Retrovirus budding may constitute a port of entry for drug carriers

AbstractThis paper investigates the relation between viral infection and cell uptake of liposomes and nanoparticles. A defective virus was used to infect two types of cells: cells allowing virus budding (psi2neo cells) and cells bereft of a virus exit process (NIH 3T3 cells). This study has revealed that cell uptake of pH-sensitive-liposomes is highly dependent on the virus exit process, since it ensued only when virus budding occurred. This preferential uptake of pH-sensitive liposomes by infected cells was not carrier-specific because similar uptake was observed with non-biodegradable fluorescent nanoparticles using confocal microscopy. Also, inhibition of neo gene expression by oligonucleotide pH-sensitive-liposomes was only observed in the cell system (psi2neo) endowed with a virus exit process. Finally, increased membrane fluidity was noted in the infected cells, possibly reflecting membrane perturbation due to virus budding. We suggest that this membrane perturbation may be the key to the uptake of the different colloidal carriers. Infected cells could, thus, constitute a natural target for particulate drug carriers

an 8-year multi-centre observational study

Background Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. Methods The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. Results From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. Conclusion The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events

Weight gain at 3 months of antiretroviral therapy is strongly associated with survival: evidence from two developing countries

BACKGROUND: In developing countries, access to laboratory tests remains limited, and the use of simple tools such as weight to monitor HIV-infected patients treated with antiretroviral therapy should be evaluated. METHODS: Cohort study of 2451 Cambodian and 2618 Kenyan adults who initiated antiretroviral therapy between 2001 and 2007. The prognostic value of weight gain at 3 months of antiretroviral therapy on 3-6 months mortality, and at 6 months on 6-12 months mortality, was investigated using Poisson regression. RESULTS: Mortality rates [95% confidence interval (CI)] between 3 and 6 months of antiretroviral therapy were 9.9 (7.6-12.7) and 13.5 (11.0-16.7) per 100 person-years in Cambodia and Kenya, respectively. At 3 months, among patients with initial body mass index less than or equal to 18.5 kg/m (43% of the study population), mortality rate ratios (95% CI) were 6.3 (3.0-13.1) and 3.4 (1.4-8.3) for those with weight gain less than or equal to 5 and 5-10%, respectively, compared with those with weight gain of more than 10%. At 6 months, weight gain was also predictive of subsequent mortality: mortality rate ratio (95% CI) was 7.3 (4.0-13.3) for those with weight gain less than or equal to 5% compared with those with weight gain of more than 10%. CONCLUSION: Weight gain at 3 months is strongly associated with survival. Poor compliance or undiagnosed opportunistic infections should be investigated in patients with initial body mass index less than or equal to 18.5 and achieving weight gain less than or equal to 10%

Nouvelles approches thérapeutiques anti-inflammatoires et antiparasitaires dans les trypanosomoses

La trypanosomose humaine africaine (THA) et les trypanosomoses animales sont causees par l'inoculation vectorielle de trypanosomes. Différentes espèces de glossines sont vectrices des deux trypanosomes pathogènes pour l'Homme, Trypanosoma brucei gambiense en Afrique de l'Ouest et du Centre, et Trypanosoma brucei rhodesiense en Afrique de l'Est. Au point de piqure, se développe un chancre d'inoculation, puis le parasite envahit le sang et le tissu lymphatique (stade I), enfin, le franchissement de la barrière hémato-méningée définit la phase neurologique de l'affection (stade II). En raison du caractère fatal de l'évolution, le traitement est indispensable, bien que non dénué de toxicité. La suramine et la pentamidine, médicaments du stade I sont plus ou moins bien tolérés, et responsables de réactions médicamenteuses diverses. Le traitement de la phase II fait appel a un dérivé de l'arsenic, l'Arsobal®, qui est responsable, dans 5 a 10% des cas, d'encéphalopathies arsenicales mortelles. De plus, dans les trypanosomoses, de profondes modifications du système immunitaire sont observées. Une hypergammaglobulinemie, de nombreux auto-anticorps, et un syndrome inflammatoire intense sont observes tout au long de la maladie. Ce syndrome inflammatoire, lie a une production exagérée et persistante de cytokines pro-inflammatoires comme le TNF-[alpha], est également responsable d'une partie de la symptomatologie. En effet, il existe une corrélation entre la sévérité de la maladie et le taux de TNF-[alpha] circulant. Par ailleurs, dans les trypanosomoses animales, le role des radicaux libres a également été mis en évidence. C'est dire l'importance de la découverte de nouvelles approches thérapeutiques et cibles moléculaires dans les trypanosomoses. Les polyphenols végétaux possèdent de nombreuses propriétés, en particulier anti-infectieuses et anti-inflammatoires. Parmi les molécules testées, le quercetol s'est révélé très intéressant car il agit sur les deux versants de la pathologie, d'une part en possédant une activité trypanocide et, d'autre part, en inhibant la réponse inflammatoire induite par le parasite. Des études in vitro (cocultures parasites-cellules humaines) ont montre que l'activité trypanocide du quercetol s'exerce a des doses non toxiques pour les cellules humaines. Celle-ci est perçue pour des doses 300 fois plus élevées. L'étude de l'effet trypanocide du quercetol a révélé un nouveau mécanisme de destruction du parasite, l'apoptose, pouvant être visualisée par cryométrie de flux. Le quercetol et des molécules de structure voisine représentent donc une nouvelle approche thérapeutique très intéressante car peu toxique, peu onéreuse, et disponible dans les pays où sévissent les trypanosomoses. Différents polyphenols sont en cours d'étude, pour trouver une molécule active, susceptible de franchir la barrière hémato-méningée, et utilisable en phase neurologique de la THA. (Texte intégral

Corynebacterium mucifaciensin an immunocompetent patient with cavitary pneumonia

BACKGROUND: Corynebacterium mucifaciens has been mainly isolated from skin, blood and from other normally-sterile body fluids. It has rarely been described as a human pathogen since its description. CASE PRESENTATION: We herein report the first case of cavitary pneumonia due to C. mucifaciens in an immunocompetent man returning from Maghreb. CONCLUSION: C. mucifaciens should be considered as important human pathogen in patients with severe illness and compatible history of exposure even in individuals with no clearly identified immunosuppression

Evaluation of the diagnostic accuracy of prototype rapid tests for human African trypanosomiasis

Peer reviewedPublisher PD

The antigen presenting potential of Vγ9Vδ2 T-cells during Plasmodium falciparum blood-stage infection.

During Plasmodium falciparum infections, erythrocyte-stage parasites inhibit dendritic cell maturation and function; compromising development of effective anti-malarial adaptive immunity. Human Vγ9Vδ2 T-cells can act in vitro as APCs and induce αβ T-cell activation. However, the relevance of this activity in pathophysiological contexts in vivo has remained elusive. Since Vγ9Vδ2 T-cells are activated during the early immune response against P.falciparum infection, we investigated whether they could contribute to the instruction of adaptive immune responses toward malaria parasites. In P.falciparum-infected patients,Vγ9Vδ2 T-cells presented an increased surface expression of APC-associated markers HLA-DR and CD86. In response to infected red blood cells in vitro, Vγ9Vδ2 T-cells readily up-regulated surface expression of HLA-DR, HLA-ABC, CD40, CD80, CD83 and CD86, induced naive αβ T-cell responses, and cross-presented soluble prototypical protein to antigen-specific CD8+ T-cells. Our findings indicate that P. falciparum parasites induce genuine APC properties in Vγ9Vδ2 T-cells and qualify this subset as an alternative professional APC in malaria patients, which could be harnessed for therapeutic interventions and vaccine design

Imported Cutaneous Melioidosis in Traveler, Belgium

SCOPUS: le.jinfo:eu-repo/semantics/publishe