Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in Calves

Abstract

Cryptosporidium parvum produces a prolonged watery diarrhea unresponsive to conventional antimicrobials. Because of reported efficacy of antibody-based immunotherapy, we studied the effect of inexpensive, commercially available oral bovine serum concentrate (BSC) in experimental cryptosporidiosis. Twenty-four calves were treated with 57 g/d BSC (n ϭ 12) or soy protein (n ϭ 12) added to their standard whey protein-based milk replacer (227 g/2 L twice daily). Of the 24, 9 were also treated with L-glutamine (GLN), 8 g/L (50 mM) in the milk (5 calves in the BSC group and 4 in the soy group). Animals were inoculated with 10 8 cryptosporidium oocysts per os on d 8 of life and received oral rehydration on d 12-14. Eight uninfected controls were treated with BSC or soy protein. Fecal and urine volume and urinary Cr-EDTA excretion were measured. Animals were killed on d 18 of life. Cryptosporidiosis induced severe watery diarrhea lasting Ͼ9 d and produced a 25% increase in intestinal permeability, a 33% decrease in villous surface area, and a 40% reduction in mucosal lactase specific activity. Glutamine treatment had no effect on the diarrhea or any of the intestinal tests; and therefore pooled data were used to compare the 12 calves treated with BSC with the 12 treated with soy. In animals receiving BSC, peak diarrheal volume and intestinal permeability were reduced 33%, fewer oocysts were shed, intestinal crypts were significantly deeper, and villous surface area returned to normal by 9 d after infection (all p Յ 0.05). BSC should be studied as a treatment for human cryptosporidiosis. Cryptosporidiosis is a major enteric pathogen found globally in infants with acute and chronic diarrhea, and is a cause of persistent diarrhea in 10%-20% of patients with AIDS. Cryptosporidium parvum is also the most widespread enteropathogen identified in neonatal calves. Ninety percent of American dairy farms harbor this coccidian, and 92% of asymptomatic adult cows have specific anti-C. parvum IgG, IgG1, IgG2, and IgM antibodies (1). Neonatal calves experience high morbidity, but low mortality with monoinfections, although mixed infections result in a much greater rate of mortality (2). The epidemic potential of this organism was realized in Milwaukee in 1993, when over 400,000 residents contracted the infection from contaminated municipal water sources (3). Presently, there is no available antimicrobial to kill cryptosporidium; in fact, there is no treatment to stimulate bowel repair from any infectious agent in infants with serious or chronic diarrhea.We have shown that cryptosporidial diarrhea is both malabsorptive and secretory in nature, produced by partial mucosal destruction as well as elevated levels of prostaglandin E 2 and prostacyclin, the latter of which activate enteric secretomotor neurons (4). We have also found beneficial effects of growth factors (present in serum and colostrum) in enhancing bowel repair in rotavirus diarrhea and after intestinal ischemic injury (5, 6). Recently, Lembcke (7) showed in Peruvian children...

Effect of animal plasma proteins on intestinal damage and recovery of neonatal pigs infected with rotavirus☆

“…However, shedding was not measured quantitatively and may have been different between diets, but not detectable by the method used. Reductions in diarrhea volume and severity have been previously observed in cryptosporidia-infected calves [15], E. coli-infected pigs [16] and calves [33], and Staphylococcus aureus enterotoxin B-infected rats [34] fed with plasma proteins. In these models of protozoal and bacterial diarrhea, and our viral model of diarrhea, the similar responses observed could relate to a common mechanism despite differences in pathogen and mode of diarrhea induction.…”

“…Other studies also have shown that plasma proteins improve intestinal health during pathogen-induced diarrhea. Calves infected with cryptosporidia had greater villus surface area and lactase activity when fed with plasma proteins [15]. Furthermore, E. coliinfected piglets fed with plasma proteins had less histological damage to the intestinal epithelium [16].…”

“…A recent report demonstrated that Cryptosporidiuminfected calves fed with bovine serum concentrate produced less diarrheal volume and had reduced intestinal permeability resulting in improved rate of intestinal recovery [15]. Piglets fed with plasma proteins and challenged with Escherichia coli K88 recovered from diarrhea more quickly [16] and had reduced intestinal inflammation [17].…”

Cryptosporidium parvum-Specific CD4 Th1 Cells from Sensitized Donors Responding to Both Fractionated and Recombinant Antigenic Proteins

“…Antibody therapy for C. parvum infection has been mainly proposed for persons with AIDS or with other immunodeficiencies. However, studies that have treated a significant number of persons with bovine colostrum from cows that were hyperimmunized with C. parvum oocysts have shown conflicting results (18,22,33,42,43). In light of these findings, the host cell immune response seems to be the only effective form of defense.…”

A rat model of mild intestinal inflammation induced byStaphylococcus aureusenterotoxin B

“…There is evidence that Ig and other functional components present in SDP and IC are well conserved and are highly functional, providing immunological benefits (46) . For example, they reduce the intestinal inflammation produced by pathogenic bacteria and viruses (47) or by protozoa (48) . The results of our studies on the effects of animal plasma preparations on intestinal inflammation indicate that these supplements can reduce, and in some cases prevent, the inflammatory syndrome induced by SEB.…”