Science Editor

Rotavirus, and the diarrhea it causes, has provided many a Western parent with stories from the trenches. But it also causes true tragedy for many a parent in the developing world, where millions of children die of diarrhea each year.

A paper in the July 1, 2008, issue of the Proceedings of the National Academy of Sciences reported new findings on how rotavirus, which is one of the major culprits causing diarrhea in North America as well as the developing world, does its damage.

The past year has seen approval of two rotavirus vaccines; but as researchers stated in the article, there is "a continuing need to better understand the mechanisms of rotavirus replication and pathogenesis."

In their paper, the scientists showed that NSP4 enterotoxin produced by rotavirus binds to cells via matrix proteins known as integrins on neighboring cells, leading to the activation of several signaling pathways.

Specifically, cells need to have alpha1beta1 or alpha2beta1 integrins to be susceptible to rotaviral toxin. NSP4 that could not bind to those integrins was not as effective as wild-type NSP4 at inducing diarrhea in newborn mice.

The authors said that blocking the interaction between NSP4 and the integrins may be a treatment strategy for rotavirus-induced diarrhea, and that their findings "further [distinguished] this viral virulence factor from other microbial enterotoxins."

Those other microbial enterotoxins - specifically, those produced by E. coli - also have been the subject of recent news.

A bout of traveler's diarrhea tends at the very least to be the low moment of the trip where it is picked up. And it can lead to longer-term complications as well. Traveler's diarrhea can predispose its sufferers to irritable bowel syndrome.

To date, treatment is indirect. Rather than treating the E. coli itself, it aims to prevent serious consequences by minimizing fluid loss. But rotavirus, even for Western tourists who have access to care for a bout of E. coli-induced traveler's diarrhea - even in those cases where it includes a trip to the ER - rarely does it lead to the death that diarrhea can cause in developing nations.

Recent research, though, may offer hope to both locals and tourists who pick up the enterotoxic E. coli that are responsible for a goodly chunk of bacterial diarrhea cases. In the June 24, 2008, issue of PNAS, researchers reported on a compound that inhibits the receptor activated by heat-stable enterotoxin, one of the main toxins produced by diarrhea-causing E. coli strains.

The researchers describe the mechanism of action of their compound - named BPIPP - as "complex and indirect," but the net effect appeared to be that chloride ions were prevented from moving into the intestine and take water with them. In cultured human colon cells and rabbit intestines, treatment with the compound led to reduced fluid secretion by the cells and buildup in the intestines, respectively.

The research reported in PNAS last week was still in the preclinical phase. Further down the clinical pipeline, researchers reported on a successful Phase II trial of a traveler's diarrhea vaccine in the June 14, 2008, issue of The Lancet.

The 170 participants in the study received either two doses of biotechnology company Iomai Corp.'s skin patch or a placebo, two to three weeks apart, with the last dose administered a week before travel. Compared to participants receiving placebo, there were fewer cases of moderate as well as severe diarrhea in the vaccinated group, and the illness was shorter and less severe for those vaccinated patients that did fall ill.

There also were fewer cases of newly diagnosed irritable bowel syndrome in the vaccinated group, though the latter finding was not statistically significant.

Gaithersburg, Md.-based Iomai, which is developing the vaccine for use by both travelers and children living in developing nations, plans to initiate a Phase III program for the vaccine in 2009.