Target product profile to guide development of next generation diagnostic test for Salmonella enterica: Responding to the crisis of drug resistant typhoid

BACKGROUND: A rapid point-of-care diagnostic test is essential for detecting and differentiating Salmonella enterica serovars Typhi and Paratyphi while also assessing antimicrobial susceptibility to support evidence-based treatment in low-resource settings. This manuscript outlines the key features of an ideal Target Product Profile (TPP) for a typhoid diagnostic that integrates antimicrobial susceptibility testing , addressing the needs of patients in resource-limited low- and middle-income countries (LMICs). METHODS: The TPP has been developed through a two-round Delphi survey, incorporating feedback from key stakeholders. RESULTS: Antibody detection tests currently available and used in endemic LMICs, suffer from challenges due to pre-existing titres from past infections or vaccinations. Next generation of antibody detection diagnostics tests can achieve enhanced accuracy by amending the threshold values and/or combining with other biomarkers. Molecular techniques such as CRISPR-based detection, droplet digital PCR, recombinase polymerase amplification, helicase-dependent amplification and loop-mediated isothermal amplification have the potential to revolutionise detection of typhoid by improving precision and speed of diagnosis. These nucleic acid-based methods offer high sensitivity and specificity while overcoming the limitations of antigen and antibody based tests, which are prone to false positives and cross-reactivity. To enable effective antimicrobial resistance detection, the test should incorporate key antibiotic resistance markers as these are crucial for tracking emerging multidrug-resistant Salmonella enterica strains and guiding appropriate treatment. CONCLUSIONS: Integrating molecular antimicrobial resistance detection with pathogen identification, can prove to be transformative for clinical management of typhoid in low resource settings and have direct impact on rising drug resistant typhoid rates.