Soil Sample Analysis of Contaminated Animal Burial Sites.

Environmental contamination with spores poses clear threats to livestock that play key roles in the economies of pastoral communities. Regular monitoring of contaminated sites is particularly important in anthrax-endemic parts of the world, such as Kars province in eastern Türkiye, where the Veterinary Microbiology Department of Kafkas University has conducted an anthrax surveillance programme for over 30 years. We reviewed the microbiological results of 232 soil samples collected during 2009-2023, from sites known to be contaminated with spores following burial or butchering of infected animal carcasses.

Quantifying in vitro B. anthracis growth and PA production and decay: a mathematical modelling approach.

Protective antigen (PA) is a protein produced by Bacillus anthracis. It forms part of the anthrax toxin and is a key immunogen in US and UK anthrax vaccines. In this study, we have conducted experiments to quantify PA in the supernatants of cultures of B.

Marmosets as models of infectious diseases.

Animal models of infectious disease often serve a crucial purpose in obtaining licensure of therapeutics and medical countermeasures, particularly in situations where human trials are not feasible, i.e., for those diseases that occur infrequently in the human population.

Layering vaccination with antibiotic therapy results in protection and clearance of in Balb/c mice.

Melioidosis is a disease that is difficult to treat due to the causative organism, being inherently antibiotic resistant and it having the ability to invade, survive, and replicate in an intracellular environment. Combination therapy approaches are routinely being evaluated in animal models with the aim of improving the level of protection and clearance of colonizing bacteria detected. In this study, a subunit vaccine layered with the antibiotic finafloxacin was evaluated against an inhalational infection with in Balb/c mice.

A self-amplifying RNA vaccine provides protection in a murine model of bubonic plague.

Mice were immunized with a combination of self-amplifying (sa) RNA constructs for the F1 and V antigens of at a dose level of 1 μg or 5 μg or with the respective protein sub-units as a reference vaccine. The immunization of outbred OF1 mice on day 0 and day 28 with the lowest dose used (1 μg) of each of the saRNA constructs in lipid nanoparticles protected 5/7 mice against subsequent sub-cutaneous challenge on day 56 with 180 cfu (2.8 MLD) of a 2021 clinical isolate of termed 10-21/S whilst 5/7 mice were protected against 1800cfu (28MLD) of the same bacteria on day 56.

Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice.

Venezuelan equine encephalitis virus (VEEV) is a disease typically confined to South and Central America, whereby human disease is characterised by a transient systemic infection and occasionally severe encephalitis, which is associated with lethality. Using an established mouse model of VEEV infection, the encephalitic aspects of the disease were analysed to identify biomarkers associated with inflammation. Sequential sampling of lethally challenged mice (infected subcutaneously) confirmed a rapid onset systemic infection with subsequent spread to the brain within 24 h of the challenge.

Efficacy of finafloxacin in a murine model of inhalational glanders.

, the causative agent of glanders, is principally a disease of equines, although it can also infect humans and is categorized by the U.S. Centers for Disease Control and Prevention as a category B biological agent.

Considerations in the design of animal infection pilot studies.

Ethical research with experimental systems (animals or humans) requires a rationale for the number of subjects to be included in a study. Standard methods for estimating sample size are not fit-for-purpose when the experimenter cannot predict the effect size/outcome with any certainty. These types of studies are often designated "pilot study"; however, there are few guidelines for sample size needed for a pilot study.

An Investigation into the Re-Emergence of Disease Following Cessation of Antibiotic Treatment in Balb/c Mice Infected with Inhalational .

is the causative agent of melioidosis, a multifaceted disease. A proportion of the mortality and morbidity reported as a result of infection with this organism may be due to the premature cessation of antibiotic therapy typically lasting for several months. The progression of re-emergent disease was characterised in Balb/c mice following cessation of a 14 day treatment course of co-trimoxazole or finafloxacin, delivered at a human equivalent dose.

Investigation of a combination therapy approach for the treatment of melioidosis.

The efficacy of finafloxacin as a component of a layered defense treatment regimen was determined and against an infection with . Doxycycline was down-selected from a panel of antibiotics evaluated and used in combination with finafloxacin in a Balb/c mouse model of inhalational melioidosis. When treatment was initiated at 24 h post-infection with , there were no differences in the level of protection offered by finafloxacin or doxycycline (as monotherapies) when compared to the combination therapy.

Early Isolates of SARS-CoV-2 Result in Different Pathogenesis in the Transduced Mouse Model of COVID-19.

A transduced mouse model of SARS-CoV-2 infection was established using Balb/c mice. This was achieved through the adenovirus-vectored delivery of the hACE2 gene, to render the mice transiently susceptible to the virus. The model was characterised in terms of the dissemination of hACE2 receptor expression, the dissemination of three SARS-CoV-2 virus variants in vivo up to 10 days following challenge, the resulting histopathology and the clinical signs induced in the mice.

Histopathological and Immunological Findings in the Common Marmoset Following Exposure to Aerosolized SARS-CoV-2.

There is an enduring requirement to develop animal models of COVID-19 to assess the efficacy of vaccines and therapeutics that can be used to treat the disease in humans. In this study, six marmosets were exposed to a small particle aerosol (1-3 µm) of SARS-CoV-2 VIC01 that delivered the virus directly to the lower respiratory tract. Following the challenge, marmosets did not develop clinical signs, although a disruption to the normal diurnal temperature rhythm was observed in three out of six animals.

Predictors of Survival after Vaccination in a Pneumonic Plague Model.

The need for an updated plague vaccine is highlighted by outbreaks in endemic regions together with the pandemic potential of this disease. There is no easily available, approved vaccine. Here we have used a murine model of pneumonic plague to examine the factors that maximise immunogenicity and contribute to survival following vaccination.

The Innate Immune Response in the Marmoset during the Acute Pneumonic Disease Caused by Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, a severe human infection that is difficult to treat with antibiotics and for which there is no effective vaccine. Development of novel treatments rely upon appropriately characterized animal models. The common marmoset (Callithrix jacchus) has been established at Defense Science and Technology laboratories (DSTL) as a model of melioidosis.

A Stochastic Intracellular Model of Anthrax Infection With Spore Germination Heterogeneity.

We present a stochastic mathematical model of the intracellular infection dynamics of in macrophages. Following inhalation of spores, these are ingested by alveolar phagocytes. Ingested spores then begin to germinate and divide intracellularly.

Investigative study into whether an insect repellent has virucidal activity against SARS-CoV-2.

A small-scale study with Mosi-guard Natural spray, an insect repellent containing Citriodiol, was performed to determine if it has virucidal activity against SARS-CoV-2. A liquid test examined the activity of the insect repellent and the individual components for virucidal activity. A surface contact test looked at the activity of the insect repellent when impregnated on a latex surface as a synthetic skin for potential topical prophylactic application.

Finafloxacin Is an Effective Treatment for Inhalational Tularemia and Plague in Mouse Models of Infection.

Infection with aerosolized or can lead to lethal disease in humans if treatment is not initiated promptly. Finafloxacin is a novel fluoroquinolone which has demonstrated broad-spectrum activity against a range of bacterial species , and in humans, activity which is superior in acidic, infection-relevant conditions. Human-equivalent doses of finafloxacin or ciprofloxacin were delivered at 24 h (representing prophylaxis) or at 72 or 38 h (representing treatment) postchallenge with or , respectively, in BALB/c mouse models.

Quantification of Ebola virus replication kinetics in vitro.

Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g.

Stochastic dynamics of Francisella tularensis infection and replication.

We study the pathogenesis of Francisella tularensis infection with an experimental mouse model, agent-based computation and mathematical analysis. Following inhalational exposure to Francisella tularensis SCHU S4, a small initial number of bacteria enter lung host cells and proliferate inside them, eventually destroying the host cell and releasing numerous copies that infect other cells. Our analysis of disease progression is based on a stochastic model of a population of infectious agents inside one host cell, extending the birth-and-death process by the occurrence of catastrophes: cell rupture events that affect all bacteria in a cell simultaneously.

An Investigation of the Effect of Transfected Defective, Ebola Virus Genomes on Ebola Replication.

As the ongoing outbreak in the Democratic Republic of Congo illustrates, Ebola virus disease continues to pose a significant risk to humankind and this necessitates the continued development of therapeutic options. One option that warrants evaluation is that of defective genomes; these can potentially parasitize resources from the wild-type virus and may even be packaged for repeated co-infection cycles. Deletion and copy-back defective genomes have been identified and reported in the literature.

The Fluoroquinolone Finafloxacin Protects BALB/c Mice Against an Intranasal Infection With Strain SchuS4.

The efficacy of the novel fluoroquinolone finafloxacin was evaluated as a potential therapeutic and , following an intranasal infection of strain SchuS4 in BALB/c mice. We demonstrated that short treatment courses of finafloxacin provide high levels of protection, with a single dose resulting in a significant increase in time to death when compared to ciprofloxacin. In addition, following investigation into the window of opportunity for treatment, we have shown that finafloxacin can provided protection when administered up to 96 h post-challenge.

The treatment of melioidosis: is there a role for repurposed drugs? A proposal and review.

: Melioidosis is a significant health problem within endemic areas such as Southeast Asia and Northern Australia. The varied presentation of melioidosis and the intrinsic antibiotic resistance of , the causative organism, make melioidosis a difficult infection to manage. Often prolonged courses of antibiotic treatments are required with no guarantee of clinical success.

Supporting fathers who want to be involved in providing healthcare for their child.

An increasing number of fathers want to be involved in providing healthcare for their child. Nurses endeavouring to include fathers in care are hindered by a lack of evidence-based guidelines outlining how best to engage with, educate and upskill this parent. Fathers remain a relatively understudied parent and there are insufficient data to validate guidelines.

Role of DNA Repair and Protective Components in Bacillus subtilis Spore Resistance to Inactivation by 400-nm-Wavelength Blue Light.

The high intrinsic decontamination resistance of spores is important medically (disease) and commercially (food spoilage). Effective methods of spore eradication would be of considerable interest in the health care and medical product industries, particularly if the decontamination method effectively killed spores while remaining benign to both humans and sensitive equipment. Intense blue light at a ∼400 nm wavelength is one such treatment that has drawn significant interest.