Abstract
Enteric (typhoid) fever remains a problem in low- and middle-income countries that lack the infrastructure to maintain sanitation and where inadequate diagnostic methods have restricted our ability to identify and control the disease more effectively. As we move into a period of potential disease elimination through the introduction of typhoid conjugate vaccine (TCV), we again need to reconsider the role of typhoid diagnostics in how they can aid in facilitating disease control. Recent technological advances, including serology, transcriptomics, and metabolomics, have provided new insights into how we can detect signatures of invasive Salmonella organisms interacting with the host during infection. Many of these new techniques exhibit potential that could be further explored with the aim of creating a new enteric fever diagnostic to work in conjunction with TCV. We need a sustained effort within the enteric fever field to accelerate, validate, and ultimately introduce 1 (or more) of these methods to facilitate the disease control initiative. The window of opportunity is still open, but we need to recognize the need for communication with other research areas and commercial organizations to assist in the progression of these diagnostic approaches. The elimination of enteric fever is now becoming a real possibility, but new diagnostics need to be part of the equation and factored into future calculations for disease control.
Highlights
Enteric fever is associated with a broad spectrum of clinical disease, ranging from asymptomatic to severe symptoms, such as fever, malaise, headache, and complications of ileal ulceration including perforation and profuse hemorrhage
Almost all techniques for diagnosing an infectious disease focus on (1) the direct detection of the pathogen of interest, or (2), the indirect detection of the pathogen via a measurement derived from the host response to the infecting agent, indicating recent exposure or active infection. he development of new rapid diagnostics for enteric fever has been a challenge for decades, with blood culture remaining the only real widely used standard against which new tests and intervention strategies are evaluated. he performance of blood culture in detecting S
Various eforts have been made to improve the accuracy of the standard against which to perform diagnostic evaluations, including the use of composite endpoints or Bayesian latent class modeling analysis [8,9,10]
Summary
Recent technological advances, including serology, transcriptomics, and metabolomics, have provided new insights into how we can detect signatures of invasive Salmonella organisms interacting with the host during infection. Many of these new techniques exhibit potential that could be further explored with the aim of creating a new enteric fever diagnostic to work in conjunction with TCV. We describe several such new and innovative approaches for the identiication and early validation of acute enteric fever through transcriptomics, metabolite proiling, and the humoral response to the organisms We discuss these new techniques and their pros and cons as we move into a new era of typhoid control and elimination
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