Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses andVibrio cholerae

Abstract

Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni.

Hydrological Regime and Water Shortage as Drivers of the Seasonal Incidence of Diarrheal Diseases in a Tropical Montane Environment

“…Exploring the seasonality of diarrhea reflects the relative predominance of its etiological agents and can provide new information for future, targeted vaccination programs and scheduled health information campaigns [15]. Further, understanding the determinants of seasonality can help in the development of early warning systems [16].…”

What Is the Reservoir of Emergent Human Norovirus Strains?

“…In developing countries, they are likely an even more substantial cause of severe disease, as supported by an estimate that they cause over one million clinic visits and 200,000 deaths in young children annually in this setting (2). Although a recent global enteric multicenter study (GEMS) questioned whether human noroviruses are indeed a significant cause of disease in developing nations (3), it is important to recognize that the viral detection assay used in that study was extremely outdated and much less sensitive than well-established quantitative and broadly reactive reverse transcription-PCR assays in common use today; thus, the GEMS very likely grossly underestimated the norovirus disease burden. This argument is strongly supported by innumerable reports of norovirus detection in ϳ20% of children hospitalized with diarrhea from all parts of the world.…”

Nieuwe vaccins

“…Een gerandomiseerde placebogecontroleerde fase I/IIstudie bij volwassenen op Cuba (2010), waarbij deelnemers een challenge met El Tor V. cholerae kregen toegediend één maand post vaccinatie, toonde bevredigende immunogeniciteit. Fase I-en II-studies bij kinderen in cholera-endemische gebieden zullen worden uitgevoerd, alvorens fase III-studies aan te vangen [24,28].…”

“…Doses van 2 × 10 E 7 KVE en 2 × 10 E 8 KVE van Peru-15 werden gebruikt en resulteerden beide in een significante toename van antibacteriële antistoffen. In tegenstelling tot eerdere studies met volwassenen, was de anticholeratoxine IgG-respons echter suboptimaal en wordt gepostuleerd dat een hogere dosis vaccin nodig zou kunnen zijn bij kinderen woonachtig in endemische gebieden [24,28].…”