Source:Charmandari E, Meadows N, Patel M, et al. Plasma nitrate concentrations in children with infectious and non-infectious diarrhea.
J Pediatr Gastroenterol Nutr.

These authors from the Royal London School of Medicine studied plasma nitrate levels in 3 groups of patients: those with acute infectious gastroenteritis (14); those with non-infectious diarrhea (13); and healthy controls (14). The investigators theorized that patients with infectious diarrhea might have higher levels of plasma nitrate concentrations than those with non-infectious diarrhea or controls. Their data indicate that children with infectious diarrhea had significantly higher (P<.0003) plasma nitrate levels than those children with non-infectious diarrhea and controls. This preliminary study did not include a sufficient number of patients to establish an upper limit of normal “cut-off” value for plasma nitrate concentration since the range in infectious diarrhea was fairly large.

We are becoming increasingly aware of the importance of nitric oxide (NO) as a mediator of both physiologic and pathologic responses. Bacterial lipopolysaccharides and lipoteichoic acids stimulate inducible NO synthase which, in turn, results in increased plasma and urinary NO concentrations.1,2 NO levels appear to correlate with host response to infection, as well as improved clinical outcome in one study of children infected with falciparum malaria.1,3,4 Overproduction of NO appears to play an important role in the pathogenesis of acute and chronic inflammation. One of the above authors has previously shown that plasma and urinary nitrate concentrations are elevated in infectious diarrhea.5 Furthermore, previous studies have shown that plasma nitrate is elevated in inflammatory bowel disease (IBD) when compared to control patients;6 however, bacterial and viral infections resulted in even higher elevated plasma and urinary nitrate levels than IBD or controls. Plasma and urinary nitrate levels are dependent on renal function and dietary nitrogen intake during the infectious process, which may account for some of the observed variability seen in the patients with infectious diarrhea in this study. If validated with larger numbers of patients, this technique could provide a rapid and potentially sensitive and specific method for distinguishing infectious from non-infectious causes of diarrhea, perhaps within minutes after being performed. Unfortunately, this technique does not appear to differentiate bacterial from viral causes of gastroenteritis. It may well be that the determination of urinary nitrate concentration is as useful as plasma nitrate concentration; however, future studies are necessary to examine this question.

There seems to be lots of movement when it comes to identifying new serologic, urinary, and fecal markers for classifying the nature of diarrhea in children. Two months ago (see AAP Grand Rounds, November 2001;6:52–53), we learned that fecal calprotectin may help to differentiate the diarrhea seen in inflammatory bowel disease from other etiologies. Now we read that plasma and urinary nitrate levels may be useful in determining whether or not the diarrhea is infectious. These are only pilot studies and, therefore, we need to follow future runs of these tests to learn their sensitivity, specificity,...

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