Comparing the immune response to a novel intranasal nanoparticle PLGA vaccine and a commercial BPI3V vaccine in dairy calves

peer-reviewedBackground There is a need to improve vaccination against respiratory pathogens in calves by stimulation of local immunity at the site of pathogen entry at an early stage in life. Ideally such a vaccine preparation would not be inhibited by the maternally derived antibodies. Additionally, localized immune response at the site of infection is also crucial to control infection at the site of entry of virus. The present study investigated the response to an intranasal bovine parainfluenza 3 virus (BPI3V) antigen preparation encapsulated in PLGA (poly dl-lactic-co-glycolide) nanoparticles in the presence of pre-existing anti-BPI3V antibodies in young calves and comparing it to a commercially available BPI3V respiratory vaccine. Results There was a significant (P < 0.05) increase in BPI3V-specific IgA in the nasal mucus of the BPI3V nanoparticle vaccine group alone. Following administration of the nanoparticle vaccine an early immune response was induced that continued to grow until the end of study and was not observed in the other treatment groups. Virus specific serum IgG response to both the nanoparticle vaccine and commercial live attenuated vaccine showed a significant (P < 0.05) rise over the period of study. However, the cell mediated immune response observed didn’t show any significant rise in any of the treatment groups. Conclusion Calves administered the intranasal nanoparticle vaccine induced significantly greater mucosal IgA responses, compared to the other treatment groups. This suggests an enhanced, sustained mucosal-based immunological response to the BPI3V nanoparticle vaccine in the face of pre-existing antibodies to BPI3V, which are encouraging and potentially useful characteristics of a candidate vaccine. However, ability of nanoparticle vaccine in eliciting cell mediated immune response needs further investigation. More sustained local mucosal immunity induced by nanoparticle vaccine has obvious potential if it translates into enhanced protective immunity in the face of virus outbreak

VISCERAL LEISHMANIASIS IN PETROLINA, STATE OF PERNAMBUCO, BRAZIL, 2007-2013

Visceral leishmaniasis is a life-threatening disease of great public health relevance in Brazil. The municipality of Petrolina is an endemic area in the State of Pernambuco, Brazil. This study was designed to assess the recent expansion of VL in the municipality ofPetrolina, Pernambuco. Patients data were obtained from the Brazilian National Information System for Notifiable Diseases (SINAN). A total of 111 records from 2007 to 2013 were investigated, of which 69 were residents in Petrolina. The disease has predominantly affected 1-4 year old children (34.8%). Most of the patients were males (59.4%). Co-infection with human immunodeficiency virus occurred in 14.5% of the cases. The criterion most frequently used was the clinical and epidemiological confirmation (59.4%), with clinical cure in 78.3% of cases and one fatal outcome. Visceral leishmaniasis is endemic in Petrolina with transmission levels varying from moderate to high. The present study has shown the precariousness of the use of diagnostic tests in primary healthcare units, and this misuse has interfered with the diagnosis and treatment of cases

Rickettsia felis, an emerging flea-transmitted human pathogen

Rickettsia felis was first recognised two decades ago and has now been described as endemic to all continents except Antarctica. The rickettsiosis caused by R. felis is known as flea-borne spotted fever or cat-flea typhus. The large number of arthropod species found to harbour R. felis and that may act as potential vectors support the view that it is a pan-global microbe. The main arthropod reservoir and vector is the cat flea, Ctenocephalides felis, yet more than 20 other species of fleas, ticks, and mites species have been reported to harbour R. felis. Few bacterial pathogens of humans have been found associated with such a diverse range of invertebrates. With the projected increase in global temperature over the next century, there is concern that changes to the ecology and distribution of R. felis vectors may adversely impact public health

Dengue in an elderly patient

Although elderly populations are more exposed to the risk of getting dengue, the clinical peculiarities of this disease in this age range are not well known. This report is about an 80-year-old woman with dengue complications, self-medicated with salicylate. Literature indicates a more severe clinical condition, high hospitalization rate and significant mortality. This is caused by previous infections by other serotypes of this arbovirus, presence of chronic diseases, immunosenescence and high drug consumption, especially salicylates and the like. Analyses are required in a public health perspective in order to help health professionals that care for patients with dengue in this age range.Embora cada vez mais populações idosas estejam expostas ao risco de contrair dengue, pouco se sabe sobre peculiaridades clínicas desta doença nesta faixa etária, fato este que motivou este relato sobre octogenária com dengue agravada por automedicação de salicilato. A literatura consultada aponta para quadro clínico mais grave, elevado índice de hospitalizações e mortalidade significativa. Deve-se isto a infecções prévias com outros sorotipos desta arbovirose, presença de doenças crônico degenerativas, imunosenescência e alto consumo de medicamentos, particularmente salicilatos e similares. Análises, sob a ótica da saúde pública, são necessárias para auxiliar aos profissionais de saúde que assistem pacientes com dengue nesta faixa etári

Genomic signatures of local adaptation reveal source-sink dynamics in a high gene flow fish species

Understanding source-sink dynamics is important for conservation management, particularly when climatic events alter species' distributions. Following a 2011 'marine heatwave' in Western Australia, we observed high recruitment of the endemic fisheries target species Choerodon rubescens, towards the cooler (southern) end of its distribution. Here, we use a genome wide set of 14 559 single-nucleotide polymorphisms (SNPs) to identify the likely source population for this recruitment event. Most loci (76%) showed low genetic divergence across the species' range, indicating high levels of gene flow and confirming previous findings using neutral microsatellite markers. However, a small proportion of loci showed strong patterns of differentiation and exhibited patterns of population structure consistent with local adaptation. Clustering analyses based on these outlier loci indicated that recruits at the southern end of C. rubescens' range originated 400 km to the north, at the centre of the species' range, where average temperatures are up to 3 °C warmer. Survival of these recruits may be low because they carry alleles adapted to an environment different to the one they now reside in, but their survival is key to establishing locally adapted populations at and beyond the range edge as water temperatures increase with climate change

Altered mRNA expression of genes related to nerve cell activity in the fracture callus of older rats: A randomized, controlled, microarray study

BACKGROUND: The time required for radiographic union following femoral fracture increases with age in both humans and rats for unknown reasons. Since abnormalities in fracture innervation will slow skeletal healing, we explored whether abnormal mRNA expression of genes related to nerve cell activity in the older rats was associated with the slowing of skeletal repair. METHODS: Simple, transverse, mid-shaft, femoral fractures with intramedullary rod fixation were induced in anaesthetized female Sprague-Dawley rats at 6, 26, and 52 weeks of age. At 0, 0.4, 1, 2, 4, and 6 weeks after fracture, a bony segment, one-third the length of the femur, centered on the fracture site, including the external callus, cortical bone, and marrow elements, was harvested. cRNA was prepared and hybridized to 54 Affymetrix U34A microarrays (3/age/time point). RESULTS: The mRNA levels of 62 genes related to neural function were affected by fracture. Of the total, 38 genes were altered by fracture to a similar extent at the three ages. In contrast, eight neural genes showed prolonged down-regulation in the older rats compared to the more rapid return to pre-fracture levels in younger rats. Seven genes were up-regulated by fracture more in the younger rats than in the older rats, while nine genes were up-regulated more in the older rats than in the younger. CONCLUSIONS: mRNA of 24 nerve-related genes responded differently to fracture in older rats compared to young rats. This differential expression may reflect altered cell function at the fracture site that may be causally related to the slowing of fracture healing with age or may be an effect of the delayed healing

PCSK9 genetic variants and risk of type 2 diabetes: a mendelian randomisation study

BACKGROUND: Statin treatment and variants in the gene encoding HMG-CoA reductase are associated with reductions in both the concentration of LDL cholesterol and the risk of coronary heart disease, but also with modest hyperglycaemia, increased bodyweight, and modestly increased risk of type 2 diabetes, which in no way offsets their substantial benefits. We sought to investigate the associations of LDL cholesterol-lowering PCSK9 variants with type 2 diabetes and related biomarkers to gauge the likely effects of PCSK9 inhibitors on diabetes risk. METHODS: In this mendelian randomisation study, we used data from cohort studies, randomised controlled trials, case control studies, and genetic consortia to estimate associations of PCSK9 genetic variants with LDL cholesterol, fasting blood glucose, HbA1c, fasting insulin, bodyweight, waist-to-hip ratio, BMI, and risk of type 2 diabetes, using a standardised analysis plan, meta-analyses, and weighted gene-centric scores. FINDINGS: Data were available for more than 550 000 individuals and 51 623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0·09 mmol/L, 95% CI 0·02 to 0·15), bodyweight (1·03 kg, 0·24 to 1·82), waist-to-hip ratio (0·006, 0·003 to 0·010), and an odds ratio for type diabetes of 1·29 (1·11 to 1·50). Based on the collected data, we did not identify associations with HbA1c (0·03%, -0·01 to 0·08), fasting insulin (0·00%, -0·06 to 0·07), and BMI (0·11 kg/m(2), -0·09 to 0·30). INTERPRETATION: PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins. FUNDING: British Heart Foundation, and University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre.This work was supported by a British Heart Foundation Programme Grant (RG/10/12/28456). AFS is funded by University College London Hospitals NHS Foundation Trust (UCLH) National Institute for Health Research (NIHR) Biomedical Research Centre (BRC10200) and by a UCL springboard population science fellowship. FWA is supported by a Dekker scholarship-Junior Staff Member 2014T001–Netherlands Heart Foundation and UCL Hospitals NIHR Biomedical Research Centre. ADH is an NIHR Senior Investigator. Funding information and acknowledgments for studies contributing data are reported in the appendix