Use of Salmonella enterica Serovar Typhi Hemolysin E and Lipopolysaccharide IgA to Identify Enteric Fever Cases, South Asia

Existing methods to identify patients infected with Salmonella enterica serovar Typhi or Paratyphi are not adequately accurate, affordable, or efficient. We evaluated the performance of antibodies to Salmonella Typhi hemolysin E (HlyE) and lipopolysaccharide (LPS) in Bangladesh, Nepal, and Pakistan for enteric fever case identification. We measured plasma concentrations of HlyE and LPS IgA in blood culture–confirmed enteric fever case-patients and in febrile controls with laboratory-confirmed alternative etiologies. Combining LPS and HlyE IgA discriminated enteric fever cases from other febrile illnesses with an area under the receiver operating characteristic curve (AUC) of 0.93 (specificity 86% at a fixed 90% sensitivity). LPS IgA alone performed nearly as well (AUC 0.92). In children <5 years of age, the combined biomarkers outperformed either biomarker alone (AUC 0.96 vs. 0.94 for HlyE, 0.93 for LPS). Our findings support use of HlyE and LPS IgA–based assays for enteric fever diagnosis in endemic settings.