Abstract
A milk immunoglobulin concentrate (MIC) containing antibodies to enteropathogenic E. coli strains was prepared by hyperimmunisation of pregnant cows and using the milk obtained during the first 6 to 8 days of lactation. The sterile concentrate contained 70 to 80% protein and 35 to 40% immunoglobulin. The antibacterial activity was measured by bacterial passive agglutination, bacteriostatic activity in vitro, phagocytic clearance in vivo, and a protection test in mice. Though differences in titers were observed, adequate immunologic activity was demonstrated by these tests.
Clinical studies were performed with 60 patients (aged 10 days to 18 months) suffering from diarrhoea with isolation of enteropathogenic E. coli. They were treated for 10 days with MIC and stool cultures were done prior to, during, and 2, 3 and 4 days after termination of treatment. Among 51 patients infected with E. coli strains incorporated in the vaccine, stool cultures became negative in 43 (84.3%) after treatment with MIC and 8 remained positive. Nine patients infected with strains O 78: K 80(B-) and O 114: K-(B-)-which were not included in the vaccine used for immunisation—served as controls. Only one patient in this group became negative. If all patients receiving antibiotics for non intestinal infections during the treatment period are omitted the results remained unaltered: MIC was effective in 32 out of 38 patients (84.2%). These differences were highly significant.
These results provide evidence that treatment with specific MIC is effective in eliminating enteropathogenic E. coli from the intestine.
Similar content being viewed by others
References
Amster, H.: Unpublished results, 1977
Avrameas, S., Taubou, B., Chuilon, S.: Gluteraldehyde, cyanuric chloride and tetraazotized O-dianisidine as coupling reagents in the passive hemagglutination test. Immunochemistry 6, 67–76 (1969)
Ballabriga, A., Hilpert, H., Isliker, H.: Immunity of the infantile gastrointestinal tract and implications on modern infant feeding. Nestlé Research News 1974/75, p. 25–45 (1976) (see also: Acta Paediatr. Belg. 29, 126)
Bockemühl, J., Fricke, G., Seeliger, H. P. R.: Enteritisfälle durch E. coli O 142 K 86 H 34 in einer Frühgeborenenstation. Mit einem Diskussionsbeitrag zur Frage der pathogenetischen Bedeutung “enteropathogener Coli-Typen”. Zbl. Bakt. Hyg., I. Abt. Orig. A 243 197–206 (1979)
Braun, O. H.: Über die infektionsverhütende Wirkung der Muttermilch und deren mögliche Ursachen. Klin. Pädiat. 188, 297–310 (1976)
Brodhage, H.: Harnstoff-Extrakte aus gramnegativen Bakterien in der indirekten Hämagglutinationsreaktion. Z. Hygiene 148, 94–104 (1961)
Bullen, C. L., Willis, A. T.: Resistance of the breast-fed infant to gastroenteritis. Brit. Med. J. 1971 III, 338
Conrath, T. B.: Handbook of microtiter procedures 1972
Demierre, G., Rivier, D., Hilpert, H., Gerber, H., Zinkernagel, R. M.: Adhérence de E. coli pathogènes aux cellules épithéliales de la muqueuse intestinale du lapin. Effet inhibiteur d'un lactosérum colostral bovin hyperimmun et de différents glucides. Path. Microbiol. 42, 137–146 (1975)
Drachmann, R. H.: Acute infections gastroenteritis. Ped. Clin. North. Amer. 21, 711 (1974)
Dupont, H. L., Formal, S. B., Hornick, R. B., Snyder, M. J., Libonati, J. P., Sheahan, D. G., La Brec, E. H., Kallas, J. P.: Pathogenesis of E. coli diarrhea. New Engl. J. Med. 285, 1–9 (1971)
Evans, D. G., Evans, D. J., Dupont, H. L.: Virulence factors in enterotoxigenic E. coli. J. Infect. Dis. 136, 118–123 (1977)
Gangarosa, E. J., Merson, M. H.: Epidemiologic assessment of the relevance of the so-called enteropathogenic serogroups of E. coli in diarrhea. N. Engl. J. Med. 296, 1210 (1977)
Gerrard, J. W.: Breast-feeding: Second thoughts. Pediatrics 54, 757 (1974)
Gindrat, J. J., Gothefors, L., Hanson, L. A., Winberg, J.: Antibodies in human milk against E. coli of the serogroups most commonly found in neonatal infections. Acta paediat., Uppsala 61, 587 (1972)
Goldman, A. S., Smith, C. W.: Host resistance factors in human milk. J. Pediat. 82, 1082–1090 (1973)
Grüttner, R., Leiber, D. V.: Vorzüge der Ernährung mit Muttermilch. Mschr. Kinderheilk. 124, 25–31 (1976)
Gyles, C. L.: Relationship among heat-labile enterotoxins of E. coli and Vibrio cholerae. J. Infect. Dis. 129, 277–283 (1974)
Hanson, L. A., Winberg, J.: Breast milk and defence against infection in the newborn. Arch. Dis. Child. 47, 845 (1972)
Hanson, L. A., Brandtzaeg, P.: Secretory antibody systems. In: Immunologic disorders in infants and children, p. 76. Philadelphia: Saunders 1973
Hilpert, H., Amster, H., Pahud, J. J., Gerber, H.: Tests on the immunobiological activity of specific bovine anti-E. coli milk antibodies. Nestlé Research News 1974/1975, p. 130 (1974/75a)
Hilpert, H., Gerber, H., de Peyer, E., Nusslé, D.: Gastrointestinal passage of bovine anti-E. coli milk immunoglobulins (Ig) in infants. Nestlé Research News 1974/75, p. 134–138 (1974/75); see also: Acta Paediatr. Belg. 29, 125–135 (1976)
Hilpert, H., Gerber, H., Amster, H., Pahud, J. J., Ballabriga, A., Arcalis, L., Farriaux, F., de Peyer, E., Nusslé, D.: Bovine milk immunoglobulins (Ig), their possible utilisation in industrially prepared infant's milk formulae. In “Food and Immunology”, Swedish Nutrition Foundation Symposium XIII, 1977, p. 182
Levy, J.-M., Stoll, C., Minck, R., Rousset, A., Le Minor, L.: Utilisation par voie orale d'anticorps spécifiques dans le traitement et la prévention des infections entérales à E. coli pathogène des nourrissons. Ann. Pédiat. 20, 841–844 (1973)
Mancini, G., Carbonara, A. O., Heremans, J. F.: Immunochemical quantitation of antigens by single radial immunodiffusion. Immunochemistry 2, 235 (1965)
Marcy, M. S.: Microorganisms responsible for neonatal diarrhea. In: Infections diseases of the foetus and newborn infant, edit. by Remington and Klein, Saunders Co. 1976
Mata, L. J., Urrutia, J. J.: Intestinal colonisation of breast-fed children in a small area of low socio-economic level. Ann. N.Y. Acad. Sci. 176, 93 (1971)
Otto, H., Takamiya, H., Vogt, A.: A two-stage method for cross-linking antibody globulin to ferritin by gluteraldehyde. J. Immun. Methods 3, 137–146 (1973)
Reaburn, J. A.: Antibiotics and immunodeficiency. Lancet 1972 II, 954
Rham de, O., Isliker, H.: Proteolysis of bovine immunoglobulins. Int. Archs. Allergy appl. Immun. 55, 61–69 (1977)
Rowe, B., Scotland, S. M., Gross, R. J.: Enterotoxigenic E. coli causing infantile enteritis in Britain. Lancet 1977 I, 90–91
Sack, R. B., Jakobs, B., Mitra, R.: Antitoxin responses to infections with enterotoxigenic Escherichia coli. J. Infect. Dis. 129, 330–335 (1972)
Sever, J. L.: Application of a microtechnique to viral serological investigations. J. Immunol. 88, 320–329 (1961)
Williams, R. C., Gibbons, R. J.: Inhibition of bacterial adherence by secretory immunoglobulin A: A mechanism of antigen disposal. Science 177, 697 (1972)
Zinkernagel, R. M., Hilpert, H., Gerber, H.: The digestion of colostral bovine immunoglobulins in infants. Experientia 28, 741 (1972)
Zinkernagel, R. M., Colombini, A.: Passive orale immunization with bovine immunoglobulins: Enteropathogenic E. coli from infants and bovine anti-E. coli lactoserum assayed in the rabbit ileal loop model. Med. Microbiol. Immunol. 162, 1–7 (1975)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mietens, C., Keinhorst, H., Hilpert, H. et al. Treatment of infantile E. coli gastroenteritis with specific bovine anti-E. coli milk immunoglobulins. Eur J Pediatr 132, 239–252 (1979). https://doi.org/10.1007/BF00496847
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00496847