RESUMO
BACKGROUND: Under normal conditions, the expression of CD14, which is the principal receptor for bacterial lipopolysaccharide, is down-regulated in the intestinal mucosa but increases in response to inflammatory stimuli. The aim of the present study was to investigate whether fecal CD14 levels increased in response to infection with diarrheagenic Escherichia coli and whether single nucleotide polymorphisms (SNPs) in the CD14 gene were associated with an increased susceptibility to traveler's diarrhea (TD) in US visitors to Mexico. METHODS: Six SNPs located at the promoter, exon, and untranslated regions of CD14 were typed in a prospective cohort study of 1360 visitors to Mexico at risk for TD. Stools from visitors with TD were studied for enteric pathogens by culture, colony hybridization, and polymerase chain reaction. Fecal soluble CD14 (sCD14) was measured in a subgroup of 203 adults with diarrhea and 66 healthy controls by enzyme-linked immunosorbent assay. RESULTS: The minor allele frequencies for CD14 SNPs were significantly different among the various racial and ethnic groups studied. Two SNPs in the promoter region of CD14 (-159 C > T; rs2569190 and -4191 C > T; rs5744441) were found to be associated with TD in White visitors. The -159 TT genotype was associated with a higher risk for TD (Relative risk [RR], 1.21; 95% confidence interval [CI], 1.05-1.38; P = .008), whereas individuals with the -4191 TT genotype were protected from infection (RR, 0.82; 95% CI, 0.71-0.92; P = .006). Subjects with TD excreted higher levels of fecal CD14 than did healthy controls (33,480 pg/mL vs 6178 pg/mL; P < .02). Fecal sCD14 levels were higher in stool samples from visitors with TD and the -159 TT genotype than they were in visitors with the CC/CT genotypes (P = .02), and stool samples from subjects with the -4191 CC genotype had higher fecal sCD14 levels than did stool samples from visitors with the CT/TT (P = .005) genotype. In a multivariate analysis with haplotypes constructed with the 6 SNPs studied, subjects with the haplotype containing the -159 C and the -4191 T allele were less likely to acquire TD (P = .015). CONCLUSIONS: Our study suggests that CD14 levels increase in response to bacterial diarrhea and that polymorphisms in the CD14 gene influence susceptibility to TD. Intestinal CD14 plays an important role in the innate immune response to enteric pathogens.
Assuntos
Diarreia/genética , Infecções por Escherichia coli/genética , Receptores de Lipopolissacarídeos/genética , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Viagem , Adolescente , Adulto , Canadá , Estudos de Coortes , Diarreia/epidemiologia , Diarreia/imunologia , Suscetibilidade a Doenças , Ensaio de Imunoadsorção Enzimática , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/imunologia , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Receptores de Lipopolissacarídeos/análise , Masculino , México , Hibridização de Ácido Nucleico , Reação em Cadeia da Polimerase , Estudos Prospectivos , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Up to 60% of the US visitors to Mexico develop travelers' diarrhea (TD). In Mexico, rates of diarrhea have been associated with the rainy season and increase in ambient temperature. However, the seasonality of the various diarrheagenic Escherichia coli pathotypes in travelers has not been well described. OBJECTIVE: A study was undertaken to determine if ambient temperature and rainfall have an impact on the acquisition of TD due to different diarrheagenic E coli pathotypes in Mexico. METHODS: We conducted a cohort study of the US adult students traveling to Cuernavaca, Mexico, who were followed during their stay and provided a stool sample with the onset of TD. The presence of E coli was analyzed by a direct fecal multiplex polymerase chain reaction for common E coli pathotypes including enterotoxigenic, enteropathogenic, enteroinvasive, shiga toxin-producing, and enteroaggregative E coli (ETEC, EPEC, EIEC, STEC, and EAEC respectively). The presence of pathotypes was correlated with daily rainfall, average, maximum, and minimum temperatures. RESULTS: A total of 515 adults were enrolled from January 2006 to February 2007. The weekly attack rate of TD for newly arrived travelers was lower in the winter months (range 6.8%-16.3%) than in summer months (range 11.5%-25%; p = 0.05). The rate of ETEC infection increased by 7% for each degree centigrade increase in weekly ambient temperature (p = 0.003). In contrast, EPEC and EAEC were identified in similar proportions during the winter and summer seasons. CONCLUSIONS: Temperature variations in central Mexico influenced the rate of ETEC but not EAEC-associated diarrhea in the US visitors. This epidemiological finding could influence seasonal recommendations for the use of ETEC vaccines in Mexico.
Assuntos
Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Escherichia coli/isolamento & purificação , Fezes/microbiologia , Estudantes/estatística & dados numéricos , Viagem , Adulto , Diarreia/epidemiologia , Diarreia/microbiologia , Escherichia coli Enteropatogênica/isolamento & purificação , Escherichia coli Enterotoxigênica/isolamento & purificação , Escherichia coli/classificação , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Estações do Ano , Escherichia coli Shiga Toxigênica/isolamento & purificação , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Campylobacter jejuni is an unusual cause of travelers' diarrhea acquired in Mexico, but previous studies have relied only on stool culture for diagnosis. We conducted a cohort study to determine if antibody seroconversion to C jejuni would better reflect the occurrence of infection acquired in Mexico. Serum IgG, IgA, and IgM antibodies to Campylobacter seroconverted in only 2 of 353 participants (0.6%). These data further support that C jejuni infection is an unusual cause of travelers' diarrhea in US visitors to Mexico.
Assuntos
Anticorpos Antibacterianos/análise , Infecções por Campylobacter/imunologia , Campylobacter jejuni/fisiologia , Diarreia/microbiologia , Imunoglobulinas/análise , Viagem , Adolescente , Adulto , Infecções por Campylobacter/diagnóstico , Infecções por Campylobacter/epidemiologia , Campylobacter jejuni/isolamento & purificação , Criança , Estudos de Coortes , Diarreia/diagnóstico , Diarreia/epidemiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Masculino , México , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Osteoprotegerin (OPG), an immunoregulatory member of the TNF receptor superfamily, is expressed in inflamed intestinal mucosa. We investigated whether OPG is produced by intestinal epithelial cells and tested the hypothesis that single-nucleotide polymorphisms (SNPs) in the gene encoding OPG (TNFRSF11B) are associated with traveler's diarrhea (TD) among North American travelers to Mexico. METHODS: OPG concentration was measured in the supernatants of T84 cells infected with various diarrheagenic Escherichia coli pathotypes. Genotyping was performed for 4 SNPs in the OPG gene for 968 North American travelers with or without TD. Stool samples from travelers with TD were evaluated for the presence of enteric pathogens. RESULTS: T84 cells produced higher OPG levels in response to infection with various diarrheagenic E. coli pathotypes than with E. coli controls (P<.05). A SNP in the exon 1 region of the OPG gene (OPG+1181G>C) was associated with TD in white travelers who stayed in Mexico for >1 week during the summer (P=.009) and for TD due to nonsecretory pathogens (P=.001). CONCLUSIONS: Our study suggests that OPG is secreted by intestinal epithelial cells in response to enteropathogens and that a polymorphism in the OPG gene is associated with an increased susceptibility to TD.
Assuntos
Diarreia/genética , Infecções por Escherichia coli/genética , Osteoprotegerina/genética , Osteoprotegerina/metabolismo , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Análise de Variância , Linhagem Celular , Distribuição de Qui-Quadrado , Diarreia/epidemiologia , Diarreia/imunologia , Diarreia/microbiologia , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Fezes/química , Fezes/microbiologia , Feminino , Predisposição Genética para Doença , Humanos , Inflamação/microbiologia , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Masculino , México , Pessoa de Meia-Idade , Fatores de Risco , ViagemRESUMO
We studied 1,179 North American travelers who visited Mexico from 2005 to 2007. Travelers' diarrhea (TD) was reported by 521 (44%) participants. Among subjects with TD, 218 cases were examined for cryptosporidiosis by polymerase chain reaction (PCR) and enzyme-linked immunoassays (ELISA). There were 14 (6%) cases of cryptosporidiosis and 141 cases (64%) of bacterial diarrhea. Compared with bacterial diarrhea, a longer stay in Mexico was a risk factor for cryptosporidiosis. Additionally, Cryptosporidium cases passed greater number of watery stools (P < 0.05), suffered more episodes of diarrhea (P < or = 0.05), and were more likely to experience tenesmus (P < or = 0.05) compared with bacterial causes of TD. ELISA detected seven (3%) cases of Cryptosporidium, whereas PCR identified an additional seven cases (6%). Speciation by 18SrRNA sequencing showed that 13 cases were caused by C. parvum and only 1 case was caused by C. hominis. ELISA showed a sensitivity of 50% and specificity of 100% compared with PCR.
Assuntos
Criptosporidiose/epidemiologia , Diarreia/epidemiologia , Diarreia/parasitologia , Viagem , Adolescente , Adulto , Animais , Canadá/epidemiologia , Cryptosporidium/classificação , Ensaio de Imunoadsorção Enzimática , Humanos , México/epidemiologia , Razão de Chances , Reação em Cadeia da Polimerase , Fatores de Risco , Sensibilidade e Especificidade , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
Up to 60% of U.S. visitors to Mexico develop traveler's diarrhea (TD), mostly due to enterotoxigenic Escherichia coli (ETEC) strains that produce heat-labile (LT) and/or heat-stable (ST) enterotoxins. Distinct single-nucleotide polymorphisms (SNPs) within the interleukin-10 (IL-10) promoter have been associated with high, intermediate, or low production of IL-10. We conducted a prospective study to investigate the association of SNPs in the IL-10 promoter and the occurrence of TD in ETEC LT-exposed travelers. Sera from U.S. travelers to Mexico collected on arrival and departure were studied for ETEC LT seroconversion by using cholera toxin as the antigen. Pyrosequencing was performed to genotype IL-10 SNPs. Stools from subjects who developed diarrhea were also studied for other enteropathogens. One hundred twenty-one of 569 (21.3%) travelers seroconverted to ETEC LT, and among them 75 (62%) developed diarrhea. Symptomatic seroconversion was more commonly seen in subjects who carried a genotype producing high levels of IL-10; it was seen in 83% of subjects with the GG genotype versus 54% of subjects with the AA genotype at IL-10 gene position -1082 (P, 0.02), in 71% of those with the CC genotype versus 33% of those with the TT genotype at position -819 (P, 0.005), and in 71% of those with the CC genotype versus 38% of those with the AA genotype at position -592 (P, 0.02). Travelers with the GCC haplotype were more likely to have symptomatic seroconversion than those with the ATA haplotype (71% versus 38%; P, 0.002). Travelers genetically predisposed to produce high levels of IL-10 were more likely to experience symptomatic ETEC TD.
Assuntos
Toxinas Bacterianas/metabolismo , Diarreia/genética , Escherichia coli Enterotoxigênica/patogenicidade , Enterotoxinas/metabolismo , Infecções por Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Viagem , Adulto , Diarreia/imunologia , Diarreia/microbiologia , Diarreia/fisiopatologia , Escherichia coli Enterotoxigênica/metabolismo , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/fisiopatologia , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estados UnidosRESUMO
BACKGROUND AND AIMS: Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial pathogen isolated from travelers suffering of diarrhea. Exposure to heat-labile toxin (LT) produces a high rate of seroconversion. However, the role of LT-producing ETEC (LT-ETEC) as a cause of diarrhea is controversial. We conducted a cohort study in US students traveling to Mexico to assess the ETEC-LT seroconversion rate after natural exposure. METHODS: Participants provided a serum sample on arrival and departure and a stool sample when ill. ETEC-LT immunoglobulin G antibodies were measured by enzyme-linked immunosorbent assay, and LT-ETEC were detected by means of polymerase chain reaction done on fecal DNA. RESULTS: A total of 422 participants with a mean age of 34.5 years were followed a mean of 19.9 days; 304 were females (72.0%), and 319 (75.6%) traveled during the summer months. In total, 177 individuals (41.9%) developed travelers' diarrhea and 33.9% had LT-ETEC identified in their stools. Among individuals having an LT-ETEC strain, 74% seroconverted compared to 11% of those not having diarrhea (p < 0.0001). When analyzed with a logistic regression model, the odds of seroconversion were significantly reduced in participants not having LT-ETEC in their stool (odds ratio = 0.1, p < 0.0001) after adjusting for season, length of stay, age, gender, race, and ethnicity. CONCLUSION: In US young adults traveling to Mexico, ETEC-LT seroconversion reliably identifies individuals naturally exposed to ETEC and correlates with symptomatic illness, length and season of travel.
Assuntos
Toxinas Bacterianas/isolamento & purificação , Diarreia/microbiologia , Enterotoxinas/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Viagem/estatística & dados numéricos , Adulto , Fatores Etários , Diarreia/epidemiologia , Ensaio de Imunoadsorção Enzimática , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli , Fezes/microbiologia , Feminino , Humanos , Imunoglobulina G/sangue , Masculino , México , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Fatores de Risco , Estações do Ano , Testes Sorológicos , Fatores Sexuais , Estudantes/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
Large field studies of travelers' diarrhea for multiple destinations are limited by the need to perform stool cultures on site in a timely manner. A method for the collection, transport, and storage of fecal specimens that does not require immediate processing and refrigeration and that is stable for months would be advantageous. This study was designed to determine if enterotoxigenic Escherichia coli (ETEC) and enteroaggregative E. coli (EAEC) DNA could be identified from cards that were processed for the evaluation of fecal occult blood. U.S. students traveling to Mexico during 2005 to 2007 were monitored for the occurrence of diarrheal illness. When ill, students provided a stool specimen for culture and occult blood by the standard methods. Cards then were stored at room temperature prior to DNA extraction. Fecal PCR was performed to identify ETEC and EAEC in DNA extracted from stools and from occult blood cards. Significantly more EAEC cases were identified by PCR that was performed on DNA that was extracted from cards (49%) or from frozen feces (40%) than from culture methods that used HEp-2 adherence assays (13%) (P < 0.001). Similarly, more ETEC cases were detected from card DNA (38%) than from fecal DNA (30%) or by culture that was followed by hybridization (10%) (P < 0.001). The sensitivity and specificity of the card test were 75 and 62%, respectively, compared to those for EAEC by culture and were 50 and 63%, respectively, compared to those for ETEC. DNA extracted from fecal cards that was used for the detection of occult blood is of use in identifying diarrheagenic E. coli.
Assuntos
Diarreia/microbiologia , Infecções por Escherichia coli/diagnóstico , Escherichia coli/isolamento & purificação , Sangue Oculto , Reação em Cadeia da Polimerase/métodos , Adolescente , Adulto , Aderência Bacteriana , Técnicas Bacteriológicas/métodos , Linhagem Celular , DNA Bacteriano/genética , Escherichia coli/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Manejo de Espécimes , Temperatura , Viagem , Estados UnidosRESUMO
BACKGROUND: Diarrhea affects 40%-60% of travelers from industrialized nations who visit developing countries and is due to bacterial, viral, and parasitic agents. Lactoferrin is bactericidal to enteric pathogens, modulates the intestinal immune response, and is excreted in stool in response to infection with intestinal organisms. We investigated the impact that selected single-nucleotide polymorphisms (SNPs) in the human lactoferrin gene have on susceptibility to traveler's diarrhea. METHODS: Adults who had recently arrived in Mexico were studied prospectively for the occurrence and causal agent(s) of traveler's diarrhea, and genotyping was performed for 9 distinct lactoferrin SNPs. RESULTS: Of the 9 SNPs studied, only 1 SNP (located in exon 15) was associated with traveler's diarrhea (P=.004). When compared with healthy travelers, and after adjustment for known risk factors for traveler's diarrhea (such as age and duration and season of travel), subjects with the T/T genotype in amino acid position 632 were more likely to develop traveler's diarrhea (67% vs. 33%; relative risk [RR], 1.4; 95% CI, 1.2-1.7; P<.001), to have diarrhea with a pathogen identified (RR, 1.3; 95% CI, 1.1-1.6; P=.03), and to have a marker of intestinal inflammation in stool specimens (blood, mucus, or white blood cells; 52% vs. 38%; P=.036). The association was also significant when norovirus was not identified in stool samples (RR, 1.34; 95% CI, 1.06-1.34; P=.01). CONCLUSIONS: The T/T genotype in position codon 632 of the lactoferrin gene is associated with susceptibility to diarrhea in North Americans traveling to Mexico.