Global WACh

Gut Health and Child Survival Scientific Priority Area

The Challenge

Although dramatic progress has been made in reducing child deaths globally over the past several decades, millions of children continue to die annually in low and middle-income countries, primarily from infectious diseases. Our group focuses on targeting interventions and approaches to improve survival, growth, and development among the most vulnerable children globally, specifically those related to enteric and neglected tropical diseases.

Our Response

We seek to bring together clinicians, epidemiologists, microbiologists, researchers, and implementation scientists who share a common goal of improving outcomes among the most vulnerable populations globally. Our team currently leads multiple clinical trials and implementation research studies to better understand the unique host, pathogen, environmental, and health system determinants of child health. Equipped with this information and appropriate strategies for delivering evidence-based interventions, we strive to ensure children survive and reach their developmental potential.

Areas of Focus

Child Survival

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 an illness.

Within 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.

Growth and Nutrition

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 the USA dedicated to identifying risk factors that increase mortality, hospital readmission, and poor recovery in children who are malnourished and suffering from acute infection.

Enteric Disease and Function

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 Shigella infections, household Cryptosporidium transmission studies, and clinical trials testing the feasibility of integrated approaches to eliminating soil-transmitted helminths.

Neglected Tropical Diseases

Neglected tropical diseases, or NTDs, are a group of infections that disproportionately affect populations without adequate access to safe water, housing, or sanitation.  Often referred to as diseases of poverty, NTDs perpetuate inequities through associated morbidities such as blindness (trachoma and onchocerciasis), severe anemia, impaired growth and cognitive development (soil-transmitted helminths), elephantiasis (lymphatic filariasis), and other chronic conditions that prevented infected individuals from reaching their full income earning potential.  Our team has a suite of studies, including clinical trials and implementation research studies, that address opportunities to interrupt the transmission of several NTDs through the delivery of community-based interventions that are acceptable, feasible, and delivered with high coverage. 

Highly Vulnerable Populations

Implementation Science

Many of our studies include both a focus on the clinical effectiveness of new or existing therapeutics, as well as opportunities to improve the delivery of the evidence-based interventions.  Our research uses implementation science methods to determine the acceptability, appropriateness, cost, feasibility, fidelity, reach, and sustainability of different strategies to increase the impact of clinical interventions.  At the core of our implementation science work is a focus on equity and stakeholder engagement. 

 

 

Collaborators

Faculty Directors

Patricia Pavlinac
MSc, PhD
Assistant Professor
Global Health

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

Faculty and Technical Advisors

Kristjana Ásbjörnsdóttir
MPH, PhD
Acting Assistant Professor
Epidemiology

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

Sam Kariuki
MSc, PhD
Director, Center for Microbiology Research
Kenya Medical Research Institute

Carol Levin
MSc, PhD
Clinical Associate Professor
Global Health

Meshack Liru
MMed
Head Pediatrician
Homa Bay County Referral Hospital

Christine McGrath
MPH, PhD
Assistant Professor
Global Health

Arianna Means
MPH, PhD
Acting Assistant Professor
Global Health

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

Kirk Tickell
MBBS, MPH, PhDc
PhD Candidate
Epidemiology

Indi Trehan
MD, MPH
Associate Professor
Pediatrics and Global Health [Adjunct]

Ana Weil
MD, MPH
Acting Instructor
Medicine

Staff

Alyson Shumays
MPH
Research Program Manager

Ann Van Haney
MBA
Grant and Contract Manager

Omid Afzal
Grant Specialist

Rowena de Saram
Program Coordinator, Assistant to Judd Walson

Christina Sherry
MPH
Research Coordinator

Emily Yoshioka
MPH
Research Coordinator

Hannah Atlas
MPH
Research Coordinator

Jeanne Goodman
MPH
Project Manager
DeWorm3

Jusufu Paye
MPH
Project Manager
NTD Community of Practice

Liz Blanton
MPH
Research Scientist

Sarah Lawrence
MPH
Research Coordinator
CHAIN-MITS

Alex Schaefer
MPA
Data Manager

Amy Roll
MPH
Implementation Science Data Analyst

Chloe Morozoff
MPH
Implementation Science Data Analyst

Danny Carreon
MS
Data Quality Officer

Emily Pearman
MPH
Data Quality Manager

Mareme Diakhate
MPH
Data Manager

Trainees

Shawon Riffat Ara
MBBS, MPH
PhD Student
Epidemiology

Marie-Claire
Gwayi-Chore

MS, PhDc
PhD Candidate
Global Health

Dorothy Mangale
MSc
PhD Student
Global Health

Brooks Morgan
MSPH
PhD Student
Epidemiology

Ruchi Tiwari
MPH
PhD Student
Epidemiology

Stephanie
Tornberg-Belanger

MPH, PhDc
PhD Candidate
Epidemiology

Adino
Tesfahun Tsegaye

MPH
PhD Student
Epidemiology

 

Our Research

Antibiotics for Children with Severe Diarrhea (ABCD)

The ABCD Trial is a multi-site, double-blind, randomized trial that aims to determine if the addition of azithromycin to the standard management of care for acute non-bloody watery diarrhea for high-risk children in Sub-Saharan Africa and South Asia aged 2 to 23 months could reduce mortality and improve growth. 

Sponsor:  World Health Organization (PO 201941581)

Award Years:  07/08/2014 – 07/31/2019

Principal Investigators:  Judd Walson, Benson Singa

Primary Contact:  Patricia Pavlinac

Click here to read the study protocol.

 

Azythromycin to Prevent Post-discharge Morbidity and Mortality in Kenyan Children (AZM)

The Toto Bora Trial is a randomized, double-blind, placebo-controlled trial that aims to determine whether a short course of azithromycin (10 mg/kg on day 1 and 5 mg/kg on days 2-5) given to 1-59 month-old children with recent acute illness being discharged from hospitals reduces re-hospitalization, morbidity, and mortality. 

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

Award Years:  04/01/2015 – 02/29/2021

Principal Investigators:  Judd Walson, Benson Singa

Primary Contact:  Patricia Pavlinac

Click here to read the study protocol.

 

The Epidemiology of Extended Spectrum Beta Lactamase and Macrolide Resistance Genes in Kenyan Children Discharged from Hospital (AZM Royalty Grant)

 

The AZM Royalty Grant aims to establish the burden, risk factors, and potential sharing of antibiotic resistance determinants using bacterial isolates from children recently discharged from hospital enrolled in the Toto Bora Trial.

Sponsor:  University of Washington Royalty Research Fund

Award Years:  9/1/2020 – 9/30/2021

Principal Investigator:  Patricia Pavlinac

Primary Contact:  Patricia Pavlinac

 

The role of enteric pathogens and antimicrobial resistance in driving clinical and nutritional deterioration, and azithromycin’s potential effect, among children discharged from hospital in Kenya (AZM Enterics)

Utilizing samples collected in the Toto Bora Trial, the AZM Enterics nested study utilizes aims determine associations between enteric bacterial pathogens detected at hospital discharge and risk of death, re-hospitalization, and growth failure in the six-month post-discharge and to evaluate if detection of these pathogens prior to randomization modifies azithromycin’s efficacy.

Sponsor:  National Institute of Allergy and Infectious Diseases (5R01AI150978)

Award Years:  03/15/2020 – 02/8/2025

Principal Investigators:  Patricia Pavlinac, Benson Singa

Primary Contact: Hannah Atlas

 

Enterics for Global Health (EFGH), Shigella surveillance study

EFGH is a two-year facility-based, cross-sectional multi-country surveillance and longitudinal study at seven sites in Africa, Asia, and Latin America focusing on children under 36 months of age presenting with moderate-to-severe diarrhea (MSD) to generate data and quickly implement rigorous/efficient Shigella vaccine trials, accelerating the time to vaccine availability for children in low-middle income countries.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  10/30/2019 – 12/31/2021

Principal Investigator:  Patricia Pavlinac

Primary Contact:  Patricia Pavlinac

 

 

Potential modulation of the intestinal microbiome by HIV and antibiotics and implications for EPEC susceptibility and severity

The EPEC study is a cross-sectional study that aims to determine if a reduction in bacterial diversity through antibiotics use or HIV infection is associated with severe enteropathogenic Escherichia coli (EPEC) infection in HIV-exposed Kenyan children aged 6-12 months. 

Sponsor:  National Institutes of Health (2R21HD094639)

Award Years:  09/21/2017 – 08/31/2019

Principal Investigator:  William DePaulo

Primary Contact: Patricia Pavlinac

Click here to read the study protocol.

 

Childhood Acute Illness and Nutrition Network (CHAIN) Cohort Study

The CHAIN study is a multi-site, prospective, observational cohort study that aims to characterize the biomedical and social risk factors for mortality in acutely ill children (based on MUAC) aged 1 week to 2 years from four African and two South Asian countries in hospitals and after discharge. The CHAIN Consortium seeks to examine infectious, immunological, metabolic, nutritional, and other biological factors that link anthropometric status with risk of in-patient and post-discharge mortality. CHAIN includes several sub-studies, including MITS in CHAIN, Immunology, Body Composition, TB, Neurodevelopment, Breast Milk Composition, Enteric Function, HIV, Macronutrient Deficiencies, Social Science, and Skin CHAIN. 

Sponsor:  University of Oxford (R41463/CN031 MOD03)

Award Years:  09/15/2015 – 09/30/2021

Principal Investigator:  Judd Walson

Primary Contact: Kirk Tickell

Click here to read the study protocol.

 

The CHAIN Consortium

The CHAIN Consortium is a nested case-control study examining infectious, immunologic, metabolic, nutritional, and other biological mechanisms that link anthropometric status with risk for in-patient and post-discharge mortality, and are independently associated with mortality. The consortium is made up of laboratory partners from around the world.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  11/25/2019 – 6/30/2022

Principal Investigator:  Judd Walson

Primary Contact: Kirk Tickell

 

Surveillance and Epidemiologic Evaluation of COVID-19 in children with severe acute malnutrition and HIV in Kenya

Through the partnership of Clinical Information Network (CIN) and CHAIN, the CHAIN-COVID prospective cohort study in Kenya aims to estimate the incidence of COVID and describe the clinical profile of highly vulnerable children and adults with SARS-CoV-2, including those with HIV and malnutrition. In addition, this study also aims to examine the use of respiratory care interventions and determine the impact of local COVID response on the ability of the Kenyan health system to continue delivering other health services.  

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  05/01/2020 – 6/30/2021

Principal Investigator:  Judd Walson, Benson Singa

Primary Contact: Kirk Tickell

Click here to read the study protocol.

 

Prevalence and Correlates of Pediatric Guidelines Deviation Across 9 Health Facilities in Kenya

The Pediatric Guideline study combines secondary data analysis and primary qualitative data collection from the CHAIN Network to understand drivers influencing provider adherence to or deviation from pediatric treatment guidelines and to design evidence-based interventions that can be applied to address adherence barriers.

Sponsor:  National Institutes of Health (5R03HD099270)

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

Principal Investigator:  Arianna Means, Benson Singa

Primary Contact: Arianna Means

 

Minimally Invasive Tissue Sampling to Improve Understanding of Cause of Death in Children (MITS in CHAIN)

Case fatality rates among children hospitalized with acute illness are unacceptably high, even when current standards of care are applied. The Childhood Acute Illness and Nutrition (CHAIN) Cohort study aims to identify risk factors for and causes of death (CoD) among hospitalized children aged 2-23 months. Exact CoD are often unknown and difficult to establish, especially for malnourished children. This study aims to improve the understanding of CoD among well-characterized children who die during inpatient admission for acute illness across a spectrum of undernutrition in Malawi. We also introduce 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 have commenced social sciences research to understand health worker, parent, and community leader’s concerns about MITS and barriers and facilitators to acceptance of MITS in Malawi.

Sponsor:  University of Oxford

Award Years:  09/15/2017 – 09/30/2021

Principal Investigators:  Donna Denno, Weiger Voskuijl

Primary Contact:  Sarah Lawrence

 

Minimally Invasive Tissue Sampling (MITS) for Lung Pathology and Immune Response in Fatal COVID-19 Patients in Malawi (MITS COVID-19)

Even with access to optimum healthcare and intensive management, including mechanical ventilation in high-income settings COVID-19, caused by the SARS-CoV-2 virus kills 0.5 – 2% of infected individuals through a rapidly developing diffuse parenchymal lung disease and severe hypoxia. A vaccine may take many months to develop and longer to deploy. The virus may infect over 50% of the world’s population and without better treatments could cause upwards of 40 million deaths. Immunomodulation is a major prong of treatment investigatory efforts and may be particularly important as the pandemic spreads in low- and middle-income countries (LMICs), including sub-Saharan Africa (SSA), with much diminished intensive care capacity. Higher rates of malaria, HIV, and malnutrition may influence pathogenesis and immune response in these settings. To most effectively and safely target this immunomodulation it is important to understand the tissue-specific immune responses that drive severe disease in tissue, in particular in the lung.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  08/03/2020 – 08/02/2021

UW Consortium Principal Investigator:  Donna Denno

Primary Contact:  Sarah Lawrence

 

Maternal Administered Malnutrition Monitoring System (Mama Aweza Trial)

The Mama Aweza Trial is a randomized controlled trial that aims to establish the efficacy and feasibility of a novel malnutrition screening approach, in which caregivers are taught to use MUAC tapes. The caregivers are enrolled in a semi-automated mHealth SMS system that provides health education and MUAC monitoring support to improve early identification and linkage to care for malnourished Kenyan children aged 6-12 months. 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:  Thrasher Research Fund

Award Years: 02/01/2019 – 03/31/2022

Principal Investigators:  Christine McGrath, Benson Singa

Primary Contact: Kirk Tickell

Click here to read the study protocol.

 

Effects of Human Milk Oligosaccharides (HMO) and Gut Microbiome on Growth and Morbidity in HIV-Exposed Uninfected (HEU) Infants - the Tunza Mwana Study

The Tunza Mwana study is a prospective cohort study that aims to evaluate the association between maternal HIV infection, HMO composition, and the infant gut microbiome, and identify breast milk-mediated pathways associated with morbidity and linear growth in HEU infants born to Kenyan pregnant women between 28-42 weeks’ gestation. 

Sponsor:  National Institutes of Health (5R01HD096999)

Award Years:  04/24/2019 – 03/31/2024

Principal Investigators:  Christine McGrath, Benson Singa

Primary Contact:  Christina Sherry

 

 

Optimizing nutritional care for HIV exposed children in Migori and Homa Bay Counties - The Lishe Bora Study

The Lishe Bora study uses qualitative data collection and systems analysis process mapping to evaluate provider adherence to HIV nutrition guidelines for HIV-exposed Kenyan children under two years of age in Migori and Homa Bay Counties to identify gaps in the care cascades and opportunities to more comprehensively integrate HIV and nutritional care. 

Sponsor:  University of Washington Center for AIDS Research (CFAR) New Investigator Award

Award Years:  11/16/2020 – 11/15/2022

Principal Investigator:  Arianna Means

Primary Contact:  Emily Yoshioka

 

 

Feasibility of Interrupting the Transmission of Soil-transmitted Helminths (DeWorm3)

The DeWorm3 Study is a series of community cluster randomized controlled trials that aim to determine the feasibility of interrupting soil-transmitted helminth transmission in focal geographical areas (Benin, India, and Malawi) by expanding the targeted population and the frequency of mass drug administration with albendazole. A follow-on investment to DeWorm3 aims to work with the extraction and real-time PCR-based testing of DeWorm3 stool samples for helminth infection to finalize the validation of this methodology, ensuring adequate accuracy, precision and reproducibility, and run approximately 100,000 samples from the 3 DeWorm3 countries through this high-throughput qPCR protocol to assess if the prevalence of STH is <2% soon after mass drug administration.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  11/05/2015 – 9/30/2023

Principal Investigator:  Judd Walson

Primary Contact:  Arianna Means

Click here to read the study protocol.

Click here to read the implementation science protocol.

 

DeWorm3 DAC Trial Planning Grant (DeWorm3 Go!)

The DeWorm3 Go! grant supports the expedited analysis of DeWorm3 data to inform data collection and analytical materials designed for use at study midline (after 3 years of MDA) and endline (after two years of surveillance). The analysis will derive interim biological, social, program, and economic- level correlates of MDA treatment coverage across four rounds of community-wide MDA, and inform the development of a targeted policy profile systematically inform the optimal characteristics and requirements of a practical operational guideline for STH transmission interruption programs.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  7/23/2020 – 7/22/2021

Principal Investigator:  Arianna Means

Primary Contact:  Arianna Means

 

Neglected Tropical Disease Community of Practice (NTD CoP)

The NTD Community of Practice aims to foster professional development, pride and identity, community-based decision-making, access to technical expertise, and networking through a collaborative platform of African NTD program managers working to solve common neglected tropical disease implementation and management challenges.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  9/28/2020 – 9/14/2023

Principal Investigator:  Arianna Means

Primary Contact:  Jusufu Paye

 

 

Strengthening Economic Evaluation for Multi-sectoral Strategies for Nutrition (SEEMS-Nutrition)

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.

Sponsor:  Bill and Melinda Gates Foundation

Award Years:  11/05/2018 – 10/31/2020

Principal Investigator:  Carol Levin

Primary Contact:  Carol Levin