Protocol for the PATHOME Study: A Cohort Study on Urban Societal Development and the Ecology of Enteric Disease Transmission among Infants, Domestic Animals, and the Environment

Introduction. Global morbidity from enteric infections and diarrhea remains high in children in low- and middle-income countries (LMICs), despite significant investment over recent decades in health systems and global water and sanitation infrastructure. Other types of societal changes may be required to reduce disease burden. Ecological research on the influence of household and neighborhood societal development on pathogen transmission dynamics between humans, animals, and the environment could identify more effective strategies for preventing enteric infections. Methods and analysis. The "enteric pathome" - i.e., the communities of viral, bacterial, and parasitic pathogens transmitted from human and animal feces through the environment is taxonomically complex in high burden settings. This integrated cohort-exposure assessment study leverages natural socio-economic spectrums of development to study how pathome complexity is influenced by household and neighborhood development. We are enrolling under 12-month-old children in low- and middle-income neighborhoods of two Kenyan cities (Nairobi and Kisumu) into a short-cohort study involving repeat testing of child feces for enteric pathogens. A mid-study exposure assessment documenting infrastructural, behavioral, spatial, climate, environmental, and zoonotic factors characterizes pathogen exposure pathways in household and neighborhood settings. These data will be used to inform and validate statistical and agent-based models that identify individual or combined intervention strategies for reducing multi-pathogen transmission between humans, animals, and environment in urban Kenya. Ethics and dissemination. The protocols for human subjects' research were approved by Institutional Review Boards at the University of Iowa (ID 202004606) and AMREF Health Africa (ID ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (NACOSTI) (ID# P/21/8441). The study was registered on Clinicaltrials.gov (Identifier: [NCT05322655][1]). Protocols for research on animals were approved by the University of Iowa Animal Care and Use Committee (ID 0042302). STRENGTHS AND LIMITATIONS OF THE STUDY This cohort-exposure assessment study will provide new evidence on the nature of household and neighborhood developmental strategies that are most effective at preventing critical multi-pathogen transmission pathways among humans, animals, and environment in cities of low- and middle-income countries. We study middle class households and neighborhoods to test counterfactual theories about meeting basic developmental standards to reduce pathogen transmission. Our data collection uses objective methods to comprehensively document socioeconomic, weather, infrastructural, spatial, behavioral, environmental, zoonotic, and human data, including use of both selective culture and molecular methods to characterize pathogen community patterns. The observational study design is vulnerable to unmeasured confounders. The living conditions in middle-class households and neighborhoods may not offset hygiene conditions in the overall urban environment enough to alter enteric pathogen transmission patterns. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement The Pathogen Transmission and Health Outcome Models of Enteric Disease (PATHOME) study is supported by the National Institutes of Health (NIH) Fogarty International Center (FIC) through the Evolution and Ecology of Infectious Disease funding mechanism (1 R01 TW011795, years 2020-2025). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocols for human subjects research were approved by Institutional Review Boards at the University of Iowa (ID - 202004606) and AMREF Health Africa (ID - ESRC P887/2020), and a national permit was obtained from the Kenya National Commission for Science Technology and Innovation (NACOSTI) (ID# P/21/8441). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05322655&atom=%2Fmedrxiv%2Fearly%2F2023%2F05%2F28%2F2023.05.26.23290617.atom