Standard protocols for performance evaluation of typhoid fever in-vitro diagnostic assays in laboratory and field...

Typhoid fever is a leading public health problem in India and other South East Asian countries. Its diagnosis traditionally relies on culture methods with poor sensitivity, and serological methods with limited role in endemic areas. Incorrect diagnosis results in antibiotic misuse, disease complications, emergence and spread of multidrug-resistant strains. There is a need to develop quality diagnostic tests for effective and early diagnosis of typhoid fever. This will help in early patient management, disease burden estimation, and assessing the impact of public health interventions including vaccines.

This paper describes standard protocols for conducting pre-licensure (analytical) and field (clinical) performance evaluation of in-vitro diagnostic tests that detect S. Typhi antigens or antibodies or gene segments in blood/serum/plasma samples.

The analytical performance evaluation protocol describes diagnostic accuracy studies for three different IVD formats using well-characterized clinical samples, and the field validation protocol describes the methodology for conducting a cross-sectional study for assessing IVD performance in acute undifferentiated febrile illness. The latter may also be used to establish a typhoid sample biobank. Both the protocols use statistically significant sample size and describe a detailed sample panel (including cross reactive specimens).

These protocols will help in robust evaluation of IVDs for typhoid, especially in endemic areas and in absence of a predicate device. To the best of our knowledge, this is the first such comprehensive guidance document of their kind, which may be adapted across similar settings.