Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China

Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex® and Typhidot-M® in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO≥80 & TH>A), a positive Tubex® test (≥4) and a positive Typhidot-M® test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.