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.
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.
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.
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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.
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:
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.
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.