Contamination of Emergency Medical Vehicles and Risk of Infection to Paramedic First Responders and Patients by Antibiotic-Resistant Bacteria: Risk Evaluation and Recommendations from Ambulance Case Studies

Contamination of emergency medical vehicles with pathogenic microbes poses a potential threat to public health considering the many millions of ambulance responses that are made globally each year. This risk of infection is to the patients, to their companions who may travel with them, and to the paramedic first responders whose work involves pre- or inter-hospital transfer. This applies particularly to contamination by those infectious disease-causing microbes for which the threat is heightened because of their recognized resistance to leading antimicrobial agents. Determining the risks should facilitate the advancement of best practices to enhance infection control of routine outbreaks and during a major emergency such as a disease pandemic or a bioterrorism event. This may merit the introduction of amended guidelines for ambulance cleaning and disinfection to achieve more effective pre-hospital infection control among the worldwide community of emergency service providers

Diagnosis of Dengue: Strengths and Limitations of Current Techniques and Prospects for Future Improvements

Dengue is an increasingly common mosquito-borne, flaviviral disease of significant public health concern. The disease is endemic throughout tropical and subtropical regions, placing almost half of the world’s population at risk, and each year approaching 100 million people in around 130 countries are infected. There is acknowledged to be four antigenically distinct serotypes of the virus, and arguably a fifth, each of which elicits a full spectrum of clinical disease. This ranges from asymptomatic self-limiting infection to life-threatening severe manifestations characterized by plasma leakage, bleeding, and/or organ failure. Recovery from primary infection by one serotype provides life-long immunity against reinfection by that particular serotype, whereas with subsequent infections by other serotypes, the risk of developing severe dengue is increased. Rising mortality and morbidity rates caused by infection in recent years are attributable partly to a lack of availability of effective antiviral therapies and vaccines. In this context, early detection of infection with sensitive and specific laboratory tools and the prompt clinical management of this disease is a health care priority. Although a variety of techniques are currently used for laboratory diagnosis of dengue, no single methodology satisfies the ideal requirement for both sensitivity and specificity, while also being rapid and inexpensive. Newer detection tools that can fill this acknowledged gap in dengue diagnosis are urgently required

Prospects and Pitfalls of Pregnancy-Associated Malaria Vaccination Based on the Natural Immune Response to Plasmodium falciparum VAR2CSA-Expressing Parasites

Pregnancy-associated malaria, a manifestation of severe malaria, is the cause of up to 200,000 infant deaths a year, through the effects of placental insufficiency leading to growth restriction and preterm delivery. Development of a vaccine is one strategy for control. Plasmodium falciparum-infected red blood cells accumulate in the placenta through specific binding of pregnancy-associated parasite variants that express the VAR2CSA antigen to chondroitin sulphate A on the surface of syncytiotrophoblast cells. Parasite accumulation, accompanied by an inflammatory infiltrate, disrupts the cytokine balance of pregnancy with the potential to cause placental damage and compromise foetal growth. Multigravid women develop immunity towards VAR2CSA-expressing parasites in a gravidity-dependent manner which prevents unfavourable pregnancy outcomes. Although current vaccine design, targeting VAR2CSA antigens, has succeeded in inducing antibodies artificially, this candidate may not provide protection during the first trimester and may only protect those women living in areas endemic for malaria. It is concluded that while insufficient information about placental-parasite interactions is presently available to produce an effective vaccine, incremental progress is being made towards achieving this goal

Vaccine Development against Dengue, a Viral Disease of Increasing Significance to Global Public Health

Dengue is a mosquito-borne viral disease of humans that is a major public health concern in tropical and subtropical regions of the world. The increasing mortality and morbidity rates caused by infection in recent years are attributable partly to a lack of availability of effective antiviral therapies and vaccines. In a concerted attempt to arrest this global expansion, several dengue vaccine candidates have progressed from pre-clinical testing into clinical trials. However, the advancement of vaccine development has manifest challenges to be overcome. A principal tenet underpinning dengue vaccine design is balanced immunity to all five recognised virus serotypes, but difficulties in achieving optimal attenuation of each virus and interference between individual attenuated viruses are significant hurdles to successful implementation. Currently, the most advanced vaccine candidate, the recombinant, live-attenuated ChimeriVax-DEN1-4 preparation developed by Sanofi Pasteur, is likely to achieve licensure at the completion of phase III trials and undergo population safety surveillance. Subunit and DNA vaccines are also in various stages of clinical evaluation. The intrinsic rationale is to produce a safe, efficacious and cost-effective vaccine. While this remains an achievable goal, progress is limited by an incomplete understanding of dengue viral pathogenesis, together with a lack of suitable animal models for fundamental pre-clinical development. This editorial highlights current approaches and future directions for vaccine strategies to combat the global expansion of this infectious disease

Host-Virus Interactions in Dengue Infection indicate Targets for Detection and Therapeutic Interventions

Dengue is a mosquito-transmitted viral infectious disease that is endemic to 110 countries spanning tropical and subtropical regions. While infection is typically asymptomatic, symptoms of the estimated 50-100 million clinical cases are often debilitating and occasionally life-threatening, resulting in as many as 5 million hospitalisations annually. Consequently, the World Health Organization regards dengue as a significant global public health concern. Immense challenges exist in both formulating and constructing an efficacious vaccine for prophylaxis and in developing therapeutics for cure. Although there have been numerous molecular studies of the interaction between host and virus, and the metabolic pathways of several proteins are implicated in dengue virus replication, their biological significance remains unclear. It is important to consider clinical, immunopathological and epidemiological features to decipher the complexity of disease and to unravel the mechanisms attributed to its progression. This editorial emphasises the critical events causing vascular endothelial permeability, which underpins the manifestations in humans of dengue haemorrhagic fever and dengue shock syndrome

Interplay between T Regulatory and T Helper 17 Lymphocytes in Modulation of Immunity to Blood Stage Malaria Infection

Malaria claims millions of lives worldwide each year. While a pro-inflammatory immune response is required to control parasite replication and promote clearance of infected erythrocytes, considerable disease pathology is caused by an excessive and dysregulated inflammatory reactivity to blood stage infection. Clinical symptoms, including fever and chills, correspond to production by CD4+ T helper (Th) lymphocytes of high levels of pro-inflammatory cytokines including tumour necrosis factor-α, interleukin-12 and interferon- γ in response to parasite components released upon erythrocyte rupture. Differentiation into specific effector Th subsets is directed by polarizing cytokines and expression of master transcription factors. From a perspective of homeostasis, further regulatory Th subsets have been described that secrete specific cytokines to modulate the effector immune response and thus play a pivotal role in protecting the body from direct and indirect pathogenic effects of malaria infection. In particular, T regulatory (Treg) lymphocytes are associated with immune tolerance and play a crucial role in suppressing the host response by inhibiting the function of effector subsets such as Th1 and Th17. This prevents inflammation produced downstream by (non-T) effectors cells. Treg lymphocytes, exemplified by CD4+CD25+Foxp3+ cells, gradually increase in number during infection to achieve and maintain the homeostasis of an otherwise imbalanced T cell response. This editorial discusses the production of Treg and Th17 lymphocytes and the interrelated roles played by their signature cytokines during malaria infection and considers the contribution of each to parasite clearance or progression

Quorum Sensing in Biofilm

Quorum sensing (QS) is a complex system of communication used by bacteria, including several notable pathogens that pose a significant threat to public health. The central role of QS in biofilm activity has been demonstrated extensively. The small extracellular signaling molecules, known as autoinducers, that are released during this process of cell-to-cell communication play a key part in gene regulation. QS is involved in such diverse intracellular operations as modulation of cellular function, genetic material transfer, and metabolite synthesis. There are three main types of QS in bacteria, metabolites of which may form the target for novel treatment approaches. The autoinducing peptide system exists only in Gram-positive bacteria, being replaced in Gram-negative species by the acyl-homoserine lactone system, whereas the autoinducer-2 system occurs in both

Biofilm Formation by Pathogenic Bacteria: Applying a Staphylococcus aureus Model to Appraise Potential Targets for Therapeutic Intervention

Carried in the nasal passages by up to 30% of humans, Staphylococcus aureus is recognized to be a successful opportunistic pathogen. It is a frequent cause of infections of the upper respiratory tract, including sinusitis, and of the skin, typically abscesses, as well as of food poisoning and medical device contamination. The antimicrobial resistance of such, often chronic, health conditions is underpinned by the unique structure of bacterial biofilm, which is the focus of increasing research to try to overcome this serious public health challenge. Due to the protective barrier of an exopolysaccharide matrix, bacteria that are embedded within biofilm are highly resistant both to an infected individual's immune response and to any treating antibiotics. An in-depth appraisal of the stepwise progression of biofilm formation by S. aureus, used as a model infection for all cases of bacterial antibiotic resistance, has enhanced understanding of this complicated microscopic structure and served to highlight possible intervention targets for both patient cure and community infection control. While antibiotic therapy offers a practical means of treatment and prevention, the most favorable results are achieved in combination with other methods. This review provides an overview of S. aureus biofilm development, outlines the current range of anti-biofilm agents that are used against each stage and summarizes their relative merits

The potential for modification in cloning and vitrification technology to enhance genetic progress in beef cattle in Northern Australia

AbstractRecent advances in embryology and related research offer considerable possibilities to accelerate genetic improvement in cattle breeding. Such progress includes optimization and standardization of laboratory embryo production (in vitro fertilization – IVF), introduction of a highly efficient method for cryopreservation (vitrification), and dramatic improvement in the efficiency of somatic cell nuclear transfer (cloning) in terms of required effort, cost, and overall outcome. Handmade cloning (HMC), a simplified version of somatic cell nuclear transfer, offers the potential for relatively easy and low-cost production of clones. A potentially modified method of vitrification used at a centrally located laboratory facility could result in cloned offspring that are economically competitive with elite animals produced by more traditional means. Apart from routine legal and intellectual property issues, the main obstacle that hampers rapid uptake of these technologies by the beef cattle industry is a lack of confidence from scientific and commercial sources. Once stakeholder support is increased, the combined application of these methods makes a rapid advance toward desirable traits (rapid growth, high-quality beef, optimized reproductive performance) a realistic goal. The potential impact of these technologies on genetic advancement in beef cattle herds in which improvement of stock is sought, such as in northern Australia, is hard to overestimate