Characterising Livestock System Zoonoses Hotspots

A systematic review of the published literature was undertaken, to explore the ability of different types of model to help identify the relative importance of different drivers leading to the development of zoonoses hotspots. We estimated that out of 373 papers we included in our review, 108 papers touched upon the objective of 'Assessment of interventions and intervention policies', 75 addressed the objective of 'Analysis of economic aspects of disease outbreaks and interventions', 67 the objective of 'Prediction of future outbreaks', but only 37 broadly addressed the objective of 'Sensitivity analysis to identify criteria leading to enhanced risk'. Most models of zoonotic diseases are currently capturing outbreaks over relatively short time and largely ignoring socio-economic drivers leading to pathogen emergence, spill-over and spread. In order to study long-term changes we need to understand how socio-economic and climatic changes affect structure of livestock production and how these in turn affect disease emergence and spread. Models capable of describing this processes do not appear to exist, although some progress has been made in linking social and economical aspects of livestock production and in linking economics to disease dynamics. Henceforth we conclude that a new modelling framework is required that expands and formalises the 'one world, one health' strategy, enabling its deployment in the re-thinking of prevention and control strategies. Although modelling can only provide means to identify risks associated with socio-economic changes, it can never be a substitute for data collection. Finally, we note that uncertainty analysis and uncertainty communication form a key element of modelling process and yet are rarely addressed

A review of mathematical models of influenza A infections within a host or cell culture: lessons learned and challenges ahead

Most mathematical models used to study the dynamics of influenza A have thus far focused on the between-host population level, with the aim to inform public health decisions regarding issues such as drug and social distancing intervention strategies, antiviral stockpiling or vaccine distribution. Here, we investigate mathematical modeling of influenza infection spread at a different scale; namely that occurring within an individual host or a cell culture. We review the models that have been developed in the last decades and discuss their contributions to our understanding of the dynamics of influenza infections. We review kinetic parameters (e.g., viral clearance rate, lifespan of infected cells) and values obtained through fitting mathematical models, and contrast them with values obtained directly from experiments. We explore the symbiotic role of mathematical models and experimental assays in improving our quantitative understanding of influenza infection dynamics. We also discuss the challenges in developing better, more comprehensive models for the course of influenza infections within a host or cell culture. Finally, we explain the contributions of such modeling efforts to important public health issues, and suggest future modeling studies that can help to address additional questions relevant to public health

Decision Support System for Soybean Rust (Phakopsora pachyrhizi) Management using QnD

The objective of this project is to design a decision support system for soybean rust management using gaming software that incorporates farmer's decision making in the face of risks from soybean rust. Learning from past actions and neighbor's actions are also incorporated. Farmers observe rust outbreak in the current and past periods and decide over how much of land to allocate between soybean, corn and other crops. This decision is influenced by maximization of expected profits criterion which entails crop rotation choices that are based upon perceived risks, yield drags and input costs from altering optimum rotation patterns. Adoption of new technology in terms of selecting better rust management practices is also analyzed in an adaptive management framework. The software meets the need of guiding policy formulation besides training stakeholders in making economically sound choices in the absence of empirical data over pest infestation.Research Methods/ Statistical Methods,

Predictive modeling of influenza in New England using a recurrent deep neural network

Predicting seasonal variation in influenza epidemics is an ongoing challenge. To better predict seasonal influenza and provide early warning of pandemics, a novel approach to Influenza-Like-Illness (ILI) prediction was developed. This approach combined a deep neural network with ILI, climate, and population data. A predictive model was created using a deep neural network based on TensorFlow 2.0 Beta. The model used Long-Short Term Memory (LSTM) nodes. Data was collected from the Center for Disease Control, the National Center for Environmental Information (NCEI) and the United States Census Bureau. These parameters were temperature, precipitation, wind speed, population size, vaccination rate and vaccination efficacy. Temperature was confirmed as the greatest predictor for ILI rates, with precipitation providing a small increase in predictive power. After training, the model was able to predict ILI rates 10 weeks out. As a result of this thesis, a framework was developed that may be applied to weekly ILI tracking as well as early prediction of outlier pandemic years

Viral factors in influenza pandemic risk assessment

The threat of an influenza A virus pandemic stems from continual virus spillovers from reservoir species, a tiny fraction of which spark sustained transmission in humans. To date, no pandemic emergence of a new influenza strain has been preceded by detection of a closely related precursor in an animal or human. Nonetheless, influenza surveillance efforts are expanding, prompting a need for tools to assess the pandemic risk posed by a detected virus. The goal would be to use genetic sequence and/or biological assays of viral traits to identify those non-human influenza viruses with the greatest risk of evolving into pandemic threats, and/or to understand drivers of such evolution, to prioritize pandemic prevention or response measures. We describe such efforts, identify progress and ongoing challenges, and discuss three specific traits of influenza viruses (hemagglutinin receptor binding specificity, hemagglutinin pH of activation, and polymerase complex efficiency) that contribute to pandemic risk

Humoral immune response after seasonal influenza vaccination

Introduction: Seasonal vaccination provides short-lasting and strain specific protection. Different factors influence efficacy and effectiveness and are related to the vaccine and the receptor. Those include adjuvants and strains contained, and age and sex of the receptor. The major target of antibodies after vaccination and infection is the hemagglutinin(HA) head with a limited number of immunodominant classically defined antigenic sites(Sb, Sa, Cb, Ca1 and Ca2) leading to strain-specific protection. In contrast, the HA stalk is subdominant and more conserved, and anti-stalk antibodies are cross-reactive among strains of the same phylogenetic group. Objective: To evaluate the humoral response after seasonal influenza vaccination considering vaccine composition, age and sex; and determine specific humoral responses against classically defined antigenic sites of the HA head and the stalk domain of influenza A virus. Methods: A total of 4,818 patients were recruited yearly during 28 seasons(1990-2018) from the Sentinel Surveillance Network of Castile and Leon (Spain). Three retrospective and two prospective designs were used. Serological analyses were conducted in samples obtained before and 28 days after seasonal vaccination by the National Influenza Centre of Valladolid (Spain) and the Mount Sinai Hospital of New York(US). Antibody levels against the HA head and stalk were measured by hemagglutination inhibition assay(HAI) and ELISAs. This research was approved by an Ethics Committee(PI 21-2314). Statistical analysis was performed taking significance at p<0.05. Results: Manuscript 1: Higher humoral response was found in the elderly against the A(H3N2) subtype with the adjuvanted influenza vaccine(FI 3.4, SCR 46%) compared to non-adjuvanted vaccine(FI 2.7,SCR 38.8%). However, the non-adjuvanted vaccine induced a better response against A(H1N1)pdm09(FI 4.5, SCR 57.3%) compared to the adjuvanted one(FI 3.2, SCR 45.8%) in the same group. Manuscript 2: Higher humoral response in terms of SCR against classical influenza A (H1N1), A(H1N1)pdm09 subtype and B/Victoria lineage(40.6%, 52.4% and 23.2%) were found in elderly women compared to elderly men(30.2%, 42.0% and 18.9%); and in FI(3.7 vs. 3.0) against A(H1N1)pdm09 in the same comparison. Manuscript 3: Significant heterotypic humoral responses were found between both influenza B lineages, but always lower than the homotypic response. Young adults showed higher homotypic(GMTi 3.2, SCR 41.6%) and heterotypic responses(GMTi 1.7, SCR 18.6%) with B/Victoria vaccine compared to the elderly while similar responses were found with B/Yamagata vaccine. Manuscript 4: Antibodies before vaccination were significantly reduced against all antigenic sites in the elderly and only against Sb and Ca2 in young adults compared to the Wt. Response to vaccination was reduced against all viruses compared to the Wt for the adjuvanted vaccine and only against Sb and Ca2 for the non-adjuvanted vaccine. The strongest reduction was observed against Sb followed by Ca2. Manuscript 5: All age groups elicited a significant increase of anti-stalk antibodies after seasonal influenza vaccination except for &#8805; 80-year-old cohort. Additionally, < 65-year-old vaccinees had higher titers against phylogenetic group 1 HAs vs. group 2. Similarly, <50-year-old showed higher increase of anti-stalk antibody titers(GMFR 1.69) compared to &#8805; 80-year-old(GMFR 1.08) for group 1. Conclusions: Age and sex play a role in vaccine responses with higher responses in elderly women compared to men against A(H1N1)pdm09. Better responses against this subtype were found with non-adjuvanted vaccines, while adjuvanted vaccines responded better against the A(H3N2) subtype in the elderly. However, seasonal vaccination can boost the induction of cross-reactive anti-stalk antibodies against phylogenetic groups 1 and 2 of HAs, with higher responses in younger populations. The immunodominance hierarchy of antigenic sites of HA head of the A(H1)pdm09 viruses is dominated by Sb followed by Ca2, but age and adjuvants can broaden responses towards subdominant epitopes. Finally, vaccination with a trivalent influenza vaccine provides cross-reactive protection against the B/lineage not contained.Introducción: La protección tras la vacunación antigripal es limitada y específica de cepa. Diferentes factores influyen en la eficacia y efectividad relacionados con la vacuna y con el receptor incluyendo: adyuvantes y composición; y edad y sexo. La principal diana de los anticuerpos tras la vacunación es la cabeza de la hemaglutinina (HA), inmunodominante y con capacidad de unión a un número limitado de sitios antigénicos(Sb, Sa, Cb, Ca1 y Ca2). En cambio, los anticuerpos frente al tallo de la HA, mucho más conservado y subdominante, presentan reactividad cruzada entre diferentes cepas del mismo grupo filogenético. Objetivo:Evaluar la respuesta humoral antigripal tras la vacunación considerando la composición de la vacuna, la edad y el sexo de los receptores; y, determinar las respuestas específicas frente a los sitios antigénicos clásicos de la cabeza y al tallo de la HA del virus de la gripe A. Métodos:Se reclutaron 4.818 pacientes durante 28 temporadas de gripe(1990-2018) por la Red Centinela de Vigilancia de Castilla y León(España). Se utilizaron tres diseños retrospectivos y dos prospectivos. Los análisis serológicos fueron realizados por el Centro Nacional de Gripe de Valladolid(España) y el Hospital Mount Sinai de Nueva York(EE.UU.), en muestras obtenidas antes y 28 días post-vacunación. Se detectaron anticuerpos frente a la cabeza y frente al tallo de la HA mediante ensayos de inhibición de la hemaglutinación (RIH) y ELISAs. Esta investigación fue aprobada por un Comité ético(PI 21-2314). Se realizó el análisis estadístico considerando significante p<0,05. Resultados Manuscrito 1: Se observó mayor respuesta en ancianos frente a A(H3N2) con vacuna adyuvada (RIC 3,4; 46%) en comparación con vacuna no adyuvada (RIC 2,7; TSC 38,8%). Sin embargo, la no adyuvada indujo una mejor respuesta frente a A(H1N1)pdm09 (RIC 4,5;TSC 57,3%) que la adyuvada (RIC 3,2;TSC 45,8%) en el mismo grupo etario. Manuscrito 2: Se encontró mayor respuesta frente a A(H1N1) clásico, A(H1N1)pdm09 y el linaje B/Victoria (TSC: 40,6%, 52,4% y 23,2%) en mujeres ancianas comparadas con hombres ancianos(TSC: 30,2%, 42,0% y 18,9%).También frente a A(H1N1)pdm09 en la misma comparación(RIC:3,7 vs. 3,0). Manuscrito 3: Se encontraron respuestas humorales heterotípicas frente a ambos linajes de gripe B, pero siempre inferiores a la homóloga. Los adultos mostraron respuestas homólogas(RIC:3,2;TSC:41,6%) y heterotípicas(RIC:1,7;TSC:18,6%) mayores con la vacuna de B/Victoria que los ancianos y similares con la vacuna B/Yamagata. Manuscrito 4: Los anticuerpos pre-vacunales se redujeron frente a todos los epítopos en ancianos y frente a Sb y Ca2 en adultos vs. Wt. La respuesta a la vacunación adyuvada se redujo frente a todos virus vs. Wt y sólo frente a Sb y Ca2 con vacuna no adyuvada. La mayor reducción se observó frente a Sb>Ca2. Manuscrito 5: Todos los grupos etarios aumentaron los anticuerpos frente al tallo tras la vacunación, excepto &#8805;80años. Además, los <65años presentaron títulos mayores frente al grupo filogenético 1 que al 2. Igualmente, los <50años mostraron un aumento mayor de anticuerpos frente al tallo del grupo 1 (RIC:1,69) en comparación con los &#8805;80años (RIC:1,08). Conclusiones: La edad y el sexo juegan un papel clave en las respuestas vacunales, siendo mayores en mujeres>65años que en hombres de la misma edad frente a A(H1N1)pdm09. Se observaron mejores respuestas a este subtipo con vacunas no adyuvadas, y frente a A(H3N2) con vacunas adyuvadas en ancianos . Sin embargo, la vacuna estacional puede inducir anticuerpos anti-tallo de los grupos filogenéticos 1 y ,2 con mayores respuestas en jóvenes. La inmunodominancia de los epítopos de la cabeza de la HA de los virus A(H1)pdm09 está dominada por Sb>Ca2; pudiendo ampliarse hacia epítopos subdominantes por la edad y los adyuvantes. Por último, la vacunación con una vacuna trivalente proporciona protección cruzada contra el linaje B no contenido en ella.Escuela de DoctoradoDoctorado en Investigación en Ciencias de la Salu

The social and political lives of zoonotic disease models: Narratives, science and policy

Zoonotic diseases currently pose both major health threats and complex scientific and policy challenges, to which modelling is increasingly called to respond. In this article we argue that the challenges are best met by combining multiple models and modelling approaches that elucidate the various epidemiological, ecological and social processes at work. These models should not be understood as neutral science informing policy in a linear manner, but as having social and political lives: social, cultural and political norms and values that shape their development and which they carry and project. We develop and illustrate this argument in relation to the cases of H5N1 avian influenza and Ebola, exploring for each the range of modelling approaches deployed and the ways they have been co-constructed with a particular politics of policy. Addressing the complex, uncertain dynamics of zoonotic disease requires such social and political lives to be made explicit in approaches that aim at triangulation rather than integration, and plural and conditional rather than singular forms of policy advice.ESR

New pandemics: HIV and AIDS, HCV and chronic hepatitis, Influenza virus and flu

New pandemics are a serious threat to the health of the entire world. They are essentially of viral origin and spread at large speed. A meeting on this topic was held in Lyon, France, within the XIXth Jacques Cartier Symposia, a series of France-Québec meetings held every year. New findings on HIV and AIDS, on HCV and chronic hepatitis, and an update on influenza virus and flu were covered during this meeting on December 4 and 5, 2006. Aspects of viral structure, virus-host interactions, antiviral defenses, drugs and vaccinations, and epidemiological aspects were discussed for HIV and HCV. Old and recent data on the flu epidemics ended this meeting.The meeting sponsors were the Centre Jacques Cartier, the Agence Nationale de Recherches sur le SIDA et les hépatites (ANRS) France, the Ecole Normale Supérieure en Sciences de Lyon, The Réseau SIDA et Maladies Infectieuses from the Fond de la Recherche en Santé du Québec (FRSQ), The Institut de Recherches Cliniques de Montréal (IRCM), Boehringer Ingelheim, Sanofi Aventis, ViroChem Pharma and Merck Frosst. The authors thank the speakers for their meeting abstracts and comments that helped writing this review