TY - JOUR
T1 - Host fecal mRNAs predicted environmental enteric dysfunction among children with moderate acute malnutrition in Sierra Leone
AU - Singh, Akriti
AU - Potani, Isabel
AU - Griswold, Stacy P.
AU - Suri, Devika
AU - Langlois, Breanne
AU - Shen, Ye
AU - Walton, Shelley M.
AU - Ho Chui, Kenneth Kwan
AU - Manary, Mark J.
AU - Webb, Patrick
AU - Rogers, Beatrice L.
AU - Rosenberg, Irwin H.
N1 - Funding Information:
Financial support: This work was made possible by the generous support of the American people through the U.S. Agency for International Development’s Bureau for Humanitarian Assistance (USAID/ BHA) and the Legacy Office of Food for Peace (FFP) under the terms of Contract No. AID-OAA-C-16-00020, managed by Tufts University.
Funding Information:
Acknowledgments: We thank the study participants and their caregivers. Liquid nitrogen for the EED substudy was supplied by the Department of Biological Sciences, Njala University. Samples were stored in Sierra Leone at the University of Makeni Infectious Disease Research Laboratory (UniMak-IDRL), established as a legacy laboratory after the West African Ebola outbreak of 2013–2016. The UniMak-IDRL was established and maintained by funding from the Wellcome Trust (References: 097997/Z/11/A and 206298/B/17/Z) to Ian Goodfellow (University of Cambridge and University of Makeni).
Funding Information:
We thank the study participants and their caregivers. Liquid nitrogen for the EED substudy was supplied by the Department of Biological Sciences, Njala University. Samples were stored in Sierra Leone at the University of Makeni Infectious Disease Research Laboratory (UniMak-IDRL), established as a legacy laboratory after the West African Ebola outbreak of 2013?2016. The UniMak-IDRL was established and maintained by funding from the Wellcome Trust (References: 097997/Z/11/A and 206298/B/17/Z) to Ian Goodfellow (University of Cambridge and University of Makeni). This work was made possible by the generous support of the American people through the U.S. Agency for International Development?s Bureau for Humanitarian Assistance (USAID/ BHA) and the Legacy Office of Food for Peace (FFP) under the terms of Contract No. AID-OAA-C-16-00020, managed by Tufts University.
Publisher Copyright:
Copyright © 2021 by The American Society of Tropical Medicine and Hygiene
PY - 2021/11
Y1 - 2021/11
N2 - Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference $ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L $ 0.2) and severe EED (%L $ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.
AB - Examining the role of environmental enteric dysfunction (EED) in child growth requires noninvasive, field-appropriate biomarkers. Alternatives to the traditionally used lactulose:mannitol (L:M) test have been explored, but few studies have compared the L:M test to host fecal mRNA transcripts. The objectives of this study were to examine whether 1) host fecal mRNA transcripts could predict presence and severity of EED, measured using the L:M test, and 2) EED modifies the effect of specialized nutritious foods (SNFs) on recovery from moderate acute malnutrition (MAM). This substudy was nested within a cluster randomized trial comparing four SNFs in the treatment of MAM among children 6 to 59 months in Sierra Leone. EED was assessed at enrollment using the L:M test and 15 host fecal mRNA transcripts on 522 children. Recovery from MAM was defined as achieving mid-upper arm circumference $ 12.5 cm within 12 weeks of supplementation. Random forest classification models were used to examine prediction of presence and severity of EED by host fecal mRNA transcripts. Logistic regression was used to test for effect modification by L:M test variables including % lactulose excreted (%L). Eight host fecal mRNA transcripts (AQP9, REG3A, IFI30, DECR1, BIRC3, SELL, PIK3AP1, DEFA6) identified EED (%L $ 0.2) and severe EED (%L $ 0.45) with high sensitivity and specificity. The L:M test variables did not modify the effect of SNFs on recovery from MAM. In this study, we found host fecal mRNA transcripts that could be biomarkers of EED but did not find EED to modify the effect of SNFs on MAM treatment.
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U2 - 10.4269/ajtmh.21-0348
DO - 10.4269/ajtmh.21-0348
M3 - Article
C2 - 34460425
AN - SCOPUS:85119612772
SN - 0002-9637
VL - 105
SP - 1376
EP - 1382
JO - American Journal of Tropical Medicine and Hygiene
JF - American Journal of Tropical Medicine and Hygiene
IS - 5
ER -