Treating severe malaria

BackgroundRectal artesunate has been shown to reduce death and disability from severe malaria caused by delays in reaching facilities capable of providing appropriate treatment.Acceptability of this mode of drug delivery in Laos is not known. In 2009 the acceptability of rectal treatments was evaluated among the general Lao population and Lao doctors in a national survey.MethodsA cross sectional survey was performed of 985 households selected through a multi-stage random sampling process from 85 villages in 12/18 provinces and of 315 health staff randomly selected at each administrative level.ResultsOut of 985 families, 9% had used the rectal route to treat children (the main indication was seizures or constipation). The population considered it less effective than other routes. Other concerns raised included pain (28%), discomfort for children (40%) and the possibility of other side effects (20%). Of 300 health staff surveyed (nurses 44%, doctors 66%), only 51% had already used the rectal route with a suppository, mostly to treat fever (76%). Health staff working in provincial hospitals had more experience of using the rectal route than those in urban areas. The majority (92%) were keen to use the rectal route to treat malaria although oral and intramuscular routes were preferred and considered to be more efficacious.Discussion and conclusionUse of rectal treatments is uncommon in Laos and generally not considered to be very effective. This view is shared by the population and health care workers. More information and training are needed to convince the population and health staff of the efficacy and advantages of the rectal route for malaria treatment.

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“…Treatment delays cost lives [ 8 ]. Access to effective treatment in remote areas needs to be improved.…”

Section: Discussionmentioning

confidence: 99%

Knowledge and acceptability of the rectal treatment route in Laos and its application for pre-referral emergency malaria treatment

Inthavilay¹,

Franchard²,

Yang³

et al. 2010

Malar J

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“…For complicated and severe malaria, however, intravenous AS, as monotherapy, is still in first line treatment for both adults and children in Asian countries [39], and some areas in Africa [41]. Trying to replace quinine (which has been the principal drug used to treat severe malaria for nearly 400 years) with a more effective, less expensive, and better tolerated drug [42], an initial trial using intramuscular AM demonstrated less toxicity but no clear mortality benefit over quinine [43][44][45]. More recent trials have used intravenous AS with a more favorable pharmacokinetic profile [46,47].…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

Li¹,

Weina²,

Milhous³

2007

CDTH

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Artemisinin and its derivatives were discovered to be highly effective antimalarial drugs, which combine potent, rapid antimalarial activity with a wide therapeutic index and an absence of clinically important resistance. Artemisinins as a group are poorly efficacious at curing malaria as monotherapy. However, this shortfall is being overcome by using oral artemisinin-based combination therapy (ACT) and intravenous artesunate (AS) in sequential administration with slower acting antimalarial drugs. Pharmacokinetic and pharmacodynamic (PK/PD) evaluations demonstrate that the rapid efficacy of artemisinins is principally due to the drug peak concentration (C max ), and other pharmacokinetic parameters, such as drug exposure level (AUC) and drug exposure time (half-life) tend to be of minor significance. The evaluation also demonstrated that AS is a superior in PK/PD achievements either following oral or intravenous administration when compared to other four artemisinin drugs. Most recently, a decrease in mortality (34.7%) has been demonstrated in a large study using intravenous AS, as opposed to the standard of care quinine injection. The fast efficacy and less mortality show that current artemisinins have great advantage over other antimalarials in ACTs for uncomplicated malaria and in sequential therapy of AS injection for severe and complicated malaria.

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“…[12][13][14] More recent trials have used intravenous AS with a more favorable pharmacokinetic profile. 15,16 The SEAQUAMAT trial, a multicenter randomized trial conducted in Bangladesh, Thailand, Myanmar, Indonesia, India, and Vietnam, recently reported a 34.7% reduction in all-cause mortality associated with intravenous AS compared with intravenous quinine.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic Profiles of Artesunate After Single Intravenous Doses at 0.5, 1, 2, 4, and 8 mg/kg in Healthy Volunteers: A Phase I Study

Cantilena²,

Leary³

et al. 2009

The American Journal of Tropical Medicine and Hygiene

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Abstract. The pharmacokinetics of good manufacturing process injection of artesunate (AS) were evaluated after single doses at 0.5, 1, 2, 4, and 8 mg/kg with a 2-minute infusion in 40 healthy subjects. Drug concentrations were analyzed by validated liquid chromatography and mass spectrometry system (LC-MS/MS) procedures. The drug was immediately converted to dihydroartemisinin (DHA), with elimination half-lives ranging 0.12-0.24 and 1.15-2.37 hours for AS and DHA, respectively. Pharmacokinetic model-dependent analysis is suitable for AS, whereas DHA fits both model-dependent and -independent methods. Although DHA concentration was superior to that of AS with a 1.12-1.87 ratio of area under the curve (AUC) DHA/AS , peak concentration of AS was much higher than that of DHA, with a 2.80-to 4.51-fold ratio of peak concentration (C max AS/DHA ). Therefore, AS effectiveness has been attributed not only to its rapid hydrolysis to DHA, but also to itself high initial C max .

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Treating severe malaria

Cited by 6 publications

References 13 publications

Knowledge and acceptability of the rectal treatment route in Laos and its application for pre-referral emergency malaria treatment

Knowledge and acceptability of the rectal treatment route in Laos and its application for pre-referral emergency malaria treatment

Pharmacokinetic and Pharmacodynamic Profiles of Rapid-Acting Artemisinins in the Antimalarial Therapy

Pharmacokinetic Profiles of Artesunate After Single Intravenous Doses at 0.5, 1, 2, 4, and 8 mg/kg in Healthy Volunteers: A Phase I Study

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