On the impact of ethanol on the rejection and transfer mechanism during ultrafiltration of a charged macromolecule in water/ethanol.

Ultrafiltration (UF) is a sustainable membrane separation technique. It could be useful for the concentration/purification of bio-sourced molecules that are extracted either by pure ethanol or by water/ethanol mixtures. Nevertheless, the process optimization requires an in-depth understanding of the transfer mechanisms of solute through membranes, especially for charged solutes, that are nowadays not sufficiently documented. Previous studies achieved in aqueous media have shown that the rejection of charged solutes by an UF membrane involves at least three mechanisms: convection, diffusion and electrostatic interactions. The present study aims at a systematic analysis of the transfer mechanisms of a model protein (lysozyme) in water/ethanol mixtures (100/0-70/30 v/v) during UF by a zirconia inorganic membrane. The influence of the pH varying in the 4-9 range and of the ionic strength (I) is also discussed. The ionic strength I can be adjusted by addition of an indifferent electrolyte (NaCl) only aiming at the screening of the electrostatic interactions or by addition of a selectively adsorbed electrolyte(KH2PO4) that is able to change the isoelectric pH of the protein and thus to modulate the electrostatic interactions in a different way when compared to NaCl. Of course, both salts have an impact on the protein rejection in UF. The results are analysed using the CDE model previously developed in our group to explain the behaviour of a single protein during UF in water and accounting for convection, diffusion and electrophoretic migration. The applicability of the CDE model in water/ethanol mixtures up to 70/30 v/v is finally shown.

Safety and immunogenicity of a recombinant Plasmodium falciparum AMA1-DiCo malaria vaccine adjuvanted with GLA-SE or Alhydrogel® in European and African adults: A phase 1a/1b, randomized, double-blind multi-centre trial.

BACKGROUND: Plasmodium falciparum Apical Membrane Antigen 1 Diversity Covering (PfAMA1-DiCo) candidate vaccine is a formulation of three recombinant variants of AMA1 designed to provide broader protection against parasites with varying AMA1 sequences. METHODS: In this staggered phase Ia/Ib randomized, double blind trial, healthy French adults received AMA1-DiCo with either Alhydrogel® (n=15) or GLA-SE (n=15). Following a safety assessment in French volunteers, GLA-SE was chosen for the phase Ib trial where healthy Burkinabe adults received either AMA1-DiCo/GLA-SE (n=18) or placebo (n=18). AMA1-DiCo (50µg) was administered intramuscularly at baseline, Week 4 and 26. RESULTS: AMAI-DiCo was safe, well tolerated either with Alhydrogel® or GLA-SE. In European volunteers, the ratios of IgG increase from baseline were about 100 fold in Alhydrogel® group and 200-300 fold in GLA-SE group for the three antigens. In African volunteers, immunization resulted in IgG levels exceeding those observed for the European volunteers with a 4-fold increase. DiCo-specific IgG remained higher 26weeks after the third immunization than at baseline in both European and African volunteers. Induced antibodies were reactive against whole parasite derived from different strains. CONCLUSION: AMA1-DiCo vaccine was safe and immunogenic whatever the adjuvant although GLA-SE appeared more potent than Alhydrogel® at inducing IgG responses. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02014727; PACTR201402000719423.

Hepatitis B virus reactivation in patients with solid tumors receiving systemic anticancer treatment.

BACKGROUND: Hepatitis B virus (HBV) reactivation is a well-known risk during chemotherapy for hematological malignancies with reported rates ranging between 14% and 72%. However, there is a paucity of data regarding HBV infection management and reactivation risk in patients receiving systemic treatments for solid tumors. DESIGN: We conducted a PubMed search for publications from January 1990 until May 2016 related to HBV reactivation. The search terms were 'hepatitis B reactivation', cross-referenced with 'chemotherapy', then 'hepatitis B' cross-referenced with International Non-proprietary Name of each of the most used chemotherapy drugs in solid tumors. RESULTS: From these data, a grading of HBV reactivation risk and recommendations for management are given for most frequently used anticancer drugs in solid tumors. CONCLUSION: Most drugs used for the treatment of solid tumors can induce hepatitis B reactivation in HBs antigen-positive patients. HBV screening can be recommended before systemic treatment initiation. Pre-emptive antiviral treatment can reduce the risk of HBV reactivation and prevent chemotherapy disruption.

Mechanisms of action of particles used for fouling mitigation in membrane bioreactors.

Adding chemicals to the biofluid is an option to mitigate membrane fouling in membrane bioreactors. In particular, previous studies have shown that the addition of particles could enhance activated sludge filterability. Nevertheless, the mechanisms responsible for the improved filtration performance when particles are added are still unclear. Two main mechanisms might occur: soluble organic matter adsorption onto the particles and/or cake structure modification. To date, no studies have clearly dissociated the impact of these two phenomena as a method was needed for the in-line characterization of the cake structure during filtration. The objective of this study was thus to apply, for the first time, an optical method for in-situ, non-invasive, characterization of cake structure during filtration of a real biofluid in presence of particles. This method was firstly used to study local cake compressibility during the biofluid filtration. It was found that the first layers of the cake were incompressible whereas the cake appeared to be compressible at global scale. This questions the global scale analysis generally used to study cake compressibility and highlights the interest of coupling local characterization with overall process performance analysis. Secondly, the impact of adding submicronic melamine particles into the biofluid was studied. It appears that particles added into the biofluid strongly influence the cake properties, making it thicker and more permeable. Furthermore, by using liquid chromatography with an organic carbon detector to determine the detailed characteristics of the feed and permeate, it was shown that the modification of cake structure also affected the retention of soluble organic compounds by the membrane and thus the cake composition. Simultaneous use of a method for in-situ characterization of the cake structure with a detailed analysis of the fluid composition and monitoring of the global performance is thus a powerful method for evaluating cake structure and composition and their impact on global process performance. The use of this methodology should allow "cake engineering" to be developed so that cake properties (structure, composition) can be controlled and process performance optimized.

Validity of self-reported vaccination status among French healthcare students.

Data on validity of self-reported vaccinations are scarce. This study, performed on healthcare students in Paris (France), aimed to evaluate this validity for occupational vaccinations. The validity of self-reported vaccination status was compared with written information. A total of 432 students were enrolled. Sensitivity rates for BCG, hepatitis B and measles were over 74%. For diphtheria-tetanus-polio and pertussis, sensitivity was below 50%. Specificity was between 70 and 95% for dTP-pertussis, and below 35% for all others. Overall, the validity of self-reported information was low, meaning that checking medical records remains the preferable strategy for assessing immunization status.

Measles immunity and measles vaccine acceptance among healthcare workers in Paris, France.

BACKGROUND: In Europe, including France, a measles outbreak has been ongoing since 2008. Unprotected healthcare workers (HCWs) may contract and spread the infection to patients. AIM: The objective of this study was to evaluate HCWs' measles immunity and vaccine acceptance in our setting. METHODS: In a survey-based study conducted in three university hospitals in Paris, 351 HCWs were included between April and June 2011. The following data were collected at enrolment: age, hospital unit, occupation, history of measles infection and vaccination, previous measles serology and acceptance of a measles vaccination in case of seronegativity. Sera were tested for the presence of specific anti-measles IgG antibodies using the CAPTIA(®) measles enzyme-linked immunosorbent assay. FINDINGS: The mean age of the participating HCWs was 36 years (range: 18-67) and 278 (79.2%) were female. In all, 104 four persons (29.6%) declared a history of measles, and 90 (25.6%) declared never having received a measles vaccination. Among the 351 HCWs included in the study, 322 (91.7%) were immunized against measles (IgG >90 mIU/mL). The risk factors for not being protected were age [18-29 years, adjusted odds ratio: 2.7 (95% confidence interval: 1.1-6.9) compared with ≥30 years], no history of measles infection or vaccination. The global acceptance rate for a measles vaccination, before knowing their results, was 78.6%. CONCLUSION: In this cohort of HCWs, 8.3% were susceptible to measles; the group most represented were aged <30 years. Acceptance of the measles vaccine was high. A vaccination campaign in healthcare settings should target specifically healthcare students and junior HCWs.

Survey of vaccination policies in French healthcare institutions.

OBJECTIVE: The survey was implemented to describe vaccination policies for healthcare professionals in French healthcare institutions. METHODS: A cross-sectional survey based on questionnaires was sent to occupational physicians and chairpersons of hospital infection prevention and control committees (HIPC) of 38 institutions between November 2010 and January 2011. RESULTS: Twenty-nine occupational physicians and 26 hospital infection prevention and control committees chairpersons (HIPC), from 30 institutions answered (response rate: 79%), 70% of the institutions were university hospitals. Overall, 76% of occupational physicians and 85% of HIPC chairpersons reported that information and awareness campaigns about vaccination recommendations for healthcare professionals were usually conducted in their establishment. Fifty-nine percent of occupational physicians and 31% of HIPC chairpersons reported that they were aware of the vaccine coverage rates of professionals in their institution. The occupational physicians reported that they suggested diphtheria, tetanus, polio, influenza, and acellular pertussis vaccination to all staff at their annual visit in 100%, 97%, and 62% of cases, respectively. Varicella and measles vaccinations were never suggested in 31% and 17% of cases, respectively. Among respondents, 55% of physicians reported that they had already managed a pertussis epidemic, and 42% a measles epidemic, and in both of these cases an awareness campaigns were usually conducted (93% and 96%). CONCLUSIONS: The vaccine coverage rates of healthcare professionals in French healthcare institutions remain insufficiently documented and could be improved.

Vaccination coverage among medical residents in Paris, France.

Medical residents are particularly exposed to the risk of occupational infection. We aimed to determine the vaccination coverage in residents with an anonymous self-reporting electronic questionnaire. A total of 250 residents took part in this survey. Vaccination rates were particularly high for mandatory vaccinations (diphtheria, tetanus, poliomyelitis, hepatitis B virus and tuberculosis). Regarding recommended vaccinations (influenza, 45.6%; pertussis, 65.2%; measles, 62.8%; varicella, 62.8%), rates were insufficient to prevent hospital epidemics, but higher than those reported in other healthcare workers. Further immunization programmes should target residents, and not only senior healthcare workers, with a critical role for occupational medicine departments.

Immunogenicity and safety of the influenza A H1N1v 2009 vaccine in cancer patients treated with cytotoxic chemotherapy and/or targeted therapy: the VACANCE study.

BACKGROUND: Influenza vaccination is recommended to cancer patients undergoing chemotherapy, but vaccine coverage remains low. During the 2009 influenza pandemic, French recommendations were to vaccinate immunocompromised patients with two doses of adjuvanted vaccine. This study aimed to evaluate vaccine immunogenicity in cancer patients receiving chemotherapy. PATIENTS AND METHODS: VACANCE is a prospective open-label study that evaluated the immunogenicity and safety of two doses of AS03A-adjuvanted H1N1v vaccine in cancer patients receiving cytotoxic and/or targeted therapies. Serum haemagglutination-inhibited antibody titres against influenza A H1N1v were measured at days 1, 21, and 42, to estimate the proportion of participants with antibody titres ≥ 1 : 40 [seroprotection rate (SPR)], the efficacy of seroconversion, and factors that increased the geometric mean titre. RESULTS: Sixty-five patients were included. At baseline, 5% of patients had vaccine strain titres of specific haemagglutination inhibition antibodies that were ≥ 1 : 40. After one and two doses of vaccine, SPRs were 48% and 73%, respectively, and seroconversion rates were 44% and 73%, respectively. Vaccine-related adverse events were mild to moderate. CONCLUSIONS: A single dose of AS03-adjuvanted A/H1N1 vaccine triggered a low immune response in cancer patients on chemotherapy depending on their treatment type and frequency. Two doses are needed for these cancer patients.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

Low immunogenicity of seasonal trivalent influenza vaccine among patients receiving docetaxel for a solid tumour: results of a prospective pilot study.

BACKGROUND: Patients receiving cytotoxic therapy for solid tumours are at risk of severe influenza. However, few data are available regarding the immunogenical efficacy of influenza vaccine in these patients. METHODS: In this prospective study, 25 patients with breast (n=13) or prostate (n=12) cancer received a trivalent inactivated influenza vaccine along with docetaxel (Taxotere) administration. The influenza virus type A and B antibody titres were measured using haemagglutinin inhibition (Garten et al, 2009) before and 21 days after the vaccination. Seroconversion rate was defined as the percentage of patients with an increase in the serum titres ≥ 4 after vaccination. RESULTS: Median age was 65 years (range: 33-87 years); 52% were females. Seroconversion rates were low: 28% (95% CI: 23.1-33.3) for H1N1, 8% (95% CI: 7.7-8.3) for H3N2 and 16% (95% CI: 7.7-25) for the B strain. The geometric mean titres ratios were 2.16 (H1N1), 1.3 (H3N2) and 1.58 (B). No serious adverse event (AE) related to the vaccine was reported. All the reported AE were from mild-to-moderate intensity. CONCLUSION: In the patients receiving docetaxel for solid tumours, influenza vaccine triggers an immune response in only one third. Strategies using more immunogenic influenza vaccines must be evaluated in such patients.

[Current events in vaccination]. / Actualités en matière de vaccination.

The annual meeting of the Infectious Disease Society of America (IDSA); which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve--but for how long?--the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55%, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

Diagnostic contribution of positron emission tomography with [18F]fluorodeoxyglucose for invasive fungal infections.

Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [¹8F]fluorodeoxyglucose ([¹8F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [¹8F]FDG ([¹8F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [¹8F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-7 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [¹8F]FDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [¹8F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [¹8F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [¹8F]FDG-PET was performed to assess the evolution of the disease. [¹8F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [¹8F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.

Accidental blood exposures among medical residents in Paris, France.

Accidental blood exposure (ABE) exposes healthcare workers, including medical residents, to the risk of occupational infection. We aimed to determine the characteristics of ABEs in residents with an anonymous self-reporting electronic questionnaire. A total of 350 residents (33% from surgical disciplines) entered this survey. One hundred and eighty-five residents (52%) reported at least one ABE during their residency (median, 2; range, 1-25), 53% of which occurred in operating theatres. Sixty-nine per cent of residents followed the current procedures for local disinfection. ABEs were notified to the hospital administration by 62% of residents, but only 51% of residents were referred to the occupational medicine department. The most frequently reported concerns following ABEs were human immunodeficiency virus (52%) and hepatitis C virus infection (39%). In 74% of cases, the serological status of the index patient was investigated. Only 54% of residents were aware of their hepatitis B surface antibody titres. Medical residents behaved inappropriately in 33% of cases in this survey. Further educational programmes should include residents, and not only senior healthcare workers, in order to improve individual behaviours.

Report of the 2nd "French Clinical Vaccinology Meeting Jean-Gerard Guillet": immunization and respiratory diseases.

The 2nd French Clinical Vaccinology conference held on 20th April 2009 in Paris (France) was a unique opportunity to discuss basic and translational research in vaccinology and its implications for patients for respiratory diseases. This conference is organized by the Clinical Research Center Cochin-Pasteur, that has been involved for several years clinical research in vaccines. We report on here the key findings of the conference, especially the immunization of the chronic respiratory diseases, the clinical effectiveness of vaccines and the development of new vaccines in pulmonology.

Knowledge, attitudes and vaccination coverage of healthcare workers regarding occupational vaccinations.

OBJECTIVES: Immunization of healthcare workers (HCWs) is a major issue for infection control in healthcare facilities. The aim of this study was to evaluate knowledge regarding occupational vaccinations, HBV, varicella and influenza vaccination rates and attitudes towards influenza vaccine among HCWs. DESIGN AND SETTING: A cross-sectional survey was conducted in two wards (Medicine and Paediatrics) of a 1182-bed teaching hospital in Paris, France. METHODS: A standardized, anonymous, self-administered questionnaire was used. RESULTS: Of 580 HCWs, 395 (68%) completed the questionnaire. Knowledge about the occupational vaccinations of HCWs was low. HBV (69%), tuberculosis (54%) and influenza (52%) were the most cited vaccinations. Paediatric staff was more aware of influenza and pertussis immunizations (p<.05). HBV vaccination rate was 93%, among whom 65% were aware of their immune status. Influenza vaccination rate for 2006-2007 was 30% overall, ranging from 50% among physicians to 20% among paramedical staff (p<.05). Physicians based their refusal on doubts about vaccine efficacy, although paramedics feared side effects. Influenza vaccination was associated with knowledge of vaccine recommendations [OR=1.75, 95% CI: 1.13-2.57] and contact with patients [OR=3.05, 95% CI: 1.50-5.91]. CONCLUSIONS: Knowledge of recommended occupational vaccinations is insufficient in HCWs, except for HBV and influenza. Although the HBV vaccine coverage of HCWs is satisfactory, a large proportion of them is unaware of immune status. Influenza vaccine coverage remains low, especially among paramedical staff because of fear of side effects. As vaccine coverage is associated with knowledge, educational campaigns should be strengthened to increase the adhesion of HCWs to vaccinations.

[Hepatic steatosis: an emerging cause of cirrhosis in HIV patients]. / La stéatose hépatique: une maladie émergente chez les patients infectés par le VIH.

Hepatic steatosis is an emerging cause of morbidity in antiretroviral therapy (ART)-experienced HIV patients. The influence of steatosis on fibrosis is poorly understood. We report two cases of rapid evolution of disseminated macrovacuolar steatofibrosis to cirrhosis. Both patients had no history of alcohol abuse, nor intravenous drug use and were tested negative for HCV (PCR RNA) and had no HBS antigen. Patient 1 had a past history of hypertrygliceridemia, but controlled with dietetic measures for 4 years prior to biopsy. The first hepatic biopsy showed a disseminated macrovacuolar steatosis (>80%). The patient had then cytolysis and an uncontrolled HIV viral load. The second biopsy was performed two years later, and HIV was controlled by a new line of ART. It showed a regression of the steatosis (10%) and a progression of the fibrosis with signs of cirrhosis. Patient 2 had a long history of HIV infection. He also had an uncontrolled dyslipidemia. The first biopsy was realised during a period of uncontrolled HIV infection and elevated liver enzymes. The biopsy showed a major macrovacuolar steatosis (>80%). The second biopsy was realised 6 years after and showed the same steatosis and signs of cirrhosis. The HIV infection was then under control. Observations reported here show a rapid evolution of liver steatosis to cirrhosis in HIV positive / HCV negative patients, despite the control of HIV infection. The implication of HAART remains unclear. In the era of HAART, liver steatosis can rapidly evoluate to cirrhosis without any risk factor except ART.