Temporal Patterns and Risk Factors of Diarrheal Comorbidity among Children aged < 5 years in Rural Western Kenya: Evidence from Three Consecutive Enteric Studies - 2008-2024

Sub-Saharan Africa bears the highest burden of diarrhea, often complicated by comorbidities that delay diagnosis, hinder treatment, and worsen outcomes. As the epidemiology of diarrheal disease evolves, understanding comorbidity patterns is critical for effective public health responses. We examined the temporal patterns and risk factors of diarrheal comorbidity in Kenyan children aged < 5. We conducted secondary pooled analysis with a retrospective cohort design leveraging data from the Global Enteric Multicenter Study (GEMS, 2008-2012), the Vaccine Impact on Diarrhea in Africa (VIDA, 2015-2018), the Enteric for Global Health (EFGH) Shigella surveillance study (2022-2024). The outcome was comorbidity count, defined by Integrated Management of Childhood Illnesses case definitions and clinician diagnoses of ten conditions: malaria, bacterial infection, pneumonia, severe acute malnutrition (SAM), meningitis, acute febrile illness (AFI), respiratory Illness (non-pneumonia), anemia, stunting and wasting. Temporal trends were assessed using descriptive statistics and the Cochran-Armitage trend test. Risk factors were identified using generalized estimating equations with a Poisson distribution, adjusting for clustering. We analyzed data from 4,148 children with moderate-to-severe diarrhea; 90.3% had [&ge;] one comorbidity, with a declining trend across studies: GEMS (92.9%), VIDA (89.3%), and EFGH (86.6%). Pneumonia (49.5%), malaria (48.3%), and stunting (24.7%) were most common comorbidities. The proportion of children with only one comorbidity increased (28.9% [2008] to 49.7% [2024]), while multiple comorbidities declined. Traditional comorbidities (malaria, pneumonia, wasting, SAM) significantly decreased, while AFI, anemia, and non-pneumonia respiratory illness increased. Multivariable analysis identified older age, lower caregiver education, dehydration, vomiting, and high respiratory rate as drivers of higher comorbidity counts, while female sex was associated with fewer comorbidities. Despite the high prevalence, we observed a 25-29% decline in comorbidity burden and a fundamental shift in disease profiles. Our findings support the need for a shift from single-disease control to integrated disease management.