The effect of mefloquine-artemether compared with quinine on patients with complicated falciparum malaria

Shwe, Tin; Myint, Pe Than; Htut, Ye; Myint, Win; Soe, Lin

doi:10.1016/0035-9203(88)90187-3

Cited by 33 publications

(7 citation statements)

References 2 publications

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“…Drugs for chloroquine-resistant malaria are quinine, sulfadoxine-pyrimethamine combination, mefloquine, artesunate and its derivatives, halfantrine and certain antibiotics. [21] This is a hospital based study representing only tip of iceberg of the patients of malaria in community. This study was done in admitted patients in the tertiary care center.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological profile of malaria in Bareilly

Mittra¹,

Pandey²

2017

Int J Med Sci Public Health

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Section: Discussionmentioning

confidence: 99%

Clinicopathological profile of malaria in Bareilly

Mittra¹,

Pandey²

2017

Int J Med Sci Public Health

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“…This could be due to thick blood films for asexual parasitaemia being taken every 12 hours, whereas other studies took them every four hours, every six hours, and then every 12 hours. The accuracy of parasite clearance has been shown to improve with frequent (four to six hourly) measurement of parasitaemia 11 – 13. The parasite clearance time after oral, intramuscular, or rectal artemether is shorter in patients with uncomplicated malaria than in those with complicated malaria 14…”

Section: Discussionmentioning

confidence: 99%

“…The reason for the lower death rate with artemether is not clear. Several trials in south east Asian adults with severe malaria indicated that treatment with artemesinin derivatives might halve mortality 12 13…”

Section: Discussionmentioning

confidence: 99%

Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial

Aceng¹,

Byarugaba²,

Tumwine³

2005

BMJ

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Objective To compare the efficacy and safety of rectal artemether with intravenous quinine in the treatment of cerebral malaria in children. Design Randomised, single blind, clinical trial. Setting Acute care unit at Mulago Hospital, Uganda's national referral and teaching hospital in Kampala. Participants 103 children aged 6 months to 5 years with cerebral malaria. Intervention Patients were randomised to either intravenous quinine or rectal artemether for seven days. Main outcome measures Time to clearance of parasites and fever; time to regaining consciousness, starting oral intake, and sitting unaided; and adverse effects. Results The difference in parasitological and clinical outcomes between rectal artemether and intravenous quinine did not reach significance (parasite clearance time 54.2 (SD 33.6) hours v 55.0 (SD 24.3) hours, P = 0.90; fever clearance time 33.2 (SD 21.9) hours v 24.1(SD 18.9 hours, P = 0.08; time to regaining consciousness 30.1 (SD 24.1) hours v 22.67 (SD 18.5) hours, P = 0.10; time to starting oral intake 37.9 (SD 27.0) hours v 30.3 (SD 21.1) hours, P = 0.14). Mortality was higher in the quinine group than in the artemether group (10/52 v 6/51; relative risk 1.29, 95% confidence interval 0.84 to 2.01). No serious immediate adverse effects occurred. Conclusion Rectal artemether is effective and well tolerated and could be used as treatment for cerebral malaria.

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“…Parasite clearance times, fever reduction times, and coma resolution times in general are improved for patients treated with AM or AS relative to those for patients treated with standard antimalarial treatment regimens (18,21,22,28,29,31,33). Early recrudescence of parasites, however, has necessitated either multidrug chemotherapy or increasingly higher doses of AM and AS (22).…”

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confidence: 99%

Neurotoxicity of artemisinin analogs in vitro

Wesche

DeCoster

Tortella

et al. 1994

Antimicrob Agents Chemother

109

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The sesquiterpene endoperoxide antimalarial agents arteether and artemether have been reported to cause neurotoxicity with a discrete distribution in the brain stems of rats and dogs after multiple doses. The nature and distribution of the brain lesions suggest a specific neuronal target, the identity of which is unknown. In order to further investigate artemisinin analog-induced neurotoxicity, we evaluated several in vitro models: fetal rat primary neuronal cultures, fetal rat secondary astrocyte cultures, and transformed neuronal cultures (rat-derived neuroblastoma NG108-15 and mouse-derived neuroblastoma Neuro-2a). Results indicate that toxicity was specific for neuronal cell types but not glial cells. Neurotoxicity, as indexed by liberation of lactate dehydrogenase and/or inhibition of radiolabelled-leucine uptake, was seen in all three neuronal culture types, implicating a common target. In vitro neurotoxicity was dose and time dependent. Acute exposure to drug results in delayed, but not immediate, manifestations of cell toxicity. Structure-activity comparisons indicate that substitutions at positions 9 and 10 and stereoisomerism at position 10 of the artemisinin backbone influence the degree of toxicity. The endoperoxide is necessary but not sufficient for toxicity. Sodium artesunate and dihydroartemisinin, a metabolite common to all artemisinin analogs currently being developed for clinical use, are the most potent of all analogs tested. These results are consistent with a specific neuronal target, but the identity of the target(s) remains unknown.Artemisinin (qinghaosu) (QHS) is a sesquiterpene lactone endoperoxide isolated from Artemisia annua, an herb used traditionally in China for the treatment of fevers (19). Semisynthetic analogs of QHS, such as artemether (AM), arteether, sodium artesunate (AS), and sodium artelinate (AL), are approximately equipotent in vitro and are currently being considered for development as potent rapidly acting schizonticides for use in treatment of severe malaria in regions where strains of chloroquine-and multidrug-resistant Plasmodium falciparum prevail (19,27 derivatives (4-6). Dogs given high doses of arteether displayed a progressive syndrome of clinical neurological defects with terminal cardiorespiratory collapse and death. The selective discrete distribution of neuronal necrosis in brain stems of both rats and dogs treated with multiple doses of AM and arteether is consistent with a specific neuronal target. It is unclear, however, whether the neuronal injury is a result of drug (or metabolite) interaction with membrane-bound neurotransmitter receptors, intracellular enzymes, or intracellular organelles. The purpose of the present study was to evaluate the neurotoxicity of QHS analogs and related compounds in vitro: to determine whether the toxicity is specific for neurons; to identify initial structure-activity relationships within the QHS drug group; and to establish a rapid, reliable, quantitatively reproducible in vitro model as a tool to investigate neuronal ...

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The effect of mefloquine-artemether compared with quinine on patients with complicated falciparum malaria

Cited by 33 publications

References 2 publications

Clinicopathological profile of malaria in Bareilly

Clinicopathological profile of malaria in Bareilly

Rectal artemether versus intravenous quinine for the treatment of cerebral malaria in children in Uganda: randomised clinical trial

Neurotoxicity of artemisinin analogs in vitro

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