Gut Health and Child Survival

Our Challenge

Even among children who survive diarrhea, multiple episodes of the disease and the underlying enteric infections can lead to chronic malnutrition, increased risk of lower respiratory tract infections, cognitive disabilities, and poor school performance.  These consequences hold extreme economic and societal implications.

Our Response

We are a collaboration of clinicians, epidemiologists and microbiologists, based both in Seattle and internationally, who share a common goal of preventing and treating the adverse effects of enteric and diarrheal disease.  Our team currently leads multiple clinical trials and observational studies to better understand the unique host, pathogen, and environmental determinants of why some children fail to recover from common infections.  Equipped with this information and appropriate interventions, we strive to ensure children survive and reach their developmental potential.

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Our Priority Areas

Many children suffer an elevated risk of mortality and chronic malnutrition months after acute infectious illnesses. This prolonged risk may be due to inadequately treated or new bacterial infections, a prolonged state of inflammation as a result of the infection and its associated treatment, or immune-deficiencies that arise after illness.

Within two clinical trials we are testing whether empiric use of a broad spectrum antibiotic improves post-infection survival in Kenyan children.  Through data and samples collected in these studies, we are building a platform to identify mechanisms and, eventually, to test additional interventions for reducing the short and long-term consequences of infectious diseases in children.

Recent estimates suggest that almost half of all childhood deaths are attributed to malnutrition. The relationship between malnutrition and enteric diseases is cyclical; malnutrition is a serious consequence of enteric and diarrheal disease and undernourished children experience a higher risk of death after infection.

Our team is leading a multi-country network of clinical research centers from Sub-Saharan Africa, South East Asia, the UK and USA dedicated to identifying risk factors that increase mortality, hospital readmission, and poor recovery in children who are malnourished and suffering from acute infection.

Specific bacterial and parasitic enteric infections contribute a disproportionate burden to diarrheal disease, malnutrition, and poor academic performance.  We conduct an array of evidence-generating activities to inform international prevention and treatment policy of specific enteric infections including literature reviews challenging current management guidelines for Shigellainfections, household Cryptosporidium transmission studies, and clinical trials testing the feasibility of integrated approached to eliminating soil-transmitted helminths.

Scientific Priority Co-Directors

Patty Pavlinac
PhD, MSc
Assistant Professor, Global Health

Judd Walson
MD, MPH
Professor, Global Health, Medicine, Pediatrics
Adjunct Professor, Epidemiology

Faculty Leads

Kristjana Ásbjörnsdóttir
PhD, MPH
Acting Assistant Professor, Epidemiology

Carol Levin
PhD, MSc
Clinical Associate Professor, Global Health

Christopher Kemp
PhD, MPH
Acting Assistant Professor
Global Health

Christine McGrath
PhD, MPH
Assistant Professor, Global Health

Arianna Means
PhD, MPH
Acting Assistant Professor, Global Health

Technical Advisors

Donna Denno
MD, MPH
Professor, Global Health and Pediatrics;  Adjunct Professor, Health Services

Benson Singa
MBChB, MPH
Research Scientist, Kenya Medical Research Institute; Affiliate Assistant Professor, Global Health

Kirk Tickell
MBBS, MPH
PhD in Epidemiology Student
Lead Epidemiologist, CHAIN

Staff

Liz Blanton
MPH
Research Scientist

Devon Bushnell
Program Operations Specialist
SEEMS-Nutrition

Danny Carreon
MS
Data Quality Officer
CHAIN

Rowena de Saraam
Program Coordinator

Sean Galagan
MSPH
Research Consultant
DeWorm3

Sarah Lawrence
MPH
Research Coordinator
MITS

Chloe Morozoff

Chloe Morozoff
MPH
Implementation Science Consultant

Elizabeth Orlan
MSPH
Implementation Science Data Analyst

Emily Pearman

Emily Pearman
MPH
Data Quality Manager
DeWorm3

Christina Sherry
MPH
Research Coordinator
HMO

Alyson Shumays
MPH
Research Program Manager

Ann Van Haney
MBA
Grant and Contract Specialist

Trainees

Hannah Atlas
BA
MPH Student in Global Health

Mame Mareme Diakhate
BS
MPH Student in Global Health

Jeanne Goodman
BA
MPH Student in Global Health

Marie-Claire Gwayi-Chore
MS
PhD Student in Global Health Implementation Science

Stephanie Tornberg-Belanger
MS, MPH
PhD Candidate in Epidemiology

Our Research

Sponsor:  World Health Organization (PO 201941581)

Award Years:  07/08/2014 – 03/31/2019

Principal Investigators:  Judd Walson

Co-Investigators:  Patty Pavlinac, Christine McGrath

Trainees:  Stephanie Tornberg-Belanger

This trial aims to determine the efficacy of two antibiotics in reducing risk of death in children less than two years of age with diarrhea and dehydration or malnutrition through a double-blind placebo-controlled clinical trial. The study is designed to provide clear evidence in favor or against using antibiotics to treat diarrhea, to inform a revision of current World Health Organization (WHO) diarrhea guidelines.

Sponsor:  National Institutes of Child Health and Human Development (5R01HD079695-04)

Award Years:  04/01/2015 – 02/29/2020

Principal Investigator:  Judd Walson

Co-Investigators:  Joseph Babigumira (Global Health and Pharmacy [Adjunct], UW), Patty Pavlinac, Christine McGrath, Benson Singa

Trainees:  Rebecca Brander, Kirk Tickell

Toto Bora, an expression meaning “healthy baby” in Kiswahili, is a randomized, double-blind, placebo-controlled trial aimed at reducing childhood morbidity and mortality post-hospitalization.  A recent trial found that mass administration of azithromycin reduced mortality by half among children receiving the intervention in Ethiopia.  The Toto Bora team will determine the efficacy of azithromycin provided at discharge in reducing mortality and re-hospitalization rates in Kenyan children age 1-59 months.  The Toto Bora Trial began enrollment in June of 2016 and is estimated to be complete data collection in June 2019.

Click here to view the study protocol.

Sponsor:  University of Oxford (R41463/CN031 MOD03)

Award Years:  09/15/2015 – 09/30/2021

Principal Investigator:  Judd Walson

Co-Investigators:  Donna Denno, Arianna Rubin Means, Christine McGrath, Patty Pavlinac, Benson Singa

Trainees:  Mareme Diakhate, Jeanne Goodman, Kirk Tickell

The CHAIN Network seeks to build the evidence base for the care of sick, undernourished children in resource-limited settings.  At the core of the network is a group of global experts creating a cohort of acutely ill children from Sub-Saharan Africa, South East Asia, the UK and USA, and who are dedicated to reducing childhood mortality caused by co-morbid severe illness and malnutrition.  The multi-site, multi-country observational study is expected to close in 2019.

Sponsor Award:  University of Oxford (B9R00880 MOD02)

Award Years:  09/15/2017 – 09/30/2019

Principal Investigator:  Donna Denno

Case fatality rates among children hospitalized with acute illness are unacceptably high, even when current standards of care are applied. The minimally invasive tissue sampling (MITS) sub-study aims to improve the understanding of causes of death (CoD) among children who die during inpatient admission for acute illness across a spectrum of undernutrition. We also propose a novel strategy – post-mortem intestinal endoscopy and tissue sampling to assess its feasibility and as a method to understand the contribution of intestinal pathology to mortality. Additionally, we propose to conduct qualitative research to understand community members and leaders concerns about MITS and barriers and facilitators to acceptance of MITS in Malawi.

Sponsor:  Natural History Museum (SON15004)

Award Years:  11/05/2015 – 10/15/2020

UW Consortium Principal Investigators:  Arianna Rubin Means, Judd Walson

UW Consortium Co-Investigators:  Kristjana Ásbjörnsdóttir, Jared Baeten (Medicine, Global Health, Allergy and Infectious Diseases and Epidemiology, UW), Barbra Richardson (Biostatistics and Global Health, UW)

Staff:  Liza Blanton, Chloe Morozoff, Elizabeth Orlan, Emily Pearman

Trainees:  Marie-Claire Gwayi-Chore

Over 1.45 billion people are infected with soil-transmitted helminths (STHs), including 845 million children, in some of the world’s poorest communities. The DeWorm3 project tests the feasibility of eliminating STHs or intestinal worms and developing cost-effective methods for scaling up elimination programs. DeWorm3 aims specifically to:

  • Demonstrate the feasibility of eliminating STHs using existing and intensified mass drug administration (MDA) strategies, specifically by leveraging existing lymphatic filariasis elimination platforms
  • Inform the guidelines, policies, and operational plans needed to successfully achieve STH elimination
  • Link qualitative and operational studies of the acceptability and feasibility of different strategies to ongoing field trials, guiding future implementation and scale-up plans.

Click here to view the study protocol.

Sponsor:  Natural History Museum (SUT17001)

Award Years:  06/01/2018 – 05/30/2019

Principal Investigator:  Arianna Rubin Means

Co-Investigators:  Kristjana Ásbjörnsdóttir, Jared Baeten (Medicine, Global Health, Allergy and Infectious Diseases and Epidemiology, UW), Barbra Richardson (Biostatistics and Global Health, UW)

This proposed collaboration with the Children’s Investment Fund Foundation (CIFF) will be conducted alongside the CIFF investment to the India National Deworming Programme.  This implementation science research will generate evidence to maximize cross-disease coordination and drug coverage in an effort to interrupt the transmission of soil transmitted helminths (STH) in India.  The purpose of these activities is to generate and disseminate evidence needed by the Indian government to inform national priorities and policy development.

Click here to view the study protocol.

Sponsor:  National Institutes of Health (1R01HD096999)

Award Years:  04/24/2019 – 03/31/2024

Principal Investigators:  Christine McGrath

Co-Investigators:  Grace John-Stewart, Judd Walson, Donna Denno, Barbra Richardson (Biostatistics and Global Health, UW)

Staff:  Christina Sherry

The proposed study will evaluate the association between maternal HIV infection, human milk oligosaccharides (HMO) composition, and the infant gut microbiome, and identify HMO-mediated pathways associated with morbidity and linear growth in HIV-exposed uninfected infants. We will prospectively enroll and follow HIV-infected and HIV-uninfected women and their infants in Kenya, a region where interactions between undernutrition and high HIV prevalence pose challenges to childhood growth.

Sponsor:  UW/Fred Hutch Center for AIDS Research (CFAR) New Investigator Award

Award Years:  08/01/2019 – 7/31/2020

Principal Investigators:  Arianna Rubin Means

Co-Investigators:  Christine McGrath, Benson Singa

Mentors::  Judd Walson, Gabrielle O’Malley (Global Health/I-TECH), Grace John-Stewart

HIV-exposed children with acute malnutrition are at increased risk of poor growth, cognitive delay, and death.  Adherence to malnutrition screening and treatment guidelines is low, and barriers to providing guideline adherent
care for HIV-exposed children are unknown.  This study utilizes a mixed-methods approach to generate information regarding the extent to which HIV-exposed children with or at risk of malnutrition receive guideline adherent
care, multi-level factors influencing their care, and opportunities to address modifiable bottlenecks to service delivery and optimize care.

Sponsor:  National Institutes of Health (R21HD094639-01)

Award Years:  09/21/2017 – 08/31/2019

Principal Investigator:  William DePaulo (UW Medicine)

Co-Investigators:  Heather Jaspan (Pediatrics-Infectious Diseases, UW), Patty Pavlinac, Judd Walson

Trainees:  Hannah Atlas

This proposal seeks to address an important gap in our understanding of enteric infections that occur in an intestinal environment with a low bacterial diversity. It proposes a conceptually innovative hypothesis that the chronic viral infection itself does not drive EPEC virulence, but rather the reduced gut microbial diversity caused by the infection. Importantly, this proposal will evaluate whether restoration of diversity via fecal microbiota transplants can be used a treatment strategy.

Sponsor:  Thrasher Research Fund

Award Years: 02/01/2019 – 03/31/2022

Principal Investigator:  Christine McGrath

Co-Investigators:  Carol Levin (Global Health, UW), Barbra Richardson (Biostatistics and Global Health, UW), Kirk Tickell, Jennifer Unger

This proposal is a randomized controlled trial in western Kenya.  Mothers will be taught to measure their child’s mid-upper arm circumference (MUAC) at 6 or 9-month immunization visits and during 6-month follow up they will receive weekly SMS messages prompting them to measure and send their child’s MUAC to a computer system which will alert a health worker when a child with malnutrition is identified.  This scalable childhood growth monitoring system could enable nutrition programs in low and middle income countries to optimize screening coverage, leading to early identification of malnutrition, lower costs and a reduction in global under-five mortality.

Sponsor:  National Institutes of Health (1 R03 HD 099270-01)

Award Years:  09/17/2019 – 08/31/20201

Principal Investigator:  Judd Walson, Arianna Means

Co-Investigator: Donna Denno

This study will utilize existing CHAIN cohort data from nine health facilities in six countries to evaluate the frequency with which health providers deviate from established pediatric treatment guidelines, and factors that influence deviation. We will extract diagnostic and treatment criteria from each of the six country national guidelines, specifically for pneumonia, diarrhea, and severe acute malnutrition (SAM) sub-syndromes. We will map these criteria across CHAIN cohort data to identify the frequency with which providers deviate from the national guidelines on which they have been trained. We will additionally analyze CHAIN intake data to identify patient-level, provider-level, and contextual factors influencing provider deviation from guidelines.

Sponsor:  Bill & Melinda Gates Foundation

Award Years: 11/05/2018 – 10/31/2020

Principal Investigator:  Carol Levin

Staff:  Devon Bushnell

Trainee:  Christopher Kemp

SEEMS-Nutrition is a new three-year project that aims to fill an information gap on costs, cost-effectiveness, and benefits of scaling up food system strategies in resource-constrained areas combating malnutrition.  In the spirit of multi-sectoral collaboration, the SEEMS-Nutrition project is working in partnership with the Global Alliance for Improved Nutrition (GAIN)International Food Policy Research Institute (IFPRI)International Livestock Research Institute (ILRI) Helen Keller International (HKI), and Results for Development (R4P).  Their findings will allow program implementers and policymakers to make informed decisions about which nutrition interventions to prioritize to address healthy food systems, dietary intake, and improved nutritional status.  Such interventions can help improve maternal and child health outcomes by promoting optimal dietary and feeding practices during critical windows of time when nutritional needs are the greatest.