lactoferrin and Meningitis

To evaluate the safety and explore the efficacy of recombinant human lactoferrin (talactoferrin [TLf]) to reduce infection.. We conducted a randomized, double blind, placebo-controlled trial in infants with birth weight of 750-1500 g. Infants received enteral TLf (n = 60) or placebo (n = 60) on days 1 through 28 of life; the TLf dose was 150 mg/kg every 12 hours. Primary outcomes were bacteremia, pneumonia, urinary tract infection, meningitis, and necrotizing enterocolitis (NEC). Secondary outcomes were sepsis syndrome and suspected NEC. We recorded clinical, laboratory, and radiologic findings, along with diseases and adverse events, in a database used for statistical analyses.. Demographic data were similar in the 2 groups of infants. We attributed no enteral or organ-specific adverse events to TLf. There were 2 deaths in the TLf group (1 each due to posterior fossa hemorrhage and postdischarge sudden infant death), and 1 death in the placebo group, due to NEC. The rate of hospital-acquired infections was 50% lower in the TLf group compared with the placebo group (P < .04), including fewer blood or line infections, urinary tract infections, and pneumonia. Fourteen infants in the TLf group weighing <1 kg at birth had no gram-negative infections, compared with only 3 of 14 such infants in the placebo group. Noninfectious outcomes were not statistically significantly different between the 2 groups, and there were no between-group differences in growth or neurodevelopment over a 1-year posthospitalization period.. We found no clinical or laboratory toxicity and a trend toward less infectious morbidity in the infants treated with TLf.. ClinicalTrials.gov: NCT00854633.

Topics: Administration, Oral; Bacteremia; Cross Infection; Double-Blind Method; Enterocolitis, Necrotizing; Female; Follow-Up Studies; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Lactoferrin; Male; Meningitis; Pneumonia; Protective Agents; Sepsis; Treatment Outcome; Urinary Tract Infections

Topics: Humans; Lactoferrin; Lactoglobulins; Meningitis; Meningitis, Viral

Cerebrospinal fluid measurements of lactoferrin and alpha-1-antitrypsin showed significant elevation in bacterial meningitis in children. 8 of 10 lactoferrin values and 6 of 11 alpha-1-antitrypsin values were above the upper range of controls. Both proteins correlated well with the total number of leukocytes in the cerebrospinal fluid. C-reactive protein, measured by either agglutination or radial immunodiffusion in the cerebrospinal fluid, failed to demonstrate any usefulness in diagnosing bacterial meningitis. Neither elevated serum C-reactive protein in cases of bacterial meningitis, nor sepsis, gave detectable concentrations of C-reactive protein in the cerebrospinal fluid.

Topics: Adolescent; alpha 1-Antitrypsin; C-Reactive Protein; Child; Child, Preschool; Humans; Immunoglobulin G; Infant; Lactoferrin; Lactoglobulins; Meningitis

ECP (eosinophil cationic protein) has been measured by means of a specific radioimmunoassay in the cerebrospinal fluid (CSF) from 210 individuals with various diseases affecting the central nervous system. In the same specimens lactoferrin and albumin were measured as well, as indicators of neutrophil-involved inflammation and damage to the blood-brain barrier. From a patient reference group (n = 39) the upper "normal" limit for ECP was estimated to 1.7 microgram/l. In patients with acute cerebrovascular disease (n = 108) ECP levels were elevated in 38% of the cases which was a significantly (P less than 0.001) greater proportion than seen for lactoferrin (7%). In patients with acute infections of the CNS (n = 30) 67% had raised ECP levels with significantly higher levels (P less than 0.001) in those having bacterial infections. The ECP levels were significantly correlated (P less than 0.001) to the lactoferrin-levels in the whole infectious group. In patients with tumours (n = 25) raised levels of ECP were found in 67% of those with malignant and in 6% of those having benign tumours. This difference was statistically significant (P = 0.001). The ECP levels were closely related to those of lactoferrin (P less than 0.001) and albumin (P less than 0.005). Of the patients with multiple sclerosis (n = 19) 25% had raised ECP levels. This proportion was not significantly different from those having raised lactoferrin levels. In three patients extremely high ECP levels (70-455 micrograms/l) were found and a causal relationship between ECP and the brain tissue damage in these patients is suggested. In comparison with the neutrophil-related data the findings suggest a preferential involvement of eosinophils in some diseases affecting the central nervous system.

Topics: Adolescent; Adult; Aged; Blood Proteins; Brain Neoplasms; Central Nervous System Diseases; Cerebrovascular Disorders; Eosinophil Granule Proteins; Female; Humans; Lactoferrin; Male; Meningitis; Middle Aged; Multiple Sclerosis; Ribonucleases; Serum Albumin

The changes in intraneutrophilic and plasma concentrations of the three antibacterial proteins lysozyme, lactoferrin, and myeloperoxidase were studied sequentially during acute bacterial infection in nine patients. Intraneutrophilic concentrations of the three proteins were decreased by more than 50% during the 1st week of infection, followed by a slow increase over the following 2 weeks. Nadir values coincided with maximal toxic granulation of the neutrophils. The data suggest that neutrophilic granulocytes are deficient during early bacterial infection, possibly because of deficient synthesis of antibacterial proteins in the bone marrow, and that neutrophil toxic granulation is the visual counterpart of this defect. The plasma concentrations of the three proteins showed considerable differences: whereas plasma lysozyme did not show any sequential changes, plasma myeloperoxidase was high at the start of infection and quickly decreased towards normal values, and plasma lactoferrin, high in the first samples, showed a secondary peak 1 week after onset of disease, before normalization was seen. These differences may result from differences in the signals are specific for the individual antibacterial protein and not for the different types of neutrophil granules.

Topics: Adult; Aged; Bacterial Infections; Blood Bactericidal Activity; Humans; Lactoferrin; Lactoglobulins; Meningitis; Middle Aged; Muramidase; Neutrophils; Peroxidase; Peroxidases; Pneumococcal Infections; Time Factors