Analyse des réseaux sociaux appliquée à l'organisation d'événements sportifs : le cas de la World Gymnaestrada Lausanne 2011

Au cours des trente dernières années, de nombreuses villes, régions et pays, ont développé des politiques publiques d'accueil systématique d'événements sportifs. La concurrence globalisée qui en résulte demande des ressources dont les pouvoirs publics ne disposent pas nécessairement. Dès lors, la stratégie de développement par l'accueil d'événements sportifs est généralement rendue possible par un regroupement d'acteurs issus du secteur public, privé et du milieu associatif sous la forme d'une coalition. C'est à cette fragmentation de la gouvernance urbaine et au fonctionnement du réseau qui en découle que s'intéresse ce cahier. En prenant comme cas d'étude la World Gymnaestrada Lausanne 2011, il nous a été possible d'appliquer une analyse des réseaux sociaux à la coalition qui s'est formée autour de la manifestation. Cette approche, récente pour analyser les événements sportifs dans le contexte des villes européennes, nous a permis d'observer une prédominance des pouvoirs publics dans le réseau entourant la manifestation. Les observations suggèrent également que l'organisation de l'événement, et sa réussite, permet aux autorités de la ville de Lausanne de gagner en légitimité auprès des acteurs du réseau.

Immunodetection of Helicobacter sp. and the associated expression of ABO blood group antigens in the gastric mucosa of captive and free-living New World primates in the Amazon region

The histo-blood group ABH antigens were first described in humans. These antigens are only present on erythrocytes from great apes and humans, while in more primitive animals they are found in tissues and body fluids. The ABH antigens are mainly distributed in tissues exposed to the external environment and potentially serve as ligands for pathogens or inhibitors of tissue connections. The objective of this paper was two-fold: (i) to determine the presence of Helicobacter sp. in the gastric mucosa of 16 captive and 24 free-living New World monkeys and (ii) to evaluate the presence of histopathological alterations related to bacterial infection and the associated expression of ABH antigens in the tissue. Stomach tissues from 13 species of monkey were assessed using haematoxylin-eosin and modified Gram staining (Hucker) methods. An immunohistochemical analysis of the tissue revealed the presence of infectious bacteria that were characteristic of the genus Helicobacter sp. The results demonstrate that various species of monkey might be naturally infected with the Helicobacter sp. and that there is an increased susceptibility to infection. This study serves as a comparative analysis of infection between human and non-human primates and indicates the presence of a new species of Helicobacter.

Malaria-related anaemia: a Latin American perspective

Malaria is the most important parasitic disease worldwide, responsible for an estimated 225 million clinical cases each year. It mainly affects children, pregnant women and non-immune adults who frequently die victims of cerebral manifestations and anaemia. Although the contribution of the American continent to the global malaria burden is only around 1.2 million clinical cases annually, there are 170 million inhabitants living at risk of malaria transmission in this region. On the African continent, where Plasmodium falciparum is the most prevalent human malaria parasite, anaemia is responsible for about half of the malaria-related deaths. Conversely, in Latin America (LA), malaria-related anaemia appears to be uncommon, though there is a limited knowledge about its real prevalence. This may be partially explained by several factors, including that the overall malaria burden in LA is significantly lower than that of Africa, that Plasmodium vivax, the predominant Plasmodium species in the region, appears to display a different clinical spectrus and most likely because better health services in LA prevent the development of severe malaria cases. With the aim of contributing to the understanding of the real importance of malaria-related anaemia in LA, we discuss here a revision of the available literature on the subject and the usefulness of experimental animal models, including New World monkeys, particularly for the study of the mechanisms involved in the pathogenesis of malaria.

Not so disadvantaged: Portuguese migrants in Switzerland have a better access to healthcare and health status than Portuguese residents

Background: Most migrant studies have compared health characteristics between migrants and nationals of the host country. We aimed at comparing health characteristics of migrants with nationals from their home country. Methods: Portuguese national health survey (2005-6; 30,173 participants aged 18-75 years) and four national health surveys conducted in Switzerland (2002, 2004, 2007 and 2011, totalling 1,170 Portuguese migrants of the same age range). Self-reported data on length of stay, cardiovascular risk factors, healthcare use and health status were collected. Results: Resident Portuguese were significantly older and more educated than migrants. Resident Portuguese had a higher mean BMI and prevalence of obesity than migrants. Resident Portuguese also reported more frequently being hypertensive and having their blood pressure screened within the last year. On the contrary, migrant Portuguese were more frequently smokers, had a medical visit in the previous year more frequently and self-rated their health higher than resident Portuguese. After adjustment for age, gender, marital status and education, migrants had a higher likelihood smoking, of having a medical visit the previous year, and of self-rating their current health as good or very good than resident Portuguese. Compared to Portuguese residents, cholesterol screening in the previous year was more common only among migrants living in Switzerland for more than 17 years. Conclusion: Portuguese migrants in Switzerland do not differ substantially from resident Portuguese regarding most cardiovascular risk factors. Migrants appear to benefit from higher healthcare accessibility and consider themselves healthier than Portuguese residents.

Footprints of a trypanosomatid RNA world: pre-small subunit rRNA processing by spliced leader addition trans-splicing

The addition of a capped mini-exon [spliced leader (SL)] through trans-splicing is essential for the maturation of RNA polymerase (pol) II-transcribed polycistronic pre-mRNAs in all members of the Trypanosomatidae family. This process is an inter-molecular splicing reaction that follows the same basic rules of cis-splicing reactions. In this study, we demonstrated that mini-exons were added to precursor ribosomal RNA (pre-rRNA) are transcribed by RNA pol I, including the 5' external transcribed spacer (ETS) region. Additionally, we detected the SL-5'ETS molecule using three distinct methods and located the acceptor site between two known 5'ETS rRNA processing sites (A' and A1) in four different trypanosomatids. Moreover, we detected a polyadenylated 5'ETS upstream of the trans-splicing acceptor site, which also occurs in pre-mRNA trans-splicing. After treatment with an indirect trans-splicing inhibitor (sinefungin), we observed SL-5'ETS decay. However, treatment with 5-fluorouracil (a precursor of RNA synthesis that inhibits the degradation of pre-rRNA) led to the accumulation of SL-5'ETS, suggesting that the molecule may play a role in rRNA degradation. The detection of trans-splicing in these molecules may indicate broad RNA-joining properties, regardless of the polymerase used for transcription.

Leprosy frequency in the world, 1999-2010

In 1991, the World Health Organization (WHO) committed to reducing the prevalence of leprosy to below 1 in 10,000 inhabitants by 2000. Significant improvements in leprosy control have occurred, but leprosy remains a public health problem in many countries due to its high incidence and rate of transmission. This paper reviews data published by the WHO in the years 2000, 2005 and 2010. These data sets included 148 countries or territories that reported to the WHO at least once. Only four countries reported higher prevalence rates in 2010 than in 2000 and eight reported higher case detection rate (CDR) in 2009 than in 1999. Prevalence rate reductions were greater for the first five-year period examined, while CDR reductions were greater in the second five-year period. Thirty-six countries and territories reported at least one prevalence value higher than 1 per 10,000 inhabitants and 32 reported at least one CDR value higher than 9 per 100,000 inhabitants. A total of 39 countries fit at least one of these criteria and all were located in tropical regions.

Hansen's disease: a vanishing disease?

The introduction, implementation, successes and failures of multidrug therapy (MDT) in all Hansen's disease endemic countries are discussed in this paper. The high efficacy of leprosy treatment with MDT and the global reduction of prevalence led the World Health Organization, in 1991, to establish the goal of elimination of Hansen's disease (less than 1 patient per 10,000 inhabitants) to be accomplished by the year 2000. Brazil, Nepal and East Timor are among the few countries that didn't reach the elimination goal by the year 2000 or even 2005. The implications of these aspects are highlighted in this paper. Current data from endemic and previously endemic countries that carry a regular leprosy control programme show that the important fall in prevalence was not followed by the reduction of the incidence. This means that transmission of Mycobacterium leprae is still an issue. It is reasonable to conclude that we are still far from the most important goal of Hansen's disease control: the interruption of transmission and reduction of incidence. It is necessary to emphasize to health managers the need of keeping Hansen's disease control activities to better develop control programmes in the future. The recent international proposal to interrupt the transmission of leprosy by the year 2020 seems to unrealistic and it is discussed in this paper. The possibility of epidemiological impact related to the human immunodeficiency virus/Hansen's disease coinfection is also considered.

Comparison of two rapid tests for anti-phenolic glycolipid-I serology in Brazil and Nepal

The diagnosis of leprosy continues to be based on clinical symptoms and early diagnosis and treatment are critical to preventing disability and transmission. Sensitive and specific laboratory tests are not available for diagnosing leprosy. Despite the limited applicability of anti-phenolic glycolipid-I (PGL-I) serology for diagnosis, it has been suggested as an additional tool to classify leprosy patients (LPs) for treatment purposes. Two formats of rapid tests to detect anti-PGL-I antibodies [ML immunochromatography assay (ICA) and ML Flow] were compared in different groups, multibacillary patients, paucibacillary patients, household contacts and healthy controls in Brazil and Nepal. High ML Flow intra-test concordance was observed and low to moderate agreement between the results of ML ICA and ML Flow tests on the serum of LPs was observed. LPs were "seroclassified" according to the results of these tests and the seroclassification was compared to other currently used classification systems: the World Health Organization operational classification, the bacilloscopic index and the Ridley-Jopling classification. When analysing the usefulness of these tests in the operational classification of PB and MB leprosy for treatment and follow-up purposes, the ML Flow test was the best point-of-care test for subjects in Nepal and despite the need for sample dilution, the ML ICA test yielded better performance among Brazilian subjects. Our results identified possible ways to improve the performance of both tests.

Evaluation of the WHO classification of dengue disease severity during an epidemic in 2011 in the state of Ceará, Brazil

In 2009, the World Health Organization (WHO) issued a new guideline that stratifies dengue-affected patients into severe (SD) and non-severe dengue (NSD) (with or without warning signs). To evaluate the new recommendations, we completed a retrospective cross-sectional study of the dengue haemorrhagic fever (DHF) cases reported during an outbreak in 2011 in northeastern Brazil. We investigated 84 suspected DHF patients, including 45 (53.6%) males and 39 (46.4%) females. The ages of the patients ranged from five-83 years and the median age was 29. According to the DHF/dengue shock syndrome classification, 53 (63.1%) patients were classified as having dengue fever and 31 (36.9%) as having DHF. According to the 2009 WHO classification, 32 (38.1%) patients were grouped as having NSD [4 (4.8%) without warning signs and 28 (33.3%) with warning signs] and 52 (61.9%) as having SD. A better performance of the revised classification in the detection of severe clinical manifestations allows for an improved detection of patients with SD and may reduce deaths. The revised classification will not only facilitate effective screening and patient management, but will also enable the collection of standardised surveillance data for future epidemiological and clinical studies.

Risk of symptomatic dengue for foreign visitors to the 2014 FIFA World Cup in Brazil

Brazil will host the FIFA World Cup™, the biggest single-event competition in the world, from June 12-July 13 2014 in 12 cities. This event will draw an estimated 600,000 international visitors. Brazil is endemic for dengue. Hence, attendees of the 2014 event are theoretically at risk for dengue. We calculated the risk of dengue acquisition to non-immune international travellers to Brazil, depending on the football match schedules, considering locations and dates of such matches for June and July 2014. We estimated the average per-capita risk and expected number of dengue cases for each host-city and each game schedule chosen based on reported dengue cases to the Brazilian Ministry of Health for the period between 2010-2013. On the average, the expected number of cases among the 600,000 foreigner tourists during the World Cup is 33, varying from 3-59. Such risk estimates will not only benefit individual travellers for adequate pre-travel preparations, but also provide valuable information for public health professionals and policy makers worldwide. Furthermore, estimates of dengue cases in international travellers during the World Cup can help to anticipate the theoretical risk for exportation of dengue into currently non-infected areas.

The remarkable journey of adaptation of the Plasmodium falciparum malaria parasite to New World anopheline mosquitoes

Plasmodium falciparum originated in Africa, dispersed around the world as a result of human migration and had to adapt to several different indigenous anopheline mosquitoes. Anophelines from the New World are evolutionary distant form African ones and this probably resulted in a more stringent selection of Plasmodium as it adapted to these vectors. It is thought that Plasmodium has been genetically selected by some anopheline species through unknown mechanisms. The mosquito immune system can greatly limit infection and P. falciparum evolved a strategy to evade these responses, at least in part mediated by Pfs47, a highly polymorphic gene. We propose that adaptation of P. falciparum to new vectors may require evasion of their immune system. Parasites with a Pfs47 haplotype compatible with the indigenous mosquito vector would be able to survive and be transmitted. The mosquito antiplasmodial response could be an important determinant of P. falciparum population structure and could affect malaria transmission in the Americas.

Prophylactic isolated limb perfusion for localized, high-risk limb melanoma: results of a multicenter randomized phase III trial. European Organization for Research and Treatment of Cancer Malignant Melanoma Cooperative Group Protocol 18832, the World Health Organization Melanoma Program Trial 15, and the North American Perfusion Group Southwest Oncology Group-8593.

PURPOSE: Patients with primary cutaneous melanoma > or = 1.5 mm in thickness are at high risk of having regional micrometastases at the time of initial surgical treatment. A phase III international study was designed to evaluate whether prophylactic isolated limb perfusion (ILP) could prevent regional recurrence and influence survival. PATIENTS AND METHODS: A total of 832 assessable patients from 16 centers entered the study; 412 were randomized to wide excision (WE) only and 420 to WE plus ILP with melphalan and mild hyperthermia. Median age was 50 years, 68% of patients were female, 79% of melanomas were located on a lower limb, and 47% had a thickness > or = 3 mm. RESULTS: Median follow-up duration is 6.4 years. There was a trend for a longer disease-free interval (DFI) after ILP. The difference was significant for patients who did not undergo elective lymph node dissection (ELND). The impact of ILP was clearly on the occurrence-as first site of progression - of in-transit metastases (ITM), which were reduced from 6.6% to 3.3%, and of regional lymph node (RLN) metastases, with a reduction from 16.7% to 12.6%. There was no benefit from ILP in terms of time to distant metastasis or survival. Side effects were higher after ILP, but transient in most patients. There were two amputations for limb toxicity after ILP. CONCLUSION: Prophylactic ILP with melphalan cannot be recommended as an adjunct to standard surgery in high-risk primary limb melanoma.

Characterization of SKI-1/S1P-mediated processing of Arenavirus glycoprotein precursors

Arenaviruses are rodent-born world-wide distributed negative strand RNA viruses that comprise a number of important human pathogens including Lassa virus (LASV) which causes more than 3 00'000 infections annually in Western Africa. Lymphocytic choriomeningitis virus (LCMV) is the prototypic member of the arenavirus family, which is divided in two major subgroups according to serological properties and geographical distribution, the Old World and New World arenaviruses. The envelope glycoprotein precursors (GPCs) of arenaviruses have to undergo proteolytic processing to acquire biological function and to be incorporated into progeny virions. A cellular enzyme is responsible for this processing: the Subtilisin Kexin Isozyme-1 or Site-1 protease (SKI- 1/S1P). In this thesis we have studied the relationship between SKI-1/S1P and the envelope GPs of arenaviruses. In a first project, we investigated the molecular interactions between SKI-1/SIP and arenavirus GPCs. Using SKI-1/SIP mutants, we confirmed previously published observations locating LCMV GPC and LASV GPC processing in the Late Golgi/TGN and ER/cis-Golgi, respectively. A single mutation in the cleavage site of LCMV was sufficient to re-locate SKI- 1/SIP-mediated processing from the late Golgi/TGN to the ER/cis-Golgi. We then demonstrated that the transmembrane domain, the C-terminal tail and the phosphorylation sites of SKI-1/S1P are dispensable for GPC processing. Additionally we identified a SKI- 1/S1P mutant defective for autoprocessing at site Β, B' that was selectively impaired in processing of viral GPCs but not cellular substrates. We also showed that a soluble variant of SKI-1/SIΡ was unable to cleave envelope GPs at the cell surface when added in the culture medium. This study highlighted a new target for small molecule inhibitors that would specifically impair GPC but not cellular substrate processing. In a second project, we identified and characterized two residues: LASV GPC Y253 and SKI-1/S1P Y285 that are important for the SKI-1/SIP-mediated LASV GPC cleavage. An alignment of GPC sequences revealed a conserved aromatic residue in P7 position in the GPCs of Old World and Clade C of New World arenaviruses. Mutations in GPC at position P7 impaired processing efficiency. In SKI-1/S1P, mutating Y285 into A negatively affected processing of substrates containing aromatic residues in P7, without affecting others. This property could be used to develop specific drugs targeting SKI-1/SIP-mediated cleavage of LASV GPC without affecting cellular substrates. As a third project we studied the role of the SKI-1/SIP-mediated processing and the unusual stable signal peptide (SSP) for the folding and secretion of soluble forms of the ectodomain of LASV and LCMV glycoproteins. We provide evidence that the transmembrane domain and the cytosolic tail are crucial for the stability of the prefusion conformation of arenavirus GP and that the SSP is required for transport and processing of full-length GP, but not the soluble ectodomain per se. Taken together, these results will lead to a better understanding of the complex interactions between arenavirus GPCs and SKI-1/S IP, paving the avenue for the development of novel anti-arenaviral therapeutics. - Les Arenavirus sont des virus à ARN négatif distribués mondialement et portés par les rongeurs. Cette famille de virus comprend des virus hautement pathogènes pour l'homme comme le virus de Lassa (LASV) qui cause plus de 300Ό00 infections par année en Afrique de l'Ouest. Le virus de la chorioméningite lymphocytaire (LCMV) est le représentant de cette famille qui est divisée en deux sous-groupes selon des critères sérologiques et de distributions géographiques: arenavirus du Nouveau et de l'Ancien monde. Les glycoprotéines d'enveloppe de ces virus (GPCs) doivent être clivées pour être incorporées dans le virus et ainsi lui permettre d'être infectieux. Une enzyme cellulaire est responsable de ce clivage : la Subtilisin Kexin Isozyme-1 ou protéase Site-1 (SKI-l/SlP). Dans cette thèse, nous avons étudié la relation entre cette enzyme cellulaire et les GPs des arenavirus. Dans un premier temps, nous avons étudié les interactions moléculaires entre SKI- 1/S1P et GPC. A l'aide de mutants de SKI-l/SlP, nous avons confirmé des résultats précédemment publiés montrant que les glycoprotéines d'enveloppe de LASV sont clivés dans le réticulum endoplasmique/cis-Golgi alors que celles de LCMV sont clivées dans le Golgi tardif/TGN. Une seule mutation dans le site de clivage de la glycoprotéine de LCMV est suffisante pour changer le compartiment cellulaire dans lequel est clivée cette glycoprotéine. Ensuite, nous avons démontré que le domaine transmembranaire, la partie cytosolique C-terminale ainsi que les sites de phosphorylations de cette enzyme ne sont pas indispensables pour permettre le clivage de GPC. De plus, nous avons identifié un mutant de SKI-l/SlP dans lequel Γ autoprocessing au site B,B' est impossible, incapable de cliver GPC mais toujours pleinement fonctionnelle envers ses substrats cellulaires. Nous avons également démontré qu'une forme soluble de SKI-l/SlP ajoutée dans le milieu de culture n'est pas capable de couper GPC à la surface de la cellule. Cette étude a défini une nouvelle cible potentielle pour un médicament qui inhiberait le clivage des glycoprotéines des arenavirus sans affecter les processus normaux de la cellule. Dans un second project, nous avons identifié deux acides aminés, LASV GPC Y253 et SKI-l/SlP Y285, qui sont important pour le clivage de LASV GPC. Un alignement des séquences de clivage des GPCs a montré qu'un résidu aromatique est conservé en position P7 du site de clivage chez tous les arenavirus de l'Ancien monde et dans le clade C des arenavirus du Nouveau monde. Une mutation de cet acide aminée dans GPC réduit l'efficacité de clivage par SKI-l/SlP. Mutation de la tyrosine 285 de SKI-l/SlP en alanine affecte négativement le clivage des substrats contenant un résidu aromatique en position P7 sans affecter les autres. Cette propriété pourrait être utilisée pour le développement de médicaments spécifiques ciblant le clivage de GPC. Finalement, nous avons étudié le rôle du processing accomplit par SKI-l/SlP et du signal peptide pour le pliage et la sécrétion de formes solubles des glycoprotéines de LASV et LCMV. Nous avons montré que le domaine transmembranaire et la partie cytosolique de GP sont crucials pour la stabilité de la conformation pre-fusionnelle des GPs et que SSP est nécessaire pour le transport et le processing de GP, mais pas de son ecto-domaine soluble. En conclusion, les résultats obtenus durant cette thèse permettrons de mieux comprendre les interactions complexes entre SKI-l/SlP et les glycoprotéines des arenavirus, ouvrant le chemin pour le développement de nouveaux médicaments anti-arénaviraux.