Typhoid fever is one of the most important causes of febrile illness globally. Accurate diagnosis is paramount due to severity of illness and ~10% mortality rate if untreated. However, highly sensitive and specific methods for typhoid fever diagnosis are lacking. In resource-poor endemic countries diagnostic methods are inadequate: often relying heavily on the Widal test or clinical observation. Both methods have limitations which often lead to patients receiving inappropriate treatment. The gold standard remains bone marrow culture, which is rarely conducted due to the invasiveness of the procedure; thus, blood culture remains the mainstay of diagnosis in well-resourced settings. Immune assays have been developed and are potentially suitable for use in endemic and non-endemic settings.

In the highlands of Papua New Guinea typhoid fever has been endemic for approximately30 years, with past studies demonstrating a high prevalence. Recently we evaluated two commercially available typhoid rapid diagnostic tests (TUBEX TF, Typhidot), a prototype (TR-02) and the currentlyusedWidal test using a composite reference standard of blood culture and real-time PCR. A total of 530 blood samples were collected from outpatients who were clinically diagnosed with typhoid fever from two health facilities. Our results reiterate the weakness of the Widal test, and demonstrate that thecurrently available immunoassays have shortcomings that are likely to preclude them from widespread application. However, the prototype test had a sensitivity and specificity of ≥85% relative to the composite reference standard.Based on its performance in our evaluation theprototype may be suitable for widespread use in endemic settings.Nonetheless, renewed effort is required to develop better diagnostic assays for typhoid fever, and disease prevention strategies and public health education are required.