Major Role for Amphotericin B–Flucytosine Combination in Severe Cryptococcosis

BACKGROUND: The Infectious Diseases Society of America published in 2000 practical guidelines for the management of cryptococcosis. However, treatment strategies have not been fully validated in the various clinical settings due to exclusion criteria during therapeutic trials. We assessed here the optimal therapeutic strategies for severe cryptococcosis using the observational prospective CryptoA/D study after analyzing routine clinical care of cryptococcosis in university or tertiary care hospitals. METHODOLOGY/PRINCIPAL FINDINGS: Patients were enrolled if at least one culture grew positive with Cryptococcus neoformans. Control of sterilization was warranted 2 weeks (Wk2) and 3 months (Mo3) after antifungal therapy onset. 208 HIV-positive or -negative adult patients were analyzed. Treatment failure (death or mycological failure) at Wk2 and Mo3 was the main outcome measured. Combination of amphotericin B+flucytosine (AMB+5FC) was the best regimen for induction therapy in patients with meningoencephalitis and in all patients with high fungal burden and abnormal neurology. In those patients, treatment failure at Wk2 was 26% in the AMB+5FC group vs. 56% with any other treatments (p<0.001). In patients treated with AMB+5FC, factors independently associated with Wk2 mycological failure were high serum antigen titer (OR [95%CI] = 4.43[1.21-16.23], p = 0.025) and abnormal brain imaging (OR = 3.89[1.23-12.31], p = 0.021) at baseline. Haematological malignancy (OR = 4.02[1.32-12.25], p = 0.015), abnormal neurology at baseline (OR = 2.71[1.10-6.69], p = 0.030) and prescription of 5FC for less than 14 days (OR = 3.30[1.12-9.70], p = 0.030) were independently associated with treatment failure at Mo3. CONCLUSION/SIGNIFICANCE: Our results support the conclusion that induction therapy with AMB+5FC for at least 14 days should be prescribed rather than any other induction treatments in all patients with high fungal burden at baseline regardless of their HIV serostatus and of the presence of proven meningoencephalitis

Significant Reduction of Antibiotic Use in the Community after a Nationwide Campaign in France, 2002–2007

Didier Guillemot and colleagues describe the evaluation of a nationwide programme in France aimed at decreasing unnecessary outpatient prescriptions for antibiotics. The campaign was successful, particularly in reducing prescriptions for children

Long-term cellular immunity of vaccines for Zaire Ebola Virus Diseases

Recent Ebola outbreaks underscore the importance of continuous prevention and disease control efforts. Authorized vaccines include Merck’s Ervebo (rVSV-ZEBOV) and Johnson & Johnson’s two-dose combination (Ad26.ZEBOV/MVA-BN-Filo). Here, in a five-year follow-up of the PREVAC randomized trial (NCT02876328), we report the results of the immunology ancillary study of the trial. The primary endpoint is to evaluate long-term memory T-cell responses induced by three vaccine regimens: Ad26–MVA, rVSV, and rVSV–booster. Polyfunctional EBOV-specific CD4+ T-cell responses increase after Ad26 priming and are further boosted by MVA, whereas minimal responses are observed in the rVSV groups, declining after one year. In-vitro expansion for eight days show sustained EBOV-specific T-cell responses for up to 60 months post-prime vaccination with both Ad26-MVA and rVSV, with no decline. Cytokine production analysis identify shared biomarkers between the Ad26-MVA and rVSV groups. In secondary endpoint, we observed an elevation of pro-inflammatory cytokines at Day 7 in the rVSV group. Finally, we establish a correlation between EBOV-specific T-cell responses and anti-EBOV IgG responses. Our findings can guide booster vaccination recommendations and help identify populations likely to benefit from revaccination

Estimation du coût des violences au sein du couple et de leur incidence sur les enfants en France en 2012 : synthèse de la troisième étude française de chiffrage

Objectifs – Le coût des violences au sein du couple et de leurs conséquences sur les enfants (VSCE) a été calculé pour l’année 2012 en France. Comme dans d’autres études, ce type de calcul contribue depuis quelque vingt ans à faire des violences interpersonnelles une question de santé publique. Nous en discutons la méthode, les résultats et l’apport possible à des politiques sanitaires.Matériel-méthodes – L’étude s’appuie sur 1) des données administratives ; 2) des enquêtes en population générale (prévalence et incidence des phénomènes, étayage des causalités entre violences subies et santé) ; 3) des études spécifiques (données en population générale ou à vocation clinique) ; 4) des compléments qualitatifs recueillis auprès d’experts pour les données les plus lacunaires. Pour la valorisation monétaire des VSCE, c’est la « valeur de la vie statistique » qui est utilisée, selon l’estimation réalisée en France en 2013.Résultats – Le coût total des VSCE est estimé à 3,6 milliards d’euros en 2012, dont 21,5% de coûts directs (médicaux ou non), 66,8% de coûts indirects et 11,7% de coûts pesant sur les enfants. Tant pour les dépenses imputables aux VSCE (coût d’opportunité) que pour les manques à gagner qu’elles engendrent, leurs coûts sont massivement déterminés par la victimation des femmes dans le couple.Discussion – L’augmentation du coût des VSCE depuis la première étude française s’explique par la possibilité de nouveaux chiffrages et ouvre des discussions sur certaines hypothèses émises, dans chacune des études menées, sur des postes spécifiques de coût. Elle s’explique surtout par un accroissement du consentement à payer : renchérie, la « valeur de la vie statistique » vient alourdir le volume et la part des coûts indirects. Des données quantitatives manquent, particulièrement pour les enfants. Des données qualitatives nouvelles permettraient aussi de mieux interpréter la rare et statistiquement atypique victimation des hommes.Conclusion – Le calcul du coût confirme le fardeau considérable des VSCE dans une logique « burden of disease ». Les données restent à compléter et l’opérationnalisation de l’instrument « coût » dans les politiques sanitaires demeure encore inachevée

Classification and Regression Trees for Bacterial Vaginosis Diagnosis in Pregnant Women Based on High-Throughput Quantitative PCR

International audienceBacterial vaginosis (BV) diagnosis in pregnancy is based on the Nugent score, which consists of semiquantitation of bacterial morphotypes. Limited data exist concerning molecular-based diagnosis in asymptomatic pregnant women. Using high-throughput quantitative PCR, 34 microorganisms were screened in asymptomatic pregnant women and compared with the Nugent score. Three-hundred and four vaginal samples had a Nugent score <7 (69.9%) and 131, a Nugent score ≥7 (30.1%), consistent with BV. More pregnant women with BV share Atopobium vaginae, bacterial vaginosis associated bacteria-2, Gardnerella spp., Mobiluncus curtisii, Mo. mulieris, Mycoplasma hominis, Ureaplasma urealyticum, Prevotella bivia, Megasphaera 1, and Megasphaera 2 in their vaginal sample. Fewer pregnant women with BV share Lactobacillus crispatus, L. gasseri, L. jensenii, and Enterococcus faecalis in their vaginal sample (P < 0.001). Classification and regression tree analysis was performed to determine which combinations of detected bacteria optimally diagnose BV in this population. A set of only four bacteria of 34 microorganisms (A. vaginae, Gardnerella spp., L. crispatus, and P. bivia) was the best combination to identify BV in a cohort of asymptomatic pregnant women, with a sensitivity of 77.1%, and specificity of 97.0% compared with the Nugent score. The quantitative PCR in the present study responds to the limits of the Nugent score by implementing an easily reproducible quantitative assay to assess the absence of BV in pregnancy

Les pouvoirs locaux dans la France du centre et de l'ouest (VIIIe-XIe siècles)

Cet ouvrage est le fruit d'une réflexion commune lancée par ses deux directeurs qui, au fil de leurs travaux de leurs discussions et de leurs entretiens, ont à de nombreuses reprises eu envie d'établir des ponts et des passerelles entre la société féodale chère à l'un et le monde carolingien qui retenait l'attention de l'autre. À de nombreuses reprises, ils se sont retrouvés sur des interrogations communes qui touchaient aux aspects les plus pragmatiques de ces mondes, où les enjeux de pouvoir, le contrôle de la terre et de la société, la transmission de son rang et de son importance continuaient à puiser leur origine et leurs méthodes dans un passé magnifié. Aussi leur a-t-il paru utile d'associer à leur démarche d'autres chercheurs des universités de l'Ouest pour tenter une synthèse au niveau des pouvoirs locaux, car c'est à ce niveau d'encadrement, où les soucis d'une mutation politique due à l'effacement des souverains carolingiens est le moins sensible, qu'on est le mieux à même de percevoir les continuités, les mutations graduelles, les nouvelles stratégies visant à permettre à ceux qui se veulent quelqu'un de tenir le rang auquel ils prétendent. Volontairement chaque auteur s'est circonscrit dans une espace étroit pour permettre d'établir des comparaisons et saisir ainsi les principes communs comme les diversités qui président à l'action des pouvoirs locaux dans la France du centre et de l'ouest du VIIIe au XIe siècle

Lancet Infect Dis

Background Long-term protection and herd immunity induced by existing pertussis vaccines are imperfect, and a need therefore exists to develop new pertussis vaccines. This study aimed to investigate the safety, colonisation, and immunogenicity of the new, live attenuated pertussis vaccine, BPZE1, when given intranasally. Methods This phase 1b, double-blind, randomised, placebo-controlled, dose-escalation study was done at the phase 1 unit, Karolinska Trial Alliance, Karolinska University Hospital, Stockholm, Sweden. Healthy adults (18–32 years) were screened and included sequentially into three groups of increasing BPZE1 dose strength (107 colony-forming units [CFU], 108 CFU, and 109 CFU), and were randomly assigned (3:1 within each group) to receive vaccine or placebo. Vaccine and placebo were administered in phosphate-buffered saline contained 5% saccharose as 0·4 mL in each nostril. The primary outcome was solicited and unsolicited adverse events between day 0 and day 28. The analysis included all randomised participants who received a vaccine dose. Colonisation with BPZE1 was determined by repeatedly culturing nasopharyngeal aspirates at day 4, day 7, day 11, day 14, day 21, and day 28 after vaccination. Immunogenicity, as serum IgG and IgA responses were assessed at day 0, day 7, day 14, day 21, day 28, 6 months, and 12 months after vaccination. This trial is registered at Clinicaltrials.gov, NCT02453048. Findings Between Sept 1, 2015, and Feb 3, 2016, 120 participants were assessed for eligibility, 48 of whom were enrolled and randomly assigned (3:1) to receive vaccine or placebo, with 12 participants each in a low-dose, medium-dose, and high-dose vaccine group. Adverse events between day 0 and day 28 were reported by one (8%, 95% CI 0–39) of 12 participants in both the placebo and low-dose groups, and two (17%; 2–48) of 12 participants in both the medium-dose and high-dose groups, including cough of grade 2 or more, oropharyngeal pain, and rhinorrhoea and nasal congestion. During this time, none of the participants experienced any spasmodic cough, difficulties in breathing, or adverse events following immunisation concerning vital signs. The tested doses of BPZE1 or placebo were well tolerated, with no apparent difference in solicited or unsolicited adverse events following immunisation between groups. Colonisation at least once after vaccination was observed in 29 (81%; 68–93) of 36 vaccinated participants. The tested vaccine doses were immunogenic, with increases in serum IgG and IgA titres against the four B pertussis antigens from baseline to 12 months. Interpretation The tested vaccine was safe, induced a high colonisation rate in an adult population, and was immunogenic at all doses. These findings justify further clinical development of BPZE1 to ultimately be used as a priming vaccine for neonates or a booster vaccine for adolescents and adults, or both

Mycobacterium avium and Mycobacterium abscessus complex target distinct cystic fibrosis patient subpopulations

Background Clinical observations suggest that Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABSC) may affect cystic fibrosis (CF) patients with different characteristics and risk factors, but this has never been demonstrated within a single prospective cohort. Methods We studied 50 MABSC-positive and 23 MAC-positive patients from a French prevalence study of non‐tuberculous mycobacteria (NTM) in CF. Risk factors specifically associated with MABSC and MAC were analyzed by nested case–control studies, with two NTM-negative controls matched by age, sex and center for each case. Results MAC-positive patients were significantly older than MABSC-positive patients (mean [SD] age, 23.1 [10.2] vs 17.4 [8.3] years, p=0.013), and were also older at CF diagnosis (mean [SD] age, 12.9 [16.1] vs 3.1 [7.7] years, p=0.015); they tended to be less frequent of the ΔF508/ΔF508 genotype (33.3 vs 61.1%, p=0.17) and to use pancreatic extracts less frequently (82.4 vs 97.6%, p=0.07). Risk factors identified by multivariate analysis were: i) in the MAC case–control study, an older age at CF diagnosis (p=0.004); ii) in the MABSC case–control study, at least one course of intravenous antibiotics (p=0.01) and more frequent isolation of Aspergillus (p=0.03). Conclusions MAC affects adult patients with a mild form of CF, whereas MABSC affects younger patients with more severe CF and more frequent intravenous antimicrobial treatment