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Background: Cerebral malaria (CM) is a neuropathology which remains one of the deadliest forms of malaria among African children. The kinetics of the pathophysiological mechanisms leading to neuroinflammation and the death or survival of patients during CM are still poorly understood. The increasing production of cytokines, chemokines and other actors of the inflammatory and oxidative response by various local actors in response to neuroinflammation plays a major role during CM, participating in both the amplification of the neuroinflammation phenomenon and its resolution. In this study, we aimed to identify risk factors for CM death among specific variables of inflammatory and oxidative responses to improve our understanding of CM pathogenesis. Methods: Children presenting with CM (n = 70) due to P. falciparuminfection were included in southern Benin and divided according to the clinical outcome into 50 children who survived and 20 who died. Clinical examinationwas complemented by fundoscopic examination and extensive blood biochemical analysis associated with molecular diagnosis by multiplex PCR targeting 14 pathogens in the patients’ cerebrospinal fluid to rule out coinfections. Luminex technology and enzyme immunoassay kits were used to measure 17 plasma and 7 urinary biomarker levels, respectively. Data were analysedby univariate analysis using the nonparametric Mann‒Whitney U test and Chi2 Pearson test. Adjusted and multivariate analyses were conducted separately for plasma and urinary biomarkers to identify CM mortality risk factors. Results: Univariate analysis revealed that higher plasma levels of TNF, IL-1β, IL-10, IL-8, CXCL9, granzyme B, and angiopoietin-2 and lower urinary levels of PGEM were associated with CM mortality. The multivariate logistic analysis highlighted elevated plasma levels of IL-8 as the main risk factor for death during CM. Values obtained during follow-up at D3 and D30 revealed immune factors associated with disease resolution, including plasma CXCL5, CCL17, CCL22, and urinary 15-F2t-isoprostane. Conclusions: These results provide important insight into our understanding of CM pathogenesis and clinical outcome and may have important therapeutic implications.

ObjectivesThe emergence of SARS-CoV-2 variants raised questions over the extent to which vaccines designed in 2020 have remained effective. We aimed to assess whether vaccine status was associated with the severity of Omicron SARS-CoV-2 infection in hospitalised patients.MethodsWe conducted an international, multicentric, retrospective study in 14 centres (Bulgaria, Croatia, France, Turkey). We collected data on patients hospitalised ≥24 hours between 01/12/2021 and 03/03/2022, with PCR-confirmed infection at a time of exclusive Omicron circulation, with hospitalisation related or not to the infection. Patients who had received prophylaxis by monoclonal antibodies were excluded. Patients were considered fully vaccinated if they had received at least 2 injections of either mRNA and/or ChAdOx1-S, or 1 injection of Ad26.CoV2-S vaccines.ResultsAmong the 1215 patients (median [IQR] age 73.0 [57.0; 84.0]; 51.3% males), 746 (61.4%) were fully vaccinated. In multivariate analysis, being vaccinated was associated with lower 28-day mortality (RR=0.50 [0.32-0.77]), ICU admission (R=0.40 [0.26-0.62], and oxygen requirement (RR=0.34 [0.25-0.46]), independently of age and comorbidities. When co-analysing these Omicron patients with 948 Delta patients from a study we recently conducted, Omicron infection was associated with lower 28-day mortality (RR=0.53 [0.37-0.76]), ICU admission (R=0.19 [0.12-0.28], and oxygen requirements (RR=0.50 [0.38-0.67]), independently of age, comorbidities and vaccination status.ConclusionsmRNA- and adenovirus-based vaccines have remained effective on severity of Omicron SARS-CoV-2 infection. Omicron is associated with a lower risk of severe forms, independently of vaccination and patient characteristics.

Les infections asymptomatiques ne sont pas rares ; les signes cliniques associent le plus souvent des signes généraux et des signes respiratoires ; ils sont polymorphes et non spécifiques. La tomodensitométrie thoracique est un outil important d’aide au diagnostic et de triage pour les patients dont l’état justifie une hospitalisation. Les deux complications principales de la maladie sont d’une part la détresse respiratoire par aggravation de la pneumonie, qui survient le plus souvent après sept à dix jours d’évolution dans le cadre d’un orage cytokinique, et la maladie thromboembolique d’autre part. Le taux de létalité est de l’ordre de 2 %. La prise en charge en milieu hospitalier comporte l’oxygénation le plus souvent et toujours la prévention de la maladie thromboembolique. Les surinfections bactériennes sont rares. Le remdésivir permettrait de raccourcir la durée des signes cliniques chez des patients hospitalisés et sous oxygénothérapie. La dexaméthasone permettrait de réduire la létalité chez les patients dont l’état justifie une ventilation mécanique. Le développement de nombreux candidats vaccins suscite beaucoup d’espoir pour accélérer la sortie de pandémie.

BackgroundThe diffusion of the SARS-CoV-2 delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status.MethodsWe retrospectively analysed data from patients hospitalised in 10 centres with a SARS-CoV-2 infection (delta variant) from July to November 2021: i) all patients who had completed their primary vaccination at least 14 days before hospital admission; and ii) the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression.FindingsWe included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older, more frequently males, and with more comorbidities. They were less often admitted for Covid-19 (59·3% vs. 75·1%, pConclusionsAmong patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.

Objective We aimed to investigate whether anakinra, an interleukin-1receptor inhibitor, could improve outcome in moderate COVID-19 patients. Methods In this controlled, open-label trial, we enrolled adults with COVID-19 requiring oxygen. We randomly assigned patients to receive intravenous anakinra plus optimized standard of care (oSOC) vs. oSOC alone. The primary outcome was treatment success at day 14 defined as patient alive and not requiring mechanical ventilation or extracorporeal membrane oxygenation. Results Between 27th April and 6th October 2020, we enrolled 71 patients (240 patients planned to been enrolled): 37 were assigned to the anakinra group and 34 to oSOC group. The study ended prematurely by recommendation of the data and safety monitoring board due to safety concerns. On day 14, the proportion of treatment success was significantly lower in the anakinra group 70% (n = 26) vs. 91% (n = 31) in the oSOC group: risk difference—21 percentage points (95% CI, -39 to -2), odds ratio 0.23 (95% CI, 0.06 to 0.91), p = 0.027. After a 28-day follow-up, 9 patients in the anakinra group and 3 in the oSOC group had died. Overall survival at day 28 was 75% (95% CI, 62% to 91%) in the anakinra group versus 91% (95% CI, 82% to 100%) (p = 0.06) in the oSOC group. Serious adverse events occurred in 19 (51%) patients in the anakinra group and 18 (53%) in the oSOC group (p = 0·89). Conclusion This trial did not show efficacy of anakinra in patients with COVID-19. Furthermore, contrary to our hypothesis, we found that anakinra was inferior to oSOC in patients with moderate COVID-19 pneumonia.

Background: The interplay between cancer and IE has become of increasing interest. This study sought to assess the prevalence, baseline characteristics, management, and outcomes of IE cancer patients in the ESC EORP EURO-ENDO registry.Methods: Three thousand and eighty-five patients with IE were identified based on the ESC 2015 criteria. Three hundred and fifty-nine (11.6%) IE cancer patients were compared to 2,726 (88.4%) cancer-free IE patients.Results: In cancer patients, IE was mostly community-acquired (74.8%). The most frequently identified microorganisms were S. aureus (25.4%) and Enterococci (23.8%). The most frequent complications were acute renal failure (25.9%), embolic events (21.7%) and congestive heart failure (18.1%). Theoretical indication for cardiac surgery was not significantly different between groups (65.5 vs. 69.8%, P = 0.091), but was effectively less performed when indicated in IE patients with cancer (65.5 vs. 75.0%, P = 0.002). Compared to cancer-free IE patients, in-hospital and 1-year mortality occurred in 23.4 vs. 16.1%, P = 0.006, and 18.0 vs. 10.2%; P < 0.001, respectively. In IE cancer patients, predictors of mortality by multivariate analysis were creatinine > 2 mg/dL, congestive heart failure and unperformed cardiac surgery (when indicated).Conclusions: Cancer in IE patients is common and associated with a worse outcome. This large, observational cohort provides new insights concerning the contemporary profile, management, and clinical outcomes of IE cancer patients across a wide range of countries.

Purpose: Kidney Transplant Recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation and outcome. While infective endocarditis (IE) is among such complications in KTRs, literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. Methods: We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria), in adult KTRs from January 2007 to December 2018 were included, as well as two controls per case, and followed until December 31 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan-Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Results: Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated only age was significantly associated with the occurrence of IE in our study (63.8 years for cases vs. 55.6 years for controls, P=0.03) Patient and death-censored graft survival were greatly diminished five years after IE compared to controls being 50.3% vs. 80.6% (p

Kidney transplant recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation, and outcome. While infective endocarditis (IE) is among such complications in KTRs, the literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria) in adult KTRs from January 2010 to December 2018 were included, as well as two controls per case, and followed until 31 December 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan–Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus, and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated, age, vascular nephropathy, and elevated calcineurin inhibitor through levels were significantly associated with the occurrence of IE in our study. Patient and death-censored graft survival were greatly diminished five years after IE, compared to controls being 50.3% vs. 80.6% (p &lt, 0.003) and 29.7% vs. 87.5% (p &lt, 0.002), respectively. IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant.

Objectives To determine whether hydroxychloroquine decreases the risk of adverse outcome in patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk of worsening. Methods We conducted a multicentre randomized double-blind placebo-controlled trial evaluating hydroxychloroquine in COVID-19 patients with at least one of the following risk factors for worsening: need for supplemental oxygen, age ≥75 years, age between 60 and 74 years and presence of at least one co-morbidity. Severely ill patients requiring oxygen therapy >3 L/min or intensive care were excluded. Eligible patients were randomized in a 1:1 ratio to receive either 800 mg hydroxychloroquine on day 0 followed by 400 mg per day for 8 days or a placebo. The primary end point was a composite of death or start of invasive mechanical ventilation within 14 days following randomization. Secondary end points included mortality and clinical evolution at days 14 and 28, and viral shedding at days 5 and 10. Results The trial was stopped after 250 patients were included because of a slowing down of the pandemic in France. The intention-to-treat population comprised 123 and 124 patients in the placebo and hydroxychloroquine groups, respectively. The median age was 77 years (interquartile range 58–86 years) and 151/250 (60.4%) patients required oxygen therapy. The primary end point occurred in 9/124 (7.3%) patients in the hydroxychloroquine group and 8/123 (6.5%) patients in the placebo group (relative risk 1.12; 95% CI 0.45–2.80). The rates of positive SARS-CoV-2 RT-PCR tests at days 5 and 10 were 72.8% (75/103) and 57.1% (52/91) in the hydroxychloroquine group, versus 73.0% (73/100) and 56.6% (47/83) in the placebo group, respectively. No difference was observed between the two groups in any of the other secondary end points. Conclusion In this underpowered trial involving mainly older patients with mild to moderate COVID-19, patients treated with hydroxychloroquine did not experience better clinical or virological outcomes than those receiving the placebo. Trial registration ClinicalTrials.gov Identifier: NCT04325893 ( https://clinicaltrials.gov/ct2/show/NCT04325893 ).

Resume En 2017, la Societe de pathologie infectieuse de langue francaise a mis a jour ses recommandations sur le traitement et la prevention, antivectorielle et medicamenteuse, du paludisme d’importation. Le pharmacien d’officine doit les connaitre afin d’etre en mesure d’analyser la strategie mise en place par le prescripteur et de donner des conseils aux voyageurs.

International audience; Paecilomyces sp. are emerging pathogens in immunocompromised patients. We report here a case of Paecilomyces variotii fungemia, cured with amphotericin and anidulafungin, illustrating difficulties of early diagnosis and therapeutic choice in such rare fungal infection.

IntroductionIn 2016, an estimated 216 million cases and 445 000 deaths of malaria occurred worldwide, in 91 countries. In Benin, malaria causes 26.8% of consultation and hospitalisation motif in the general population and 20.9% in children under 5 years old.The goal of the NeuroCM project is to identify the causative factors of neuroinflammation in the context of cerebral malaria. There are currently very few systematic data from West Africa on the aetiologies and management of non-malarial non-traumatic coma in small children, and NeuroCM will help to fill this gap. We postulate that an accurate understanding of molecular and cellular mechanisms involved in neuroinflammation may help to define efficient strategies to prevent and manage cerebral malaria.Methods and analysisThis is a prospective, case-control study comparing cerebral malaria to uncomplicated malaria and non-malarial non-traumatic coma. This study takes place in Benin, precisely in Cotonou for children with coma and in Sô-Ava district for children with uncomplicated malaria. We aim to include 300 children aged between 24 and 71 months and divided in three different clinical groups during 12 months (from December 2017 to November 2018) with a 21 to 28 days follow-up for coma. Study data, including clinical, biological and research results will be collected and managed using CSOnline-Ennov Clinical.Ethics and disseminationEthics approval for the NeuroCM study has been obtained fromComité National d’Ethique pour la Recherche en santéof Benin (n°67/MS/DC/SGM/DRFMT/CNERS/SA; 10/17/2017). NeuroCM study has also been approved byComité consultatif de déontologie et d’éthiqueof Institut de Recherche pour le Développement (IRD; 10/24/2017). The study results will be disseminated through the direct consultations with the WHO’s Multilateral Initiative on Malaria (TDR-MIM) and Roll Back Malaria programme, through scientific meetings and peer-reviewed publications in scientific or medical journals, and through guidelines and booklets.

Background Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. Methods Antimalarial studies typically report the risk of recrudescence derived using the Kaplan–Meier (K–M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K–M method (1 minus K–M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K–M curves was assessed using the log-rank test, and the equality of CIFs using Gray’s k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray’s sub-distributional hazard model. Results Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K–M approach was 0.04% (interquartile range (IQR): 0.00–0.27%, Range: 0.00–3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson’s correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30–0.46] or new infection [ρ: 0.43; 95% CI 0.35–0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K–M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. Conclusions The 1 minus K–M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings. Electronic supplementary material The online version of this article (10.1186/s12936-019-2837-4) contains supplementary material, which is available to authorized users.

Data centered on antibiotics usage and their determinants in African pediatric populations are limited. In order to define the determinants of antibiotics prescriptions (ABPr), we analyzed the data of a birth cohort in Benin. From 2007 to 2009, 538 infants were followed from birth to 18 months in three different health centers. The following determinants were assessed: infants' clinical findings at consultations, mothers' and children's characteristics at birth, and health parameters recorded at scheduled follow-up of general health parameters. Multilevel logistic models were performed for analysis. Among the 4394 consultations, fever represented 53.7 % of consultations, 64.1 % of which were non-malarial fevers. Antibiotics were prescribed during 44.2 % of the consultations and the proportion of ABPr differed significantly among health centers (p

Introduction La morbidite et la mortalite dues au paludisme ont diminue ces 20 dernieres annees, alors que les infections virales du systeme nerveux central ont ete recemment identifiees comme une cause importante d’hospitalisation avec coma en Afrique de l’Est, ou le paludisme est endemique. Notre objectif etait de decrire l’etiologie, la prise en charge et le pronostic des comas non traumatiques chez le jeune enfant au Benin. Materiels et methodes Cette etude prospective a ete menee dans deux hopitaux universitaires. Tous les enfants VIH-negatifs âges de 2 a 6 ans, ayant un coma avec score de Blantyre inferieur ou egal a 2 ont ete inclus. En plus d’un bilan a la recherche des signes de gravite du paludisme, une hemoculture, une PCR syndromique « fievre tropicale » (Fast Track Diagnosis, Luxembourg) et une analyse du liquide cephalorachidien (LCR), comprenant une PCR multiplex (Biofire, Merieux, France) et une recherche d’adenovirus, ont ete effectuees. Tous les enfants atteints de paludisme ont ete traites avec de l’artesunate par voie intraveineuse. Les patients ont egalement eu acces a d’autres traitements, dont des transfusions sanguines, prescrits a la discretion du medecin. Resultats Entre mars et novembre 2018, 84 enfants ont ete inclus, dont 50 filles (sex-ratio : 0,68) avec un âge moyen de 43 ± 13 mois. Une fievre etait rapportee chez tous les patients, avec une duree d’evolution moyenne de 4 (1–14) jours. Pour 90 % d’entre eux (76/84), des soins avaient ete dispenses par un professionnel de sante avant l’admission, mais seuls 11 enfants avaient recu un traitement oral antipaludeen adequat. Le paludisme etait la seule cause de coma identifiee chez 72 patients (86 %). Six avaient une co-infection (1 meningite purulente decapitee, 1 bacteriemie a Staphylococcus aureus, 1 bacteriemie a Streptococcus, 1 encephalite a West Nile Virus, 1 encephalite a HHV6 et 1 encephalite a adenovirus) et 6 avaient un coma non palustre (1 bacteriemie a E. coli, 1 dengue, 4 indetermines). Vingt enfants (23 %) ont recu une antibiotherapie par ceftriaxone, et la plupart (58/84) ont recu des transfusions sanguines. Le taux de letalite etait de 30 % (26/84), dont 19 deces (23 %) dans les 24 heures suivant l’admission. Sur les 49 enfants suivis a j28, 20 (41 %) avaient des difficultes a marcher, 2 des difficultes a voir, et 1 des difficultes a entendre. Conclusion Le neuropaludisme reste de loin la cause la plus frequente de coma non traumatique dans la zone etudiee, avec un taux de letalite eleve malgre un acces a des soins standardises. Pour la plupart des enfants, le parcours de soin n’a pas abouti a un traitement antipaludeen precoce et efficace. Le paludisme doit etre prevenu, mais les efforts de prevention ne doivent pas releguer au second plan le renforcement necessaire des capacites de prise en charge des formes potentiellement fatales de la maladie.

International audience; Liposomal amphotericin B (LAmb) may fail to heal Leishmania infantum visceral leishmaniasis (VL) in the immunodeficient host. There are currently no guidelines on how to treat such patients and efficacy of miltefosine monotherapy seems limited in this indication. We present 2 cases of patients with VL and AIDS for which LAmb had to be interrupted (one because of toxicity, one because of treatment failure) and who were treated effectively with pentamidine followed by miltefosine.

Bacterial diseases of the nervous system comprise a broad range of diseases with their related pathogens. Many bacterial infections can spread to the nervous system, most of them by the hematogenous route. Some, like bacterial meningitis, represent a high disease burden worldwide, which disproportionally affects young children and deserves vigorous interventions for prevention by vaccination. There is a preponderance of tuberculous meningitis, which still has a poor prognosis, in infants and small children and in patients with AIDS. Along with a significant mortality, a high proportion of patients with bacterial and tuberculous meningitis survive with sequelae, most often in poor-resource healthcare settings. Intracellular bacteria, spirochetes, can also cause meningitis and meningoencephalitis. Leprosy, which affects peripheral nerves, is rarely lethal but can result in significant disabilities. Following the Maternal and Neonatal Tetanus Elimination Initiative, global deaths from neonatal tetanus were dramatically reduced but tetanus still kills infants and adults.

Introduction Tick bites, which may lead to Lyme disease, often prompt patients to consult their primary care physicians (PCPs). The aim of the present study was to assess how and how often PCPs in the Franche-Comte region of France manage tick bites. Material and methods Standardized questionnaires were sent to a random sample of 400 PCPs in the Franche-Comte region, requesting their voluntary and anonymous participation. The questionnaires collected socio-demographic details and practice-related information about tick-bite prophylaxis, Lyme serology, and tick-borne encephalitis vaccination. Results The crude response rate was 54.5% of the PCPs contacted. Tick-bite prophylaxis was prescribed as per current guidelines. However, Lyme serology seemed to be largely overprescribed for tick bites and in case of erythema migrans. A clear lack of knowledge about tick-borne encephalitis vaccination was also observed. Discussion PCPs provide the first line of care for patients presenting with tick bites. This study showed that although PCPs of the Franche-Comte region manage tick bites as per current guidelines, they need further training on Lyme serology limitations and availability of tick-borne encephalitis vaccination.

Artemisinin-based combination therapies (ACTs) are the main option to treat malaria, and their efficacy and susceptibility must be closely monitored to avoid resistance. We assessed the association of Plasmodium falciparum polymorphisms and ex vivo drug susceptibility with clinical effectiveness. Patients enrolled in an effectiveness trial comparing artemether-lumefantrine ( n = 96), fixed-dose artesunate-amodiaquine ( n = 96), and sulfadoxine-pyrimethamine ( n = 48) for the treatment of uncomplicated malaria 2007 in Benin were assessed. pfcrt , pfmdr1 , pfmrp1 , pfdhfr , and pfdhps polymorphisms were analyzed pretreatment and in recurrent infections. Drug susceptibility was determined in fresh baseline isolates by Plasmodium lactate dehydrogenase enzyme-linked immunosorbent assay (ELISA). A majority had 50% inhibitory concentration (IC 50 ) estimates (the concentration required for 50% growth inhibition) lower than those of the 3D7 reference clone for desethylamodiaquine, lumefantrine, mefloquine, and quinine and was considered to be susceptible, while dihydroartemisinin and pyrimethamine IC 50 s were higher. No association was found between susceptibility to the ACT compounds and treatment outcome. Selection was observed for the pfmdr1 N86 allele in artemether-lumefantrine recrudescences (recurring infections) (4/7 [57.1%] versus 36/195 [18.5%]), and of the opposite allele, 86Y, in artesunate-amodiaquine reinfections (new infections) (20/22 [90.9%] versus 137/195 [70.3%]) compared to baseline infections. The importance of pfmdr1 N86 in lumefantrine tolerance was emphasized by its association with elevated lumefantrine IC 50 s. Genetic linkage between N86 and Y184 was observed, which together with the low frequency of 1246Y may explain regional differences in selection of pfmdr1 loci. Selection of opposite alleles in artemether-lumefantrine and artesunate-amodiaquine recurrent infections supports the strategy of multiple first-line treatment. Surveillance based on clinical, ex vivo , molecular, and pharmacological data is warranted.

International audience; The prognosis of vertebral alveolar echinococcosis (AE) is poor. We report on the unique outcome of a patient with preexisting liver cirrhosis, in whom a diagnosis of vertebral AE was established on vertebral histopathology (D4 corporectomy in 2010 for paraplegia). Therapeutic drug monitoring of albendazole (ABZ) showed that a low dosage was appropriate. The patient recovered and ABZ withdrawal was decided in 2014, with no relapse 18 months later. In this patient, infection was purely or mainly localized in the dorsal spine, and this may have been favored by liver cirrhosis. A longer follow-up is, however, needed to confirm cure.

Introduction Cette etude est centree sur la prise en charge des comas pediatriques non traumatiques dans une zone urbaine de l’Afrique de l’Ouest. Dans un contexte de recul de la mortalite palustre, une etude systematique des etiologies de comas est attendue. Une etude realisee au Malawi a montre une prevalence elevee d’infections virales du systeme nerveux central (SNC). L’analyse des liquides cerebro-spinaux (LCS) des enfants inclus a ete systematiquement proposee. Materiels et methodes C’est une etude prospective bicentrique. Les criteres d’inclusion etaient un âge compris entre 24 et 71 mois et des troubles de la conscience avec un score de Blantyre ≤ 2. Les criteres d’exclusion etaient un test de diagnostic rapide VIH positif, l’absence de consentement parental, une origine traumatique ou toxique du coma, une pathologie neurologique preexistante. Tous les enfants inclus avaient un bilan biologique sanguin incluant une recherche du paludisme (goutte epaisse (GE)). Ils etaient eligibles a une ponction lombaire en l’absence de contre-indication. Outre l’analyse bacteriologique et cytochimique, une PCR multiplex (14 cibles) a ete realisee sur les LCS. Resultats De mars a novembre 2018, 85 enfants ont ete inclus et 73 (85,9 %) LCS ont ete preleves. Le geste etait contre-indique pour 9 enfants et pour 3 d’entre eux, la tentative s’est soldee par un echec ; 11 des 12 enfants sans analyse du LCS avaient une GE positive. Parmi les 10 LCS (13,7 %) montrant une reaction cellulaire > 10 elements/mm3, seul un prelevement avait les caracteristiques d’une meningite purulente decapitee. Aucun examen direct ou culture ne s’est revele positif. Huit de ces enfants (80 %) avaient une GE positive. Parmi les 63 LCS sans pleiocytose, 2 cultures polymicrobiennes ont ete interpretees comme des contaminations. Cinquante-cinq (87,3 %) de ces enfants avaient une GE positive. La PCR a ete realisee sur 62 LCS et a objective une co-infection virale par un herpes virus humain type 6 HHV6 (GE positive) ; aucune autre etiologie infectieuse n’a ete retrouvee. Conclusion Les atteintes infectieuses bacteriennes ou virales du SNC constituent une tres faible proportion des etiologies de comas pediatriques non traumatiques dans cette population. Les atteintes neurologiques dues au paludisme demeurent de tres loin la premiere etiologie et les co-infections semblent rarissimes.

Resume But de l’etude Les auteurs ont conduit une evaluation de la conformite de l’antibiotherapie probabiliste dans un centre hospitalier de niveau I. Patients et methodes L’etude de conformite des prescriptions d’antibiotiques a ete realisee de maniere retrospective a partir des dossiers medicaux des patients admis aux urgences en 2011 au centre hospitalier Louis-Jaillon pour infection respiratoire basse. Le referentiel utilise s’appuyait sur les recommandations de l’Agence francaise de securite sanitaire des produits de sante (AFSSAPS) en coordination avec la Societe de pathologie infectieuse de langue francaise (SPILF) edite en 2010. Resultats Quarante patients ont ete inclus. La moyenne d’âge etait de 75,7 ans. Pour les 40 patients, une antibiotherapie a ete debutee aux urgences. Le taux de conformite est de 55 %. La ceftriaxone etait la molecule la plus prescrite (65 %) suivie de l’ofloxacine (55 %) et de l’amoxicilline-acide clavulanique (32 %). Parmi les prescriptions non conformes (45 %), 77 % consistaient en une bitherapie non justifiee associant majoritairement (83 %) ceftriaxone et ofloxacine. Conclusion Le taux de conformite de 55 % retrouve dans cette etude rentre dans la fourchette des taux decrits dans la litterature. Cependant, l’utilisation excessive de fluoroquinolones est deletere pour l’ecologie microbienne du patient et de l’hopital, du fait du risque d’apparition de resistances aux fluoroquinolones et d’enterobacteries productrices de beta-lactamases a spectre elargi.

Introduction La Trypanosomiase humaine africaine est une parasitose endemique dans certaines regions d’Afrique subsaharienne. Elle peut etre responsable d’atteinte encephalitique severe pouvant aller jusqu’au deces si elle n’est pas prise en charge a temps. Observation Nous rapportons ici le cas d’une jeune patiente de 21 ans originaire du Congo, arrivee en France recemment. Celle-ci a presente rapidement des troubles du comportement, de l’humeur, du sommeil et un syndrome confusionnel, pour lesquels elle a consulte aux urgences a plusieurs reprises. Un syndrome infectieux est apparu par la suite. La ponction lombaire retrouvait dans le LCR 225 elements. l’IRM cerebral retrouvait des hypersignaux diffus de la substance blanche bilateral, en sequence FLAIR, sus et sous tentoriels. La serologie positive dans le LCR a permis de porter le diagnostic de meningoencephalite a Trypanosoma brucei. La patiente a beneficie d’un traitement anti-infectieux par Eflornithine et Nifurtimox. L’evolution clinique a 6 mois mettait en evidence des sequelles neuro psychologiques avec une labilite thymique, un syndrome dysexecutif, et des troubles phasiques. L’IRM cerebral de controle montrait une nette regression des hypersignaux de la substance blanche. Discussion La description des cas de meningoencephalites a Trypanosomiases et notamment la description des lesions cerebrales a l’IRM est assez rare dans la litterature. Un diagnostic est possible avec de simples serologies et des traitements antibiotiques efficaces existent a la phase cerebrale. Cependant la meconnaissance de cette pathologie peut aboutir a un retard diagnostic et a une issue fatale. Conclusion La trypanosomiase humaine africaine peut se rencontrer dans nos hopitaux par les migrants ou les voyageurs. Un diagnostic precoce de la phase cerebrale pourrait permettre de limiter les sequelles neurologiques.

Background. We compared sulfadoxine-pyrimethamine (SP) with unsupervised artemether-lumefantrine (AL) and unsupervised amodiaquine-artesunate (ASAQ) fixed-dose formulation for the treatment of uncomplicated malaria in children in Benin. Methods. This open-label, noninferiority comparative trial included children aged 6―60 months. The follow-up period was 6 weeks, and the primary objective was a comparison of polymerase chain reaction (PCR)―adjusted effectiveness rates at day 28. Results. The study included 240 children (48 received SP, and 96 each received AL and ASAQ). The intention-to-treat analysis showed effectiveness rates on day 28 of 20.8%, 78.1 %, and 70.5% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 27.1%, 83.3%, and 87.4%, respectively. The per-protocol analysis (217 patients) showed effectiveness rates on day 28 of 21.7%, 88.0%, and 76.1% for SP, AL, and ASAQ, respectively. After adjustment for PCR results, these rates were 28.3%, 94.0%, and 93.2%, respectively. SP was less effective than the other drugs in the PCR-adjusted analysis, whereas AL and ASAQ were equally effective. The rate of new infection was higher among children treated with ASAQ than among those treated with AL. Conclusions. This was the first trial, to our knowledge, to compare unsupervised AL with unsupervised ASAQ fixed-dose formulation; both treatments provided high PCR-adjusted day 28 effectiveness rates. Efficacy rates for SP were surprisingly low. Clinical trials registration. NCT00460369.

International audience; Short-course (less than 7 days) antibiotic treatments have been rarely assessed in the management of leptospirosis. We analyzed the charts of patients hospitalized with confirmed and probable leptospirosis in a teaching hospital between 1994 and 2012. Of 89 patients with confirmed or probable leptospirosis, 21 patients (11 confirmed, 10 probable - 14 uncomplicated and 7 severe forms) admitted between 2001 and 2012 received ceftriaxone (1-2 g daily) for less than 7 days. Apyrexia was obtained within 2 days of treatment in all patients and no relapse was observed. These data support the hypothesis that short-course treatments of 3-6 days with ceftriaxone (1-2 g per day) may be an option in the treatment of uncomplicated and severe forms of leptospirosis responding quickly to therapy. This hypothesis deserves being confirmed in further clinical studies.

Since 2008, the French guidelines have promoted the systematic use of 30 mg/day of primaquine for the radical cure of Plasmodium vivax and Plamodium ovale infections. We observed three relapses in 10 patients with P vivax acquired in French Guiana. No relapses were seen in West African P ovale patients.

How to quickly identify patients who should be treated for leptospirosis is a challenge. The interest of polymerase chain reaction (PCR) assays is currently being evaluated and rapid tests which can be used outside of the specialised laboratory, have recently been developed. Leptospires are sensitive to many antibiotics and few clinical studies have been made to compare different treatment options. Doxycycline is standard therapy in early leptospirosis treatment and chemoprophylaxis. Intravenous penicillin has been considered the drug of choice in late and severe disease, although it is now challenged by ceftriaxone, which use is easier. Ciprofloxacin may be combined with standard therapy in uveitis. Adjunctive therapies proposed in the management of severe forms of leptospirosis and Jarisch-Herxheimer reactions, are reviewed.

Resume Objectifs Au cours de l’annee 1999, les associations d’antiretroviraux de premiere ligne pour traiter l’infection par le VIH se sont diversifiees. L’objectif de notre travail est double : definir les facteurs associes d’une part au succes primaire, d’autre part a l’echappement virologique pour les patients chez qui un premier traitement antiretroviral (ARV) a ete debute entre 1999 et 2000. Methode Il s’agit d’une etude retrospective multicentrique rassemblant 6 CISIH (Centre d’information et de soins de l’immunologie humaine) du Nord-Est de la France. Les donnees sont issues des dossiers medicaux des patients. Le succes primaire correspond a une charge virale plasmatique (CVP) 1 000 copies ARN-VIH/ml, lors de 2 mesures consecutives apres un succes primaire. L’analyse statistique, monovariee et multivariee, a ete effectuee a l’aide du logiciel SAS 8.2 (Sas Institute Inc.). Resultats L’analyse concerne 123 patients, dont 19 % sont au stade C lorsque le traitement ARV est debute. La valeur mediane des CD4 est de 233/mm3 et celle de la charge virale plasmatique de 72 900 copies/ml. La duree mediane de suivi est de 20,7 mois moyenne (ecart type) : 20,6 (6,7). Les traitements initiaux sont distribues de la maniere suivante : 2 inhibiteurs nucleosidiques de la transcriptase inverse (INTI) + 1 inhibiteur non nucleosidique de la transcriptase inverse (INNTI), n = 66 (54 %) ; 2 INTI +1 inhibiteur de protease, n = 44 (36 %) ; 3 INTI, n = 13 (10 %). La proportion de succes primaire est de 81,3 % (100/123). La proportion d’echappement virologique est de 6 % (6/123). L’absence de modification du traitement ARV initial avant ou a M4 ainsi que la bonne observance therapeutique a M4 sont statistiquement associees au succes primaire en analyse univariee (p respectifs : 0,004 et 0,04) et multivariee (p a 0,009 et 0,03). La proportion d’echappement est plus elevee chez les patients dont le taux initial de CD4 est inferieur a 200/mm3 (p = 0,09). Conclusion Dans cette cohorte, la tolerance et l’observance du premier traitement sont associees au succes primaire. Ce travail souligne le role de l’observance dans le succes primaire et renforce la necessite d’une aide a l’observance.

A double-blind, placebo-controlled study was conducted to measure the impact of malaria prophylaxis with atovaquone/proguanil (A-P) on the immunogenicity of vaccines against typhoid fever and cholera, Salmonella serotype Typhi Ty21a and Vibrio cholerae CVD103-HgR, respectively. A total of 330 Gabonese schoolchildren were assigned to receive either A-P or placebo for 12 weeks. Vaccination occurred 3 weeks after the start of prophylaxis, and immunogenicity was assessed 4 weeks after vaccination. The protective efficacy of A-P against Plasmodium falciparum malaria was of 97% (95% confidence interval, 79%-100%). The 2 treatment groups did not differ significantly with regard to changes in antibody titers after vaccination (P=.96 for anti-S. Typhi IgG antibodies, P=.07 for anti-S. Typhi IgA antibodies, and P=.64 for vibriocidal antibodies). The A-P combination was highly effective for malaria prophylaxis, without interfering with the in vivo immunogenicity of CVD103-HgR and Ty21a vaccines, and it could therefore be simultaneously administered with these vaccines.