Effectiveness of zinc supplementation on diarrhea and average daily gain in pre-weaned dairy calves: A double-blind, block-randomized, placebo-controlled clinical trial.

The objective of this clinical trial was to evaluate the effectiveness of zinc supplementation on diarrhea and average daily weight gain (ADG) in pre-weaned dairy calves. A total of 1,482 healthy Holstein heifer and bull calves from a large California dairy were enrolled at 24 to 48 hours of age until hutch exit at approximately 90 days of age. Calves were block-randomized by time to one of three treatments: 1) placebo, 2) zinc methionine (ZM), or 3) zinc sulfate (ZS) administered in milk once daily for 14 days. Serum total protein at enrollment and body weight at birth, treatment end, and hutch exit were measured. Fecal consistency was assessed daily for 28 days post-enrollment. For a random sample of 127 calves, serum zinc concentrations before and after treatment and a fecal antigen ELISA at diarrhea start and resolution for Escherichia coli K99, rotavirus, coronavirus, and Cryptosporidium parvum were performed. Linear regression showed that ZM-treated bull calves had 22 g increased ADG compared to placebo-treated bulls (P = 0.042). ZM-treated heifers had 9 g decreased ADG compared to placebo-treated heifers (P = 0.037), after adjusting for average birth weight. Sex-stratified models showed that high birth weight heifers treated with ZM gained more than placebo-treated heifers of the same birth weight, which suggests a dose-response effect rather than a true sex-specific effect of ZM on ADG. Cox regression showed that ZM and ZS-treated calves had a 14.7% (P = 0.015) and 13.9% (P = 0.022) reduced hazard of diarrhea, respectively, compared to placebo-treated calves. Calves supplemented for at least the first five days of diarrhea with ZM and ZS had a 21.4% (P = 0.027) and 13.0% (P = 0.040) increased hazard of cure from diarrhea, respectively, compared to placebo-treated calves. Logistic regression showed that the odds of microbiological cure at diarrhea resolution for rotavirus, C. parvum, or any single fecal pathogen was not different between treatment groups. Zinc supplementation delayed diarrhea and expedited diarrhea recovery in pre-weaned calves. Additionally, zinc improved weight gain differentially in bulls compared to heifers, indicating a research need for sex-specific dosing.

Oral delivery of L-arginine stimulates prostaglandin-dependent secretory diarrhea in Cryptosporidium parvum-infected neonatal piglets.

OBJECTIVES: To determine if oral supplementation with L-arginine could augment nitric oxide (NO) synthesis and promote epithelial defense in neonatal piglets infected with Cryptosporidium parvum. MATERIALS AND METHODS: Neonatal piglets were fed a liquid milk replacer and on day 3 of age infected or not with 10(8) C. parvum oocysts and the milk replacer supplemented with L-arginine or L-alanine. Milk consumption, body weight, fecal consistency, and oocyst excretion were recorded daily. On day 3 postinfection, piglets were euthanized and serum concentration of NO metabolites and histological severity of villous atrophy and epithelial infection were quantified. Sheets of ileal mucosa were mounted in Ussing chambers for measurement of barrier function (transepithelial resistance and permeability) and short-circuit current (an indirect measurement of Cl secretion in this tissue). RESULTS: C. parvum-infected piglets had large numbers of epithelial parasites, villous atrophy, decreased barrier function, severe watery diarrhea, and failure to gain weight. L-Arginine promoted synthesis of NO by infected piglets, which was unaccompanied by improvement in severity of infection but rather promoted epithelial chloride secretion and diarrhea. Epithelial secretion by infected mucosa from L-arginine-supplemented piglets was fully inhibited by the cyclooxygenase inhibitor indomethacin, indicating that prostaglandin synthesis was responsible for this effect. CONCLUSIONS: Results of these studies demonstrate that provision of additional NO substrate in the form of L-arginine incites prostaglandin-dependent secretory diarrhea and does not promote epithelial defense or barrier function of C. parvum-infected neonatal ileum.

Cryptosporidiosis: laboratory investigations and chemotherapy.

Much progress has been achieved in the last decade in terms of development of laboratory techniques, reagents and in vivo models. They have undoubtedly contributed to better and more accurate investigations. Despite a concerted effort by many investigators, however, breakthroughs have been minimal. The development of adequate in vitro and in vivo techniques for drug screening, and the intensified and systematic screening, has so far not resulted in the discovery of an effective therapy. The reason for the failure may well be due to the unique biological niche the parasite occupies (discussed at length in the first chapter in this volume). Its location beneath the cell membrane, but outside the cell cytoplasm, may prove a crucial element that needs to be considered when designing new therapeutic approaches. Laboratory investigations on two drugs currently used against chronic Cryptosporidium parvum in acquired immune deficiency syndrome (AIDS) are discussed. This chapter also provides information and the rationale for work in progress in our laboratory that relates to the development of novel approaches for control of the disease. This includes the identification of molecular targets of parasite origin for drug design, and studies on the structure-activity relationships of partially effective drugs with a view to synthesize more effective derivatives. Other investigations attempt to establish the role of secretory antibody, and the merit of repeated mucosal immunizations as a means of providing protection to individuals with AIDS who are at risk of developing chronic C. parvum infection.

Prevalencia de Cryptosporidium en muestras de materia fecal llevadas a diez laboratorios del Area Metropolitana de Bucaramanga, Colombia

Con la técnica de Kinyoun para Cryptosporodium se estudiaron 1988 muestras de materia fecal llevadas para estudio a diez laboratorios del área metropolitana de Bucaramanga, Colombia. Correspondían a 103 lactantes, 113 preescolares, 201 escolares, 1162 adultos jóvenes, 322 adultos mayores y 87 ancianos; 55.48 por ciento eran mujeres y el 97.94 por ciento vivían en zona urbana. Un 13.93 por ciento pertenecían a personas con diarrea. Se encontraron tres muestras positivas, todas en menores de dos años y con diarrea: 2.91 por ciento de los lactantes y el 4.69 por cientode los lactantes con diarrea. Con esto se confirma la presencia del parásito en el Nororiente colombiano, con una prevalencia similar a la encontrada en otras partes del país

Resolution of Cryptosporidium infection in an AIDS patient after improvement of nutritional and immune status with octreotide.

An AIDS patient with severe large volume diarrhea and malnutrition due to cryptosporidial infection is presented. The patient, who was not receiving zidovudine, was treated with octreotide with resolution of diarrhea leading to improvement in nutritional status, immune functions, and subsequently, resolution of the Cryptosporidium infection. This case points out the need for adequate nutrition in AIDS patients and highlights the relationship of nutrition and the immune system.