Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Abus sexuel parmi les colporteuses adolescentes dans l'Etat d' Anambra au Nigéria

Street hawking exposes young girls to all forms of hazards, including sexual abuse. This descriptive study examines the size of the problem and the consequences of sexual abuse on juvenile female street hawkers randomly recruited from two urban towns in Anambra State of Nigeria. Data was collected with semi structured, interviewer administered questionnaires. The mean age of the female hawkers was 13.0 + 2.2 years. Out of 186 respondents, 130 (69.9%) had been sexually abused with 32 (17.2%) having had penetrative sexual intercourse (28.1% were forced and 56.3% submitted willingly) while hawking. Majority (59.4%) of the sexual partners were adults. Other types of sexual abuse experienced include inappropriate touches (106 cases; 81.5%) and verbal abuses (121 cases; 93.1%).. There was low awareness of the twin risks of pregnancy (43.1%) and sexually transmitted infections (54.3%) following sexual abuse among the respondents. Sexual abuse of young female hawkers is an issue of great public health importance. Poverty alleviation, health education and protective child right policies will decrease its prevalence and the associated risks.L'activité des colporteuses expose les jeunes filles à toutes sortes de risques y compris l'abus sexuel. Cette étude descriptive examine l'ampleur du problème et les conséquences de l'abus sexuel sur les colporteuses qui ont été recrutées au hasard dans deux villes urbaines dans l'Etat d'Anambra au Nigéria. Des données ont été collectées à l'aide des questionnaires semi-structurés et administérs par l'enquêteur. L'âge moyen des colporteuses était 13,0+2,2 ans. 136 (69,9%) sur les 186 enquêtées ont subi l'abus sexuel d'une maniére ou d'une autre. Trente-deux (17, 2%) parmi les colporteuses ont eu des rapports sexuels avec pénétration quand elles étaient en train de marchander des produits. De ce nombre, 28,1% ont été forcées et 56,3% se sont soumises volontairement. La majorité (59,4%) des partenaires sexuels étaient des adultes. D'autres formes d'abus sexuels que les 130 colporteuses ont subis comprennent les touches inappropriées (106 cas . 81,5%) et des abus verbaux (121 cas ; 93,1%). La conscience du double risque de la grossesse (43,1%) et des infections sexuellement transmissibles (54,3%) suite à l'abus sexuel est peu élevée. L'abus sexuel subi par les colporteuses engagées dans le travail des enfants est une question de santé publique de grande importance. Les efforts du gouvernement pour remédier à la pauvreté, pour promouvoir l'éducation de la santé et les politiques des droits de l'enfant protecteurs, aideront beaucoup a réduire sa prévalence et la prévalence des risques qui y sont associés

Calculate FIR length perl script

<p>Supplementary file for the article " Two-dimensional data binning for the analysis of genome architecture in filamentous plant pathogens and other eukaryotes".</p> <p>Script for the calculation of intergenic region length in perl.</p

Host Protein BSL1 Associates with <em>Phytophthora infestans</em> RXLR Effector AVR2 and the <em>Solanum demissum</em> Immune Receptor R2 to Mediate Disease Resistance:Effector AVR2 Associates with BSL1

Plant pathogens secrete effector proteins to modulate plant immunity and promote host colonization. Plant nucleotide binding leucine-rich repeat (NB-LRR) immunoreceptors recognize specific pathogen effectors directly or indirectly. Little is known about how NB-LRR proteins recognize effectors of filamentous plant pathogens, such as Phytophthora infestans. AVR2 belongs to a family of 13 sequence-divergent P. infestans RXLR effectors that are differentially recognized by members of the R2 NB-LRR family in Solanum demissum. We report that the putative plant phosphatase BSU-LIKE PROTEIN1 (BSL1) is required for R2-mediated perception of AVR2 and resistance to P. infestans. AVR2 associates with BSL1 and mediates the interaction of BSL1 with R2 in planta, possibly through the formation of a ternary complex. Strains of P. infestans that are virulent on R2 potatoes express an unrecognized form, Avr2-like (referred to as A2l). A2L can still interact with BSL1 but does not promote the association of BSL1 with R2. Our findings show that recognition of the P. infestans AVR2 effector by the NB-LRR protein R2 requires the putative phosphatase BSL1. This reveals that, similar to effectors of phytopathogenic bacteria, recognition of filamentous pathogen effectors can be mediated via a host protein that interacts with both the effector and the NB-LRR immunoreceptor

Fragments d’intime. Amours, corps, et solitudes aux marges urbaines

Dans les espaces urbains marqués par la précarisation, les sphères de l’intime se fragilisent. Cet ouvrage explore la vie émotionnelle, affective et sociale de personnes de toutes origines, souvent marquées par l’épreuve de l’exil, dans un quartier « chaud » de Bruxelles, où les relations hommes/femmes, les quêtes affectives et sexuelles sont d’une grande complexité. L’auteure y a longuement fréquenté des prostituées, des errants avec ou sans papiers, des jeunes issus des anciennes et nouvelles migrations, turques en particulier. Elle restitue ici, avec finesse et délicatesse, leurs histoires et contextes de vie, qui contribuent à façonner leurs rapports au corps, à l’autre sexe et à la solitude. Éprouvés mais altiers, marginalisés mais créatifs, brisés mais tenaces, les interlocuteurs de l’ethnologue font face à l’insécurité sociale et intime. Celle-ci peut devenir une quête initiatique, où s’invente une autre vie urbaine, souterraine et alternative. Il en va ainsi de la prostitution libre et courtisane, vécue comme un métier de service ; des squats semi-organisés qui protègent de la rue les couples et les grands célibataires ; des couples mixtes et des inventions transculturelles qui décloisonnent les ghettos urbains. À travers la vie intérieure et secrète de ses interlocuteurs, Pascale Jamoulle nous invite à découvrir les mondes off des grandes métropoles, à voir comment s’invente la mondialisation par le bas de l’échelle sociale