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1
Badenhorst, Liezl. « The dissolution analysis of sulfadoxine/pyrimethamine combination tablets / Liezl Badenhorst ». Thesis, North-West University, 2007. http://hdl.handle.net/10394/1791.
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Obua, Celestino. « Fixed-dose chloroquine and sulfadoxine/pyrimethamine treatment of malaria : outcome and pharmacokinetic aspects / ». Stockholm, 2007. http://diss.kib.ki.se/2007/978-91-7357-144-9/.
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Gillet, Philippe. « Hepatite medicamenteuse au fansidar : a propos d'un cas et revue de la litterature ». Amiens, 1992. http://www.theses.fr/1992AMIEM024.
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Manoir, Milena du. « Résistance de Plasmodium falciparum à la sulfadoxine-pyriméthamine : données épidémiologiques et modélisation ». Thesis, Toulouse 3, 2018. http://www.theses.fr/2018TOU30147.
Texte intégralRésumé :
En 2016, 216 millions de cas et 445000 décès liés au paludisme ont été reportés par l'Organisation Mondiale de la Santé (OMS), 90 % de ces cas ont eu lieu sur le continent africain, très majoritairement causés par Plasmodium falciparum. Chez les femmes enceintes le paludisme peut avoir de lourdes conséquences en termes de morbidité et de mortalité aussi bien pour la mère que pour l'enfant à venir. Outre l'utilisation de moustiquaires imprégnées, l'OMS recommande l'utilisation d'un traitement préventif intermittent par sulfadoxine-pyriméthamine (SP) pour les femmes enceintes des zones endémiques d'Afrique sub-saharienne. La résistance du parasite à la SP est un réel problème en l'absence d'alternative thérapeutique et le niveau de résistance est déjà très élevé dans certaines régions d'Afrique. Cette résistance est causée par différents polymorphismes nucléotidiques simples (SNPs) sur les gènes codant pour DHPS et DHFR. Ces mutations modifient la structure 3D de ces enzymes, diminuant leur liaison à la SP. Ce travail s'est attaché à faire un état des lieux récent de la prévalence des mutations des gènes pfdhfr et pfdhps à travers 7 sites d'Afrique Centrale. Un octuple mutant combinant trois mutations sur le gène pfdhfr et cinq mutations sur le gène pfdhps (CirnI + vagKgs) a été découvert à Yaoundé en 2015 ; nous l'avons retrouvé au Nigeria et au Cameroun mais pour la première fois à un haut niveau de prévalence à Maroua (52,2%). Sur plusieurs sites d'Afrique Centrale, nous décrivons l'augmentation de la prévalence de la mutation K540E, typique des parasites résistants de l'Afrique de l'Est et sur laquelle se base l'implémentation de la SP par l'OMS. D'autre part, à partir d'un modèle d'homologie de pfDHPS, nous avons utilisé des techniques de dynamique moléculaire pour mieux comprendre les modifications de la structure 3D liées à différents haplotypes d'intérêts retrouvés en Afrique Centrale. Cette partie de l'étude propose une autre approche pour évaluer et visualiser l'effet structurel des mutations, élément supplémentaire à la compréhension de leur impact sur la résistance à la SPMalaria was responsible for 445 000 death and 216 million new cases worldwide in 2016, 90% of these cases occurred in Africa. Pregnant women are particularly susceptible to malaria, resulting in medical consequences on both mother and child. In the endemic countries of sub Saharan Africa, in addition to the use of insecticidal nets, the World Health Organization (WHO) recommends a preventive treatment against Plasmodium falciparum malaria in pregnancy using Sulfadoxine Pyrimethamine (SP). Resistance of the parasite to SP is a significant problem in the absence of alternative treatment and the level of resistance is very high in some regions of Africa. This resistance is mediated by several single nucleotide polymorphisms (SNPs) in the genes coding for DHPS and DHFR, changing the 3D structure of the two target proteins and decreasing drug binding. This study offers an updated view of the epidemiology of these mutations throughout Central Africa. We identified for the first time the octuple mutant combining 3 mutations on pfdhfr gene and 5 mutations on pfdhps gene (CirnI + vagKgs), discovered in 2015 in Yaoundé, as the major haplotype in Maroua, northern Cameroon (52,2%). On several Central-African sites, we describe the increase of the prevalence of the typically East-African K540E mutation on which is based the implementation of SP by the WHO. Knowledge of the prevalence of resistance markers is crucial for the adaptation of SP recommendation in Central Africa. This study also explores the changes occurring in the 3D structure of the most common mutated pfDHPS haplotypes identified in our epidemiology study, using molecular dynamics on a homology model of the protein. It offers a new vision of the effect of the mutations on the structure, a further step to understanding the impact of mutations in resistance
5
Cisse, Badara. « Seasonal preventive treatment with artesunate and sulfadoxine pyrimethamine prevents malaria in Senegalese children ». Thesis, London School of Hygiene and Tropical Medicine (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.421682.
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Letillois, Claire. « Suivi clinique et immunologique de 71 cas de toxoplasmose congenitale traites ». Reims, 1994. http://www.theses.fr/1994REIMM010.
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7
Bojang, Kalifa Abubakr. « Chemoprophylaxis with sulfadoxine-pyrimethamine to prevent morbidity in Gambian children treated for severe anaemia ». Thesis, London School of Hygiene and Tropical Medicine (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.500046.
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GRAUBY, SAINT-LEBE MARIE-NOELLE. « Chimio-resistances de plasmodium falciparum : cas de la sulfadoxine-pyrimethamine et de la quinine ». Aix-Marseille 2, 1993. http://www.theses.fr/1993AIX20113.
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Silveira, Quelhas Diana Iris. « Immune responses to "Plasmodium falciparum" in Mozambican infants receiving Intermittent Preventive Treatment with Sulfadoxine Pyrimethamine ». Doctoral thesis, Universitat de Barcelona, 2011. http://hdl.handle.net/10803/51637.
Texte intégralRésumé :
Malaria has a high toll on the lives of infants and children under the age of five in endemic areas. Control, and more recently, elimination agendas consist on implementing several measures simultaneously, including vector control, vaccines and drugs. The current Millenium Development Goals aim at reducing malaria mortality and morbidity in the two most vulnerable groups: pregnant women and children.
Intermittent Preventive Treatment in Infants with Sulphadoxine‐Pyrimethamine (IPTi-SP) delivered through routine EPI vaccination programs has shown to be efficacious in different transmission settings and the WHO has recently recommended its implementation as a malaria control tool. However, one of the main concerns has been the potential impairment of acquisition of naturally acquired immunity, and this could be a concern regarding IPTi.
This thesis reports on a series of studies conducted in a malaria endemic area of Manhiça, Mozambique, to assess the impact of IPTi‐SP on the development of immune responses to the Plasmodium falciparum parasite. In this work, we measured antibody and cellular immune parameters considered to be the most appropriate markers of protective immunity against malaria identified to date.
The most consistent finding was that IPTi-SP does not modify the magnitude of the immune responses acquired over the first two years of age in Mozambican children. In addition, we described the factors that affect the antibody and cellular immune responses, and reported those that correlated with prospective malaria incidence.
Based on the studies presented herein, we can conclude that IPTi‐SP does not interfere with immune responses that are considered major contributors to the acquisition of protective immunity to malaria in early infancy.
In summary, this thesis contributes to a more complete assessment of IPTi as a control measure that will possibly be implemented in the near future in malaria endemic areas of Africa and of the world. In addition, it aims to contribute to advance the knowledge on the acquisition of natural immunity in infancy which is poorly understood. Furthermore, this information will help to understand the factors that should be taken into account when designing and deploying other control measures for this age group.
10
Billi, Borchert Lea. « Wirksamkeit und Verträglichkeit von IPTi mit Sulfadoxine-Pyrimethamine zur Prophylaxe gegen Anämie und Malaria in Gabun im ersten Lebensjahr / ». Tübingen, 2009. http://opac.nebis.ch/cgi-bin/showAbstract.pl?sys=000276774.
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Cassam, Yasmin. « The effect of falciparum malaria prevalence on the effectiveness of intermittent preventive treatment with Sulfadoxine-Pyrimethamine during pregnancy in reducing low birth weight in southern Mozambique ». Diss., University of Pretoria, 2012. http://hdl.handle.net/2263/29732.
Texte intégralRésumé :
Malaria infection is a major cause of morbidity and mortality in tropical countries, and particularly in Mozambique. Recently substantial resources have been used to reduce the burden of malaria in Mozambique. These include the distribution of insecticide treated bed-nets, indoor residual insecticide spraying, access to artemisinin-based combination treatment (ACT), and intermittent preventive treatment of pregnant women with sulfadoxine-pyrimetamine (SP-IPTp). The most important benefit of SP-IPTp in malaria endemic areas has been the increase in birth weight, thus increasing the probability of child survival. The SP-IPTp policy was based on evidence of its effectiveness in areas of high intensity malaria transmission. The effect of SP-IPTp has been less evident in the presence of high coverage with insecticide treated bed-nets. It is not know whether reducing the risk of malaria through effective vector control using indoor residual insecticide spraying and large-scale deployment of ACTs has a similar effect in reducing the impact of SP-IPTp on birth weight. At the same time, increasing resistance of SP could be compromising the effect of SP-IPTp on birth weight, as could co-infection with HIV. The aim of this study was to determine if the effect of SP-IPTp on reduction in risk of low birth weight is modified by Plasmodium falciparum malaria prevalence. This retrospective antenatal record review, analyzed 20867 antenatal records from 2005 to 2007 from public health facilities in Maputo and Gaza provinces, southern Mozambique. One or two doses of SP-IPTp does not have any effect on reducing the risk of low birth weight, while women who had at least three doses of SP-IPTp had a 15% lower risk of their babies being born with low birth weigh compared with fewer doses, (OR=0.85; 95% CI 0.73 – 1.00; p=0.053). The risk of babies being born with low birth weight was reduced by 28% when both malaria prevalence and dhfr / dhps mutation prevalence are low, (OR=0.72; 95% CI 0.51 – 1.00), but this effect was no longer significant with higher malaria prevalence and or mutation prevalence. SP-IPTp has an effect on reducing low birth weight with three or more doses, and in areas where malaria prevalence and mutation prevalence are low. CopyrightDissertation (MSc)--University of Pretoria, 2013.
Clinical Epidemiology
unrestricted
12
Djaman, Allico Joseph Mazabraud André. « Évaluation de la chimiorésistance de Plasmodium falciparum à différents antipaludiques (chloroquine, sulfadoxine-pyriméthamine, quinine) et profil génétique des isolats correspondants ». Créteil : Université de Paris-Val-de-Marne, 2003. http://doxa.scd.univ-paris12.fr:80/theses/th0211111.pdf.
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Djaman, Allico Joseph. « Évaluation de la chimiorésistance de Plasmodium falciparum à différents antipaludiques (chloroquine, sulfadoxine-pyriméthamine, quinine) et profil génétique des isolats correspondants ». Paris 12, 2003. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002111110204611&vid=upec.
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Depuis la notification en 1986 des premiers cas de résistance de P. Falciparum en Côte d'Ivoire, relativement peu d'études ont été consacrées à l'évaluation de la chimio-résistance dans ce pays. Il nous a paru nécessaire de mettre en place un système de surveillance de la résistance de P. Falciparum aux antipaludiques au moyen des tests d'efficacité thérapeutique à la chloroquine (CQ) et à la sulfadoxine-pyriméthamine (SP), in vitro à la chloroquine, la pyriméthamine et la quinine. Une approche plus fondamentale basée sur la PCR, la RFLP à l'aide d'endonucléases spécifiques et du séquençage des fragments d'ADN des gènes dhfr, dhps, pfmdr 1 de chaque isolat de P. Falciparum ont été réalisées. Les résultats de l'efficacité thérapeutique ont révélé 21,7 % d'échecs thérapeutiques précoces (ETP), 3,6 % d'échecs cliniques tardifs et 19,3 % d'échecs parasitologiques tardifs contre 55,4 % de réponses cliniques et parasitologiques adéquates (RCPA) à la chloroquine. 36,2 % des isolats mis en culture étaient chloroquino-résistants (CQ-R). Quant à la sulfadoxine-pyriméthamine, 23,6 % d'échecs thérapeutiques (ET) et 76,4 % de réponses cliniques adéquates ont été observés. 39 % des isolats testés in vitro étaient hautement résistants à la pyriméthamine (PYR). Par contre, aucun isolat quinino-résistant n'a été mis en évidence dans cette étude. L'analyse du polymorphisme de taille des fragments d'ADN des isolats de P. Falciparum a révélé 100 % d'isolats K76T chez les enfants ayant un ET à chloroquine et 71,4 % d'isolats K76T au sein des isolats CQ-R. Cependant, 11,8 % des enfants ayant une RCPA portaient des isolats pfcrt mutants. Les mutations affectant les gènes dhfr et dhps ont concerné respectivement 26,4 % et 93,4 % des isolats étudiés. Si les isolats dhfr mutants étaient portés par 85,7 % des enfants ayant un ETP, les mutants dhps étaient présents chez 100 % de ces enfants. De plus, 85,4 % de ces isolats dhfr mutants étaient hautement résistants à la PYR. En définitive, ces résultats reposent le problème de l'utilisation de la CQ et de la SP comme médicament de première et de deuxième intention en Côte d'Ivoire en général et à Abidjan en particulier. Ils peuvent servir de base de données au programme national de lutte contre le paludisme dans le pays pour une meilleure utilisation et une rationalisation des antipaludiques usuelsSince the notification in 1986 of the first cases of P. Falciparum resistance in Côte d'Ivoire, relatively few studies have been devoted to the assessment of chemio-resistance in the country. It appeared necessary to us to set up a monitoring system of the resistance of P. Falciparum to antimalarial drugs by means of the tests of therapeutic efficacy to chloroquine (CQ) and sulfadoxine-pyrimethamine (SP), in vitro to chloroquine, pyrimethamine and quinine. A more fundamental approach based on the PCR, the RFLP using specific endonucleases and the sequencing of DNA fragments of dhfr, dhps, pfmdr-1 genes of P. Falciparum isolates have been achieved. The results of the therapeutic efficacy revealed 21. 7% of early therapeutic failures (ETF), 3. 6% of late clinical failures (LCF) and 19. 3% of late parasitological failures (LPF) against 55. 4% of adequate clinical and parasitological responses (ACPR) to chloroquine. 36. 2% of the isolates were chloroquino-resistant (CQ-R). As for the sulfadoxine-pyriméthamine, 23. 6% of therapeutic failures (TF) and 76. 4% of adequate clinical and parasitological responses were observed. 39% of the isolates tested in vitro were highly resistant to pyrimethamine (PYR). On the other hand, no quinino-resistant isolate was highlighted in this study. The analysis of the polymorphism of size of P. Falciparum DNA fragments revealed 100% of isolates K76T in the children having therapeutic failures to chloroquine and 71. 4% of isolates K76T within the CQ-R isolates. However, 11. 8% of the children having ACPR carried pfcrt mutant isolates. The changes affecting the dhfr and dhps genes concerned respectively 26. 4% and 93. 4% of the studied isolates. If the mutant dhfr isolates were carried by 85. 7% of the children having ETF, the mutants dhps were present at 100% of these children. Moreover, 85. 4% of these dhfr mutant isolates were highly resistant to the PYR. Ultimately, these results rest the problem of the use of the chloroquine and the sulfadoxine-pyrimethamine as first and second line drug in Côte. D'Ivoire in general and in Abidjan in particular. These results can also be used as a basis of data for the National Program of Fight against Malaria in the country for a better use and a rationalization of usual antimalarial drugs
14
Allen, Elizabeth. « Efficacy of sulfadoxine-pyrimethamine with and without artesunate for the treatment of uncomplicated malaria in Mozambique : a randomised controlled trial ». Master's thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/9321.
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Includes bibliographical references (leaves 83-88).[Background and rationale] Malaria accounts for a large public health burden in Mozambique and a treatment policy with effective anti-malarials is a key component of their malaria control programme. Artemisinin-based combination therapies (ACTs) are now generally considered as the best treatment for uncomplicated falciparum malaria; the use of artesunate (AS) in combination with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organisation (WHO). Mozambique policy-makers recommended that an ACT be implemented and studied in 2003. Therefore this RCT was conducted to compare SP monotherapy with AS, plus SP in order to provide further evidence of available treatment options in the region. [Trial design and methods] A prospective multi-centre, open-label, parallel-group randomised clinical trial (RCT) was conducted at 4 public health facilities in Maputo Province, Mozambique during the malaria seasons of 2003 - 2004 and 2004 - 2005. Eligible patients were aged over 1 year with body weight over 10kg and uncomplicated Plasmodium falciparum malaria (parasitaemia less than 500 000 asexual parasites/ml blood with axillary temperature less than or equal to 37.5oC or a history of fever). Patients were excluded if they took other anti- malarials or folate within 7 days, had moderately severe/severe malaria, history of G6PD deficiency or allergy to study drugs, or serious underlying disease. Patients were randomly assigned to sulfadoxine-pyrimethamine (SP): a single oral 25/1.25mg per kg dose on Day 0, with a maximum of 3 tablets), or artesunate (AS) plus SP: SP as above, plus single oral doses of 4mg/kg AS on Days 0, 1 and 2 with a maximum daily dose of 4 tablets). The study aimed to compare the efficacy of SP monotherapy to SP in combination with AS as first line treatment of uncomplicated falciparum malaria. The primary objective was the comparison of the time to treatment failure (the relative hazard of treatment failure) between groups using standard WHO response to treatment definitions for low to moderate malaria transmission areas, modified to a 42 day follow up. Randomisation was computer-generated with sequential allocation concealed in opaque sealed envelopes. Treatments were open-label, however laboratory staff responsible for parasite density measurements (in order to determine the primary efficacy end point) were blinded to treatment allocation.
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Zongo, Issaka. « Efficacy, safety, tolerability of Dihydroartemisinine-Piperaquine and Sulfadoxine-Pyrimethamine plus Amodiaquine for Seasonal Malaria Chemoprevention (SMC) in children in Burkina Faso ». Thesis, London School of Hygiene and Tropical Medicine (University of London), 2014. http://researchonline.lshtm.ac.uk/2026584/.
Texte intégralRésumé :
Children in areas of highly seasonal malaria transmission in the Sahel should receive SMC with sulfadoxine-pyrimethamine plus amodiaquine (SPAQ). These drugs retain their efficacy in the areas where SMC is recommended, but alternative regimens are needed if SMC is used in other areas or if these drugs start to lose efficacy. The aim of this study was to investigate the suitability of dihydroartemisin-piperaquine (DHAPQ) for SMC, using a non-inferiority trial design. 1500 children randomized to receive SPAQ or DHAPQ monthly from August to October, and a cohort of untreated children outside the trial, were followed-up for malaria. SPAQ was more efficacious than DHAPQ, but the difference was within the margin set for non-inferiority. Both regimens gave a very high level of protection lasting 4 weeks. Protection was related to dosage. Both regimens were well tolerated, incidence of mild adverse events decreased in successive months, consistent with toleration to study drugs. In malaria cases, the frequency of the CVIET haplotype of pfcrt, the 86Y polymorphism of pfmdr1, and pfdhfr59 and dhps437 mutations, was greater among children who received SPAQ than in untreated children. However the number of cases, and the prevalence of parasitaemia, was much lower in treated children, reducing the scope for SMC to select for resistance. The frequency of the CVIET haplotype of PfCRT, thought to be associated with resistance to PQ, was not increased in children treated with DHAPQ. There was an enormous burden of malaria in the untreated children. SMC with SPAQ should be introduced for children in Burkina Faso without delay. DHAPQ is a potential alternative regimen in areas where SPAQ cannot be used but there are some drawbacks associated with its use. There is a need to develop alternative long-acting drugs with simple regimens that can be used for chemoprevention of malaria.
16
Dzinjalamala, Fraction Kunseu. « The role of the pharmacokinetics, host folate levels and parasite mutations in the in vivo efficacy of pyrimethamine-sulfadoxine against Plasmodium falciparum ». Doctoral thesis, University of Cape Town, 2003. http://hdl.handle.net/11427/3279.
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Knobloch, Andreas. « Therapie der unkomplizierten Malaria tropica mit Chloroquin und Sulfadoxin-Pyrimethamin bei Kindern in Tamale, Ghana ». Doctoral thesis, [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=976577437.
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Mulenga, Modest. « A randomised controlled trial of atovaquone/proguanil versus sulfadoxine/pyrimethamine, with or without folic acid supplementation in the treatment of severe malarial anaemia ». Thesis, London School of Hygiene and Tropical Medicine (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406034.
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Wessels, Johanna Christina. « International pharmacopoeia monographs : antimalarial dosage forms / J.C. Wessels ». Thesis, North-West University, 2010. http://hdl.handle.net/10394/4920.
Texte intégralRésumé :
Malaria is a disease affecting millions of people in 109 malarious countries and
territories, causing approximately one million deaths annually. In 2004 one of the
parasites causing human malaria, Plasmodium falciparum, was among the leading
global causes of death from a single infectious agent, especially in Africa (WHO,
2008:23).
Treatment of this disease with single active pharmaceutical ingredients has led to the
emergence of resistant P. falciparum parasites, resulting in the most severe form of
this illness. Alarmingly, the poor quality of commercially available antimalarial
products, especially in Africa, has increasingly been reported as a major cause of
resistance to antimalarials. In Pakistan it was found that a P. falciparum epidemic
that initially was attributed to drug resistance, was actually caused by substandard
sulfadoxine/pyrimethamine products, causing a 50 times higher incidence of malaria
in these areas than elsewhere (Leslie et al., 2009:1758). Other results indicated that
up to 10% of sulfadoxine/pyrimethamine tablets, sampled in six African countries,
failed the assay test, whilst up to 40% failed the USP dissolution test. Furthermore,
the World Health Organization (WHO) reported that 20 - 90% of products failed
quality requirements during 1999 and 2000 in seven African countries (WHO,
2003:263).
Cases like these have raised the awareness of the vast number of inferior products
that are being distributed. The subsequent need for establishing mechanisms to proactively
detect substandard medicines, specifically antimalarials, easily and
effectively had indirectly led to the origin of this study, long before it was formally
undertaken.
Testing monographs for pharmaceutical products are developed to formalise, or
standardise, the regulation of pharmaceutical dosage forms. Problems have,
however, been reported with regards to the inadequacy of existing antimalarial
monographs in assuring quality medicines, fit for their intended use. The WHO had requested the Research Institute for Industrial Pharmacy,
incorporating the Centre for Quality Assurance of Medicines (RIIP®/CENQAM®), both
operating at the Potchefstroom Campus of the North–West University, to develop
monographs for three immediate–release antimalaria dosage forms, namely
amodiaquine tablets, sulfadoxine/pyrimethamine fixed–dose combination tablets and
mefloquine tablets. The undertaking of these projects, to develop specifications for
the quality control of these pharmaceutical products, formed the object of this
research study.
Data had been accumulated since 2000, as a result of continuous requests by the
WHO to help solve problems that had been experienced with analytical test
methods, especially from manufacturers. These requests either led to the refinement
of existing methods, or to the development of new ones. The success with
which these outcomes were implemented worldwide, finally led to the decision to
publish these research findings under the umbrella of this project.
The proud product is a comprehensive package of tests for three commercial
antimalarial products, the outcomes of which are hoped to contribute towards the
combat against resistance formation to these important disease fighters.Thesis (Ph.D. (Pharmaceutics))--North-West University, Potchefstroom Campus, 2011.
20
Briand, Valérie. « Traitement préventif intermittent (TPI) pour la lutte contre le paludisme au cours de la grossesse : effet sur la santé de la mère et de l’enfant au Bénin : essai randomisé, ouvert, comparant sulfadoxine-pyriméthamine versus méfloquine en traitement intermittent ». Paris 6, 2008. http://www.theses.fr/2008PA066412.
Texte intégralRésumé :
En Afrique sub-saharienne, le paludisme gestationnel est une cause majeure de faible poids de naissance et d’anémie maternelle. Sa prévention repose sur le traitement préventif intermittent (TPI) par la sulfadoxine-pyriméthamine (SP), pour laquelle les résistances se développent de façon importante. Au Bénin, nous avons conduit le premier essai clinique évaluant la méfloquine (MQ), versus SP, pour le TPI. Cet essai a montré que les deux traitements étaient équivalents pour prévenir les faibles poids de naissance et que la MQ avait une activité antiparasitaire plus importante. En revanche, sa tolérance a été moins bonne. S’il n’y a pas de raison impérative de modifier les recommandations actuelles pour le TPI, il est probable que cela s’avère nécessaire dans les années à venir. Notre essai a confirmé que la MQ était une option intéressante pour le TPI. Toutefois, en raison de sa tolérance moyenne il nous paraît prématuré de la recommander dans l’immédiat, sans plus d’études complémentaires.
21
Lazaro, José Enrico. « Études pharmacologiques d'Heptyle prodigiosine et de Crambescidine, produits naturels antipaludiques d'origine marine : activités in vitro, in vivo et mutagénique ». Paris 6, 2002. http://www.theses.fr/2002PA066428.
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Savage, Emma Jane. « An evaluation of village based delivery of sulfadoxine-pyrimethamine for malaria control in pregnancy and the use of material anaemia and birthweight as indicators of malaria burden in pregnancy ». Thesis, University of Liverpool, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.406720.
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Dicko, Alassane. « Le Traitement Intermittent Préventif comme stratégie de lutte contre le paludisme chez les enfants ». Thesis, Bordeaux 2, 2010. http://www.theses.fr/2010BOR21767/document.
Texte intégralRésumé :
Le paludisme est l’une des maladies infectieuses la plus fréquente au monde avec 40% de la population mondiale exposée. En dépit des stratégies actuelles de lutte notamment la prise en charge rapide des cas, l’utilisation de matériaux imprégnés et la pulvérisation intra domiciliaire d’insecticide, le paludisme reste une des premières causes de morbidité et de mortalité notamment en Afrique subsaharienne. Cette partie du monde totalise à elle seule plus de 90% des cas de décès par paludisme dont 88% chez les enfants de moins de moins de 5 ans. En absence de vaccin utilisable en santé publique, il y a donc un besoin urgent de trouver une stratégie efficiente et simple de contrôle du paludisme. Le traitement préventif intermittent (TPI) définie comme l’administration d’un antipaludique à dose curative à des intervalles de temps prédéfinis réduit l’incidence du paludisme et apparaît aujourd’hui comme une des stratégies les plus prometteuses. Cette stratégie couplée au Programme Elargi de Vaccination (PEV) chez les enfants de moins de 1 an réduit l’incidence du paludisme de 30%. Des résultats plus importants sont obtenus chez les enfants de 0 à 5 ans voire de 0 à 10 ans lorsque la stratégie est appliquée en ciblant la saison de transmission. Nos travaux de recherche au Mali ont porté sur :- l’impact de la mise en œuvre du TPI couplé à la vaccination du PEV (TPin) sur i) la résistance P. falciparum à la Sulfadoxine pyrimethamine (SP), ii) la couverture des vaccins du PEV, iii) le taux de mortalité des enfants âgés de 4 à 18 mois.- l’efficacité du TPI chez les enfants ciblant la saison de transmission (TPIe) dans un contexte de faible et de forte couverture en des Moustiquaires Imprégnés d’Insecticides (MII). Nos résultats ont montré qu’après une année de mise en œuvre à l’échelle du district sanitaire, le TPIn a entrainé une augmentation de la couverture des vaccins du PEV. Cette couverture était de 53% en zone de non-intervention contre 69.5% en zone d’intervention (p<0.01). Il y a eu une réduction de la mortalité globale de 27% (RR= 0,73, IC95% : 0,55-0,97, p=0,029) chez les enfants âgés de 4 à 18 mois. Les fréquences des marqueurs moléculaires de la résistance de P. falciparum à SP en début et en fin la mise en œuvre et entre la zone d’intervention et la zone de non –intervention après une année de mise en œuvre étaient similaires. Deux doses de SP données en TPI à 8 semaines d’ intervalle durant la saison de transmission réduit le taux d’incidence du paludisme pendant la saison de transmission de 69,4% chez les enfants de moins de 5 ans et de 63,4% chez les enfants de 5-10 ans dans un contexte de très faible utilisation de MII (<5%). Dans une autre étude que nous avons menée, le TPI avec SP + Amodiaquine (AQ) donné en 3 occasions à un mois d’ intervalle pendant la saison de transmission a réduit le taux d’ incidence du paludisme clinique non compliqué de 82% (IC à 95%: 78%– 85%; P<0.001) et les formes graves de paludisme de 87% (IC à 95% 42% – 99%, P=0.001) chez les enfants âgés de 3 à 59 mois en dépit un taux d’utilisation des MII de plus de 99%. Nous n’avons pas documenté d’événement indésirable grave lié à l’utilisation de la SP ou de la SP + AQ en TPI durant ces deux études. Nos résultats étayent la recommandation du TPI, ciblant la saison de transmission ou couplée au PEV, pour la lutte antipaludique chez les enfantsMalaria is one of the most common infectious diseases in the world and 40% of the world population is exposed to malaria. Despite the current control strategies such as rapid diagnosis and treatment of disease cases, use of insecticide impregnated materials and indoor residuals spraying with insecticides, malaria remained a main cause of morbidity and mortality particularly in sub Saharan Africa. More than 90% of the deaths due to malaria occurred in this region and 88% of these deaths occurred in children aged less than 5 years of age. In absence of vaccine that can be used in public health, there is an urgent need for a simple and efficient control strategy. Malaria intermittent preventive treatment (IPT) defined as the administration of curative dose of anti-malarial drug at predefined time intervals, appears as one of the most promising strategies. Given through the Expanded Program of Immunization (EPI), the strategy reduced the incidence of malaria by 30%. More drastic reductions were obtained in children aged 0-5 years and even 0-10 years when the malaria transmission season was targeted for the administration of the strategy. Our research work in Mali has assessed the following:- The impact of implementation of IPT administrated through EPI (IPTi) on: i) the resistance of P. falciparum to Sulfadoxine pyrimethamine (SP); ii) EPI vaccine coverage, and iii) mortality of children of 4-18 months of age. - The efficacy of IPT in children targeting the malaria transmission season (IPTe) in a context of low and high coverage of insecticide impregnated nets (ITN).We have found that the implementation of IPTi at the district level has resulted in an augmentation of the EPI vaccine coverage. The EPI vaccine coverage was 53% in the non-intervention zone compared to 69.5% in the intervention zone (p<0,01). There was a reduction in all cause mortality of 27% (RR= 0.73, 95% CI : 0.55-0.97, p=0.029) in children aged 4-18 months. The frequencies of molecular markers of the resistance of P. falciparum to SP were similar at the beginning and the end of the one year implementation period and between the intervention and non-intervention zones.Two doses of SP given at 8 weeks interval during the transmission season, reduced the incidence of malaria episodes during the transmission season by 69.4% in children aged less than 5 years and by 63.4% in children aged 5-10 years in a context of very low ITN use (<5%). In another study that we have conducted, IPT with SP + Amodiaquine (AQ) given at three occasions at one month interval during the transmission season reduced the incidence rate of clinical malaria by 82% (95% CI: 78%– 85%; P<0.001), and the incidence of severe and complicated malaria by 87% (95% IC 42% – 99%, P=0.001) in children aged 3 to 59 months of age despite an ITN use of greater than 99%.There was no serious adverse event related to the use of SP or SP+AQ in IPT during the two studies. Our results support the recommendation of IPT targeting the transmission season and IPT given through the EPI for malaria control in children
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Maïga, Diakité Oumou Soumana. « Efficacité de deux schémas de traitement préventif intermittent du paludisme à la sulfudoxine-pyriméthamine chez la femme enceinte au Mali ». Paris 6, 2009. http://www.theses.fr/2009PA066283.
Texte intégralRésumé :
Introduction : Actuellement dans la région africaine, l’OMS recommande l'administration d'un Traitement Préventif Intermittent (TPI) au cours de la grossesse. Il existe des données, sur l'efficacité du TPI deux doses de SP pendant la grossesse. Cependant, iI n'existe pratiquement pas d'informations à notre connaissance en Afrique de l’Ouest sur l'efficacité du TPI à trois doses pendant la grossesse versus deux doses. Objectif : L’objectif de ce travail était d’évaluer l’efficacité de la sulfadoxine- pyriméthamine (SP) en 3 doses versus 2 doses dans le traitement préventif intermittent du paludisme chez la femme enceinte dans le cercle de Bla, au Mali. Avant la mise en place de cet essai clinique, nous avons évalué l’impact de la chimio-prévention SP/TPI et de l’utilisation des moustiquaires imprégnées d’insecticides dans les cercles de Bla (zone d’intervention) et de Baraouéli (zone témoin), région de Ségou sur les indicateurs du paludisme pendant la grossesse. Méthodes et patients : L’évaluation de l’impact de la chimio prévention sur les indicateurs du paludisme pendant la grossesse a été conduite sous forme d’une étude transversale qui s’est déroulée de mars à juin 2004 chez les femmes ayant accouchées dans les centres de santé des deux districts. Notre deuxième étude a été conduite sous forme d’essai clinique randomisé ouvert à deux bras de traitement TPI/SP deux doses versus trois doses chez les femmes enceintes d’avril 2006 à mars-juin 2008 dans le cercle de Bla au Mali. Résultats : Les résultats de l’évaluation de l’impact de la chimio prévention ont monté une prévalence plus faible de l’infection placentaire dans la zone d’intervention par rapport au site témoin (8,2% à Bla contre 17,7% à Baraouéli ; p<0,001). Le taux de faibles poids de naissance était relativement plus élevé dans le site de Baraouéli (13,63% vs. 12,10%) sans différence statistiquement significative (p= 0,37). Pour l’étude SP/TPI 2 versus 3 doses, à l’accouchement, les résultats de l’essai ont montré que les femmes qui ont reçu trois doses avaient des taux d’infection palustres périphériques et placentaires plus faibles par rapport à celles qui ont reçu deux doses (p<0,001). La fréquence de faibles poids de naissance et de la prématurité étaient significativement plus faibles chez les nouveau-nés de mères ayant reçu trois doses (p <0,001) comparativement au bras de traitement deux doses. En revanche, nous n’avons pas observé de différence statistiquement significative entre les deux bras de traitement en terme de prévalence de l’anémie, d’effets secondaires et de décès néonataux (p>0,05). L’analyse moléculaire des marqueurs de résistance à la SP a montré qu’il n’y avait pas de différence statistiquement significative entre les deux bras en termes de sélection de mutants résistants (p > 0,05). Conclusion : Le ‘‘paquet’’d’intervention utilisé dans le cercle de Bla pour la prévention du paludisme pendant la grossesse était efficace contre l’infection placentaire et améliorait le poids des nouveaux nés à la naissance. L’utilisation du TPI/SP trois doses est plus efficace en termes de réduction de la prévalence de la parasitémie périphérique et placentaire, de la fréquence des faibles poids de naissance, de la prématurité. Cette stratégie n’occasionnerait pas plus d’effets secondaires ni plus de sélection de mutants résistants à la SP.
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Kimbeni, Malongo Trésor. « Développement d'électrodes sélectives pour l'analyse de composés d'intérêt pharmaceutique : antipaludéens et halogénures ». Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210504.
Texte intégralRésumé :
RESUMELe travail de thèse porte sur le développement d’électrodes sélectives originales et performantes pour l’analyse de composés d’intérêt pharmaceutique.
La partie introductive traite des notions relatives à l’électrochimie mais également de notions sur les molécules médicamenteuses étudiées, en l’occurrence les principes antipaludéens et l’iode.
La partie expérimentale se subdivise en deux parties distinctes selon le type d’électrodes sélectives auxquelles font appel les techniques électrochimiques.
La première partie concerne l’élaboration, la caractérisation et l’application des électrodes potentiométriques à membrane polymérique incluant une paire d’ions et sélectives à diverses molécules organiques pharmacologiquement actives (antipaludéens). Leur application aussi bien en analyse pharmaceutique qu’en cinétique de dissolution est décrite.
La deuxième partie est consacrée à l’élaboration d’un type de senseur ampérométrique original à pâte de carbone à base d’argent micronisé ou colloïdal et à la comparaison de ses performances avec l’électrode d’argent métallique. L’intérêt analytique est mis en évidence par la détermination quantitative des iodures.
Les différents aspects susceptibles d’influencer leur comportement, dont la nature des agents précipitants (tétraphénylborate de sodium et le tétrakis (4-chlorophényl) borate de potassium) et de plastifiants ont été investigués.
Les bonnes performances des ces électrodes en analyse quantitative ont permis d’explorer les possibilités de leur utilisation à l’étude de la cinétique de dissolution.
L’ampérométrie à électrode à pâte de carbone modifiée à base d’argent à l’échelle micronisée (35% m/m) couplée à la chromatographie liquide ionique s’est avérée très sensible vis-à-vis des iodures en particulier et des halogénures en général. Les facteurs susceptibles d’influencer les grandeurs de séparation et la réponse de l’électrode ont été investigués et l’exploitation du signal ampérométrique permet le dosage sélectif et rapide de faibles concentrations en iodures. Les informations fournies par les mesures réalisées en voltampérométrie cyclique à l’aide des mêmes électrodes permettent une bonne compréhension mécanistique quant au mode de détection ampérométrique évitant ainsi toute confusion à ce sujet et permettant l’optimisation du processus de détection.
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ABSTRACT
This thesis describes the development of original and high performance selective electrodes for the analysis of several pharmaceutical compounds.
The introduction describes the pharmaceutical compounds of interest (antimalarial drugs and iodine) and provides an overall understanding of the electrochemical groundwork pertaining to their analysis.
The experimental aspect of the thesis is divided into two parts, each according to the type of electrode and electrochemical technique used for the analysis.
The first part describes the design, characterization, and application of polymer membrane based ion selective potentiometric electrodes. Selectivity was provided by including ion pairs of several antimalarial drugs into the membrane. The feasibility of use of these electrodes in pharmaceutical analysis as well as in dissolution trials is also described in this part.
The second part describes the design of an original silver-modified carbon paste amperometric sensor and compares its performances to those of a plain metallic silver electrode. The electrode has been modified by silver microparticles or by silver nanoparticles. Quantitative iodine determination serves to prove the usefulness of this new sensor in analytical chemistry.
Different aspects, such as the nature of the counter ions (sodium tetraphenylborate and potassium tetrakis (4-chlorophenyl) borate) and the plastifying agents that are likely to influence electrode behaviour have been investigated.
Since the electrodes have been shown to perform well in quantitative analysis, the possibility of use in dissolution trials was explored.
Micronized silver-modified carbon paste electrode (35% Ag m/m) coupled to anionic-exchange liquid chromatography with amperometric detection was shown to be very sensitive with regards to the assay of halogenides in general and iodide in particular. After having investigated the various factors likely to influence chromatographic separation and electrode response, it was shown that the sensor could be used to rapidly and selectively determine low iodide concentrations in complex samples. Cyclic voltammetric analysis provided information concerning the mechanisms allowing amperometric detection, thus allowing an optimisation of the detection procedures.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Nsimba, Basile. « Epidémiologie du paludisme chimiorésistant en milieu urbain au Congo : Part 1 : Efficacité de la sulfadoxine-pyréthamine versus chloroquine dans le traitement du paludisme à Plasmodium falciparum non compliqué. Part 2 : Etude de la distribution des marqueurs moléculaires de la chimiorésistance combinée avec l'évaluation de la pression médicamenteuse ». Aix-Marseille 2, 2005. http://www.theses.fr/2005AIX20679.
Texte intégralRésumé :
Au Congo, des efforts urgents sont nécessaires pour aider ce pays à changer sa politique nationale de traitement contre le paludisme. Malgré son taux d'échecs thérapeutiques élevé et inacceptable, la chloroquine (CQ) est encore largement utilisée comme traitement de première intention du paludisme à Plasmodium falciparum non compliqué. Notre étude a été menée dans le cadre du programme national de lutte contre le paludisme, en deux phases entre 1999 et 2002, chez des enfants de 6-59 mois atteints d'accès palustre simple dans les deux plus grandes régions urbaines, Pointe-Noire et Brazzaville, qui à elles seules regroupent environ 60% de la population du Congo. En utilisant le test standard d'efficacité thérapeutique de l'OMS avec une période de suivi des patients de 14 jours, nous avons comparé dans la première phase de l'étude l'efficacité de la CQ versus sulfadoxine/pyriméthamine (SP) par la méthode LQAS de l'OMS; la deuxième phase consistait à déterminer le niveau réel de résistance de P. Falciparum à SP. Cette étude combinait également l'évaluation de l'utilisation des antipaludiques dans la communauté et de la fréquence de distribution des marqueurs moléculaires de résistance à la CQ (mutation pfcrt-K76T) et à la SP (mutations des gènes dhfr/dhps) dans les isolats de P. Falciparum par les méthodes de PCR et séquençage. Les résultats ont montré un taux d'échecs thérapeutiques significativement > 25% à la CQ tandis qu'aucun échec clinique ou parasitologique n'a été enregistré pour la SP. On a noté la présence de la mutation pfcrt-K76T dans la quasitotalité des isolats de P. Falciparum (96. 4%, n = 138) indiquant un niveau élevé de résistance à la CQ. Le quintuple mutant (dhfr-S108N, N51I, C59R et dhps-A437G ou S436A, K540E) responsable de la résistance clinique à SP n'a pas été trouvé en raison de l'absence de la mutation dhps-K540E dans les isolats testés (n = 144), d'où l'évidence de l'excellente efficacité de SP. En conclusion, la stratégie qui consiste à combiner la SP avec un autre antipaludique efficace, bien toléré et moins cher est essentielle au Congo. Les combinaisons thérapeutiques à base des dérivés d'artémisinine (ACTs) recommandées par l'OMS depuis 2001 sont efficaces mais elles ne sont pas pour l'heure des options alternatives idéales et recommandables au niveau programmatique à cause de leur coût trop élevé. La mutation dhps-K540E pourrait être utilisée comme outil d'alerte précoce de l'émergence de la résistance à SP dans cette population. La mauvaise utilisation des antipaludiques observée dans cette communauté urbaine devrait être prise en compte dans le processus du changement de politique du traitement du paludismeIn Congo, urgent efforts are needed to help with the revision of the national antimalarial drug policy. Despite its high and unacceptable treatment failure rate, chloroquine (CQ) is still extensively used as first-line treatment for uncomplicated Plasmodium falciparum malaria. Our study was conducted within the context of national malaria control programme, in two phases between 1999 and 2002, in children aged 6-59 months with uncomplicated malaria in Pointe-Noire and Brazzaville, the two largest cities that contain approximately 60% of the population of Congo. Using the standard 14-day WHO therapeutic efficacy test, we compared in the first phase of the study the efficacy of CQ versus sulfadoxine/pyrimethamine (SP) performing the WHO LQAS method; basing on our study design we determined the actual proportion of treatment failures of SP in the second phase. This study also combined assessing antimalarial drug use in the community and the frequency distribution of resistance molecular markers to CQ (pfcrt-K76T mutation) and to SP (mutations in dhfr/dhps genes) among pretreatment P. Falciparum isolates by PCR and sequencing methods. Results demonstrated a treatment failure rate significantly >25% for CQ, while no clinical or parasitologic failure was observed for SP. Regarding genotyping results, Pfcrt (K76T) mutation was present in almost all isolates (96. 4%, n =138) indicating that resistance to CQ is present at a high frequency. The quintuple mutant (dhfr-S108N, N51I, C59R and dhps-A437G or S436A, K540E) considered as molecular marker for clinical SP-resistance was not found because dhps-K540E mutation was absent in all isolates tested (n = 144); this is clear evidence for the excellent efficacy of SP. In conclusion, the strategy of combining SP with other affordable, effective and cheap antimalarial-drugs is essential in Congo. Artemisinin-based combination therapies (ACTs) recommended by WHO since 2001 are the best alternative regimens for malaria treatment but inaccessible to the needy because of their high-cost. The complete absence of the dhps-K540E mutation is a deterrent component for using this molecular marker as an early warning tool for SP resistance testing in that population. Poor compliance issues related to the antimalarial drug use including inappropriate manufacturing practices observed in this urban community require intensive attention and should be taken into account in the process of changing antimalarial treatment policy
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Malm, Mikaela. « Drug Analysis : Bioanalytical Method Development and Validation ». Doctoral thesis, Uppsala universitet, Analytisk kemi, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8547.
Texte intégralRésumé :
This thesis describes bioanalytical methods for drug determination in biological matrixes, with drugs in focus used against diseases largely affecting low-income countries. Solid-phase extraction is used for sample cleanup, and processed samples are analyzed by liquid chromatography. Developed bioanalytical methods are validated according to international guidelines. Eflornithine (DFMO) is a chiral drug, used for treating human African trypanosomiasis. A bioanalytical method for determination of DFMO enantiomers in plasma is presented. The enantiomers are detected by evaporative light-scattering detection. The method has been applied to determination of D-DFMO and L-DFMO in rats, after intravenous and oral administration of racemic DFMO. It is concluded that DFMO exhibits enantioselective absorption, with the more potent enantiomer L-DFMO being less favored. Sulfadoxine (SD) and sulfamethoxazole (SM) are sulfa-drugs used for malaria and pneumonia respectively. Two methods are described for simultaneous determination of SD and SM in capillary blood sampled on filter paper. The former method allows direct injection of extracts from dried blood spots (DBS), while for the latter method solid-phase extraction is added. Pre-analytical factors contributing to measurement uncertainty is also discussed, and it is concluded that it is of high importance that homogeneity in type of sampling paper and sampling volume is assured. Piperaquine (PQ) is an antimalarial, increasingly used in artemisinin combination therapy. A method for determination of piperaquine in DBS is presented. By using a monolithic LC column, a very short LC analysis of two minutes per sample is achieved. A method for simultaneous determination of three antiretroviral drugs i.e. lamivudine (3TC), zidovudine (AZT) and nevirapine (NVP), in DBS samples is described. The method is applied to drug determination in two subjects after receiving standard antiretroviral treatment. Conclusion is that the method is suitable for determination of 3TC and NVP, and to some extent for AZT.
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Mariam, Nakintu. « Detection of mutations in dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) in Plasmodium falciparum in eastern Sudan ». Thesis, Uppsala universitet, Institutionen för medicinsk biokemi och mikrobiologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-155295.
Texte intégral
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Hogan, Benedikt [Verfasser], et Jürgen [Akademischer Betreuer] May. « Folgeuntersuchung von Kindern nach einer intermittierenden präventiven Behandlung der Malaria mit Sulfadoxin-Pyrimethamin / Benedikt Hogan. Betreuer : Jürgen May ». Hamburg : Staats- und Universitätsbibliothek Hamburg, 2012. http://d-nb.info/1025150635/34.
Texte intégral
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ISIDORO, Gisela Aleixo. « Marcadores moleculares de resistência de Plasmodium falciparum `Sulfadoxina-Pirimetamina após a mudança de políticas de tratamento da malária em Angola ». Master's thesis, Instituto de Higiene e Medicina Tropical, 2018. http://hdl.handle.net/10362/53501.
Texte intégralRésumé :
A malária causada por Plasmodium falciparum é, entre as doenças infeciosas e parasitárias, uma das maiores causas de mortalidade mundial. O diagnóstico atempado e correto são elementos chave para um programa de controlo da malária bem-sucedido. No entanto, controlo e tratamento têm sido bastante dificultados pelo aparecimento e disseminação da resistência dos parasitas aos antimaláricos mais utilizados nas últimas décadas, nomeadamente a cloroquina. Este facto conduziu à introdução de outros antimaláricos (ex. pirimetamina e sulfadoxina), assim como a modificação de esquemas terapêuticos e a inclusão de novas associações. Nas áreas endémicas de África, das 5 espécies de Plasmodium que infetam o homem, Plasmodium falciparum, é o que representa maior prevalência e virulência, uma vez que desenvolveu resistência a maioria dos antimaláricos atualmente em uso. De todos os grupos de risco, na mulher grávida a malária é considerada um grave problema de saúde pública pelas consequências que podem ocorrer tanto na mãe como no feto. O tratamento intermitente preventivo (TIP) com sulfadoxina e pirimetamina (SP) para grávidas foi uma das estratégias adotadas pela Organização Mundial de Saúde neste grupo de risco. A resistência aos fármacos utilizados tem colocado em causa esta intervenção e pode ter impato na sua eficácia e custo-benefício, pelo que é fundamental a caracterização dos marcadores moleculares que estão na sua origem. A resistência à SP utilizada no TIP na grávida tem vindo a aumentar e surge com a presença de mutações pontuais nas regiões codificantes de 2 genes, o dihidrofolato redutase (dhfr) e o dihidropteroato sintase (dhps), assim, é importante perceber qual o papel que o sequestro na placenta poderá desempenhar no aparecimento/manutenção da resistência a estes fármacos. Este estudo envolveu mulheres grávidas em trabalho de parto nas Maternidades Lucrécia Paím e Hospital Geral Especializado Augusto Ngangula, de Abril de 2006 a Fevereiro de 2008, com o objetivo de caracterizar a malária placentária por P. falciparum em Luanda, Angola. Nas amostras positivas por PCR foi efetuada a caracterização da prevalência de marcadores de resistência através da técnica de sequenciação genética pelo método de Sanger, para detetar as mutações A16V, N51I, C59R, S108N e I164L no pfdhfr e S436A, A437G, K540E, A581G e A613S/T no pfdhps. Das 81 mulheres com amostras de sangue de 3 compartimentos (cordão umbilical, sangue periférico, e placenta), observou-se uma prevalência dos SNPs no gene pfdhfr 108N de 96%, 51I de 89,2% e 59R de 40,5%, no gene pfdhps 437G de 98,2%, 540E de 19,3%. Dos haplótipos 51I/59R/108N de 29,7%, do 437G/540E 19,3% e 20% de prevalência do quíntuplo mutante pfdhfr/pfdhps 51I/59R/108N/437G/540E. Estes resultados sugerem que o uso de SP para o TIP em Angola é viável.Malaria caused by Plasmodium falciparum is one of the major causes of worldwide mortality among infectious and parasitic diseases. Early and correct diagnosis, are the key element for a successful malaria control program. However, the control and treatment have been greatly hampered by the appearance and dissemination of parasite resistance to the most commonly used antimalarials in recent decades, namely chloroquine. This fact led to the introduction of other antimalarials (eg. pyrimethamine and sulfadoxine), as well as to a modification of therapeutic schemes and the inclusion of new associations. In endemic areas of Africa, among the 5 Plasmodium species that infect humans, P. falciparum, is the one that represents greater prevalence and virulence, since it developed resistance to most of the antimalarials currently in use. Malaria in pregnant woman, is considered a serious public health problem because of the consequences on both the mother and the fetus. Intermittent preventive treatment with sulphadoxine and pyrimethamine (SP) was one of the strategies adopted by the World Health Organization to control the disease in this risk group. The resistance to the currently available drugs has been challenging this intervention and may impact on its efficacy and cost-effectiveness, so it is fundamental to characterize the molecular markers that are at its origin. The resistance to SP used in TIP in the pregnant women has been increasing and arises with the presence of point mutations in the coding regions of 2 genes, dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps), so, it is important to understand which is the role that sequestration in the placenta may play in the onset / maintenance of resistance to these drugs. This study involved pregnant women in labor at the Lucrécia Paím Maternities and Augusto Ngangula General Specialized Hospital, from April 2006 to February 2008, with the objective of characterizing placental malaria by P. falciparum in Luanda, Angola. In the PCR-positive samples, the prevalence of resistance markers was determined using the Sanger method to detect the mutations A16V, N51I, C59R, S108N and I164L in pfdhfr and S436A, A437G, K540E, A581G and A613S/T in pfdhps. Of the 81 women with 3 compartment (blood samples, umbilical cord, peripheral blood, and placenta), a prevalence of SNPs in the pfdhfr gene 108N with 96%, 51I with 89,2% and 59R 40,5%. In the pfdhps gene 437G with 98,2%, 540E with 19,3%. Of the haplotypes 51I / 59R/108N with 29,7%, of the 437G/540E with 19,3% and 20% of the quintuple mutant prevalence of pfdhfr/pfdhps 51I/59R/108N/437G/540E. These results suggest that the use of SP for TIP in Angola needs to be reviewed.
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Salas, Hermoza Carola Janette. « Marcadores moleculares asociados a Plasmodium falciparum resistente a sulfadoxina-pirimetamina en las localidades de Caballococha y Padre Cocha, región Loreto, Perú ». Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2007. https://hdl.handle.net/20.500.12672/2483.
Texte intégralRésumé :
El objetivo de esta investigación retrospectiva, fue determinar la asociación existente entre mutaciones puntuales en los genes dihidrofolato reductasa (Pfdhfr) y dihidropteroato sintasa (Pfdhps) de Plasmodium falciparum y la respuesta clínica en pacientes con diagnóstico de malaria no complicada causada por P. falciparum, admitidos en un estudio de eficacia in vivo de sulfadoxina-pirimetamina (SP) llevado a cabo en dos áreas de la región Loreto en 1999. Se tomaron muestras de sangre de 86 pacientes antes de administrarles SP, las que se analizaron usando PCR-anclado específico de alelo para estudiar a los codones S108N/T, N51I, C59R, I164L y C50R del gen Pfdhf y los codones A436G, A437G, K540E, A581G y A613S/T del gen Pfdhps, encontrándose que las infecciones causadas por parásitos con 3 mutaciones en Pfdhfr (108Asn/51Ile/164Leu) y 2 (581Gli/437Gli) ó 3 mutaciones en Pfdhps (581Gli/437Gli/540Glu) denominados el quíntuple mutante y el séxtuple mutante, respectivamente, se encontraban asociadas con la falla del tratamiento con SP. Además, se estableció que cuanto más alto era el número de mutaciones tanto en Pfdhfr como en Pfdhps, más alto era el riesgo de fallar al tratamiento con SP, según resultado del análisis de regresión logística empleado para asociar a estas dos variables. Este estudio contribuye en brindar evidencias científicas de la asociación existente entre las variables en la región Loreto contribuyendo a su validación y su futuro uso para estudios de vigilancia de fármaco resistencia a SP no solo en el Perú sino en general para los países de América del Sur que comparten territorio de la selva Amazónica.-- The objective of this retrospective study was to determine the asociation between point mutations in dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) Plasmodium falciparum genes, and clinical outcome of patients with non complicated P.falciparum malaria diagnosis, admitted to a in vivo sulphadoxine-pirymethamine (SP) drug efficacy study conducted in 1999, in two areas of Loreto region. We used allelic specific-nested PCR to analize 86 blood samples collected before SP treatment, and study mutations at codons S108N/T, N51I, C59R, I164L and C50R in Pfdhfr and codons A436G, A437G, K540E, A581G y A613S/T in Pfdhps genes, and found that Infections caused by parasites harbouring 3 mutations in Pfdhfr (108Asn/51Ile/164Leu) and either 2 or 3 mutations in Pfdhps (581Gly/437Gly and 540Glu) called the quintuple and sextuple mutants, respectively, were associated to failure with SP treatment. Logistic regression analysis was used to look for association between the variables, helping to establish the higher the number of mutations in both Pfdhfr and Pfdhps genes, the higher the risk of treatment failures when using SP.The contribution of this study is to provide scientific evidences of the association between both variables in Loreto region supporting its validation and future application in surveillance studies for SP drug resistance, that can be conducted not only in Peru but also in South American countries that share the Amazon basin territory.
Tesis
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MIGUEL, Elisa. « Estudo da prevalência da malária na mulher grávida submetida ao tratamento intermitente e preventivo com sulfadoxina e pirimetamina e sua associação com anemia ». Master's thesis, Instituto de Higiene e Medicina Tropical, 2011. http://hdl.handle.net/10362/14001.
Texte intégralRésumé :
A malária é causada por parasitas de género Plasmodium e transmitida por mosquitos fêmea do género Anopheles. A doença é endémica em regiões tropicais e intertropicais e constituí uma das maiores causas de morbilidade e mortalidade principalmente no continente Africano. Segundo os dados da OMS ocorrem anualmente 300 a 500 milhões de casos clínicos e um milhão de mortes. Durante a gravidez, a malária é frequente e mais grave, com maior incidência nos países da África subsaariana. As mulheres grávidas têm maior risco de contrair a doença e muitas vezes em formas mais graves com associação à anemia. O objectivo deste estudo foi caracterizar a ocorrência dos casos de malária em mulheres grávidas submetidas ao tratamento intermitente preventivo (TIP) com a Sulfadoxina/ Pirimetamina (SP) nas Províncias de Benguela e Huíla. Neste estudo constatamos que todas as grávidas que participaram tinham tido episódios de malária antes da gravidez quer na província de Benguela tal como na província da Huíla. No total, 633 mulheres grávidas foram analisadas e apresentavam um valor de hemoglobina abaixo dos 14g/dl.
A prevalência de malária em grávidas sujeitas a TIP foi significativamente menor (p< 0.01) do que nas grávidas que não a fizeram, respectivamente 4,5% e 10,0%, conforme esperado e descrito anteriormente por outros autores.
Todos os casos de malária detectados corresponderam a Plasmodium falciparum, não se tendo verificado nenhuma infecção mista, de acordo com os métodos utilizados.
O valor médio da hemoglobina nas grávidas foi inferior ao esperado em grávidas seguidas em consulta pré-natal, e existe uma diferença significativa entre os valores encontrados na Província de Benguela e da Huíla (significativamente mais elevados nesta última).
O teste rápido Paracheck-pf detectou a presença de Plasmodium falciparum em maior número do que a microscopia óptica. Por constrangimentos logísticos, o número de amostras submetidas a teste molecular (PCR) não foi suficiente para se tirarem conclusões.Malaria is a disease transmitted caused by the parasite Plasmodium which is transmitted to the host by the bite of a female Anopheles mosquito. Malaria remains the major cause of morbidity and mortality especially in Africa and it affects mainly children under five and pregnant women. During pregnancy women are more susceptible to malaria and often get the most severe form of malaria which is accompanied by anemia. The aim of this study was to assess the success of the preventive intermittent treatment with Sulphadoxine/Pyrimethamine in pregnant women and also assess the degree of anemia associated with this treatment in the regions of Benguela and Huila situated in the Republic of Angola. The results of this study have shown in a total of 633 women that participated in this study, almost all of them had experienced episodes of malaria before the pregnancy and the levels of hemoglobin at the time this study was carried out was below 14g/dl. Malaria prevalence in pregnant women subjected to TIP was significantly lower than in women not on TIP, respectively 4,5% and 10%. All the detected malaria cases corresponded to P. falciparum. Mixed or other species infections were not detected. The mean hemoglobin value was lower than expected, for consultation-followed women, and these levels were significantly higher in Huila Province, when compared to Benguela. The rapid diagnostic tests detected Plasmodium falciparum in greater number, when compared to microscopy. Due to logistics constraints the number of PCR analyzed samples does not allow us to draw any conclusions.
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RODRIGUES, Ana Júlia Pinto Fonseca Sieuve Afonso. « Studies on the genetics of artemisinin resisteance in malaria ». Doctoral thesis, Instituto de Higiene e Medicina Tropical, 2007. http://hdl.handle.net/10362/59129.
Texte intégralRésumé :
A existência de estirpes do parasita, Plasmodium falciparum resistentes a multiplos fármacos tais como; cloroquina (CQ) e sulfadoxina-pirimetamina (SP) é um dos problemas mais graves no controlo da malária.
Novos fármacos, como a artemisinina (ART) e seus derivados, particularmente em combinação com outros fármacos, são cada vez mais utilizados no tratamento da malaria.
Embora até ao momento a fármaco-resistência estável à ART quer in vitro quer in vivo não tenha sido registada, o seu surgimento seria desastroso devido á falta de alternativas.
O trabalho apresentado nesta tese descreve a selecção de resistência estável a ART e ao artesunato (ATN). Este trabalho foi realizado usando o modelo roedor de malária Plasmodium chabaudi chabaudi (Plasmodium chabaudi).
Duas linhas parasitáricas diferentes, AS-15CQ e AS-30CQ, foram feitas crescer na presença de concentrações crescentes de ATN e ART, e que no final apresentavam uma resistência de 6 e 15 vezes superior ao ATN e à ART, respectivamente (estas novas linhas obtidas foram nomeadas AS-ATN e AS-ART).
A resistência é estável mesmo após clonagem, congelamento/descongelamento, passagem sanguínea na ausência de pressão de fármaco e transmissão através do mosquito vector.
A sequência nucleotídica e o número de cópias dos genes descritos como moduladores putativos de resistência à ART: mdr1, cg10, tctp e atp6; foi comparada entre parasitas resistentes e sensíveis. Não tendo sido encontradas alterações na sequência ou no número de cópias destes genes.
Numa tentativa de identificar os genes encolvidos na resistância à ART e ao ATN a técnica de Linkage Group Selection (LGS) foi utilizada e dois cruzamentos genéticos entre os clones fármaco-resistentes; AS-ART e AS-ATN e o clone geneticamente distinto dos anteriores e sensível aos fármacos em estudos; AJ; foram realizados. Foram encontrados sobre selecção em ambos os cruzamentos genéticos quatro loci; cromossomas de P. chabaudi 1, 2, 6 e 8.
Atendendo a que, a selecção no cromossoma 2 era mais forte, este locus foi submetido a análises genéticas subsequentes. Tendo sido encontradas duas mutações diferentes (V739F e V770F) num gene que codifica para um enzima de desubiquitinação (ubp-1).As implicações destes resultados serão discutidas.Resistance of Plasmodium falciparum to multiple drugs including chloroquine (CQ) and sulfadoxine-pyrimethamine (SP) is a major problem in malaria control. New drugs, such as artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria. Although stable resistance to ART has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. The work presented in this thesis describes the selection of parasites with stable resistance to ART and artesunate (ATN), and their genetic analysis. This work was carried out using the rodent malaria parasite Plasmodium chabaudi chabaudi (Plasmodium chabaudi). Two different rodent malaria parasite lines AS-15CQ and AS-30CQ were continually passaged in the presence of increasing concentrations of ATN or ART, respectively. After selection, these lines, named AS-ATN and AS-ART, showed 6-fold and 15-fold increased resistance to ATN and ART respectively. Resistance remained stable after cloning, freeze/thawing, blood passage in the absence of drug pressure and transmission through mosquitoes. The nucleotide sequences and the gene copy number of the possible genetic modulators of ART resistance mdr1, cg10, tctp and atp6; were compared between sensitive and resistant parasites. No mutations or changes in the gene copy number of these genes were found. Linkage Group Selection (LGS) was used to investigate the genetic basis of ART resistance. Genetic crosses between AS-ART or AS-ATN and the ART-sensitive clone AJ were analysed before and after drug treatment. Using quantitative markers, a genetic locus on chromosome 2 was found to be under strong selection. Loci on chromosomes 1, 8 and 14 of P. chabaudi also appear to be under selection. On chromosome 2, two different mutations V739F and V770F in a de-ubiquitinating enzyme (ubp-1) were identified in AS-ATN and AS-ART respectively, relative to their sensitive progenitors. The implications of these results are discussed.
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Manirakiza, Alexandre. « Utilisation du test de diagnostic rapide(paracheck-pf®) en consultation prénatale dans le cadre du traitement antipaludique à Bangui, République Centrafricaine ». Thesis, Aix-Marseille, 2012. http://www.theses.fr/2012AIXM5040/document.
Texte intégralRésumé :
Entre juin et septembre 2009, nous avons réalisé une étude transversale pour évaluer l'état de la prise en charge du paludisme chez la femme enceinte à Bangui. Les résultats de cette évaluation ont montré que dans les services de consultation prénatale (CPN) de Bangui, 28,8% des femmes enceintes reçoivent à titre curatif au moins une prescription de médicament antipaludique pendant leur grossesse. La quinine et les combinaisons à base d'artémisinine, antipaludiques compatibles avec la grossesse, sont prescrites dans des proportions de 56,7% et 26,8% respectivement. Par contre, la confirmation du paludisme par un examen de laboratoire est réalisée seulement dans 18,9% des cas avant la prescription du traitement. Les deux doses recommandées de traitement préventif intermittent du paludisme par la sulfadoxine-pyrimethamine (TPIsp) sont administrées à 30,5% des femmes pendant leur grossesse. Les moustiquaires imprégnées d'insecticide à longue durée (MIILD) sont utilisées par 42,4% des femmes enceintes. Malgré ce, la prévalence de la parasitémie placentaire à l'accouchement est relativement faible (4%). Ces données nous ont amené à réaliser une étude dont l'objectif était d'évaluer l'intérêt de l'introduction d'un test de diagnostic rapide (TDR) sur la rationalisation du traitement du paludisme chez les femmes enceintes lors des CPN. Entre octobre 2009 et octobre 2011, nous avons réalisé une étude sur une cohorte de 76 femmes enceintes. Le nombre de traitements antipaludiques après confirmation du paludisme par TDR Paracheck-Pf® lors des CPN a été déterminé sur cette cohorteFrom June to September 2009, we designed a cross-sectional study aiming to assess malaria management during pregnancy in antenatal health care in Bangui. Our findings showed that antimalarials are prescribed to 28.8% of pregnant women attending antenatal clinics (ANCs) in Bangui. Quinine and artemisinin combined therapies are widely used (56.7% and 26.8% respectively). However, laboratory diagnosis of malaria infection is performed for solely 18.9% of consultants. The recommended two doses of intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTsp) are given to 30.5% of pregnant women, while 42.4% of them use the insecticides treated nets (ITNs). Nonetheless, the prevalence of placental malaria at delivery is relatively low (4%). From those preliminary data of our study we assessed the impact of a systematic rapid diagnosis test (RDT) of malaria during pregnancy on antimalarials prescription, during the period from October 2009 and October 2011. The proportions of antimalarial treatment episodes were compared in two groups of women: a cohort of 76 pregnant women presenting at their ANCs visits, in which a systematic screening of malaria with the RDT Paracheck-Pf® was performed and a control group of women who delivered in the same period. Our findings showed that in the cohort, there was a proportion of 13.8 % of positive RDT, hence requiring antimalarial treatment, while the proportion of antimalarials prescriptions in the control group was 26.3% (P = 0.0001). The avoidable rate of unnecessary antimalarials prescriptions was estimated at 47%
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Mkopi, Abdallah Bakari. « Meta-analysis of intermittent treatment with sulfadoxine-pyrimethamine in pregnancy in malaria endemic areas ». Thesis, 2002. https://hdl.handle.net/10539/25704.
Texte intégralRésumé :
A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in fulfilment of the requirements for the degree
of
Master of Science in Medicine in Epidemiology and Biostatistics
Johannesburg, 2002.To systematically evaluate the efficacy of double dose of sulfadoxine-pyremithamine (SP/SP) treatment in pregnancy in malaria endemic areas. Methods - The relevant articles were retrieved by a computerized search of Medline, Cochrane Review, Pub Med and Google with the following key words, sulfadoxine-pyrimethamine, intermittent, pregnancy, Quasi- experimental studies and Randomised Control Trials. Three reviewers identified only 2 papers meeting the inclusion criteria set for the study. Systematic quantitative review was performed.
IT2018
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Mngomezulu, Nicros Magangeni. « The role of mutations in uncomplicated Plasmodium falciparum malaria and sulfadoxine pyrimethamine efficacy in Mpumalanga Province, South Africa ». Thesis, 2006. http://hdl.handle.net/10539/1829.
Texte intégralRésumé :
Faculty of Science
School of Animal,Plant,Enviromental Sciences
0311595p
NicrosM@social.mpu.gov.zaThe antifolate combination of sulfadoxine and pyrimethamine (SP) is one of few remaining affordable drug combinations available for wide-scale treatment of uncomplicated Plasmodium falciparum malaria in Africa. In vivo studies of SP efficacy conducted during 1998, 2000 and 2002 at the Naas sentinel site in Mpumalanga province, South Africa, demonstrated a gradual non-significant increase in late treatment failure (LTF) and early treatment failure (ETF) resistance to SP, while gametocyte carriage increased significantly between 1998 and 2002 (p < 0.0001). This study aimed to determined and compare the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) resistant haplotypes in P. falciparum parasites from patients treated with SP in three consecutive standardized in vivo therapeutic efficacy studies in Mpumalanga province, since implementation of SP as first line treatment in 1998, and to investigate associations between the presence of mutations and treatment outcomes after SP treatment. Four hundred-and-three samples were studied and 358 yielded polymerase chain reaction products. A novel high throughput sequence-specific oligonucleotide probe-based approach was used to examine the resistance status of the three in vivo P. falciparum populations. Screening for the presence of all known point mutations in dhfr and dhps genes revealed that only five dhfr and three dhps allelic haplotypes were present. In all the samples investigated, point mutations were identified only at codons 108, 51 and 59 of the dhfr gene and at codons 347 and 540 of the dhps gene. The prevalence of dhfr resistant haplotypes was 35.4% in 1998, 38.7% in 2000, and 41.0% in 2002, while the prevalence of dhps resistant haplotypes was 9.7% in 1998, 7.2% in 2000 and 41.6% in 2002, the latter representing a significant increase (p < 0.002). The prevalence in both dhfr and dhps gene resistant haplotypes were selected gradually during the three in vivo studies in Mpumalanga province. Infection with parasites having triple dhfr mutations and double dhps mutations, "the quintuple mutant", was associated with SP treatment failure (p < 0.001). Mutations at both dhfr and dhps loci may be important predictors of SP resistance in Mpumalanga province.
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Knobloch, Andreas [Verfasser]. « Therapie der unkomplizierten Malaria tropica mit Chloroquin und Sulfadoxin-Pyrimethamin bei Kindern in Tamale, Ghana / von Andreas Knobloch ». 2005. http://d-nb.info/976577437/34.
Texte intégral
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Hommerich, Lena [Verfasser]. « Molekulare Marker der Resistenz von Plasmodium falciparum gegen Sulfadoxin-Pyrimethamin bei Schwangeren in Ghana im Kontext intermittierender präventiver Therapie / von Lena Hommerich ». 2010. http://d-nb.info/1010724703/34.
Texte intégral
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Greutélaers, Katja Carolin [Verfasser]. « Effektivität von Sulfadoxin-Pyrimethamin zur Behandlung symptomatischer, unkomplizierter Plasmodium-falciparum-Malaria bei Kindern im Alter zwischen 6 - 59 Monaten in Lambaréné, Gabun / vorgelegt von Katja Carolin Greutélaers, geb. Szywon ». 2009. http://d-nb.info/997932279/34.
Texte intégral
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Buchholz, Ulrike C. [Verfasser]. « Der Einfluss intermittierender präventiver Behandlung von Säuglingen mit Sulfadoxin-Pyrimethamin auf die Multiplizität der Infektion mit Plasmodium falciparum und deren Bedeutung als immunologischer Parameter beim Kleinkind / von Ulrike C. Buchholz ». 2011. http://d-nb.info/1012919455/34.
Texte intégral
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Emenike, Obiageli Ugwumsinachi. « Knowledge and use of intermittent prevention for malaria among pregnant women attending antenatal clinics in health centers in the Federal Capital Territory, Nigeria ». Diss., 2016. http://hdl.handle.net/10500/21592.
Texte intégralRésumé :
Background
Plasmodium falciparum malaria during pregnancy poses a substantial risk to mother and foetus. In recent years, convincing evidence has shown that preventive methods such as the use of insecticide treated bed nets (ITNs) and intermittent preventive treatment (IPT) in pregnancy with sulphadoxine-pyrimethamine (IPTp-sp) can greatly reduce the adverse effects of malaria during pregnancy.
Purpose
The main purpose of the study was to assess the knowledge and use of Intermittent Preventive Treatment of Malaria among pregnant women receiving Antenatal Care at the primary health centers of the Federal Capital Territory, Abuja Nigeria.
Methods
A quantitative, descriptive, cross-sectional study was conducted Structured questionnaires were administered to 300 pregnant women aged between 18 and 49 years. Data was analysed using Statistical Package for Social Sciences (SPSS) 22.
Results
The results revealed that most of the respondents had knowledge about IPT, majority of the respondents had received IPT drugs, in the clinic, but unfortunately none of them were supervised by a health worker during taking of the drug. Few of the respondents did not take the drugs at all for fear of complication, some of them did not know exactly how many tablets were given to them and there was poor adherence to the Directly Observed Therapy (DOT) scheme.
Conclusion
Knowledge of malaria and IPT was good and many pregnant women received the drugs and used it, but some of them had challenges and did not use the drugs.Health Studies
M.P.H.