Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 165
Filtrar
1.
Microbiome ; 9(1): 180, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34470652

RESUMO

BACKGROUND: Probiotics have been used to regulate the gut microbiota and physiology in various contexts, but their precise mechanisms of action remain unclear. RESULTS: By population genomic analysis of 418 Bifidobacterium longum strains, including 143 newly sequenced in this study, three geographically distinct gene pools/populations, BLAsia1, BLAsia2, and BLothers, were identified. Genes involved in cell wall biosynthesis, particularly peptidoglycan biosynthesis, varied considerably among the core genomes of the different populations, but accessory genes that contributed to the carbohydrate metabolism were significantly distinct. Although active transmission was observed inter-host, inter-country, inter-city, intra-community, and intra-family, a single B. longum clone seemed to reside within each individual. A significant negative association was observed between host age and relative abundance of B. longum, while there was a strong positive association between host age and strain genotype [e.g., single nucleotide polymorphisms in the arginine biosynthesis pathway]. Further animal experiments performed with the B. longum isolates via using a D-galactose-induced aging mouse model supported these associations, in which B. longum strains with different genotypes in arginine biosynthesis pathway showed divergent abilities on protecting against host aging possibly via their different abilities to modify the metabolism of gut microbes. CONCLUSIONS: This is the first known example of research on the evolutionary history and transmission of this probiotic species. Our results propose a new mechanistic insight for promoting host longevity via the informed use of specific probiotics or molecules. Video abstract.


Assuntos
Bifidobacterium longum , Microbioma Gastrointestinal , Probióticos , Sulfaleno , Envelhecimento , Animais , Galactose , Microbioma Gastrointestinal/genética , Humanos , Camundongos
2.
Malar J ; 17(1): 409, 2018 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-30400908

RESUMO

BACKGROUND: Despite the development of resistance to Plasmodium falciparum malaria, sulfadoxine-pyrimethamine is still effective for intermittent preventive treatment of malaria in pregnancy (IPTp). In Tanzania, more than 10 years have passed since sulfadoxine-pyrimethamine and sulfamethopyrazine-pyrimethamine (SPs) were reserved for IPTp only. However, the retail pharmaceutical outlet dispensers' knowledge and their compliance with the policies have not been recently explored. Therefore, this study was designed to investigate dispensers' knowledge about these medications together with their actual dispensing practices, a decade since they were limited for IPTp use only. METHODS: This descriptive cross-sectional study was conducted between February and July 2017 in all municipalities of Dar-es-Salaam city. Data were collected by direct interviews using a structured questionnaire to assess knowledge and a simulated client approach was used to assess the actual practice of medicine dispensers. Data analysis was done by using SPSS version 20 and Chi square test was used to test significant differences in proportions between different categorical variables. A p-value of less than 0.05 was considered to be statistically significant. RESULTS: A random sample of 422 medicine dispensers participated in this study whereby 185 (43.8%) were from community pharmacies and 237 (56.2%) from accredited drug dispensing outlets. The study revealed that SPs were available in 76% of the community pharmaceutical outlets in Dar es Salaam. In general majority of the dispensers (64%) had moderate to high knowledge about SPs and their indication. About 80% of the dispensers were aware that SP is reserved for IPTp. However, irrespective of the level of knowledge, almost all dispensers (92%) were willing to dispense the medicines for the purpose of treating malaria, contrary to the current Tanzania malaria treatment guideline. CONCLUSION: Majority of the medicine dispensers in the community pharmaceutical outlets were knowledgeable about SPs and their indications. Disappointingly, almost all dispensers irrespective of their levels of knowledge were willing to dispense SPs for treatment of malaria contrary to the available treatment guidelines.


Assuntos
Antimaláricos/uso terapêutico , Competência Clínica/estatística & dados numéricos , Malária Falciparum/prevenção & controle , Malária/prevenção & controle , Farmácias/estatística & dados numéricos , Complicações Parasitárias na Gravidez/prevenção & controle , Estudos Transversais , Combinação de Medicamentos , Feminino , Humanos , Gravidez , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Sulfaleno/uso terapêutico , Sulfonamidas/uso terapêutico , Tanzânia
3.
J Pharm Biomed Anal ; 129: 558-570, 2016 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-27505128

RESUMO

A simple, cost effective, accurate, and precise RP-HPLC method was developed for the simultaneous determination of sulfalene and sulfadoxine in fixed dose dual combinations with pyrimethamine together with their related substances. Proprietary products containing these combinations are often being prescribed in malaria endemic countries. Quantification of the active compounds and impurity profiling was achieved using two standard C18 columns with a mobile phase being composed of 60% (v/v) of a 0.05M KH2PO4 buffer solution (pH=2.6) and 40% (v/v) of methanol, applying an isocratic elution mode and a detection wavelength of 215nm. The method allows a quick quantitative determination of sulfadoxine and sulfalene and the separation of the respective impurities within a total runtime of approximately 15min and was validated with respect to specificity, linearity, precision, accuracy, limits of detection and quantification, robustness, and stability of the standard and sample solutions. The method is simpler than the corresponding method described in the International Pharmacopoeia and the United States Pharmacopoeia in terms of being easy to apply, being less time consuming, and utilizing reagents and chemicals which are cost efficient.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Pirimetamina/química , Sulfadoxina/química , Sulfaleno/química , Comprimidos/química , Estabilidade de Medicamentos , Indicadores e Reagentes/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
4.
Microbiol Immunol ; 59(1): 1-12, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25400245

RESUMO

Bifidobacterium, one of the major components of intestinal microflora, shows anti-influenza virus (IFV) potential as a probiotic, partly through enhancement of innate immunity by modulation of the intestinal immune system. Bifidobacterium longum MM-2 (MM-2), a very safe bacterium in humans, was isolated from healthy humans and its protective effect against IFV infection in a murine model shown. In mice that were intranasally inoculated with IFV, oral administration of MM-2 for 17 consecutive days improved clinical symptoms, reduced mortality, suppressed inflammation in the lower respiratory tract, and decreased virus titers, cell death, and pro-inflammatory cytokines such as IL-6 and TNF-α in bronchoalveolar lavage fluid. The anti-IFV mechanism of MM-2 involves innate immunity through significant increases in NK cell activities in the lungs and spleen and a significant increase in pulmonary gene expression of NK cell activators such as IFN-γ, IL-2, IL-12 and IL-18. Even in non-infected mice, MM-2 administration also induced significant enhancement of both IFN-γ production by Peyer's patch cells (PPs) and splenetic NK cell activity. Oral administration of MM-2 for 17 days activates systemic immunoreactivity in PPs, which contributes to innate immunity, including NK cell activation, resulting in an anti-IFV effect. MM-2 as a probiotic may function as a prophylactic agent in the management of an IFV epidemic.


Assuntos
Bifidobacterium/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Células Matadoras Naturais/imunologia , Infecções por Orthomyxoviridae/imunologia , Probióticos/administração & dosagem , Administração Oral , Animais , Citocinas/biossíntese , Modelos Animais de Doenças , Feminino , Perfilação da Expressão Gênica , Pulmão/imunologia , Pulmão/patologia , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/patologia , Baço/imunologia , Sulfaleno , Análise de Sobrevida
5.
J Org Chem ; 79(16): 7332-41, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-25032516

RESUMO

Bifidobacteria are dominant members of the microbial community in the intestinal tract of infants, and studies have shown that glycolipids extracted from the cell surface of these bacteria elicit beneficial immune responses. Accordingly, the identification and structural characterization of glycolipids from the cell wall of bifidobacteria is the first step in correlating glycolipid structure with biological activity. Using whole cell MALDI as a screening tool, we herein present for the first time the identification and structural elucidation of the major polar lipids from Bifidobacterium longum subs. infantis. The lipids identified include an unprecedented plasmenyl cyclophosphatidic acid and a mixed acetal glycolipid, with the latter subsequently being isolated and found to suppress the innate immune response.


Assuntos
Bifidobacterium/química , Glicolipídeos/química , Intestinos/química , Intestinos/imunologia , Intestinos/microbiologia , Lipídeos/química , Sulfaleno/química , Aderência Bacteriana/imunologia , Bifidobacterium/imunologia , Bifidobacterium/metabolismo , Glicolipídeos/metabolismo , Humanos , Lipídeos/imunologia , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
6.
Molecules ; 16(9): 8083-97, 2011 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-21934646

RESUMO

A rational approach was used to synthesize a new set of 15 1H-1,2,4-triazol-3-yl benzenesulfonamide derivatives with the aim of developing new antimalarial lead compounds. These derivatives were prepared in yields between 50% and 62%, and their structures were elucidated using IR, ¹H-, ¹³C-, ¹9F-NMR, MS and elemental analysis. A docking study based on sulfonamides previously used against malaria identified trifluoromethyl-substituted derivatives to be the best lead compounds for new antimalarial drug development.


Assuntos
Antimaláricos/síntese química , Compostos de Flúor/síntese química , Sulfonamidas/síntese química , Triazóis/síntese química , Sequência de Aminoácidos , Antimaláricos/química , Domínio Catalítico , Simulação por Computador , Sequência Conservada , Ciclização , Di-Hidropteroato Sintase/química , Desenho de Fármacos , Compostos de Flúor/química , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Plasmodium falciparum/enzimologia , Ligação Proteica , Sulfadiazina/química , Sulfadoxina/química , Sulfaleno/química , Sulfonamidas/química , Termodinâmica , Triazóis/química
8.
Malar J ; 10: 70, 2011 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-21443809

RESUMO

Recent publications put a serious warning regarding the inefficacy of sulphadoxine-pyrimethamine (SP) for the intermittent preventive treatment of malaria in young children (IPTi). Recommendations for other therapies are being made. By using a different and better sulphonamide (sulphamethoxypyrazine), it is possible to manufacture fixed dose combination pills with artesunate and pyrimethamine. This combination permits a full therapy over 24 hours (dosing interval being 12 hours). It is recommended that this combination should be tested in future field studies of IPTi.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária/tratamento farmacológico , Malária/prevenção & controle , Pirimetamina/administração & dosagem , Sulfaleno/administração & dosagem , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Artesunato , Criança , Combinação de Medicamentos , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Lactente , Plasmodium/efeitos dos fármacos , Pirimetamina/uso terapêutico , Sulfaleno/uso terapêutico
9.
Lancet Infect Dis ; 10(9): 603-11, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20705516

RESUMO

BACKGROUND: Schistosomiasis is an important parasitic disease in Kenya. Decreasing susceptibility of schistosomes to praziquantel, the major drug used to reduce disease morbidity, has made assessment of new antischistosomal drugs a priority. We aimed to assess the safety and efficacy of an artesunate-based combination drug in the treatment of schistosomiasis. METHODS: In this open-label randomised trial in Rarieda district of western Kenya, we enrolled school children (aged 6-15 years) who had Schistosoma mansoni infection according to duplicate Kato-Katz thick smears from a stool sample. Computer-generated block randomisation was used to assign children (1:1) to receive artesunate (100 mg) with sulfalene (also known as sulfamethoxypyrazine; 250 mg) plus pyrimethamine (12.5 mg) as one dose every 24 h for 3 days or one dose of praziquantel (40 mg/kg per day). The primary efficacy endpoint was the number of participants cured 28 days after treatment. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01054651. RESULTS: Between October and December, 2009, 212 children were enrolled and assigned to receive artesunate with sulfalene plus pyrimethamine (n=106) or praziquantel (n=106). 69 patients (65%) were cured in the praziquantel treatment group compared with 15 (14%) in the artesunate with sulfalene plus pyrimethamine treatment group (p<0.0001). Adverse events were less common in patients taking artesunate with sulfalene plus pyrimethamine than in those taking praziquantel (22% [n=23] vs 49% [n=52], p<0.0001), and no drug-related serious adverse events occurred. INTERPRETATION: The standard treatment with praziquantel is more effective than artesunate with sulfalene plus pyrimethamine in the treatment of children with S mansoni infection in western Kenya. Whether artemisinin-based combination therapy has a role in the treatment of schistosomiasis is unclear.


Assuntos
Artemisininas/uso terapêutico , Pirimetamina/uso terapêutico , Esquistossomose mansoni/tratamento farmacológico , Sulfaleno/uso terapêutico , Adolescente , Amebicidas/efeitos adversos , Amebicidas/uso terapêutico , Animais , Antiprotozoários/efeitos adversos , Antiprotozoários/uso terapêutico , Artemisininas/efeitos adversos , Artesunato , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Humanos , Lactente , Quênia , Masculino , Pirimetamina/efeitos adversos , Schistosoma mansoni , Esquistossomose mansoni/classificação , Sulfaleno/efeitos adversos
10.
J Trop Pediatr ; 56(6): 398-406, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20144932

RESUMO

Combination therapy with artemesinin or non-artemesinin-based antimalarials (ACTs or NACTs) are known to retard the development and progression of drug resistance in Plasmodium falciparum (P. falciparum). The optimal antimalarial combinations in Africa are yet unknown. We evaluate the therapeutic efficacy and effects on gametocyte carriage of Artemether-Lumefantrine (AL) and Amodiaquine-Sulfalene/Pyrimethamine (ASP) in children with P. falciparum malaria in an endemic area. One-hundred and thirty-nine children aged ≤ 10 years with uncomplicated P. falciparum malaria were enrolled. The primary end points were adequate clinical and parasitological response (ACPR), late parasitological failure(LPF), late clinical failure (LCF) and early treatment failure (ETF). Polymerase chain reaction (PCR)-corrected cure rates on days 14-42 and gametocyte carriage rates were determined. Fever clearance time was significantly shorter (P = 0.009) with ASP, but parasite clearance time was similar with both regimens. Day 28 cure rates were 91.4 and 89.9% (PCR-corrected) for AL and ASP respectively. Both regimens were well tolerated. Overall, gametocyte carriage before and following treatment were similar. Both combinations were found effective and comparable for treatment of acute, uncomplicated, P. falciparum malaria.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Gametogênese/efeitos dos fármacos , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Amodiaquina/uso terapêutico , Artemeter , Combinação Arteméter e Lumefantrina , Pré-Escolar , Cloroquina/administração & dosagem , Combinação de Medicamentos , Resistência a Medicamentos , Quimioterapia Combinada , Etanolaminas/uso terapêutico , Feminino , Fluorenos/uso terapêutico , Seguimentos , Humanos , Lactente , Lumefantrina , Malária Falciparum/parasitologia , Masculino , Nigéria , Plasmodium falciparum/genética , Plasmodium falciparum/crescimento & desenvolvimento , Reação em Cadeia da Polimerase , Pirimetamina/uso terapêutico , Sulfaleno/uso terapêutico , Resultado do Tratamento
11.
Malar J ; 9: 378, 2010 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-21194422

RESUMO

BACKGROUND: Several studies have demonstrated the efficacy of artemisinin-combination therapy (ACT) across malaria zones of the world. Fixed dose ACT with shorter courses and fewer tablets may be key determinants to ease of administration and compliance. METHODS: Children aged one year to 13 years presenting with uncomplicated Plasmodium falciparum malaria were recruited in Ibadan, south-western Nigeria. A total of 250 children each were randomly assigned to receive three doses of artesunate/sulphamethoxypyrazine/pyrimethamine (AS + SMP) (12 hourly doses over 24 hours) or three doses of artesunate/amodiaquine (AS + AQ) (daily doses over 48 hours). Efficacy and safety of the two drugs were assessed using a 28-day follow-up and the primary outcome was PCR- corrected parasitological cure rate and clinical response. RESULTS: There were two (0.4%) early treatment failures, one in each treatment arm. The PCR corrected cure rates for day 28 was 97.9% in the AS + AQ arm and 95.6% in the AS + SMP arm (p = 0.15). The re-infection rate was 1.7% in the AS + AQ arm and 5.7% in the AS + SMP arm (p = 0.021). The fever clearance time was similar in the two treatment groups: 1 - 2 days for both AS + SMP and AS + AQ (p = 0.271). The parasite clearance time was also similar in the two treatment groups with 1 - 7 days for AS + SMP and 1 - 4 days for AS + AQ (p = 0.941). The proportion of children with gametocytes over the follow-up period was similar in both treatment groups. Serious Adverse Events were not reported in any of the patients and in all children, laboratory values (packed cell volume, liver enzymes, bilirubin) remained within normal levels during the follow-up period but the packed cell volume was significantly lower in the AS + SMP group. CONCLUSIONS: This study demonstrates that AS + SMP FDC given as three doses over 24 hours (12-hour intervals) has similar efficacy as AS + AQ FDC given as three doses over 48 hours (24-hour interval) for the treatment of uncomplicated Plasmodium falciparum malaria in children in Nigeria. Both drugs also proved to be safe. Therefore, AS + SMP could be an alternative to currently recommended first-line ACT with continuous resistance surveillance.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/tratamento farmacológico , Adolescente , Amodiaquina/administração & dosagem , Amodiaquina/efeitos adversos , Antimaláricos/efeitos adversos , Artemisininas/efeitos adversos , Artesunato , Criança , Pré-Escolar , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Humanos , Lactente , Masculino , Nigéria , Pirimetamina/administração & dosagem , Pirimetamina/efeitos adversos , Sulfaleno/administração & dosagem , Sulfaleno/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
12.
PLoS One ; 4(10): e6732, 2009 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-19802383

RESUMO

BACKGROUND: This study was conducted to determine the efficacy of the antimalarial artemisinin-based combination therapy (ACT) artesunate +sulfamethoxypyrazine/pyrimethamine (As+SMP), administered in doses used for malaria, to treat Schistosoma haematobium in school aged children. METHODOLOGY/PRINCIPAL FINDINGS: The study was conducted in Djalakorodji, a peri-urban area of Bamako, Mali, using a double blind setup in which As+SMP was compared with praziquantel (PZQ). Urine samples were examined for Schistosoma haematobium on days -1, 0, 28 and 29. Detection of haematuria, and haematological and biochemical exams were conducted on day 0 and day 28. Clinical exams were performed on days 0, 1, 2, and 28. A total of 800 children were included in the trial. The cure rate obtained without viability testing was 43.9% in the As+SMP group versus 53% in the PZQ group (Chi(2) = 6.44, p = 0.011). Egg reduction rates were 95.6% with PZQ in comparison with 92.8% with As+SMP, p = 0.096. The proportion of participants who experienced adverse events related to the medication was 0.5% (2/400) in As+SMP treated children compared to 2.3% (9/399) in the PZQ group (p = 0.033). Abdominal pain and vomiting were the most frequent adverse events in both treatment arms. All adverse events were categorized as mild. CONCLUSIONS/SIGNIFICANCE: The study demonstrates that PZQ was more effective than As+SMP for treating Schistosoma haematobium. However, the safety and tolerability profile of As+SMP was similar to that seen with PZQ. Our findings suggest that further investigations seem justifiable to determine the dose/efficacy/safety pattern of As+SMP in the treatment of Schistosoma infections. TRIAL REGISTRATION: ClinicalTrials.gov NCT00510159.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/administração & dosagem , Combinação de Medicamentos , Praziquantel/administração & dosagem , Schistosoma haematobium/metabolismo , Esquistossomose Urinária/tratamento farmacológico , Sulfaleno/administração & dosagem , Adolescente , Animais , Artesunato , Criança , Método Duplo-Cego , Feminino , Humanos , Masculino , Pirimetamina/administração & dosagem , Fatores de Tempo
14.
Malar J ; 8: 63, 2009 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-19366448

RESUMO

BACKGROUND: The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. METHODS: Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP) three-day (once daily for 3 days) regimen (N = 476) or AS-SMP 24-hour (0 h, 12 h, 24 h) regimen (N = 458) or artemether-lumefantrine (AL), the regular 6 doses regimen (N = 450). The primary objective was to demonstrate non-inferiority (using a margin of -6%) of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. RESULTS: The PCR corrected 28-day cure rate on the intention to treat (ITT) analysis population were: 96.0%(457/476) in the AS-SMP three-day group, 93.7%(429/458) in the AS-SMP 24-hour group and 92.0%(414/450) in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437) in the AS-SMP three-day group, 99.5%(416/419) in the AS-SMP 24-hour group and 99.7(391/394)% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea) which were slightly higher in the AS-SMP 24-hour group. CONCLUSION: AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. TRIAL REGISTRATION: NCT00484900 http://www.clinicaltrials.gov.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Etanolaminas/uso terapêutico , Fluorenos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Plasmodium falciparum/efeitos dos fármacos , Pirimetamina/uso terapêutico , Sulfaleno/uso terapêutico , Animais , Antimaláricos/administração & dosagem , Antimaláricos/efeitos adversos , Combinação Arteméter e Lumefantrina , Artemisininas/administração & dosagem , Artemisininas/efeitos adversos , Artesunato , Criança , Pré-Escolar , Esquema de Medicação , Combinação de Medicamentos , Quimioterapia Combinada , Etanolaminas/administração & dosagem , Etanolaminas/efeitos adversos , Feminino , Fluorenos/administração & dosagem , Fluorenos/efeitos adversos , Humanos , Lactente , Malária Falciparum/epidemiologia , Masculino , Plasmodium falciparum/isolamento & purificação , Gravidez , Estudos Prospectivos , Pirimetamina/administração & dosagem , Pirimetamina/efeitos adversos , Sulfaleno/administração & dosagem , Sulfaleno/efeitos adversos , Comprimidos , Resultado do Tratamento
15.
Chemotherapy ; 54(3): 201-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18560227

RESUMO

The activities of artemether-lumefantrine and amodiaquine-sulfalene-pyrimethamine against sexual-stage parasites were evaluated in 42 of 181 Nigerian children with uncomplicated Plasmodium falciparum malaria who had gametocytaemia before, during or after treatment with the two combination therapies. The children were randomized to the standard dose regimens. Clinical recovery from illness occurred in all children who carried gametocytes. Gametocytaemia was detected in 20 patients (11%) before treatment and in another 22 patients (12.2%) after treatment. Gametocyte carriage rates were similar in both combination treatment groups, but the area under the curve of gametocytaemia plotted against time was 8-fold higher in the amodiaquine-sulfalene-pyrimethamine-treated than in the artemether-lumefantrine-treated children. The pretreatment gametocyte sex ratio was female biased in both treatment groups. During follow-up, there was a short-lived but significant increase in the gametocyte sex ratio in children treated with amodiaquine-sulfalene-pyrimethamine but not in those treated with artemether-lumefantrine. These results indicate that both combination therapies had moderate effects on gametocyte carriage, but artemether-lumefantrine may be more potent at reducing transmissibility in P. falciparum malaria by exerting greater effects on post-treatment gametocyte density and gametocyte sex ratio.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/crescimento & desenvolvimento , Amodiaquina/uso terapêutico , Animais , Artemeter , Artemisininas/uso terapêutico , Criança , Pré-Escolar , Quimioterapia Combinada , Etanolaminas/uso terapêutico , Feminino , Fluorenos/uso terapêutico , Humanos , Lumefantrina , Masculino , Pirimetamina/uso terapêutico , Sulfaleno/uso terapêutico , Taxa de Sobrevida , Resultado do Tratamento
16.
Int J Infect Dis ; 12(4): 430-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18343702

RESUMO

OBJECTIVES: Malaria kills approximately 1.5 to 2.7 million people each year. Despite the introduction of artemisinin-based combination therapies (ACTs), the treatment of malaria is hampered by problems such as inadequate efficacy, recrudescence, early re-infection, low patient compliance, and high cost price of drugs. This study tested the hypothesis that the co-formulated fixed dose combination (FDC) artesunate/sulfamethoxypyrazine/pyrimethamine (As/SMP) administered as a 24-hour therapy with a dose interval of 12 hours is as efficacious and safe as the administration of the same drug over 3 days given with a dose interval of 24 hours, for the treatment of uncomplicated Plasmodium falciparum malaria in Ivory Coast. METHOD: Two hundred and twenty-one patients presenting with uncomplicated P. falciparum malaria were randomly assigned to either one of the two dosing schemes. Treatment efficacy was assessed using the current 28-day World Health Organization protocol, success being determined by absence of recrudescence and parasitemia on day 28. RESULTS: Both treatment regimens were highly efficacious, with a success rate of 100% (111/111) for the 3-day therapy and 99% (109/110) for the 24-hour therapy. Only one patient in the 24-hour therapy group showed late treatment failure. No serious adverse events or significant laboratory abnormalities were seen. CONCLUSION: The 24-hour therapy is as well tolerated and efficacious as the same medicament administered over 3 days. This low cost and simplified three-pill treatment is certain to improve compliance.


Assuntos
Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Malária Falciparum/tratamento farmacológico , Pirimetamina/administração & dosagem , Succinatos/administração & dosagem , Sulfaleno/administração & dosagem , Criança , Costa do Marfim , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino
17.
Ann Trop Med Parasitol ; 102(1): 39-44, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18186976

RESUMO

Although artemisinin and its derivatives are widely used for the treatment of malaria, they also have antischistosomal activity. In a small study in eastern Sudan, the effects of the treatment of uncomplicated, Plasmodium falciparum malaria with artesunate-sulfamethoxypyrazine-pyrimethamine (AS-SMP) and artemether-lumefantrine (AT-LU) on co-infections with Schistosoma mansoni were therefore investigated. Faecal samples from 14 of the 306 patients screened on presentation, at the start of a clinical trial of antimalarial treatment, were found to contain Schistosoma mansoni eggs. For the treatment of their malaria, the 14 egg-positive cases, who were aged 6-40 years (mean = 13.7 years), were each subsequently treated with three tablets of a fixed combination of AS-SMP, with a 12-h (six patients) or 24-h interval (five patients) between each tablet, or with six doses of AT-LU given over 3 days. When checked 28 and 29 days after the initiation of treatment, all 14 patients were found stool-negative for schistosome eggs. These results indicate that AS-SMP and AT-LU are currently very effective treatments not only for uncomplicated, P. falciparum malaria but also for S. mansoni infections.


Assuntos
Antimaláricos/uso terapêutico , Malária Falciparum/tratamento farmacológico , Schistosoma mansoni/efeitos dos fármacos , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/uso terapêutico , Adolescente , Adulto , Animais , Combinação Arteméter e Lumefantrina , Artemisininas/uso terapêutico , Artesunato , Criança , Combinação de Medicamentos , Quimioterapia Combinada , Doenças Endêmicas , Etanolaminas/uso terapêutico , Fezes , Fluorenos/uso terapêutico , Humanos , Malária Falciparum/complicações , Contagem de Ovos de Parasitas , Pirimetamina/uso terapêutico , Schistosoma mansoni/parasitologia , Esquistossomose mansoni/complicações , Sesquiterpenos/uso terapêutico , Sudão , Sulfaleno/uso terapêutico
18.
Am J Trop Med Hyg ; 77(4): 612-6, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17978058

RESUMO

In view of the changing policy towards artemisinin-based combination therapies (ACTs), the efficacy, tolerance, and degree of re-infection of two ACTs were investigated: artesunate plus sulfadoxine/pyrimethamine (As + SP) and AS plus sulfamethoxypyrazine/pyrimethamine (As + SMP). One hundred three children were assigned to receive As + SP and 109 to receive As + SMP. In spite of the high incidence of resistance to SP, As + SP showed satisfactory results consistent with recent recommendations for ACTs (adequate clinical and parasitologic response on day 28 [ACPR] > or = 90%), but results with As + SMP fulfilled the most stringent criteria (ACPR > or = 95%). The absence of side effects and the low price of these drugs make them it worth to reconsider national therapies in favor of either of these two drug combinations.


Assuntos
Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Malária Falciparum/tratamento farmacológico , Pirimetamina/uso terapêutico , Sesquiterpenos/uso terapêutico , Sulfadoxina/uso terapêutico , Sulfaleno/uso terapêutico , Artemisininas/administração & dosagem , Artesunato , Criança , Pré-Escolar , Combinação de Medicamentos , Resistência a Múltiplos Medicamentos , Feminino , Hemoglobinas/metabolismo , Humanos , Lactente , Malária Falciparum/sangue , Malária Falciparum/parasitologia , Masculino , Ruanda , Sesquiterpenos/administração & dosagem
20.
New Microbiol ; 30(3): 299-302, 2007 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-17802914

RESUMO

We evaluated the frequency of seroconversion for toxoplasmosis in seronegative recipients of thoracic solid organ transplants with seronegative or seropositive donors and the efficacy of chemoprophylaxis with pyrimethamine+sulfametopirazine. One hundred and sixty one patients seronegative for toxoplasmosis were followed-up at different intervals. Six patients out of 79 R-/D- and twelve out of 82 R-/D+ seroconverted after chemoprophylaxis interruption. There was no difference between matched and mismatched recipients as to the frequency of seroconversion which therefore could not be related to donor seropositivity. Seroconversions were almost asymptomatic. All positive recipients should be tested if symptoms of infection are present.


Assuntos
Transplante de Coração , Transplante de Pulmão , Toxoplasma/imunologia , Toxoplasmose/epidemiologia , Adulto , Animais , Anticorpos Antiprotozoários/sangue , Antiprotozoários/uso terapêutico , Quimioterapia Combinada , Feminino , Humanos , Imunoensaio , Itália/epidemiologia , Masculino , Pirimetamina/uso terapêutico , Kit de Reagentes para Diagnóstico , Vigilância de Evento Sentinela , Estudos Soroepidemiológicos , Sulfaleno/uso terapêutico , Toxoplasmose/sangue , Toxoplasmose/prevenção & controle , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...