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Reducing Usage Barriers : Employing AI-based Image Analysis in a Diagnostic PlatformSvensson, Viktoria, Lindberg, Stina January 2024 (has links)
Neglected Tropical Diseases (NTDs) currently affect approximately 1.6 billion people worldwide, predominantly impacting populations with limited resources and access to healthcare. The study employs an interdisciplinary approach within the field of diagnostics and information technology to investigate the application of computer vision in developing diagnostic tools with the aim of fighting the spread of neglected tropical diseases (NTDs). By leveraging advancements in the field of computer vision, the research seeks to enhance diagnostic accuracy and efficiency by lowering the usage barriers of the diagnostic tool. The research explores the feasibility of using computer vision to differentiate between various characteristics of images generated by a microscope in a diagnostic setting. The aim is to determine the most suitable method for image analysis in the diagnostic setting, comparing conventional image processing techniques, such as image filtering and color models, with Artificial Intelligence (AI)-based methods. The results revealed that the complexity of the images rendered conventional image filters and color models inadequate, highlighting the necessity of alternative methodologies, such as AI. The findings suggest that AI-based approaches are better suited to handle the intricate details and variations present in the images captured by the microscope by offering more accurate and reliable diagnostic capabilities. However, the model trained on single-labeled images required an additional technique for addressing images containing multiple characteristics, namely thresholding. Thresholds were essential for effecting the model's final prediction to suit the specific use case. By implementing thresholds, the model could, to a higher degree, distinguish between overlapping features within the images, ensuring more accurate classification and enhancing overall performance in the diagnostic setting. The final result presents a promising AI model that has the potential to reduce the usage barriers of the diagnostic tool. Hence, this study represents a small step in the right direction toward the larger goal of fighting the spread of neglected tropical diseases.
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Dengue diagnostics and therapeutic interventions in Viet NamTricou, Vianney M. January 2011 (has links)
Dengue is a major public health problem that affects tens of millions of people annually in tropical and sub-tropical countries. This acute viral infection happens to be severe and even life threatening but there is still no available drug or vaccine. Previous studies have noted early higher viral burden in patients who develop more severe symptoms suggesting that administration of a potent and safe antiviral may prevent progression to severe dengue. To verify this hypothesis, we have conducted the first RCT directed towards reducing the viral burden in vivo by administrating chloroquine (CQ), a cheap and well-tolerated drug that inhibits DENV in vitro with concentrations achievable in vivo, to 307 Vietnamese adults with suspected dengue (257 of them were laboratory-confirmed cases). Unfortunately, we did not see an effect of CQ on the duration of infection. However in patients treated with CQ, we observed a trend towards a lower incidence of severe forms. We did not find any differences in the immune response that can explain this trend. We also found more adverse events, primarily vomiting, with CQ. In addition, we have explored the relationships between clinical features, antibody responses and virological markers in these patients. We found that the early magnitude of viremia is positively associated with disease severity and there are serotype dependent differences in infection kinetics. We found as well that DENV was cleared faster and earlier in patients with secondary infections. To complete this study, we have also evaluated 2 rapid lateral flow tests for the diagnosis of dengue in a panel of plasma samples from 245 RT-PCR confirmed dengue patients and 47 with other febrile illnesses. Our data suggest that the NS1 test component of these tests are highly specific and have similar levels of sensitivity (~60%). Both NS1 assays were significantly more sensitive for primary than secondary dengue. The IgM parameter in the SD Duo test improved overall test sensitivity without compromising specificity. All these findings are of major importance for further anti-viral drug testing.
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Maladies infectieuses, écosystèmes et pauvreté : le cas de l'ulcère de Buruli au Cameroun / Infectious diseases, ecosystems and poverty : the case of Buruli ulcer in CameroonGarchitorena Garcia, Andrés 11 December 2014 (has links)
Comprendre les rétroactions entre les maladies infectieuses, la structure des écosystèmes et le développement économique est nécessaire pour alléger le fardeau des maladies tropicales négligées. Ce groupe d'infections parasitaires, virales, et bactériennes est étroitement associé à des conditions géographiques, environnementales, sanitaires et économiques particulières aux régions tropicales. A travers l'étude de l'ulcère de Buruli, une maladie émergente et négligée associé à une morbidité et handicap très importants dans des régions tropicales, ce travail de thèse s'intéresse aux interactions complexes entre ces différents composants des systèmes épidémiologiques. Combinant un travail de terrain important pour la collecte des données environnementales avec une approche de recherche multidisciplinaire, cette thèse vise à améliorer notre compréhension des différents aspects de l'écologie et de l'épidémiologie de cette maladie infectieuse. Notamment, la dynamique de son agent pathogène, M. ulcerans, est caractérisée pour un large éventail d'écosystèmes et communautés aquatiques au Cameroun, permettant d'identifier les facteurs environnementaux permettant sa propagation. En outre, nous évaluons la transmission de l'agent pathogène de l'environnement à l'homme et l'impact de la maladie sur le développement économique des populations endémiques. Ainsi, ce travail montre comment les dynamiques écologiques, épidémiologiques, environnementales et économiques interagissent de concert, mettant en évidence de façon criante le besoin d'une telle approche interdisciplinaire dans l'étude des maladies tropicales négligées. / Understanding the feedbacks between infectious diseases, ecosystem structure and economic development is necessary to alleviate the burden of Neglected Tropical Diseases. This group of parasitic, viral, and bacterial infections is closely associated with particular geographical and environmental conditions mainly present in the tropics, thriving under conditions of poverty, inefficient sanitation and malnutrition. This PhD thesis works through the case study of Buruli ulcer, an emerging and neglected infectious disease associated with a great morbidity and disability burden in tropical regions. Relying on an extensive environmental field survey and a multidisciplinary research approach, this PhD attempts to gain a better understanding of different aspects of the ecology and epidemiology of Buruli ulcer. Notably, the dynamics of its pathogen, M. ulcerans are characterized for a wide range of freshwater ecosystems and aquatic communities in Cameroon, and the environmental drivers of M. ulcerans presence are investigated. Furthermore, we assess the transmission of the pathogen from the environment to humans and the impact of the disease on the economic development of endemic populations. Thus, this work shows how the interplay between ecological, epidemiological and economic dynamics interact together and calls for an urgent need to apply such inter-disciplinary approach to decrease the burden of neglected tropical diseases.
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Identificação e avaliação imunológica de potenciais epítopos de linfócitos T CD4+ e T CD8+ no proteoma de Leishmania (Viannia) braziliensisSILVA, Rafael de Freitas e 06 September 2016 (has links)
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Previous issue date: 2016-09-06 / As leishmanioses são doenças causadas por protozoários do gênero Leishmania e
estão presentes em 98 países e territórios e possuem incidência anual de 2
milhões de casos. A Leishmania (Viannia) braziliensis (L.V. braziliensis) é uma das
principais espécies causadoras da leishmaniose cutânea (LC) no Brasil. Apesar
disso, ainda não há uma vacina segura e eficaz para ser utilizada em seres
humanos. Nesse sentido, o objetivo deste trabalho foi identificar no proteoma
predito de L.V. braziliensis, potenciais epítopos de linfócitos T e avaliá-los por meio
de ensaios imunológicos. No primeiro capítulo, o proteoma predito de L.
braziliensis foi comparado ao de outras espécies e analisado quanto a presença de
epítopos. Nessa etapa foram encontrados epítopos derivados de mais de 8 mil
proteínas conservadas entre diferentes espécies de Leishmania. Os epítopos
foram clusterizados e então utilizados para etapa de docagem molecular com
estruturas de MHC I e MHC II depositadas no Protein Data Bank. A docagem
molecular resultou em epítopos peptídicos de 15 aminoácidos com alta afinidade
de ligação às moléculas de MHC I e MHC II. Os 10 melhores resultados foram
então sintetizados e avaliados, in vitro, quanto à capacidade de estimular a
proliferação de células mononucleares do sangue periférico (PBMC) de indivíduos
com LC após o tratamento (PT). Os resultados indicaram que 50% das moléculas
testadas apresentaram capacidade de estimular, significativamente (p<0,05), a
proliferação celular quando comparado às células de indivíduos saudáveis que não
vivem em região endêmica para LC. No segundo capítulo, os peptídeos foram
avaliados quanto à capacidade de estimular a proliferação de PBMC de indivíduos
com LC em sua fase ativa (AD) e indivíduos moradores de área endêmica para LC
resistentes à infecção (RT). Em paralelo, quantificou-se a expressão do fator de
transcrição T-bet em PBMC de indivíduos PT, e citocinas dos perfis Th1, Th2 e
Th17 foram mensuradas no sobrenadante de cultura das células de indivíduos PT
e AD. Os resultados demonstraram altos níveis de proliferação nas células do
grupo RT para todos os peptídeos testados. Além disso, níveis significativos de Tbet
foram observados em linfócitos T CD4+ e CD8+ após estímulo com seis
peptídeos. Níveis significativos de IFN-γ, TNF e IL-6 foram observados no
sobrenadante das células do grupo PT com quatro dos peptídeos testados. Altos
níveis dessas citocinas também foram encontrados no sobrenadante do grupo AD.
No terceiro capítulo, avaliou-se o efeito dos peptídeos sobre células dendríticas de
medula (BMDC) murinas, produção de citocinas de sobrenadante, e células
dendríticas esplênicas murinas após estímulo com os peptídeos. Verificou-se altos
níveis de MHC II e CD40 em uma subpopulação de BMDC estimuladas com as
moléculas e altos níves de TNF e IL-6 após 48h de estímulo. Para as células
esplênicas, foram observados altos níveis de subpopulações celulares
expressando CD11b+, IL-12p70+, CD205+ e CD11b+ após estímulo com o peptídeo
que teve o melhor resultado in silico. Por fim, os resultados indicam o grande
potencial imunogênico que os epítopos identificados apresentam, o que dá suporte
ao desenvolvimento futuro de abordagens vacinais. / The leishmaniasis are diseases caused by protozoans from the genus
Leishmania which are present in 98 countries and territories, with an annual
incidence of 2 million cases. Among the other species, Leishmania (Viannia)
braziliensis is the main specie implicated with cutaneous leishmaniasis (CL) in
Brazil. Besides that, there is no safe and effective vaccine against leishmaniasis
to be applied in humans. In this context, the aim of this work was to identify in
the predicted proteome of L. braziliensis potential CD4+ and CD8+ T cell
epitopes and evaluate them by immunological assays. In the first chapter, the
predicted proteome of L. braziliensis was compared with other species and
analyzed for the presence of epitopes. In this step, epitopes from more than
8,000 conserved proteins were found among other species of Leishmania. The
epitopes were clustered and then used for the molecular docking with MHC I
and MHC II structures deposited in the Protein Data Bank. This approach
resulted in 15 aminoacids peptide epitopes with high binding affinity for MHC I
and MHC II. The 10 best results were synthesized and evaluated in vitro for
their capacity to stimulate the proliferation of peripheral blood mononuclear cells
(PBMC) of individuals with CL post treatment (PT). The results have shown that
50% of the tested molecules had the capacity to stimulate, significantly
(p<0.05), cell proliferation when compared with cells of healthy individuals living
in non-endemic regions. For the second chapter, the peptides were evaluated
for their capacity to stimulate the proliferation of PBMC from CL individuals with
active disease (AD) and of individuals resistant to infection (RT) living in
endemic region. In parallel, the T-bet transcription factor expression was
quantified in PBMC of PT individuals, and cytokines from the Th1, Th2 and
Th17 profiles were measured in culture supernatant of PT and AD groups. High
levels of cell proliferation in the RT group were demonstrated for all peptides
tested. Moreover, significant levels of T-bet in CD4+ and CD8+ T cells were
verified after stimulation with six peptides. For IFN-γ, TNF and IL-6, significant
levels were detected in the supernatant of cultures from the PT group with four
peptides tested. High levels of these same cytokines were also present in the
supernatant of AD group. In the third chapter, the peptide effects over murine
bone marrow dendritic cells (BMDC), the production of cytokines in the
supernatant and murine spleen dendritic cell subsets were evaluated after
peptide stimuli. High levels of MHC II and CD40 were verified for stimulated
BMDC and high levels of TNF and IL-6 after 48h of stimuli. For spleen cells,
high levels of cells expressing CD11b+, IL-12p70+, CD205+ e CD11b+ were
observed after stimulation with the peptide which showed the best in silico
result. In conclusion, the results indicate the great immunogenic potential of the
identified peptides and support the further development of vaccine approaches
using those molecules.
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Dengue and development: a critical political ecologyMulligan, Kate 04 1900 (has links)
<p>Policies for the control of dengue fever often construct the mosquito-borne virus as a disease of poverty, and call for disease control through “development” to meet the needs of poor populations and impoverished or unsanitary spaces. However, exceptions to the narrative of a rich/poor dengue divide persist in non-poor urban environments across the world. One example is Malaysia's new administrative capital city of Putrajaya – a wealthy and centrally planned new city with among the highest rates of dengue in the country.</p> <p>This dissertation drew on theories of ecosocial epidemiology and urban political ecology to investigate and contextualize the geography of dengue and development in Putrajaya. Key informant interviews and critical discourse analysis found that infectious disease control fell well below other urban priorities for the city, and that globally dominant dengue control strategies targeted toward poor populations were inappropriately transferred to Putrajaya's non-poor local environment. A systematic review of the research literature found no clear evidence showing an association between dengue and conditions of poverty. These findings challenge conventional thinking by policy makers about epidemiological transition and the social determinants of health.</p> <p>The dissertation addresses the dearth of research into the world's neglected tropical diseases (NTDs); in particular, gaps in our understanding of the biopolitical and socioecological contexts (sites of urban governance, sites of health policy development and implementation, and sites of academic research) in which policies for NTDs like dengue are determined, enacted and justified. The dissertation further identifies non-poor urban environments – in particular those undergoing rapid development, such as Putrajaya – as key spaces for future geographic and political ecological research related to epidemiological transition, economic development and the social and environmental determinants of health.</p> / Doctor of Philosophy (PhD)
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專利池對非洲治療公衛相關被忽略的熱帶疾病之研究 / Study of patent pool in treatment of public health related neglected tropical diseases in Africa范家堃, Fan, Chia Kwung Unknown Date (has links)
「被忽視」的熱帶疾病(NTDs)中的寄生蟲疾病(Parasitic Diseases; PDs)除對非洲人群健康之危害甚鉅外,並進而對非洲地區社經體系造成嚴重衝擊與造成巨大的「失能調整人年」損失。由於不易取得治療PDs傳統基本藥物的問題,許多非洲民眾便以其部落社區的傳統治療師所採用的傳統草藥來進行PDs的治療,雖然這些傳統草藥容易取得,但是成分的內容和藥效品質甚或產生嚴重的致命副作用。雖然TRIPS協定第31條和杜哈宣言的第五和第六段對於製藥能力不足或大部分皆無製藥能力的貧窮國家,可以基於「國家緊急危難或其它緊急狀況」的事由,以強制授權方式取得專利藥或較便宜的學名藥以解決造成國家危難的特定公共健康事件,但是國際大藥廠認為無利可圖,不願意花費資金投注於預防或治療此類疾病藥物的相關研發外,高收入的國家為保護其大藥廠的藥物專利,也往往使用一些經濟制裁手段逼迫上述國家就制定國內專利法以保護其藥物專利。雖然經杜哈宣言修正TRIPS協定第31(f)條有關強制授權對外出口的障礙,但是出口國對於強制授權程序與是否能取得政治上和藥廠業者的支持,仍充滿困難。應用「專利池」可以減少交易成本或法律爭議而可調和「強制授權」與解決「權利耗盡」的爭議,有助於解決非洲開發中國家取得專利藥物的困境。PDs造成非洲開發中國家民眾失能等長期痛苦與健康生活損失,類推適用SARS模式,可依TRIPS協定第31條(b)與杜哈宣言第五段(c)將之視為「造成國家緊急危難或其它緊急狀況」的重大公共健康的事由而可行使強制授權。雖然「生醫專利池BVGH」的「非獨家個別授權與免授權費」的操作模式與傳統電信技術專利池不盡相同,但因藥廠不願投入治療PDs的傳統基本藥物存在的副作用與抗藥性的新藥研發,為鼓勵對治療PDs的藥物進行創新研發, BVGH彈性的授權方式與免繳交授權費,將有利於解決開發中國家未來取得新專利藥的困境。除BVGH外,建議結合全球獎勵基金以「激勵拉拔」的方式獎助願意投入治療PDs新藥研發並將專利自願授權給BVGH的藥廠。鑒於全球暖化與最近中東難民潮大量湧進歐洲,罕見的PDs可預期會大量傳播開來,將嚴重衝擊歐洲等先進國家良好的公共衛生體系,而使得「NTDs尤其是PDs不再只是專屬於貧窮國家的疾病,亦將常現於富有的先進國家」。這些NTDs疾病將提供藥廠進行新藥研發的利基,然而在未來可能產生專利池的反競爭問題,導致支配市場獨占性的隱憂值得關注。 / Parasitic diseases (PDs) not only cause the huge health hazards to African populations, but also they further severely impact on African socio-economic system as resulting in huge economic and health losses as assessed by disability adjusted life-years. Since it is not easy for Africans to access the essential medicine to treat PDs, many of them will seek for the help of local healers in tribal communities to treat PDs. Although these traditional herbs are readily available, the content and quality of drug ingredients may even cause serious fatal side effects. Poor countries with insufficiencies or lacks of the pharmaceutical capacities may still access the patented medicines or cheaper generics to solve the national crisis caused by the specific public health events through compulsory licensing (CL) based on "national emergency or the other emergency situations" according to TRIPS Article 31 and Doha Declaration on the fifth and sixth paragraph due to that the large international pharmaceutical companies consider unprofitable, unwilling to spend money to invest on the research and development (R&D) of new drugs for prevention or treatment purpose. Moreover, the high-income countries also tend to exert some of the economic sanctions to force those poor countries to enact national patent law in order to protect drug patents. Furthermore, the mandatory obstacle of exportation authorized by CL from the amended TRIPS Agreement Article 31 (f) by the Doha Declaration has been improved; nevertheless, it is still fraught with difficulties in utilization of CL for the exporting countries because this should be dependent on whether they may actually get the supports from political and the pharmaceutical industry. Application of patent pools model may benefit to reduce transaction costs or legal dispute thus reconciling and resolving issues related to CL as well as doctrine of patent exhaustion and that it is beneficial to help solve dilemma for African countries to access patented drugs. Because Africans severely suffer from disabled caused by PDs thus leading to long-term pain and health life losses, African countries can grant CL as PDs may be regarded as national crisis like SARS causing "national emergency or the other emergency situations" as authorized from TRIPS Agreement Article 31 (f) and Doha Declaration paragraph 5 (c). Although the practice of individual licensing with royalty-free for BVGH is somewhat different from that of traditional patent pools, this licensing practice mode is beneficial to innovation in new drugs R&D to improve the side effects and drug-resistance of traditional essential medicines and help African countries to access patented new drugs in the future. Finally, it is recommended to cooperate with Award Foundation to encourage incentive for pharmaceutical companies which contribute most to new drugs R&D and voluntary licensing to BVGH. Owing to global warming and recent emergence of huge refugees into Europe rare PDs will be obviously spread out thus causing severe impacts on well-established public health system as leading to emergence of PDs in developed countries like Europe. Altogether, such situations definitely provide a good incentive in new drugs R&D for pharmaceutical companies; however, it guarantees concerns on anti-competitive and monopoly issues derived by biomedical pools in the future.
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