Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum

Rump, J. A.; Arndt, R.; Arnold, Amber; Bendick, Christoph; Dichtelmüller, H.; Franke, Marry E.I.; Helm, E. B.; Jager, Herbert de; Kampmann, Beate; Kolb, Philipp; Kreuz, W.; Lissner, R; Meigel, W; Ostendorf, P.; Peter, Hans‐Hartmut; Plettenberg, Andreas; Schedel, I.; Stellbrink, HJ; Stephan, W.

doi:10.1007/bf00184800

Cited by 71 publications

(79 citation statements)

References 27 publications

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“…First, Ig in the BSC may have facilitated a reduction in number of viable parasites. Previous studies in human cryptosporidiosis have shown efficacy of immune bovine colostrum in some studies (20) and lack of efficacy in others (21). In our study, reduced oocyst shedding in BSC-treated calves was seen, but oocysts remained in the stool at the end of the study.…”

Section: Bovine Serum Concentrate For Cryptosporidiosiscontrasting

confidence: 44%

Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in Calves

Hunt

Armstrong

et al. 2002

Pediatr Res

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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...

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Section: Bovine Serum Concentrate For Cryptosporidiosiscontrasting

confidence: 44%

Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in Calves

Hunt

Armstrong

et al. 2002

Pediatr Res

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“…Despite exhaustive attempts at chemotherapy with a wide variety of drugs, including many that are effective against related apicomplexan parasites, no efficacious treatment for cryptosporidiosis has been identified. Passive immunotherapy with hyperimmune bovine colostral immunoglobulin (HBC Ig) has, however, shown some ability to ameliorate the clinical symptoms of disease in humans (29,62,77,88,93,(108)(109)(110). HBC Ig inhibits sporozoite invasion in vitro and neutralizes sporozoite infectivity in animal models of cryptosporidiosis (5, 9, 10, 23, 69-71, 84-86, 107).…”

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confidence: 99%

Cloning and Sequence Analysis of a Highly PolymorphicCryptosporidium parvumGene Encoding a 60-Kilodalton Glycoprotein and Characterization of Its 15- and 45-Kilodalton Zoite Surface Antigen Products

2000

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The apicomplexan parasite Cryptosporidium parvum is a major cause of serious diarrheal disease in both humans and animals. No efficacious chemo-or immunotherapies have been identified for cryptosporidiosis, but certain antibodies directed against zoite surface antigens and/or proteins shed by gliding zoites have been shown to neutralize infectivity in vitro and/or to passively protect against, or ameliorate, disease in vivo. We previously used monoclonal antibody 11A5 to identify a 15-kDa surface glycoprotein that was shed behind motile sporozoites and was recognized by several lectins that neutralized parasite infectivity for cultured epithelial cells. Here we report the cloning and sequence analysis of the gene encoding this 11A5 antigen. Surprisingly, the gene encoded a 330-amino-acid, mucin-like glycoprotein that was predicted to contain an N-terminal signal peptide, a homopolymeric tract of serine residues, 36 sites of O-linked glycosylation, and a hydrophobic C-terminal peptide specifying attachment of a glycosylphosphatidylinositol anchor. The singlecopy gene lacked introns and was expressed during merogony to produce a 60-kDa precursor which was proteolytically cleaved to 15-and 45-kDa glycoprotein products that both localized to the surface of sporozoites and merozoites. The gp15/45/60 gene displayed a very high degree of sequence diversity among C. parvum isolates, and the numerous single-nucleotide and single-amino-acid polymorphisms defined five to six allelic classes, each characterized by additional intra-allelic sequence variation. The gp15/45/60 single-nucleotide polymorphisms will prove useful for haplotyping and fingerprinting isolates and for establishing meaningful relationships between C. parvum genotype and phenotype.Cryptosporidium parvum, a protozoan parasite of the phylum Apicomplexa, is an enteric pathogen that infects humans and many animals and causes an acute diarrheal disease (30, 61). Cryptosporidiosis is self-limiting in immunocompetent individuals (22,25,116) but is often chronic and life-threatening in immunocompromised patients, such as those with AIDS (20,22,72,76,78) or in persons with weakened immune systems, for example, malnourished children and the elderly (18,24,27,46,89). Despite exhaustive attempts at chemotherapy with a wide variety of drugs, including many that are effective against related apicomplexan parasites, no efficacious treatment for cryptosporidiosis has been identified. Passive immunotherapy with hyperimmune bovine colostral immunoglobulin (HBC Ig) has, however, shown some ability to ameliorate the clinical symptoms of disease in humans (29,62,77,88,93,(108)(109)(110). HBC Ig inhibits sporozoite invasion in vitro and neutralizes sporozoite infectivity in animal models of cryptosporidiosis (5, 9, 10, 23, 69-71, 84-86, 107). Although the exact identities of the HBC Ig neutralization antigens are unknown, several candidate molecules have been identified (8,39,69,(84)(85)(86)107). The majority are protein or glycoprotein antigens present on the zoite surface ...

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“…Higher doses of a product derived from colostrum of nonimmunized cows have previously been effectively employed in AIDS patients with chronic diarrhea due to Cryptosporidia 30 or of unknown etiology. 31,32 However, the poor clinical condition of BMT recipients may reduce the possibility of exploring the benefits of dose escalation. A possible strategy for improving a future therapeutic preparation would be to increase the concentration of antibodies against crucial surface determinants on the yeast cells such as adhesion molecules and/or to deliver with excipient to increase mucosal adherence and dwelling time.…”

Section: Discussionmentioning

confidence: 99%

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients

Tollemar

Gross

Dolgiras

et al. 1999

Bone Marrow Transplant

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Summary:Candida overgrowth and invasion constitute a serious threat with a high mortality in BMT recipients. Currently available topical antifungal prophylaxis is largely ineffective, and as resistance to existing, absorbable drugs for systemic use is rapidly developing, new forms of therapy are needed. We investigated the effect of oral treatment of BMT recipients with a bovine immunoglobulin product derived from animals immunized against several Candida species. The natural Candida colonization was first followed in 19 patients to establish the colonization pattern. Half of the patients were found to be colonized prior to transplantation and altogether 72% were colonized at some point during follow-up. Those with a high pre-transplant concentration of Candida in saliva (Ͼ100 CFU/ml) remained colonized throughout the BMT treatment period. The therapeutic effect was monitored in two other patient groups. The first group consisted of nine patients, where, due to a low number of primary colonized patients, response in colonized patients was suggestive of a therapeutic effect. In the second group, 10 patients with a high level of colonization (Ͼ100 CFU/ml) were given 10 g daily of the product in three divided doses. The results suggest a treatment-related reduction in Candida colonization in a majority (7/10) of patients and one patient became completely negative. As no adverse effects were noted, our findings encourage additional studies in immunocompromised, transplant patients.

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Treatment of diarrhoea in human immunodeficiency virus-infected patients with immunoglobulins from bovine colostrum

Cited by 71 publications

References 27 publications

Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in Calves

Oral Bovine Serum Concentrate Improves Cryptosporidial Enteritis in Calves

Cloning and Sequence Analysis of a Highly PolymorphicCryptosporidium parvumGene Encoding a 60-Kilodalton Glycoprotein and Characterization of Its 15- and 45-Kilodalton Zoite Surface Antigen Products

Fungal prophylaxis by reduction of fungal colonization by oral administration of bovine anti-Candida antibodies in bone marrow transplant recipients

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