Landscape epidemiology of an insect-vectored plant-pathogenic bacterium : Candidatus Liberibacter solanacearum in carrots in Finland

Crop diseases may be affected by landscape composition, but limited quantitative information is available. We studied the effects of landscape factors on the incidence of the psyllid-transmitted bacterium Candidatus Lib-eribacter solanacearum (CLso) haplotype C in carrots in Finland. Samples were collected from 104 carrot fields in 2013 and 2014. The relationship between CLso incidence and landscape data was analysed using logistic regression. The probability of CLso infection significantly increased with increasing area of carrot cultivation, up to a 10 km radius. Spruce biomass (spruce is the winter shelter of the main vector, Trioza apicalis,) within 200 m distance from the field edges affected CLso infection in landscapes with a low to medium area proportion of carrot cultivation but not in landscapes with a high proportion of carrot fields. Disease incidence was higher on clay soils than on mineral soils. The findings illustrate the importance of movement of the vector between carrot and spruce and highlight this disease as a landscape-scale disease syndrome, which needs to be managed also at the landscape level. Moderating the proportion of carrot fields in a carrot production landscape could be a key to manage the disease by breaking the epidemic cycle at the landscape level.Peer reviewe

Anti-influenza chemotherapies

The recent outbreaks of avian influenza A (H5N1) virus have called attention to the need for antiviral treatments to use in the event of pandemic influenza. The goal of antiviral treatments is also to reduce symptoms and complications associated with seasonal epidemics. Two classes of antiviral drugs, M2 proton channel inhibitors (amantadine, rimantadine) and neuraminidase inhibitors (zanamivir, oseltamivir), are effective for the chemoprophylaxis and treatment of influenza. Antiviral resistance is especially frequent with treatment with M2 inhibitors, and limits their clinical use. Resistance to oseltamivir during treatment has been described recently in several Vietnamese patients infected with H5N1. A close monitoring of antiviral resistance is needed, as is further research into the development of new agents, potentially targeting other viral proteins such as hemagglutinin or polymerase, and which could be used in combination chemotherapies.L'actuelle épizootie de grippe A (H5N1) souligne la nécessité de traitements antiviraux pour faire face à une éventuelle pandémie grippale. Les traitements anti-influenza ont aussi pour objectif de réduire les symptômes et complications survenant lors des épidémies saisonnières. Deux classes d'antiviraux, les inhibiteurs du canal à protons M2 (amantadine, rimantadine), et les inhibiteurs de neuraminidase (zanamivir, oseltamivir), ont une efficacité prophylactique et thérapeutique. L'émergence de virus résistants est particulièrement fréquente lors du traitement avec les inhibiteurs de M2, et limite leur utilisation. Le développement d'une résistance à l'oseltamivir a été décrit chez plusieurs patients infectés avec le virus H5N1. Une surveillance étroite de la résistance aux anti-viraux s'impose, ainsi que le développement de nouveaux composés, pouvant cibler éventuellement d'autres protéines virales telles que l'hémagglutinine ou la polymérase, et pouvant être utilisés en polychimiothérapies

Standard ganciclovir dosing results in slow decline of cytomegalovirus viral loads

BACKGROUND: Cytomegalovirus (CMV) can cause severe disease, including rejection in transplant recipients. Ganciclovir and its oral prodrug valganciclovir have been used as first-line therapy for CMV disease in transplant recipients. The exposure targets of ganciclovir are not exactly known, and toxicity and resistance have interfered with ganciclovir therapy. OBJECTIVES: To evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of ganciclovir in transplant recipients. METHODS: We used patient data from a previous observational study on ganciclovir therapeutic drug monitoring (TDM) in prophylaxis and therapy. The ganciclovir concentrations and CMV viral loads were determined during routine clinical care. The PK/PD population modelling and simulations were done with non-parametric methodology using the Pmetrics program. RESULTS: Eighty-five patients were included in the PK modelling. The final PK model was a two-compartment model with first-order absorption and elimination. A subset of 17 patients on CMV therapy were included in the PD modelling. A median of 4 (range 2–8) viral loads were obtained per patient. A simulation of 10 000 patients showed that an approximately 1 log(10) reduction of CMV viral load will be observed after 12.5 days at the current recommended dose. CONCLUSIONS: The developed linked PK/PD population model and subsequent PD simulations showed slow decline of CMV viral load and it appears that dosing of (val)ganciclovir in this study might have been inadequate to achieve fast reduction of viral load. It is clear that further studies are needed to specify the PD effects of ganciclovir by performing systematic measurements of both ganciclovir concentrations and CMV viral loads

Enhancement of the influenza A hemagglutinin (HA)-mediated cell-cell fusion and virus entry by the viral neuraminidase (NA).

International audienceBACKGROUND: The major role of the neuraminidase (NA) protein of influenza A virus is related to its sialidase activity, which disrupts the interaction between the envelope hemagglutinin (HA) protein and the sialic acid receptors expressed at the surface of infected cells. This enzymatic activity is known to promote the release and spread of progeny viral particles following their production by infected cells, but a potential role of NA in earlier steps of the viral life cycle has never been clearly demonstrated. In this study we have examined the impact of NA expression on influenza HA-mediated viral membrane fusion and virion infectivity. METHODOLOGY/PRINCIPAL FINDINGS: The role of NA in the early stages of influenza virus replication was examined using a cell-cell fusion assay that mimics HA-mediated membrane fusion, and a virion infectivity assay using HIV-based pseudoparticles expressing influenza HA and/or NA proteins. In the cell-cell fusion assay, which bypasses the endocytocytosis step that is characteristic of influenza virus entry, we found that in proper HA maturation conditions, NA clearly enhanced fusion in a dose-dependent manner. Similarly, expression of NA at the surface of pseudoparticles significantly enhanced virion infectivity. Further experiments using exogenous soluble NA revealed that the most likely mechanism for enhancement of fusion and infectivity by NA was related to desialylation of virion-expressed HA. CONCLUSION/SIGNIFICANCE: The NA protein of influenza A virus is not only required for virion release and spread but also plays a critical role in virion infectivity and HA-mediated membrane fusion