ABSTRACT
Introducción. El síndrome urémico hemolítico (SUH) es una entidad infectocontagiosa producida por Escherichia coli productora de toxina Shiga. El objetivo fue evaluar el riesgo de contagio y evolución clinica entre hermanos con SUH típico. Población y métodos. Se analizaron las historias clínicas de los niños con SUH típico desde 1997 a 2012. Se utilizó, como criterio de inclusión, a parejas de hermanos. Se definió un puntaje de gravedad. Resultados. Se registraron 133 pacientes con SUH; 40 tenían hermanos y 4 progresaron a SUH (10%). La edad media de los 4 pares de hermanos fue de 29,3 meses (DE ± 11,5) y 5 (62,5%) eran niñas. El tiempo medio entre casos fue de 5,7 días (DE ± 3). El SUH presentó un mayor puntaje de gravedad en los hermanos que se enfermaron en segundo lugar. Conclusión. El riesgo para desarrollar SUH entre hermanos fue 10% y la evolución clínica del segundo hermano fue más desfavorable.
Introduction. Hemolytic uremic syndrome (HUS) isaninfectious disease caused by Shiga toxin-producing Escherichia coli. The objective of this study was to assess the risk of transmission and clinical course between siblings with typical HUS. Population and methods. Medical records of children with typical HUS between 1997 and 2012 were reviewed. Sibling pairs were established as inclusion criteria. A severity score was defined. Results. A total of 133 patients with HUS were recorded; 40 had siblings and 4 progressed to HUS (10%). The mean age of the 4 sibling pairs was 29.3 months old (SD ± 11.5); 5 (62.5%) were girls. The mean time between each case was 5.7 days (SD ± 3). HUS was more severe in the siblings who became infected in the second place. Conclusion. The risk of HUS transmission between siblings was 10%, and the clinical course of the second sibling was less favorable.
Subject(s)
Humans , Infant , Child, Preschool , Hemolytic-Uremic Syndrome/epidemiology , Risk , Prevalence , Retrospective Studies , Hemolytic-Uremic Syndrome/geneticsABSTRACT
Background & objectives: Shiga toxin producing Escherichia coli (STEC) is an important zoonotic foodborne pathogen, capable of causing haemorrhagic colitis (HC) and haemolytic uremic syndrome (HUS). As data from India on human infections caused by STEC are limited, this study was carried out for hospital based surveillance for STEC as a causative agent of diarrhoea, bloody diarrhoea and HUS at a tertiary care centre and to study the virulence gene profile and strain relatedness by multi locus variable tandem repeat analysis (MLVA). Methods: A total of 600 stool samples were studied. Stool samples of every fifth patient presenting with non-bloody diarrhoea, all cases of bloody diarrhoea and diarrhoea associated HUS (D+HUS) were collected from October 2009 to September 2011. Stool samples were cultured for STEC and characterization of STEC was done by serogrouping, virulence genes analysis, and MLVA typing. Results: STEC were isolated as a sole pathogen from 11 stool samples [5 of 290 (1.7%) non-blood diarrhoea and 5 of 300 (1.6%) blood diarrhoea cases]. STEC was also isolated from one fatal case of HUS who was an eight month old child. Only six of 11 isolates were positive for stx2 gene, whereas stx1 was present in all 11 isolates. Only one isolate was positive for eae. Other adhesion genes present were iha in five isolates, followed by toxB and efa1 in two each and saa gene in one, isolate. Among the plasmid encoded genes, espP, hly and etpD were each present in one isolate each. In the MLVA typing, diverse profiles were obtained except two untypeable isolates from different patients shared the same MLVA profile. Both these isolates were not epidemiologically linked. Interpretation & conclusions: This study demonstrated that STEC could be a causative agent of diarrhoea, bloody diarrhoea and sporadic HUS. However, further work needs to be done to study and explore the prevalence of these organisms in the food chain in this region.
Subject(s)
Adult , Child , Child, Preschool , Diarrhea/drug therapy , Diarrhea/genetics , Diarrhea/microbiology , Escherichia coli Infections/drug therapy , Escherichia coli Infections/genetics , Escherichia coli Infections/microbiology , Feces/microbiology , Female , Hemolytic-Uremic Syndrome/drug therapy , Hemolytic-Uremic Syndrome/genetics , Hemolytic-Uremic Syndrome/microbiology , Humans , India , Infant , Male , Middle Aged , O Antigens/genetics , O Antigens/isolation & purification , Serogroup , Shiga-Toxigenic Escherichia coli/genetics , Shiga-Toxigenic Escherichia coli/isolation & purification , Shiga-Toxigenic Escherichia coli/pathogenicityABSTRACT
We investigated ADAMTS13 activity as well as the ADAMTS13 gene mutation in children with hemolytic uremic syndrome (HUS). Eighteen patients, including 6 diarrhea-negative (D-HUS) and 12 diarrhea-associated HUS (D+HUS) patients, were evaluated. The extent of von Willebrand factor (VWF) degradation was assayed by multimer analysis, and all exons of the ADAMTS13 gene were PCR-amplified using Taq DNA polymerase. The median and range for plasma activity of ADAMTS13 in 6 D-HUS and 12 D+HUS patients were 71.8% (22.8-94.1%) and 84.9% (37.9-119.9%), respectively, which were not statistically significantly different from the control group (86.4%, 34.2-112.3%) (p>0.05). Five ADAMTS13 gene mutations, including 2 novel mutations [1584+2T>A, 3941C>T (S1314L)] and 3 polymorphisms (Q448E, P475S, S903L), were found in 2 D-HUS and one D+HUS patients, which were not associated with deficiency of ADAMTS13 activity. Whether these mutations without reduced ADAMTS13 activity are innocent bystanders or predisposing factors in HUS remains unanswered.
Subject(s)
Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , ADAM Proteins/genetics , Hemolytic-Uremic Syndrome/genetics , Mutation , Polymorphism, GeneticABSTRACT
La causa y mecanismo de la lesión de la célula endotelial (CE) y el mecanismo que provoca la trombosis son los hechos fisiopatológicos más importantes y aún no totalmente conocidos como el Sindrome Urémico Hemolítico/Púrpura Trombocitopénica Trombótica (SUH/PTT). En el SUH asociado a Toxina de Shiga, la lesión de la CE es provocada por la toxina, que penetra a la célula a través de un receptor glicolipídico (Gb3) y altera la síntesis de proteínas celulares a nivel de los ribosomas, provocando la muerte celular por injuria o apoptosis. Existirían mecanismos que amplifican o facilitan la lesión endotelial por la toxina, a través de secreciones de citoquinas inflamatorias, activación de neutrófilos, etc. También se postula que existen factores condicionantes para la aparición de este síndrome, que podrían ser inmunológicos o genéticos. En las otras formas clínicas de SUH/PTT, idiopáticas, secundarias o familiares, tanto esporádicas como recurrentes, el mecanismo de la lesión de la CE no es conocido, pero pueden ser múltiples de acuerdo con cuál sea el cuadro clínico con el que se asocia (idiopático, infecciones, drogas, embarazo, enfermedades autoinmunes, etc.) También podrían existir mecanismos amplificadores de la lesión endotelial (citoquinas) y factores genéticos de predisposición, como el déficit de factor H del complemento en SUH familiar o esporádicos. En cuanto al mecanismo de la trombosis, la lesión o activación de la CE, al disminuir su tromborresistencia y aumentar su capacidad trombogénica, puede inducir la trombosis por múltiples mecanismos (activación de coagulación, activación plaquetaria e hipofibrinolisis). Se enfatizan las alteraciones de su membrana con disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución de los sistemas inhibidores de coagulación, expresión de Factor Tisular, disminución del sistema de ectoadepeasa (CD39), la liberación de FvW, etc., como mecanismos trombogénicos relevantes. Las modificaciones del FvW ("multímeros ultragrandes" o "multímeros pequeños") por una alteración en el clivaje de su molécula que genera multímeros con mayor afinidad y actividad agregante plaquetaria, es un mecanismo importante para mantener y aumentar el proceso trombótico, pero no parece ser el único mecanismo trombogénico en esta patología. La descripción reciente de "déficit congénito de la proteasa de FvW" en casos de PTT familiares y de déficit funcional de esta "proteasa"...
Subject(s)
Humans , Endothelium, Vascular/injuries , Escherichia coli O157/pathogenicity , Escherichia coli O157/physiology , Purpura, Thrombotic Thrombocytopenic/complications , Purpura, Thrombotic Thrombocytopenic/physiopathology , Hemolytic-Uremic Syndrome/complications , Hemolytic-Uremic Syndrome/physiopathology , Hemolytic-Uremic Syndrome/genetics , Thrombosis/physiopathology , von Willebrand Factor/physiology , Endopeptidases/deficiency , Epoprostenol , Genetic Predisposition to Disease , Platelet Aggregation InhibitorsABSTRACT
A Síndrome Hemolítico-Urêmica (SHU) apresenta-se como um grupo heterogêneo de doenças caracterizadas por anemia hemolítica microangiopática, plaquetopenia e insuficiência renal aguda. A lesäo histopatológica típica é a microangiopatia trombótica. A SHU hereditária ou familiar é rara e apresenta um prognóstico pior quando comparada à forma clássica ou epidêmica. Os autores relatam o caso de uma criança que apresentou o quadro clínico e histopatológico de SHU e que apresentava nos antecedentes familiares paternos, 4 adultos de 2 geraçöes com quadro de hipertensäo arterial grave, associada a gestaçäo em 2 casos, com evoluçäo para insuficiência renal. Com base nos dados clínicos e histopatológicos e através do heredograma desta família, os autores sugerem que neste caso o fator determinante da SHU possa ter sido devido a um gene autossômico dominante.
Subject(s)
Humans , Female , Child, Preschool , Adult , Hemolytic-Uremic Syndrome/genetics , Hemolytic-Uremic Syndrome/pathologyABSTRACT
Thirty-four hemolytic uremic syndrome (HUS) patients and ninety-five family members were studied to determine the frequency of infection with verocytotoxin-producing Escherichia coli (VTEC) in household contacts using three diagnostic criteria: VTEC strains isolation and characterization, detection of free fecal VT (FVT) and VT-neutralizing antibodies (VT-NAbs). Gastrointestinal tract symptoms occurend in one to six family members in 8 (23.5 per cent) of the index cases, the week before admission to hospital or simultaneously. The control group consisted of 34 children with acute gastroenteritis who did not develop HUS. Cumulative evidence of VTEC infection was found in 13 (38.2 per cent) of 34 HUS patients, in 30 (31.6 per cent) of 95 family members and in 10 (29.4 per cent) of 34 control children. The serotypes of VTEC isolated were O157:H7 and O25: H2. The prevalent VT type was VT2 in VTEC and FVT; and VT1 in VT-NAbs. Both parents had the same infection rate by fecal toxin or serological data (11.1 per cent FVT, 32 per cent VT-NAbs). These were higher than those detected in siblings (6.2 per cent FVT, 23.5 per cent VT-NAbs) and grandparents (0 per cent FVT, 18 per cent VT-NAbs). Of 16 patients without evidence of infection, 3 had household contacts with FVT and 13 with VT-NAbs. Our results show the wide dissemination of VTEC in the population of Argentina and that family members of HUS patients are usualy infectd. Therefore, person-to-person transmission may play an important role in the high incidence of HUS in our country.