Rectal Carriage of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative Bacilli in Community Settings in Madagascar

BACKGROUND: Extended-spectrum ß-lactamase-producing Enterobacteria (ESBL-PE) emerged at the end of the 1980s, causing nosocomial outbreaks and/or hyperendemic situations in hospitals and long-term care facilities. In recent years, community-acquired infections due to ESBL-PE have spread worldwide, especially across developing countries including Madagascar. OBJECTIVES: This study aimed to determine the prevalence and risk factors of intestinal carriage of ESBL-PE in the community of Antananarivo. METHODS: Non-hospitalized patients were recruited in three health centers in different socio economic settings. Fresh stool collected were immediately plated on Drigalski agar containing 3 mg/liter of ceftriaxone. Gram-negative bacilli species were identified and ESBL production was tested by a double disk diffusion (cefotaxime and ceftazidime +/- clavulanate) assay. Characterization of ESBLs were perfomed by PCR and direct sequencing . Molecular epidemiology was analysed by Rep-PCR and ERIC-PCR. RESULTS: 484 patients were screened (sex ratio  = 1.03, median age 28 years). 53 ESBL-PE were isolated from 49 patients (carrier rate 10.1%). The isolates included Escherichia coli (31), Klebsiella pneumoniae (14), Enterobacter cloacae (3), Citrobacter freundii (3), Kluyvera spp. (1) and Pantoae sp.(1). In multivariate analysis, only the socioeconomic status of the head of household was independently associated with ESBL-PE carriage, poverty being the predominant risk factor. CONCLUSIONS: The prevalence of carriage of ESBL in the community of Antananarivo is one of the highest reported worldwide. This alarming spread of resistance genes should be stopped urgently by improving hygiene and streamlining the distribution and consumption of antibiotics

Three-dimensional cartography of functional territories in the human striatopallidal complex by using calbindin immunoreactivity

International audienceThis anatomic study presents an analysis of the distribution of calbindin immunohistochemistry in the human striatopallidal complex. Entire brains were sectioned perpendicularly to the mid-commissural line into 70-microm-thick sections. Every tenth section was immunostained for calbindin. Calbindin labeling exhibited a gradient on the basis of which three different regions were defined: poorly labeled, strongly labeled, and intermediate. Corresponding contours were traced in individual sections and reformatted as three-dimensional structures. The poorly labeled region corresponded to the dorsal part of the striatum and to the central part of the pallidum. The strongly labeled region included the ventral part of the striatum, the subcommissural part of the external pallidum but also the adjacent portion of its suscommissural part, and the anterior pole of the internal pallidum. The intermediate region was located between the poorly and strongly labeled regions. As axonal tracing and immunohistochemical studies in monkeys show a similar pattern, poorly, intermediate, and strongly labeled regions were considered as the sensorimotor, associative, and limbic territories of the human striatopallidal complex, respectively. However, the boundaries between these territories were not sharp but formed gradients of labeling, which suggests overlapping between adjacent territories. Similarly, the ventral boundary of the striatopallidal complex was blurred, suggesting a structural intermingling with the substantia innominata. This three-dimensional partitioning of the human striatopallidal complex could help to define functional targets for high-frequency stimulation with greater accuracy and help to identify new stimulation sites

Delineation of the basal ganglia in MR images of patients by automatic registration of a multimodal atlas based on histological and MR data

International audienceno abstrac

A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data

This paper describes the construction of an atlas of the human basal ganglia. The successive steps of the construction were as follows. First a postmortem specimen was subjected to a MRI acquisition prior to extraction of the brain from the skull. The brain was then cryosectioned (70 mum thickness). One section out of ten (80 sections) was Nissl-stained with cresyl violet, another series of 80 sections was immunostained for the calcium binding protein calbindin. Contours of basal ganglia nuclei including their calbindin-stained functional subdivisions, fiber bundles and ventricles (n=80 structures) were traced from histological sections and digitized. A novelty of this atlas is the MRI acquisition, which represents the core data element of the study. MRI was used for the coregistration of the atlas data and permitted, through multimodal (Nissl, calbindin, images of cryosectioning, T1 and T2 MRI) and 3D optimization, the production of anatomically and geometrically consistent 3D surfaces, which can be sliced through any desired orientation. The atlas MRI is also used for its deformation to provide accurate conformation to the MRI of living patients, thus adding information at the histological level to the patient's MRI volume. This latter aspect will be presented in a forthcoming paper

Elaboration of a three-dimensional, functional and registrable atlas of the human basal ganglia

International audienceno abstrac

A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery.

International audienceThe cardinal symptoms in Parkinson's disease (PD), akinesia, rigidity and tremor, are only observed when the striatal level of dopamine is decreased by 60-80%. During the preclinical phase of PD, compensatory mechanisms are probably involved in delaying the appearance of motor symptoms. In a MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) monkey model of PD, a spontaneous recovery has been reported after initial intoxication suggesting that compensatory mechanisms are activated in this model as well. Assuming that mechanisms are similar in these phenomena, the study of recovery in monkeys following MPTP intoxication may enable identification of compensatory mechanisms involved in the preclinical phase of PD. In order to maximize the temporal similarity between PD and the MPTP model, we assessed a new progressive monkey model in which spontaneous recovery is expressed systematically and to characterize it based on (1) its behavioural features, and (2) the presence of compensatory mechanisms revealed by an immunohistological approach comparing dopaminergic and serotoninergic innervation between monkeys either exhibiting behavioural recovery or stable motor symptoms. This immunohistological study focused on the substantia nigra, striatum and pallidum, and their anatomical and functional subdivisions: sensorimotor, associative and limbic. The behavioural analysis revealed that with progressive MPTP intoxication motor symptoms were initially expressed in all monkeys. Observable recovery from these symptoms occurred in all monkeys (7/7) within 3-5 weeks after the last MPTP injection, and most exhibited a full recovery. In contrast, acute intoxication induced stable motor symptoms. Despite this obvious behavioural difference, immunohistological methods revealed that the loss of dopaminergic cell bodies in substantia nigra was substantial and similar in both MPTP-treated groups. However, quantification of fibres revealed that recovered monkeys displayed more dopaminergic and serotoninergic fibres than those with stable motor symptoms in sensorimotor and associative territories of striatum and more dopaminergic fibres in internal pallidum. This study provides a new model of PD where all monkeys expressed functional recovery from motor symptoms despite a large dopaminergic neuronal loss. The immunohistological results suggest that both dopamine and serotonin could be implicated in the compensatory mechanisms

Delineation of the basal ganglia in MR images of patients by automatic registration of a multimodal atlas based on histological and MR data

International audienceno abstrac

Cholinergic mesencephalic neurons are involved in gait and postural disorders in Parkinson disease

Gait disorders and postural instability, which are commonly observed in elderly patients with Parkinson disease (PD), respond poorly to dopaminergic agents used to treat other parkinsonian symptoms. The brain structures underlying gait disorders and falls in PD and aging remain to be characterized. Using functional MRI in healthy human subjects, we have shown here that activity of the mesencephalic locomotor region (MLR), which is composed of the pedunculopontine nucleus (PPN) and the adjacent cuneiform nucleus, was modulated by the speed of imagined gait, with faster imagined gait activating a discrete cluster within the MLR. Furthermore, the presence of gait disorders in patients with PD and in aged monkeys rendered parkinsonian by MPTP intoxication correlated with loss of PPN cholinergic neurons. Bilateral lesioning of the cholinergic part of the PPN induced gait and postural deficits in nondopaminergic lesioned monkeys. Our data therefore reveal that the cholinergic neurons of the PPN play a central role in controlling gait and posture and represent a possible target for pharmacological treatment of gait disorders in PD