Pathogenesis of infectious diarrhea: GUT PHYSIOLOGY Part 13

GUT PHYSIOLOGY Part 13Campylobacter species: While the clinical picture of Campylobacter jejuni infection, the transmission of the pathogen and epidemiology of disease are all fairly well understood, attempts to understand the genetic and molecular basis of the virulence of this pathogen and of the factors that poise the host toward susceptibility to infection and severity of clinical enterocolitic disease, are only beginning. The clinical picture of the pathogenesis of C jejuni infection has been summarized in a comprehensive review. C jejuni and related species are the most common bacterial causes of diarrhea in many industrialized countries. In developing countries, the most common clinical presentation is mild watery diarrhea, whereas in developed countries, disease often manifests as a severe inflammatory diarrhea. No evidence has yet been found to suggest that the watery type and severe bloody types of diarrhea can be explained in terms of a C jejuni equivalent of the ETEC and EHEC mechanisms described above. Current thinking proposes that the different disease patterns reflect the immunological status of the host. Those with full immunity experience no clinical disease, whereas those with no preimmunity experience the full blown bloody diarrhea and those with partial immunity, watery diarrhea.

The incubation period can range from one to seven days, and acute diarrhea can last for one to two days with abdominal pain, which may persist after diarrhea has stopped. Diarrheal stools often contain fresh blood, mucus and an inflammatory exudate with leukocytes; bacteremia may also occur although it is rarely reported. Infected mucosae may be edematous and hyperemic with petechial hemorrhages. The disease, even its severe form, tends to be self-limiting, despite the fact that organisms may be isolated for several weeks after resolution of the symptoms. We do, however, know that there is a strong correlation between infection with C jejuni and Guillain-Barre syndrome, which is the most notable complication of C jejuni infection. Guillain-Barre syndrome is a peripheral neuropathy believed to be an autoimmune phenomenon arising from molecular mimicry between the polysaccharide side chains of C jejuni and neural gangliosides. buy prednisone

While there are reasonable models for studying colonization and initial invasion, there is a problem regarding experimental animal models in which to reproduce the extreme form of bloody diarrhea seen in humans. This constitutes a major reason why very little is known about the detailed mechanisms of pathogenicity of this hugely important pathogen. Most work to date has been carried out with in vitro cell systems from which two new claims have been made. A novel mechanism for internalization of C jejuni into Caco-2 cells has been proposed involving caveolae, which are nonclathrin-coated plasma membrane invaginations to which several cell-signalling molecules have been localized. Others recently claimed to have demonstrated, for the first time, the equivalent of a type III system for secreting proteins into eukaryotic cells, but this interpretation of the data is not supported by reference to the complete genome sequence, which has recently been completed. However, the C jejuni situation is probably about to change dramatically. A new strategy has been outlined based on the use of the new technology of ‘microarrays’. By this means, and by reference to the genomic atlas, it is theoretically possible to identify which genes are expressed under different sets of experimental conditions, including those that mimic the infection environment. Doubtless, a plethora of new data are about to be generated from which we hope to learn more of the disease-conferring attributes of C jejuni and related species.

This entry was posted in Diarrhea and tagged Bibrio cholerae, Clostridium difficile, Diarrhea, Escherichia coli, Shigella dysenteri.