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This study investigated the implementation of the roll back malaria (RBM) programme at household and at health post levels and examined factors that negatively impact on malaria prevention and control activities. Quantitative, descriptive, analytic crosssectional research, guided by the conceptual framework of the Health Belief Model, was conducted. Structured interviews were conducted with 857 women (for the household survey in phase 1) and 53 health extension workers (HEWs) in phase 2 of the study, in nine malaria endemic districts of Sidama Zone, southern Ethiopia. Data were analysed using SPSS version 20. The study’s findings indicate that 53.3% (n=457) of the household respondents and 24.5% (n=13) of the HEWs had low levels of overall malaria-related knowledge. Household respondents aged 25-34 years, (p<0.01); regularly received malaria-related information, (p<0.001) and the less poor women (p<0.001) had good levels of knowledge. Of the households, 38.9% (n=333) reported poor RBM practices. Wealth, knowledge, perceived threat of malaria and perceived benefits of implementing malaria preventive measures were positively associated with good RBM practices. Indoor residual spraying (63.6%; 422 out of 664), consistent use of insecticide treated bed nets (51.6%; 368 out of 713), and environmental sanitation (38.6%; 331 out of 857) were the most commonly implemented malaria prevention strategies in the study area. Out of the 252 reported malaria cases, 53.6% (n=135) occurred among children under five years of age who also comprised 50.0% (n=16) of 32 reported malaria-related deaths. The RBM practices were poorly implemented in the study area despite malaria prevention and control efforts. Slow progress in behavioural changes among household members, lack of transportation services for referring malaria patients, lack of support given to HEWs and lack of feedback and supervision from higher level health care facilities were identified as potential challenges facing RBM implementation in the study area. Future efforts need to focus on effective behavioural changes based on intervention studies and regular monitoring of the RBM programme. The workloads of the HEWs should also be reconsidered and lay health educators should be used more effectively. Health posts should always have sufficient anti-malaria drugs and other resource such as rapid diagnostic kits. / Health Studies / D. Litt. et Phil. (Health Studies)

This study investigated the implementation of the roll back malaria (RBM) programme at household and at health post levels and examined factors that negatively impact on malaria prevention and control activities. Quantitative, descriptive, analytic crosssectional research, guided by the conceptual framework of the Health Belief Model, was conducted. Structured interviews were conducted with 857 women (for the household survey in phase 1) and 53 health extension workers (HEWs) in phase 2 of the study, in nine malaria endemic districts of Sidama Zone, southern Ethiopia. Data were analysed using SPSS version 20. The study’s findings indicate that 53.3% (n=457) of the household respondents and 24.5% (n=13) of the HEWs had low levels of overall malaria-related knowledge. Household respondents aged 25-34 years, (p<0.01); regularly received malaria-related information, (p<0.001) and the less poor women (p<0.001) had good levels of knowledge. Of the households, 38.9% (n=333) reported poor RBM practices. Wealth, knowledge, perceived threat of malaria and perceived benefits of implementing malaria preventive measures were positively associated with good RBM practices. Indoor residual spraying (63.6%; 422 out of 664), consistent use of insecticide treated bed nets (51.6%; 368 out of 713), and environmental sanitation (38.6%; 331 out of 857) were the most commonly implemented malaria prevention strategies in the study area. Out of the 252 reported malaria cases, 53.6% (n=135) occurred among children under five years of age who also comprised 50.0% (n=16) of 32 reported malaria-related deaths. The RBM practices were poorly implemented in the study area despite malaria prevention and control efforts. Slow progress in behavioural changes among household members, lack of transportation services for referring malaria patients, lack of support given to HEWs and lack of feedback and supervision from higher level health care facilities were identified as potential challenges facing RBM implementation in the study area. Future efforts need to focus on effective behavioural changes based on intervention studies and regular monitoring of the RBM programme. The workloads of the HEWs should also be reconsidered and lay health educators should be used more effectively. Health posts should always have sufficient anti-malaria drugs and other resource such as rapid diagnostic kits. / Health Studies / D. Litt. et Phil. (Health Studies)

Malaria is both a preventable and curable disease if treated early and appropriately. However, it is estimated that every 30 seconds a child dies of malaria in sub-Saharan Africa. The use of innovative eHealth/mHealth tools for malaria that seamlessly integrate into the workflow of healthcare workers could potentially ameliorate this problem. Successful design and development of these tools require an overarching understanding of the socio-technical context for the problems and opportunities in the application domain. A series of studies involving malaria management in the Millennium Village Project (MVP) cluster in rural Ghana were performed. A new method introduced by the author was applied to prioritize health information needs of stakeholders that have the potential to have a higher impact in solving health related problems. The result of applying this method was a group of impactful interventions for the MVP malaria program in Ghana. Findings from this study were validated with the MVP Ghana eHealth team, and after mutual agreement, an eHealth/mHealth intervention around malaria supply chain management was selected for further study. User-Centered Design (UCD) methods were adapted for use in a resource poor setting. Functional and non-functional requirements were identified. A low fidelity prototype was created and early usability inputs were collected. A high fidelity prototype was created to provide decision support to health workers through visualizations of stock levels and recommendations of quantities to order. Results from evaluation studies of the high fidelity prototype with end users suggest that they perceive the prototype as both easy to use and useful, with a potential for adoption and with a low risk of implementation. Usability problems found during the course of the study should be addressed to increase the potential of adoption. To obtain a more complete list of usability issues, both users’ and experts’ evaluations are recommended as well as the use of native and foreign test facilitators.

A maioria das cepas de Plasmodium falciparum mostra-se resistente à cloroquina (CQ), considerado o antimalárico ideal. A busca por novos agentes terapêuticos bem como a restauração do efeito antimalárico de fármacos disponíveis, através da associação a agentes moduladores da resistência (AMR), vem sendo enfatizada. Entretanto, ausência de efeito modulador da resistência e efeito antiplasmódico intrínseco foram observados quando AMR clássicos, como o fenotiazínico clorpromazina e o iminodibenzílico desipramina, foram ensaiados in vitro em isolados brasileiros de P. falciparum resistentes à CQ. Sabe-se que a ação antiparasitária de compostos de natureza tricíclica, como os fenotiazínicos, foi descrita há mais de um século e continua a ser de interesse. Em adição, vale notar a ocorrência de farmacóforo comum, formado por sistema heteroaromático, ligado a átomo de nitrogênio, secundário ou terciário, por cadeia lateral de três a quatro átomos de carbono, entre compostos quinolínicos antimaláricos, fármacos psicotrópicos e AMR. Este trabalho teve como objetivo estudar, por emprego da modelagem molecular, características estereo-eletrônicas e lipofílicas e a interação a nível molecular de compostos de natureza tricíclica (fenotiazínicos e iminodibenzílicos) com a hematina (provável sítio de ação da CQ) comparando ao antimalárico CQ. Semelhanças estéreo-eletrônicas e lipofílicas puderam ser visualizadas entre as moléculas da CQ e dos compostos tricíclicos. No entanto, algumas distinções ausência de planaridade e maior densidade eletrônica sobre os anéis tricíclicos dos anéis heterocíclicos quando comparadas à CQ. Tais características se fizeram refletir na interação com a hematina, como demonstrado nos estudos de ancoramento como também nos estudos de UV-VIS e de Raman Ressonante. / The most Plasmodium falciparum strains show resistance to chloroquine (CQ), yet considered the ideal antimalaric agent. The search for new therapeutic compounds and the restoration of the antimalarial effect of available drugs through the association with modulating agents has been emphasized. However, lack of modulating effect and intrinsic antiplasmodial activity were observed when classic modulating agents, such phenothiazine chlorpromazine and iminodibenzylic desipramine, were tested in vitro against Brazilian isolated resistant of P. falciparum to CQ. The antiparasitic action of tricyclic compounds as the phenotiazine class has been described for more than a century and continues to be of interest. In addition, it was noted the occurrence of common pharmacophore, formed by a heteroaromatic system, a secondary or tertiary nitrogen atom, linked by a side chain of three to four carbon atoms, present among the quinoline antimalarials, the psychotropic drugs and the modulating agents of chloroquine resistance. The goal of this work was by using molecular modeling to study stereo-electronic features and lipophilic characteristics and the interaction on molecular level of tricyclic compounds (phenothiazines and iminodibenzylics) with hematin (probable site of action of CQ) in comparison to antimalaric CQ. In results, similarities stereo-electronic and lipophilic could be viewed between the molecules of CQ and tricyclic compounds. However different features could be noticed such as absence of planarity and a higher electronic density on the tricyclic rings when compared to CQ. These features shown to be relevant to interaction with the &#181;-oxo dimer of hematin, as observed in docking studies and UV-VIS and Resonance Raman.

<p>Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home / care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001 / Goodman, et al, 2007 / Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria.</p>

<p>Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home / care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001 / Goodman, et al, 2007 / Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria.</p>

A maioria das cepas de Plasmodium falciparum mostra-se resistente à cloroquina (CQ), considerado o antimalárico ideal. A busca por novos agentes terapêuticos bem como a restauração do efeito antimalárico de fármacos disponíveis, através da associação a agentes moduladores da resistência (AMR), vem sendo enfatizada. Entretanto, ausência de efeito modulador da resistência e efeito antiplasmódico intrínseco foram observados quando AMR clássicos, como o fenotiazínico clorpromazina e o iminodibenzílico desipramina, foram ensaiados in vitro em isolados brasileiros de P. falciparum resistentes à CQ. Sabe-se que a ação antiparasitária de compostos de natureza tricíclica, como os fenotiazínicos, foi descrita há mais de um século e continua a ser de interesse. Em adição, vale notar a ocorrência de farmacóforo comum, formado por sistema heteroaromático, ligado a átomo de nitrogênio, secundário ou terciário, por cadeia lateral de três a quatro átomos de carbono, entre compostos quinolínicos antimaláricos, fármacos psicotrópicos e AMR. Este trabalho teve como objetivo estudar, por emprego da modelagem molecular, características estereo-eletrônicas e lipofílicas e a interação a nível molecular de compostos de natureza tricíclica (fenotiazínicos e iminodibenzílicos) com a hematina (provável sítio de ação da CQ) comparando ao antimalárico CQ. Semelhanças estéreo-eletrônicas e lipofílicas puderam ser visualizadas entre as moléculas da CQ e dos compostos tricíclicos. No entanto, algumas distinções ausência de planaridade e maior densidade eletrônica sobre os anéis tricíclicos dos anéis heterocíclicos quando comparadas à CQ. Tais características se fizeram refletir na interação com a hematina, como demonstrado nos estudos de ancoramento como também nos estudos de UV-VIS e de Raman Ressonante. / The most Plasmodium falciparum strains show resistance to chloroquine (CQ), yet considered the ideal antimalaric agent. The search for new therapeutic compounds and the restoration of the antimalarial effect of available drugs through the association with modulating agents has been emphasized. However, lack of modulating effect and intrinsic antiplasmodial activity were observed when classic modulating agents, such phenothiazine chlorpromazine and iminodibenzylic desipramine, were tested in vitro against Brazilian isolated resistant of P. falciparum to CQ. The antiparasitic action of tricyclic compounds as the phenotiazine class has been described for more than a century and continues to be of interest. In addition, it was noted the occurrence of common pharmacophore, formed by a heteroaromatic system, a secondary or tertiary nitrogen atom, linked by a side chain of three to four carbon atoms, present among the quinoline antimalarials, the psychotropic drugs and the modulating agents of chloroquine resistance. The goal of this work was by using molecular modeling to study stereo-electronic features and lipophilic characteristics and the interaction on molecular level of tricyclic compounds (phenothiazines and iminodibenzylics) with hematin (probable site of action of CQ) in comparison to antimalaric CQ. In results, similarities stereo-electronic and lipophilic could be viewed between the molecules of CQ and tricyclic compounds. However different features could be noticed such as absence of planarity and a higher electronic density on the tricyclic rings when compared to CQ. These features shown to be relevant to interaction with the &#181;-oxo dimer of hematin, as observed in docking studies and UV-VIS and Resonance Raman.

Made available in DSpace on 2015-04-20T12:31:29Z (GMT). No. of bitstreams: 1 Rodrigo Cesar das Neves Amorim.pdf: 5191612 bytes, checksum: 928eb24ece47b6a34630736ce7c58e0c (MD5) Previous issue date: 2009-09-11 / Conselho Nacional de Desenvolvimento Científico e Tecnológico / Isobrucein B (2) and neosergeolide (5) are quassinoids which are obtained from Picrolemma sprucei. These compounds have proven in vitro antitumor, antimalarial, anthelminthic, cytotoxic, insecticide and leishmanicidal activities. Herein, in vitro techniques were used to investigate a range of biological activities of 2 and 5 and known semi-synthetic derivative 1,12-diacetylisobrucein B (21) and 12-acetylneosergeolide (22). These compounds were evaluated for general toxicity toward the brine shrimp species Artemia franciscana, cytotoxicity toward human tumour cells, larvicidal activity toward the dengue fever mosquito vector Aedes aegypti and antimalarial activity against the human malaria parasite Plasmodium falciparum. 2 and 5 exhibited the greatest antimalarial activity against multidrug-resistant P. falciparum K1 strain. 2 and 5 (LC50 = 3.2-4.4 mg/L) displayed greater lethality than derivative 22 (LC50 = 75.0 mg/L) toward A. aegypti larvae, while derivative 21 was inactive. Biological assays were also performed with extracts and fractions obtained from P. sprucei fruit. A TLC densitometry method was developed to mensurate the quassinoids content in fruits extracts and fractions. This analysis determinate that only chloroform fractions presents significative content of 2 and 5 and this data is related to the biological activities. Infusions of the stems of P. sprucei are used in the Amazon region as antimalarials. They contain 2 and 5. An LC-(+)-ESI-MS/MS method was developed and applied to the determination of 2 and 5 in P. sprucei infusions. The concentrations of 2 and 5 in the stem infusion were found to be 60.1 and 774 μg L-1, respectively / Isobruceína B (2) e a neosergeolida (5) são quassinóides obtidos de Picrolemma sprucei. Essas substâncias possuem atividade antitumoral, antimalárica, anti-helmíntica, citotóxica, inseticida e leishmanicida in vitro já comprovadas. Neste trabalho, técnicas in vitro foram utilizadas para investigar uma variedade de atividades biológicas de 2 e 5 e dos derivados semi-sintéticos 1,12-diacetilisobruceína B (21) e 12-acetilneosergeolida (22). Essas substâncias foram avaliadas quanto à sua toxicidade geral frente a larvas do microcrustáceo Artemia franciscana, citotoxicidade frente a células tumorais humanas em colaboração com o laboratório de Oncologia da UFC, sob coordenação da Profa. Cláudia Pessoa, atividade larvicida frente a larvas do mosquito vetor da dengue Aedes aegypti e atividade antimalárica frente ao parasita causador da malária humana Plasmodium falciparum. 2 e 5 exibiram elevada atividade antimalárica frente à cepa multiresistente de P. falciparum K1 (CI50 1,0-4,0 ng/mL). 2 e 5 (CL50 3,2-4,4 mg/L) apresentaram letalidade bem mais elevada do que o derivado 22 frente a larvas de A. aegypti, ao passo que o derivado 21 se mostrou inativo. Ensaios biológicos também foram realizados com extratos e frações obtidos de frutos de P. sprucei. Um método baseado em CCD-densitometria foi desenvolvido para mensurar o teor de quassinóides nos frutos e frações destes frutos. Essas análises determinaram que apenas as frações obtidas em clorofórmio apresentam teores significativos de 2 e 5 e esses teores estão relacionados às atividades biológicas. Infusões dos caules de P. sprucei são utilizadas na Amazônia . Um método baseado em LC-(+)-ESI-MS/MS foi desenvolvido e aplicado para determinar o teor de 2 e 5 em infusões de P. sprucei. As concentrações de 2 e 5 nas infusões de caules são de 60,1 e 774 μg L-1, respectivamente

Magister Public Health - MPH / Malaria is a health, social and economic burden in Nigeria and consistently ranks amongst the four most common causes of childhood deaths. Treatment of malaria is usually started at home; care is only sought from the health facility when the treatment is ineffective (McCombie, 1996). Patent medicine vendors (PMVs) have been identified as a widely patronized source for drugs used in the home treatment of malaria (Breiger et al, 2001; Goodman, et al, 2007; Salako et al, 2001). Inadequate or poor knowledge and practices in the use of anti-malaria drugs (AMDs) increases morbidity and mortality, undermines therapeutic efficacy, and promotes the emergence and spread of drugresistant malaria. Aim: The aim of the study was to describe and quantify the knowledge and self-reported practices of PMVs in the use of antimalarials, particularly artemisinin-based combination therapies (ACTs), in a poor urban community in Lagos state, Nigeria. / South Africa