Modeling the Worldwide Spread of Pandemic Influenza: Baseline Case and Containment Interventions

We present a study of the worldwide spread of a pandemic influenza and its possible containment at a global level taking into account all available information on air travel. We studied a metapopulation stochastic epidemic model on a global scale that considers airline travel flow data among urban areas. We provided a temporal and spatial evolution of the pandemic with a sensitivity analysis of different levels of infectiousness of the virus and initial outbreak conditions (both geographical and seasonal). For each spreading scenario we provided the timeline and the geographical impact of the pandemic in 3,100 urban areas, located in 220 different countries. We compared the baseline cases with different containment strategies, including travel restrictions and the therapeutic use of antiviral (AV) drugs. We show that the inclusion of air transportation is crucial in the assessment of the occurrence probability of global outbreaks. The large-scale therapeutic usage of AV drugs in all hit countries would be able to mitigate a pandemic effect with a reproductive rate as high as 1.9 during the first year; with AV supply use sufficient to treat approximately 2% to 6% of the population, in conjunction with efficient case detection and timely drug distribution. For highly contagious viruses (i.e., a reproductive rate as high as 2.3), even the unrealistic use of supplies corresponding to the treatment of approximately 20% of the population leaves 30%-50% of the population infected. In the case of limited AV supplies and pandemics with a reproductive rate as high as 1.9, we demonstrate that the more cooperative the strategy, the more effective are the containment results in all regions of the world, including those countries that made part of their resources available for global use.Comment: 16 page

Health monitoring of wildlife in France : SAGIR network and epidemiological monitoring of chiroptera rabies

Two wildlife surveillance networks centralised at AFSSA-LERRPAS are presented. SAGIR network is a generalist network monitoring wildlife diseases in France. Collected data also provide information on the potential reservoir or vector status of wild animals for pathogens transmissible to man or domestic animals. The use of this network to monitor avian influenza in wild birds in France is described. The bat rabies monitoring network specialises in one disease and it must take into account the protected status of bats.Deux réseaux de surveillance de la faune sauvage centralisés à l'AFSSA-LERRPAS sont présentés. Le réseau SAGIR est un réseau généraliste de surveillance et d'alerte des maladies de la faunesauvage en France. Les données recueillies permettent aussi de connaître le statut potentiel de réservoir ou de vecteur des animaux sauvages vis-à-vis de certains agents pathogènes transmissibles à l'homme ou aux animaux domestiques. L'utilisation de ce réseau comme moyen de surveillance de l'influenza aviaire chez les oiseaux sauvages est détaillée. Le réseau de surveillance de la rage des chauves-souris est consacré à une seule maladie. Le fonctionnement doit prendre en compte le statut protégé des espèces suivies

Experimental infection of Foxes with European bat Lyssaviruses type-1 and 2

<p>Abstract</p> <p>Background</p> <p>Since 1954, there have been in excess of 800 cases of rabies as a result of European Bat <it>Lyssaviruses </it>types 1 and 2 (EBLV-1, EBLV-2) infection, mainly in Serotine and Myotis bats respectively. These viruses have rarely been reported to infect humans and terrestrial mammals, as the only exceptions are sheep in Denmark, a stone marten in Germany and a cat in France. The purpose of this study was to investigate the susceptibility of foxes to EBLVs using silver foxes (<it>Vulpes vulpes</it>) as a model.</p> <p>Results</p> <p>Our experimental studies have shown that the susceptibility of foxes to EBLVs is low by the intramuscular (IM) route, however, animals were sensitive to intracranial (IC) inoculation. Mortality was 100% for both EBLV-1 (~4.5 logs) and EBLV-2 (~3.0 logs) delivered by the IC route. Virus dissemination and inflammatory infiltrate in the brain were demonstrated but virus specific neutralising antibody (VNA) was limited (log(ED₅₀) = 0.24–2.23 and 0.95–2.39 respectively for specific EBLV-1 and EBLV-2). Foxes were also susceptible, at a low level, to peripheral (IM) infection (~3.0 logs) with EBLV-1 but not EBLV-2. Three out of 21 (14.3%) foxes developed clinical signs between 14 and 24 days post-EBLV-1 infection. None of the animals given EBLV-2 developed clinical disease.</p> <p>Conclusion</p> <p>These data suggest that the chance of a EBLV spill-over from bat to fox is low, but with a greater probability for EBLV-1 than for EBLV-2 and that foxes seem to be able to clear the virus before it reaches the brain and cause a lethal infection.</p

Estimating the global burden of endemic canine rabies

Background: Rabies is a notoriously underreported and neglected disease of lowincome countries. This study aims to estimate the public health and economic burden of rabies circulating in domestic dog populations, globally and on a country-by-country basis, allowing an objective assessment of how much this preventable disease costs endemic countries.&lt;p&gt;&lt;/p&gt; Methodology/Principal Findings: We established relationships between rabies mortality and rabies prevention and control measures, which we incorporated into a model framework. We used data derived from extensive literature searches and questionnaires on disease incidence, control interventions and preventative measures within this framework to estimate the disease burden. The burden of rabies impacts on public health sector budgets, local communities and livestock economies, with the highest risk of rabies in the poorest regions of the world. This study estimates that globally canine rabies causes approximately 59,000 (95% Confidence Intervals: 25- 159,000) human deaths, over 3.7 million (95% CIs: 1.6-10.4 million) disability-adjusted life years (DALYs) and 8.6 billion USD (95% CIs: 2.9-21.5 billion) economic losses annually. The largest component of the economic burden is due to premature death (55%), followed by direct costs of post-exposure prophylaxis (PEP, 20%) and lost income whilst seeking PEP (15.5%), with only limited costs to the veterinary sector due to dog vaccination (1.5%), and additional costs to communities from livestock losses (6%).&lt;p&gt;&lt;/p&gt; Conclusions/Significance: This study demonstrates that investment in dog vaccination, the single most effective way of reducing the disease burden, has been inadequate and that the availability and affordability of PEP needs improving. Collaborative investments by medical and veterinary sectors could dramatically reduce the current large, and unnecessary, burden of rabies on affected communities. Improved surveillance is needed to reduce uncertainty in burden estimates and to monitor the impacts of control efforts.&lt;p&gt;&lt;/p&gt

Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self-and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR

Increased Expression of Toll-Like Receptors by Monocytes and Natural Killer Cells in ANCA-Associated Vasculitis

INTRODUCTION: Toll-like receptors (TLRs) are a family of receptors that sense pathogen associated patterns such as bacterial cell wall proteins. Bacterial infections are associated with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV). Here, we assessed the expression of TLRs 2, 4, and 9 by peripheral blood leukocytes from patients with AAV, and investigated TLR mediated responses ex vivo. METHODS: Expression of TLRs was determined in 38 AAV patients (32 remission, 6 active disease), and 20 healthy controls (HC). Membrane expression of TLRs 2, 4, and 9, and intracellular expression of TLR9 by B lymphocytes, T lymphocytes, NK cells, monocytes and granulocytes was assessed using 9-color flowcytometry. Whole blood from 13 patients and 7 HC was stimulated ex vivo with TLR 2, 4 and 9 ligands and production of cytokines was analyzed. RESULTS: In patients, we observed increased proportions of TLR expressing NK cells. Furthermore, patient monocytes expressed higher levels of TLR2 compared to HC, and in a subset of patients an increased proportion of TLR4(+) monocytes was observed. Monocytes from nasal carriers of Staphylococcus aureus expressed increased levels of intracellular TLR9. Membrane expression of TLRs by B lymphocytes, T lymphocytes, and granulocytes was comparable between AAV patients and HC. Patients with active disease did not show differential TLR expression compared to patients in remission. Ex vivo responses to TLR ligands did not differ significantly between patients and HC. CONCLUSIONS: In AAV, monocytes and NK cells display increased TLR expression. Increased TLR expression by these leukocytes, probably resulting from increased activation, could play a role in disease (re)activation

Quelques traits caractéristiques de l'Afghanistan

Some characteristic outlines of Afghanistan. Afghanistan may appear a very original country among the other nations of the Thirld World. This montainous land long a crossroads and a starting point for central Asian invasions, hardly succeeded in avoiding the colonial rule. Till the beginning of the 20th century, it has been totally closed to foreigners, and its economy is still backward although it ameliorates and is getting more modern thanks to external aid and a general economic plan. However, Afghanistan does not offer yet the main characteristics of an under-developed country, except in the largest cities where problems appeared when new patterns of living replaced obsolete structures.L'Afghanistan présente par rapport aux autres nations du Tiers Monde une originalité assez marquée. Ce pays de hautes montagnes, jadis carrefour ou point de départ d'invasions, a échappé à la domination coloniale. Totalement fermé jusqu'au début du XXe siècle à toute pénétration étrangère, son économie encore très arriérée se modernise peu à peu sous les effets conjugués de l'aide internationale et de la planification. Néanmoins, à l'exception des plus grandes villes qui ont subi le choc provoqué par la dislocation des structures traditionnelles, on n'y trouve pas les caractères généralement représentatifs de là situation de sous-développement.Barrat Jacques. Quelques traits caractéristiques de l'Afghanistan. In: Annales de Géographie, t. 81, n°444, 1972. pp. 206-229

L'eau dans le monde, par Michael Overman

Barrat Jacques. L'eau dans le monde, par Michael Overman. In: Annales de Géographie, t. 81, n°448, 1972. pp. 745-746

L'eau dans le monde, par Michael Overman

Barrat Jacques. L'eau dans le monde, par Michael Overman. In: Annales de Géographie, t. 81, n°448, 1972. pp. 745-746