Rectal versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria in Kampala, Uganda: A Randomized, Double-Blind Clinical Trial

Achan, Jane; Byarugaba, Justus; Hubert, Bernard; Tumwine, James

doi:10.1086/522972

Cited by 24 publications

(22 citation statements)

References 21 publications

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“…A recent survey in Uganda found that rectal artemisinins were available in only 5% of the health facilities despite the fact that this is the recommended pre-referral drug [78]. A feasible alternative is rectal quinine, which has been found to have comparable efficacy with intravenous quinine in the management of severe malaria in children [79-84] (Table 2) and could play a more significant role than currently acknowledged as pre-referral treatment for severe malaria. More recent studies in Senegal and Mali provide additional support for the efficacy and feasibility of this route and also show that a pre-referral kit of rectal quinine was acceptable to both caretakers and health workers [85,86].…”

Section: Quinine In the Management Of Severe Malariamentioning

confidence: 99%

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Achan

Talisuna

Erhart

et al. 2011

Malar J

792

466

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Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

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Section: Quinine In the Management Of Severe Malariamentioning

confidence: 99%

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Achan

Talisuna

Erhart

et al. 2011

Malar J

792

466

View full text Add to dashboard Cite

show abstract

“…Despite this widespread use, data on quinine efficacy are limited. Two previous studies conducted in pediatric populations provide evidence of good efficacy in the management of cerebral malaria (Aceng et al, 2005; Achan et al, 2007). However, in another recent Ugandan study, 23% of children with uncomplicated malaria experienced genotype-corrected recrudescence within 28 days after quinine treatment, compared to no failures after AL treatment (Achan et al, 2009).…”

Section: Malaria Control In Ugandamentioning

confidence: 99%

“…Intramuscular administration may also be utilized, but is associated with complications including sterile abscess formation and sciatic nerve paralysis. Another option is rectal administration, which has shown good efficacy (Achan et al, 2007). Due to limitations in administration, length of treatment, tolerability, and efficacy, replacements for quinine for the treatment of severe malaria are of interest.…”

Section: Malaria Control In Ugandamentioning

confidence: 99%

Malaria in Uganda: Challenges to control on the long road to elimination

Yeka¹,

Gasasira²,

Mpimbaza³

et al. 2012

Acta Tropica

196

208

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Malaria remains one of the leading health problems of the developing world, and Uganda bears a particularly large burden from the disease. Our understanding is limited by a lack of reliable data, but it is clear that the prevalence of malaria infection, incidence of disease, and mortality from severe malaria all remain very high. Uganda has made progress in implementing key malaria control measures, in particular distribution of insecticide impregnated bednets, indoor residual spraying of insecticides, utilization of artemisinin-based combination therapy to treat uncomplicated malaria, and provision of intermittent preventive therapy for pregnant women. However, despite enthusiasm regarding the potential for the elimination of malaria in other areas, there is no convincing evidence that the burden of malaria has decreased in Uganda in recent years. Major challenges to malaria control in Uganda include very high malaria transmission intensity, inadequate health care resources, a weak health system, inadequate understanding of malaria epidemiology and the impact of control interventions, increasing resistance of parasites to drugs and of mosquitoes to insecticides, inappropriate case management, inadequate utilization of drugs to prevent malaria, and inadequate epidemic preparedness and response. Despite these challenges, prospects for the control of malaria have improved, and with attention to underlying challenges, progress toward the control of malaria in Uganda can be expected.

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“…Despite the associated adverse effects, quinine is still second-line treatment regimen and a drug of choice for severe malaria in Uganda. 18 Most of the quinine regimens recommended by various countries provide plasma concentrations ranging between 3.5 and 10.0 mg/mL, 17 concentrations favorable for cinchonism. Inadequate treatment with quinine, in most cases, results from fear for quinine toxicity, and nonadherence is one of the major causes for emergency of parasite resistance to the drug.…”

Section: Introductionmentioning

confidence: 99%

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

Mukonzo¹,

Waako²,

Ogwal-Okeng³

et al. 2010

Therapeutic Drug Monitoring

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Quinine is one of the most effective antimalarial drugs, although its clinical use is limited as a result of its narrow safety margin. Quinine is a substrate of the polymorphic p-glycoprotein and CYP3A4/3A5. This study aimed to examine the effects of genetic variations in ABCB1 and CYP3A5 genes, sex, demographic, and biochemical variables (serum albumin, creatinine, alanine aminotransferase and albumin) on quinine disposition among Ugandans. Quinine (600 mg) was orally administered to 140 healthy volunteers. Quinine and its metabolite 3-hydroxyquinine concentrations were determined from 16-hour postdose plasma by high-performance liquid chromatography. CYP3A5 activity was measured using quinine/3-hydroxyquinine ratio (metabolic ratio). Genotyping for a total of 20 single nucleotide polymorphisms in ABCB1 (n = 13) and CYP3A5 (n = 7) was done using Taqman and minisequencing on microarray. There were 20.5- and 13-fold variations in body weight-adjusted plasma quinine concentrations (mean +/- standard deviation, 5.26 +/- 2.5 mumol/L; range, 0.88-18.10 mumol/L) and quinine-to-3-hydroxyquinine metabolic ratio (mean +/- standard deviation, 7.68 +/- 3.3 mumol/L; range, 1.66-22.3 mumol/L), respectively. Weight-adjusted plasma quinine concentration was significantly influenced by sex and ABCB1 haplotype. There was a significant sex difference in quinine metabolic ratio, women being faster metabolizers than men (P = 0.01). CYP3A5 genotype/haplotype significantly (P = 0.03) influenced quinine disposition with a clear CYP3A5*1 gene dose effect. The result confirms that quinine disposition is influenced mainly by sex as well as by ABCB1 and CYP3A5 genotypes. Despite being fast metabolizers, women display higher quinine bioavailability than men in Uganda. This may have clinical significance in determining an individual's susceptibility to quinine-associated adverse reactions such as cinchonism.

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Rectal versus Intravenous Quinine for the Treatment of Childhood Cerebral Malaria in Kampala, Uganda: A Randomized, Double-Blind Clinical Trial

Cited by 24 publications

References 21 publications

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Malaria in Uganda: Challenges to control on the long road to elimination

Genetic Variations in ABCB1 and CYP3A5 as well as Sex Influence Quinine Disposition Among Ugandans

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