A STUDY ON RECTAL CARRIAGE OF MULTIRESISTANT GRAM-NEGATIVE BACILLI IN CHILDREN ATTENDING PEDIATRIC HOSPITAL AMBOHIMIANDRA, MADAGASCAR

Introduction: Gram-negative bacilli are often responsible for rectal colonization in children. These bacilli normally sensitive to third generation cephalosporins (3GC) have acquired disturbing antibiotic resistance in recent years, hence the interest of our study. The aims are to monitor the epidemiological evolution resistance of Enterobacteriaceae with antibiotics in particular β-lactams, estimate the prevalence of enterobacteria responsible for rectal colonization and their resistance to 3GC. Material and methods: This is a descriptive prospective study of Enterobacteriaceae in children attending Ambohimiandra Hospital for a period of 3 months (from 01 August to 31 October 2015). We have done a rectal swab of all the children whom we have parental consent. The samples were processed at the Laboratory of Medical Biology Faravohitra. The parameters studied are the antecedent of therapy antibiotic, notion of recent hospitalization and the results of microbiological examinations. Results: Of the 55 bacteriological samples obtained, 39 strains of Enterobacteriaceae were isolated, Escherichia coli (n = 12), Enterobacter cloacae (n = 13), Citrobacter spp (n = 1), Salmonella spp. (N = 5) and Shigella spp (n = 2), Proteus mirabilis (n = 1). Six isolated strains (50%) of Escherichia coli showed resistance to ceftriaxone, of which 4 (33.33%) produced ESBL. Conclusion: Gram-negative bacilli responsible for colonization of the digestive tract have several resistances to β-lactams, in particular 3GC, by the production of enzymes (Expanded spectrum beta-lactamase or ESBL and cephalosporinase or CASE) which hydrolyze these antibiotics. Measures to combat the spread of these phenomena resistance must be implemented in the Malagasy community to limit them. KEYWORDS: Rectal porous; Gram negative bacillus; ESBL; Multiresistence

Evaluation of Phenotypic Variations in the Antibiotics Sensitivity of Escherichia Coli by Repeated Exposure

Enterobacteriaceae, in particular Escherichia coli, are habitual residents of the gastrointestinal tract, capable of causing a large number of infections. The MIC varies according to the bacterial strains and the antibiotics used, hence the need to carry out antibiotic sensitivity tests. The objective of this study is to evaluate the behavior of Escherichia coli after repeated exposure to the same antibiotic to demonstrate a possible correlation between excessive intake of antibiotics and bacterial resistance. A prospective and descriptive study was carried out in the Laboratory of Microbiology of Fundamental and Applied Biochemistry (Faculty of Sciences Antananarivo) during the month of November 2019. The strains studied were the reference strain Escherichia coli ATCC 25922 provided by the Laboratory and two clinical strains from the Microbiology Laboratory of the Joseph Ravoahangy Andrianavalona University Hospital Center (CHU JRA) Antananarivo. Repeated exposure to Tobramycin and Ofloxacin of these strains were performed. The results of our study showed that most E. coli is exposed to the antibiotic, the more it develops resistance. The evolution of E. coli\u27s sensitivity is different in the presence of Tobramycin with MICs up to 4 times the starting value while in the presence of Ofloxacin, the MIC increases to 125 times the initial value. This difference may be due to the different target of the antibiotic which causes the bacteria to develop variable mechanisms to escape it. Key words: E. coli - MIC - antibiotics - repeated exposur

Evaluation of Phenotypic Variations in the Antibiotics Sensitivity of Escherichia Coli by Repeated Exposure

Enterobacteriaceae, in particular Escherichia coli, are habitual residents of the gastrointestinal tract, capable of causing a large number of infections. The MIC varies according to the bacterial strains and the antibiotics used, hence the need to carry out antibiotic sensitivity tests. The objective of this study is to evaluate the behavior of Escherichia coli after repeated exposure to the same antibiotic to demonstrate a possible correlation between excessive intake of antibiotics and bacterial resistance. A prospective and descriptive study was carried out in the Laboratory of Microbiology of Fundamental and Applied Biochemistry (Faculty of Sciences Antananarivo) during the month of November 2019. The strains studied were the reference strain Escherichia coli ATCC 25922 provided by the Laboratory and two clinical strains from the Microbiology Laboratory of the Joseph Ravoahangy Andrianavalona University Hospital Center (CHU JRA) Antananarivo. Repeated exposure to Tobramycin and Ofloxacin of these strains were performed. The results of our study showed that most E. coli is exposed to the antibiotic, the more it develops resistance. The evolution of E. coli's sensitivity is different in the presence of Tobramycin with MICs up to 4 times the starting value while in the presence of Ofloxacin, the MIC increases to 125 times the initial value. This difference may be due to the different target of the antibiotic which causes the bacteria to develop variable mechanisms to escape it. Key words: E. coli - MIC - antibiotics - repeated exposur

SEROPREVALENCE OF HIV, HBV, HCV, SYPHILIS AMONG DONORS OF BLOOD AT THE NATIONAL CENTER OF BLOOD TRANSFUSION ANTANANARIVO IN 2014

Introduction: Currently, routine screening for HIV, hepatitis B and C and syphilis is done in most blood banks in the world. Methods: We conducted a prospective descriptive study at the National Blood Transfusion Center (CNTS) Antananarivo for a period of 7 months from January to July 2014, which aims to assess the socio-clinical factors accompanying ineligibility of blood products and to determine the seroprevalence of HIV, hepatitis B, C and syphilis of the blood donors who have spent at CNTS HU JRA Antananarivo during this period. All donors who have abnormal results of microbiological examinations were included. The parameters used and studied were age, sex, marital status, blood and results microbiological examinations for HIV, hepatitis B, C, and syphilis. The prevalence of blood donors who presented a serological abnormality is 3.95% with a predominance of donors with hepatitis B (72.93%) followed by syphilis (18.29%) of the hepatitis C (6.95%) and HIV (1.80%) and a predominance of young people. Conclusion: At the CNTS Antananarivo, the HBV is the main definitive reason for exclusion of these donors. This high prevalence is a real public health problem for the country\u27s health authorities. The search for maximum safety in blood transfusion through firstly a better selection of blood donors by implementing a policy of strong loyalty and other early diagnosis of major diseases transmissible by blood and likely to infect the recipient. KEYWORDS: Antananarivo; Blood donor; Microbiology; Seroprevalence

SEROPREVALENCE OF HIV, HBV, HCV, SYPHILIS AMONG DONORS OF BLOOD AT THE NATIONAL CENTER OF BLOOD TRANSFUSION ANTANANARIVO IN 2014

Introduction: Currently, routine screening for HIV, hepatitis B and C and syphilis is done in most blood banks in the world. Methods: We conducted a prospective descriptive study at the National Blood Transfusion Center (CNTS) Antananarivo for a period of 7 months from January to July 2014, which aims to assess the socio-clinical factors accompanying ineligibility of blood products and to determine the seroprevalence of HIV, hepatitis B, C and syphilis of the blood donors who have spent at CNTS HU JRA Antananarivo during this period. All donors who have abnormal results of microbiological examinations were included. The parameters used and studied were age, sex, marital status, blood and results microbiological examinations for HIV, hepatitis B, C, and syphilis. The prevalence of blood donors who presented a serological abnormality is 3.95% with a predominance of donors with hepatitis B (72.93%) followed by syphilis (18.29%) of the hepatitis C (6.95%) and HIV (1.80%) and a predominance of young people. Conclusion: At the CNTS Antananarivo, the HBV is the main definitive reason for exclusion of these donors. This high prevalence is a real public health problem for the country's health authorities. The search for maximum safety in blood transfusion through firstly a better selection of blood donors by implementing a policy of strong loyalty and other early diagnosis of major diseases transmissible by blood and likely to infect the recipient. KEYWORDS: Antananarivo; Blood donor; Microbiology; Seroprevalence

Modulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations

Drug addiction is a chronic and relapsing disorder that leads to compulsive drug intake despite deleterious consequences. By increasing dopamine (DA) in the mesolimbic system, drugs of abuse hijack the brain reward circuitry, which is critical for the development of enduring behavioral alterations. DA mainly acts onto DA D1 (D1R) and D2 (D2R) receptor subtypes, which are positively and negatively coupled to adenylyl cyclase, respectively. Extensive research has aimed at targeting these receptors for the treatment of addiction, however this often results in unwanted side-effects due to the implication of DA receptors in numerous physiological functions. A growing body of evidence indicates that the physical interaction of DA receptors with other receptors can finely tune their function, making DA receptor heteromers promising targets for more specific treatment strategies. An increasing number of articles highlighted the ability of both D1R and D2R to form heteromers, however, most studies carried out to date stem from observations in heterologous systems and the biological significance of DA receptor heteromers in vivo is only emerging. We focused this review on studies that were able to provide insights into functions on D1R and D2R heteromers in drug-evoked adaptations and discuss the limitations of current approaches to study receptor heteromers in vivo. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.Rôle des heteromères formés par les récepteurs dopamine-glutamate et de signalisation dépendante du calcium nucléaire associée dans l'addictionImpact de la composition lipidique membranaire sur la transmission dopaminergique dépendante du récepteur D2 et la motivationProgram Initiative d’Excellenc

Séroprévalence de la cysticercose et facteurs de risque associés chez un groupe de patients vus au Centre Hospitalier Régional de Référence d’Antsirabe, Madagascar

Introduction: A Madagascar, la cysticercose, maladie causée par la forme larvaire de Taenia solium, demeure un problème de santé publique. En 2003, la séroprévalence de la cysticercose variait entre 7% et 21% avec un taux plus élevé dans les régions centrales de l’île. Toutefois, depuis une dizaine d’année, les données épidémiologiques concernant la cysticercose humaine restent limitées. Notre étude a pour objectif de déterminer, chez les patients issus de la région de Vakinankaratra et qui sont suspects cliniquement, la séroprévalence de la cysticercose par Western blot ainsi que les facteurs de risque associés. Méthodes: Il s’agit d’une étude descriptive transversale menée sur une période de 6 mois au sein du Centre Hospitalier Régional de Référence d’Antsirabe. Tous les patients inclus dans l’étude ont répondu à un questionnaire clinique recueillant leurs caractéristiques sociodémographiques et culturelles ainsi que leurs habitudes alimentaires et leurs symptômes cliniques. Résultats: La séroprévalence de la cysticercose retrouvée dans la population d’étude était de 14,8% (35/237). Ce taux ne diffère pas significativement selon le sexe, l’âge, la consommation de viande de porc ou le mode de préparation de la viande (p > 0,05). Par contre, une différence significative (p < 0,05) a été observée chez les sujets présentant des nodules sous-cutanés ou un résultat de cysticercose antérieur positif. Conclusion: L’index élevé d’exposition à Taenia solium retrouvé dans notre étude justifie le renforcement des mesures de contrôle et de prévention déjà implantés dans le pays

Acid fast bacillus pulmonary and extra pulmonary in a laboratory of university hospital center in Antananarivo, Madagascar since 2003-2014

Background: Tuberculosis has even been a grave public health problem in Madagascar, one of the main causes responsible for death at the hospital for active and productive people.Methods: It was a descriptive and analytical retrospective study of patient records admitted for the research of acid-fast bacillus (AFB) pulmonary and extra pulmonary from January 2003 to December 2014 at the microbiology laboratory of the University Hospital Joseph Ravoahangy Andrianavalona (HU-JRA) Antananarivo, Madagascar. We did this study in order to describe the epidemiology of pulmonary and extra pulmonary tuberculosis at the laboratory. All of the requests about researching AFB for bacterial analysis have been received. Incomplete folders have been rejected. Age, sex, clinic information and the results of AFB research have been analyzed.Results: During 12 years, 1060 requests have been received to research AFB with 89 cases (8.39%) of positivity. Patients were between 9 months and 93 years old. The middle patient age was 41.7 years. Sex-ratio of infected patients was 1.36. There was a significant difference between gender and positive cases (p=0,001). 82 positive cases (93.77%) were pulmonary localization and 7 cases of extra pulmonary (6.23%).Conclusions: Despite the lack of screening, the high rate of bacillary pulmonary tuberculosis found was one of the great epidemiological importances because of their contagiousness. It is obvious that only health actions cannot solve the problem of tuberculosis.

A cluster randomized controlled trial for assessing POC-CCA test based praziquantel treatment for schistosomiasis control in pregnant women and their young children: study protocol of the freeBILy clinical trial in Madagascar.

BACKGROUND: Mass drug administration (MDA) of praziquantel is one of the main control measures against human schistosomiasis. Although there are claims for including pregnant women, infants and children under the age of 5 years in high-endemic regions in MDA campaigns, they are usually not treated without a diagnosis. Diagnostic tools identifying infections at the primary health care centre (PHCC) level could therefore help to integrate these vulnerable groups into control programmes. freeBILy (fast and reliable easy-to-use-diagnostics for eliminating bilharzia in young children and mothers) is an international consortium focused on implementing and evaluating new schistosomiasis diagnostic strategies. In Madagascar, the study aims to determine the effectiveness of a test-based schistosomiasis treatment (TBST) strategy for pregnant women and their infants and children up until the age of 2 years. METHODS: A two-armed, cluster-randomized, controlled phase III trial including 5200 women and their offspring assesses the impact of TBST on child growth and maternal haemoglobin in areas of medium to high endemicity of Schistosoma mansoni. The participants are being tested with the point of care-circulating cathodic antigen (POC-CCA) test, a commercially available urine-based non-invasive rapid diagnostic test for schistosomiasis. In the intervention arm, a POC-CCA-TBST strategy is offered to women during pregnancy and 9 months after delivery, for their infants at 9 months of age. In the control arm, study visit procedures are the same, but without the POC-CCA-TBST procedure. All participants are being offered the POC-CCA-TBST 24 months after delivery. This trial is being integrated into the routine maternal and child primary health care programmes at 40 different PHCC in Madagascar's highlands. The purpose of the trial is to assess the effectiveness of the POC-CCA-TBST for controlling schistosomiasis in young children and mothers. DISCUSSION: This trial assesses a strategy to integrate pregnant women and their children under the age of 2 years into schistosomiasis control programmes using rapid diagnostic tests. It includes local capacity building for clinical trials and large-scale intervention research. TRIAL REGISTRATION: Pan-African Clinical Trial Register PACTR201905784271304. Retrospectively registered on 15 May 2019

Rôle des hétéromères formés par les récepteurs de la dopamine et du glutamate dans les adaptations à long terme induites par la cocaïne

Addictive substances hijack reward-dependent learning by increasing dopamine (DA) in the mesolimbic system, in particular in the striatum, where it modulates durably excitatory glutamatergic transmission and contributes to the establishment of persistent behavioral alterations. The integration of dopaminergic and glutamatergic signals within the striatum is achieved by the medium-size spiny neurons of the striatum (MSN), which form two mostly segregated populations: the MSN of the "direct pathway" expressing DA D1 receptors (D1R-MSN) and those of the "indirect pathway" which express the DA D2 receptors (D2R-MSN). A prevailing hypothesis is that the surge of DA evoked by drugs of abuse facilitates D1R-MSN activation through the stimulation of D1R, which promotes reinforcement, whereas the D2R-mediated inhibition of D2R-MSN prevent their so-called anti-reward action. Our laboratory has previously shown that the physical interaction (i.e. heteromerization) between D1R and the NMDA glutamate receptor (NMDAR) was necessary for the facilitation of glutamatergic transmission by DA in D1R-MSN. Conversely, others have shown that the D2R/NMDAR interaction underlies the inhibitory effect of DA on NMDAR signaling in D2R-MSN.However, the modulation and function of these heteromers in vivo in responses to cocaine are still unknown. Using the “proximity ligation assay” technique, we found that locomotor sensitization induced by repeated exposure to cocaine is associated with the formation of D1R/NMDAR heteromers in the Nucleus Accumbens (NAc) and the Dorsal Striatum, while the D2R/GluN2B heteromerization is mainly observed within the NAc. To identify the roles of the DAR/NMDAR heteromers in the different phases of the molecular, morphological and behavioral adaptations induced by cocaine in vivo, we designed a viral-based approach to disrupt the DAR/NMDAR heteromers in a controlled manner over time owing to a doxycycline-dependent promoter. We found that the disruption of the D1R/NMDAR interaction in the NAc blocks cocaine-evoked long-term synaptic plasticity in D1R-MSN and the development of both psychomotor sensitization and conditioned place preference (CPP). By contrast, blocking the D2R/NMDAR interaction interferes with the maintenance of cocaine psychomotor sensitization and CPP. The observation of a preferential involvement of the D2R/GluN2B heteromers in the maintenance of behavioral responses to cocaine and their lack of effect in natural reward suggests that this subtype of heteromers could be a promising therapeutic target. Based on this hypothesis, we developed the detection of D2R/NMDAR complexes from human post-mortem striatal tissues prepared from individuals with a history of psychostimulants dependence or healthy subjects. This allowed us to show that, despite a sharp decrease in D2R expression, the proportion of D2R forming heteromers with NMDAR is three-fold higher in addict subjects compared to healthy controls. This work therefore reinforces the evidence of the central role of interactions between the dopaminergic and glutamatergic systems in drug responses and identifies the DAR/NMDAR heteromers as molecular targets with therapeutic potential not only in addiction but also for the numerous psychiatric disorders associated with an imbalance between dopaminergic and glutamatergic transmissions.Les substances addictives détournent les apprentissages par la récompense en augmentant la dopamine (DA) dans le système mésolimbique, en particulier dans le striatum, où elle module durablement la transmission glutamatergique excitatrice et contribue à la mise en place d’altérations comportementales persistantes. L’intégration des signaux dopaminergique et glutamatergique au sein du striatum est réalisée par les neurones moyen épineux du striatum (MSN), qui forment deux populations majoritairement distinctes : les MSN de la « voie directe » exprimant les récepteurs D1 de la DA (D1R-MSN) et ceux de la « voie indirecte » qui expriment les récepteurs D2 de la DA (D2R-MSN). Une hypothèse qui prévaut à l’heure actuelle est que la libération de DA induite par les drogues active les D1R-MSN, ce qui promeut le renforcement, alors qu’elle inhibe les D2R-MSN, diminuant ainsi leurs fonctions « anti-renforcement ». Les travaux du laboratoire ont montré que l’interaction physique (i.e. hétéromérisation) entre le D1R et le récepteur NMDA (NMDAR) du glutamate était nécessaire à la facilitation de la transmission glutamatergique par la DA dans les D1R-MSN. À l'inverse, d'autres travaux ont montré que l'interaction D2R / NMDAR sous-tend l'effet inhibiteur de DA sur la signalisation NMDAR dans les D2R-MSN. Toutefois, la modulation et la fonction de ces hétéromères in vivo dans les réponses induites par la cocaïne sont encore inconnues. À l'aide du test de « proximity ligation assay », nous avons montré que la sensibilisation locomotrice induite par des expositions répétées à la cocaïne est associée à la formation d'hétéromères D1R/NMDAR dans le Noyau Accumbens (NAc) et le Striatum Dorsal, tandis que l'hétéromérisation D2R/GluN2B est majoritairement observée au sein du NAc. Pour identifier les rôles des hétéromères DAR / NMDAR dans les différentes phases des adaptations moléculaires, morphologiques et comportementales induites par la cocaïne in vivo, nous avons conçu une approche virale pour perturber les hétéromères DAR / NMDAR de manière contrôlée dans le temps grâce à un promoteur dépendant de la doxycycline. Nous avons constaté que la perturbation de l'interaction D1R / NMDAR dans le NAc bloque la mise en place des altérations synaptiques induites par la cocaïne dans les D1R-MSN ainsi que le développement de la sensibilisation locomotrice et de la préférence de lieu conditionné par la cocaïne (CPP). A l’inverse, le blocage de l'interaction D2R / NMDAR interfère avec le maintien de la sensibilisation psychomotrice et de la CPP à la cocaïne. L’observation d’un rôle préférentiel des hétéromères D2R/GluN2B dans la maintenance des réponses comportementales à la cocaïne et leur absence d’effet dans le cas d’une récompense naturelle suggèrent que ce sous-type d’hétéromère pourrait être une cible thérapeutique à envisager. J’ai donc mis au point la détection des complexes D2R / NMDAR à partir des tissus striataux humains post-mortem issus d’individus avec un historique de dépendance aux psychostimulants ou des sujets sains. Ceci m’a permis de montrer, qu’en dépit d’une forte baisse de l’expression du D2R, la proportion de D2R formant des hétéromères avec les NMDAR est trois fois supérieure chez les sujets dépendants par rapport au sujets sains. Ce travail renforce donc les évidences en faveur d’un rôle central des interactions entre les systèmes dopaminergique et glutamatergiques dans les réponses aux drogues et identifie les hétéromères DAR / NMDAR comme des cibles moléculaires avec un potentiel thérapeutique non seulement dans la dépendance aux drogues mais également pour les nombreux troubles psychiatriques associés à un déséquilibre entre les transmissions dopaminergiques et du glutamatergiques