Human exposures to by-products from animals suspected to have died of anthrax in Bangladesh: An exploratory study

Anthrax is a zoonotic disease caused by the bacterium Bacillus anthracis that is considered endemic in Bangladesh, where cases among animals and people have been reported almost annually since 2009. Contaminated by-products from animals are suspected to play a role in transmission to people, but minimal information is known on the supply chain of these potentially contaminated products. Between April 2013 and May 2016, we conducted a qualitative study in 17 villages located in five districts in Bangladesh, which had experienced suspected anthrax outbreaks. The study explored how by-products from suspected animal cases were collected, discarded, processed, distributed and used by people. We conducted open-ended interviews, group discussions and unstructured observations of people's exposure to animal by-products. The practice of slaughtering acutely ill domestic ruminants before they died was common. Respondents reported that moribund animals were typically butchered, and the waste products were discarded in nearby rivers, ditches, bamboo bushes, or on privately owned land. Regardless of health status before death, very few carcasses were buried, and none were incinerated or burned. The hides were reportedly used to make wallets, belts, shoes, balls and clothing. Discarded bones were often ground into granular and powder forms to produce bone meal and fertilizer. Therefore, given anthrax is endemic in the study region, livestock with acute onset of fatal disease or found dead with no known cause of death may be an anthrax case and subsequently pose a health risk to those involved in the collection and processing of the carcass, as well as the end-user of these products. Improved bio-security practices and safe carcass disposal measures could reduce the risk of human exposure, but resource and other constraints make implementation a challenge. Therefore, targeting at-risk animal populations for vaccination may be the most effective strategy to reduce anthrax outbreaks, protect the supply chain and reduce the risk of exposure to B. anthracis

Epidemiology and genetic characterization of Peste des petits ruminants virus in Bangladesh

Peste des petits ruminants (PPR) is an acute, highly contagious disease responsible for high morbidity and mortality rates in susceptible sheep and goats. Adequate knowledge of the diversity of circulating strains of PPR virus will help livestock authorities choose appropriate vaccines. The objective of this study was to describe the epidemiology of PPR and characterize the strains circulating in Bangladesh. Veterinarians enrolled goats showing signs consistent with PPR, including diarrhoea, fever and respiratory distress, from three veterinary hospitals. Post-treatment follow up was carried out to ascertain health outcomes of the goats. Faecal and throat swab samples were collected from the goats and tested for PPRV RNA using real-time reverse transcription polymerase chain reaction (rRT-PCR). Nucleotide sequence-based phylogenetic analyses of two structural genes, the nucleocapsid (N gene), and the haemagglutinin (H gene) were studied to determine the genetic variations of PPRV strains. Of the 539 goats enrolled, 38% (203/539) had detectable RNA for PPRV. We were able to follow up with 91% (184/203) of the PPRV infected goats; 44 of them died (24%). PPRV was more frequently identified in the summer (45%) than in the rainy season (29%) (Odds ratio = 1.9, 95% confidence interval: 1.3–3.1). Bangladeshi strains were phylogenetically similar to the lineage IV PPRV strains; showing particularly strong affiliation with Tibetan and Indian strains. PPR is a common viral infection of the goats in Bangladesh, with a high case-fatality rate. This study confirms the circulation of lineage IV PPRV in the country with unique amino acid substitutions in N and H proteins and provides baseline data for vaccine development and implementation

Vaccine Potential of Nipah Virus-Like Particles

Nipah virus (NiV) was first recognized in 1998 in a zoonotic disease outbreak associated with highly lethal febrile encephalitis in humans and a predominantly respiratory disease in pigs. Periodic deadly outbreaks, documentation of person-to-person transmission, and the potential of this virus as an agent of agroterror reinforce the need for effective means of therapy and prevention. In this report, we describe the vaccine potential of NiV virus-like particles (NiV VLPs) composed of three NiV proteins G, F and M. Co-expression of these proteins under optimized conditions resulted in quantifiable amounts of VLPs with many virus-like/vaccine desirable properties including some not previously described for VLPs of any paramyxovirus: The particles were fusogenic, inducing syncytia formation; PCR array analysis showed NiV VLP-induced activation of innate immune defense pathways; the surface structure of NiV VLPs imaged by cryoelectron microscopy was dense, ordered, and repetitive, and consistent with similarly derived structure of paramyxovirus measles virus. The VLPs were composed of all the three viral proteins as designed, and their intracellular processing also appeared similar to NiV virions. The size, morphology and surface composition of the VLPs were consistent with the parental virus, and importantly, they retained their antigenic potential. Finally, these particles, formulated without adjuvant, were able to induce neutralizing antibody response in Balb/c mice. These findings indicate vaccine potential of these particles and will be the basis for undertaking future protective efficacy studies in animal models of NiV disease

Time-varying bispectral analysis of visually evoked multi-channel EEG

Theoretical foundations of higher order spectral analysis are revisited to examine the use of time-varying bicoherence on non-stationary signals using a classical short-time Fourier approach. A methodology is developed to apply this to evoked EEG responses where a stimulus-locked time reference is available. Short-time windowed ensembles of the response at the same offset from the reference are considered as ergodic cyclostationary processes within a non-stationary random process. Bicoherence can be estimated reliably with known levels at which it is significantly different from zero and can be tracked as a function of offset from the stimulus. When this methodology is applied to multi-channel EEG, it is possible to obtain information about phase synchronization at different regions of the brain as the neural response develops. The methodology is applied to analyze evoked EEG response to flash visual stimulii to the left and right eye separately. The EEG electrode array is segmented based on bicoherence evolution with time using the mean absolute difference as a measure of dissimilarity. Segment maps confirm the importance of the occipital region in visual processing and demonstrate a link between the frontal and occipital regions during the response. Maps are constructed using bicoherence at bifrequencies that include the alpha band frequency of 8Hz as well as 4 and 20Hz. Differences are observed between responses from the left eye and the right eye, and also between subjects. The methodology shows potential as a neurological functional imaging technique that can be further developed for diagnosis and monitoring using scalp EEG which is less invasive and less expensive than magnetic resonance imaging

Competing Actions of Type 1 Angiotensin II Receptors Expressed on T Lymphocytes and Kidney Epithelium during Cisplatin-Induced AKI.

Inappropriate activation of the renin-angiotensin system (RAS) contributes to many CKDs. However, the role of the RAS in modulating AKI requires elucidation, particularly because stimulating type 1 angiotensin II (AT1) receptors in the kidney or circulating inflammatory cells can have opposing effects on the generation of inflammatory mediators that underpin the pathogenesis of AKI. For example, TNF-α is a fundamental driver of cisplatin nephrotoxicity, and generation of TNF-α is suppressed or enhanced by AT1 receptor signaling in T lymphocytes or the distal nephron, respectively. In this study, cell tracking experiments with CD4-Cre mT/mG reporter mice revealed robust infiltration of T lymphocytes into the kidney after cisplatin injection. Notably, knockout of AT1 receptors on T lymphocytes exacerbated the severity of cisplatin-induced AKI and enhanced the cisplatin-induced increase in TNF-α levels locally within the kidney and in the systemic circulation. In contrast, knockout of AT1 receptors on kidney epithelial cells ameliorated the severity of AKI and suppressed local and systemic TNF-α production induced by cisplatin. Finally, disrupting TNF-α production specifically within the renal tubular epithelium attenuated the AKI and the increase in circulating TNF-α levels induced by cisplatin. These results illustrate discrepant tissue-specific effects of RAS stimulation on cisplatin nephrotoxicity and raise the concern that inflammatory mediators produced by renal parenchymal cells may influence the function of remote organs by altering systemic cytokine levels. Our findings suggest selective inhibition of AT1 receptors within the nephron as a promising intervention for protecting patients from cisplatin-induced nephrotoxicity