Host factors, inflammatory markers, and clinical outcomes of Naegleria fowleri meningoencephalitis

Abstract Background Primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri carries historical case fatality rates (CFR) exceeding 97%. The 2025 Kerala outbreak, the largest documented globally, provided an unprecedented opportunity to identify host factors and inflammatory correlates influencing survival under standardised management. Methods We conducted a prospective observational study of 200 laboratory-confirmed PAM cases across six districts of Kerala, India (January–November 2025). All patients received protocolised amphotericin B ± miltefosine. Demographic, clinical, and laboratory data were collected, including inflammatory biomarkers (IL-6, TNF-α, IL-1β, neutrophil-to-lymphocyte ratio), pathogen burden (qPCR), and treatment timing. Multivariable logistic regression identified mortality predictors; bootstrap resampling and E-value sensitivity analyses assessed robustness. Results Here we show that among 200 patients (median age 41 years; 50% male), 134 with resolved outcomes yield a CFR of 45·5% (95% CI 37·3–54·5%; 61 deaths, 73 recoveries). Diabetes mellitus is the only statistically significant predictor of mortality in the adjusted model (adjusted OR 2·59; 95% CI 1·01–6·66; p = 0·048), though the proximity of the lower confidence bound to unity warrants cautious interpretation. This association remains consistent across sensitivity analyses (bootstrap 95% CI 1·06–8·74; E-value 4·62). Asthma demonstrates a protective association in univariable analysis (OR 0·37; p = 0·021), though this finding remains hypothesis-generating. Early treatment (≤2 days) shows a trend toward improved survival ( p = 0·084). Inflammatory biomarkers show no association with outcome, though CSF pathogen burden correlates significantly with admission neurological severity. Conclusions Under standardised treatment, diabetes mellitus emerges as a key host determinant of PAM mortality. The dissociation between inflammatory markers and outcomes suggests neurological fate may be determined early in infection, with immediate clinical implications as climate change expands the geographic range of N. fowleri .