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BACKGROUND: Primary hyperoxalurias (PHs) are rare genetic diseases that increase the endogenous level of oxalate, a waste metabolite excreted predominantly by the kidneys and also the gut. Treatments aim to improve oxalate excretion, or reduce oxalate generation, to prevent kidney function deterioration. Oxalobacter formigenes is an oxalate metabolizing bacterium. This Phase III, double-blind, placebo-controlled randomized trial investigated the effectiveness of orally administered Oxabact™, a lyophilized O. formigenes formulation, at reducing plasma oxalate levels in patients suffering from PH. METHODS: Subjects (≥ 2 years of age) with a diagnosis of PH and maintained but suboptimal kidney function (mean estimated glomerular filtration rate at baseline < 90 mL/min/1.73 m2) were eligible to participate. Subjects were randomized to receive Oxabact or placebo twice daily for 52 weeks. Change from baseline in plasma oxalate concentration at Week 52 was the primary study endpoint. RESULTS: Forty-three subjects were screened, 25 were recruited and one was discontinued. At Week 52, O. formigenes was established in the gut of subjects receiving Oxabact. Despite decreasing plasma oxalate level in subjects treated with Oxabact, and stable/increased levels with placebo, there was no significant difference between groups in the primary outcome (Least Squares mean estimate of treatment difference was - 3.80 µmol/L; 95% CI: - 7.83, 0.23; p-value = 0.064). Kidney function remained stable in both treatments. CONCLUSIONS: Oxabact treatment may have stabilized/reduced plasma oxalate versus a rise with placebo, but the difference over 12 months was not statistically significant (p = 0.06). A subtle effect observed with Oxabact suggests that O. formigenes may aid in preventing kidney stones. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Hiperoxaluria Primaria , Hiperoxaluria , Cálculos Renales , Humanos , Hiperoxaluria/terapia , Hiperoxaluria Primaria/terapia , Oxalobacter formigenes/metabolismo , Oxalatos , Cálculos Renales/metabolismoRESUMEN
BACKGROUND: Primary hyperoxaluria type 1 (PH1) is an autosomal recessive metabolic disorder caused by inherited mutations in the AGXT gene encoding liver peroxisomal alanine:glyoxylate aminotransferase (AGT). PH1 is a clinically and genetically heterogeneous disorder. The aim of our study was to analyze and characterize the mutational spectrum of PH1 in Tunisian patients. MATERIALS AND METHODS: Molecular studies of 146 Tunisian patients suspected with PH were performed by PCR/Restriction fragment length polymorphism (RFLP) to detect seven mutations described as the most common. Direct sequencing for the 11 exons was performed in patients in whom any mutation was not identified. RESULTS: The genetic diagnosis of PH1 was confirmed in 62.3% of patients. The first molecular approach based on PCR/restriction enzyme test was positive in 37.6% of patients, whereas the second molecular approach based on whole gene sequencing was successful in 24% of cases. Twelve pathogenic mutations were detected in our cohort. Two mutations were novel, and five were detected for the first time in Tunisians. The three most frequent mutations were p.Ile244Thr, p.Gly190Arg, and c.33dupC, with a frequency of 43.4%, 21.4%, and 13.1%, respectively. CONCLUSION: The two novel mutations detected in our study extend the spectrum of known AGXT gene mutations. The screen for the mutations identified in this study can provide a useful, cost-effective, and first-line investigation in Tunisian PH1 patients.
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Hiperoxaluria Primaria/genética , Transaminasas/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Haplotipos , Humanos , Lactante , Masculino , Persona de Mediana Edad , Mutación Missense , Adulto JovenRESUMEN
BACKGROUND: Oral steroid treatment is the first line of therapy for childhood nephrotic syndrome (NS). However, resistance to this treatment has been observed in some patients. Here, we investigated the association of two steroid metabolism-related genes with susceptibility to childhood NS and the steroid response. METHODS: We genotyped the single nucleotide polymorphisms (SNP) of MDR-1 [C1236T (rs1128503), G2677T/A (rs2032582), and C3435T (rs1045642)] and the CYP3A5 gene (A6986G) in 63 NS patients and 110 age and gender matched controls by PCR-RFLP. RESULTS: Based on multivariate logistic regression analysis carrying the G2677A A allele seemed to multiply both the risk of NS and the risk of developing glucocorticoid (GC) resistance by three-fold (OR = 3.50, [1.37 - 7.06] , p < 0.001, OR = 3.07, [1.06 - 26.10], p = 0.048, respectively). When combined into haplotype, the TAT (1236_T, 2677_A, and 3435_T) haplotype conferred a two-fold NS risk (OR = 2.26, [1.11 - 4.58], p = 0.023) and almost three-fold risk to develop resistance to GC (OR = 2.69, [1.12 - 8.79], p = 0.044). However, TAT carriers seemed to have less risk to develop NS at late age (OR = 0.34, [0.12 - 0.92], p = 0.037). The C1236T (MDR-1) and the A6986G (CYP3A5) polymorphisms showed a trend of association to GC resistance but these associations did not reach the statistical significance (OR = 2.83, [0.54 - 14.67], p = 0.294), (OR = 2.11, [0.53 - 8.38], p = 0.28), respectively. CONCLUSIONS: Here we report that only the G2677A polymorphism was associated to NS susceptibility and steroid resistance. The TAT haplotype was associated with NS susceptibility especially at an early age and with steroid resistance.
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Citocromo P-450 CYP3A/genética , Síndrome Nefrótico/genética , Esteroides/uso terapéutico , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Niño , Genotipo , Haplotipos , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Polimorfismo GenéticoRESUMEN
BACKGROUND: Primary hyperoxaluria type 1 (PH1), is a rare and heterogeneous disease and one of major causes of renal insufficiency in Tunisia, caused by mutations in the AGXT gene. 33-34InsC mutation, was mainly described in children with a severe clinical feature leading to early death, but it was uncommonly reported in adult patients. METHODS: Common mutations in AGXT were tested using PCR/RFLP technique in 111 patients (68 adult, 43 children) with suspected PH1. RESULTS: We described 16 cases (eight adult and eight children) with a 33-34InsC mutation with a median age of 24 years [6 months - 73 years]. All children were in end stage renal disease (ESRD) at the median age of 3 years due to lithiasis and/or nephrocalcinosis. Unfortunately, 75% of them died with a median age of 2.5 years. For the majority of adults only spontaneous elimination of urolithiasis were noted, 37.5% preserved until now a normal renal function and 62.5% of them reached ESRD at the median age of 55.8 ± 12.31 years old. CONCLUSION: In this study 33-34InsC mutation gives a controversial clinical effect in children and adults. The implication of other genetic and/or environmental factors can play a crucial role in determining the ultimate phenotype.
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Heterocigoto , Hiperoxaluria Primaria/epidemiología , Hiperoxaluria Primaria/genética , Mutación/genética , Transaminasas/genética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Hiperoxaluria Primaria/diagnóstico , Lactante , Masculino , Persona de Mediana Edad , Linaje , Estudios Retrospectivos , Resultado del Tratamiento , Túnez/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Primary hyperoxaluria type 3 (PH3) is due to mutations in the recently identified 4-hydroxy-2-oxoglutarate aldolase (HOGA1) gene. PH3 might be the least severe form with a milder phenotype with good preservation of kidney function in most patients. The aim of this study was to report three PH3 cases carrying mutations in HOGA1. MATERIALS AND METHODS: Genetic analysis of HOGA1 was performed in patients with a high clinical suspicion of PH after sequencing of AGXT and GRHPR genes, which was negative. Also, a complete AGXT/GRHPR MLPA was performed in these patients in order to detect large deletions/insertions. RESULTS AND DISCUSSION: Two different HOGA1 gene mutations were identified: the p.Pro190Leu in a homozygous state and the p.Gly287Val in two patients in homozygous and heterozygous carriers. The median age at onset of clinical symptoms was 3.93 years. Most of the patients had a positive family history for recurrent urolithiasis. The p.Pro190Leu mutation was reported with impaired renal function at follow-up; however, the p.Gly287Val was presented with normal renal function. All patients were presented with urolithiasis, but only one had a nephrocalcinosis. CONCLUSION: This study expanded the number of PH3 patients from 63 to 66 cases. The p.Pro190Leu and the p.Gly287Val mutations found in this study can provide a first-line investigation in Tunisian PH1 patients.
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Hiperoxaluria Primaria/genética , Mutación/genética , Oxo-Ácido-Liasas/genética , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Humanos , Masculino , TúnezRESUMEN
The ß hemoglobinopathies [ß-thalassemia (ß-thal) and structural hemoglobin (Hb) variants such as Hb S (HBB: c.20A > T) and Hb E (HBB: c.79G > A)] are among the most common inherited diseases worldwide. In Tunisia, due to the high prevalence of consanguineous marriages, the recurrent risk of this disease is high. The average prevalence of hemoglobinopathies is 4.48%, reaching 12.50% in some focus regions. The molecular investigations on thalassemia contributed to establishing the spectrum of mutations in the Tunisian population. The total number of HBB gene mutations identified was 24. The two most frequent mutations, codon 39 (C > T) (HBB: c.118C > T) and IVS-I-110 (G > A) (HBB: c.93-21G > A) accounted for 70.0% of the total encountered ß-thal cases. These two mutations together with IVS-I-2 (T > G) (HBB: c.92 + 2T > G) and the Hb S variant account for more than 90.0% of all HBB genetic variants in Tunisia. Thus, developing rapid, inexpensive and reliable mutation-specific molecular diagnostic assays targeting our Tunisian populations is our aim to facilitate routine detection of hemoglobinopathies. In this report, we describe the successful application of the multiplex minisequencing assay as an alternative strategy for genetic diagnosis of HBB gene disorders in Tunisia.
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Mutación , Globinas beta/genética , Talasemia beta/epidemiología , Talasemia beta/genética , Genotipo , Humanos , Fenotipo , Análisis de Secuencia de ADN , Túnez/epidemiologíaRESUMEN
BACKGROUND: Patients with Down syndrome are at a higher risk of developing autoimmune disorders such as thyroiditis, diabetes, and celiac disease compared with the general population. Although some diseases are well known to be associated with Down syndrome, others such as idiopathic pulmonary hemosiderosis and ischemic stroke due to protein C deficiency remain rare. CASE PRESENTATION: We report a case of a 2.5-year-old Tunisian girl with Down syndrome and hypothyroiditis admitted with dyspnea, anemia, and hemiplegia. Chest X-ray showed diffuse alveolar infiltrates. Laboratory tests showed severe anemia with hemoglobin of 4.2 g/dl without hemolysis. A diagnosis of idiopathic pulmonary hemosiderosis was confirmed by bronchoalveolar lavage showing numerous hemosiderin-laden macrophages, with a Golde score of 285 confirming the diagnosis of pulmonary hemosiderosis. Concerning hemiplegia, computed tomography showed multiple cerebral hypodensities suggestive of cerebral stroke. The etiology of these lesions was related to protein C deficiency. CONCLUSION: Idiopathic pulmonary hemosiderosis remains a severe disease, which is rarely associated with Down syndrome. The management of this disease in Down syndrome patients is difficult, especially when associated with an ischemic stroke secondary to protein C deficiency.
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Síndrome de Down , Hemosiderosis , Accidente Cerebrovascular Isquémico , Enfermedades Pulmonares , Deficiencia de Proteína C , Accidente Cerebrovascular , Femenino , Humanos , Niño , Preescolar , Síndrome de Down/complicaciones , Hemiplejía , Deficiencia de Proteína C/complicaciones , Enfermedades Pulmonares/diagnóstico , Accidente Cerebrovascular/complicaciones , Hemosiderosis/complicaciones , Hemosiderosis/diagnóstico , Hemosiderosis/patologíaRESUMEN
Pulmonary mucoepidermoid carcinoma (PMEC) in children is a rare entity. The diagnosis is often unrecognized, often treated as pneumonia, a more frequent diagnosis at this age. Case presentation: The authors report in this article, the case of a 12-year-old child with a clinical history of chronic cough evolving for 6 months with recurrent episodes of pneumonia. The presence of a foreign body was suggested on the thoracic computed tomography (CT). PMEC was histopathologically determined on biopsy. Fluorine-18-fluorodesoxyglucose positron emission tomography (18 F-FDG PET)/CT was performed as part of the extension work-up prior to surgical management. Clinical discussion: Preoperative imaging with 18F-FDG PET/CT seems to be a valuable tool for predicting tumor grade, nodal stage, and postsurgical prognosis in mucoepidermoid carcinoma. PMEC patients with high 18F-FDG PET/CT uptake may need extensive mediastinal lymph node dissection and adjuvant therapy. Conclusion: PMEC has different presentations depending on the degree of tumor differentiation on PET/CT whose input in the management of these rare cancers requires further studies.
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OBJECTIVES: Early diagnosis in Turner syndrome is desirable to optimize growth and puberty and yet, it is often made late. Here, we aim to identify age at diagnosis, clinical features at presentation and potential strategies to improve the care of TS girls. METHODS: Retrospective study, including patients from 14 care centers across Tunisia including neonatal and pediatric care units, adult endocrinology and genetics departments. RESULTS: We identified 175 patients with TS, karyotype showing 45, xmonosomy in 83(47.4â¯%) with mosaicism in 37(20â¯%). Mean ± SD, median (range) age at diagnosis available in 173 patients was 13 ± 9.2,12 (birth-48) years. The diagnosis was antenatal in 4(2.3â¯%), from birth-2 years in 14 (8â¯%)with lymphoedema (8)and dysmorphic features (9),2-12 years in 53 (35.5â¯%) including 35 with short stature, 13-18 years in 43(28.8â¯%) with short stature(28) and delayed puberty(14) and 35(23.5â¯%) after 18 years, related to ovarian insufficiency (20) and short stature (11). The associated malformations were cardiac in 14 (12.8â¯%), renal in 22 (19.6â¯%). A total of 56 girls (32â¯%) had proven gonadal dysgenesis and 13 (7â¯%) had otological problems. Parental height was available in 71 girls (40â¯%) of whom 59 were below the lower end of parental target range (LTR) (83â¯%). CONCLUSIONS: This first Tunisian multicenter study, the first African of its kind, reveals that more than half of Turner syndrome cases are diagnosed after the age of 12 years. Subsequently, national strategies for an earlier TS diagnosis are needed such as measuring and plotting parental heights as well as introducing a systematic height screening at 5 years in Tunisia with a view to carrying out a re-audit in five years' time.
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Hipogonadismo , Síndrome de Turner , Embarazo , Niño , Recién Nacido , Adulto , Humanos , Femenino , Síndrome de Turner/epidemiología , Síndrome de Turner/genética , Síndrome de Turner/diagnóstico , Estudios Retrospectivos , Cariotipificación , CariotipoRESUMEN
INTRODUCTION: Kawasaki syndrome (KS) is a systemic vasculitis of unknown etiology that affects medium and small blood vessels. The aim of our study is to analyze coronary artery lesions in children with KS and their risk factors. MATERIAL AND METHODS: All children under the age of 15 years-old presenting KS and admitted in the pediatric department of three university hospital (Sahloul hospital, and Farhat Hached hospital of Sousse, Ibn El Jazzar hospital of Kairoun) from January 2000 to December 2018 were included. RESULTS: Sixty-five patients were included in our study. The mean age at diagnosis was of 29.9 months [2-120 months] and the sex ratio was of 1.7. Echocardiography was performed in all patients. It showed coronary dilation in 37% of patients with coronary artery diameter of 4.2 mm on average [3.2-7mm]. The coronary aneurysm was small in 19 cases and medium in 5 cases. No giant aneurysm has been identified. In univariate analysis, the predictors of coronary artery lesions were male sex, atypical form, fever duration more than 10 days, hepatic cytolysis, thrombocytosis and anemia. In multivariate analysis, only the last four parameters were the predictive factors of the coronary artery involvement. CONCLUSION: Several risk factors can be used to determine which children are predisposed to develop coronary dilations. In case of patient with risk factors, intravenous immunoglobulins should be initiated early to avoid these serious complications.
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Aneurisma Coronario , Enfermedad de la Arteria Coronaria , Síndrome Mucocutáneo Linfonodular , Adolescente , Niño , Aneurisma Coronario/diagnóstico por imagen , Aneurisma Coronario/epidemiología , Aneurisma Coronario/etiología , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad de la Arteria Coronaria/etiología , Vasos Coronarios , Femenino , Humanos , Lactante , Masculino , Síndrome Mucocutáneo Linfonodular/complicaciones , Síndrome Mucocutáneo Linfonodular/diagnóstico , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Steroid-resistant nephrotic syndrome (NS) remains one of the most intractable causes of end-stage renal disease in the first two decades of life. Several genes have been involved including NPHS1, NPHS2, WT1, PLCE1, and LAMB2. Our aim was to identify causative mutations in these genes, in 24 children belonging to 13 families with NS manifesting with various ages of onset. We performed haplotype analysis and direct exon sequencing of NPHS1, NPHS2, PLCE1, LAMB2, and the relevant exons 8 and 9 of WT1. Ten different pathogenic mutations were detected in seven families concerning four genes (NPHS1 (3/7), LAMB2 (2/7), NPHS2 (1/7), and WT1 (1/7)). Five of the detected mutations were novel; IVS9+2 T>C and p.D616G in NPHS1; p.E371fsX16 in NPHS2, and p.E705X and p.D1151fsX23 in LAMB2. Nine of 24 patients failed to be categorized by mutational analysis. Our study extends the spectrum of abnormalities underlying NS, by reporting novel mutations in the NPHS1 and NPHS2 genes and the first cases of LAMB2 mutations in Tunisia. Congenital and infantile NS can be explained by mutations in NPHS1, NPHS2, WT1, or LAMB2 genes. The identification of additional genes mutated in NS can be anticipated.
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Análisis Mutacional de ADN , Péptidos y Proteínas de Señalización Intracelular/genética , Laminina/genética , Proteínas de la Membrana/genética , Proteínas WT1/genética , Adolescente , Niño , Preescolar , Exones , Femenino , Genotipo , Humanos , Lactante , Recién Nacido , Masculino , Mutación , Síndrome Nefrótico/congénito , Síndrome Nefrótico/genética , Linaje , Túnez , Adulto JovenRESUMEN
BACKGROUND: Primary hyperoxaluria type I (PH1) is a rare genetic disorder characterized by allelic and clinical heterogeneity. Four mutations (G170R, 33_34insC, I244T and F152I) account for more than 50% of PH1 alleles and form the basis for diagnostic genetic screening for PH1. We aimed to analyze the prevalence of these specific mutations causing PH1, and to provide an accurate tool for diagnosis of presymptomatic patients as well as for prenatal diagnosis in the affected families. METHODS: Polymerase chain reaction/Restriction Fragment Length Polymorphism, were used to detect the four mutations in the AGXT gene in DNA samples from 57 patients belonging to 40 families. RESULTS: Two mutations causing PH1 were detected in 24 patients (42.1%), with a predominance of the I244T mutation (68% of patients) and 33_34insC (in the remaining 32%). In 92% of cases, mutated alleles were in homozygous state. The presented clinical features were similar for the two mutations. The age of onset was heterogeneous with a higher frequency of the pediatric age. In 58.3% of cases, the presentation corresponded to advanced renal disease which occurred early (< 5 years) in the two mutations. In adolescents, only the I244T mutation was detected (41.1%). I244T and 33_34insC mutations were observed in adult patients, with 17.6% and 12.5% respectively. CONCLUSION: Limited mutation analysis can provide a useful first line investigation for PH1. I244T and 33_34insC presented 28.2% of identified mutations causing disease in our cohort. This identification could provide an accurate tool for prenatal diagnosis in the affected families, for genetic counselling and for detection of presymptomatic individuals.
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Hiperoxaluria/diagnóstico , Hiperoxaluria/genética , Mutación/genética , Transaminasas/genética , Adolescente , Adulto , Alelos , Niño , Preescolar , Femenino , Pruebas Genéticas , Humanos , Hiperoxaluria/epidemiología , Lactante , Masculino , Persona de Mediana Edad , Diagnóstico Prenatal , Estudios Retrospectivos , Túnez/epidemiología , Adulto JovenRESUMEN
B-type natriuretic peptide (BNP) is a biomarker of cardiovascular disease that is common in adults with chronic kidney disease (CKD). However, in children with CKD, the range and predictive power of BNP concentrations are not known. We aimed to determine the effect of HD on BNP, as well as the prognostic impact of BNP, in end-stage renal disease (ESRD) children undergoing hemodialysis (HD). Thirty-five children with chronic renal failure (16 boys age 12.1 ± 3.7 years) on maintenance HD were included. BNP level was measured, and Doppler echocardiography was performed 30 min before (pre-HD BNP) and 30 min after (post-HD BNP) HD in each patient. An adverse event was defined as all-cause death and heart failure hospitalization. The median pre-HD BNP, the post-HD BNP, and the change in BNP were, respectively, 240 pg/ml (72 to 3346), 318 pg/ml (79 to 3788), and 9 pg/ml (-442 to 1889). Pre-HD BNP concentration was negatively correlated with left ventricular (LV) ejection fraction (r = -0.41, P = 0.018). During a mean follow-up of 39 ± 14 months, 6 patients died, and 3 were hospitalized for heart failure. Using univariate analysis, BNP before and after HD as well as Doppler tissue imaging velocities had a strong graded relationship with adverse events. Cox proportional hazards model demonstrated that pre-HD body weight (P = 0.008), pre-HD BNP (P = 0.011), and post-HD BNP (P = 0.038) remained independent predictors of adverse outcome. Even in case of ESRD, BNP still strongly correlated with LV systolic and diastolic dysfunction and was associated with mortality in HD children.
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Fallo Renal Crónico/fisiopatología , Fallo Renal Crónico/terapia , Péptido Natriurético Encefálico/sangre , Diálisis Renal , Disfunción Ventricular Izquierda/fisiopatología , Adolescente , Biomarcadores/sangre , Peso Corporal/fisiología , Causas de Muerte , Niño , Preescolar , Estudios de Cohortes , Ecocardiografía Doppler , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/mortalidad , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Volumen Sistólico/fisiología , Disfunción Ventricular Izquierda/mortalidad , Adulto JovenRESUMEN
Introduction. Respiratory syncytial virus (RSV) is the most frequently identified viral agent in children with lower respiratory tract infection (LRTI). No data are available to date regarding RSV genotypes circulating in Tunisia.Aim. The aim of the present study was to investigate the genetic variability of the glycoprotein G gene in Tunisian RSV strains.Methodology. Nasopharyngeal aspirates were collected from infants hospitalized for LRTI in five Tunisian hospitals. All specimens were screened for RSV by a direct immunofluorescence assay (DIFA). To molecularly characterize Tunisian RSV strains, a phylogenetic analysis was conducted. Randomly selected positive samples were subjected to reverse transcription PCR amplifying the second hyper-variable region (HVR2) of the G gene.Results. Among a total of 1417 samples collected between 2015 and 2018, 394 (27.8â%) were positive for RSV by DIFA. Analysis of 61 randomly selected RSV strains revealed that group A RSV (78.7â%) predominated during the period of study as compared to group B RSV (21.3â%). The phylogenetic analysis showed that two genotypes of RSV-A were co-circulating: the ON1 genotype with a 72-nt duplication in HVR2 of the G gene was predominant (98.0â% of RSV-A strains), while one RSV-A strain clustered with the NA1 genotype (2.0â%). Concerning Tunisian group B RSV strains, all sequences contained a 60-nt insertion in HVR2 and a clustered BA10 genotype.Conclusion. These data suggest that RSV-A genotype ON1 and RSV-B genotype BA10, both with duplications in the G gene, were widely circulating in the Central coastal region of Tunisia between 2015 and 2018.
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Filogenia , Infecciones por Virus Sincitial Respiratorio/virología , Virus Sincitial Respiratorio Humano/genética , Preescolar , Femenino , Genotipo , Humanos , Lactante , Masculino , Epidemiología Molecular , Infecciones por Virus Sincitial Respiratorio/epidemiología , Virus Sincitial Respiratorio Humano/clasificación , Virus Sincitial Respiratorio Humano/aislamiento & purificación , Estaciones del Año , Túnez/epidemiologíaRESUMEN
Introduction. Group A Rotavirus (RVA) is known to be a major cause of acute gastroenteritis (AGE) in children but its role as a potential pathogen in immunocompetent adults is probably underestimated.Aim. To compare RVA infections in patients from different age groups.Methodology. Fecal samples were collected from patients aged from birth to 65 years, hospitalized or consulting for AGE between 2015 and 2017. All samples were screened by RT-PCR for the detection of VP6 gene specific of RVA. RVA-positive samples were VP7 and VP4 genotyped using multiplex semi-nested RT-PCR. Full-length VP7 gene of G9-positive strains were sequenced and submitted for phylogenetic analysis.Results. Of 1371 stool specimens collected from children (<5 years; n=454), older children (5 to <15 years; n=316) and adults (15-65 years; n=601), 165 (12.0â%) were RVA-positive. RVA detection rates were significantly higher in children and adults than in older children (15.8â% and 12.1 Vs 6.3â%, respectively; P<0.001). While RVA infections were mostly detected during the coldest months in children, they were observed all year-round in patients aged >5 years. Although G1P[8] remained the most prevalent combination (41.7â%) detected in children, G9P[8] strains widely predominated in adults (58.1â%), followed by G2P[4] (12.9â%). All characterized G9 strains clustered in the modern lineage III.Conclusion. RVA play an important role in AGE not only in children but also in adults. The findings of a wide G9 predominance in patients >5 years highlights the need for continuing surveillance in both pediatric and mature populations.
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Diarrea/virología , Infecciones por Rotavirus/virología , Rotavirus/aislamiento & purificación , Adolescente , Adulto , Anciano , Antígenos Virales/genética , Proteínas de la Cápside/genética , Niño , Preescolar , Heces/virología , Femenino , Genotipo , Humanos , Lactante , Masculino , Persona de Mediana Edad , Filogenia , Rotavirus/clasificación , Rotavirus/genética , Túnez , Adulto JovenRESUMEN
AIM: To establish a preliminary national report on clinical and genetic features of cystic fibrosis (CF) in Tunisian children as a first measure for a better health care organization. METHODS: All children with CF diagnosed by positive sweat tests between 1996 and 2015 in children's departments of Tunisian university hospitals were included. Data was recorded at diagnosis and during the follow-up from patients' medical records. RESULTS: In 12 departments, 123 CF children were collected. The median age at diagnosis was 5 months with a median diagnosis delay of 3 months. CF was revealed mostly by recurrent respiratory tract infections (69.9%), denutrition (55.2%), and/or chronic diarrhea (41.4%). The mean sweat chloride concentration was 110.9mmol/L. At least one mutation was found in 95 cases (77.2%). The most frequent mutations were Phe508del (n=58) and E1104X (n=15). Fifty-five patients had a Pseudomonas Aeruginosa chronic colonization at a median age of 30 months. Cirrhosis and diabetes appeared at a mean age of 5.5 and 12.5 years respectively in 4 patients each. Sixty-two patients died at a median age of 8 months. Phe508del mutation and hypotrophy were associated with death (p=0.002 and p<0.001, respectively). CONCLUSION: CF is life-shortening in Tunisia. Setting-up appropriate management is urgent.
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Fibrosis Quística/epidemiología , Niño , Fibrosis Quística/complicaciones , Diarrea/etiología , Femenino , Humanos , Lactante , Masculino , Desnutrición/etiología , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/etiología , Estudios Retrospectivos , Túnez/epidemiología , Adulto JovenRESUMEN
Introduction. Tunisia is an intermediate hepatitis B virus (HBV) endemic country. The vaccination against hepatitis B was introduced in 1995 including four doses with a first dose administrated at birth. Decreasing the level of antibodies against hepatitis B surface antigen (anti-HBs) over time can be alarming. This study was conducted to explore the anti-HBV immune response among children under 6 years old, vaccinated according to the national vaccination schedule, by evaluating the immunological response to primary vaccination and by exploring the anamnestic immune response to a booster dose.Methods. We conducted a cross-sectional prospective study from June 2016 to June 2017 (n=180), based on voluntary participation. Children were recruited from the public pediatric ward sectors in Sahloul University Hospital of Sousse in Central Tunisia. An anti-HB titre was determined based on electro-chemiluminescence micro-particle immunoassay (ECLIA), using Elecsys Anti-HBs II kit, Roche.Results. Mean age at the time of enrollment in the study was 33±14.8 months. The seroprotection rate was 77.2â%. The anti-HB titre differed significantly between the different age groups (P=0.002). The predicting variable for having no seroprotective antibody level was older age. Children with anti-HB levels <10 IU l- 1 were offered an additional dose of HBV vaccine. Anamnestic response 1 month after the challenge dose was observed in 100â% of subjects. The probability of developing a high antibody response, following the booster dose increased in conjunction with an increased pre-booster antibody level.Conclusion. The response to a booster dose suggests the persistence of immune memory in almost all vaccinated individuals. Although a booster dose increases substantially anti-HB titre, the clinical relevance of such an increase remains unknown.
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Anticuerpos contra la Hepatitis B/inmunología , Vacunas contra Hepatitis B/administración & dosificación , Virus de la Hepatitis B/inmunología , Hepatitis B/inmunología , Niño , Preescolar , Estudios Transversales , Femenino , Hepatitis B/virología , Antígenos de Superficie de la Hepatitis B/administración & dosificación , Antígenos de Superficie de la Hepatitis B/inmunología , Vacunas contra Hepatitis B/inmunología , Humanos , Memoria Inmunológica , Lactante , Masculino , Estudios Prospectivos , Túnez , VacunaciónRESUMEN
Tfifha M, Kamoun T, Mama N, Mestiri S, Hassayoun S, Zouari N, Jemni H, Abroug S. Childhood sclerosing cholangitis associations in a Tunisian tertiary care hospital: a many-faceted disease. Turk J Pediatr 2019; 61: 905-914. Sclerosing cholangitis (SC) is a liver disorder affecting children and adults, causing chronic cholestasis and secondary biliary cirrhosis. The purpose of this study was to present different associated diseases to SC in a Tunisian tertiary care hospital. Six patients were identified with SC associated with other diseases, four males and two females. The first symptom was liver enlargement in all cases with abnormal liver biochemistry. A moderate increase in AST and ALT levels was registered in all cases with moderate cholestasis in 4 patients. Three of them presented an auto-immune condition. Two patients were diagnosed with auto-immune hepatitis prior to SC and Crohn disease in only one patient. One developed linear IgA bullous dermatosis. Three patients were diagnosed with Multisystemic Langerhans Cell Histiocytosis (LCH). The primary site of LCH was the liver associated secondary to insipidus diabetes (one case), mastoiditis (two cases) and chest localization (one case). The outcome of those patients was variable with poor prognosis especially for SC secondary to LCH. No patient underwent liver transplantation. SC is a rare disorder with variable clinical presentations. To our knowledge, this is the first report of this condition in Tunisian and North African children. Diagnosis and treatment of SC and its associations remains a challenge, especially because there is still no effective medical therapy aimed at preventing disease progression. Pediatric liver transplantation is the only life-extending therapeutic alternative for patients with end-stage liver failure. Liver transplantation has not been performed on young children in our country.
Asunto(s)
Colangitis Esclerosante/epidemiología , Centros de Atención Terciaria/estadística & datos numéricos , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Lactante , Masculino , Túnez/epidemiologíaRESUMEN
The aim of the present study was to report the molecular characterization of human group A rotaviruses (RVAs) circulating in Tunisia. Stool specimens were collected from children under 5 years of age who had been hospitalized or were consulting for gastroenteritis in Tunisian hospitals between 2015 and 2017. All samples were screened by reverse-transcription polymerase chain reaction (RT-PCR) for the detection of the VP6 gene specific for RVA. RVA-positive samples were further analysed for G/P genotyping by semi-nested multiplex RT-PCR. Among 454 tested samples, 72 (15.8â%) were positive for RVA. G1P[8] was the most prevalent detected strain (41.7%), followed by G9P[8] (32.8%), G2P[4] (7.5%), G12P[8] (7.5%), G1P[6] (3.0%), G2P[8] (1.5%) and G3P[8] (1.5%), with mixed infections in 4.5â% of cases. In the absence of a national anti-rotavirus vaccination strategy, RVAs remain the primary aetiological agent for gastroenteritis in Tunisian children.
Asunto(s)
Gastroenteritis/virología , Infecciones por Rotavirus/virología , Rotavirus/genética , Proteínas de la Cápside/genética , Preescolar , Heces/virología , Gastroenteritis/epidemiología , Variación Genética , Genotipo , Humanos , Lactante , Recién Nacido , Epidemiología Molecular , Prevalencia , ARN Viral/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Rotavirus/aislamiento & purificación , Infecciones por Rotavirus/epidemiología , Estaciones del Año , Análisis de Secuencia de ADN , Túnez/epidemiologíaRESUMEN
BACKGROUND: In spite of its rarity, the haemolytic and uremic syndrome (HUS) constitutes the first aetiology of acute renal insufficiency (ARI) in child. AIM: The aim of this work is to analyze clinical and evolutive aspects of the HUS in child. METHOD: We studied retrospectively 17 cases of HUS in child enrolled in the paediatrics' department of Sahloul Hospital during eight years period (1996 to 2003). RESULTS: It is about four boys and 13 girls (sex-ratio = 0.3) aged three months to nine years (mean age: 32 months). Typical HUS was observed in eight child and atypical HUS in the nine others which three presenting a familial form and one associated with steroid resistant nephrotic syndrome. Diagnosis of HUS was established on the classic triad of the disease (anaemia, thrombopenia and ARI) and/or by the histology. Extra-renal manifestations (neurological or digestive involvement) were observed in 11 patients. A blood transfusion was indicated in 13 patients presenting severe anaemia. Peritoneal dialysis was indicated for nine patients while three others required haemodialysis because renal insufficiency had evolved quickly to the end stage. Thirteen cases of HUS (eight typical and five atypical) have received plasma therapy during two to five days. The short-term evolution was favourable with recuperation of normal renal function in seven cases (five with typical SHU and two with atypical SHU). Three children developed terminal renal insufficiency and were currently in haemodialysis. Five patients (four cases of atypical HUS and one case of typical HUS) died of the continuations of the ARI and/or nosocomial infection. CONCLUSION: The HUS remains a serious illness because of the risk of complications that can occur to short and long-term. Currently, the specific treatment is only recommended in patients presenting an atypical form of HUS.