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Antimalarial Treatment (antimalarial + treatment)
Selected AbstractsAntimalarial treatment may have a time-dependent effect on lupus survival: Data from a multinational Latin American inception cohortARTHRITIS & RHEUMATISM, Issue 3 2010Samuel K. Shinjo Objective To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. Methods Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). Results Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6,98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6,11 months, 146 (12.8%) for 1,2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41,8.37), 2.7 (95% CI 1.41,4.76), and 0.54 (95% CI 0.37,0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18,4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39,0.99). Conclusion Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. [source] ORIGINAL ARTICLE: Probability of emergence of antimalarial resistance in different stages of the parasite life cycleEVOLUTIONARY APPLICATIONS (ELECTRONIC), Issue 1 2009Wirichada Pongtavornpinyo Abstract Understanding the evolution of drug resistance in malaria is a central area of study at the intersection of evolution and medicine. Antimalarial drug resistance is a major threat to malaria control and directly related to trends in malaria attributable mortality. Artemisinin combination therapies (ACT) are now recommended worldwide as first line treatment for uncomplicated malaria, and losing them to resistance would be a disaster for malaria control. Understanding the emergence and spread of antimalarial drug resistance in the context of different scenarios of antimalarial drug use is essential for the development of strategies protecting ACTs. In this study, we review the basic mechanisms of resistance emergence and describe several simple equations that can be used to estimate the probabilities of de novo resistance mutations at three stages of the parasite life cycle: sporozoite, hepatic merozoite and asexual blood stages; we discuss the factors that affect parasite survival in a single host in the context of different levels of antimalarial drug use, immunity and parasitaemia. We show that in the absence of drug effects, and despite very different parasite numbers, the probability of resistance emerging at each stage is very low and similar in all stages (for example per-infection probability of 10,10,10,9 if the per-parasite chance of mutation is 10,10 per asexual division). However, under the selective pressure provided by antimalarial treatment and particularly in the presence of hyperparasitaemia, the probability of resistance emerging in the blood stage of the parasite can be approximately five orders of magnitude higher than in the absence of drugs. Detailed models built upon these basic methods should allow us to assess the relative probabilities of resistance emergence in the different phases of the parasite life cycle. [source] Antimalarial treatment may have a time-dependent effect on lupus survival: Data from a multinational Latin American inception cohortARTHRITIS & RHEUMATISM, Issue 3 2010Samuel K. Shinjo Objective To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. Methods Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). Results Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6,98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6,11 months, 146 (12.8%) for 1,2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41,8.37), 2.7 (95% CI 1.41,4.76), and 0.54 (95% CI 0.37,0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18,4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39,0.99). Conclusion Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. [source] The influence of antimalarial treatment on IL-1,, IL-6 and TNF-, mRNA expression on UVB-irradiated skin in systemic lupus erythematosusBRITISH JOURNAL OF DERMATOLOGY, Issue 5 2008A. Wozniacka Summary Background, There are very few data addressing the mechanisms of antimalarial treatment benefit locally within the skin of patients with lupus erythematosus, at the level of cytokine messenger RNA (mRNA) expression. Objectives, The aim of this study was to evaluate whether 3 months of monotherapy with chloroquine influences the mRNA skin expression of interleukin (IL)-1,, IL-6 and tumour necrosis factor-, (TNF-,) in nonirradiated and locally ultraviolet B (UVB) irradiated nondiseased skin of patients with systemic lupus erythematosus (SLE). Patients/Methods, Skin biopsies were collected from 14 patients with SLE 24 h after irradiation at one site and from an adjacent unirradiated site, before and after 3 months of chloroquine treatment. Messenger RNA levels for IL-1,, IL-6 and TNF-, were determined by relative quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results, There were no significant differences in the levels of mRNA cytokine expressions in the unirradiated sites before and after 3 months of chloroquine administration. In the irradiated sites, the expression of all three cytokine mRNA levels was significantly higher than in the unirradiated group, approximately 24 h after irradiation, before chloroquine treatment. Significantly lower expression of IL-1,, IL-6 and TNF-, mRNAs was noted in irradiated skin samples after 3 months of chloroquine treatment. Conclusions, These results demonstrate the local inhibitory effects of chloroquine on UVB-induced upregulation in the mRNA expression of proinflammatory cytokines in irradiated skin of SLE patients, and provide further insight into the apparent immunomodulatory, anti-inflammatory and photoprotective properties of chloroquine. [source] Development and validation of a simple thin layer chromatographic method for the analysis of artemisinin in Artemisia annua L. plant extractsBIOMEDICAL CHROMATOGRAPHY, Issue 5 2008Els Marchand Abstract Owing to the development of parasite resistance to standard antimalarial treatments like chloroquine and sulfadoxine,pyrimethamine, the demand for Artemisia annua, a key ingredient for new and highly effective antimalarial drugs, is huge. Therefore selective and precise methods to determine the content of artemisinin in dry plant material and in raw impure extracts are needed. In this work a method is described for the clear separation and extraction of artemisinin from other plant components in the Artemisia annua L. plant by thin-layer chromatography (TLC). To obtain optimal extraction and recovery efficiency, several parameters were evaluted, including choice of extraction solvent, TLC plate type and sensitivity between UV and visible light. Method validation was performed on both the dry plant material and non-purified plant extracts. Toluene presented the highest extraction efficiency compared with petroleum ether, hexane and methanol. Reversed-phase plates showed more concentrated spots than normal-phase plates, while the sensitivity of the analysis in UV was comparable to that in visible light but less precise. The impure plant extracts were analyzed by both TLC and HPLC-UV at 215 nm and both methods met the requirements for linearity, selectivity, precision and accuracy. Hence, the proposed TLC method can easily be used for both qualitative and quantitative control of the raw plant extract in areas where advanced methods are scarce. Copyright © 2007 John Wiley & Sons, Ltd. [source] | ||||||||||