Considerations for using ETEC and Shigella disease burden estimates to guide vaccine development strategy

Abstract

Enterotoxigenic E. coli (ETEC) and Shigella are enteropathogens causing significant global morbidity and mortality, particularly in low-income countries. No licensed vaccine exists for either pathogen, but candidates are in development, with the most advanced candidates potentially approaching pivotal efficacy testing within the next few years. A positive policy recommendation for introduction of any vaccine, following licensure, depends on evidence of vaccine cost-effectiveness and impact on morbidity and mortality. The mortality estimates for these two pathogens have fluctuated over recent years, which has led to uncertainty in the assessment of their relative public health importance for use in low and middle-income countries. This paper summarizes the various ETEC and Shigella disease burden estimates, based on a review of current literature and informal consultations with leading stakeholders in enteric disease modelling. We discuss the factors that underpin the variability, including differences in the modelling methodology; diagnostic tools used to ascertain diarrheal etiology; epidemiological setting; the data that are available to incorporate; and absolute changes in the total number of diarrheal deaths over time. We consider the further work that will strengthen the evidence needed to support future decision making with respect to recommendations on the relative utility of these vaccines.

Enterotoxigenic E. coli virulence gene regulation in human infections

“…ETEC | enterotoxigenic E. coli | FNR | toxin | cfa E nterotoxigenic Escherichia coli (ETEC) is a global Gramnegative diarrheal pathogen of the small intestine that infects up to 200 million people worldwide each year (1). ETEC infections result in ∼100,000 deaths annually and rely on a trio of classical ETEC virulence factors to cause disease (2)(3)(4). The prototypical ETEC strain H10407 harbors heat-labile (LT) and heat-stable (ST) enterotoxins along with the colonization factor antigen I (CFA/I) adhesin (5).…”

Update on vaccines for enteric pathogens

“…ETEC, one of several pathotypes of diarrhoeagenic E. coli, causes a secretory diarrhoea that can range in presentation from mild discomfort to a cholera-like illness. It is a highly prevalent bacterial cause of childhood diarrhoea in LMICs [76], with recent under-5 mortality estimates ranging between 7000 and 76,000 per year [77], and a leading cause of travellers' diarrhoea (30e50% of cases) [55,56,78,79]. As with Shigella, its dual importance in global public health and travel medicine has galvanized efforts to develop a safe and effective ETEC vaccine.…”

Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies

“…A major complication in infants and children is toxic megalocolon, while after clearance of the infection, other possible complications include hemolytic-uremic syndrome, characterized by renal failure, low platelet and red blood cell levels, and a 35% fatality rate, as well as post reactive arthritis, where patients may suffer from chronic arthritis of the joints for years after a shigellosis episode [7,8]. Shigella has a very low infectious dose, estimated to be 10 to 100 bacteria, and it remains a major public health concern with an estimated 165 million cases occurring worldwide every year, including up to 100,000 deaths, particularly in children under 5 years of age [9,10].…”