The intracellular Gram-negative pathogen Francisella tularensis is the causative agent of tularaemia and is prevalent in many countries in the northern hemisphere. To determine whether the common marmoset (Callithrix jacchus) would be a suitable non-human primate model of inhalational tularaemia, a pathophysiology study was undertaken. Ten animals were challenged with ∼102 c.f.u. F. tularensis strain SCHU S4 (F. tularensis subsp. tularensis). To look for trends in the infection, pairs of animals were sacrificed at 24 h intervals between 0 and 96 h post-challenge and blood and organs were assessed for bacteriology, pathology and haematological and immunological parameters. The first indication of infection was a raised core temperature at 3 days post-challenge. This coincided with a number of other factors: a rapid increase in the number of bacteria isolated from all organs, more pronounced gross pathology and histopathology, and an increase in the immunological response. As the disease progressed, higher bacterial and cytokine levels were detected. More extensive pathology was observed, with multifocal lesions seen in the lungs, liver and spleen. Disease progression in the common marmoset appears to be consistent with human clinical and pathological features of tularaemia, indicating that this may be a suitable animal model for the investigation of novel medical interventions such as vaccines or therapeutics.

Susceptibility and lethality studies of inhalational tularaemia were undertaken using the common marmoset (Callithrix jacchus) to determine its suitability as a non-human primate model. Pairs of marmosets were exposed to varying challenge doses of Francisella tularensis by the airborne route and monitored for up to 14 days postchallenge (p.c.). Lethal infection was achieved following a retained dose of less than 10 bacterial colony-forming units (CFU). However, precise LD(50) determination was not possible. The model was characterized using a target challenge dose of approximately 100 CFU. Increased core body temperature was the first indicator of disease, at approximately 2.5 days p.c. Overt clinical signs were first observed 12-18 h after the temperature increase. Significantly decreased activity was observed after approximately 3 days. All animals succumbed to infection between 4.5 and 7 days p.c. At postmortem examination, gross pathology was evident in the liver, spleen and lungs of all animals and high bacterial numbers were detected in all the organs assessed. Bacteraemia was demonstrated in all animals postmortem. Histopathological observations included severe suppurative bronchopneumonia, severe multifocal pyogranulomatous hepatitis, splenitis and lymphadenitis. Tularaemia disease progression in the common marmoset therefore appears to be consistent with the disease seen in humans and other animal models. The common marmoset may therefore be considered a suitable model for further studies of inhalational tularaemia.

Background Hospital‐acquired acute kidney injury (AKI) in humans and dogs increases morbidity and nonsurvival. Azotemia at presentation has been associated with a poor outcome in horses; however, prevalence and consequences of hospital‐acquired AKI are unreported. Hypothesis/Objectives To evaluate the prevalence of AKI in hospitalized horses, risk factors associated with AKI, and the effect of AKI on short‐term survival. We hypothesized that the prevalence of AKI in horses is similar to that reported in other domestic mammalian species and would be associated with nonsurvival. Animals Adult horses hospitalized for >2 days from which a minimum of 2 measurements of serum creatinine concentration were available. Methods Retrospective cohort study. Clinical records were reviewed and horses grouped according to their baseline serum creatinine concentration and change in serum creatinine concentration from baseline. The associations between signalment, diagnosis, and treatment variables, and the presence of azotemia or AKI were assessed using multinomial logistic regression. The relationship between these conditions and survival to discharge was evaluated. Results Three hundred twenty‐five horses were included; 4.3% (14/325) had azotemia at baseline and 14.8% (48/325) developed AKI. There were no significant associations between investigated risk factors and development of AKI. The presence of azotemia and AKI did not significantly affect survival to discharge (P = .08 and .81, respectively). Conclusions and Clinical Importance The prevalence of AKI in this population of hospitalized horses is similar to that reported in dogs and humans; however, in this study population, there was less impact on morbidity and short‐term survival.

The early diagnosis of microbial infection is critical to the clinical instigation of effective post-exposure prophylaxis or therapy. However, diagnosis of infection is often attempted only when there are overt clinical signs, and for some of the serious human pathogens, this may jeopardize the efficacy of therapy. We have used a miniaturised sealed, implantable transponder incorporating a calibrated temperature sensor with an external receiver system, to monitor core body temperature (Tc) remotely. We have observed early changes in the diurnal rhythm of Tc, after infection of mice with bacterial pathogens. Changes in Tc preceded overt clinical signs by 3-10 h following challenge with Yersinia pestis, which causes acute infection, In contrast, changes in Tc were detected 11 days before clinical signs in mice exposed to Burkholderia pseudomallei, which causes a chronic syndrome. Significantly, mice pre-vaccinated against Y.pestis infection showed only slight and transient disruption to the diurnal rhythm for Tc, in the absence of clinical signs, when challenged with 10(6) median lethal doses of Y.pestis. This remote monitoring technology could be used to monitor changes in more than one physiological parameter and extrapolation of these data to the clinic would define the available therapeutic window in which diagnosis and post-exposure prophylaxis could be instigated, after a suspected exposure.

This study was undertaken to determine the antibacterial activity of eight cationic antimicrobial peptides towards strains of genomovars I-V of the Burkholderia cepacia complex (Bcc) in timekill assays. All but one of the peptides failed to show activity against the panel of test strains. The exception was magainin II, a 23 aa peptide isolated from the epidermis of the African clawed frog, Xenopus laevis, which exhibited significant bactericidal activity for Bcc genomovars most frequently associated with lung infection of patients with cystic fibrosis. In vitro studies indicated that magainin II protected a human bronchial epithelial cell line (BEAS-2B) from killing by Bcc and suggest that this peptide may have therapeutic potential against these organisms. INTRODUCTIONOrganisms of the Burkholderia cepacia complex (Bcc) are associated with chronic opportunistic lung infections of patients suffering from cystic fibrosis (CF) and chronic granulomatous disease (Mahenthiralingam et al., 2000). Infections with Bcc are often coupled with a particularly poor prognosis, resulting in a rapid and fatal decline in pulmonary function due to necrotizing pneumonia and sepsis (Isles et al., 1984). This fatal decline in clinical condition has been termed 'cepacia syndrome' and has not been identified with any other CF-associated pathogen.The Bcc comprises 15 distinct species formerly known as genomovars of B. cepacia (Vanlaere et al., 2008). Of these, the majority of infections in CF are attributed to Burkholderia multivorans and Burkholderia cenocepacia in both the UK and the USA Reik et al., 2005), although all genomovars have been recovered from CF patients (Ortega et al., 2005). Eradication of an established Bcc infection is rarely achieved owing to the high intrinsic resistance of the genus to antimicrobial agents (Coenye et al., 2001). Although preventative strategies are considered the principal approach for management of Bcc infections (Jones & Webb, 2003), combination therapy may be used, extending the spectrum of antimicrobial activity across multiple antibiotic classes (Bonacorsi et al., 1999).Novel antimicrobial therapeutic agents are urgently required due to the threat of naturally resistant and antibiotic-resistant strains. Cationic antimicrobial peptides (CAMPs) have potential, as they show broad-range activity against Gram-positive and Gram-negative bacteria, viruses and some fungal species (Hancock & Lehrer, 1998). Importantly, these peptides do not present the same issue of resistance observed with conventional antibiotics (Zasloff, 2002) and often have good activity against several multidrug-resistant bacterial species (Giacometti et al., 2005a). There is also evidence that in vitro selection of CAMP-resistant mutants is difficult (Hancock & Lehrer, 1998). As previous reports have described B. cepacia as being resistant to the action of CAMPs (Denyer & Maillard, 2002;Scott et al., 1999), we aimed to determine the efficacy of a panel of antimicrobial peptides against B. cepacia from genomovars I-V. METHODSBact...