Limitations of Murine Models for Assessment of Antibody-Mediated Therapies or Vaccine Candidates against Staphylococcus epidermidis Bloodstream Infection.

Staphylococcus epidermidis is normally a commensal colonizer of human skin and mucus membranes, but, due to its ability to form biofilms on indwelling medical devices, it has emerged as a leading cause of nosocomial infections. Bacteremia or bloodstream infection is a frequent and costly complication resulting from biofilm fouling of medical devices. Our goal was to develop a murine model of S. epidermidis infection to identify potential vaccine targets for the prevention of S. epidermidis bacteremia. However, assessing the contribution of adaptive immunity to protection against S. epidermidis challenge was complicated by a highly efficacious innate immune response in mice. Naive mice rapidly cleared S. epidermidis infections from blood and solid organs, even when the animals were immunocompromised. Cyclophosphamide-mediated leukopenia reduced the size of the bacterial challenge dose required to cause lethality but did not impair clearance after a nonlethal challenge. Nonspecific innate immune stimulation, such as treatment with a Toll-like receptor 4 (TLR4) agonist, enhanced bacterial clearance. TLR2 signaling was confirmed to accelerate the clearance of S. epidermidis bacteremia, but TLR2(-/-)mice could still resolve a bloodstream infection. Furthermore, TLR2 signaling played no role in the clearance of bacteria from the spleen. In conclusion, these data suggest that S. epidermidis bloodstream infection is cleared in a highly efficient manner that is mediated by both TLR2-dependent and -independent innate immune mechanisms. The inability to establish a persistent infection in mice, even in immunocompromised animals, rendered these murine models unsuitable for meaningful assessment of antibody-mediated therapies or vaccine candidates.

Ulcer disease prophylaxis in koi carp by bath immersion with chicken egg yolk containing anti-Aeromonas salmonicida IgY.

Ulcer disease, caused by atypical Aeromonas salmonicida, is a serious concern in ornamental koi carp, because it induces skin ulceration, disfiguring ornamental fish and causing economic loses. The present study aimed to establish a novel prophylaxis with chicken egg yolk immunoglobulin, IgY, against ulcer disease and to assess its feasibility in the ornamental fish industry. Addition of egg yolk powder containing anti-A. salmonicida IgY to rearing water provided significant protection against an A. salmonicida bath infection, whereas administration of non-specific IgY did not. Consecutive immersion of fish into rearing water containing specific IgY completely prevented ulcer disease resulting from cohabitation infection, indicating that this prophylaxis could prevent infection from such type of contact. Thus, passive immunization induced by immersing fish into aquarium water containing specific IgY is a prospective prophylaxis against diseases caused by pathogens that invade the skin and gills.

Assessment of diagnostic and therapeutic approaches of Helicobacter pylori-associated iron deficiency and anemia in children with dyspeptic symptoms.

This study assessed the diagnostic approaches of Helicobacter pylori (IP)-associated iron deficiency (ID) and anemia (IDA) in children with dyspeptic symptoms and evaluated the effect of simultaneous anti-H. pylori (anti-HIP) therapy and oral iron in comparison with each of anti? HP therapy and oral iron therapy alone, on iron status as assessed by serum soluble transferrin receptor (sTfR) level. Two hundreds children with dyspeptic symptoms were subjected to clinical evaluation, stool examination, CBC, biochemical assays for serum iron parameters and measurements of serum IgG antibodies to HP and serum sTfR level by ELISA. Sixty children were found to have HP. associated ID or IDA and were randomly divided into 3 groups (20 children each). GA received 2-week anti-HP therapy plus 90-day oral iron, and GB received 2-week anti-HP therapy alone whereas group C received 90-day oral iron alone. Re-evaluation of the 3 groups was performed after 3 months of treatment initiation by repeat CBC and serum sTfR level. Children (45%) were HP-seropositive. The mean values of serum sTfR were significantly higher in HP-positive group and in HP-positive children with IDA than in HP-negative group and in HP-negative children with IDA although no significant differences were noted in hematologic variables and iron parameters between the corresponding groups and children. As regard treatment groups, there were significant improvements in the mean values of indices of IDA status (HIb, MCH, MCV, sTfR) and ID status (sTtRi) at 3 months of treatment initiation compared with their baseline values after. anti-HP triple therapy either with oral iron or without oral iron whereas the control children who were treated with oral iron alone showed insignificant changes despite oral iron administration. The improvements in these parameters were significantly greater in groups of children who received anti-HP therapy either combined with iron or alone, where compared with those who did not receive anti-HP therapy. Their magnitudes were significantly higher among children receiving anti-HP therapy combined with oral iron when compared with that receiving anti-HP therapy alone.

Current strategies in TB immunotherapy.

Currently available chemotherapy for the treatment of pulmonary tuberculosis (TB) is far from ideal, requiring multiple anti-tuberculous drugs to be taken in combination for extended time periods. This long duration of therapy, coupled with the side effects of current regimens, often results in poor patient adherence, treatment failure and the associated emergence of drug resistance with major financial implications. Thus, the development of novel, shorter treatment regimens is an urgent objective of anti-tuberculous drug discovery. Immunotherapy is an area that merits more consideration than it has previously received, not least, as it could potentially avoid the problem of pathogen resistance. However, this must be undertaken with caution, as at least part of the disease pathology is a consequence of the host immune response. Thus, the protective, and not the harmful, aspects of immunity must be stimulated. Various attempts at utilizing immunotherapy as an adjunct to chemotherapy are reviewed with particular emphasis on the evidence from human studies, including the modulation of cytokine levels, administration of environmental mycobacteria and antibody therapy, in order to modulate or enhance the host immune response to Mycobacterium tuberculosis.

Field trial assessment of the efficacy of specific egg-yolk antibody product for control of postweaning E. coli diarrhea.

Postweaning diarrhea caused by Escherichia coli is a major cause of mortality and morbidity in many swine nurseries throughout North America. Commercial products containing chicken egg-yolk antibodies specific for the control of K88+ E. coli diarrhea have been used in an attempt to prevent disease losses. The present study evaluated the use of an egg-yolk antibody product incorporated into nursery feed on two farms where K88+ E. coli diarrhea was identified as a problem. There were no differences in the prevalence of diarrhea or mortality between treatment and control pigs at either farm under routine management conditions.

Impact of guidelines to alter antitetanus prophylaxis practices and reduce costs in the emergency department.

The objective of this study was to assess the impact of an intervention to modify antitetanus prophylaxis of open wounds. This prospective, before-and-after study was conducted in an emergency department of a large metropolitan hospital. Consecutive patients with open wounds were managed according to the World Health Organization (WHO) guidelines before an intervention, then according to new guidelines afterwards. Locally developed guidelines were introduced and backed up by a teaching program, with emphasis on reducing unwarranted human tetanus immunoglobulins and costs. Serum tetanus antitoxins level was measured in postintervention patients mainly to verify the soundness of the intervention, eventually to complete patients' protection during follow-up, and to derive more reliable recommendations for the future. Main outcome measures included the number of treatments conforming to each set of guidelines, the rate of tetanus immunoglobulin prescriptions, and the cost of each strategy. Two groups of 389 and 459 patients were included. Treatment conforming to guidelines increased from 60% to 79%, undertreatment decreased from 31% to 19%, and overtreatment decreased from 9% to 2% (P < 0.001). Tetanus immunoglobulin prescriptions decreased from 23% to 1% (P < 0.001). On the basis of antitoxins level, 60% of 367 postintervention patients were correctly treated, 29% were overtreated, and 11% were undertreated. Nevertheless, with the WHO guidelines, only 49% would have been correctly treated, 39% would have been overtreated (29% with immunoglobulins), and 12% would have been undertreated (P < 0.001). Costs decreased from $32 to $24 per patient. New guidelines resulted in improved tetanus prophylaxis at reduced costs in an emergency department. Because they rely on immunization history, however, guidelines currently in use are misleading. More reliable recommendations, including a test for tetanus antibody status in some cases, are needed.