Predicting Quarantine Failure Rates

Preemptive quarantine through contact-tracing effectively controls emerging infectious diseases. Occasionally this quarantine fails, however, and infected persons are released. The probability of quarantine failure is typically estimated from disease-specific data. Here a simple, exact estimate of the failure rate is derived that does not depend on disease-specific parameters. This estimate is universally applicable to all infectious diseases

Could The Human Papillomavirus Vaccines Drive Virulence Evolution?

Definitive version as published available at: Full Cite, http://dx.doi.org/10.1098/rspb.2014.1069The human papillomavirus (HPV) vaccines hold great promise for preventing several cancers caused by HPV infections. Yet little attention has been given to whether HPV could respond evolutionarily to the new selection pressures imposed on it by the novel immunity response created by the vaccine. Here, we present and theoretically validate a mechanism by which the vaccine alters the transmission-recovery trade-off that constrains HPV's virulence such that higher oncogene expression is favoured. With a high oncogene expression strategy, the virus is able to increase its viral load and infected cell population before clearance by the vaccine, thus improving its chances of transmission. This new rapid cell-proliferation strategy is able to circulate between hosts with medium to high turnover rates of sexual partners. We also discuss the importance of better quantifying the duration of challenge infections and the degree to which a vaccinated host can shed virus. The generality of the models presented here suggests a wider applicability of this mechanism, and thus highlights the need to investigate viral oncogenicity from an evolutionary perspective.CIH

When Is Quarantine a Useful Control Strategy for Emerging Infectious Diseases?

The isolation and treatment of symptomatic individuals, coupled with the quarantining of individuals that have a high risk of having been infected, constitute two commonly used epidemic control measures. Although isolation is probably always a desirable public health measure, quarantine is more controversial. Mass quarantine can inflict significant social, psychological, and economic costs without resulting in the detection of many infected individuals. The authors use probabilistic models to determine the conditions under which quarantine is expected to be useful. Results demonstrate that the number of infections averted (per initially infected individual) through the use of quarantine is expected to be very low provided that isolation is effective, but it increases abruptly and at an accelerating rate as the effectiveness of isolation diminishes. When isolation is ineffective, the use of quarantine will be most beneficial when there is significant asymptomatic transmission and if the asymptomatic period is neither very long nor very shor

Caspase-Cleaved Tau Co-Localizes with Early Tangle Markers in the Human Vascular Dementia Brain

Vascular dementia (VaD) is the second most common form of dementia in the United States and is characterized as a cerebral vessel vascular disease that leads to ischemic episodes. Whereas the relationship between caspase-cleaved tau and neurofibrillary tangles (NFTs) in Alzheimer’s disease (AD) has been previously described, whether caspase activation and cleavage of tau occurs in VaD is presently unknown. To investigate a potential role for caspase-cleaved tau in VaD, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing a well-characterized antibody that specifically detects caspase-cleaved tau truncated at Asp421. Application of this antibody (TauC3) revealed consistent labeling within NFTs, dystrophic neurites within plaque-rich regions and corpora amylacea (CA) in the human VaD brain. Labeling of CA by the TauC3 antibody was widespread throughout the hippocampus proper, was significantly higher compared to age matched controls, and co-localized with ubiquitin. Staining of the TauC3 antibody co-localized with MC-1, AT8, and PHF-1 within NFTs. Quantitative analysis indicated that roughly 90% of PHF-1-labeled NFTs contained caspase-cleaved tau. In addition, we documented the presence of active caspase-3 within plaques, blood vessels and pretangle neurons that co-localized with TauC3. Collectively, these data support a role for the activation of caspase-3 and proteolytic cleavage of TauC3 in VaD providing further support for the involvement of this family of proteases in NFT pathology

Proteolytic Cleavage of Apolipoprotein E in the Down Syndrome Brain

Down syndrome (DS) is one of the most common genetic causes of intellectual disability and is characterized by a number of behavioral as well as cognitive symptoms. Many of the neuropathological features of early-onset Alzheimer’s disease (AD) including senile plaques and neurofibrillary tangles (NFTs) are also present in people with DS as a result of triplication of the amyloid precursor gene on chromosome 21. Evidence suggests that harboring one or both apolipoprotein E4 (APOE4) alleles may increase the risk for AD due to the proteolytic cleavage of apoE4 and a subsequent loss of function. To investigate a role for the apoE proteolysis in vivo, we compared three autopsy groups; 7 DS with AD neuropathology cases over 40 years, 5 young DS cases without AD pathology under 40 years (YDS) and 5 age-matched control cases over 40 years by immunohistochemistry utilizing an antibody that detects the amino-terminal fragment of apoE. Application of this antibody, termed the amino-terminal apoE fragment antibody (nApoECF) revealed labeling of pyramidal neurons in the frontal cortex of YDS cases, whereas in the DS-AD group, labeling with nApoECF was prominent within NFTs. NFT labeling with nApoECF was significantly greater in the hippocampus versus the frontal cortex in the same DS-AD cases, suggesting a regional distribution of truncated apoE. Colocalization immunofluorescence experiments indicated that 52.5% and 53.2% of AT8- and PHF-1-positive NFTs, respectively, also contained nApoECF. Collectively, these data support a role for the proteolytic cleavage of apoE in DS and suggest that apoE fragmentation is closely associated with NFTs

Apolipoprotein E Pathology in Vascular Dementia

Vascular dementia (VaD) is the second most common form of dementia and is currently defined as a cerebral vessel vascular disease leading to ischemic episodes. Apolipoprotein E (apoE) gene polymorphism has been proposed as a risk factor for VaD, however, to date there are few documented post-mortem studies on apoE pathology in the VaD brain. To investigate a potential role for the apoE protein, we analyzed seven confirmed cases of VaD by immunohistochemistry utilizing an antibody that specifically detects the amino-terminal fragment of apoE. Application of this antibody, termed N-terminal, apoE cleavage fragment (nApoECF) revealed consistent labeling within neurofibrillary tangles (NFTs), blood vessels, and reactive astrocytes. Labeling occurred in VaD cases that had confirmed APOE genotypes of 3/3, 3/4, and 4/4, with respect to NFTs, staining of the nApoECF co-localized with PHF-1 and was predominantly localized to large, stellate neurons in layer II of the entorhinal cortex. Quantitative analysis indicated that approximately 38.4% of all identified NFTs contained the amino-terminal fragment of apoE. Collectively, these data support a role for the proteolytic cleavage of apoE in the VaD and support previous reports that APOE polymorphism is significantly associated with susceptibility in this disease

Factors influencing Manx Shearwater grounding on the west coast of Scotland

Grounding of thousands of newly fledged petrels and shearwaters (family Procellariidae) in built‐up areas due to artificial light is a global problem. Due to their anatomy these grounded birds find it difficult to take off from built‐up areas and many fall victim to predation, cars, dehydration or starvation. This research investigated a combination of several factors that may influence the number of Manx Shearwater Puffinus puffinus groundings in a coastal village of Scotland located close to a nesting site for this species. A model was developed that used meteorological variables and moon cycle to predict the daily quantity of birds that were recovered on the ground. The model, explaining 46.32% of the variance of the data, revealed how new moon and strong onshore winds influence grounding. To a lesser extent, visibility conditions can also have an effect on grounding probabilities. The analysis presented in this study can improve rescue campaigns of not only Manx Shearwaters but also other species attracted to the light pollution by predicting conditions leading to an increase in the number of groundings. It could also inform local authorities when artificial light intensity needs to be reduced