Searching for the elusive typhoid diagnostic

Abstract

Typhoid (enteric) fever is still a common disease in many developing countries but current diagnostic tests are inadequate. Studies on pathogenesis and genomics have provided new insight into the organisms that cause enteric fever. Better understanding of the microorganisms explains, in part, why our current typhoid methodologies are limited in their diagnostic information and why developing new strategies may be a considerable challenge. Here we discuss the current position of typhoid diagnostics, highlight the need for technological improvements and suggest potential ways of advancing this area.

Figure 1

Identifying the techniques and issues which surround the development of a new enteric fever diagnostic test. Samples, targets, methods and issues.

Figure 2

The lifestyle of Salmonella Typhi in the human host and implications for diagnostics. A; For S. Typhi infection, the organism normally enters the human host through oral ingestion of an infectious dose. B; S. Typhi does not replicate in large numbers in the intestine and shedding may be sporadic and limited. C; Invasion occurs through the terminal ileum, perhaps a short time after ingestion, M cells may be the preferred portal of entry. D; S. Typhi is transferred to monocytic cells and is trafficked to the reticulo-endothelial system, potentially in a semi-dormant state. E; S. Typhi re-emerges at an unknown time from the reticulo-endothelial system, possibly as the acquired immune response is activated, and re-enters the blood stream in low numbers. F; S. Typhi seeds into the liver, the gall bladder and the bone marrow where it can reside and may be detected for months or years. G; S. Typhi can enter into the bile duct and be shed sporadically, potentially in high numbers into the environment via the intestine.