Philosophiae Doctor - PhD / The current study was, in part, prompted by the high case fatality rates for severe acute malnutrition in two district hospitals in the Eastern Cape Province in South Africa. These case fatality rates were being attributed to Human Immunodeficiency Virus infection rather than to mismanagement by nurses involved in the hospital management of SAM cases. There were also some anecdotes from clinicians in the same hospitals that, depending on the clinical stage of HIV infection, the World Health Organisation's ten-step protocol may show no effect. This left some uncertainties as to whether these guidelines are suitably designed for use during the management of HIV positive children who are severely malnourished and at different HIV clinical stages. This study sought to reinforce the design of a longstanding facility-based intervention originally developed to improve the management of severe acute malnutrition in two district hospitals in South Africa. The aim was to design an improved intervention which was implemented and evaluated to determine its potential effect on treatment outcomes, specifically in the context of high HIV comorbidity. The study also sought to provide the context for the effectiveness of this intervention, in terms of its implementation fidelity and associated moderating factors. Lastly, the study evaluated the sustainability of the intervention after it was discontinued. Methods The current study reports on the development, implementation and evaluation of an intervention to improve the management of severe acute malnutrition in two district hospitals in the Eastern Cape Province. A Sequential Explanatory Mixed Method Design was used. During the study, the effect of HIV infection, disease stage and other clinical characteristics on the survival of children with severe acute malnutrition was assessed. The relationship between the rate of weight gain and duration of hospitalisation based on HIV status and disease stage were also examined. The data were collected prospectively during the study using retrospective record review of a total of 450 severely malnourished children who were admitted and treated at the two facilities from 2009 to 2013.A pre-tested 76- item patient evaluation form was used to collect data on patient characteristics on admission, treatment processes and outcomes. Data analysis was performed using STATA13.0 and involved simple descriptive computation of quantitative variables as well as non-parametric tests to compare groups between and within hospitals. Kaplan-Meier curves and Cox proportional hazard modelling were used to analyse time to event data. The study also assessed the impact of the intervention at time intervals on outcomes of interest. The analysis focused on modelling and plotting monthly mortality statistics collected over a period of 69 months. This was done to detect related trend and level changes before, immediately (after the first two months) and after (following the two months) the removal of the intervention. Lastly ethnographic and focus group enquiries were used to explain the quantitative results. Two focus group discussions were held in each hospital with clinicians and the management staff. This was done at the end of phase three. The focus group data were analysed using the framework analysis approach.

The purpose of the study was to assess the coverage and effectiveness of the management of severe acute malnutrition project implemented in Dhas district of Borena zone, Ethiopia, from July 2010 to December 2010. Quantitative, descriptive study was conducted to assess the comparability of the outcome of community-based management of acute malnutrition in a pastoralist area to International Sphere standards using performance indicators. Data collection was done using data capturing sheet. Outpatient therapeutic programme (OPT) registers in all health facilities were the sources of data. Clinical records of children admitted to the programme (n=163) were analysed. Standard nutrition survey result was used to estimate the malnutrition prevalence and programme coverage. International Sphere standard was achieved for mortality rate but not for recovery rate, defaulter rate, length of stay and weight gain / Health Studies / M.A. (Public Health)

The purpose of the study was to assess the coverage and effectiveness of the management of severe acute malnutrition project implemented in Dhas district of Borena zone, Ethiopia, from July 2010 to December 2010. Quantitative, descriptive study was conducted to assess the comparability of the outcome of community-based management of acute malnutrition in a pastoralist area to International Sphere standards using performance indicators. Data collection was done using data capturing sheet. Outpatient therapeutic programme (OPT) registers in all health facilities were the sources of data. Clinical records of children admitted to the programme (n=163) were analysed. Standard nutrition survey result was used to estimate the malnutrition prevalence and programme coverage. International Sphere standard was achieved for mortality rate but not for recovery rate, defaulter rate, length of stay and weight gain / Health Studies / M.A. (Public Health)

Contexte : La malnutrition aiguë sévère (MAS) est un problème majeur de santé publique dans lemonde et affecte 17 millions d’enfants âgés de moins de 5 ans. La MAS induit une perte de poidsrapide, souvent associée à une dysfonction entérique environnementale (DEE). La DEE se caractérisepar une augmentation de l’inflammation, de la perméabilité intestinale, une diminution de la taille des villosités et de l’absorption des nutriments. La DEE peut ainsi limiter l’efficacité des protocolesde stabilisation et de re-nutrition chez l’enfant dénutri.L’objectif de cette thèse a été de développer un modèle de dénutrition avec entéropathie pour évaluer des laits thérapeutiques enrichis en nutriments ciblant la fonction de barrière intestinale.Résultats : Lors de la phase de développement du modèle, plusieurs approches ont été testées comme la restriction calorique, le régime hypoprotéiné, l’utilisation de lipopolysaccharides et de l’indométacine. Seule la combinaison d’un gavage quotidien d’indométacine pendant une semaine chez des souris dénutries par un régime pauvre en protéines a permis de développer un retard de croissance associé à une entéropathie. Suite à la validation de ce modèle, nous avons évalué la supplémentation du lait thérapeutique F-75 avec de la glutamine, de la leucine, de la gomme arabique et des levures séléniées. La glutamine et la leucine améliorent la fonction de barrière intestinale. Dans nos conditions expérimentales, l’enrichissement du lait thérapeutique avec la glutamine et la leucine combinés a eu des effets limités sur la fonction de barrière. La gomme arabique et les levures séléniées ont des propriétés prébiotiques et probiotiques et exercent des effets bénéfiques sur la barrière intestinale. L’enrichissement du lait thérapeutique avec l’association de ces deux composés permet d’inhiber l’inflammation intestinale et d’augmenter l’abondance de bactéries bénéfiques comme Faecalibacterium prausnitzii.Conclusion : Les travaux réalisés au cours de cette thèse ont permis de développer un nouveau modèle de dénutrition avec entéropathie. Le lait thérapeutique enrichi en gomme arabique et levures séléniées exerce des effets bénéfiques sur la fonction de barrière intestinale dans notre modèle. / Background : Severe acute malnutrition (SAM) is a global health issue affecting 17 million children under the age of 5. SAM induces rapid weight loss and is often associated with environmental enteric dysfunction (EED). EED is characterized by intestinal hyperpermeability and inflammation, villus blunting and nutrient malabsorption. EED might, therefore, limit stabilization and re-nutrition protocol efficacy. Objectives : This thesis aimed to develop an undernutrition model with enteropathy to evaluate the effect of a therapeutic milk enriched with nutrients on gut barrier function. Results : During preclinical model development, several approaches were tested: calorie restriction, low-protein diet, use of lipopolysaccharides and indomethacin. Only daily indomethacin gavage during one week in protein-energy undernourished mice induced growth faltering associated with enteropathy. After preclinical model validation, we evaluated the effect of therapeutic milk supplemented with glutamine, leucine, gum arabic and/or selenium-enriched yeast on gut barrier function. Glutamine and leucine induce beneficial effects on gut barrier function. In ourexperimental conditions, therapeutic milk enriched with a combination of glutamine and leucine had a limited impact on this parameter. Gum arabic and selenium-enriched yeasts have prebiotic and probiotic properties on gut barrier function. Therapeutic milk supplemented with gum arabic and selenium-enriched yeast inhibited intestinal inflammation and enhanced specific bacteria abundance such as Faecalibacterium prausnitzii.Conclusion : The studies conducted during this thesis permitted to develop a new model of undernutrition with enteropathy. Therapeutic milk enriched with arabic gum and selenium-enriched yeast triggered beneficial effects on gut barrier function in our preclinical model.

Introducción: El AA.HH. Pacífico de Villa se encuentra en el distrito de Chorrillos. Las características demográficas más importantes es que presenta un inadecuado abastecimiento de red pública de agua y desagüe, estas condiciones son una de las causas que produce desnutrición infantil en esta comunidad. Objetivo: Disminuir la alta prevalencia de desnutrición aguda en niños menores de 5 años en el AA.HH. Pacífico de Villa, Chorrillos en el año 2020. Análisis del problema: Se analizaron los factores causales de la desnutrición aguda infantil y se determinó como causas a la inadecuada lactancia materna, carencia de conocimiento de una alimentación saludable y los malos hábitos de higiene. Alternativas: Las alternativas fueron: 1) Charlas sobre la lactancia materna, 2) Charlas sobre la elaboración de un plato saludable e 3) Información sobre el correcto lavado de manos, estas acciones se realizaron en un contexto de la pandemia de la COVID19 en el Perú Resultados: Fueron alentadores, reflejando que las alternativas cumplieron el objetivo, gracias a la colaboración activa de los pobladores de AAHH Pacífico Villa. Se evalúo las acciones mediante un pre-test y post-test donde los resultados en este último fueron de un 100% en las preguntas sobre lactancia y en la elaboración de un plato saludable. Esto se contrastó con los videos y fotos que envió la población. Conclusiones: Este trabajo de intervención contribuyó a mejorar los conocimientos del lavado de manos y elaboración de un plato saludable con un impacto de disminuir la desnutrición infantil en la comunidad del AA.HH. Pacífico de Villa. / Introduction: The AA.HH. Pacifico de Villa is located in the district of Chorrillos. The most important demographic characteristics is that it has an inadequate supply of the public water and sewage network, these conditions are one of the causes that produce child malnutrition in this community. Objective: Reduce the high prevalence of acute malnutrition in children under 5 years of age in the AA.HH. Pacifico de Villa, Chorrillos in 2020. Analysis of the problem: The causal factors of acute child malnutrition were analyzed and inadequate breastfeeding, lack of knowledge of healthy eating and poor hygiene habits were determined as causes. Alternatives: The alternatives were: 1) Talks about breastfeeding, 2) Talks about preparing a healthy dish, and 3) Information about proper hand washing, these actions were carried out in the context of the COVID19 pandemic in the Peru Results: They were encouraging, reflecting that the alternatives met the objective, thanks to the active collaboration of the residents of AAHH Pacifico Villa. The actions were evaluated through a pre-test and post-test where the results in the latter were 100% in the questions about breastfeeding and in the preparation of a healthy dish. This was contrasted with the videos and photos that the population sent. Conclusions: This intervention work contributes to improving the knowledge of hand washing and preparation of healthy avocado with an impact on reducing child malnutrition in the community of AAHH Pacifico Villa. / Tesis