Adjunctive therapy for cerebral malaria and other severe forms of<i>Plasmodium falciparum</i>malaria

John, Chandy C.; Kutamba, Elizabeth; Mugarura, Keith; Opoka, Robert O.

doi:10.1586/eri.10.90

Cited by 117 publications

(101 citation statements)

References 82 publications

(82 reference statements)

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“…Nanostructured lipid carrier [32] and lipid nanoparticles [61] of artemether have shown improved antimalarial activity in P. berghei model. Peter's four-day suppressive test was performed on AAN at two dose levels viz, 100 and 50% of therapeutic dose of the drug using P. berghei-infected Swiss albino mice.…”

Section: In Vivo Antimalarial Efficacy In P Berghei Infected Micementioning

confidence: 99%

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Sidhaye¹,

Bhuran²,

Zambare³

et al. 2016

Nanomedicine

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Aim: The intra-erythrocytic development of the malarial parasite is dependent on active uptake of nutrients, including human serum albumin (HSA), into parasitized red blood cells (pRBCs). We have designed HSA-based nanoparticles as a potential drug-delivery option for antimalarials. Methods: Artemether-loaded nanoparticles (AAN) were designed and antimalarial activity evaluated in-vitro/in-vivo using Plasmodium falciparum/Plasmodium berghei species, respectively. Results: Selective internalisation of AAN into Plasmodiuminfected RBCs in preference to healthy erythrocytes was observed using confocal-imaging.In-vitro studies showed 50% dose reduction for AAN as compared to drug-only controls to achieve IC50 levels of inhibition. The nanoparticles exhibited 2-fold higher peak drug concentrations in RBCs with antimalarial activity at 50% of therapeutic doses in P.bergeiinfected mice. Conclusion: HSA-based nanoparticles offer safe and effective approach for selective targeting of antimalarial drugs.

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Section: In Vivo Antimalarial Efficacy In P Berghei Infected Micementioning

confidence: 99%

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Sidhaye¹,

Bhuran²,

Zambare³

et al. 2016

Nanomedicine

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“…Further experiments are required to identify which receptors are recognized by P. berghei parasites and discern the specific parasite stages of the intraerythrocytic cycle that bind. Ultimately, this could reveal how parasites use cytoadherence to evade the immune system inside the host, how they contribute to the severity of disease, and how therapies work at interfering with this binding to lessen the global burden of CM (91,92).…”

Section: Discussionmentioning

confidence: 99%

Cytoadherence of Plasmodium berghei-Infected Red Blood Cells to Murine Brain and Lung Microvascular Endothelial CellsIn Vitro

et al. 2013

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dSequestration of infected red blood cells (iRBC) within the cerebral and pulmonary microvasculature is a hallmark of human cerebral malaria (hCM). The interaction between iRBC and the endothelium in hCM has been studied extensively and is linked to the severity of malaria. Experimental CM (eCM) caused by Plasmodium berghei ANKA reproduces most features of hCM, although the sequestration of RBC infected by P. berghei ANKA (PbA-iRBC) has not been completely delineated. The role of PbAiRBC sequestration in the severity of eCM is not well characterized. Using static and flow cytoadherence assays, we provide the first direct in vitro evidence for the binding of PbA-iRBC to murine brain and lung microvascular endothelial cells (MVEC). We found that basal PbA-iRBC cytoadherence to MVECs was significantly higher than that of normal red blood cells (NRBC) and of RBC infected with P. berghei K173 (PbK173-iRBC), a strain that causes noncerebral malaria (NCM). MVEC prestimulation with tumor necrosis factor (TNF) failed to promote any further significant increase in mixed-stage iRBC adherence. Interestingly, enrichment of the blood for mature parasites significantly increased PbA-iRBC binding to the MVECs prestimulated with TNF, while blockade of VCAM-1 reduced this adhesion. Our study provides evidence for the firm, flow-resistant binding to endothelial cells of iRBC from strain ANKA-infected mice, which develop CM, and for less binding of iRBC from strain K173-infected mice, which develop NCM. An understanding of P. berghei cytoadherence may help elucidate the importance of sequestration in the development of CM and aid the development of antibinding therapies to help reduce the burden of this syndrome.

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“…However no single adjunct therapy has yet shown clear efficacy in improving the outcome of treatment of cerebral malaria. 6 There is hope that vitamin A may be of use as in vitro studies have shown that retinol levels corresponding to normal serum levels can suppress growth of Plasmodium falciparum 7 while community based studies have shown significant reduction in malaria episodes in children in whom vitamin A was supplemented. 8 The real immunogenic mechanisms of action of vitamin A is not yet clear.…”

Section: Introductionmentioning

confidence: 99%

Effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mulago hospital: a randomized controlled trial

Mwanga-Amumpaire¹,

Ndeezi²,

Jk³

2012

Af Hlth Sci

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Background: Malaria is a leading cause of mortality in Uganda accounting for 25% of deaths among children. Hitherto no adjunct therapy has been identified to improve outcome of cerebral malaria. Retinol suppresses growth of P.falciparum, scavenges free radicals, and exhibits synergistic action with quinine in parasite clearance. Objective: To determine the effect of vitamin A supplementation on treatment outcome of cerebral malaria Methods: In this randomised double-blind placebo controlled clinical trial we studied 142 children aged 6-59 months admitted with cerebral malaria in Mulago Hospital, Kampala. Children were randomised to either vitamin A or placebo and followed for 7 days. The main outcome measures were coma recovery time, time for convulsions to stop, and parasite and fever clearance. Secondary outcomes were overall mortality and time taken to start oral feeds. Results: There was no difference in the coma recovery time (p=0.44), resolution of convulsions (p=0.37), fever clearance (p=0.92), parasite clearance (p=0.12), and starting oral feeds between the two treatment groups. Mortality was higher (16.2%) in the placebo than in the vitamin A group (8.1%): RR 1.4; 95% CI 1.0-2.1. Conclusions: Vitamin A as adjunct therapy did not significantly reduce coma duration but there were fewer deaths in the vitamin A arm.

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Adjunctive therapy for cerebral malaria and other severe forms ofPlasmodium falciparummalaria

Cited by 117 publications

References 82 publications

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Bio-inspired artemether-loaded human serum albumin nanoparticles for effective control of malaria-infected erythrocytes

Cytoadherence of Plasmodium berghei-Infected Red Blood Cells to Murine Brain and Lung Microvascular Endothelial CellsIn Vitro

Effect of vitamin A adjunct therapy for cerebral malaria in children admitted to Mulago hospital: a randomized controlled trial

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