymerization after T-cell receptor activation compared with normal expression and J14 function when wild-type SLP76 was introduced. CONCLUSIONS: The hypomorphic mutation in SLP76 tones down the hyperinflammation due to STX11 deletion, resulting in a combined immunodeficiency that overshadows the hemophagocytic lymphohistiocytosis phenotype. To our knowledge, this study represents the first report of the opposing effects of 2 gene defects on the disease in a patient with an inborn error of immunity.

A Quality improvement initiative to reduce central line-associated bloodstream infections in a neonatal intensive care unit in a low-and-middle-income country.

BACKGROUND: Premature and sick neonates in the neonatal intensive care unit (NICU) are in need of central lines placing them at high risk of contracting a central line-associated bloodstream infection (CLABSI). CLABSI extends length of stay to 10-14 days post negative cultures and increases morbidity, use of multiple antibiotics, mortality and hospital cost. To reduce CLABSI rate at the American University of Beirut Medical Center NICU, the National Collaborative Perinatal Neonatal Network developed a quality improvement project to reduce CLABSI rate by 50% over a 1-year period and to sustain reduced CLABSI rate. METHODS: Central line insertion and maintenance bundles were implemented for all infants admitted to the NICU necessitating central lines placement. Bundles included hand washing, wearing protective material and sterile drapes during central lines insertion and maintenance. RESULTS: CLABSI rate decreased by 76% from 4.82 (6 infections; 1244 catheter days) to 1.09 (2 infection; 1830 catheter days) per 1000 CL days after 1 year. Following the bundles' success in reducing CLABSI rate, they were incorporated permanently to NICU standard procedure and bundle checklists were added to the medical sheets. CLABSI rate was maintained at 1.15 per 1000 CL days during the second year. It then decreased to 0.66 per 1000 CL days in the third year before reaching zero in the fourth year. In total, zero CLABSI rate was sustained for 23 consecutive months. CONCLUSION: Reducing CLABSI rate is necessary to improving newborn quality of care and outcome. Our bundles were successful in drastically reducing and sustaining a low CLABSI rate. It was even successful in achieving a zero CLABSI unit for 2 years.

The Middle East and North Africa Diagnosis and Management Guidelines for Inborn Errors of Immunity.

Human inborn errors of immunity (IEI) are a group of 485 distinct genetic disorders affecting children and adults. Signs and symptoms of IEI are heterogeneous, and accurate diagnosis can be challenging and depends on the available human expertise and laboratory resources. The Middle East and North Africa (MENA) region has an increased prevalence of IEI because of the high rate of consanguinity with a predominance of autosomal recessive disorders. This area also exhibits more severe disease phenotypes compared with other regions, probably due to the delay in diagnosis. The MENA-IEI registry network has designed protocols and guidelines for the diagnosis and treatment of IEI, taking into consideration the variable regional expertise and resources. These guidelines are primarily meant to improve the care of patients within the region, but can also be followed in other regions with similar patient populations.

Multisystem inflammatory syndrome in children (MIS-C) and "Near MIS-C": A continuum?

Introduction: Reports of multisystem inflammatory syndrome in children (MIS-C), following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, have been increasing worldwide, with an incidence varying significantly across studies based on the definition used for the diagnosis. At our tertiary medical center in Lebanon, we encountered several cases that presented a diagnostic challenge because they mimicked MIS-C but did not meet the US Centers for Disease Control and Prevention (CDC) definition. We decided to review these cases and describe their features in comparison with cases that met the CDC criteria of MIS-C and those that had an alternative diagnosis. Methods: This is a retrospective chart review of subjects aged <19 years old admitted to the American University of Beirut Medical Center (AUBMC) between March 1, 2020, and May 31, 2021, with suspected or confirmed MIS-C, following documented COVID-19 infection, with sufficient or insufficient criteria for diagnosis. Subjects were classified into 3 groups: "MIS-C", "Near MIS-C" and "Alternative Diagnosis". Results: A total number of 29 subjects were included in our cohort. Fever was present in all subjects. In the MIS-C group, evidence for cardiovascular system involvement was the most common feature followed by the mucocutaneous and gastrointestinal systems. In the "Near MIS-C" and "Alternative Diagnosis" group, gastrointestinal symptoms were the most common with only one patient with cardiac abnormalities and none with coagulopathy. Subjects with typical MIS-C presentation had higher inflammatory markers when compared to subjects in the other groups. Almost all the subjects had positive IgG for SARS-CoV-2. Of the 29 subjects, the Royal College of Paediatrics and Child Health (RCPCH) case definition would have identified all suspected cases without an alternative diagnosis as MIS-C, whereas the World Health Organization (WHO) and the CDC definitions would have excluded 6 and 10 subjects, respectively. Conclusion: MIS-C presents a diagnostic challenge due to the nonspecific symptoms, lack of pathognomonic findings, and potentially fatal complications. More research is needed to fully understand its pathogenesis, clinical presentation spectrum, and diagnostic criteria. Based on our experience, we favor the hypothesis that MIS-C has a continuum of severity that necessitates revisiting and unifying the current definitions.

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

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.

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

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.

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

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.

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

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

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.

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

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.

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

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.

A young child with HIV and unsteady gait: A case report.

BACKGROUND: We would like to raise awareness about the toxicities related to the added excipients present in the oral solution of Liponavir/ritonavir in particular alcohol and propylene glycol. CASE PRESENTATION: In this case report, we describe an 18 month-old child with a newly diagnosed HIV infection on antiretroviral therapy (ART). She developed shortly after starting the ART unsteady gait and imbalance. CONCLUSIONS: The excipient-excipient interaction in Lopinavir/ritonavir may contribute to major toxicities not only in premature neonates and infants; but also in older children specifically from Asian ethnicity.

Case Report: A Delayed Diagnosis of Congenital Syphilis-Too Many Missed Opportunities.

Congenital syphilis remains a significant public health problem nowadays. We describe the presentation of an infant with a delayed diagnosis of congenital syphilis, with a negative initial non-treponemal test. Our aim is to shed light on the incidence of missed prevention, the importance of awareness, maternal screening, and early diagnosis.

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

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. AK2G100S and AK2A182D 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.

Viral Etiology of Acute Respiratory Infections in Pediatric Patients in 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.