Environmental enteric dysfunction (EED) is an inflammatory syndrome postulated to contribute to stunted child growth and to be associated with intestinal dysbiosis and nutrient malabsorption. However, the small intestinal contributions to EED remain poorly understood. This study aimed to assess changes in the proximal and distal intestinal microbiota in the context of stunting and EED and to test for a causal role of these bacterial isolates in the underlying pathophysiology. We performed a cross-sectional study in two African countries recruiting roughly 1,000 children aged 2 to 5 years and assessed the microbiota in the stomach, duodenum, and feces. Upper gastrointestinal samples were obtained from stunted children and stratified according to stunting severity. Fecal samples were collected. We then investigated the role of clinical isolates in EED pathophysiology using tissue culture and animal models. We find that small intestinal bacterial overgrowth (SIBO) is extremely common (>80%) in stunted children. SIBO is frequently characterized by an overgrowth of oral bacteria, leading to increased permeability and inflammation and to replacement of classical small intestinal strains. These duodenal bacterial isolates decrease lipid absorption in both cultured enterocytes and mice, providing a mechanism by which they may exacerbate EED and stunting. Further, we find a specific fecal signature associated with the EED markers fecal calprotectin and alpha-antitrypsin. Our study shows a causal implication of ectopic colonization of oral bacterial isolated from the small intestine in nutrient malabsorption and gut leakiness in vitro. These findings have important therapeutic implications for modulating the microbiota through microbiota-targeted interventions.
Background: Child undernutrition is a global health issue that is associated with poor sanitation and an altered intestinal microbiota. Immunoglobulin (Ig) A mediates host-microbial homeostasis in the intestine, and acutely undernourished children have been shown to have altered IgA recognition of the fecal microbiota. We sought to determine whether chronic undernutrition (stunting) or intestinal inflammation were associated with antibody recognition of the microbiota using two geographically distinct populations from the Afribiota project. Fecal bacteria from 200 children between 2 and 5 years old in Antananarivo, Madagascar, and Bangui, Central African Republic (CAR), were sorted into IgA-positive (IgA+) and IgA-negative (IgA−) populations by flow cytometry and subsequently characterized by 16S rRNA gene sequencing to determine IgA-bacterial targeting. We additionally measured IgG+ fecal bacteria by flow cytometry in a subset of 75 children. Results: Stunted children (height-forage z-score ≤ −2) had a greater proportion of IgA+ bacteria in the fecal microbiota compared to non-stunted controls. This trend was consistent in both countries, despite the higher overall IgA-targeting of the microbiota in Madagascar, but lost significance in each country individually. Two of the most highly IgA-recognized bacteria regardless of nutritional status were Campylobacter (in CAR) and Haemophilus (in both countries), both of which were previously shown to be more abundant in stunted children; however, there was no association between IgA-targeting of these bacteria and either stunting or inflammatory markers. IgGbound intestinal bacteria were rare in both stunted and non-stunted children, similar to levels observed in healthy populations.
La prise en charge de l'atrésie de l'œsophage est encore limitée par la précarité des plateaux techniques à Madagascar. Les cas décrits dans ce travail ont pour objectif de relater nos possibilités thérapeutiques et de décrire les progrès à réaliser pour optimiser le traitement de cette pathologie congénitale. Nous avons recueilli tous les dossiers ayant pour motif d’entrée au service de Réanimation Chirurgicale du CHU JRA, Antananarivo, une atrésie de l’œsophage. Nous en avons retenu les tous premiers cas qui ont survécu sur une période de 42 mois entre janvier 2011 et juin 2014. Parmi 17 admissions pour atrésie de l’œsophage, trois nouveau-nés à terme, admis successivement en Réanimation Chirurgicale, présentant un type III d'atrésie; premiers patients, à Madagascar, ayant survécu au décours de leur intervention. Une seule patiente avait présenté des malformations associées. Ces trois bébés ont été extubés précocement au bloc opératoire, sous oxygénothérapie jusqu'à une ventilation spontanée efficace. Des séances de kinésithérapie postopératoire permettaient d'améliorer l'état respiratoire des nouveau-nés. La mortalité globale de cette pathologie en 42 mois a été de 76,5%. Malgré ces premiers succès, des progrès restent à entreprendre dans le traitement de cette anomalie congénitale ; de son diagnostic jusqu'à la période postopératoire. L'amélioration du plateau technique, surtout ventilatoire et du support nutritionnel permettrait d'avoir des résultats plus probants, tout comme dans les pays où des progrès ont été réalisés sur le plan de la réanimation.
Objective: The aim of this study was to present the first cases of spinal anesthesia, in newborns and infants, preterm / ex-prematures, in order to determine its feasibility and its potential harmlessness, in Antananarivo – Madagascar. Indeed, spinal anesthesia is a low cost technique and can limit respiratory complications, postoperative apnea a contrario with pediatric general anesthesia which can lead to perioperative risks.Results: In a retrospective, descriptive, seven-year (2013 to 2019) period study, conducted in the University Hospital Joseph Ravoahangy Andrianavalona, 69 patients’ data files planned to have spinal anesthesia were recorded. These pediatric patients were predominantly male (sex ratio = 2.8) and 37 [28 - 52] days old. The smallest anesthetized child weighed 880g; the youngest was 4 days old. Twenty-seven (27) of them were premature and 20.3% presented respiratory diseases. They were mostly scheduled for hernia repair (90%). Spinal anesthesia was performed, with a Gauge 25 Quincke spinal needle, after 2 [1 - 2] attempts with hyperbaric bupivacaine of 4 [3.5 - 4] mg. Failure rate was 5.8%. The heart rate was stable throughout perioperative period and no complications were observed.
Background Variceal upper gastrointestinal bleeding is a dreadful complication of portal hypertension with a significant morbidity and mortality. Different prognostic scores can be used. However, in the local context of Madagascar, the completion of paraclinical investigations can be delayed by the limited financial means of patients. Hence, determining clinical mortality risk factors of variceal upper gastrointestinal bleeding could be interesting. The aim of the study was to evaluate the clinical mortality risk factors of variceal gastrointestinal bleeding (VUGIB). Method An observational, cohort retrospective study was conducted over an 8-year period (2010–2017), at the surgical intensive care unit of the J.R. Andrianavalona University Hospital, Antananarivo, in patients admitted for VUGIB confirmed by upper gastrointestinal endoscopy and whose clinical examination was performed at admission. The primary endpoint was intensive care unit (ICU) mortality. Univariate analysis and multivariate logistic regression analysis were performed to identify risk factors for ICU mortality, with OR defining odds ratio. A p value <0.05 was considered significant. Results 1920 patients were admitted for gastrointestinal bleeding of any digestive causes; the source of bleeding was variceal in 269 patients (14%). The predominantly male population (sex ratio = 2.5), aged 47.1 ± 13.7 years was mostly American Society of Anesthesiologists (ASA) 1 classification (58.4%). In 56.5% of patients, the gastrointestinal bleeding had not occurred before. The mortality rate was 16.0%. Three major clinical factors of mortality were identified: previous endoscopic band variceal ligation (OR = 12.57 [2.18–72.58], p = 0.005), tachycardia >120 bpm (OR = 2.91 [1.04–8.14], p = 0.041), and ascites (OR = 3.80 [1.85–7.81], p < 0.001). Conclusion Upper gastrointestinal bleeding may be life-threatening. The mortality scores are certainly useful; however, the identification of clinical factors is interesting in countries like Madagascar, pending the results of paraclinical investigations.
La profession médicale est un métier stressant, pouvant engendrer un syndrome d'épuisement professionnel ou burnout syndrom (BOS). Le but de cette étude était de déterminer les degrés du BOS (faible, moyen, élevé) de par ses dimensions et les facteurs liés à l'activité professionnelle du médecin qui lui étaient corrélés. Il s'agit d'une étude transversale, en 2012, par auto-questionnaire, auprès des médecins du Centre Hospitalier de Soavinandriana et du Centre Hospitalier Universitaire, Joseph Ravoahangy Andrianavalona. Des tests de corrélation et de régression linéaire ont été effectués (SigmaStat ® 3.5). Le taux de réponse à l'enquête a été de 47,1% sur 138 médecins hospitaliers. Le nombre de dossiers retenus était de 48. La population de l'étude était à prédominance masculine (sex ratio: 1,8) avec un âge médian de 37 [25-59] ans. Les internes de spécialité et les médecins assistants représentaient 56,3% de la population. Selon l'ancienneté 16,7% étaient dans le métier depuis moins d'un an. Le burnout syndrom a été observé dans 51,2 % des cas avec un degré élevé pour 4,2% des médecins. Le titre avait une corrélation significative avec le syndrome d'épuisement professionnel et son degré (p=0,0142 et p=0,0362), notamment l'épuisement émotionnel (p=0,0414). L'apparition du BOS n'était ni corrélé avec l'ancienneté du médecin ni avec le secteur d'activité. Le BOS existe en milieu hospitalier, surtout lié au titre du médecin. Il est essentiel de le diagnostiquer au plus tôt pour en éviter ses conséquences délétères.
Objective The aim of this study was to present the first cases of spinal anesthesia, in newborns and infants, preterm/ex-prematures, in order to determine its feasibility and its potential harmlessness, in Antananarivo—Madagascar. Indeed, spinal anesthesia is a low cost technique and can limit respiratory complications, postoperative apnea a contrario with pediatric general anesthesia which can lead to perioperative risks. Results In a retrospective, descriptive, 7-year (2013 to 2019) period study, conducted in the University Hospital Joseph Ravoahangy Andrianavalona, 69 patients’ data files planned to have spinal anesthesia were recorded. These pediatric patients were predominantly male (sex ratio = 2.8) and 37 [28–52] days old. The smallest anesthetized child weighed 880 g; the youngest was 4 days old. Twenty-seven (27) of them were premature and 20.3% presented respiratory diseases. They were mostly scheduled for hernia repair (90%). Spinal anesthesia was performed, with a Gauge 25 Quincke spinal needle, after 2 [1–2] attempts with hyperbaric bupivacaine of 4 [3.5–4] mg. Failure rate was 5.8%. The heart rate was stable throughout perioperative period and no complications were observed.
Eukaryotes have historically been studied as parasites, but recent evidence suggests they may be indicators of a healthy gut ecosystem. Here, we describe the eukaryome along the gastrointestinal tract of children aged 2–5 years and test for associations with clinical factors such as anaemia, intestinal inflammation, chronic undernutrition and age. Children were enrolled from December 2016—May 2018 in Bangui, Central African Republic and Antananarivo, Madagascar. We analyzed a total of 1104 samples representing 212 gastric, 187 duodenal, and 705 fecal samples using a metabarcoding approach targeting the full ITS2 region for fungi, and the V4 hypervariable region of the 18S rRNA gene for the overall eukaryome. Roughly half of all fecal samples showed microeukaryotic reads. We find high inter-subject variability, only a handful of taxa that are likely residents of the gastrointestinal tract, and frequent co-occurrence of eukaryotes within an individual. We also find that the eukaryome differs between the stomach, duodenum and feces and is strongly influenced by country of origin. Our data show trends toward higher levels of Fusarium equiseti, a mycotoxin producing fungus, and lower levels of the protist Blastocystis in stunted children compared to non-stunted controls. Overall, the eukaryome is poorly correlated with clinical variables. Our study is of one of the largest cohorts analyzing the human intestinal eukaryome to date and the first to compare the eukaryome across different compartments of the gastrointestinal tract. Our results highlight the importance of studying populations across the world to uncover common features of the eukaryome in health.
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