Cryptosporidiosis in immunocompetent individuals. enteropathogens and safety associated with breast-feeding.5, 6, 7, 8 After the first few months of existence, increasing connection with other individuals and the environment, including introduction of artificial feeding, increases the risk of exposure to enteropathogens. For most pathogens, the incidence of acute diarrhea peaks in children between 6 months and 4 years old.9 Neonatal diarrhea is more common in underdeveloped areas, where low educational levels, crowding, and poor standards of medical care, environmental sanitation, and personal hygiene prefer early contact with enteropathogens. As the incidence of neonatal gastroenteritis increases, there is a proportional increase in neonatal Carglumic Acid deaths because medical care for the poor often is definitely inadequate.10, 11 For very low birth weight babies ( 1500g), the death rate from diarrhea is 100-fold greater than for higher-birth-weight babies.12 This chapter discusses the pathogenesis, analysis, treatment, and prevention of gastroenteritis based on the available knowledge about pathogens that can cause neonatal diarrhea. Pathogens that hardly ever or by no means cause acute diarrhea in neonates are not discussed. After an overview of host defense mechanisms and protective factors in human milk, the remainder of the chapter is usually devoted to specific pathogens that cause inflammatory or noninflammatory diarrhea. ENTERIC HOST DEFENSE MECHANISMS The neonate is usually a host that is uniquely susceptible to enteric infections. Neonates have not experienced the opportunity to develop local or systemic immune responses, and in the first Carglumic Acid few days of life, they have not acquired the highly important enteric flora that protects the normal adult gastrointestinal tract.13, 14, 15, 16, 17, 18 Still less is known about the barrier effect of the neonates gastric acidity,19 intestinal mucus,20 or motility,21, 22 each of which provides protection against gastrointestinal tract infections in older infants, children, and adults. The gastric acid barrier appears to be least effective during the first months of life. The average gastric pH level of the newborn is usually high (pH 4 to 7; mean, 6).23, 24 Even though pH falls to low levels by the end of the first day of life (pH 2 to 3 3),23 it subsequently rises again; by 7 to 10 days of life, the hydrochloric acid output of the neonatal belly is usually far less than that of older infants and children.24, 25 The buffering action of frequent milk feedings and the short gastric emptying time26, 27, 28, 29 interpose additional factors in the neonate that would be expected to permit viable ingested organisms to reach the small intestine. The intestinal epithelium serves as a nutrient absorptive machine, barrier to pathogen access, and regulator of inflammation. Intestinal epithelial cells have receptors for bacterial products and produce chemokines (e.g., interleukin [IL]-8, monocyte chemotactic protein type 1 [MCP-1], granulocyte macrophage-cell stimulating factor [GM-CSF]) and proinflammatory cytokines (e.g., IL-6, tumor necrosis factor- [TNF-], IL-1) in response to invasion by enteropathogens.30 The gut epithelium orchestrates the immune response. However, in the newborn, phagocytic, chemotactic, and match functions are immature. B and T lymphocyte functions are impaired, resulting in a preferential IgM production in response to antigenic activation. IgG is usually actively transferred from mother to infant across Rabbit polyclonal to ADCK4 the placenta at about 32 weeks gestation and peaks by about 37 weeks; premature neonates, especially those given birth to before 28 weeks gestation, are deficient in these maternally derived serum antibodies.31 PROTECTIVE FACTORS IN HUMAN MILK The importance of breast-feeding infants for the prevention of diarrheal disease has long been emphasized.13, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 Published studies reporting the association between breast-feeding and diarrhea are considerable and suggest that infants who are breast-fed suffer fewer episodes of diarrhea than Carglumic Acid those who are not. This protection is usually best during a childs first 3 months of life and declines with increasing age. During the period of weaning, partial breast-feeding confers protection that is intermediate between that gained by infants who are exclusively breast-fed and that by those who are exclusively bottle-fed. A striking demonstration of the protection afforded by breast-feeding of newborns has been provided by Mata and Urrutia13 in their studies of a population of infants born in a rural Guatemalan village. Despite extremely poor sanitation and the demonstration of fecal organisms in the colostrum and milk of almost one third of mothers,46 diarrheal disease did not occur in any newborns. The incidence of diarrhea rose significantly only after these infants reached 4 to 6 6 months aged, at which time solids and.