Clinical characteristics and an admission-time predictive model for severe scrub typhus and secondary HLH in adults

Scrub typhus can rapidly progress to severe disease with multi-organ dysfunction. Secondary hemophagocytic lymphohistiocytosis (HLH) is an increasingly recognized hyperinflammatory complication associated with high mortality, but adult data and simple admission-time risk tools remain limited.

We conducted a single-center retrospective cohort study of hospitalized adults with scrub typhus at the First Affiliated Hospital of Guangzhou Medical University (May 2013-July 2025). Severe scrub typhus was defined by major organ involvement, shock, or in-hospital death. Variables available at admission were compared between severe and non-severe groups. Independent predictors were identified using multivariable logistic regression, and model performance was evaluated using ROC analysis. Among severe cases, HLH was identified according to standard diagnostic criteria, and clinical characteristics were compared between HLH and non-HLH patients.

Among 135 patients, 44 (32.6%) developed severe scrub typhus and overall in-hospital mortality was 2.2% (3/135). Lower hemoglobin (Hb) (OR 0.965, 95% CI 0.947-0.982), higher serum creatinine (SCr) (OR 1.019, 95% CI 1.008-1.029), and lower fibrinogen (FIB) (OR 0.629, 95% CI 0.435-0.909) were independent predictors of severe disease. A parsimonious three-variable model showed good discrimination (AUC = 0.843). At the sensitivity-prioritized ROC threshold, sensitivity was 88%, specificity 46%, and the Youden index 0.34. HLH was identified in 6 patients overall, including 5 patients among the severe cases. Among severe patients, HLH cases showed higher observed in-hospital mortality than non-HLH cases (40.0% vs. 2.6%). They also had more severe thrombocytopenia and greater coagulation and organ-function abnormalities.

A simple admission-time triad (Hb, SCr, and FIB) provides an interpretable tool for early identification of severe scrub typhus in hospitalized adults. HLH cases showed higher observed mortality and more severe thrombocytopenia/coagulation derangement; however, these findings should be interpreted descriptively due to the small number of cases.