Adjunctive Therapies for Malaria

Higgins, Sarah J.; Elphinstone, Robyn E.; Kain, Kevin C.

doi:10.1007/978-1-4614-8757-9_123-1

Cited by 2 publications

(1 citation statement)

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“…The host immune response plays a central role in the onset, severity and outcome of malaria infections, and this has accelerated the search for immunomodulatory adjunctive therapies that could improve clinical outcome. To date, several putative adjunctive strategies have been tested in severe malaria, however with disappointing results [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

Varo

Crowley

Sitoe

et al. 2017

Malar J

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BackgroundDespite the widespread use and availability of rapidly acting anti-malarials, the fatality rate of severe malaria in sub-Saharan Africa remains high. Adjunctive therapies that target the host response to malaria infection may further decrease mortality over that of anti-malarial agents alone. Peroxisome proliferator-activated receptor-gamma agonists (e.g. rosiglitazone) have been shown to act on several pathways implicated in the pathogenesis of severe malaria and may improve clinical outcome as an adjunctive intervention.MethodsIn this study, the safety and tolerability of adjunctive rosiglitazone in paediatric uncomplicated malaria infection was evaluated in Mozambique, as a prelude to its evaluation in a randomized controlled trial in paediatric severe malaria. The study was a prospective, randomized, double-blind, placebo-controlled, phase IIa trial of rosiglitazone (0.045 mg/kg/dose) twice daily for 4 days versus placebo as adjunctive treatment in addition to Mozambican standard of care (artemisinin combination therapy Coartem®) in children with uncomplicated malaria. The primary outcomes were tolerability and safety, including clinical, haematological, biochemical, and electrocardiographic evaluations.ResultsThirty children were enrolled: 20 were assigned to rosiglitazone and 10 to placebo. Rosiglitazone treatment did not induce hypoglycaemia nor significantly alter clinical, biochemical, haematological, or electrocardiographic parameters.ConclusionsAdjunctive rosiglitazone was safe and well-tolerated in children with uncomplicated malaria, permitting the extension of its evaluation as adjunctive therapy for severe malaria.The trial is registered with Clinicaltrials.gov, NCT02694874

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Section: Introductionmentioning

confidence: 99%

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

Varo

Crowley

Sitoe

et al. 2017

Malar J

Self Cite

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New developments in anti-malarial target candidate and product profiles

Burrows

Duparc

Gutteridge

et al. 2017

Malar J

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A decade of discovery and development of new anti-malarial medicines has led to a renewed focus on malaria elimination and eradication. Changes in the way new anti-malarial drugs are discovered and developed have led to a dramatic increase in the number and diversity of new molecules presently in pre-clinical and early clinical development. The twin challenges faced can be summarized by multi-drug resistant malaria from the Greater Mekong Sub-region, and the need to provide simplified medicines. This review lists changes in anti-malarial target candidate and target product profiles over the last 4 years. As well as new medicines to treat disease and prevent transmission, there has been increased focus on the longer term goal of finding new medicines for chemoprotection, potentially with long-acting molecules, or parenteral formulations. Other gaps in the malaria armamentarium, such as drugs to treat severe malaria and endectocides (that kill mosquitoes which feed on people who have taken the drug), are defined here. Ultimately the elimination of malaria requires medicines that are safe and well-tolerated to be used in vulnerable populations: in pregnancy, especially the first trimester, and in those suffering from malnutrition or co-infection with other pathogens. These updates reflect the maturing of an understanding of the key challenges in producing the next generation of medicines to control, eliminate and ultimately eradicate malaria.

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Adjunctive Therapies for Malaria

Cited by 2 publications

References 57 publications

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria

New developments in anti-malarial target candidate and product profiles

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