Randomized controlled trial of Hepatitis B virus vaccine in HIV-1-infected patients comparing two different doses

BACKGROUND: Co-infection with hepatitis B virus (HBV) and human immunodeficiency virus (HIV) is not infrequent as both share same route of exposure. The risk of developing chronic hepatitis B virus is 6%, in general population but can reach 10–20% in HBV/HIV co-infected patients. When compared to general population, the response rate to HBV vaccine in HIV-infected patients is diminished, so previous studies have tried to improve this response using variety of schedules, doses and co-administration of immunomodulators. The purpose of this study was to evaluate two doses of recombinant HBV vaccine (10 or 40 μg), IM at 0, 1 and 6 months. Vaccination response was measured 30–50 days after last dose; titers of >9.9 IU/L were considered positive. RESULTS: Seventy-nine patients were included, 48 patients (60.7%) serconverted. Thirty-nine patients (49.3%) received 10 μg vaccine dose, 24 patients (61.5%) seroconverted. Forty patients (50.7%) received 40 μg vaccine dose, 24 (60%) seroconverted. There were no differences between two doses. A statistically significant higher seroconversion rate was found for patients with CD4 cell counts at vaccination ≥ 200 cel/mm3 (33 of 38 patients, 86.8%), compared with those with CD4 < 200 cel/mm3 (15 of 41, 36.6%), [OR 11.44, 95% IC 3.67–35.59, p = 0.003], there were no differences between two vaccine doses. Using the logistic regression model, CD(4 )count <200 cel/mm(3 )were significantly associated with non serologic response (p = 0.003). None other variables such as gender, age, risk exposure for HIV, viral load, type or duration of HAART or AIDS-defining illness, were asociated with seroconversion. CONCLUSION: In this study, an increase dose of HBV vaccine did not show to increase the rate of response in HIV infected subjects. The only significant findings associated to the response rate was that a CD4 count ≥ 200 cel/mm(3), we suggest this threshold at which HIV patients should be vaccinated

Use of Aerial Laser Scanning to Assess the Effect on C Sequestration of Oak (Quercus ilex L. subsp. ballota [Desf.]Samp-Q. suber L.) Afforestation on Agricultural Land

Conversion of agricultural lands to forest plantations to mitigate rising atmospheric carbon dioxide (CO2) has been proposed, but it depends on accurate estimation of the on-site carbon (C) stocks distribution. The use of aerial laser scanning (ALS) data is a rapidly evolving technology for the quantification of C stocks. We evaluated the use of allometric models together with high-density ALS data for the quantification of biomass and soil C stocks in a 14-year-old Quercus ilex and Q. suber plantation in Southwestern Spain. In 2010, a field survey was performed and tree dasometric and biomass variables were measured. Forty-five soil profiles (N = 180 soil samples) were taken systematically and the soil organic C content (SOC) was determined. Biomass and soil organic C values were regressed against individual dasometric variables and total tree height was used as a predictor variable. Aerial laser scanning data were acquired with a point density of 12 points m−2. Relationships among ALS metrics and tree height were determined using stepwise regression models and used in the allometric models to estimate biomass and SOC C stocks. Finally, a C stock map of the holm-cork oak cover in the study area was generated. We found a tree total biomass of 27.9 kg tree−1 for holm oak and 41.1 kg tree−1 for cork oak. In the holm oak plantation, the SOC content was 36.90 Mg ha−1 for the layer 0–40 cm (SOC40) under the tree crown and 29.26 Mg ha−1 for the inter-planted area, with significant differences from the reference agricultural land (33.35 Mg ha−1). Linear regression models were developed to predict the biomass and SOC at the tree scale, based on tree height (R2 >0.72 for biomass, and R2 >0.62 for SOC). The overall on-site C stock in the holm-cork oak plantation was 35.11 Mg ha−1, representing a net C stock rise of 0.47 Mg ha−1 yr−1. The ALS data allows a reliable estimation of C stocks in holm and cork oak plantations and high-resolution maps of on-site C stocks are useful for silvicultural planning. The cost of ALS data acquisition has decreased and this method can be generalised to plantations of other Mediterranean species established on agricultural lands at regional scales. However, an increase of filed data and the availability of local biomass and, in particular, SOC will improve accurate quantification of the C stocks from allometric equations, and extrapolation to large planted areas

Long-Term Carbon Sequestration in Pine Forests under Different Silvicultural and Climatic Regimes in Spain

Proactive silviculture treatments (e.g., thinning) may increase C sequestration contributing to climate change mitigation, although, there are still questions about this effect in Mediterranean pine forests. The aim of this research was to quantify the storage of biomass and soil organic carbon in Pinus forests along a climatic gradient from North to South of the Iberian Peninsula. Nine experimental Pinus spp trials were selected along a latitudinal gradient from the pre-Pyrenees to southern Spain. At each location, a homogeneous area was used as the operational scale, and three thinning intensity treatments: unthinned or control (C), intermediate thinning (LT, removal of 30–40% of the initial basal area) and heavy thinning (HT, removal of 50–60%) were conducted. Growth per unit area (e.g., expressed as basal area increment-BAI), biomass, and Soil Organic Carbon (SOC) were measured as well as three sets of environmental variables (climate, soil water availability and soil chemical and physical characteristics). One-way ANOVA and Structural Equation Modelling (SEM) were used to study the effect of thinning and environmental variables on C sequestration. Biomass and growth per unit area were higher in the control than in the thinning treatments, although differences were only significant for P. halepensis. Radial growth recovered after thinning in all species, but it was faster in the HT treatments. Soil organic carbon (SOC10, 0–10 cm depth) was higher in the HT treatments for P. halepensis and P. sylvestris, but not for P. nigra. SEM showed that Pinus stands of the studied species were beneficed by HT thinning, recovering their growth quickly. The resulting model explained 72% of the variation in SOC10 content, and 89% of the variation in silvicultural condition (basal area and density) after thinning. SOC10 was better related to climate than to silvicultural treatments. On the other hand, soil chemical and physical characteristics did not show significant influence over SOC10- Soil water availability was the latent variable with the highest influence over SOC10. This work is a new contribution that shows the need for forest managers to integrate silviculture and C sequestration in Mediterranean pine plantations

An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy.We expressed the globular HA receptor binding domain, referred to here as HA(63-286)-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA(63-286)-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model.Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3.

CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain. Methods: In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were bla OXA-48 (263/377), bla KPC-3 (62/377), bla VIM-1 (28/377), and bla NDM-1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5). Conclusion: This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3

Open source clinical science for emerging infections

International audienc

Human Milk Secretory Antibodies against Attaching and Effacing Escherichia coli Antigens

Secretory immunoglobulin A (sIgA) is a primary factor responsible for preventing attachment of enteropathogens to gut epithelium in breastfeeding infants. We compared the frequency of sIgA to major surface antigens of enterohemorrhagic Escherichia coli (EHEC) in milk of 123 women from the United States and Mexico to determine whether regional differences existed in the frequency of antibodies to these surface antigens. In both groups of women, milk commonly has sIgA against various EHEC lipopolysaccharides, EspA, EspB, intimin, and less frequently against Shiga toxin. The study suggests that persons living in the U.S. are exposed to attaching/effacing enteropathogens more frequently than is generally assumed. The low frequency of antibodies to Stx1 (in 12% of Mexican and in 22% of U.S. samples) suggests that the rare appearance of hemolytic uremic syndrome in adults is not due to neutralization of toxin at the gut level. Only anti-EspA is found in most milk samples from both populations of women. EspA may represent a useful target for an immunization strategy to prevent EHEC disease in humans

Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors

Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006-May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 x 10(9) cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables

Influenza symptoms and their impact on elderly adults: randomised trial of AS03-adjuvanted or non-adjuvanted inactivated trivalent seasonal influenza vaccines.

Patient-reported outcomes (PROs) are particularly relevant in influenza vaccine trials in the elderly where reduction in symptom severity could prevent illness-related functional impairment

Vacuna tetravalente de influenza en los programas nacionales de inmunización para los países de América Latina

Since 2012-2013 influenza season, World Health Organization (who) recommends the formulation of tetravalent vaccines. Globally, many countries already use tetravalent vaccines in their national immunization programs, while in Latin America only a small number. Two Influenza b lineages co-circulate, their epidemiological behavior is unpredictable. On average they represent 22.6% of influenza cases and more than 50% in predominant seasons. The lack of concordance between recommended and circulating strains was 25 and 32% in the 2010-2017 and 2000-2013 seasons, respectively. There are no clinical differences between influenza A and B. It occurs more frequently from five to 19 years of age. Influenza b has a higher proportion of attributable deaths than influenza a (1.1 vs. 0.4%), or 2.65 (95% ci 1.18-5.94). A greater number of hospitalizations when the strains mismatch (46.3 vs. 28.5%; p <.0001). Different evaluations have demonstrated its cost effectiveness. The compilation of this information supports the use of quadrivalent vaccines in Latin American countries.Revisión por pare