N J White

..Artemisinin derivative combinations are particularly effective. Ensuring adequate treatment of the relatively few heavily infected patients would slow the emergence of resistance...

..This suggests that antimalarial drugs should not be used alone in treatment, but always in combination, as in the treatment of tuberculosis or HIV, and that the combination should include artemisinin or one of its derivatives...

..Probenecid coadministration may allow considerable dose saving for oseltamivir, but more information on OC penetration into respiratory secretions is needed to devise appropriate dose regimens...

..The limit of detection was 0.257 ng/mL for artemisinin and the calibration range was 1.03-762 ng/mL using 50 microL plasma. The method was free from matrix effects as demonstrated both graphically and quantitatively...

..These results suggest that artemisinin derivatives are more effective than quinine in preventing pathologic processes in parasitized erythrocytes that contribute to microvascular obstruction in severe malaria...

..017) after treatment with an artemisinin derivative than after treatment with quinine. Parasitization of red cells leads to changes in the erythrocyte that shorten their survival even if the parasite is removed subsequently...

..011). Both treatments were well tolerated. Imipenem is a safe and effective treatment for acute severe melioidosis and may be considered an alternative to ceftazidime...

..Similar trends were observed in Vietnam where artemisinin is widely used. Combination therapies that include an artemisinin derivative could have a major role in the control of malaria and the spread of drug resistance...

..CONCLUSIONS: The oral antimalarial bioavailability following artemether was significantly lower than that after artesunate. Artemether oral antimalarial bioavailability is reduced in acute malaria...

..3 (70:30, v/v) at a flow rate of 1 mL/min. The assay was implemented for the analysis of artesunate for injection purchased from Guilin Pharmaceutical Company in China...

..5 (4.3-10.2) h] than after a low-salt diet [10.0 (7.6-14.8) h] (P = 0.04). CONCLUSION: Dietary salt does not affect the relative oral bioavailability of quinine sulphate...

..These various pitfalls have undoubtedly contributed to the large inter-subject variation in plasma concentration profiles and derived pharmacokinetic parameters for these important antimalarial drugs...

..Characterisation of these pharmacokinetic-pharmacodynamic relationships provided the basis for dosage optimisation, an approach that could be applied to other antimalarial drugs...

..Further studies are needed to determine whether i.r. artemether would be an effective treatment of severe malaria in the rural tropics in situations where oral or parenteral administration is not possible...

..Artemether is a well tolerated and rapidly effective parenteral treatment for severe malaria in children, and would be especially valuable in areas with chloroquine-resistant P falciparum...

..The PfHRP-2 dipstick test provides a useful indicator of recent severe malaria, but does not predict the therapeutic response...

..Validation of over-curve samples ensured that it would be possible with dilution if samples went outside the calibration range...

..The windows were examined for the currently available antimalarials. Drugs with elimination half-lives of less than 1 day, such as the artemisinins and quinine, do not select for resistance during the elimination phase...

..There is no benefit evident from combining parenteral administration of these 2 antimalarial drugs in the acute phase of treatment...

..At this dose the relative risk (95% confidence interval) for death or disability was 5.3 (2.6-11.2) for artemether recipients. Intramuscular artemether is significantly more neurotoxic than intramuscular artesunate in this murine model...

..This simple method of culturing P. vivax ex vivo is suitable for antimalarial susceptibility and immunoparasitology studies...

..4 microg/ml and an MIC of 0.7 microg/ml for uncomplicated falciparum malaria in Thailand. To ensure a cure, the minimum parasiticidal concentration must be exceeded during four asexual cycles (>6 days)...

..7 [0.1-3.5] versus 2.6 [0.1-12.1]; P < 0.001). These results suggest that antimalarial antibodies may play an important supportive role in the therapeutic response to antimalarial drugs during acute falciparum malaria...

..It was found that this could lead to an underestimation of the true concentration with 50% despite the use of a deuterated internal standard...

..The results suggest that the risk of DEET accumulating in the fetus is low and that DEET is safe to use in later pregnancy...

..The results showed that log-log transformation without weighting was the simplest model to fit the calibration data and ensure good predictability for this data set...

..These results are reassuring, but further information about the safety of these valuable antimalarials in pregnancy is needed...

..The method was free from matrix effects as demonstrated both graphically and quantitatively...

..The system opens new possibilities for the study of in vitro drug sensitivity under conditions mimicking in vivo pharmacokinetics, and the selection of anti-malarial drug resistance and associated parasite biological and genomic changes...

..Similar effects were observed with uninfected rbc from patients with severe malaria after treatment with artesunate but not after quinine. The mechanisms underlying this potentially beneficial effect on rbc adherence are not known...

..Preliminary studies have shown that artemisinin and its derivatives artesunate and artemether are effective when given intrarectally. More studies are needed to establish the optimum regimen...

..050 microg/mL and 0.025 microg/mL, respectively, for 100 microL plasma. Long-term storage stability studies of amoxicillin in plasma indicate that a temperature of -80 degrees C is necessary to prevent degradation of amoxicillin...

..The dosing regimen has been simplified from four doses to once daily over 3 days. More information on efficacy in Africa, and more pharmacokinetic and efficacy data in children are needed...

..The suppression did not affect the quantification of OP...

..The results demonstrate that short-course treatment with dapsone plus either proguanil or chlorproguanil is ineffective for the treatment of falciparum malaria in Thailand...

..Therefore, APACHE II scores and either IL-6 or IL-10 concentration may be the most reliable parameters for stratification of patients in future studies of severe gram-negative sepsis...

..Pre-dose titres correlated with renal function; renal function was the most important predictor of mortality. Determination of serum inhibitory or bactericidal titres is unhelpful in the management of severe melioidosis...

..Those drugs with a particularly vulnerable profile, in which a single or double point mutation confers high level resistance, should not be deployed alone and should always be combined with an artemisinin derivative...

..01). The three mutations at the pvdhfr codons for residues 57, 58, and 117 are associated with high levels of S-P resistance in P. vivax. These mutations presumably arose from selection pressure...

..The factors affecting parasite clearance are reviewed. Methods of presentation and the approaches to analysis are discussed...

....

..The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%...

..A global subsidy would make these drugs more affordable and available. ACTs are central to current malaria elimination initiatives, but there are concerns that tolerance to artemisinins may be emerging in Cambodia...

..01). In current antibacterial treatment regimens, short-course azithromycin has inferior antimalarial activity compared to clindamycin or the tetracyclines...

..How parasites persist despite apparently adequate antimalarial treatment remains unresolved...

..These findings suggest that the lack of IL-2, through either a defect in its production or inhibition of its activity, may be the basis of the Ag-specific immune unresponsiveness in acute P. falciparum malaria...

..There was no evidence that diarrhoea, headache, and abdominal pain were associated with mefloquine use. High-dose mefloquine is well tolerated but should be given as a split dose...

..5; 0.1M) (50:50, v/v) at a flow rate of 1.0mL/min. The assay was implemented for the analysis of Tamiflu purchased over the Internet and at local pharmacies in Thailand and Vietnam...

..The SDS-PAGE protein and lectin-binding profiles of both groups of Ara- isolates were also found to be different from those of the Ara+ biotype...

..To assess the prevalence of counterfeit antimalarial drugs in Southeast (SE) Asia...

..falciparum parasitemia at presentation. The PfHRP-2 dipstick test may be a useful adjunct to microscopy in areas where mixed infections are common...

..025) but had significantly lower day 7 piperaquine concentrations (P = 0.024) and total piperaquine exposures (P = 0.021), suggesting that an increased dose regimen for young children should be evaluated...

..A throat swab should be cultured in all cases of suspected melioidosis...

..The results indicate that rosettes do resist the physiological shear forces that are encountered in the venular side of the circulation and could thus contribute to microvascular obstruction in falciparum malaria...

..The use of 96-well plate format and short chromatographic run has increased the daily sample throughput four times. The assay is particularly suitable for large therapeutic drug monitoring studies using day 7 sampling...

..To assess kinetic of cryptococci in the cerebrospinal fluid (CSF) and outcome of AIDS-associated cyptococcal meningitis after high-dose amphotericin B...

..With improvements in health care and diagnostic microbiology in endemic areas of Asia, and increased travel, melioidosis will probably be recognised increasingly during the next decade...

..pseudomallei from avirulent B. thailandensis or even identifying closely related species of Burkholderia...

..Heat-killed bacteria from all LPS groups could similarly activate mouse macrophage cell line to produce nitric oxide (NO) and inducible NO synthase (iNOS)...

..The lower limit of quantification (LLOQ) and the limit of detection (LOD) were 10 and 5 ng/mL, respectively using 0.25 mL plasma. Using 1 mL of plasma, it was possible to decrease LLOQ and LOD to 2.5 and 1.25 ng/mL, respectively...

..Since this seems to be caused by oxidative damage to the red blood cell membrane, the anti-oxidant N-acetylcysteine is a promising candidate for adjunctive treatment in severe malaria, which still has a mortality rate as high as 20%...

..Rifampin should not be combined with quinine for the treatment of malaria, and the doses of quinine should probably be increased in patients who are already receiving rifampin treatment...

..48/110 (44%), respectively, P = 0.031]. CONCLUSION: Dihydroartemisinin-piperaquine did not have superior efficacy to AM for the treatment of uncomplicated falciparum malaria in Laos but was associated with fewer adverse effects...

..Adherence to the 7-day regimen and cost (US$18.50 per treatment) are likely to be the main obstacles to this regimen...

..falciparum in pregnancy, give unsatisfactory treatment responses when used as single agents. New, safe and effective regimens are needed for the treatment of pregnant women with multidrug-resistant falciparum malaria...

..2 (95% CI 1.2 to 71.3, p = 0.012). INTERPRETATION: Mefloquine is not the only risk factor for PMNS but it is a strong one. Where an effective alternative drug is available, mefloquine should not be used after treatment of severe malaria...

..falciparum strains were reached within four hours of starting treatment. Further doses produced plasma concentrations which were sustained above the putative MIC, but showed no rapid increase into the range associated with toxicity...

..Our data lend further support to a simplified once-daily treatment regimen to improve treatment adherence and efficacy and indicate that weight-adjusted piperaquine doses in children may need to be higher than in adults...

..CONCLUSION: Artesunate-atovaquone-proguanil is a promising treatment for multi-drug resistant falciparum malaria during pregnancy, but the dose of atovaquone-proguanil may need to be increased...

..The similarity with results in humans indicates the rat to be a suitable species for nonclinical in vivo piperaquine studies...

..These data are consistent with previous reports of two dominant broods in untreated humans and monkeys infected with P. falciparum, and highlight the need for an adequate duration of quinine treatment...

..2 micro g/ml/day and 4.8 micro g/ml/day, respectively. CONCLUSION: These results indicated that cigarette smoking has no significant effects on quinine pharmacokinetics or the therapeutic response in patients with falciparum malaria...

..These findings should be formally assessed by a randomized clinical trial...

..This may be mediated by oestrogen inhibition of CYP2C19 activity. The dose of PG should be increased by 50% in these groups...

..Neuropathological findings were similar in recipients of quinine (n=15) and artemether (n=6; total artemether doses received 4-44 mg/kg). No evidence was recorded for artemether-induced neurotoxic effects...

..CONCLUSION: The kinetics of DHA are modified by pregnancy. The plasma levels of the active antimalarial metabolite DHA are lower than reported previously in non-pregnant adults. Dose-optimisation studies in pregnant women are needed...

..The route of malaria acquisition did not affect the outcome of severe malaria. The management of severe malaria in IDAs is similar to that for other patients...

..5 to 12.3-fold. Both intrinsic parasite multiplication rate (an intrinsic virulence determinant), and host susceptibility and defence contribute to expansion of the parasite biomass and thus disease severity in falciparum malaria...

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..Assuming formation rate-limiting kinetics, this would support recent findings that the terminal elimination half-life of PQ has been underestimated previously...