Aeromonas-Associated Diarrhea in Children Under 5 Years: The GEMS Experience

Farah Naz Qamar Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

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Muhammad Imran Nisar Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

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Farheen Quadri Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

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Sadia Shakoor Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

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Samba O. Sow Center for Vaccine Development, Ministry of Health, Bamako, Mali.

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Dilruba Nasrin Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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William C. Blackwelder Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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Yukun Wu Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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Tamer Farag Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.
Vaccine Development and Surveillance, Bill & Melinda Gates Foundation, Seattle, Washington.

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Sandra Panchalingham Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.

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Dipika Sur Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.

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Shahida Qureshi Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.

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Abu S. G. Faruque Clinical Sciences Division, International Centre for Diarrheal Disease Research (icddr,b), Dhaka, Bangladesh.

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Debasish Saha Centre for Nutrition and Food Security (CNFS), International Centre for Diarrheal Disease Research (icddr,b), Dhaka, Bangladesh.

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Pedro L. Alonso International Health Research, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain.
Microbiology, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.

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Robert F. Breiman International Emerging Infections Program, Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC), Nairobi, Kenya.

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Quique Bassat International Health Research, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain.
ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain.

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Boubou Tamboura Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan.
Centre National d'Appui à la lutte contre la Maladie/Centre pour le Développement des Vaccins (CNAM/CVD-Mali), Bamako, Mali.

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Thandavarayan Ramamurthy Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.

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Suman Kanungo Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India.

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Shahnawaz Ahmed Centre for Nutrition and Food Security (CNFS), International Centre for Diarrheal Disease Research (icddr,b), Dhaka, Bangladesh.

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Anowar Hossain Centre for Nutrition and Food Security (CNFS), International Centre for Diarrheal Disease Research (icddr,b), Dhaka, Bangladesh.

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Sumon K. Das Centre for Nutrition and Food Security (CNFS), International Centre for Diarrheal Disease Research (icddr,b), Dhaka, Bangladesh.

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Martin Antonio Child Survival Theme, Molecular Diagnostics, Medical Research Council (MRC) Unit, Banjul, The Gambia.

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M. Jahangir Hossain Child Survival Theme, Molecular Diagnostics, Medical Research Council (MRC) Unit, Banjul, The Gambia.

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Inacio Mandomando International Health Research, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain.
Microbiology, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique.

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Sharon M. Tennant Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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Karen L. Kotloff Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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Myron M. Levine Department of Medicine, University of Maryland, Baltimore School of Medicine, Maryland.
Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland.

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Anita K. M. Zaidi Vaccine Development and Surveillance, Bill & Melinda Gates Foundation, Seattle, Washington.

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We report the clinical findings, epidemiology, and risk factors for moderate-to-severe diarrhea (MSD) associated with Aeromonas species in children 0–59 months of age, from the Global Enteric Multicenter Study, conducted at three sites in south Asia and four sites in sub-Saharan Africa. Children with MSD were enrolled along with controls matched for age, gender, and neighborhood. Pooled, age-stratified conditional logistic regression models were applied to evaluate the association of Aeromonas infection controlling for coinfecting pathogens and sociodemographic variables. A pooled, age-stratified, multivariate logistic regression analysis was done to identify risk factors associated with Aeromonas positivity in MSD cases. A total of 12,110 cases and 17,291 matched controls were enrolled over a period of 48 months. Aeromonas was identified as a significant pathogen in 736 cases of MSD in Pakistan and Bangladesh (22.2%). Aeromonas remained a significant pathogen even after adjustment for the presence of other pathogens and sociodemographic factors. Odds ratio (OR) for Aeromonas were higher in the presence of Shigella (matched OR: 6.2, 95% confidence interval [CI]: 1.9–20.2). Cases of Aeromonas were likely to present with dysentery, particularly in the 0–11 months (OR: 1.4, 95% CI 1.0–2.0) and 12–23 months (OR: 1.8, 95% CI: 1.3–2.5) age group. The odds of Aeromonas increased with increasing degree of stunting, being highest for severe stunting (OR: 10.1, 95% CI: 3.6–28.9). Aeromonas is a significant pathogen for MSD in Pakistan and Bangladesh. Presence of dysentery and co-occurrence with other pathogens, notably Shigella spp. are significant features of Aeromonas-associated diarrhea.

Author Notes

* Address correspondence to Farah Naz Qamar, Department of Pediatrics and Child Health, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi 74800, Pakistan. E-mail: farah.qamar@aku.edu

Financial support: The parent study (GEMS) was funded by the BMG foundation.

Disclosure: Farah Naz Qamar received research training support from the National Institute of Health's Fogarty International Center (1 D43 TW007585-01).

Authors' addresses: Farah Naz Qamar, Muhammad Imran Nisar, Farheen Quadri, Sadia Shakoor, Shahida Qureshi, and Anita K. M. Zaidi, Department of Paediatrics and Child Health, Aga Khan University, Karachi, Pakistan, E-mails: farah.qamar@aku.edu, imran.nisar@aku.edu, farheen.quadri@aku.edu, sadia.shakoor@aku.edu, shahida.qureshi@aku.edu, and anita.zaidi@aku.edu. Samba O. Sow, Center for Vaccine Development, Ministry of Health, Bamako, Mali, E-mail: ssow@medicine.umaryland.edu. Dilruba Nasrin, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, E-mail: dnasrin@medicine.umaryland.edu. William C. Blackwelder, Yukun Wu, Sandra Panchalingham, Sharon M. Tennant, Karen L. Kotloff, and Myron M. Levine, Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, E-mails: wblackwe@medicine.umaryland.edu, statswu@gmail.com, spanchal@medicine.umaryland.edu, stennant@medicine.umaryland.edu, kkotloff@medicine.umaryland.edu, and mlevine@medicine.umaryland.edu. Tamer Farag, Vaccine Development and Surveillance, Bill & Melinda Gates Foundation, Seattle, WA, E-mail: tamer.farag@gatesfoundation.org. Dipika Sur, Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, West Bengal, E-mail: dipikasur@hotmail.com. Abu S. G. Faruque, Clinical Sciences Division, icddr,b, Dhaka, Bangladesh, E-mail: gfaruque@icddrb.org. Debasish Saha, Centre for Nutrition and Food Security (CNFS), icddr,b, Dhaka, Bangladesh. Pedro L. Alonso and Quique Bassat, International Health Research, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain, E-mail: pedro.alonso@isglobal.es. Robert F. Breiman, International Emerging Infections Program, Kenya Medical Research Institute/Centers for Disease Control and Prevention (KEMRI/CDC), Nairobi, Kenya, E-mail: rfbreiman@emory.edu. Quique Bassat, ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic–Universitat de Barcelona, Barcelona, Spain, E-mail: quique.bassat@isglobal.org. Boubou Tamboura, Centre National d'Appui à la lutte contre la Maladie/Centre pour le Développement des Vaccins (CNAM/CVD-Mali), Bamako, Mali, E-mail: btambour@medicine.umaryland.edu. Thandavarayan Ramamurthy and Suman Kanungo, Division of Epidemiology, National Institute of Cholera and Enteric Diseases, Kolkata, India, E-mails: rama1murthy@yahoo.com and sumankanungo@gmail.com. Shahnawaz Ahmed and Sumon K. Das, Centre for Nutrition and Food Security (CNFS), icddr,b, Dhaka, Bangladesh, E-mails: shahnawz@icddrb.org and sumon@icddrb.org. Anowar Hossain, Laboratory Sciences Division, icddr,b, Dhaka, Bangladesh, E-mail: anowar@icddrb.org. Martin Antonio and M. Jahangir Hossain, Child Survival Theme, Molecular Diagnostics, Medical Research Council (MRC) Unit, Banjul, The Gambia, E-mails: mantonio@mrc.gm and jhossain@mrc.gm. Inacio Mandomando, Microbiology, Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique, E-mail: inacio.mandomando@gmail.com. Eric D. Mintz, Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, GA, E-mail: edm1@cdc.gov.

  • 1.

    Ghenghesh KS, Ahmed SF, El-Khalek RA, Al-Gendy A, Klena J, 2008. Aeromonas-associated infections in developing countries. J Infect Dev Ctries 2: 8198.

  • 2.

    Lautrop H, 1961. Aeromonas hydrophila isolated from human feces and its possible pathological significance. Acta Path Microbiol Scand 51 (Suppl 144): 299301.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Burke V, Gracey M, Robinson J, Peck D, Beaman J, Bundell C, 1983. The microbiology of childhood gastroenteritis: Aeromonas species and other infective agents. J Infect Dis 148: 6874.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Pazzaglia G, Sack RB, Salazar E, Yi A, Chea E, Leon-Barua R, Guerrero CE, Palomino J, 1991. High frequency of coinfecting enteropathogens in Aeromonas-associated diarrhea of hospitalized Peruvian infants. J Clin Microbiol 29: 11511156.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Kotloff KL, Wasserman SS, Steciak JY, Tall BD, Losonsky GA, Nair P, Morris JG Jr, Levine MM, 1988. Acute diarrhea in Baltimore children attending an outpatient clinic. Pediatr Infect Dis J 7: 753759.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Von Graevenitz A, 2007. The role of Aeromonas in diarrhea: a review. Infection 35: 5964.

  • 7.

    Albert MJ, Ansaruzzaman M, Talukder KA, Chopra AK, Kuhn I, Rahman M, Faruque ASG, Islam MS, Sack RB, Mollby R, 2000. Prevalence of enterotoxin genes in Aeromonas spp. isolated from children with diarrhea, healthy controls, and the environment. J Clin Microbiol 38: 37853790.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Janda JM, Abbott SL, 2010. The genus Aeromonas: taxonomy, pathogenicity, and infection. Clin Microbiol Rev 23: 3573.

  • 9.

    Kotloff KL, Blackwelder WC, Nasrin D, Nataro JP, Farag TH, van Eijk A, Adegbola RA, Alonso PL, Breiman RF, Faruque ASG, 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: S232S245.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Kotloff KL, Nataro JP, Blackwelder WC, Nasrin D, Farag TH, Panchalingam S, Wu Y, Sow SO, Sur D, Breiman RF, 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.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Panchalingam S, Antonio M, Hossain A, Mandomando I, Ochieng B, Oundo J, Ramamurthy T, Tamboura B, Zaidi AKM, Petri W, 2012. Diagnostic microbiologic methods in the GEMS-1 case/control study. Clin Infect Dis 55: S294S302.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Blackwelder WC, Biswas K, Wu Y, Kotloff KL, Farag TH, Nasrin D, Graubard BI, Sommerfelt H, Levine MM, 2012. Statistical methods in the Global Enteric Multicenter Study (GEMS). Clin Infect Dis 55: S246S253.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Figura N, Marri L, Verdiani S, Ceccherini C, Barberi A, 1986. Prevalence, species differentiation, and toxigenicity of Aeromonas strains in cases of childhood gastroenteritis and in controls. J Clin Microbiol 23: 595599.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Dixit S, Bhandari GP, Karmacharya DB, Shrestha S, Manandhar S, Maskey MK, 2011. Molecular screening of major bacterial enteropathogens in human stool samples from diarrhoeal outbreak sites. J Nepal Health Res Counc 9: 181185.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Sinha S, Shimada T, Ramamurthy T, Bhattacharya SK, Yamasaki S, Takeda Y, Nair GB, 2004. Prevalence, serotype distribution, antibiotic susceptibility and genetic profiles of mesophilic Aeromonas species isolated from hospitalized diarrhoeal cases in Kolkata, India. J Med Microbiol 53: 527534.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16.

    Soltan Dallal MM, Moezardalan K, 2004. Aeromonas spp associated with children's diarrhoea in Tehran: a case-control study. Ann Trop Paediatr 24: 4551.

  • 17.

    Klontz EH, Faruque AS, Das SK, Malek MA, Islam Z, Luby SP, Klontz KC, 2012. Clinical and epidemiologic features of diarrheal disease due to Aeromonas hydrophila and Plesiomonas shigelloides infections compared with Those due to Vibrio cholerae Non-O1 and Vibrio parahaemolyticus in Bangladesh. ISRN Microbiol 2012: 654819.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18.

    Lawson MA, Burke V, Chang BJ, 1985. Invasion of HEp-2 cells by fecal isolates of Aeromonas hydrophila. Infection and Immunity 47: 680683.

  • 19.

    Xu X-J, Ferguson MR, Popov VL, Houston CW, Peterson JW, Chopra AK, 1998. Role of a cytotoxic enterotoxin in Aeromonas-mediated infections: development of transposon and isogenic mutants. Infection and Immunity 66: 35013509.

    • PubMed
    • Search Google Scholar
    • Export Citation
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