Table 2.
Cerebral malaria: emerging therapeutic options.
| Therapeutics | Mode | Observation/mechanism of protection | References | Stage |
|---|---|---|---|---|
| HUMAN CEREBRAL MALARIA | ||||
| Levetiracetam (LVT1) | Single | Treatment of seizures, epilepsy and improves CM outcome in African children | http://www.clinicaltrials.gov/ct2/show/study/NCT01660672 | Clinical trial completed, Oct 2014 |
| Rosiglitazone | AP-partnered | Decreases levels of pro-inflammatory factors (IL-6 and MCP-1); elevates BDNF levels (day 2) and lowers Ang-2/Ang-1 ratio (day 3) | Serghides et al., 2014 | In vivo study |
| EXPERIMENTAL CEREBRAL MALARIA | ||||
| Heme-Oxygenase-1 (HO-1) and carbon monoxide (CO) | Adjunctive | Decreases parasitemia, prevents BBB disruption, brain microvasculature congestion, neuro-inflammation and CD8+ T-cell brain sequestration during ECM | Pamplona et al., 2007 | Experimental |
| Pressurized oxygen (HBO) therapy | Adjunctive | Prevents ECM signs; reduces expression of TNF, IFN-γ and IL-10 mRNA levels and percentage of γδ and αβ CD4+ and CD8+ T cell sequestration, prevents BBB dysfunction | Blanco et al., 2008 | Experimental |
| Thiol Pantethine | Adjunctive | Decreases circulating microparticles and protects BBB integrity | Penet et al., 2008 | Experimental |
| Nimodipine | Artemether-partnered | Prevents vasoconstriction and vascular collapse by inducing vasodilation and enhancing pial blood flow; increases survival | Cabrales et al., 2010 | Experimental |
| Artemisone | CQ-partnered | Prevents mortality at late stages of ECM | Waknine-Grinberg et al., 2010 | Experimental |
| Antioxidant therapy | CQ-partnered | Prevents the development of persistent cognitive damage | Reis et al., 2010 | Experimental |
| Flt3 ligand | Adjunctive | Helps reducing the proportion of CD8-T cells producing IFN-γ and granzyme B; decreases sequestration of PRBC | Tamura et al., 2011 | Experimental |
| Artemether + Artesunate | Combinative | Prevents death at late-stages of ECM; reduces leukocyte accumulation in brain vessels and decreases cerebral vascular inflammation | Clemmer et al., 2011 | Experimental |
| Exogenous Nitric Oxide (NO) | Single | Leads to a decreased expression of ICAM-1 and P-selectin; a lower number of adherent leukocytes and platelets in pial vessels and in venules; a reduced vascular inflammation, and albumin leakage | Zanini et al., 2011 | Experimental |
| Erythropoietin | Single | Reverses the development of ECM and degree of neural hypoxia; reduces clinical signs of CM and cerebral pathology features | Hempel et al., 2011, 2012 | Experimental |
| HJP-272 | Artemether-partnered | Decreases brain hemorrhage and increases survival | Dai et al., 2012 | Experimental |
| IDR-peptide | Adjunctive | Enhances mice survival in late stage interventions through anti-inflammatory networks | Achtman et al., 2012 | Experimental |
| Atorvastatin | Adjunctive | Prevents parasite cytoadherence and endothelial damage; enhances the pharmacologic inhibition of CXCL10 and a reduction in mortality | Taoufiq et al., 2011; Wilson et al., 2011 | Experimental |
| Rosiglitazone | Adjunctive | As an agonist of Peroxisome proliferator-activated receptor-γ (PPAR-γ), modulates host inflammatory responses and improves clinical outcome in ECM; prevents the development of brain atrophy and neurocognitive impairment | Serghides et al., 2009, 2014 | Experimental |
| Neuregulin-1 (NRG-1) | Single; Compared with Artemether | Leads to endothelial protection and reduction in BBB permeability; neuro-protective nature, decreases mortality | Li et al., 2012; Lok et al., 2012; Solomon et al., 2014 | Experimental |
| Citicoline (CTC) | Adjunctive | CTC reduces the production of microparticles in vitro; confers protection against ECM | El-Assaad et al., 2014a | Experimental |
BBB, blood-brain barrier; ECM, experimental CM; IDR-peptide, innate defense regulatory peptide; CQ, Chloroquine; AP, Atovaquone–Proguanil; BDNF, brain-derived neurotrophic factor.