Clinical phenotypes and severity stratification in pediatric diethylene glycol poisoning: a latent class analysis of the Gambia acute kidney injury outbreak.

BACKGROUND

Between June and September 2022, an outbreak of acute kidney injury (AKI) among children in The Gambia caused 66 deaths among 82 cases, linked to medicines contaminated with diethylene glycol (DEG) and ethylene glycol. Clinical heterogeneity in DEG poisoning remains poorly characterized, limiting risk stratification and resource allocation in outbreak settings. We used latent class analysis to identify distinct clinical phenotypes and their predictors.

METHODS

We conducted a secondary analysis of a case-cohort study involving 63 AKI cases and 258 controls aged ≤ 8 years. Latent class analysis, a statistical approach that identifies naturally occurring patient subgroups based on symptom patterns, used 13 binary symptom indicators to identify clinical phenotypes via an expectation-maximization algorithm. We compared models with 2-5 classes using the Bayesian Information Criterion and entropy. Multinomial logistic regression examined predictors of phenotype membership.

RESULTS

Four distinct phenotypes were identified: Classic Kidney-Fever (30.2%), Gastrointestinal-Kidney (22.2%), Cardio-Respiratory-Kidney (19.0%), and Mild/Atypical (28.6%). The 4-class model demonstrated excellent classification certainty (entropy = 0.910). The Cardio-Respiratory-Kidney phenotype showed the highest DEG exposure (83.3% vs. 44.4% in Mild/Atypical, p = .015) and was strongly predicted by exposure intensity (adjusted RRR = 6.82, 95% CI [1.45-32.10]) and younger age. Multisystem involvement (≥ 3 organ systems) occurred in 28.6% of cases vs. 0% of controls.

CONCLUSIONS

DEG-induced AKI manifests as four distinct clinical phenotypes with differing severity and exposure patterns. The severe Cardio-Respiratory-Kidney phenotype represents a critical target for prioritized intervention in resource-constrained settings. Importantly, nearly 30% of cases presented with atypical or minimally symptomatic features, underscoring the need for comprehensive case-finding and close follow-up during outbreak investigations.