Influence of the HCV subtype on the virological response to pegylated interferon and ribavirin therapy

The hepatitis C virus genotype is considered to be the most important baseline predictor of a sustained virological response in patients with chronic hepatitis C treated with pegylated interferon and ribavirin. The influence of the subtype on the sustained virological response was investigated in patients infected with genotypes 1, 4, 5, or 6. This study was done on 597 patients with chronic hepatitis C who were given pegylated interferon and ribavirin for 48 weeks. The overall rate of sustained virological response in the 597 patients was 37.8%. Univariate analysis indicated that the sustained virological response of patients infected with subtype 1b (39%) tended to be higher than that of patients infected with subtype 1a (30.6%; P = 0.06) and it was similar to those patients infected with subtypes 4a (51.3%; P = 0.12) or 4d (51.7%; P = 0.16). Multivariate analysis indicated that five factors were independently associated with sustained virological response: the age (OR 0.97; 95% CI = 0.95–0.99), absence of cirrhosis (OR: 2.92; 95% CI = 1.7–5.0; P < 0.01), absence of HIV co‐infection (OR: 2.08; 95% CI = 1.2–3.5; P < 0.01), low baseline plasma HCV RNA concentration (OR: 1.74; 95% CI = 1.2–2.6; P < 0.01), and the subtype 1b (OR: 1.61; 95% CI = 1.0–2.5; P = 0.04) or subtypes 4a and 4d (OR: 2.03; 95% CI = 1.1–3.8; P = 0.03). In conclusion, among difficult‐to‐treat genotypes, the subtype 1a is associated with a lower response to anti‐HCV therapy than subtypes 1b, 4a, and 4d. J. Med. Virol. 81:2029–2035, 2009. © 2009 Wiley‐Liss, Inc.     

Re-localisation of a biopsy site in endoscopic images and characterisation of its uncertainty

Endoscopy guided probe-based optical biopsy is a new method for detecting sites for tissue biopsy and treatment. After detection, it can be useful to provide a visual aid in the endoscopic images to the endoscopist for example for guidance of forceps to the biopsy sites detected optically. A new method for re-localisation of these sites during the endoscopic examination is presented in this paper. It makes use of a sequence of endoscopic images, where the biopsy site location is known, in order to derive the same number of epipolar lines as images in the sequence projected onto a subsequent target image where the re-localised biopsy site needs to be computed. The location of the re-localised biopsy site is found by minimisation of the sum of squared distances to the epipolar lines. The method also determines analytically the uncertainty of the re-localised biopsy site. This provides the endoscopist with a confidence region around the re-localised biopsy site and a measure of the re-localisation precision. Simulations confirmed that the analytical uncertainty has the potential to be a good estimation of the experimental uncertainty. The method was tested on a physical phantom and on real data from four patients with eight sequences of images acquired during gastroscopy. The re-localisation precision and accuracy were estimated at 1 millimetre or better, which is sufficient for re-localisation of optical biopsy sites.     

Leishmania antimony resistance: what we know what we can learn from the field

Leishmania is the causative agent of various forms of leishmaniasis, a significant cause of morbidity and mortality. The clinical manifestations of the disease range from self-healing cutaneous and mucocutaneous skin ulcers to a fatal visceral form named visceral leishmaniasis or kala-azar. In the absence of any effective vaccine, the only means to treat and control leishmaniasis is affordable medication. The treatment choice is essentially directed by economic considerations; therefore, for a large majority of countries, chemotherapy relies only on the use of cheaper antimonial compounds. The emergence of antimonial therapy failure in India linked to proven parasite resistance has stressed questions about selective factors as well as transmission risk of drug resistance. Unfortunately, in most parts of the world, the frequency of parasite antimony resistance linked to treatment failure is unknown because of a lack of information on Leishmania antimony susceptibility. This information is crucial for addressing the risk of selection and transmission of drug-resistant parasites, particularly in areas where antimony is the only chemotherapeutic alternative. However, the poor knowledge about factors that favor selection of resistant parasites, the multiplicity of the agents that can play a role in the in vivo antileishmanial activity of antimony, and the lack of a standard protocol to diagnose and survey parasite resistance all contribute to insufficient monitoring of antimony resistance. In this review, we discuss on the factors potentially involved in the selection of antimony resistance in the field and discuss on the methods available for its diagnosis.     

Nitrous oxide (N2O) prevents latent pain sensitization and long-term anxiety-like behavior in pain and opioid-experienced rats

Improving rehabilitation after a severe tissue injury does not only require a reduction in pain, but also requires alleviation of negative affects, particularly anxiety. Although opioids remain unsurpassed analgesics to relieve moderate to severe pain, it has been shown that they also induce latent pain sensitization leading to long-lasting hyperalgesia via N-methyl-D-aspartate-(NMDA)-dependent pronociceptive systems. The present study evaluated the ability of nitrous oxide (N2O), a gas with NMDA antagonist properties, to prevent latent pain sensitization and long-term anxiety-like behavior (ALB) in rats with pain and opioid experiences. On D0, the pro-inflammatory drug carrageenan was injected in one hind paw of rats treated with fentanyl (4x100 microg/kg subcutaneously). Nociceptive threshold was evaluated with the paw pressure vocalization test. Rats were re-exposed to carrageenan or exposed to repeated non-nociceptive environmental stress (NNES) 2-3 weeks later. Rats were also challenged in the elevated plus-maze 2 weeks after fentanyl administration for evaluating ALB. The preventive effects of a single 4 h 50/50% N2O-O2 exposure performed on D0 was evaluated. Fifty percent N2O strongly reduced hyperalgesia induced by a first inflammation and its enhancement by fentanyl, and prevented exaggerated hyperalgesia induced by second inflammatory pain or NNES. Moreover, we provide first evidence that a high fentanyl dose induces long-term ALB 2 weeks after its administration. When associated with fentanyl, 50% N2O prevented such long-term ALB. These results suggest that a single exposure to N2O could improve post-injury pain management and facilitate rehabilitation especially when potent analgesics as opioids have to be used.     

Speckle-resolved optical coherence tomography for mesoscopic imaging within scattering media

Light scattering poses a challenge for imaging deep in scattering media as the ballistic light exponentially attenuates with depth. In contrast to the ballistic light, the multiply scattered light penetrates deeper and also contains information about the sample. One technique to image deeper is to selectively detect only a subset of the multiply scattered light, namely the ’snake’ photons, which are predominantly forward scattered and retain more direct information than the more strongly scattered light. In this work, we develop a technique, termed speckle-resolved optical coherence tomography (srOCT), for efficiently detecting these ’snake’ photons to enable imaging deeper in scattering media. The system couples spatio-angular filtering with speckle-resolved interferometric detection to preferentially and efficiently detect the weakly scattered ’snake’ photons. With our proof-of-concept system, we demonstrate depth-resolved imaging beyond the ballistic limit, up to a depth of 90 round-trip MFPs in a scattering phantom and a depth of 4.5 mm of chicken tissue at 0.4 mm axial and lateral resolution.     

Evaluation of Vector Competence of Ixodes Ticks for Kemerovo Virus

Tick-borne viruses are responsible for various symptoms in humans and animals, ranging from simple fever to neurological disorders or haemorrhagic fevers. The Kemerovo virus (KEMV) is a tick-borne orbivirus, and it has been suspected to be responsible for human encephalitis cases in Russia and central Europe. It has been isolated from Ixodes persulcatus and Ixodes ricinus ticks. In a previous study, we assessed the vector competence of I. ricinus larvae from Slovakia for KEMV, using an artificial feeding system. In the current study, we used the same system to infect different tick population/species, including I. ricinus larvae from France and nymphs from Slovakia, and I. persulcatus larvae from Russia. We successfully confirmed the first two criteria of vector competence, namely, virus acquisition and trans-stadial transmission, for both tick species that we tested. The estimated infection rates of engorged and moulted ticks suggest specificities between viral strains and tick species/developmental stages.