Human IRF1 governs macrophagic IFN-γ immunity to mycobacteria

Inborn errors of human IFN-γ-dependent macrophagic immunity underlie mycobacterial diseases, whereas inborn errors of IFN-α/β-dependent intrinsic immunity underlie viral diseases. Both types of IFNs induce the transcription factor IRF1. We describe unrelated children with inherited complete IRF1 deficiency and early-onset, multiple, life-threatening diseases caused by weakly virulent mycobacteria and related intramacrophagic pathogens. These children have no history of severe viral disease, despite exposure to many viruses, including SARS-CoV-2, which is life-threatening in individuals with impaired IFN-α/β immunity. In leukocytes or fibroblasts stimulated in vitro, IRF1-dependent responses to IFN-γ are, both quantitatively and qualitatively, much stronger than those to IFN-α/β. Moreover, IRF1-deficient mononuclear phagocytes do not control mycobacteria and related pathogens normally when stimulated with IFN-γ. By contrast, IFN-α/β-dependent intrinsic immunity to nine viruses, including SARS-CoV-2, is almost normal in IRF1-deficient fibroblasts. Human IRF1 is essential for IFN-γ-dependent macrophagic immunity to mycobacteria, but largely redundant for IFN-α/β-dependent antiviral immunity

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Madagascar face au défi des Objectifs du millénaire pour le développement

L’engagement pris par 147 chefs d’État d’accorder un « soutien indéfectible » à la réalisation des Objectifs du millénaire pour le développement (OMD) a eu un impact fort sur la structuration de l’aide, sur la définition des politiques promues et sur leur mise en œuvre par les gouvernements des pays du Sud depuis dix ans. Mais quel en a été l’impact sur le développement des pays concernés et quelle distance reste-t-il à parcourir pour que les OMD soient atteints à l’échéance de 2015 ? Cet ouvrage propose un bilan à mi-parcours de l’état de réalisation des cinq premiers objectifs pour Madagascar. Outre un diagnostic chiffré des évolutions récentes observées en matière de pauvreté, de scolarisation, de santé ou encore d’égalité des sexes, il présence les résultats de recherches originales sur des thématiques aussi diverses que la demande d’éducation, les discriminations, la fécondité, l’occupation spatiale du territoire… Au travers d’analyses minutieuses d’économistes, de démographes, d’agronomes et de géographes, les facteurs de blocage susceptibles de freiner la marche de Madagascar vers la réalisation des OMD sont mis en lumière. Il est aujourd’hui certain que les OMD ne pourront pas être atteints en 2012, en partie du fait de la crise politique qui sévit à Madagascar depuis le début de l’année 2009. Mais en adoptant une perspective de long terme, ce livre apporte des éléments concerts, utiles pour la mise en place de politiques de lutte contre la pauvreté et la conduite d’actions de développement, dont il faudra tenir compte une fois la crise résolue

Conclusion

Au terme de cet ouvrage, il apparaît que Madagascar est encore loin d’avoir atteint les Objectifs du millénaire pour le développement. Le bilan est tout aussi mitigé concernant les objectifs du Madagascar Action Plan, y compris dans les domaines dans lesquels les ambitions ont été notablement réduites (pauvreté, par exemple). Certes, la situation varie très sensiblement d’un objectif à l’autre, mais presque aucun n’est en passe d’être atteint (tabl. 60). Avant de procéder au diagnostic chiffr..

Evolution of Arctic rivers recession flow: Global assessment and data-based attribution analysis

International audienceDue to polar amplification of climate change, high latitudes are warming up twice as fast as the rest of the world. This warming leads to permafrost thawing, which increases the thickness of the overlying active layer and modifies the subsurface hydrologic regime of the draining watershed, therefore affecting baseflow to surface water and modifying recession characteristics. The active layer thickening and the subsurface flow modification are assumed to be linearly correlated. The objective of this study is to test this assumption by quantifying the correlation between the temporal evolution of hydrologic parameters (recession slope and initial recession outflow) and 11 controlling factors (all linked to surface, subsurface and climatic conditions) for 336 Arctic catchments from 1970 to 2000. Contrary to previous studies, we demonstrate a clear decrease in recession slope and initial recession outflow over 1970-2000 for a majority of catchments at any significance level. We explain this result by identifying high topography and low permafrost extent as controlling factors that complexify the relationship between trends in recession parameters and active layer thickness evolution. The study goes further by identifying the mechanisms behind the complexification of the relationship: permafrost-extent loss, hydrologic-connectivity increase, flow-path-diversity increase, contributing drainage area multiplication. The novel aspect of the study lay behind the large number of studied catchments and the large range of controlling factors tested

Improving care for pregnant women with suspected influenza: A retrospective study before and after introduction of a rapid molecular assay.

ObjectivesDuring winter, after excluding obvious sites of infection, the most important diagnoses of isolated fever or influenza-like illness (ILI) to rule out are listeriosis and influenza, because of their severe potential outcomes and the straightforward management available for each. While awaiting laboratory results, the recommended management strategy is usually hospitalization for intravenous antibiotic therapy against potential listeria. This study sought to assess the effect of the use of a rapid test on hospitalization and antibiotic therapy rates.MethodsThe study included all pregnant women who consulted for ILI or isolated fever after clinical and laboratory investigations and had a molecular diagnostic assay for influenza during two time periods, both during influenza epidemics: before introduction of the rapid molecular assay use (period 1) and after this (period 2).ResultsThe study included 38 women during period 1 and 124 during period 2. The influenza diagnosis was confirmed for 24 of 38 (63.2%) women during period 1 and 65 of 124 (52.4%) women during period 2 (P = 0.24). The hospitalization rate fell significantly from period 1 to period 2, both in the total population (71.0% versus 44.3%, P = 0.004) and among women with confirmed influenza (83.3% versus 38.5%, PConclusionThe use of a rapid molecular assay for the diagnosis of influenza improved the management of pregnant women with an isolated fever or ILI by reducing the rates of unnecessary hospitalization and antibiotic therapy

Predictive factors of cytomegalovirus seropositivity among pregnant women in Paris, France.

Cytomegalovirus (CMV) is the most frequent cause of congenital infection. The objective of this study was to evaluate predictive factors for CMV seronegativity in a cohort of pregnant women in Paris, France.Pregnant women enrolled in a prospective cohort during the 2009 A/H1N1 pandemic were tested for CMV IgG antibodies. Variables collected were age, geographic origin, lifestyle, work characteristics, socioeconomic status, gravidity, parity and number of children at home. A multivariate logistic regression model was used to identify independent predictive factors for CMV seropositivity.Among the 826 women enrolled, 389 (47.1%) were primiparous, and 552 (67.1%) had Metropolitan France as a geographic origin. Out of these, 355 (i.e. 57.0%, 95% confidence interval (CI): [53.6%-60.4%]) were CMV seropositive: 43.7% (95% CI:[39.5%-47.9%]) in those whose geographic origin was Metropolitan France and 84.1% in those with other origins (95% CI:[79.2%-88.3%]). Determinants associated with CMV seropositivity in a multivariate logistic regression model were: (i) geographic origin (p<0.001(compared with Metropolitan France, geographic origins of Africa adjusted odds ratio (aOR) 21.2, 95% CI:[9.7-46.5], French overseas departments and territories and other origin, aOR 7.5, 95% CI:[3.9-14.6], and Europe or Asia, aOR 2.2, 95% CI: [1.3-3.7]); and (ii) gravidity (p = 0.019), (compared with gravidity = 1, if gravidity≥3, aOR = 1.5, 95% CI: [1.1-2.2]; if gravidity = 2, aOR = 1.0, 95% CI: [0.7-1.4]). Work characteristics and socioeconomic status were not independently associated with CMV seropositivity.In this cohort of pregnant women, a geographic origin of Metropolitan France and a low gravidity were predictive factors for CMV low seropositivity. Such women are therefore the likely target population for prevention of CMV infection during pregnancy in France