CAGED: CAMPYLOBACTER GENOMICS AND ENVIRONMENTAL ENTERIC DYSFUNCTION
The CAGED Study is part of the project EQUIP – Strengthening smallholder livestock systems for the future, funded by the Bill & Melinda Gates Foundation.
Principal Investigator (PI) and Lead Institution
- Arie Hendrik Havelaar, University of Florida (visit The Havelaar Lab at UF)
Collaborator Institutions and Core Investigators
- University of Florida: Dr. Sarah Mckune, Co-PI; Dr. Nitya Singh; Dr. Yang Yang; Dr. Volker Mai; Dehao Chen, Xiaolong Li
- Haramaya University: Dr. Jemal Yousuf, Co-PI; Dr. Abdulmuen Mohammed, Project Manager; Dr. Negassi Ameha; Dr. Mengistu Ketema; Dr. Nega Assefa; Dr. Yitagele Terefe; Dr. Kedir Teji Roba
- Ohio State University: Dr. Wondwossen Gebreyes, Co-PI; Dr. Getnet Yimer; Dr. Gireesh Rajashekara (Co-PI), Dr. Loic Deblais
- Washington University in St. Louis: Dr. Mark Manary, Co-PI; Dr. Isabel Ordiz
- U.S. Food and Drug Administration: Dr. Marc Allard
- Massey University of New Zealand: Dr. Nigel French
Children who lack nutritious food are likely to face many illnesses and even death. Globally, undernutrition is a major factor in the death toll of children under the age of five. The children who survive may face cognitive and emotional problems. One means of reducing such undernutrition is to increase a child’s consumption of animal-source foods; moreover, these foods are crucial for the nutritional health and livelihoods of 600 million small-scale farming families living in poverty. But does the problem stem from poor nutrition only, or are other processes involved as well?
Every parent knows that children habitually put contaminated objects in their mouths. When those children live in close contact with livestock, such as goats and chickens, they have added risks of contamination from bacteria hosted in the animals. Emerging evidence indicates that a high prevalence of bacteria—specifically from curved bacteria called Campylobacter—infects children in these settings, which leads to impaired gut health, nutrition and growth. This impairment may undermine the potential benefits of animal-source foods. Unfortunately, little is known about the reservoirs and transmission pathways of these bacteria in rural communities in low- and middle- income countries, such as Ethiopia.
Our research seeks to understand the livestock reservoirs for Campylobacter infection. It aims to gain insight into Campylobacter species composition, genomic diversity, and its presence in livestock and how they are related to these bacteria in the gut of young children. We also want to understand what the connections are between these bacteria and overall gut microflora. And, ultimately, we seek to understand how they affect the health status of children in these rural communities.
Prior to a longitudinal study, a formative, cross-sectional study was conducted in rural eastern Ethiopia to assess the prevalence of stunting, environmental enteric dysfunction (EED), and Campylobacter colonization in young children, as well as to characterize the socio-demographic background. Among the 102 sampled children aged 12 to 16 months, half were colonized by Campylobacter when tested by polymerase chain reaction, and EED biomarkers were elevated in half of them. In most children, the infections were asymptomatic (not accompanied by diarrhea and/or fever). The prevalence of stunting was 41%, higher than the Ethiopian national average. Breastfeeding was common, and more than half of the children consumed some animal source foods (mainly milk), but diversity of complementary foods was low. Water, sanitation, hygiene, and management of animal droppings were poor. Metagenomic analyses revealed a high diversity of Campylobacter species in the children’s gastrointestinal tracts. Besides the well-known species Campylobacter jejuni and C. coli, other non-thermophilic Campylobacter species related to C. fetus and C. hyointestinalis were observed frequently and in high abundance. Very little is known about the reservoirs and transmission pathways of these species. Based on limited knowledge from high-income countries, we hypothesize that livestock, including chickens and ruminants, are important reservoirs.
Our initial hypothesis, that chickens were the main reservoirs of Campylobacter colonization of young children, was not fully confirmed by the formative research findings. Ruminants may also be an important reservoir, and even human-human transmission cannot be excluded. We will conduct a prospective longitudinal study to assess the fecal-oral transmission network of Campylobacter bacteria in our study area and to quantify the role of livestock in this transmission.
The longitudinal study will be undertaken to address the following objectives:
- To assess the prevalence, species composition, and genomic diversity of thermotolerant and non-thermotolerant Campylobacter species in young children, adults, livestock and other reservoirs in the Haramaya woreda;
- To determine the attribution of Campylobacter infections in young children to humans, livestock, and other reservoirs (i.e. drinking water, soil) based on the genetic population structure of Campylobacter species circulating in these reservoirs;
- To assess the associations among the presence of Campylobacter species, gut microbiota, and the health status of children.
The longitudinal study will involve 120 children followed from birth to 18 months of age in 12 kebeles in rural eastern Ethiopia. A range of microbiological methods will be used to characterize the genetic structure of Campylobacter population in human and livestock reservoirs. Interactions between Campylobacter colonization and overall gut microflora in the children against a background of the socio-demographic environment will also be evaluated.
Given the unique opportunity of working with a well-characterized cohort of young children from the CAGED project, the EXposure Assessment of CAMpylobacter Infection in Rural Ethiopia (EXCAM) project was additionally funded by the Bill & Melinda Gates Foundation. EXCAM aims to develop and apply methodology to unravel pathways of children’s exposure to Campylobacter spp.
- Bardosh, K.L., Hussein, J.W., Sadik, E.A. et al. 2020. Chicken eggs, childhood stunting and environmental hygiene: an ethnographic study from the Campylobacter genomics and environmental enteric dysfunction (CAGED) project in Ethiopia. One Health Outlook 2, 5. https://doi.org/10.1186/s42522-020-00012-9
- Chen, D., McKune, S.L., Singh, N., Hassen, J.Y., Gebreyes, W., Manary, M.J., Bardosh, K., Yang, Y., Diaz, N., Mohammed, A., Terefe, Y., Roba, K.T., Ketema, M., Ameha, N., Assefa, N., Rajashekara, G., Deblais, L., Ghanem, M., Yimer, G., and Havelaar, A.H. 2021. Campylobacter Colonization, Environmental Enteric Dysfunction, Stunting, and Associated Risk Factors Among Young Children in Rural Ethiopia: A Cross-Sectional Study From the Campylobacter Genomics and Environmental Enteric Dysfunction (CAGED) Project. Front. Public Health, Volume 8, Article 615793. https://doi.org/10.3389/fpubh.2020.615793
- Chen, D., Mechlowitz, K., Li, X., Schaefer, N., Havelaar, A.H. and McKune, S.L. 2021. Benefits and Risks of Smallholder Livestock Production on Child Nutrition in Low- and Middle-Income Countries. Front. Nutr. 8:751686. https://doi.org/10.3389/fnut.2021.751686
- Havelaar, A.H., Brhane, M., Ahmed IA, Ahmed, I.A., Kedir, J., Chen, D., Deblais, L., French, N., Gebreyes, W.A., Hassen, J.Y., Li, X., Manary, M.J., Mekuria, Z., Ibrahim, A.M., Mummed, B., Ojeda, A., Rajashekara, G., Roba, K.T., Saleem, C., Singh, N., Usmane, I.A., Yang, Y., Yimer, G., and McKune, S. 2022. Unravelling the reservoirs for colonisation of infants with Campylobacter spp. in rural Ethiopia: protocol for a longitudinal study during a global pandemic and political tensions. BMJ Open, 12:e061311. doi:10.1136/bmjopen-2022-061311
- Magalhães, M., Ojeda, A., Mechlowitz, K., Brittain, K., Daniel, J., Roba, K.T., Hassen, J.Y., Manary, M.J., Gebreyes, W.A., Havelaar, A.H. and McKune, S.L. 2022. Socioecological predictors of breastfeeding practices in rural eastern Ethiopia. International Breastfeeding Journal, 17, 93. https://doi.org/10.1186/s13006-022-00531-3
- Terefe Y., et al. 2020. Co-occurrence of Campylobacter Species in Children From Eastern Ethiopia, and Their Association With Environmental Enteric Dysfunction, Diarrhea, and Host Microbiome. Frontiers in Public Health, 8 (99). https://doi.org/10.3389/fpubh.2020.00099
- Yimer, G., Gebreyes, W., Havelaar, A., Yousuf, J, McKune, S., Mohammed, A. and O’Mathúna, D. 2020. Community engagement and building trust to resolve ethical challenges during humanitarian crises: experience from the CAGED study. Conflict and Health 14, 68. https://doi.org/10.1186/s13031-020-00313-w
- Poster. Deblais, L. et al. 2022. Prevalence and species diversity of Campylobacter in infants and livestock reservoirs in rural households in Eastern Ethiopia. ASTMH Annual Meeting.
- Havelaar, A.H. and McKune, S.L. 2021. Balancing the nutritional benefits and infection risks of livestock in low and middle-income countries. OIE Panorama, 1:21/60-23/60.
- Blog. February 2021. Researchers return to field work for healthy infants in Ethiopia
- Video & presentation. July 2020. Livestock, Campylobacter and child nutrition: findings from the formative research of the CAGED study in rural Ethiopia
- Results Summary. June 2020. Key Findings from Formative Research of the CAGED Project
- Symposium: Livestock, Sanitation, Hygiene, and Child Growth
- Enteric and Diarrheal Diseases (Bill & Melinda Gates Foundation)
- The overarching project EQUIP – Strengthening Smallholder Livestock Systems for the Future
October 2020 research update CAGED VGM (Virtual General Meeting)
- Adequate nutrition combined with appropriate hygiene positively influence child growth, The Reporter, Ethiopia, October 6, 2018