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Oxamniquine, 6-hydroxymethyl-2-N-isopropylaminomethyl-7-nitro-1,2,3,4- tetrahydroquinoline, is a potent schistosomicide used clinically in the treatment of infections due to Schistosoma mansoni. Schistosomiasis is the second most important tropical disease after malaria. Although oxamniquine is relatively well tolerated, severe central nervous system (CNS) effects characterized by convulsions, have been reported in a small percentage of the population treated with this drug.

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Made available in DSpace on 2014-06-11T19:32:17Z (GMT). No. of bitstreams: 0 Previous issue date: 2012-07-25Bitstream added on 2014-06-13T19:02:42Z : No. of bitstreams: 1 gushi_lt_dr_botib.pdf: 860668 bytes, checksum: f4640ec40c34a33b45f1c604d7f189d2 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Leishmaniose Visceral Americana (LVA) é uma doença tropical negligenciada em expansão no Brasil, ocorrendo em áreas onde antes não havia registro. Seu agente etiológico e a Leishmania chagasi um protozoário pertencente à classe Kinetoplastida caracterizada por uma organela denominada cinetoplasto a qual possui um DNA organizado em uma rede contendo maxicírculos, responsáveis pelas funções respiratórias e minicírculos, envolvidos na pordução de RNAs-guia, os quais possuem um papel importante na edição dos RNAs dos maxicírculos. Os minicírculos são divididos em uma região convervada de aproximadamente 120 p.b. e uma região variável de aproximadamente 600 p.b. O foco desse estudo está na análise das seqüências da região variável a fim de entender sua distribuição nos diferentes estágios de vida da L. chagasi. As amostras foram coletadas de cães e pacientes sintomáticos por aspiração dos linfonodos e, em alguns casos, foram obtidas culturas primárias. A extração do DNA foi realizada com o kit comercial Nucleo Spin Blood Kit (Macherey - Nagel) seguindo as instruções do protocolo. O kDNA foi amplificado por PCR, utilizando o par de oligonucleotídeos LIN R4 - forward (5’-GGT TGG TGT AAA ATA GGG-3) e LIN 19 - reverse (5’-GAA CGC CCC TAC CCG-3’), produzindo um fragmento de aproximadamente 720 p.b. Os produtos da PCR foram clonados no vetor pTZ57R/T de acordo com o protocolo do InsTAclone PCR cloning kit. As seqüências (aproximadamente 182) foram individualmente comparadas com as depositadas no GenBank, alinhadas com o software Clustal X2 e tiveram uma árvore filogenética construída utilizando o software MEGA 4.0 adotando o algoritmo UPGMA e escolhendo um bootstrap com 1000 replicatas. A distribuição entre os diferentes hospedeiros foi homogênea. A princípio, um lato polimorfismo é observado, mas... / American Visceral Leishmaniasis (AVL) is a neglected tropical disease in expansion in Brazil currently occurring in areas where there has never been reports. Its etiologic agent is Leishmania chagasi, a protozoan belonging to the order Kinetoplastida characterized by an organelle named kinetoplast wich has a DNA organized in a network containing maxicircles, responsible for respiratory functions and minicircles, involved in the production of guide RNAs, which play a role in the RNA editing of maxicircles. The minicircles are divided into an approximately 120 b.p. conserved region and an approximately 600 b.p. variable region. The focus of this study is on the sequence analysis of the minicircles variable region in order to understand its distribution on different life stages of L. chagasi. Samples were collected from dogs and symptomatic patients by lymphonod aspiration and, in some cases, primary cultures were obtained. DNA extraction was carried out with the commercial kit Nucleo Spin Blood Kit (Macherey - Nagel) following its protocol. kDNA was amplified by PCR, using a pair of oligonucleotides LIN R4 - forward (5’-GGT TGG TGT AAA ATA GGG-3) and LIN 19 - reverse (5’-GAA CGC CCC TAC CCG-3’), producing a fragment of 720 b.p. PCR products were cloned in pTZ57R/T vector according to the InsTAclone PCR cloning kit protocol. Sequences (182) were individually compared with the ones deposited at the GENBANK, aligned with Clustal X2 software and had a phylogenetic tree constructed utilizing MEGA 4.0 software adopting UPGMA algorithm and choosing bootstrap with 1000 replicates. Sequences distribution among different hosts was homogeneous. At first, high polymorphism is observed but, when analyzed in more detail, i.e. by branch, sequences proved to be conserved and minimal SNP (Single Nucleotide Polymorphism) was found... (Complete abstract click electronic access below)

Orientador: Paulo Eduardo Martins Ribolla / Banca: Hiro Goto / Banca: Jayme Augusto de Souza Neto / Banca: Cassiano Victória / Banca: Carlos Magno Castelo Branco Fortaleza / Resumo: Leishmaniose Visceral Americana (LVA) é uma doença tropical negligenciada em expansão no Brasil, ocorrendo em áreas onde antes não havia registro. Seu agente etiológico e a Leishmania chagasi um protozoário pertencente à classe Kinetoplastida caracterizada por uma organela denominada cinetoplasto a qual possui um DNA organizado em uma rede contendo maxicírculos, responsáveis pelas funções respiratórias e minicírculos, envolvidos na pordução de RNAs-guia, os quais possuem um papel importante na edição dos RNAs dos maxicírculos. Os minicírculos são divididos em uma região convervada de aproximadamente 120 p.b. e uma região variável de aproximadamente 600 p.b. O foco desse estudo está na análise das seqüências da região variável a fim de entender sua distribuição nos diferentes estágios de vida da L. chagasi. As amostras foram coletadas de cães e pacientes sintomáticos por aspiração dos linfonodos e, em alguns casos, foram obtidas culturas primárias. A extração do DNA foi realizada com o kit comercial Nucleo Spin Blood Kit (Macherey - Nagel) seguindo as instruções do protocolo. O kDNA foi amplificado por PCR, utilizando o par de oligonucleotídeos LIN R4 - forward (5'-GGT TGG TGT AAA ATA GGG-3) e LIN 19 - reverse (5'-GAA CGC CCC TAC CCG-3'), produzindo um fragmento de aproximadamente 720 p.b. Os produtos da PCR foram clonados no vetor pTZ57R/T de acordo com o protocolo do InsTAclone PCR cloning kit. As seqüências (aproximadamente 182) foram individualmente comparadas com as depositadas no GenBank, alinhadas com o software Clustal X2 e tiveram uma árvore filogenética construída utilizando o software MEGA 4.0 adotando o algoritmo UPGMA e escolhendo um bootstrap com 1000 replicatas. A distribuição entre os diferentes hospedeiros foi homogênea. A princípio, um lato polimorfismo é observado, mas... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: American Visceral Leishmaniasis (AVL) is a neglected tropical disease in expansion in Brazil currently occurring in areas where there has never been reports. Its etiologic agent is Leishmania chagasi, a protozoan belonging to the order Kinetoplastida characterized by an organelle named kinetoplast wich has a DNA organized in a network containing maxicircles, responsible for respiratory functions and minicircles, involved in the production of guide RNAs, which play a role in the RNA editing of maxicircles. The minicircles are divided into an approximately 120 b.p. conserved region and an approximately 600 b.p. variable region. The focus of this study is on the sequence analysis of the minicircles variable region in order to understand its distribution on different life stages of L. chagasi. Samples were collected from dogs and symptomatic patients by lymphonod aspiration and, in some cases, primary cultures were obtained. DNA extraction was carried out with the commercial kit Nucleo Spin Blood Kit (Macherey - Nagel) following its protocol. kDNA was amplified by PCR, using a pair of oligonucleotides LIN R4 - forward (5'-GGT TGG TGT AAA ATA GGG-3) and LIN 19 - reverse (5'-GAA CGC CCC TAC CCG-3'), producing a fragment of 720 b.p. PCR products were cloned in pTZ57R/T vector according to the InsTAclone PCR cloning kit protocol. Sequences (182) were individually compared with the ones deposited at the GENBANK, aligned with Clustal X2 software and had a phylogenetic tree constructed utilizing MEGA 4.0 software adopting UPGMA algorithm and choosing bootstrap with 1000 replicates. Sequences distribution among different hosts was homogeneous. At first, high polymorphism is observed but, when analyzed in more detail, i.e. by branch, sequences proved to be conserved and minimal SNP (Single Nucleotide Polymorphism) was found... (Complete abstract click electronic access below) / Doutor

A research report submitted to faculty of health sciences in partial fulfillment of the requirement for the degree of Master of Science in Epidemiology in the field of implementation science University of the Witwatersrand, Johannesburg. November, 2017. / Background There is a dearth of information about how well this intervention is conducted in communities (implementation fidelity) as fidelity data are not included in routine program data. Therefore, this study measured the implementation fidelity of mass drug administration for onchocerciasis, lymphatic filariasis, and soil transmitted helminthiasis control, described factors affecting it, and determined the relationship between identified factors and implementation fidelity. Methodology A cross sectional survey was conducted in Nassarawa and Gezawa local government areas of Kano State, Nigeria, where a total 348 community directed distributors were interviewed. Scores were calculated by linearly combining responses obtained using Likert scales. Mean and median of implementation fidelity score were computed. Also, the mean of key determinants were calculated. Adjusted and unadjusted general linear regression models were then fitted to determine the relationship between implementation fidelity and identified determinants. Results The mean(SD) implementation fidelity score was 55.39(8.10) and median(IQR) was 56(60 - 49). Minimum implementation fidelity score obtained was 36 and maximum score was 72. The mean(SD) quality of delivery score, intervention complexity score, facilitation strategy score and participant responsiveness score were 16.77(2.74), 11.03(3.04), 8.83(0.99) and 4.62(0.52) respectively. Evidence of association between some factors and implementation fidelity score were found at p < 0.05. They include: intervention complexity (Adj Coef: -0.62(-0.93 to -0.30), iv facilitation strategies (Adj Coef:-1.68(-3.05 to -0.32), participants responsiveness (Adj Coef: 2.99(1.58 to 4.39), knowledge of NTD (Adj Coef: 0.75(0.36 to 1.13), CDD selection by local government staff (Adj Coef: 7.48(2.85 to 12.11), CDD who volunteered (Adj Coef: 8.38(4.59 to 12.16) CDD with formal training in a health-related field (Adj Coef: 7.34(2.61 to 12.07), and CDD participation in other public health activities (Adj Coef: -6.16(-9.49 to -2.83). Conclusion This study demonstrated the feasibility of measuring implementation fidelity of mass drug administration. In addition, key determinants such as intervention complexity and participant responsiveness were found to be important factors affecting implementation fidelity and could be the target of future implementation strategies. / LG2018