Nosocomial Outbreak of Multiple Bloodborne Viral Infections

In resource‐limited countries, nosocomial transmission of bloodborne pathogens is a major public health concern. After a major outbreak of human immunodeficiency virus (HIV) infection in ∼400 children in 1998 in Libya, we tested HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) markers in 148 children and collected epidemiological data in a subgroup of 37 children and 46 parents. HIV infection was detected in all children but one, with HCV or HBV coinfection in 47% and 33%, respectively. Vertical transmission was ruled out by analysis of parents' serology. The children visited the same hospital 1-6 times; at each visit, invasive procedures with potential blood transmission of virus were performed. HIV and HCV genotypic analyses identified a HIV monophyletic group, whereas 4 clusters of HCV sequences were identified. To our knowledge, this is the largest documented outbreak of nosocomial HIV transmissio

Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients

Background.Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. Methods.We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. Results.Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07% 2.0%. A range of 1 4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. Conclusions.Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrie

A genetic validation study reveals a role of vitamin D metabolism in the response to interferon-alfa-based therapy of chronic hepatitis C

Background: To perform a comprehensive study on the relationship between vitamin D metabolism and the response to interferon-α-based therapy of chronic hepatitis C. Methodology/Principal Findings: Associations between a functionally relevant polymorphism in the gene encoding the vitamin D 1α-hydroxylase (CYP27B1-1260 rs10877012) and the response to treatment with pegylated interferon-α (PEG-IFN-α) and ribavirin were determined in 701 patients with chronic hepatitis C. In addition, associations between serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3) and treatment outcome were analysed. CYP27B1-1260 rs10877012 was found to be an independent predictor of sustained virologic response (SVR) in patients with poor-response IL28B genotypes (15% difference in SVR for rs10877012 genotype AA vs. CC, p = 0.02, OR = 1.52, 95% CI = 1.061–2.188), but not in patients with favourable IL28B genotype. Patients with chronic hepatitis C showed a high prevalence of vitamin D insufficiency (25[OH]D3<20 ng/mL) during all seasons, but 25(OH)D3 serum levels were not associated with treatment outcome. Conclusions/Significance: Our study suggests a role of bioactive vitamin D (1,25[OH]2D3, calcitriol) in the response to treatment of chronic hepatitis C. However, serum concentration of the calcitriol precursor 25(OH)D3 is not a suitable predictor of treatment outcome

The dispersive velocity of compressional waves in magmatic suspensions

International audienceSummary The geophysical detection of magma bodies and the estimation of the dimensions, physical properties, and the volume fraction of each phase composing the magma is required to improve the forecasting of volcanic hazards and to understand transcrustal magmatism. We develop an analytical model to calculate P waves velocity in a three-phase magma consisting of crystals and gas bubbles suspended in a viscous melt. We apply our model to calculate the speed of sound as a function of the temperature in three magmas with different chemical compositions, representative of the diversity that is encountered in arc magmatism. The model employs the coupled phase theory that explicitly accounts for the exchanges of momentum and heat between the phases. We show that the speed of sound varies non-linearly with the frequency of an acoustic perturbation between two theoretical bounds. The dispersion of the sound in a magma results from the exchange of heat between the melt and the dispersed phases that affects the magnitude of their thermal expansions. The lower bound of the sound speed occurs at low frequencies for which all the constituents can be considered in thermal equilibrium, whereas the upper bound occurs at high frequencies for which the exchange of heat between the phases may be neglected. The presence of gas in a magma produces a sharp decrease in the velocity of compressional waves and generates conditions in which the dispersion of the sound is significant at the frequencies usually considered in geophysics. Finally, we compare the estimates of our model with the ones from published relationships. Differences are largest at higher frequencies and are &lt;10% for typical magma

The role of viscous particle segregation in forming chromite layers from slumped crystal slurries : insights from analogue experiments

The question of how the mineral layering in layered intrusions forms has been extensively debated for many decades. There are many types of layering and it is of course possible that a number of mechanisms are involved. Of particular interest is how chromite layers form, because these may contain valuable metals (such as platinum-group elements) in addition to Cr. One model for the formation of these layers is that they formed through slumping of semi-consolidated cumulates from the margins of the intrusion into the magma chamber. During this slumping, the grains are sorted by density and/or size differences. This study examines the viability of this process using analogue modelling. Starting materials (beads and glycerine) were scaled to match the density and size of the minerals (chromite, orthopyroxene and plagioclase) present in layered mafic-ultramafic layered intrusions and to match the density and viscosity of the silicate magma. A Perspex flume tank divided by a removable partition at one end was fully filled with glycerine. A homogenized mixture of the beads was placed in the smaller partition of the tank (representing the margins of the magma chamber). The tank was then inclined between 16° and 45°. The partition was removed and the beads flowed into the main part of the box. The experiments were recorded by video camera, allowing us to follow the dynamics of the flow during each run. Segregation of the beads was observed in the final deposits: the larger, less dense beads (representing plagioclase) concentrated at the top of the flow, with the intermediate-sized and medium density beads (representing orthopyroxene) in the middle and the smaller, denser beads (representing chromite) at the bottom, thus mimicking natural examples. In experiments where the angle of inclination was low, long, thin layers formed, such as those found in the Bushveld Complex. In experiments where the angle of inclination was high, thick but short layers formed. A dimensionless analysis allows better understanding of the dynamics of the flow. At the macroscopic scale, the flow regime is strongly influenced by the viscosity of the fluid and is considered macro-viscous, where the role of the interstitial liquid is non-negligible

Detection of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Pools of Sera Negative for Antibodies to HIV-1 and HIV-2

A total of 234 pools were prepared from 10,692 consecutive serum samples negative for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 collected at five virological laboratories (average pool size, 45 serum samples). Pools were screened for the presence of HIV-1 RNA by a modified commercial assay (Amplicor HIV-1 Monitor test) which included an additional polyethylene glycol (PEG) precipitation step prior to purification of viral RNA (PEG Amplicor assay). The sensitivity of this assay for HIV-1 RNA detection in individual serum samples within pools matches that of standard commercial assays for individual serum samples, i.e., 500 HIV-1 RNA copies per ml. Five pools were identified as positive, and each one contained one antibody-negative, HIV-1 RNA-positive serum sample, corresponding to an average of 1 infected sample per 2,138 serum samples. Retrospective analysis revealed that the five HIV-1 RNA-positive specimens originated from individuals who had symptomatic primary HIV-1 infection at the time of sample collection and who were also positive for p24 antigenemia. We next assessed the possibility of performing the prepurification step by high-speed centrifugation (50,000 × g for 80 min) of 1.5-ml pools containing 25 μl of 60 individual serum samples, of which only 1 contained HIV-1 RNA (centrifugation Amplicor assay). The sensitivity of this assay also matches the sensitivities of standard commercial assays for HIV-1 RNA detection in individual serum samples. The results demonstrate that both assays with pooled sera can be applied to the screening of large numbers of serum samples in a time- and cost-efficient manner

Minority quasispecies of drug-resistant HIV-1 that lead to early therapy failure in treatment-naive and -adherent patients

BACKGROUND: Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. METHODS: We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. RESULTS: Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07%-2.0%. A range of 1-4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. CONCLUSIONS: Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrier