The risk of pig and chicken farming for carriage and transmission of Escherichia coli containing extended-spectrum beta-lactamase (ESBL) and mobile colistin resistance (mcr) genes in Thailand.

South-East Asian countries report a high prevalence of extended-spectrum cephalosporin- (ESC-) and colistin-resistant Escherichia coli (Col-R-Ec). However, there are still few studies describing the molecular mechanisms and transmission dynamics of ESC-R-Ec and, especially, Col-R-Ec. This study aimed to evaluate the prevalence and transmission dynamics of Ec containing extended spectrum beta-lactamases (ESBL) and mobile colistin resistance (mcr) genes using a 'One Health' design in Thailand. The ESC-R-Ec and Col-R-Ec isolates of human stool samples (69 pig farmers, 155 chicken farmers, and 61 non-farmers), rectal swabs from animals (269 pigs and 318 chickens), and the intestinal contents of 196 rodents were investigated. Resistance mechanisms and transmission dynamics of Ec isolates (n=638) were studied using short and long read sequencing. We found higher rates of ESBL-Ec isolates among pig farmers (n=36; 52.2%) than among chicken farmers (n=58; 37.4 %; P<0.05) and the control group (n=61; 31.1 %; P<0.05). Ec with co-occurring ESBL and mcr genes were found in 17 (6.0 %), 50 (18.6 %) and 15 (4.7 %) samples from humans, pigs and chickens, respectively. We also identified 39 (13.7 %) human samples with non-identical Ec containing ESBL and mcr. We found higher rates of ESBL-Ec, in particular CTX-M-55, isolates among pig farmers than among non-pig farmers (P<0.01). 'Clonal' animal-human transmission of ESBL-Ec and Ec with mcr genes was identified but rare as we overall found a heterogenous population structure of Ec. The Col-R-Ec from human and animal samples often carried mcr-1.1 on conjugative IncX4 plasmids. The latter has been identified in Ec of many different clonal backgrounds.

Acute Disseminated Encephalomyelitis Following COVID-19 Infection.

Acute disseminated encephalomyelitis (ADEM) is a relatively rare, post-inflammatory, immune-mediated demyelinating central nervous system disease that is predominantly reported in pediatric populations. Following the emergence of severe acute respiratory syndrome coronavirus 2, cases of ADEM are being reported following infection with this virus. Our case report describes a male patient in his early 40s who developed severe coronavirus disease 2019 (COVID-19) that rapidly progressed to a critical disease requiring invasive mechanical ventilation and high positive end-expiratory pressure, which was complicated by extensive neurological involvement and quadriplegia. MRI of the brain showed characteristic demyelinating lesions, suggestive of ADEM. As other entities were ruled out, our patient was treated using pulse steroids and intravenous immunoglobulins. The patient showed a good response to treatment and had an overall good prognosis, despite the severity of his condition. ADEM following COVID-19 is a rare entity worldwide.

The First Documented Ibuprofen-Induced Toxic Epidermal Necrolysis in the Middle East and North Africa Region: A Case Report, Complications, and Management.

INTRODUCTION: Stevens-Johnson syndrome (SJS), Stevens-Johnson/toxic epidermal necrolysis overlap syndrome (SJS/TEN) and toxic epidermal necrolysis (TEN) are rare, acute, potentially lethal conditions, considered to be part of the severe cutaneous adverse reactions (SCARs) spectrum, with TEN being the most life-threatening. The distinction between these three entities is based on the extent of total skin surface involvement, with SJS involving < 10%, SJS/TEN involving 10-30% and TEN involving > 30% of total body surface area. These mucocutaneous reactions are most commonly caused by a hypersensitivity reaction to a drug, with infections and vaccines being possible, less common etiologies. CASE PRESENTATION: In the following case report, we summarize a rare case of a 43-year-old, previously healthy male patient who presented with TEN after taking ibuprofen, a non-steroidal anti-inflammatory drug. According to PubMed literature, this is the first documented case of ibuprofen-induced TEN in the Middle East and North Africa (MENA) region. DISCUSSION: TEN is an autoimmune bullous disorder that results in the death of keratinocytes, leading to complete dermo-epidermal separation. In the case of our patient, the desquamation was extensive, involving 70% of the total body surface area, and was complicated by a triple bacterial infection with Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The patient was treated with colistin and meropenem, in addition to supportive management, hydration and nutritional support. CONCLUSION: In the case of TEN, early diagnosis and hospitalization in a burn centre are crucial to allow rapid healing, and improve the quality of life of the affected patients. Immediate cessation of the causative mediation is critical. Supportive management, hydration, nutritional support, and maintenance of aseptic conditions are highly encouraged to reduce the mortality and morbidity associated with TEN.

Population Diversity of Antibiotic Resistant Enterobacterales in Samples From Wildlife Origin in Senegal: Identification of a Multidrug Resistance Transposon Carrying bla CTX-M-15 in Escherichia coli.

Introduction: The role of wildlife in the transmission of antimicrobial resistant (AMR) is suspected but scarcely reported in current studies. Therefore, we studied the dynamics and prevalence of antibiotic-resistant Enterobacterales in antibiotic-limited areas of Senegal. Materials and Methods: We collected fecal samples from monkeys and apes (N = 226) and non-fecal environmental samples (N = 113) from Senegal in 2015 and 2019. We grew the samples on selective media, subsequently isolated AMR Enterobacterales, and then sequenced their genomes. Results: We isolated 72 different Enterobacterales among which we obtained a resistance rate of 65% for colistin (N = 47/72) and 29% for third generation-cephalosporin (C3G) (29%, N = 21/72). Interestingly, almost 46% of our isolates, among Enterobacter sp., Citrobacter cronae and Klebsiella aerogenes, belong to 34 new STs. Moreover, the genes bla CTX-M-15, bla TEM1B , sul2, dfrA14, qnrs, aph(3''), aph(6), tetA, and tetR harbored within a transposon on the IncY plasmid of ST224 Escherichia coli were transferred and inserted into a ST10 E. coli phage coding region. Conclusion: Wildlife constitutes a rich, unexplored reservoir of natural microbial diversity, AMR genes and international resistant clones pathogenic in humans. The presence of a transposon that carries AMR genes is intriguing since no antibiotics are used in the non-human primates we studied.

Transfusion Reactions and Adverse Events.

Blood transfusions are generally safe but can carry considerable risks. This review summarizes the different types of transfusion reactions and ways to diagnose and manage them. Symptoms are often overlapping and nonspecific. When a reaction is suspected, it is critical to stop the transfusion immediately and report the reaction to the blood bank, as this can affect the patient's outcome. New evidence-based algorithms of transfusion, newer blood screening methods and donor policies and deferrals, new laboratory testing, electronic verification systems, and improved hemovigilance lead to the avoidance of unnecessary transfusions and decrease the incidence of serious transfusion reactions.

Multidrug-Resistant Klebsiella pneumoniae Clones from Wild Chimpanzees and Termites in Senegal.

Antibiotic resistance genes exist naturally in various environments far from human usage. Here, we investigated multidrug-resistant Klebsiella pneumoniae, a common pathogen of chimpanzees and humans. We screened antibiotic-resistant K. pneumoniae from 48 chimpanzee stools and 38 termite mounds (n = 415 samples) collected in protected areas in Senegal. The microsatellite method was used to identify chimpanzee individuals (n = 13). Whole-genome sequencing was performed on K. pneumoniae complex isolates to identify antibiotic-resistant genes and characterize clones. We found a high prevalence of carbapenem-resistant K. pneumoniae among chimpanzee isolates (18/48 samples from 7/13 individuals) and ceftriaxone resistance among both chimpanzee individuals (19/48) and termite mounds (7/415 termites and 3/38 termite mounds). The blaOXA-48 and the blaKPC-2 genes were carried by international pOXA-48 and pKPC-2 plasmids, respectively. The ESBL plasmid carried blaCTX-M-15, blaTEM-1B, and blaOXA-1 genes. Genome sequencing of 56 isolates identified two major clones associated with hospital-acquired infections of K. pneumoniae (ST307 and ST147) in chimpanzees and termites, suggesting circulation of strains between the two species, as chimpanzees feed on termites. The source and selection pressure of these clones in this environment need to be explored.

SCA Medium: A New Culture Medium for the Isolation of All Candida auris Clades.

Candida auris is an emerging multidrug-resistant yeast causing nosocomial infections and associated with high mortality in immunocompromised patients. Rapid identification and characterisation are necessary for diagnosis and containing its spread. In this study, we present a selective culture medium for all C. auris clades. This medium is sensitive with a limit of detection ranging between 101 and 102 CFU/mL. The 100% specificity of SCA (specific C. auris) medium is confirmed on a set of 135 Candida strains, 50 bacterial species and 200 human stool samples. Thus, this medium specifically selects for C. auris isolation from clinical samples, allowing the latter to study its phenotypic profile.

A One Health approach to assessing occupational exposure to antimicrobial resistance in Thailand: The FarmResist project.

This Southeast Asia-Europe research project will use a One Health approach to identify the major parameters responsible for the presence of animal-associated antimicrobial resistant bacteria in animal production facilities in Thailand and the risk of their transmission from animals to humans. We will focus on traditional, small, extensive pig and poultry farms where information on antibiotic use is scarce and animals live in close contact with humans. This cross-sectional study will be based on the epidemiological analysis of the antimicrobial resistance (AMR) present in fecal samples from animals and humans. Extended spectrum beta-lactamase producing Enterobacteriaceae (ESBL-E) and Enterobacteriaceae resistant to colistin will be actively searched in the feces of farm animals (pigs and poultry), small wild rodents and farmers. Phenotypic (selective plating) and genotypic (multilocus seuquence typing and sequencing) methods will be used for the detection of AMR, the identification of antibiotic resistance genes (ARGs) and the characterization of strains carrying resistance genes. Questionnaires will be administered to investigate the effects of antibiotic use, farm characteristics and biosecurity measures on the occurrence of AMR in animals. Subsequently, the fecal carriage of AMR and ARGs in farmers will be compared to a control population with no occupational contacts with animals, thus enabling an estimation of the risk of transmission of AMR/ARGs from animals to farmers.

A molecular study of Tunisian populations of Dugesia sicula (Plathelminthes, Tricladida) through an identification of a set of genes.

Cell regeneration is a natural repair of different types of tissue after an injury or a lesion, and is associated with asexual reproduction in some animals such as planarians. Its understanding and improvement could have repercussions for tissue repair and regeneration as far as humans are concerned. In this context, we have proceeded to an essential step, which is the identification of the genes involved in planarian regeneration in the model species. Dugesia sicula Lepori (D. sicula) is distributed around the Mediterranean Sea, and this population is found in most of Tunisian dams. The collection of identified genes is already known in other species. DjFoxG, DjPC2, DjotxA, and Cathepsin-D were identified by the PCR technique and their expression was confirmed by RT-PCR and in situ hybridization. DjFoxG gene, the FoxG1 homolog, is expressed throughout the planarian body, abundantly on stem cells. Consecutively, we choose a central nervous system (CNS) marker; the prohormone convertase 2 (DjPC2) gene. DjotxA was observed in the brain and especially in the region surrounding the eyes (visual cells). The regenerative cells of the gut of D. sicula were scored by the Cathepsin-D gene expression, which belongs to the aspartyl protease family. We found significant results through RT-PCR and In Situ Hybridization (ISH) techniques, confirming the expression of DjFoxG, DjPC2, DjotxA and Cathepsin-D genes in our specimens.

Distal renal tubular acidosis in a Libyan patient: Evidence for digenic inheritance.

AIM OF THE STUDY: Recent advances in understanding the underlying molecular mechanism for distal renal tubular acidosis (dRTA), led to an increased attention towards the primary and the familial forms of the disease. Mutations in ATP6V1B1 and ATP6V0A4 are usually responsible for the recessive form of the disease. Mutations in gene AE1 encoding the Cl-/HCO3- exchanger, usually present as dominant dRTA, but a recessive pattern has been recently described. Our objective is to identify the mutational spectrum responsible of dRTA in a consanguineous Libyan family. MATERIALS AND METHODS: Both ATP6V0A4 and ATP6V1B1 genes were preferentially screened in our patient. Additional whole exome sequencing (WES) in the same patient, offered a wider view on potential chromosomal rearrangements as well as the mutational spectrum of other genes involved in this disease. RESULTS: The patient is a heterozygote for two different mutations, one in each of the genes ATP6V0A4 and ATP6V1B1, while no deleterious variation was detected in the remaining genes responsible for the recessive form of dRTA. Homozygosity mapping and WES confirmed our findings and supported the hypothesis of a digenic inheritance model existing as an explanation for dRTA. CONCLUSIONS: To our knowledge, this is the first report describing a Libyan patient with dRTA who suffered from early-onset sensorineural hearing loss, with a digenic mode of inheritance, supported by the identification of two novel mutations. This study increases the understanding of how dRTA is genetically transmitted, while offers a good outline towards the molecular diagnostics and genetic counseling for dRTA in Lybians.

Technological Implications of Modifying the Extent of Cell Wall-Proanthocyanidin Interactions Using Enzymes.

The transference and reactivity of proanthocyanidins is an important issue that affects the technological processing of some fruits, such as grapes and apples. These processes are affected by proanthocyanidins bound to cell wall polysaccharides, which are present in high concentrations during the processing of the fruits. Therefore, the effective extraction of proanthocyanidins from fruits to their juices or derived products will depend on the ability to manage these associations, and, in this respect, enzymes that degrade these polysaccharides could play an important role. The main objective of this work was to test the role of pure hydrolytic enzymes (polygalacturonase and cellulose) and a commercial enzyme containing these two activities on the extent of proanthocyanidin-cell wall interactions. The results showed that the modification promoted by enzymes reduced the amount of proanthocyanidins adsorbed to cell walls since they contributed to the degradation and release of the cell wall polysaccharides, which diffused into the model solution. Some of these released polysaccharides also presented some reactivity towards the proanthocyanidins present in a model solution.

Molecular investigation of distal renal tubular acidosis in Tunisia, evidence for founder mutations.

BACKGROUND: Distal renal tubular acidosis (dRTA) is a rare genetic disease caused by mutations in different genes involved in the secretion of H+ ions in the intercalated cells of the collecting duct. Both autosomal dominant and recessive forms have been described; the latter is also associated with sensorineural hearing loss. METHODS: Twenty-two Tunisian families were analyzed for mutations in the ATP6V1B1 and ATP6V0A4 genes by direct sequencing. Dating of the founder mutations was performed. RESULTS: Two founder mutations in the ATP6V1B1 gene were found in 16/27 dRTA cases. The p.Ile386Hisfs*56 founder mutation was estimated to be older than 2400 years and no correlations were found with deafness. For the remaining patients, two mutations in the ATP6V0A4 gene, one of them being novel, were found in three Tunisian cases. The presence of a heterozygous missense mutation p.T30I, of the ATP6V1B1 gene, was identified in six patients, while no mutations of the second gene were detected. No deleterious mutations of either ATP6V1B1 or ATP6V0A were found for the two probands. CONCLUSION: Our study gives evidence of phenotypic and genotypic heterogeneity of dRTA in the Tunisian population. Five different mutations were found, two of them were due to a founder effect, and screening of these mutations could provide a rapid and valuable tool for diagnosis of dRTA.

How MRI can contribute to the diagnosis of acute demyelinating encephalomyelitis in children.

OBJECTIVE: To illustrate through 10 pediatric cases, the clinical features, course, and importance of neuroimaging (especially MRI) in guiding the diagnosis of acute disseminated encephalomyelitis (ADEM) and controlling patients after treatment. METHODS: A retrospective review of 10 pediatric cases of ADEM, with special regard to the MRI features, presenting to the Pediatric Departments, Hedi Chaker Hospital, Sfax, Tunisia between January 2002 and December 2008. RESULTS: Children with ADEM presented with variable and multiple neurological signs most often occurring after an infectious episode, especially after upper respiratory tract infection. The MRI permitted confirmation of the diagnosis by showing demyelinating lesions either in the brainstem, the cerebellum, the cerebral white and grey matter, or in the spine of all patients. CONCLUSION: Acute disseminated encephalomyelitis is characterized by multifocal demyelinating lesions resulting in varied neurological signs. The MRI is the technique of choice to show these lesions.

[Hepatopulmonary syndrome and portal hypertension]. / Syndrome hepatopulmonaire et hypertension portale.

BACKGROUND: The hepatopulmonary syndrome is known by the association of chronic hepatopathy and refractory hypoxemia linked to pulmonary vasodilatation. The hepatopathy may be an hepatic cirrhosis, a congenital porto-case shunt, a porte cavernous angioma or a portal high blood pressure. AIM: Report new cases CASE REPORT: We report the observation of a girl followed from the age of 5 years for type I auto-immune hepatitis complicated of portal high blood pressure, in whom the hepatopulmonary syndrome appears 6 years later and the diagnosis was established in front of the presence of clinical signs (cyanosis and fingers clubbing) associated to a severe hypoxia at 43 mmHg without heart attack and in front of the results of scintigraphy use with albumine micro-agregat marked to technetium 99 m which objected an increase of perfusion at the lungs and an extra pulmonary fixation (cerebral, thyroïdien and renal). In front of the severity of hypoxia and the intensity of the extra pulmonary fixation which corresponds the importance of the shunts, the hepatic transplantation shouldn't be realized and the child followed only a salt-free diet associated to a martial addition and to treatment by propanolol. CONCLUSION: The hepatopulmonary syndrome is a diagnosis to evocate in front of all hypoxia happening during the evolution of a chronic hepatopathy with portal high blood pressure. Its prognosis is severe in the absence of a hepatic transplantation.

[Vasculitis with renal involvement and antineutrophil cytoplasmic antibodies (ANCA) in a child receiving benzylthiouracil]. / Vascularite avec atteinte rénale et anticorps anticytoplasme des polynucléaires neutrophiles (ANCA) après prise de benzylthio-uracile chez l'enfant.

Vasculitis associated to antineutrophil cytoplasmic antibodies (ANCA) is a rare complication of therapy with antithyroid medication. They were mainly described in patients treated with propylthiouracil (PTU), carbimazole, methimazole and rarely by benzylthiouracil (Basden). We report a case of 12-years-old girl treated by benzylthiouracil for Grave's disease who developed after 2 years vasculitis associated with cutaneous involvement (generalized ulcer necrotic purpura) and glomerulonephritis with proteinuria of 24 hours at 26 mg/kg/day, microscopic hematuria and renal failure with creatinemia level at 135 micromol/l. The ANCA type antiMPO (myeloperoxidase) was positive. The histology study of the renal needle biopsy was in favour with focal necrotizing glomerulonephritisand crescents with different evolutive stages. The discontinuation of benzylthiouracil and the treatment by the corticoids involved a disappearance of cutaneous lesions, a negative result of proteinuria, a normalization of the renal function (creatinemia=84 micromol/l) and a disappearance of hematuria and ANCA. These results permitted to announce hypothesis that benzylthiouracil was implicated in development of vasculitis associated to ANCA.