Evaluating the accuracy of Salmonella Typhi Hemolysin E and lipopolysaccharide IgA to discriminate enteric fever from other febrile illnesses in South Asia

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Existing methods to identify patients infected with Salmonella enterica Typhi (S. Typhi) or Paratyphi are inadequately accurate, affordable, and efficient. We evaluated the discriminatory power of antibodies to S. Typhi hemolysin E (HlyE) and lipopolysaccharide (LPS) in Bangladesh, Nepal, and Pakistan. Plasma concentrations of anti-HlyE and LPS IgA were measured in blood culture-confirmed enteric fever cases and in febrile controls with laboratory-confirmed alternative etiology. Receiver operating characteristic analyses showed that combining anti-LPS and HlyE IgA distinguished enteric fever cases from other febrile illnesses with an area under the curve (AUC) of 0.93. Anti-LPS IgA alone performed nearly as well (AUC 0.92). In children under 5, the combination outperformed individual biomarkers (AUC 0.96 vs. 0.94 (HlyE), 0.93 (LPS)) and was most accurate in Bangladesh and Pakistan compared to Nepal. These findings support anti-HlyE and LPS IgA ELISA as an accurate method to identify enteric fever in endemic settings.