Association Between Stool Enteropathogen Quantity and Disease in Tanzanian Children Using TaqMan Array Cards: A Nested Case-Control Study

James A. Platts-Mills Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Jean Gratz Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Esto Mduma Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Erling Svensen Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Caroline Amour Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Jie Liu Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Athanasia Maro Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Queen Saidi Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Ndealilia Swai Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Happiness Kumburu Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Benjamin J. J. McCormick Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Gibson Kibiki Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Eric R. Houpt Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia; Haydom Lutheran Hospital, Haydom, Tanzania; Kilimanjaro Clinical Research Institute, Moshi, Tanzania; Fogarty International Center, National Institutes of Health, Bethesda, Maryland

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Etiologic studies of diarrhea are limited by uneven diagnostic methods and frequent asymptomatic detection of enteropathogens. Polymerase chain reaction-based stool pathogen quantification may help distinguish clinically significant infections. We performed a nested case-control study of diarrhea in infants from a community-based birth cohort in Tanzania. We tested 71 diarrheal samples and pre-diarrheal matched controls with a laboratory-developed TaqMan Array Card for 19 enteropathogens. With qualitative detection, no pathogens were significantly associated with diarrhea. When pathogen quantity was considered, rotavirus (odds ratio [OR] = 2.70 per log10 increase, P < 0.001), astrovirus (OR = 1.49, P = 0.01), and Shigella/enteroinvasive Escherichia coli (OR = 1.47, P = 0.04) were associated with diarrhea. Enterotoxigenic E. coli (0.15 SD decline in length-for-age z score after 3 months per log10 increase, P < 0.001) and Campylobacter jejuni/C. coli (0.11 SD decline, P = 0.003) in pre-diarrheal stools were associated with poor linear growth. Quantitative analysis can help refine the association between enteropathogens and disease in endemic settings.

Author Notes

* Address correspondence to Eric R. Houpt, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, mr4, 2144, Charlottesville, VA 22908. E-mail: erh6k@virginia.edu

Financial support: This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health Grant U01 AI075396 and Bill & Melinda Gates Foundation Global Health Grant OPP1019093 (to E.R.H.).

Authors' addresses: James A. Platts-Mills, Jean Gratz, Jie Liu, and Eric R. Houpt, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, VA, E-mails: jp5t@virginia.edu, jean.gratz@gmail.com, jl5yj@virginia.edu, and erh6k@virginia.edu. Esto Mduma, Erling Svensen, and Caroline Amour, Haydom Lutheran Hospital, Haydom, Tanzania, E-mails: estomih.mduma@haydom.co.tz, erling.svensen@cih.uib.no, and lyneamour@gmail.com. Athanasia Maro, Queen Saidi, Ndealilia Swai, Happiness Kumburu, and Gibson Kibiki, Kilimanjaro Clinical Research Institute, Moshi, Tanzania, E-mails: athanasia.maro@gmail.com, queensaidi@gmail.com, lilia2005tz@yahoo.co.uk, hk9s@virginia.edu, and g.kibiki@kcri.ac.tz. Benjamin J. J. McCormick, Fogarty International Center, National Institutes of Health, Bethesda, MD, E-mail: ben.mccormick@gmail.com.

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