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Antibiotic misuse in the animal sector is the first cause of the emergence and spreading of MDR bacteria. Prevention of infectious diseases and enhancement of animal growth are the main effects of antibiotics that push farmers and veterinarians to use this molecule in animal farms. Thus, the use of alternative solutions such as natural antimicrobial substances as well as probiotic strains is a crucial need in this sector. Enterococcus faecium CMUL1216 was isolated from healthy human baby's feces. This strain was assessed in vitro for probiotic properties including activity against many pathogens isolated from animal, human, and soil samples. CMUL1216 strain exhibits good antimicrobial activity against indicator pathogens in both planktonic and biofilm forms. In addition, CMUL1216 strain showed a strong biofilm formation. Furthermore, CMUL1216 exhibits a good anti-inflammatory effect by inducing the secretion of IL-10 in vitro. Moreover, this strain did not show any pathogenic characteristics such as hemolytic effect, presence of virulence genes as well as susceptibility to the majority of antibiotic families. E. faecium CMUL1216 could be a good candidate to be used a probiotic strain in the animal sector in order to maintain animal health and therefore reduce antibiotic resistance caused by the excessive use in this sector.

Objective The association between diabetes mellitus and tuberculosis is a health-threatening double trouble. Vulnerable populations such as refugees and conflict-displaced populations may be at higher risk of both diseases. Here, we examined the prevalence of latent tuberculosis infection (LTBI) and its associated risk factors in a population of Syrian refugees with diabetes in North Lebanon. Study design This is a cross-sectional study. Methods A total of 87 Syrian refugees with diabetes were enrolled. Demographic and clinical data were collected using a structured questionnaire, and a blood sample was obtained from each patient. LTBI was examined using the last generation QuantiFERON-TB Gold Plus assay. Results The mean age of the study population was 54.1 ± 10.5 years, and the majority were women (79.3%). LTBI was found in 1 in 5 (17/87; 19.5%) enrolled patients, with the majority being originated from Aleppo (47.05%). Infection was significantly associated only with age (P = 0.009), and its risk was 4-fold higher in patients aged ≥60 years (odds ratio: 4.1, confidence interval: 1.4–12.5, P = 0.018). Conclusion This study highlights the need to implement effective tuberculosis control strategies among refugees with diabetes, with particular attention to those at older age.

Helicobacter pylori causes chronic gastritis and plays a significant role in duodenal/gastric ulcer disease and gastric cancer. Its prevalence varies among different populations and geographical areas. Here, in a hospital-based retrospective study, we investigated the seroprevalence of H. pylori infection in northern Lebanon. We examined the records of 4000 consecutive dyspeptic patients attending 2 tertiary care centres in the North (Tripoli) and Akkar (Halba) governorates. Seropositivity for H. pylori was determined using enzyme immunoassays investigating specific anti- H. pylori IgG antibodies. The association of infection with the available patients’ demographic characteristics was also evaluated. The mean age of our study population was 36.9±16.6 years. With 2486 female and 1514 male subjects, the overall female/male ratio was 1.64. In total, H. pylori seropositivity was detected in 1367/4000 (34.2 %) tested individuals. The multivariate logistic regression analysis showed that H. pylori infection is less prevalent in female than in male examined patients [adjusted odds ratio (OR): 0.84; 95 % confidence interval (CI): 0.73–0.96; PP H. pylori . However, the prevalence of infection was markedly different in close geographical zones in this region. Additional screening studies using different screening methods are needed in the future to determine the accurate prevalence of this bacterium and its clinical implications to establish efficient national intervention strategies.

Dermatophytosis corresponds to a broad series of infections, mostly superficial, caused by a group of keratinophilic and keratinolytic filamentous fungi called dermatophytes. These mycoses are currently considered to be a major public health concern worldwide, particularly in developing countries such as those in the Middle East and North Africa (MENA) region. Here we compiled and discussed existing epidemiologic data on these infections in the MENA region. Most of the available studies were based on conventional diagnostic strategies and were published before the last taxonomic revision of dermatophytes. This has led to misidentifications, which might have resulted in the underestimation of the real burden of these infections in the MENA countries. Our analysis of the available literature highlights an urgent need for further studies based on reliable diagnostic tools and standard susceptibility testing methods for dermatophytosis, which represents a major challenge for these countries. This is crucial for guiding appropriate interventions and activating antifungal stewardship programs in the future.

Antibiotic misuse in the animal sector is the first cause of the emergence and spreading of MDR bacteria. Prevention of infectious diseases and enhancement of animal growth are the main effects of antibiotics that push farmers and veterinarians to use this molecule in animal farms. Thus, the use of alternative solutions such as natural antimicrobial substances as well as probiotic strains is a crucial need in this sector. Enterococcus faecium CMUL1216 was isolated from healthy human baby's feces. This strain was assessed in vitro for probiotic properties including activity against many pathogens isolated from animal, human, and soil samples. CMUL1216 strain exhibits good antimicrobial activity against indicator pathogens in both planktonic and biofilm forms. In addition, CMUL1216 strain showed a strong biofilm formation. Furthermore, CMUL1216 exhibits a good anti-inflammatory effect by inducing the secretion of IL-10 in vitro. Moreover, this strain did not show any pathogenic characteristics such as hemolytic effect, presence of virulence genes as well as susceptibility to the majority of antibiotic families. E. faecium CMUL1216 could be a good candidate to be used a probiotic strain in the animal sector in order to maintain animal health and therefore reduce antibiotic resistance caused by the excessive use in this sector.

Plasma IL-17A detection in Langerhans Cell Histiocytosis (LCH) is currently a source of debate. Indeed, 500-P07G (PeproTech) and 41802 (R&D Systems) anti-IL-17A antibodies have been suspected to recognize nonspecific proteins. To resolve this discrepancy, we set up two new ELISAs by using 41802 or neutralizing eBio64CAP17 (eBioscience) capture monoclonal antibodies that we compared to the commercial PeproTech ELISA kit. The three ELISAs, called E_500-P07G, E_41802 and E_eBio64CAP17, differ in their anti-IL-17A capture antibodies: either polyclonal, monoclonal or neutralizing monoclonal antibodies, respectively. Here, we show that these ELISAs had a similar capacity to specifically detect recombinant or native human IL-17A. However, a significantly lower plasma IL-17A detection was obtained with E_41802 compared to the two other ELISAs. Both E_500-P07G and E_eBio64CAP17 showed similar results. Consequently, we propose that the use of E_500-P07G and E_eBio64CAP17 may ensure more accurate and reliable results in the context of LCH studies. The highest plasma IL-17A levels in LCH patients compared to controls detected by both E_500-P07G and E_eBio64CAP17 ELISAs led us to propose these latter as reference techniques to investigate IL-17A as a potential new biomarker in LCH.•The customization of a new E_eBio64CAP17 ELISA is suitable to detect human IL-17A.•E_eBio64CAP17 ELISA protocol differs only in the anti-IL-17A capture antibody compared to the commercial E_500-P07G PeproTech kit.•Data generated using the E_eBio64CAP17 ELISA are consistent with the PeproTech kit., Graphical abstract Image, graphical abstract

International audience; Objectives: Tuberculosis (TB) is the leading infectious cause of death in the world. Cheaper and more accessible TB treatment monitoring methods are needed. Here, we evaluated white blood cell (WBC) absolute counts, lymphocyte, and monocyte proportions during TB treatment, and characterized their association with treatment failure.Methods: This multicentered prospective cohort study was based in Bangladesh, Georgia, Lebanon, Madagascar, and Paraguay. Adult, non-immunocompromised patients with culture-confirmed pulmonary TB were included and followed up after two months of treatment and at the end of therapy. Blood counts were compared to treatment outcome using descriptive statistics, logistic regression, and Receiver Operating Characteristic (ROC) analyses.Results: Between December 2017 and August 2020, 198 participants were enrolled, and 152 completed treatment, including 28 (18.5%) drug-resistant patients. The rate of cure at the end of treatment was 90.8% (138/152). WBC absolute counts decreased, and lymphocyte proportions increased throughout treatment. In multivariate analyses, baseline high WBC counts and low lymphocyte proportions were associated with positive sputum culture results at the end of treatment (WBC > 11,450 cells/mm3: p = 0.048; lymphocytes 11,450 cells/mm3 and lymphocytes

While COVID-19 continues to spread across the globe, diligent efforts are made to understand its attributes and dynamics to help develop treatment and prevention measures. The paradox pertaining to children being the least affected by severe illness poses exciting opportunities to investigate potential protective factors. In this paper, we propose that childhood vaccination against pertussis (whooping cough) might play a non-specific protective role against COVID-19 through heterologous adaptive responses in this young population. Pertussis is a vaccine-preventable infectious disease of the respiratory tract and it shares many similarities with COVID-19 including transmission and clinical features. Although pertussis is caused by a bacterium (Bordetella pertussis) while COVID-19 is a viral infection (SARS-CoV-2), previous data showed that cross-reactivity and heterologous adaptive responses can be seen with unrelated agents of highly divergent groups, such as between bacteria and viruses. While we build the arguments of this hypothesis on theoretical and previous empirical evidence, we also outline suggested lines of research from different fields to test its credibility. Besides, we highlight some concerns that may arise when attempting to consider such an approach as a potential public health preventive intervention against COVID-19.

Hepatitis E virus (HEV) is an important global public health concern. Several studies reported a higher HEV prevalence in patients undergoing regular hemodialysis (HD). In Lebanon, the epidemiology of HEV among HD patients has never been investigated previously. In this study, we examine the seroprevalence of HEV infection among 171 HD patients recruited from three hospital dialysis units in Tripoli, North Lebanon. Prevalence of anti-HEV IgG antibodies was evaluated in participant's sera using a commercial enzyme-linked immunosorbent assay (ELISA). The association of socio-demographic and clinical parameters with HEV infection in patients was also evaluated. Overall, 96 women and 75 men were enrolled in this study. Anti-HEV IgG antibodies were found positive in 37/171 HD patients showing a positivity rate of 21.63%. Among all examined variables, only the age of patients was significantly associated with seropositivity (P = 0.001). This first epidemiological study reveals a high seroprevalence of HEV infection among Lebanese HD patients. However, further evaluations that enroll larger samples and include control groups are required to identify exact causative factors of the important seropositivity rate in this population.

Background and Objectives: Several LAB species were evaluated and characterized for potential probiotic use. Besides the antimicrobial activity, probiotics showed recently a capacity to prevent and to alleviate inflammatory and chronic diseases. Immunomodulation effect is one of the modes of actions of such probiotics, called immunobiotics, which can be used in several chronic diseases such as Inflammatory Bowel Diseases (IBD). The aim of this study was to isolate, identify and char- acterize lactobacilli strains from healthy baby’s feces in order to select some strains with potential immunobiotic application especially strains which can stimulate anti-inflammatory responses. Materials and Methods: Forty-two LAB strains were isolated and identified by the MALDI-TOF / MS technique. In addi- tion, strains were subjected to several assessments such as antimicrobial activity, the capacity to form biofilm in polystyrene microplate and immunomodulation activity in a PBMC model. Results: Results showed that the majority of strains (90.4%) were identified as Lactobacillus. However, among these, only 39.4% of lactobacilli strains were not identified at the species level. All isolated lactobacilli strains showed an anti-inflam- matory effect. Moreover, 7 strains were considered as good probiotic candidates based on their characteristics such as their antibacterial activities, formation of the strongest biofilm and their ability to stimulate an anti-inflammatory response in PBMCs model. Conclusion: Two strains (Lactobacillus spp S14 and Lactobacillus spp S49) which showed the best immunobiotic char- acteristics, could be selected and evaluated more deeply in vivo model as well as in human clinical study to ensure their effectiveness in inflammatory diseases such as IBD.

The Syrian conflict has damaged key infrastructure and indirectly affected almost all parts of the Middle East and Europe, with no end in sight. Exhausting conditions created by the Syrian crisis and related massive displacement promote the emergence of numerous public health problems that fuel antimicrobial resistance (AMR) development. Here, we explore the current situation of the Syrian displaced population, and AMR inside Syria and among refugees in host countries. We then suggest a roadmap of selected key interventions and strategies to address the threat of AMR in the context of the Syrian crisis. These recommendations are intended to urge health policy-makers in governments and international health organizations to optimize and push for implementing an effective policy taking into consideration the current obstacles.

International audience; The World Health Organization (WHO) and other international organisations, including the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health and the International Union Against Tuberculosis and Lung Disease recently called for formally assessing and (re)prioritising the burden of zoonotic tuberculosis (TB) in people, due to Mycobacterium bovis [1, 2]. Its global contribution to human TB, otherwise principally caused by Mycobacterium tuberculosis, might be underestimated [2]. Nationally representative prevalence data are virtually non-existent on continents with the highest presumed burdens, i.e. in Africa and Asia [3]. In addition to causing hard-to-diagnose extrapulmonary TB more frequently, M. bovis is naturally resistant to pyrazinamide [4], a crucial drug for the standard short-course anti-TB therapy. Due to reliability issues, phenotypic susceptibility to pyrazinamide is often not tested [5]. The most commonly used phenotypic and molecular diagnostics, including the WHO-endorsed GeneXpert MTB/RIF test (Cepheid, Sunnyvale, CA, USA), do not differentiate M. bovis from M. tuberculosis [1]. Thus, M. bovis-infected patients may receive inadequate treatment, risking poorer outcomes [6]. Underdiagnosis in people also implies the existence of undetected animal and food sources and zoonotic risks escaping common TB control measures [1, 2]. In Europe, patients with M. bovis infection are often African-or southern Mediterranean-born, suggesting regional endemicity [6, 7]. We determined the prevalence of M. bovis-caused TB in a survey including all TB patients reported to the national TB programme over an 18-month period in Lebanon. In addition to its national population and >1.5 million Syrian and Palestinian refugees, this Mediterranean country hosts large numbers of migrant workers from Africa and Asia [8]. Many are from Ethiopia [8], where proportions of extrapulmonary TB and M. bovis-caused disease among TB patients apparently culminate, reaching ∼30% [9] and 15-30% (in focal studies; [10]), respectively. We used a novel targeted next-generation sequencing-based assay for extensive drug resistance detection, including resistance to pyrazinamide, and genotypic differentiation between M. bovis and M. tuberculosis [11]. This survey was approved by the Azm Center/Lebanese University ethical committee (document CE-EDST-3-2016). Clinical samples were collected from all 1104 different TB patients with presumption of pulmonary or extrapulmonary TB, based on the presence of symptoms and prior tuberculin skin testing or radiological examination in local hospitals for a number of patients, and reported to all national anti-TB centres between June 1, 2016 and November 31, 2017. All of these 1104 patients were tested by at least one of the following assays: solid (Lowenstein-Jensen) and/or liquid (BBL MGIT; Beckton Dickinson, Franklin Lakes, NJ, USA) culturing, GeneXpert MTB/RIF on sputum, and Anyplex MTB/NTM Real-time (Seegene, Seoul, Republic of Korea) on sputum or culture on solid or liquid medium. Out of these 1104, 417 were confirmed as TB positive by GeneXpert and/or Anyplex. Among these 417 patients, 354 were culture positive. Among the 354 corresponding patients, 325 were new TB patients, 22 had a previous TB history, while TB history information was unavailable for seven patients. Available DNA extracts, obtained from 348 out of 354 primary cultures by using MasterPure™ DNA Purification Kit (Epicentre, Illumina, Madison, WI, USA), were subjected to targeted sequencing, more @ERSpublications In response to recent international calls, this study reveals the nationally representative prevalence of zoonotic tuberculosis in people in a non-high income country, highlighting the need for appropriate diagnostics and treatment of these patients http://bit.ly/2l3ydDh

Langerhans cell histiocytosis (LCH) is a granulomatous inflammatory myeloid neoplasia associated with a cytokine storm in both serum and lesions. Increased levels of plasma interleukin-17A (IL-17A) in LCH patients have been reported, but this finding was not confirmed in all studies. Neurodegeneration is a devastating complication of LCH (ND-LCH). We aimed to revisit the issue of plasma IL-17A levels in LCH, by using a larger number of patients, and also to investigate the relationship between IL-17A and LCH sequelae, especially ND-LCH.Plasma samples from 68 LCH patients and 127 controls were analyzed for IL-17A levels by two ELISAs with different anti-IL-17A capture antibodies: either polyclonal or neutralizing monoclonal antibodies in 17polyAb-ELISA or 17mAb-ELISA, respectively.Both ELISAs had a similar capacity to specifically detect recombinant or native human IL-17A, as well as plasma IL-17A from LCH patients. We confirmed the finding of higher levels of plasma IL-17A in LCH patients compared to controls (p 0.0001). The association of IL-17A with LCH was independent of the ELISA used, and of gender, age, disease class activity, and pattern of tissue-organ involvement (single-system versus multi-system). ROC analyses (p 0.0001) allow to discriminate LCH patients from the control group, supporting the notion that IL-17A may be a potential biomarker for LCH. More interestingly, high IL-17A levels were significantly associated with LCH patients having sequelae, with the highest plasma levels in patients with ND-LCH (p 0.0001).The association between high levels of IL-17A and LCH was confirmed. IL-17A may be associated with ND-LCH development. This might have therapeutic implications, offering a novel target for precision therapy of ND-LCH.

Introduction: Toxoplasmosis is of dual importance in both public and veterinary health due to the respective risk of transplacental transmission in primo-infected pregnant women and economic losses caused by abortions in mammals. One of the main routes of Toxoplasma gondii transmission to humans is the consumption of raw or undercooked meats containing parasitic cysts. Here, we performed the first epidemiological study to determine the seroprevalence and the risk factors of toxoplasmosis in livestock in Lebanon. Methodology: Using a modified agglutination test with a cut-off of 1:40, we tested the positivity rate of Immunoglobulin G antibodies in the sera of 100 sheep and 80 goats collected from 18 different livestock farms located in North Lebanon between March and June 2018. Results: Anti-Toxoplasma gondii IgG antibodies were detected in 42% of sheep and 34% of goats. Adults (> 1 year) were significantly more infected by T. gondii than the lambs (< 1 year) in both species (p < 0.05). Conclusions: These findings indicated that food animals are highly exposed to T. gondii in Lebanon and could be potentially a major risk factor of T. gondii infection to humans. Consequently, national prophylactic strategies should be implemented to control and to prevent T. gondii transmission between animals and humans.

International audience; In a 12-month nationwide study on the prevalence of drug-resistant tuberculosis (TB) in Lebanon, we identified 3 multidrug-resistant cases and 3 extensively drug-resistant TB cases in refugees, migrants, and 1 Lebanon resident. Enhanced diagnostics, particularly in major destinations for refugees, asylum seekers, and migrant workers, can inform treatment decisions and may help prevent the spread of drug-resistant TB.

Background Rapid and accurate techniques are always welcomed for the detection of resistant strains of Mycobacterium tuberculosis MTB. Objectives The objective of this study is to evaluate the pyrosequencing technology for the detection of MTB resistance to Rifampicin (RIF) and Isoniazid (INH) in Syrian and Lebanese clinical strains; 66 strains resistant to INH, among them 56 resistant also to RIF, were tested. Methods Four pyrosequencing assays were optimized and applied to the following loci: rpoB rpoB RIF resistance-determining region, katG , the promoter regions of inhA and ahpC - oxyR intergenic region. Results The prevalence of mutations on codon 315 of the katG gene, inhA and ahpc - oxyR were 42.4%, 21.2% and 9.0%, respectively, which make an overall sensitivity of 72.6% for INH resistance. All RIF-resistant strains contained at least one non-synonymous codon change in the sequenced rpoB region (507–533) relative to the ATCC reference strain. The RIF drug resistance region (RRDR) sequencing identified 96 modified codons representing 34 different mutations. Conclusions The high sensitivity and the short turnaround time combined with multilocus sequencing of several isolates in parallel make pyrosequencing an attractive method for drug resistance screening for MTB .

Background Coxsackieviruses B (CV-B) are enteroviruses that have been reported to play a role in the pathogenesis of type 1 diabetes. Enteroviral RNA was detected in the gut mucosa of patients. The mucosal immunity is an interconnected network; therefore, the response to enteroviruses possibly present in the gastrointestinal mucosa can be reflected by specific antibodies in the saliva. In the present study, the anti-CV-B neutralizing activity of saliva samples from patients with type 1 diabetes was investigated. Methods Saliva samples were collected from patients and controls of 3 countries, and plasma was obtained from some of them. The anti-CV-B activity of clinical samples was determined by neutralization of the cytopathic effect induced by challenging viruses in vitro and expressed as titre value. Results Overall prevalence and levels of anti-CV-B4 activity of saliva were higher in patients (n = 181) than in controls (n = 135; P = .0002; titre values ≥ 16: odds ratio = 4.22 95% CI: 1.90-9.38 P = .0002). It has been shown that IgA1 played a role in this activity. There was no correlation between the saliva and the plasma anti-CV-B4 neutralizing activity. The neutralizing activity of saliva against CV-B1, CV-B2, CV-B3, and CV-B5 existed rarely, if at all. Increased levels of anti-CV-B4 activity were observed all along a 4 year follow-up period in patients but not in matched controls (P = .01). Conclusion There is an anti-CV-B4 activity in saliva of patients with type 1 diabetes that may be a useful marker to study the role of CV-B in the pathogenesis of the disease.

Rheumatoid arthritis (RA) and Langerhans cell histiocytosis (LCH) are common and rare diseases, respectively. They associate myeloid cell recruitment and survival in inflammatory conditions with tissue destruction and bone resorption. Manipulating dendritic cell (DC), and, especially, regulating their half-life and fusion, is a challenge. Indeed, these myeloid cells display pathogenic roles in both diseases and may be an important source of precursors for differentiation of osteoclasts, the bone-resorbing multinucleated giant cells. We have recently documented that the proinflammatory cytokine IL-17A regulates long-term survival of DC by inducing BCL2A1 expression, in addition to the constitutive MCL1 expression. We summarize bibliography of the BCL2 family members and their therapeutic targeting, with a special emphasis on MCL1 and BCL2A1, discussing their potential impact on RA and LCH. Our recent knowledge in the survival pathway, which is activated to perform DC fusion in the presence of IL-17A, suggests that targeting MCL1 and BCL2A1 in infiltrating DC may affect the clinical outcomes in RA and LCH. The development of new therapies, interfering with MCL1 and BCL2A1 expression, to target long-term surviving inflammatory DC should be translated into preclinical studies with the aim to increase the well-being of patients with RA and LCH.