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Multiscale Modelling of HIV/AIDS Transmission DynamicsMafunda, Martin Canaan 21 September 2018 (has links)
MSc (Mathematcs) / Department of Mathematics and Applied Mathematics / Infectious diseases remain a major public health concern. Well-known for causing
sickness and death, enormous pain and suffering, increased time spent on patient
care and huge economic losses due to lost production. Infectious diseases continue
to be a scourge without equal. In this work, we address the following research question:
Can we use a multiscale model of HIV/AIDS transmission dynamics to assess
the comparative effectiveness of health interventions that are implemented at different
scale domains? To achieve the set objectives of the study, we use multiscale modelling
approach, a new and emerging computational high-throughput technique
for mathematically studying problems that have many characteristics across several
scales. To be more specific, we perform three tasks in addressing the research
question. First, we develop a within-host submodel and use it to show it’s associated
limitations which only a multiscale model can resolve. Second, we develop
a between-host submodel and use it to motivate the need for multiscale modelling
of the HIV/AIDS disease system. Finally, we link the two submodels to produce a
nested HIV/AIDS multiscale model that affords us the opportunity to compare effectiveness
of five preventive and treatment HIV/AIDS health interventions. Analysis
of the multiscale model shows that it is possible to jointly study two key aspects
(immunology and epidemiology) of infectious diseases. The multiscale model
provides the means for making meaningful comparative effectiveness on available
preventive and treatment health interventions. Consequently, we employ the multiscale
model to show that impact of HIV/AIDS packages increases as more interventions
are integrated into the packages. Specifically, the study shows that combined
HAART and male circumcision is more effective than an intervention involving
HAART alone. Overall, our study successfully illustrates the utility of multiscale
modelling methodology as a tool for assessing the comparative effectiveness
of HIV/AIDS preventive and treatment interventions. For purposes of informing
public health policy, we use the study results to infer that condom use, male circumcision
and pre-exposure prophylaxis are more effective in controlling the transmission
dynamics of HIV/AIDS at the start of the epidemic as compared to when the
disease is endemic in the community while the converse is also true for HAART. / NRF
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Drug resistance genotyping and phylogenetic analysis of HIV in chronically infected antiretroviral naive patientsBaloyi, Tlangelani 18 May 2019 (has links)
MSc (Microbiology) / Department of Microbiology / Background: Antiretroviral treatment (ART) has grown to be one of the most effective
tool in the fight to control HIV/AIDS morbidity and mortality worldwide. However, due to
the emergence of drug resistant HIV, ART efficacy can be jeopardized. Drug resistant
HIV strain has a potential of becoming a major public threat, as its limit treatment options
on people living with HIV. With several findings worldwide reporting drug resistant HIV to
be currently being transmitted to ART-naïve persons, measures have been taken to
genotype drug resistant HIV prior to treatment initiation. However, in resource limited
countries such measures are not executed especially in public sectors due to the costs
associated with the required assays for genotyping.
Objective: The objectives of the study was to establish a deep sequencing protocol (Next
Generation Sequencing-NGS) using an Illumina MiniSeq Platform and subsequently
apply it to genotype HIV in chronically infected drug naïve persons for resistance
mutations and viral genotypes
Methods: HIV positive Individuals without any exposure to ART (Treatment-naive) were
recruited. Partial pol fragment (complete protease and ~1104bp reverse transcriptase)
were amplified and purified. Libraries were prepared using Nextera XT library preparation
kit, fragmented, tagmented, pooled and denatured then sequenced with Illumina MiniSeq
instrument. Consensus sequences were derived, aligned and phylogenetically analysed.
The Stanford HIV Drug Resistance Algorithm was used to infer the presence of drug
resistant mutants, at the viral minority and majority population levels.
Results and discussion: An NGS protocol to generate nucleotide sequences for drug
resistance inference was established. No major drug resistance mutations were detected
against protease, reverse transcriptase inhibitors in the study subjects investigated.
Nevertheless, V179D change was observed in one patient (8.3%). V179D has been
shown to impact a low-level resistance to NNRTI. On the other hand, several secondary
and unusual mutations at known drug sites were detected even at minority threshold level
of <20%.
Conclusion: No major drug resistance mutations was detected in the drug naïve study
population. This finding suggests that there is no risk of treatment failure to the
investigated subjects, however it is important to assess the potential phenotypic
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significance of the identified secondary resistance mutations in the context of HIV-1
subtype C. The established NGS protocol should be applied in subsequent HIV drug
resistance studies. / NRF
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Perceptions of people living in the catchment area of Madwaleni Hospital, South Africa regarding the health and social problems facing their communityWinkel, Carolin 07 December 2010 (has links)
More than 16 years post-apartheid, South Africa is still regarded as the most unequal society in the world. The government is facing various obstacles and challenges in improving the standard of living and quality of life for all its citizens, for example in facilitating the access to clean drinking water and sanitation, building houses and providing basic education. In addition, the country is facing the world’s largest HIV/AIDS epidemic with a national prevalence rate of 18.1 %, equalling approximately 5.7 million people who are currently infected. (Pressly, 2009; UNAIDS, 2008c)
Against this background, the aim of this thesis was to study the Madwaleni community, situated in a deeply rural area of the former apartheid homeland Transkei. Applying the Community Oriented Primary Care approach, a strategy of ‘community assessment and diagnosis’ was used to obtain a holistic community profile and to determine the perceptions of its community members regarding their health and social problems and needs, intending to make recommendations to health care providers working at Madwaleni Hospital regarding future health education and disease prevention programmes. (Brown and Fee, 2002)
This research used a cross-sectional design. In a preliminary survey, qualitative data was collected in short interviews with health care providers working at Madwaleni Hospital (N=46). The information served as a basis to develop and design parts of the Madwaleni community survey questionnaire. The questionnaire consisted of 36 questions, complying with the aim and objectives of this thesis. It was used for the structured interviews with the main study population, all of whom were members of the Madwaleni community (N=200), whereas half of the main study population were men and half were women, then again, half were unaware of their HIV status and half were HIV+ and had joined the Madwaleni HIV/AIDS programme.
Key findings
1) Madwaleni community profile and characteristics
Thoughtful sexual behaviour: Particularly interesting in light of the HIV/AIDS epidemic, more than 90 % of the sexually active community members were monogamous at the time of the survey. While only 36.4 % of the men and women unaware of their HIV status used condoms, 76.5 % of the HIV+ community members claimed to do so, indicating that the Madwaleni HIV wellness programme and especially its counselling and health education components are adequate and valuable in serving their purpose.
High rates of illiteracy and insufficient education: Only 56.5 % of the interviewed community members were ‘functionally literate’ at the time of the survey. Of those, only 8 % had received a matriculation and not one of the community members had received any higher degree. In addition, 19.5 % of the sampled men and women were not able to read at all.
High rates of unemployment, poverty and dependency on welfare grants: Only 20 % of the Madwaleni community members were employed at the time of the survey. Taking the daily income per capita as a reference, one third of the community members suffered from ‘moderate poverty’, defined as an income of 1 to 2 US $ per day, while the other two thirds suffered from ‘extreme poverty’, defined as an income of less than 1 US $ per day, although more than 90 % of the corresponding households received at least one type of welfare grant already.
Large household sizes and predominance of traditional dwellings: In the Madwaleni community, an average of eight people lived together per household at the time of the survey, whereas 95 % of the community members lived in traditional dwellings, constructed from freely occurring natural resources.
In need of safe drinking water, sanitary systems and access to electricity: More than 80 % of the Madwaleni community members obtained their drinking water from rivers or stagnant dams, while only 6.5 % used rain water and 9.5 % had access to piped water. In addition, almost 70 % of the community members had no access to any sanitary systems, using nearby bushes instead. Furthermore, more than 90 % had no access to electricity. The majority used paraffin for cooking, candles for lighting and wood for heating their homes.
Small-scale cultivation to provide an extra source of food: In the Madwaleni area, 90 % of the families owned a small garden patch attached to their houses, used for small-scale cultivation. In addition, almost 90 % owned livestock, mainly poultry, cattle and goats. Crops and animals were used to provide an extra source of food; however, not one of the households could solely live on subsistence farming.
Difficulties in accessing health care facilities: On average, each of the community members needed three-quarters of an hour to access their closest clinic and almost one and a half hours to reach Madwaleni Hospital, with 40 % and 60 % respectively depending on public taxi transport to get there.
No substantial improvement of the living circumstances since apartheid: Comparing the Madwaleni community characteristics with corresponding data from apartheid-times, no substantial improvement of the living circumstances and conditions could be noticed, proving that governmental and non-governmental actions, programmes and services have not yet reached all remote communities.
Similar community characteristics in the neighbouring communities: Comparing these characteristics with corresponding features of communities in the immediate or surrounding areas, namely Cwebe, Ntubeni, Mboya, Shixini and Zithulele, various similarities could be detected, indicating that the living circumstances and conditions might be generalisable to a certain degree, at least to deeply rural communities in the former Transkei area.
More disadvantaged than the general South African population: The Madwaleni community differed significantly from the general South African population in 75 % of the compared characteristics. For example, amongst the community members the illiteracy rate (21.7 % vs. 13.6 %, p = 0.002) and unemployment rate (80.5 % vs. 25.5 %, p < 0.001) were significantly higher. In addition, the ‘poverty headcount ratio of 2 US $ per day’ showed that significantly more people were suffering from poverty in the Madwaleni area (92.2 % vs. 34 %, p < 0.001). The Madwaleni community members were less likely to have access to clean drinking water, along with significantly higher proportions of them using river water as their main source of drinking water (75.5 % vs. 5.1 %, p < 0.001). Also, they were less likely to have access to any sanitation or toilet facilities (31.3 % vs. 91.8 %, p < 0.001) or to electricity (8.5 % vs. 80.2 %, p < 0.001).
2) Weightiest health and social problems as experienced by the Madwaleni community
In the Madwaleni area, the three health problems with the highest impact on the community were TB, HIV/AIDS and hypertension. On the basis of the applied 3-to-0-point rating matrix, they were rated by more than 95 % of the community members as being relevant problems, with mean values of 2.33, 2.30 and 2.14 respectively. Interestingly, women rated HIV/AIDS higher than men.
Musculoskeletal problems and headache were additional health problems with relevant impact on the Madwaleni community, rated by more than 90 %, with mean values above 1.80. While pain and discomfort experienced by PLWHA have been recognised and researched before, there are no corresponding studies on rural communities and further research is necessary to identify the contributing factors.
Additional relevant health problems: Interestingly, six health problems were rated higher by HIV untested than by HIV+ community members, namely bilharzia/ schistosomiasis, epilepsy, Herpes Zoster, HIV/AIDS, lung infections and stroke. Since the HIV+ men and women were educated about and screened for all of those diseases within the Madwaleni HIV/AIDS programme, this might explain the deviating rating patterns between the different sub-samples. Moreover, these results demonstrate that health education and disease prevention programmes are able to reduce the perceived burden of health problems and might therefore serve as a substantial argument in their favour.
Interestingly, for the Madwaleni community, social matters had a higher impact on their lives than health problems, whereas the three social problems with the highest impact on the community were alcohol abuse, dependency on social grants and smoking. They were rated by more than 98 % of the community members as being relevant problems, with mean values of 2.75, 2.73 and 2.72 respectively.
In accordance with these findings, employment & lack of work opportunities, education & illiteracy, food supply and poverty were additional social problems with relevant impact in the Madwaleni area, rated by more than 90 %, with mean values above 2.00.
3) Recommendations for future health education and disease prevention programmes
At the time of the survey, the three most relevant health education and disease prevention topics for the Madwaleni community were HIV/AIDS, TB and healthy nutrition. They were rated by more than 95 % of the community members as being relevant health education problems, with mean values of 2.65, 2.51 and 2.36 respectively.
In addition, STIs, alcohol & drug-related problems, water & sanitation and body & muscle pain were rated as the subsequent issues of relevance, with mean values above 2.00, supporting the identified community characteristics as well as the listing of the weightiest health and social problems.
In addition, valuable new insight could be gained. For instance, HIV untested men rated the topic HIV/AIDS lower than all other community members, which is particularly interesting since men only constitute a minority of 20 % of the people testing for HIV in the Madwaleni area. Besides, topics not previously considered, such as injury prevention and basic first aid, were in-fact relevant for more than 85 % of the community members and require further attention. Furthermore, deviating rating patterns between men and women and the corresponding need for gender-specific educational workshops became evident, for example, for men about prostate & testicular cancer check-up or erectile dysfunction and for women about breast & cervical cancer check-up & papsmears or nutrition & growth. In addition, HIV+ community members rated depression & stress and psychiatric diseases higher than HIV untested men and women, with further studies required to identify the underlying reasons for these deviating rating patterns.
Taking all findings from this Madwaleni community survey into consideration, health care providers working at the hospital and its peripheral clinics should first and foremost concentrate their efforts on maintaining the existing programmes, particularly, the Madwaleni HIV/ARV programme and the workshops on hypertension and diabetes mellitus. In addition, if qualified and motivated personnel can be recruited and the necessary funding can be raised, future health education and disease prevention programmes should focus on TB, alcohol & substance abuse-related problems as well as water & sanitation.
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Tolerogenní dendritické buňky jako nová buněčná terapie v diabetu I. typu / Tolerogenic dendritic cells as a novel cell-based therapy in type 1 diabetesKroulíková, Zuzana January 2019 (has links)
Utilization of tolerogenic dendritic cells (tolDCs) as a cell-based therapy represents a promising strategy in treatment of autoimmune diseases including type 1 diabetes (T1D). Numerous protocols have been established to generate tolDCs ex vivo and their therapeutic effect has been demonstrated in animal models of autoimmune diseases. In this thesis we compared three different variants of such protocols which are based on the combined treatment of bone marrow- derived DCs with vitamin D and dexamethasone applied at different time points of their maturation towards tolDCs. We assessed the efficiency of these protocols in regards of their effect on the expression of co-stimulatory molecules CD40, CD80, CD86, and MHC II and the chemokine receptor CCR7 on the surface of tolDCs. Then, we evaluated the migration pattern of antigen unloaded tolDCs in vivo as well as their effect on the induction of immune responses and cell proliferation of lymph node cells. This was achieved by labelling of tolDCs with membrane dye PKH26 and by following their migration path by flow cytometry after intraperitoneal (i.p) or subcutaneous (s.c.) injection into either left or right side of the body. On day 1, 3, 5, 7, and 9, the presence of PKH26+ tolDCs was examined in spleen, pancreatic, mesenteric, inguinal and axillary...
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Problematika infekčních chorob v povědomí žáků základních a středních škol. / Awareness of contagious disease in mind of pupils at basic and secondary schools.Peštová, Ilona January 2010 (has links)
Infectious diseases are a very hot topic nowadays in society. In recent years, there were several epidemics, infectious diseases (hepatitis A, Avian influenza, pandemic influenza A) and nobody knows when will the next "new" infection. At the outbreak of epidemics, there is great interest in the company to obtain information about the disease, but often also to unnecessary panic, because the media often publish incorrect information. It would be preferable, in order to improve public awareness and prevent the unnecessary spread of disease. Great emphasis should be given to prevent the disease - primarily on immunization, hygiene rules and principles of safe sex. Quality information should be mainly from teachers in teaching their pupils, as is clear from research books, infectious diseases are only mentioned in textbooks and the number of substantive information in them is missing. The fact that pupils of primary schools and grammar schools with basic information on infectious diseases do not meet in the classroom, evidenced by the results of a survey carried out in the 6th classes and first year at selected elementary schools and grammar schools in Prague. To raise awareness of the pupils in school was to create a methodical manual for teachers, which summarizes information about bacterial and...
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Technology as a Health Intervention and the Self-Efficacy of MenMaxwell, Karen Denise 01 January 2015 (has links)
Mortality rates in the United States are higher for men than they are for women as a result of chronic diseases such as heart disease, cancer, and diabetes. Despite these disproportionate rates, few health interventions are targeted to men, and limited knowledge exists regarding the specific components needed to design technology health tools to appeal to men. The purpose of this quantitative study was to examine the relationship between the use of technology health tools and the role of self-efficacy in men and the influence on participation in healthy lifestyle behaviors. A quasi-experimental design was used to analyze data collected from the Health Information National Trends Survey (N = 990). A group of men (n = 323) who used technology health tools were compared to a control group of men (n = 667) who did not use technology health tools. Results from the regression analysis indicated that the use of technology health tools for self-management of health behavior had a significant effect on participation in healthy lifestyle behavior (p = .026). Self-efficacy was also found to mediate the relationship between technology health tools and participation in healthy lifestyle behavior (p = .018). This study supports the United States federal government's Healthy People 2020 objective to increase the proportion of people who use Internet health management tools. The implications for positive social change include knowledge for developing targeted technology health interventions to increase the participation of men in healthy lifestyle behavior, reduce the number of men with chronic diseases, improve chronic disease management, and reduce healthcare costs in the United States.
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African-American Heterosexual Women Facing The HIV/AIDS Pandemic: Giving Voice To Sexual Decision-MakingHill, Delthea Jean 07 July 2008 (has links)
HIV infection is escalating among African-American heterosexual women in alarming rates. African-American women are 23 times as likely to be infected with the AIDS virus as white women. African-American women account for 72% of new HIV cases among women in 29 states. The risk of contracting HIV virus is highest in African-American communities, which inevitably places African-American women at higher risk than other populations of women. The purpose of this study was to advance knowledge regarding what is unknown about risky sexual behaviors among African-American heterosexual women by giving them the “voice” to share their own personal experiences in their natural environments. I examined participants’ perceptions of risk for contracting HIV/AIDS in relationships with male partners. This qualitative research design focused on a constant comparative analysis. I conducted one focus group [four members and one recorder] along with seven individual interviews, of African-American heterosexual women involved in the Women In Motion [WIM] HIV/AIDS prevention program. The following three health behavior frameworks were examined as a means of understanding the limitations of existing models of sexual risk behaviors among African-American women: The Health Belief Model (HBM), the Transtheoretical Change Model, and the Black feminist perspective. Gaps in the literature included insufficient knowledge of how cultural taboos and myths influence sexual decision-making. An overview of the findings of this study has been explicated under the following three main headings: (1) Observation, (2) Interpretation, and (3) Application. The results of the study are discussed under the following three main categories 1) Understanding Sexual Decision-Making, 2) Understanding Intimacy, and 3) Understanding HIV/AIDS Prevention With Male Partners. In conclusion, sexual decision-making in this inquiry became an all encompassing construct based on African-American women’s perceptions of how they viewed the paradox of sexual needs in intimate relationships with male partners and the risk of contracting HIV/AIDS.
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Perceptions of risk of human immunodeficiency virus infection among students in the Institute of Development Management, Gaborone, Botswana CampusMalefho, Kegomoditswe M. January 2022 (has links)
Thesis (MPH.) -- University of Limpopo, 2022 / Background: Acquired Immunodeficiency Syndrome still remains the leading cause of
death globally. Understanding students’ views about the risk of Human Immunodeficiency
Virus infection by exploring and describing their perceptions may help to design effective
Human Immunodeficiency Virus prevention interventions. The tertiary institution
environment offers a great opportunity for Human Immunodeficiency Virus high risk
behaviours, including alcohol and drug abuse, unsafe sex, multiple sexual relationships,
intergenerational and transactional sex. Despite the decline in the overall incidence of
Human Immunodeficiency Virus infection, still a significant proportion of the youth
population are at risk of Human Immunodeficiency Virus infection.
Objectives: The study was to explore and describe perception of risk of Human
Immunodeficiency Virus among students at the Institute of Development Management,
Gaborone, Botswana Campus.
Methodology: A qualitative, exploratory, descriptive study using semi-structured
interviews with purposively selected second year Public Health students was conducted.
Interviews were conducted using an interview guide. It was audio recorded until data
saturation was reached, where eight students participated in the study. Voice recordings
were transcribed verbatim and analysed thematically.
Results: The findings reveals that some participants perceive themselves to be at risk of
contracting Human Immunodeficiency Virus, while others perceive themselves as being
not at risk of Human Immunodeficiency Virus infection. Several risk factors associated
with Human Immunodeficiency Virus infection, for example, alcohol and drug abuse,
multiple concurrent sexual relationships, intergenerational and transactional sex are
revealed as challenges. They also expressed their fears in relation to Human
Immunodefiency Virus testing, pregnancy and disclosure of Human Immunodeficiency
Virus positive status due to the stigma and discrimination.
Conclusion: High risk behaviours leading to Human Immunodeficiency Virus and
Acquired Immunodeficiency Syndrome prevalence are still common among young
people, hence the need for government and all stakeholders to specifically address them
by coming up with specific behavioural intervention programmes.
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Type 1 Diabetes Diagnostic AssayJackson, LaDonya L. January 2015 (has links)
No description available.
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Strategies to reduce the use of antibiotics in commercial broiler chickens : impacts on growth performance, intestinal health and microbiotaParent, Eric 04 1900 (has links)
Il y a actuellement une pression mondiale pour revoir les pratiques d'utilisation des antimicrobiens (UAM) en production animale afin de limiter la propagation de bactéries résistantes aux antibiotiques. Conséquemment, les Producteurs de Poulet du Canada examinent la possibilité de réduire leur UAM en supprimant les antibiotiques médicalement importants en médecine humaine (AIM) des programmes préventifs avec la mise en place de leur stratégie de réduction de l’UAM. Cependant, les informations sont rares sur les conséquences de telles approches dans un contexte canadien. L'objectif de cette thèse était d'étudier les impacts sur les performances zootechniques, le contrôle des maladies intestinales et le microbiote cécal de deux stratégies de réduction de l'UAM dans des troupeaux commerciaux de poulets de chair par rapport à une UAM conventionnelle. Sur sept fermes commerciales de poulets de chair, un poulailler a été attribué aux traitements de réduction des antibiotiques pour six troupeaux consécutifs, tandis qu'un poulailler similaire sur le même site a été alloué à l'UAM conventionnelle (CONV) pour six troupeaux consécutifs (n = 84). Les stratégies de réduction des antibiotiques consistaient en l'utilisation continue d'ionophores dans l'alimentation sans (TX1) ou avec de l'acide butyrique (TX2). Aucune différence statistique (p > 0.05) n’a été notée entre TX1, TX2 et CONV sur les performances zootechniques et la santé intestinale. Les comptes d’oocystes d’Eimeria spp. étaient significativement (p < 0.05) inférieurs entre 22 et 34 jours d'âge dans les troupeaux CONV comparé aux TX1 et TX2. Le type de programme antibiotique a eu un impact relativement mineur (valeur R = 0.039), mais statistiquement significatif (p = 0.002), sur le microbiote cécal, tandis que les facteurs environnementaux ont montré les corrélations significatives (p = 0.001) les plus fortes avec le microbiote. Parmi les composantes du microbiote cécal associées à la croissance, le gain quotidien moyen (GMQ) était significativement associé à la Richesse bactérienne (p < 0.05). L’abondance relative de la famille bactérienne Lachnospiraceae fut la mesure la plus fortement corrélée à un GMQ augmenté, tandis que l’abondance relative de nombreuses familles bactériennes, incluant les Porphyromonadaceae, les Planococcaceae et les Veillonellaceae, fut corrélée à un faible GMQ. Ces taxons défavorables formaient un vaste réseau de corrélations positives entre elles, et négativement corrélées aux Lachnospiraceae. En conclusion, ces travaux ont contribué à améliorer la résilience de l'industrie avicole en fournissant des stratégies alternatives aux AIM pour prévenir les maladies intestinales. Des connaissances importantes sur le microbiote cécal des poulets de chair furent générées et pourront considérablement influencer les directions futures de la manipulation du microbiote pour favoriser la croissance. Par exemple, un paradigme important a été remis en question en illustrant que les additifs médicamenteux dans l'alimentation n’influencent que marginalement le microbiote cécal et que ce sont plutôt des facteurs environnementaux qui sont fortement impliqués dans la formation des communautés bactériennes cécales. La clé pour développer un microbiote cécal idéal chez les poulets de chair pourrait résider dans la capacité d'influencer ces facteurs, plus particulièrement l'exposition précoce à des communautés bactériennes bénéfiques et le contrôle de la flore résidente spécifique à la ferme. / There is a global pressure to review current antimicrobial use (AMU) practices in animal production and limit large-scale propagation of antibiotic resistant microorganisms. Consequently, the Chicken Farmers of Canada are examining the possibility to responsibly reduce AMU by discontinuing medically important antibiotics (MIAs) for humans from disease prevention programs of broiler chicken flocks through the implementation of their Antimicrobial Use Reduction Strategy. However, information is sparse on the consequences of such approaches in a Canadian commercial poultry production context. The general objective of this thesis was to investigate the impacts of two strategies reducing AMU in commercial broiler chicken flocks on zootechnical performance, control of intestinal diseases and the cecal microbiota compared to conventional AMU. On seven commercial broiler chicken farms, a house was allocated to the antibiotic reduction treatments for six consecutive flocks, while a similar house on the same premises was assigned to the conventional AMU (CONV) for six consecutive flocks (n = 84). The antibiotic reduction strategies consisted of continuous in-feed ionophores without (TX1) or with butyric acid (TX2). There were no statistical differences (p > 0.05) between TX1, TX2 and CONV for zootechnical performance and intestinal health. Predicted Eimeria spp. oocysts were significantly lower (p < 0.05) between 22 to 34 days of age in CONV flocks compared to TX1 and TX2. The type of antibiotic program had a relatively minor impact (R-value = 0.039), but statistically significant (p = 0.002), on the cecal microbiota composition, while environmental factors such as the farm and flock cycle showed the strongest statistically significant (p = 0.001) correlations with the microbiota composition (R-values of 0.239 and 0.374, respectively). Amongst the cecal microbiota components associated with weight gain, the average daily gain (ADG) was significantly associated with bacterial Richness (p < 0.05). The relative abundance of the bacterial family Lachnospiraceae was the most important measure correlated with ADG, while the relative abundance of numerous bacterial families, including Porphyromonadaceae, Planococcaceae and Veillonellaceae, were correlated with decreased growth rate. These unfavourable taxa formed a large network of positive correlations, indicating potential co-occurring synergies between these undesirable taxa. This network was also negatively correlated to Lachnospiraceae. In conclusion, the findings in this work contributed to improve the sustainability of the modern poultry industry by providing feasible alternatives to the practice of using MIAs for the prevention of intestinal diseases in broiler chickens. This project also generated important knowledge on the cecal microbiota of broiler chickens that could considerably influence future directions of microbiota manipulation in a perspective of improving zootechnical performance. For instance, an important paradigm was challenged by the indication that in-feed antibiotics and prebiotics may only influence marginally the microbiota during grow-out. Rather, this work suggests environmental factors are strongly involved in shaping the bacterial communities residing in the ceca of broiler chickens. Hence, the key to successfully develop an ideal cecal microbiota in broiler chickens may reside in the ability to influence such factors, more specifically the early exposure to beneficial bacterial communities and the control of farm-specific resident flora.
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