1921
Volume 97, Issue 4
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract.

Enteroaggregative (EAEC) cause acute and persistent diarrhea, mostly in children worldwide. Outbreaks of diarrhea caused by EAEC have been described, including a large outbreak caused by a Shiga toxin expressing strain. This study investigated the association of EAEC virulence factors with diarrhea in children less than 5 years. We characterized 428 EAEC strains isolated from stool samples obtained from moderate-to-severe diarrhea cases (157) and healthy controls (217) children aged 0–59 months recruited over 3 years as part of the Global Enteric Multicenter Study (GEMS) in The Gambia. Four sets of multiplex polymerase chain reaction were applied to detect 21 EAEC-virulence genes from confirmed EAEC strains that target pCVD432 (aatA) and AAIC (aaiC). In addition, Kirby-Bauer disc diffusion antimicrobial susceptibility testing was performed on 88 EAEC strains following Clinical Laboratory Standard Institute guidelines. We observed that the plasmid-encoded enterotoxin [odds ratio (OR): 6.9, 95% confidence interval (CI): 2.06–29.20, < 0.001], aggregative adherence fimbriae/I fimbriae (aggA) [OR: 2.2, 95% CI: 1.16–4.29, = 0.008], and hexosyltransferase (capU) [OR: 1.9, 95% CI 1.02–3.51, = 0.028] were associated with moderate-to-severe diarrhea among children < 12 months old but not in the older age strata (> 12 months). Our data suggest that some EAEC-virulent factors have age-specific associations with moderate-to-severe diarrhea in infants. Furthermore, our study showed that 85% and 72% of EAEC strains tested were resistant to sulphamethoxazole-trimethoprim and ampicillin, respectively. Sulphamethoxazole-trimethoprim and ampicillin are among the first-line antibiotics used for the treatment of diarrhea in The Gambia.

[open-access] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Loading

Article metrics loading...

/content/journals/10.4269/ajtmh.16-0705
2017-10-11
2017-12-13
Loading full text...

Full text loading...

/deliver/fulltext/14761645/97/4/tpmd160705.html?itemId=/content/journals/10.4269/ajtmh.16-0705&mimeType=html&fmt=ahah

References

  1. Nataro JP, Kaper JB, , 1998. Diarrheagenic Escherichia coli . Clin Microbiol Rev 11: 142201.
  2. Moyo SJ, Maselle SY, Matee MI, Langeland N, Mylvaganam H, , 2007. Identification of diarrheagenic Escherichia coli isolated from infants and children in Dar es Salaam, Tanzania. BMC Infect Dis 7: 92.[Crossref]
  3. Cobeljic M, Miljkovic-Selimovic B, Paunovic-Todosijevic D, Velickovic Z, Lepsanovic Z, Zec N, Savic D, Ilic R, Konstantinovic S, Jovanovic B, Kostic V, , 1996. Enteroaggregative Escherichia coli associated with an outbreak of diarrhoea in a neonatal nursery ward. Epidemiol Infect 117: 1116.[Crossref]
  4. Itoh Y, Nagano I, Kunishima M, Ezaki T, , 1997. Laboratory investigation of enteroaggregative Escherichia coli O untypeable:H10 associated with a massive outbreak of gastrointestinal illness. J Clin Microbiol 35: 25462550.
  5. Pai M, Kang G, Ramakrishna BS, Venkataraman A, Muliyil J, , 1997. An epidemic of diarrhoea in south India caused by enteroaggregative Escherichia coli . Indian J Med Res 106: 712.
  6. Smith HR, Cheasty T, Rowe B, , 1997. Enteroaggregative Escherichia coli and outbreaks of gastroenteritis in UK. Lancet 350: 814815.[Crossref]
  7. Adachi JA, Jiang ZD, Mathewson JJ, Verenkar MP, Thompson S, Martinez-Sandoval F, Steffen R, Ericsson CD, DuPont HL, , 2001. Enteroaggregative Escherichia coli as a major etiologic agent in traveler’s diarrhea in 3 regions of the world. Clin Infect Dis 32: 17061709.[Crossref]
  8. Januszkiewicz A, Szych J, Rastawicki W, Wolkowicz T, Chrost A, Leszczynska B, Kuzma E, Roszkowska-Blaim M, Gierczynski R, , 2012. Molecular epidemiology of a household outbreak of Shiga-toxin-producing Escherichia coli in Poland due to secondary transmission of STEC O104:H4 from Germany. J Med Microbiol 61: 552558.[Crossref]
  9. Samie A, Obi CL, Dillingham R, Pinkerton RC, Guerrant RL, , 2007. Enteroaggregative Escherichia coli in Venda, South Africa: distribution of virulence-related genes by multiplex polymerase chain reaction in stool samples of human immunodeficiency virus (HIV)-positive and HIV-negative individuals and primary school children. Am J Trop Med Hyg 77: 142150.
  10. Bielaszewska M, Mellmann A, Zhang W, Kock R, Fruth A, Bauwens A, Peters G, Karch H, , 2011. Characterisation of the Escherichia coli strain associated with an outbreak of haemolytic uraemic syndrome in Germany, 2011: a microbiological study. Lancet Infect Dis 11: 671676.[Crossref]
  11. Bhan MK, Raj P, Levine MM, Kaper JB, Bhandari N, Srivastava R, Kumar R, Sazawal S, , 1989. Enteroaggregative Escherichia coli associated with persistent diarrhea in a cohort of rural children in India. J Infect Dis 159: 10611064.[Crossref]
  12. Paul M, Tsukamoto T, Ghosh AR, Bhattacharya SK, Manna B, Chakrabarti S, Nair GB, Sack DA, Sen D, Takeda Y, , 1994. The significance of enteroaggregative Escherichia coli in the etiology of hospitalized diarrhoea in Calcutta, India and the demonstration of a new honey-combed pattern of aggregative adherence. FEMS Microbiol Lett 117: 319325.[Crossref]
  13. Harrington SM, Strauman MC, Abe CM, Nataro JP, , 2005. Aggregative adherence fimbriae contribute to the inflammatory response of epithelial cells infected with enteroaggregative Escherichia coli . Cell Microbiol 7: 15651578.[Crossref]
  14. Harrington SM, Dudley EG, Nataro JP, , 2006. Pathogenesis of enteroaggregative Escherichia coli infection. FEMS Microbiol Lett 254: 1218.[Crossref]
  15. Nataro JP, Martinez J, , 1998. Diagnosisand investigation of diarrheagenic Escherichia coli . Methods Mol Med 15: 387406.
  16. Nataro JP, Yikang D, Yingkang D, Walker K, , 1994. AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli . J Bacteriol 176: 46914699.[Crossref]
  17. Czeczulin JR, Balepur S, Hicks S, Phillips A, Hall R, Kothary MH, Navarro-Garcia F, Nataro JP, , 1997. Aggregative adherence fimbria II, a second fimbrial antigen mediating aggregative adherence in enteroaggregative Escherichia coli . Infect Immun 65: 41354145.
  18. Jonsson R, Struve C, Boisen N, Mateiu RV, Santiago AE, Jenssen H, Nataro JP, Krogfelt KA, , 2015. Novel aggregative adherence fimbria variant of enteroaggregative Escherichia coli . Infect Immun 83: 13961405.[Crossref]
  19. Savarino SJ, Fasano A, Robertson DC, Levine MM, , 1991. Enteroaggregative Escherichia coli elaborate a heat-stable enterotoxin demonstrable in an in vitro rabbit intestinal model. J Clin Invest 87: 14501455.[Crossref]
  20. Nataro JP, Steiner T, Guerrant RL, , 1998. Enteroaggregative Escherichia coli . Emerg Infect Dis 4: 251261.[Crossref]
  21. Henderson IR, Czeczulin J, Eslava C, Noriega F, Nataro JP, , 1999. Characterization of pic, a secreted protease of Shigella flexneri and enteroaggregative Escherichia coli . Infect Immun 67: 55875596.
  22. Kahali S, Sarkar B, Rajendran K, Khanam J, Yamasaki S, Nandy RK, Bhattacharya SK, Ramamurthy T, , 2004. Virulence characteristics and molecular epidemiology of enteroaggregative Escherichia coli isolates from hospitalized diarrheal patients in Kolkata, India. J Clin Microbiol 42: 41114120.[Crossref]
  23. Steiner TS, Nataro JP, Poteet-Smith CE, Smith JA, Guerrant RL, , 2000. Enteroaggregative Escherichia coli expresses a novel flagellin that causes IL-8 release from intestinal epithelial cells. J Clin Invest 105: 17691777.[Crossref]
  24. Presterl E, Nadrchal R, Wolf D, Rotter M, Hirschl AM, , 1999. Enteroaggregative and enterotoxigenic Escherichia coli among isolates from patients with diarrhea in Austria. Eur J Clin Microbiol Infect Dis 18: 209212.[Crossref]
  25. Knutton S, Shaw R, Phillips AD, Smith HR, Willshaw GA, Watson P, Price E, , 2001. Phenotypic and genetic analysis of diarrhea-associated Escherichia coli isolated from children in the United Kingdom. J Pediatr Gastroenterol Nutr 33: 3240.[Crossref]
  26. Cohen MB, Nataro JP, Bernstein DI, Hawkins J, Roberts N, Staat MA, , 2005. Prevalence of diarrheagenic Escherichia coli in acute childhood enteritis: a prospective controlled study. J Pediatr 146: 5461.[Crossref]
  27. Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, Faruque AS, Zaidi AK, Saha D, Alonso PL, Tamboura B, Sanogo D, Onwuchekwa U, Manna B, Ramamurthy T, Kanungo S, Ochieng JB, Omore R, Oundo JO, Hossain A, Das SK, Ahmed S, Qureshi S, Quadri F, Adegbola RA, Antonio M, Hossain MJ, Akinsola A, Mandomando I, Nhampossa T, Acacio S, Biswas K, O’Reilly CE, Mintz ED, Berkeley LY, Muhsen K, Sommerfelt H, Robins-Browne RM, Levine MM, , 2013. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 382: 209222.[Crossref]
  28. Boisen N, Scheutz F, Rasko DA, Redman JC, Persson S, Simon J, Kotloff KL, Levine MM, Sow S, Tamboura B, Toure A, Malle D, Panchalingam S, Krogfelt KA, Nataro JP, , 2012. Genomic characterization of enteroaggregative Escherichia coli from children in Mali. J Infect Dis 205: 431444.[Crossref]
  29. Farag TH, Nasrin D, Wu Y, Muhsen K, Blackwelder WC, Sommerfelt H, Panchalingam S, Nataro JP, Kotloff KL, Levine MM, , 2012. Some epidemiologic, clinical, microbiologic, and organizational assumptions that influenced the design and performance of the Global Enteric Multicenter Study (GEMS). Clin Infect Dis 55 (Suppl 4): S225S231.[Crossref]
  30. Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, Adegbola RA, Alonso PL, Breiman RF, Faruque AS, Saha D, Sow SO, Sur D, Zaidi AK, Biswas K, Panchalingam S, Clemens JD, Cohen D, Glass RI, Mintz ED, Sommerfelt H, Levine MM, , 2012. The Global Enteric Multicenter Study (GEMS) of diarrheal disease in infants and young children in developing countries: epidemiologic and clinical methods of the case/control study. Clin Infect Dis 55 (Suppl 4): S232S245.[Crossref]
  31. Panchalingam S, Antonio M, Hossain A, Mandomando I, Ochieng B, Oundo J, Ramamurthy T, Tamboura B, Zaidi AK, Petri W, Houpt E, Murray P, Prado V, Vidal R, Steele D, Strockbine N, Sansonetti P, Glass RI, Robins-Browne RM, Tauschek M, Svennerholm AM, Berkeley LY, Kotloff K, Levine MM, Nataro JP, , 2012. Diagnostic microbiologic methods in the GEMS-1 case/control study. Clin Infect Dis 55 (Suppl 4): S294S302.[Crossref]
  32. Cennimo D, Abbas A, Huang DB, Chiang T, , 2009. The prevalence and virulence characteristics of enteroaggregative Escherichia coli at an urgent-care clinic in the USA: a case-control study. J Med Microbiol 58: 403407.[Crossref]
  33. Benjelloun-Touimi Z, Sansonetti PJ, Parsot C, , 1995. SepA, the major extracellular protein of Shigella flexneri: autonomous secretion and involvement in tissue invasion. Mol Microbiol 17: 123135.[Crossref]
  34. Boisen N, Ruiz-Perez F, Scheutz F, Krogfelt KA, Nataro JP, , 2009. Short report: high prevalence of serine protease autotransporter cytotoxins among strains of enteroaggregative Escherichia coli . Am J Trop Med Hyg 80: 294301.
  35. Opintan JA, Bishar RA, Newman MJ, Okeke IN, , 2010. Carriage of diarrhoeagenic Escherichia coli by older children and adults in Accra, Ghana. Trans R Soc Trop Med Hyg 104: 504506.[Crossref]
  36. Navarro-Garcia F, Sears C, Eslava C, Cravioto A, Nataro JP, , 1999. Cytoskeletal effects induced by pet, the serine protease enterotoxin of enteroaggregative Escherichia coli . Infect Immun 67: 21842192.
  37. Villaseca JM, Navarro-Garcia F, Mendoza-Hernandez G, Nataro JP, Cravioto A, Eslava C, , 2000. Pet toxin from enteroaggregative Escherichia coli produces cellular damage associated with fodrin disruption. Infect Immun 68: 59205927.[Crossref]
  38. Navarro-Garcia F, Canizalez-Roman A, Luna J, Sears C, Nataro JP, , 2001. Plasmid-encoded toxin of enteroaggregative Escherichia coli is internalized by epithelial cells. Infect Immun 69: 10531060.[Crossref]
  39. Dutta PR, Cappello R, Navarro-Garcia F, Nataro JP, , 2002. Functional comparison of serine protease autotransporters of enterobacteriaceae. Infect Immun 70: 71057113.[Crossref]
  40. Eslava CVJ, Morales R, Navarro A, Cravioto A, , 1993. Identification of a protein with toxigenic activity produced by enteroaggregative Escherichia coli. Abstract of the 93rd General Meeting of the American Society for Microbiology. Washington, DC: American Society for Microbiology, 44.
  41. Eslava C, Navarro-Garcia F, Czeczulin JR, Henderson IR, Cravioto A, Nataro JP, , 1998. Pet, an autotransporter enterotoxin from enteroaggregative Escherichia coli . Infect Immun 66: 31553163.
  42. Bafandeh S, Haghi F, Zeighami H, , 2015. Prevalence and virulence characteristics of enteroaggregative Escherichia coli in a case-control study among patients from Iran. J Med Microbiol 64: 519524.[Crossref]
  43. Okeke IN, Lamikanra A, Czeczulin J, Dubovsky F, Kaper JB, Nataro JP, , 2000. Heterogeneous virulence of enteroaggregative Escherichia coli strains isolated from children in southwest Nigeria. J Infect Dis 181: 252260.[Crossref]
  44. Scheutz F, Nielsen EM, Frimodt-Moller J, Boisen N, Morabito S, Tozzoli R, Nataro JP, Caprioli A, , 2011. Characteristics of the enteroaggregative Shiga toxin/verotoxin-producing Escherichia coli O104:H4 strain causing the outbreak of haemolytic uraemic syndrome in Germany, May to June 2011. Euro Surveill 16: pii: 19889.[Crossref]
  45. Vila J, Gene A, Vargas M, Gascon J, Latorre C, Jimenez de Anta MT, , 1998. A case-control study of diarrhoea in children caused by Escherichia coli producing heat-stable enterotoxin (EAST-1). J Med Microbiol 47: 889891.[Crossref]
  46. Paiva de Sousa C, Dubreuil JD, , 2001. Distribution and expression of the astA gene (EAST1 toxin) in Escherichia coli and Salmonella . Int J Med Microbiol 291: 1520.[Crossref]
  47. Toshima H, Uenaka E, Bi Y, Nakamura H, Ogasawara J, Hase A, Kamata Y, Nishikawa Y, , 2004. Detection and isolation of Escherichia coli with a coding gene for enteroaggregative Escherichia coli heat-stable enterotoxin 1 from food and comparison with fecal isolates. J Food Prot 67: 21172122.[Crossref]
  48. Veilleux S, Holt N, Schultz BD, Dubreuil JD, , 2008. Escherichia coli EAST1 toxin toxicity of variants 17-2 and O 42. Comp Immunol Microbiol Infect Dis 31: 567578.[Crossref]
  49. Menard LP, Dubreuil JD, , 2002. Enteroaggregative Escherichia coli heat-stable enterotoxin 1 (EAST1): a new toxin with an old twist. Crit Rev Microbiol 28: 4360.[Crossref]
  50. Zhou Z, Ogasawara J, Nishikawa Y, Seto Y, Helander A, Hase A, Iritani N, Nakamura H, Arikawa K, Kai A, Kamata Y, Hoshi H, Haruki K, , 2002. An outbreak of gastroenteritis in Osaka, Japan due to Escherichia coli serogroup O166:H15 that had a coding gene for enteroaggregative E. coli heat-stable enterotoxin 1 (EAST1). Epidemiol Infect 128: 363371.[Crossref]
  51. Mendez Arancibia E, Pitart C, Ruiz J, Marco F, Gascon J, Vila J, , 2009. Evolution of antimicrobial resistance in enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli causing traveller’s diarrhoea. J Antimicrob Chemother 64: 343347.[Crossref]
  52. Ikumapayi UN, Antonio M, Sonne-Hansen J, Biney E, Enwere G, Okoko B, Oluwalana C, Vaughan A, Zaman SM, Greenwood BM, Cutts FT, Adegbola RA, , 2007. Molecular epidemiology of community-acquired invasive non-typhoidal Salmonella among children aged 2 29 months in rural Gambia and discovery of a new serovar, Salmonella enterica Dingiri. J Med Microbiol 56: 14791484.[Crossref]
  53. Aslani MM, Alikhani MY, Zavari A, Yousefi R, Zamani AR, , 2011. Characterization of enteroaggregative Escherichia coli (EAEC) clinical isolates and their antibiotic resistance pattern. Int J Infect Dis 15: e136e139.[Crossref]
  54. Raju B, Ballal M, , 2009. Multidrug resistant enteroaggregative Escherichia coli diarrhoea in rural southern Indian population. Scand J Infect Dis 41: 105108.[Crossref]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.16-0705
Loading
/content/journals/10.4269/ajtmh.16-0705
Loading

Data & Media loading...

Supplementary Data

Supplemental Figure

  • Received : 29 Aug 2016
  • Accepted : 22 May 2017

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error