Artemisinin derivatives versus quinine for cerebral malaria in African children: a systematic review

Kyu, Hmwe Hmwe; Fernández, Eduardo

doi:10.2471/blt.08.060327

Cited by 38 publications

(29 citation statements)

References 17 publications

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“…Individual parameter value ϭ population average ϫ ͩ 1 ϩ effect ϫ individual covariate value median covariate value ͪ (2) and for power relationships:…”

Section: Methodsmentioning

confidence: 99%

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Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Salman

Bendel²,

Lee

et al. 2015

Antimicrob Agents Chemother

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A lthough parenteral artesunate is the recommended initial treatment for severe malaria (1), intramuscular (i.m.) artemether is an acceptable and practical alternative (1, 2). Artemether is also a recommended first-line oral therapy in combination with the longer half-life partner drug lumefantrine for uncomplicated Plasmodium falciparum (3) and Plasmodium vivax (4) infections. There are, however, few detailed studies assessing the pharmacokinetics of artemether and its active metabolite dihydroartemisinin (DHA) in either of these settings in children.Artemether-lumefantrine is a safe and effective treatment for uncomplicated pediatric malaria (3, 4), but there is evidence of significant between-dose variability in absorption even when coadministered with a small amount of fat to improve bioavailability (5). In addition, the nausea and vomiting that are frequently associated with malaria, together with an unwell child's refusal to feed or take medications by mouth (6), can reduce the effectiveness of oral treatment through reduced adherence to the World Health Organization (WHO) recommended 3-day regimen (7). In cases of more severe malaria, there is evidence of substantial between-patient variability in the absorption of i.m. artemether (8, 9), with some acidotic children likely exposed to subtherapeutic concentrations when the recommended doses are given (9). Rectal artesunate administration is associated with more rapid absorption and initial parasite clearance than is i.m. artemether administration in severely ill children (8). However, there is also marked between-patient variability in the dispositions of artesunate and DHA, and there is evidence that some children are able to expel artesunate suppositories even in the context of close monitoring as part of a formal pharmacokinetic evaluation (10). This might help explain why artesunate suppositories do not improve mortality compared to that with a placebo in older relative to younger pediatric age groups (11).There is a clear need for a prereferral formulation of an artemisinin derivative that can be easily administered and adequately absorbed in a child who may be unconscious or uncooperative or in whom nausea and vomiting preclude oral dosing. ArTiMist (Essential Nutrition Ltd., Brough, England) is an artemether formulation in neutral oil that can be administered as a metered sublingual spray and which is more rapidly and completely absorbed than is artemether given in tablet form in healthy adult volunteers (see accompanying paper [12]). In the present study, we assessed the pharmacokinetics of ArTiMist in African children with severe malaria or in whom gastrointestinal symptoms prevented the administration of artemether-lumefantrine tablets.

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“…Individual parameter value ϭ population average ϫ ͩ 1 ϩ effect ϫ individual covariate value median covariate value ͪ (2) and for power relationships:…”

Section: Methodsmentioning

confidence: 99%

“…artemether is an acceptable and practical alternative (1,2). Artemether is also a recommended first-line oral therapy in combination with the longer half-life partner drug lumefantrine for uncomplicated Plasmodium falciparum (3) and Plasmodium vivax (4) infections.…”

mentioning

confidence: 99%

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Salman

Bendel²,

Lee

et al. 2015

Antimicrob Agents Chemother

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“…1 Patients presenting with signs of severe malaria have a mortality of approximately 20%. 2 Case management of these critically ill children requires intensive medical and nursing care, life support technologies, and laboratory support to guide clinical decision-making. However, because of resource and technological limitations in many hospitals in sub-Saharan Africa, patients are often managed with minimal laboratory guidance.…”

mentioning

confidence: 99%

Performance of Point-of-Care Diagnostics for Glucose, Lactate, and Hemoglobin in the Management of Severe Malaria in a Resource-Constrained Hospital in Uganda

Hawkes

Conroy

Opoka

et al. 2014

The American Society of Tropical Medicine and Hygiene

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Abstract. Severe malaria is frequently managed without access to laboratory testing. We report on the performance of point-of-care tests used to guide the management of a cohort of 179 children with severe malaria in a resource-limited Ugandan hospital. Correlation coefficients between paired measurements for glucose (i-STAT and One Touch Ultra), lactate (i-STAT and Lactate Scout), and hemoglobin (Hb; laboratory and i-STAT) were 0.86, 0.85, and 0.73, respectively. The OneTouch Ultra glucometer readings deviated systematically from the i-STAT values by +1.7 mmol/L. Lactate Scout values were systematically higher than i-STAT by +0.86 mmol/L. Lactate measurements from either device predicted subsequent mortality. Hb estimation by the i-STAT instrument was unbiased, with upper and lower limits of agreement of −34 and +34 g/L, and it was 91% sensitive and 89% specific for the diagnosis of severe anemia (Hb 50 g/L). New commercially available bedside diagnostic tools, although imperfect, may expedite clinical decision-making in the management of critically ill children in resource-constrained settings.

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“…With activity during a wider spectrum of the parasite life cycle, artemisinin derivatives clear parasites more rapidly than cinchona alkaloids. There are fewer side effects of artemisinin derivatives compared with quinine and quinidine [39].…”

Section: Treatment Antimalarialsmentioning

confidence: 99%

“…A meta-ana lysis of randomized controlled trials comparing arteminisin derivatives and cinchona alkaloids in the treatment of pediatric CM showed no differences in mortality or neurologic outcomes [39]. A subsequent multisite open-label study of artesunate versus quinine in over 5400 African children with severe malaria (including but not confined to CM) showed a significant decrease in mortality in those treated with artesunate (odds ratio: -0.75; 95% CI: -0.63 to -0.90) [40].…”

Section: Treatment Antimalarialsmentioning

confidence: 99%

Pediatric Cerebral Malaria: A Scourge of Africa

et al. 2012

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Cerebral malaria, defined as an otherwise unexplained coma in a patient with Plasmodium falciparum parasitemia, affects up to 1 million people per year, the vast majority of them being children living in sub-Saharan Africa. Despite optimal treatment, this condition kills 15% of those affected and leaves 30% of survivors with neurologic sequelae. The clinical diagnosis is hampered by its poor specificity, but the presence or absence of a malarial retinopathy in cerebral malaria has proven to be important in the differentiation of underlying coma etiology. Both antimalarials and intense supportive care are necessary for optimal treatment. As of yet, clinical trials of adjunctive therapies have not improved the high rates of mortality and morbidity. Survivors are at high risk of neurologic sequelae including epilepsy, neurodisabilities and cognitive–behavioral problems. The neuroanatomic and functional bases of these sequelae are being elucidated. Although adjunctive therapy trials continue, the best hope for African children may lie in disease prevention. Strategies include bednets, chemoprophylaxis and vaccine development.

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Artemisinin derivatives versus quinine for cerebral malaria in African children: a systematic review

Cited by 38 publications

References 17 publications

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Pharmacokinetics of a Novel Sublingual Spray Formulation of the Antimalarial Drug Artemether in African Children with Malaria

Performance of Point-of-Care Diagnostics for Glucose, Lactate, and Hemoglobin in the Management of Severe Malaria in a Resource-Constrained Hospital in Uganda

Pediatric Cerebral Malaria: A Scourge of Africa

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