Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

<p>Abstract</p> <p>Background</p> <p>One of the major complications of <it>Plasmodium falciparum </it>infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine.</p> <p>Methods</p> <p>The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental <it>Plasmodium berghei </it>ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining.</p> <p>Results</p> <p>AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown.</p> <p>Conclusions</p> <p>The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of <it>P. berghei </it>ANKA-infected mice.</p

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

A large outbreak of acute muscular sarcocystosis (AMS) among international tourists who visited Tioman Island, Malaysia, is described. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS in their differential diagnosi

Identifying cost-competitive greenhouse gas mitigation potential of French agriculture

The agriculture, forestry and other land use sector are responsible for 24% (10–12 Pg CO2e per year) of anthropogenic greenhouse gas (GHG) emissions worldwide, with concomitant opportunities for mitigation. A scientific panel used deliberative methods to identify ten technical measures comprising 26 sub-measures to reduce GHG emissions from agriculture in France. Their abatement potential and cost are compared. The proposed measures concern nitrogen (N) management, management practices that increase carbon stocks in soils and biomass, livestock diets, and energy production and consumption on farms. Results show that the total abatement potential can be divided into three parts. One third of the cumulated abatement potential corresponds to sub-measures that can be implemented at a negative technical cost. These sub-measures focus on increased efficiency in input use including N fertilisers, animal feed and energy. The second third are sub-measures with moderate cost (€25 per metric Mg of avoided CO2e). These require investment with no direct financial return, the purchase of particular inputs, dedicated labour time or involve production losses. Assuming additivity, the cumulated abatement is 32.3 Tg CO2e per year in 2030, but only 10 Tg (i.e. 10% of current agricultural emissions) when calculated under current inventory rules. This study confirms that a significant abatement potential exists in the agricultural sector, with two thirds of this potential at low or even negative cost. This is likely to be an underestimated as it is based on a status quo of the current agricultural system. Results also emphasise the need to upgrade inventory rules so that efforts to reduce emissions can be accounted for

Paludisme d'importation des Comores à Marseille (période 2001 à 2011)

INTRODUCTION: à Marseille, où vivent près de 80 000 personnes originaires des Comores, plus de 80% des cas de paludisme ont été contractés aux Comores. Ceci s'explique par le flux migratoire intense entre Marseille et cet archipel, qui crée un véritable couloir de connaissances entre ces deux régions. OBJECTIFS: étudier les aspects épidémiologiques, cliniques et thérapeutiques du paludisme importé des Comores à Marseille, ainsi que leurs tendances évolutives sur 11 ans, afin de mettre en évidence une éventuelle transition générationnelle. MATERIEL ET METHODES: étude rétrospective, incluant tous les cas de paludisme importé des Comores traités dans les 4 hôpitaux publics de Marseille, entre le 01 janvier 2001 et le 31 décembre 2011. RESULTATS: 64,9% des cas étaient importés des Comores soit 1437 patients inclus dans l'étude (928 adultes et 509 enfants). Une chimioprophylaxie a été suivie par 45,3% des adultes contre 79,1% des enfants (p<0,001). Dans 87,3% des cas, elle n'était pas adaptée. Plasmodium falciparum était responsable de 83,2% des cas. Parmi les 147 accès graves, aucun décès n'a été observé. Le paludisme d'importation des Comores à Marseille est responsable de 4772 jours d'hospitalisation en 11 ans. Sur les 11 années d'étude, le nombre de cas de paludisme a diminué, particulièrement en 2011 avec une baisse de 83,3% du paludisme importé des Comores par rapport à 2010 alors que le paludisme importé des autres pays est resté stable. La 2e génération de migrants a plus souvent pris une chimioprophylaxie et a un délai de recours aux soins plus court (2 jours contre 3 jours, p=0,01). Malgré une parasitémie plus élevée, la fréquence des formes sévères y est plus faible par rapport à la 1ere génération (p=0,02). DISCUSSION: Les nombre de cas de paludisme importé des Comores a chuté de façon brutale en 2011, résultat d'une stratégie mise en place en 2010 aux Comores, associant distribution de moustiquaires imprégnées et d'insecticides de masse, tests de diagnostic rapide et traitement gratuit par artémétherluméfantrine. Le nombre d'accès gaves a diminué au cours de l'étude et ont été moins fréquents chez les enfants et les adultes jeunes de la 2e génération. Aucun paludisme grave n'a été traité par astérsunate qui n'est disponible en France que depuis 2011. CONCLUSION: Malgré son statu non immun, la 2e génération et les suivantes ne sont pas plus de formes graves, signe d'une prise de conscience de la nécessite de se protéger et d'une meilleure intégration dans le système de soins. Le nombre de cas de paludisme importé des Comores à Marseille diminue régulièrement, avec une cassure en 2011, probable fruit des politiques de lutte locale.INTRODUCTION: Some 80 000 Comorians people are living in Marseille and 80% fo malaria cases diagnosed in Marseille are imported from Comoros. It reflects the important human flow between this two geographical area, generating a real channel of knowledge on Comoros-acquired malaria. OBJECTIVES OF THE STUDY: Study epdidemiological, clinical, therapeutic characteristics of Comoros-acquiered malaria in Marseille, to analyze the 11 year evolution trends and to investigate a possible transition between generation in the Comorian population in regards to malaria. PATIENTS AND METHODOLOGY: retrospectie study, includinf all patients treasted for Comoros-acquiered malaria and admitted in one of the 4 public hospitals in Marseille, between January 1st, 2001 and December, 31th 2011. RESULTS: a total of 1437 patients were included during the study period (928 adults and 509 children, median age: 30 years, sex ratio: 1,33) and represented 64,9% of all of the malaria cases. The most frequent specie was P. falciparum (83,2%) and 147 severe malaria were described with non death. Only 25,9% have taken vector measures and 45,3% of the results have taken chemoprophylaxis, vs 79,1% of the children (p<0,001). It was inappropriate in 87,3% of cases. Half of population had seen a medical practitioner before hospital. The number of Comoros-acquired malaria managed in Marseille's hospitals progressively decreased over the studied period with a dramatic fall in 2011, bith in adults (n=11) and children (n=7), while the annual incidence of malaria imported from the other countries remained rather stable. DISCUSSION: the incidence of imported malaria from Comoros in Marseille had dramatically decreased in 2011. this may result from the significant fall of malaria transmission in the visited island, thanks to control vector diffusion, use of insecticide-treated mosquito nets, early diagnosis by rapid antigenic tests and free use of artemisin combined therapy. This hypothesis is confirmed by the local data. Chrildren and young adults, descendants of migrants, had a higher parasite density because of a lower immunity, but delared less severe malaria, because of a bette information and understanding of the prevention measures. CONCLUSION: despite their non immune condition, people of the 2nd generation and the folowers did not developed more severe malaria, possibly thanks to better understanding of precention measures. The recent strong reduction of malaria cases, imported from Comoros archipelago in Marseille in 2011 is a positive event, probably explained by local control measures.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-Bib. Serv.Santé Armées (751055204) / SudocSudocFranceF

Biodefence research: what to fund now?

International audienc