Salmonella enterica Serovar Typhimurium Lacking hfq Gene Confers Protective Immunity against Murine Typhoid

Salmonella enterica is an important enteric pathogen and its various serovars are involved in causing both systemic and intestinal diseases in humans and domestic animals. The emergence of multidrug-resistant strains of Salmonella leading to increased morbidity and mortality has further complicated its management. Live attenuated vaccines have been proven superior over killed or subunit vaccines due to their ability to induce protective immunity. Of the various strategies used for the generation of live attenuated vaccine strains, focus has gradually shifted towards manipulation of virulence regulator genes. Hfq is a RNA chaperon which mediates the binding of small RNAs to the mRNA and assists in post-transcriptional gene regulation in bacteria. In this study, we evaluated the efficacy of the Salmonella Typhimurium Δhfq strain as a candidate for live oral vaccine in murine model of typhoid fever. Salmonella hfq deletion mutant is highly attenuated in cell culture and animal model implying a significant role of Hfq in bacterial virulence. Oral immunization with the Salmonella hfq deletion mutant efficiently protects mice against subsequent oral challenge with virulent strain of Salmonella Typhimurium. Moreover, protection was induced upon both multiple as well as single dose of immunizations. The vaccine strain appears to be safe for use in pregnant mice and the protection is mediated by the increase in the number of CD4+ T lymphocytes upon vaccination. The levels of serum IgG and secretory-IgA in intestinal washes specific to lipopolysaccharide and outer membrane protein were significantly increased upon vaccination. Furthermore, hfq deletion mutant showed enhanced antigen presentation by dendritic cells compared to the wild type strain. Taken together, the studies in murine immunization model suggest that the Salmonella hfq deletion mutant can be a novel live oral vaccine candidate

A prospective, multi-method, multi-disciplinary, multi-level, collaborative, social-organisational design for researching health sector accreditation [LP0560737]

BACKGROUND: Accreditation has become ubiquitous across the international health care landscape. Award of full accreditation status in health care is viewed, as it is in other sectors, as a valid indicator of high quality organisational performance. However, few studies have empirically demonstrated this assertion. The value of accreditation, therefore, remains uncertain, and this persists as a central legitimacy problem for accreditation providers, policymakers and researchers. The question arises as to how best to research the validity, impact and value of accreditation processes in health care. Most health care organisations participate in some sort of accreditation process and thus it is not possible to study its merits using a randomised controlled strategy. Further, tools and processes for accreditation and organisational performance are multifaceted. METHODS/DESIGN: To understand the relationship between them a multi-method research approach is required which incorporates both quantitative and qualitative data. The generic nature of accreditation standard development and inspection within different sectors enhances the extent to which the findings of in-depth study of accreditation process in one industry can be generalised to other industries. This paper presents a research design which comprises a prospective, multi-method, multi-level, multi-disciplinary approach to assess the validity, impact and value of accreditation. DISCUSSION: The accreditation program which assesses over 1,000 health services in Australia is used as an exemplar for testing this design. The paper proposes this design as a framework suitable for application to future international research into accreditation. Our aim is to stimulate debate on the role of accreditation and how to research it.Jeffrey Braithwaite, Johanna Westbrook, Marjorie Pawsey, David Greenfield, Justine Naylor, Rick Iedema, Bill Runciman, Sally Redman, Christine Jorm, Maureen Robinson, Sally Nathan and Robert Gibber

Pregnancy impairs the innate immune resistance to Salmonella typhimurium leading to rapid fatal infection: J.Immunol.

Typhoid fever and gastroenteritis caused by Salmonella enterica species are increasing globally. Pregnancy poses a high risk, but it is unclear how maternal immunity to infection is altered. In mice, susceptible strains die of S. enterica serovar typhimurium (ST) infection within 7 days whereas resistant mice (129 x 1/SvJ) develop a chronic infection. We found that virulent ST infection during pregnancy, in normally resistant 129 x 1/SvJ mice, evoked approximately 100% fetal loss and surprisingly >60% host fatality, with a median survival of 6 days. Splenic bacterial load was 1000-fold higher in pregnant mice. This correlated to a diminished splenic recruitment/expansion of innate immune cells: dendritic cells, neutrophils, and NK cells. In particular, the splenic expansion and activation of NK cells postinfection seen in nonpregnant mice was lacking in pregnancy. Most notably, pregnant-infected mice had decreased production of serum IL-12 and increased IL-6 levels. Moreover, uteroplacental tissue of pregnant-infected mice exhibited an approximately 40-fold increase in IL-6 mRNA expression relative to noninfected placenta, whereas IL-12p40 was not increased. In vivo blocking of IL-6 significantly reduced the splenic bacterial burden in pregnant mice yet failed to prevent fetal loss. Fetal demise correlated to the rapidity of infection; by 14 h, ST expanded to >10(5) in the placenta and had reached the fetus. Therefore, the preferential placental expansion of ST plausibly altered the inflammatory response toward IL-6 and away from IL-12, reducing the recruitment/activation of splenic innate immune cells. Thus, highly virulent pathogens may use placental invasion to alter systemic host resistance to infectionNRC publication: Ye

A double-blind, randomized, controlled trial of topical polysporin triple compound versus topical mupirocin for the eradication of colonization with methicillin-resistant Staphylococcus aureus in a complex continuing care population

BACKGROUND: Intranasal mupirocin or Polysporin Triple (PT) ointment (polymyxin B, bacitracin, gramicidin), in combination with chlorhexidine body washes, have been used for eradicating methicillin-resistant Staphylococcus aureus (MRSA), but no comparative studies have been done

Neonatal androgenization affects the intrathymic T-cell maturation in rats

The thymus structure, expression of CD4/CD8/TCR alpha beta on thymocytes and thymocyte proliferative and apoptotic indexes were analyzed in sexually immature 30-day-old and in sexually mature 60-day-old female rats neonatally androgenized (NA) by subcutaneous injection of 500 mu g testosterone propionate/day on days 1-3 and in their vehicle-administered counterparts. The treatment affected normal thymus development. Thus, at 30 days of age, there was a reduction in the thymus weight, reflecting a decrease in the main thymic compartments. However, at 60 days of age, thymus weight did not significantly differ from that in age-matched controls, since the cortical volume enlargement was followed by a proportional decrease in the medullary volume. In rats of both ages, the changes in thymic compartments most likely reflected alterations in the size of both lymphoid and nonlymphoid components. Furthermore, in NA rats, substantial changes in thymocyte phenotypic characteristics were registered, in spite of their age. In both groups of NA rats, a decrease in the relative proportion of the least mature CD4-8-TCR alpha beta- cells and in that of CD4+8- TCR alpha beta-/TCR alpha beta(low) cells followed by an increase in the percentage of their successor CD4+8+TCR alpha beta-/TCR alpha beta(low) cells was detected. In addition, in 30-day-old NA rats, the relative proportions of CD4+8+TCR alpha beta(high) cells ( just positively selected) and that of mature single positive (CD4+8- and CD4-8+) and CD4-8- double negative TCR alpha beta(high) cells, were reduced, while in 60-day-old NA rats only the percentage of CD4+8+TCR alpha beta(high) thymocytes was decreased. Thus, the study showed that the changes in the development of the hypothalamo-pituitary-gonadal axis induced by neonatal androgenization may affect the thymus development and intrathymic T-cell maturation. Copyright (C) 2005 S. Karger AG, Basel