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1.
JAMA Pediatr ; 169(11): 1040-5, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26389824

RESUMO

IMPORTANCE: A genetic polymorphism affecting FUT2 secretor status in approximately one-quarter of humans of European descent affects the expression of histo-blood group antigens on the mucosal epithelia of human respiratory, genitourinary, and digestive tracts. These histo-blood group antigens serve as host receptor sites necessary for attachment and infection of some pathogens, including norovirus. OBJECTIVE: We investigated whether an association exists between FUT2 secretor status and laboratory-confirmed rotavirus infections in US children. DESIGN, SETTING, AND PARTICIPANTS: Multicenter case-control observational study involving active surveillance at 6 US pediatric medical institutions in the inpatient and emergency department clinical settings. We enrolled 1564 children younger than 5 years with acute gastroenteritis (diarrhea and/or vomiting) and 818 healthy controls frequency matched by age and month, from December 1, 2011, through March 31, 2013. MAIN OUTCOMES AND MEASURES: Paired fecal-saliva specimens were tested for rotavirus and for secretor status. Comparisons were made between rotavirus test-positive cases and healthy controls stratified by ethnicity and vaccination status. Adjusted multivariable analyses assessed the preventive association of secretor status against severe rotavirus gastroenteritis. RESULTS: One (0.5%) of 189 rotavirus test-positive cases was a nonsecretor, compared with 188 (23%) of 818 healthy control participants (P < .001). Healthy control participants of Hispanic ethnicity were significantly less likely to be nonsecretors (13%) compared with healthy children who were not of Hispanic ethnicity (25%) (P < .001). After controlling for vaccination and other factors, children with the nonsecretor FUT2 polymorphism appeared statistically protected (98% [95% CI, 84%-100%]) against severe rotavirus gastroenteritis. CONCLUSIONS AND RELEVANCE: Severe rotavirus gastroenteritis was virtually absent among US children who had a genetic polymorphism that inactivates FUT2 expression on the intestinal epithelium. We observed a strong epidemiologic association among children with rotavirus gastroenteritis compared with healthy control participants. The exact cellular mechanism behind this epidemiologic association remains unclear, but evidence suggests that it may be rotavirus genotype specific. The lower prevalence of nonsecretors among Hispanic children may translate to an enhanced burden of rotavirus gastroenteritis among this group. Our findings may have bearing on our full understanding of rotavirus infections and the effects of vaccination in diverse populations.


Assuntos
Fucosiltransferases/genética , Gastroenterite/epidemiologia , Infecções por Rotavirus/epidemiologia , Rotavirus/isolamento & purificação , Estudos de Casos e Controles , Pré-Escolar , Fezes/virologia , Feminino , Gastroenterite/genética , Gastroenterite/virologia , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Mutação , Estudos Prospectivos , Infecções por Rotavirus/genética , Infecções por Rotavirus/virologia , Saliva/virologia , Estados Unidos
2.
Clin Infect Dis ; 60(11): 1631-8, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-25744498

RESUMO

BACKGROUND: Norovirus is a leading cause of acute gastroenteritis (AGE). Noroviruses bind to gut histo-blood group antigens (HBGAs), but only 70%-80% of individuals have a functional copy of the FUT2 ("secretor") gene required for gut HBGA expression; these individuals are known as "secretors." Susceptibility to some noroviruses depends on FUT2 secretor status, but the population impact of this association is not established. METHODS: From December 2011 to November 2012, active AGE surveillance was performed at 6 geographically diverse pediatric sites in the United States. Case patients aged <5 years were recruited from emergency departments and inpatient units; age-matched healthy controls were recruited at well-child visits. Salivary DNA was collected to determine secretor status and genetic ancestry. Stool was tested for norovirus by real-time reverse transcription polymerase chain reaction. Norovirus genotype was then determined by sequencing. RESULTS: Norovirus was detected in 302 of 1465 (21%) AGE cases and 52 of 826 (6%) healthy controls. Norovirus AGE cases were 2.8-fold more likely than norovirus-negative controls to be secretors (P < .001) in a logistic regression model adjusted for ancestry, age, site, and health insurance. Secretors comprised all 155 cases and 21 asymptomatic infections with the most prevalent norovirus, GII.4. Control children of Meso-American ancestry were more likely than children of European or African ancestry to be secretors (96% vs 74%; P < .001). CONCLUSIONS: FUT2 status is associated with norovirus infection and varies by ancestry. GII.4 norovirus exclusively infected secretors. These findings are important to norovirus vaccine trials and design of agents that may block norovirus-HBGA binding.


Assuntos
Infecções por Caliciviridae/genética , Infecções por Caliciviridae/imunologia , Fucosiltransferases/genética , Predisposição Genética para Doença , Norovirus/imunologia , Estudos de Casos e Controles , Pré-Escolar , Fezes/virologia , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Recém-Nascido , Masculino , Norovirus/classificação , Norovirus/genética , Norovirus/isolamento & purificação , Reação em Cadeia da Polimerase em Tempo Real , Estados Unidos
3.
Med Sci Educ ; 23(4): 572-577, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24634798

RESUMO

Researchers designed learner-directed journal clubs to develop literature evaluation skills in preclinical students. Sessions balanced student-led discussion with structured objectives and faculty support. During the pilot with preclinical MD/PhD students, self-rated mastery improved over all 17 measured objectives. Six exercises have since been incorporated into the full medical school curriculum.

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