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cerebral malaria

NOT Open Access | Sequential dysregulated plasma levels of angiopoietins (ANG-2 and ratios of ANG-2/ANG-1) are associated with malaria severity and mortality among hospital admitted cases in South Bastar Region of Chhattisgarh, Central India

July 28, 2021 - 14:36 -- NOT Open Access
Jain V, Thomas T, Basak S, Sharma RK, Singh N
Pathog Glob Health. 2021 Jul 26:1-12

Cerebral malaria (CM) is one of the most severe forms of P. falciparum infection, with an associated high case-fatality rate. Angiopoietins (ANG-1 and ANG-2) are important biomarkers of endothelial activation and dysfunction. This study was carried out in Maharani Hospital and associated Medical College, Jagdalpur, CG, Central India from 2010 to 2014. Based on the treatment recovery patterns, cases (n = 65) were classified as mild malaria with rapid recovery (MM-RR), n= 14; non-cerebral severe malaria with moderately fast recovery (NCSM-MFR), n= 9; CM survivors with slow recovery (CMS-SR), n= 36 and deteriorated CM non-survivors (Det-CMNS), n= 6.

NOT Open Access | Artesunate and Tetramethylpyrazine Exert Effects on Experimental Cerebral Malaria in a Mechanism of Protein S-Nitrosylation

July 14, 2021 - 09:51 -- NOT Open Access
Zheng Z, Liu H, Wang X, Zhang Y, Qu S, Yang Y, Deng S, Chen L, Zhu X, Li Y
ACS Infect Dis. 2021 Jul 13

Cerebral malaria (CM) is caused by Plasmodium falciparum, resulting in severe sequelae; one of its pathogenic factors is the low bioavailability of nitric oxide (NO). Our previous study suggested that the combination of artesunate (AS) and tetramethylpyrazine (TMP) exerts an adjuvant therapeutic effect on the symptoms of experimental CM (ECM) and that NO regulation plays an important role. In the present study, we further verified the effects of AS+TMP on cerebral blood flow (CBF) and detected NO-related indicators.

The plasma membrane calcium ATPase 4 does not influence parasite levels but partially promotes experimental cerebral malaria during murine blood stage malaria

July 7, 2021 - 08:05 -- Open Access
Ana Villegas-Mendez, Nicholas Stafford, Delvac Oceandy, et al.
Malaria Journal 2021 20:297, 2 July 2021

Recent genome wide analysis studies have identified a strong association between single nucleotide variations within the human ATP2B4 gene and susceptibility to severe malaria. The ATP2B4 gene encodes the plasma membrane calcium ATPase 4 (PMCA4), which is responsible for controlling the physiological level of intracellular calcium in many cell types, including red blood cells (RBCs). It is, therefore, postulated that genetic differences in the activity or expression level of PMCA4 alters intracellular Ca2+ levels and affects RBC hydration, modulating the invasion and growth of the Plasmodium parasite within its target host cell.

NOT Open Access | Intranasal artesunate-loaded nanostructured lipid carriers: A convenient alternative to parenteral formulations for the treatment of severe and cerebral malaria

June 15, 2021 - 15:09 -- NOT Open Access
Agbo CP, Ugwuanyi TC, Ugwuoke WI, McConville C, Attama AA, Ofokansi KC
J Control Release. 2021 Jun 10;334:224-236

Early treatment with parenteral antimalarials is key in preventing deaths and complications associated with severe and cerebral malaria. This can be challenging in 'hard-to-reach' areas in Africa where transit time to hospitals with facilities to administer drugs parenterally can be more than 6 h. Consequently, the World Health Organization has recommended the use of artesunate (ATS) suppositories for emergency treatment of patients, however, this treatment is only for children under 6 years. The intranasal route (INR) can provide a safe and effective alternative to parenteral and rectal routes for patients of all ages; thus, reducing delays to the initiation of treatment.

Whole blood transfusion improves vascular integrity and increases survival in artemether-treated experimental cerebral malaria

June 15, 2021 - 14:27 -- Open Access
Gul S, Ribeiro-Gomes FL, Moreira AS, Sanches GS, Conceição FG, Daniel-Ribeiro CT, Ackerman HC, Carvalho LJM
Sci Rep. 2021 Jun 8;11(1):12077

Pathological features observed in both human and experimental cerebral malaria (ECM) are endothelial dysfunction and changes in blood components. Blood transfusion has been routinely used in patients with severe malarial anemia and can also benefit comatose and acidotic malaria patients. In the present study Plasmodium berghei-infected mice were transfused intraperitoneally with 200 μL of whole blood along with 20 mg/kg of artemether.

NOT Open Access | Monocyte Locomotion Inhibitory Factor confers neuroprotection and prevents the development of murine cerebral malaria

June 1, 2021 - 12:17 -- NOT Open Access
Galán-Salinas A, Corral-Ruíz G, Sánchez-Torres LE, et al.
Int Immunopharmacol. 2021 May 25;97:107674.

Cerebral malaria (CM) is a neurological complication derived from the Plasmodium falciparum infection in humans. The mechanisms involved in the disease progression are still not fully understood, but both the sequestration of infected red blood cells (iRBC) and leukocytes and an exacerbated host inflammatory immune response are significant factors. In this study, we investigated the effect of Monocyte Locomotion Inhibitory Factor (MLIF), an anti-inflammatory peptide, in a well-characterized murine model of CM. Our data showed that the administration of MLIF increased the survival and avoided the neurological signs of CM in Plasmodium berghei ANKA (PbA) infected C57BL/6 mice.

Bioengineered 3D Microvessels for Investigating Plasmodium falciparum Pathogenesis

May 5, 2021 - 11:48 -- Open Access
Bernabeu M, Howard C, Zheng Y, Smith JD
Trends Parasitol. 2021 May;37(5):401-413

Plasmodium falciparum pathogenesis is complex and intimately connected to vascular physiology. This is exemplified by cerebral malaria (CM), a neurovascular complication that accounts for most of the malaria deaths worldwide. P. falciparum sequestration in the brain microvasculature is a hallmark of CM and is not replicated in animal models.

NOT Open Access | Identification of Plasmodium falciparum-specific protein PIESP2 as a novel virulence factor related to cerebral malaria

May 5, 2021 - 11:20 -- NOT Open Access
Liu X, Wu Y, Zhao Y, Huang Y, Xu K, Wang J, Pan S, Liang J
Int J Biol Macromol. 2021 Apr 30;177:535-547

Cerebral malaria (CM) is the most severe complication caused by Plasmodium falciparum infection. The pathophysiological changes caused by parasite virulence factors and the human immune response to parasites contribute to CM. To date, very few parasite virulence proteins have been found to participate in CM. Here, we employed comparative genomics analysis and identified parasite-infected erythrocyte specific protein 2 (PIESP2) to be a CM-related protein. We conducted further experimental investigations and found that PIESP2 is an immunogenic protein.

NOT Open Access | Post-Malaria Anemia Is Rare in Malawian Children with Cerebral Malaria

April 28, 2021 - 14:24 -- NOT Open Access
Guenther G, Saidi AM, Izem R, Seydel K, Postels DG
Am J Trop Med Hyg. 2021 Apr 26:tpmd201668

Artesunate therapy for severe malaria syndromes has been associated with post-treatment hemolysis and anemia. We defined post-malaria anemia as any decrease in hematocrit between the index hospitalization for severe malaria and 1 month after. We determined the incidence and severity of post-malaria anemia in Malawian children surviving cerebral malaria (CM) by analyzing hospital and follow-up data from a long-standing study of CM pathogenesis. Children enrolled before 2014 and treated with quinine (N = 258) were compared with those admitted in 2014 and after, and treated with artesunate (N = 235).

NOT Open Access | Severe stridor and profound weakness after cerebral malaria

April 14, 2021 - 16:40 -- NOT Open Access
Fuller C, Wooldridge G, Liomba A, Ray STJ
BMJ Case Rep. 2021 Apr 13;14(4):e237681

Cerebral malaria (CM) is defined by WHO as coma (Blantyre Coma Score 2 or less) in a patient with Plasmodium falciparum parasitaemia and no alternative cause of coma identified. Mortality is approximately 15%-30% in African children and up to one-third of survivors have neurological sequelae. We present a patient with severe stridor and prolonged profound weakness during an intensive care admission with CM.


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