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cerebral malaria

NOT Open Access | CD8+ T cells and human cerebral malaria: a shifting episteme

February 22, 2020 - 17:18 -- NOT Open Access
Rénia L, Grau GE, Wassmer SC
J Clin Invest. 2020 Feb 17. pii: 135510

Mosquito-transmitted Plasmodium falciparum infection can cause human cerebral malaria (HCM) with high mortality rates. The abundance of infected red blood cells that accumulate in the cerebral vasculature of patients has led to the belief that these brain-sequestered cells solely cause pathogenesis. However, animal models suggest that CD8+ T cells migrate to and accumulate in the brain, directly contributing to experimental cerebral malaria (ECM) mortality. In this issue of the JCI, Riggle et al. explored the brain vasculature from 34 children who died from HCM or other causes and frequently found CD3+ CD8+ T cells in contact with endothelial cells.

EphA2 contributes to disruption of the blood-brain barrier in cerebral malaria

February 10, 2020 - 15:54 -- Open Access
Thayer K. Darling, Patrice N. Mimche, Christian Bray, Banlanjo Umaru, Lauren M. Brady, Colleen Stone, Carole Else Eboumbou Moukoko, Thomas E. Lane, Lawrence S. Ayong, Tracey J. Lamb
PLoS Pathog 16(1):e1008261

Disruption of blood-brain barrier (BBB) function is a key feature of cerebral malaria. Increased barrier permeability occurs due to disassembly of tight and adherens junctions between endothelial cells, yet the mechanisms governing junction disassembly and vascular permeability during cerebral malaria remain poorly characterized. We found that EphA2 is a principal receptor tyrosine kinase mediating BBB breakdown during Plasmodium infection.

NOT Open Access | ZBTB7B (ThPOK) Is Required for Pathogenesis of Cerebral Malaria and Protection against Pulmonary Tuberculosis

January 27, 2020 - 13:49 -- NOT Open Access
James M. Kennedy, Anna Georges, Philippe Gros, et al.
Infect. Immun. January 2020 88:e00845-19

We used a genome-wide screen in N-ethyl-N-nitrosourea (ENU)-mutagenized mice to identify genes in which recessive loss-of-function mutations protect against pathological neuroinflammation. We identified an R367Q mutation in the ZBTB7B (ThPOK) protein in which homozygosity causes protection against experimental cerebral malaria (ECM) caused by infection with Plasmodium berghei ANKA. Zbtb7bR367Q homozygous mice show a defect in the lymphoid compartment expressed as severe reduction in the number of single-positive CD4 T cells in the thymus and in the periphery, reduced brain infiltration of proinflammatory leukocytes in P. berghei ANKA-infected mice, and reduced production of proinflammatory cytokines by primary T cells ex vivo and in vivo.

NOT Open Access | Desperately Seeking Therapies for Cerebral Malaria

January 20, 2020 - 16:28 -- NOT Open Access
Riggle BA, Miller LH, Pierce SK
J Immunol January 15, 2020, 204 (2) 327-334

Malaria is a deadly infectious disease caused by parasites of the Plasmodium spp. that takes an estimated 435,000 lives each year, primarily among young African children. For most children, malaria is a febrile illness that resolves with time, but in ∼1% of cases, for reasons we do not understand, malaria becomes severe and life threatening. Cerebral malaria (CM) is the most common form of severe malaria, accounting for the vast majority of childhood deaths from malaria despite highly effective antiparasite chemotherapy.

CD8+ T cells target cerebrovasculature in children with cerebral malaria

December 16, 2019 - 16:57 -- Open Access
Riggle BA, Manglani M, Pierce SK, et al.
J Clin Invest. 2019 Dec 10, pii: 133474

Cerebral malaria (CM) accounts for nearly 400,000 deaths annually inAfrican children. Current dogma suggests that CM results from infected RBC (iRBC)sequestration in the brain microvasculature and resulting sequelae. Therapies targetingthese events have been unsuccessful; findings in experimental models suggest that CD8+ Tcells drive disease pathogenesis. However, these data have largely been ignored becausecorroborating evidence in humans is lacking. This work fills a critical gap in ourunderstanding of CM pathogenesis that is impeding development of therapeutics.

A clinical trial of enteral Levetiracetam for acute seizures in pediatric cerebral malaria

November 7, 2019 - 21:12 -- Open Access
Birbeck GL, Herman ST, Capparelli EV, Dzinjalamala FK, Abdel Baki SG, Mallewa M, Toto NM, Postels DG, Gardiner JC, Taylor TE, Seydel KB
BMC Pediatr. 2019 Nov 1;19(1):399


Acute seizures are common in pediatric cerebral malaria (CM), but usual care with phenobarbital risks respiratory suppression. We undertook studies of enteral levetiracetam (eLVT) to evaluate pharmacokinetics (PK), safety and efficacy including an open-label, randomized controlled trial (RCT) comparing eLVT to phenobarbital.

Medical Condition: 

NOT Open Access | Fenozyme Protects the Integrity of Blood Brain Barrier against Experimental Cerebral Malaria

November 7, 2019 - 20:48 -- NOT Open Access
Zhao S, Duan H, Yang Y, Yan X, Fan K
Nano Lett. 2019 Nov 1 [Epub ahead of print]

Cerebral malaria is a lethal complication of malaria infection characterized by central nervous system dysfunction and is often not effectively treated by antimalarial combination therapies. It has been shown that the sequestration of the parasite-infected red blood cells that interact with cerebral vessel endothelial cells and the damage of the blood-brain barrier (BBB) play critical roles in the pathogenesis.

Medical Condition: 

Plasmodium vivax cerebral malaria in an adult patient in Sudan

September 23, 2019 - 14:18 -- Open Access
Maowia M. Mukhtar, Omer A. Eisawi, Seth A. Amanfo, Elwaleed M. Elamin, Zeinab S. Imam, Faiza M. Osman and Manasik E. Hamed
Malaria Journal 2019 18:316, 18 September 2019

Plasmodium vivax infection is rising in sub-Saharan Africa, where Plasmodium falciparum is responsible for more than 90% of malaria cases. While P. vivax is identified as a major cause of severe and cerebral malaria in South east Asia, the Pacific and South America, most of the severe and cerebral cases in Africa were attributed to P. falciparum. Cases of severe malaria due to P. vivax are emerging in Africa. A few severe P. vivax cases were reported in Eastern Sudan and they were underestimated due to the lack of accurate diagnosis, low parasitaemia and seldom use of rapid diagnostic tests (RDTs).

Medical Treatment: 

Blood brain barrier disruption in cerebral malaria: Beyond endothelial cell activation

July 16, 2019 - 16:18 -- Open Access
Arnulfo Tunon-Ortiz, Tracey J. Lamb
PLoS Pathog 15(6): e1007786

Breakdown of the blood brain barrier (BBB) is a feature of cerebral malaria (CM), a manifestation of infection with Plasmodium falciparum parasites that currently has a 20% fatality rate and disproportionately affects children under 5 years old.

Not Open Access | γδ-T cells promote IFN-γ–dependent Plasmodium pathogenesis upon liver-stage infection

May 20, 2019 - 14:31 -- NOT Open Access
Julie C. Ribot, Rita Neres, Ana Pamplona, et al.
PNAS May 14, 2019 116 (20) 9979-9988

Cerebral malaria (CM) is a major cause of death due to Plasmodium infection.


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