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The 1996 Runme Shaw Memorial Lecture: malaria--past, present and future

Warrell DA

Ann Acad Med Singap, 1997 May;26(3):380-7.
PMID: 9285035

Falciparum malaria may have infected Homo sapiens (and perhaps H erectus) in the Asia Pacific region for more than 100,000 years. This estimate is based on the gene frequency of alpha-thalassaemia, the protection it affords against falciparum malaria and assumptions of untreated mortality from the infection. Up until the end of the 19th century, there was a high mortality from malaria in the coastal parts of Malaya, but the malaria control campaign, begun in 1901 at Klang, was described by Sir Ronald Ross as the first successful antimalarial work in the (then) British Empire. This was extended to Singapore in 1911. When the Far Eastern Association of Tropical Medicine held its Fifth Biennial Congress in Singapore in 1923, malaria was still a major killing disease in parts of Malaya and Sarawak. The mechanism of life-threatening malaria involves cytoadherence of parasitised erythrocytes in microvascular beds, a process enhanced by the products of macrophage activation induced by malarial pyrogen. Improvements in the chemotherapy of life-threatening falciparum malaria with chloroquine and quinine have been countered by the emergence of resistant strains. Artemisinin derivatives may become the treatment of choice during the coming decade. Apart from traditional anti-mosquito methods, control of malaria now involves the use of insecticide-impregnated bed nets, new entomological strategies, including genetic manipulation of mosquitoes and selective chemoprophylaxis. Antigenic diversity and antigenic variation of the malaria parasite have so far defeated attempts to produce an effective vaccine.

Matched MeSH terms: Malaria, Cerebral/drug therapy; Malaria, Cerebral/history; Malaria, Cerebral/epidemiology; Malaria, Cerebral/prevention & control
Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria

Grau GE, Mackenzie CD, Carr RA, Redard M, Pizzolato G, Allasia C, et al.

J Infect Dis, 2003 Feb 1;187(3):461-6.
PMID: 12552430

The pathogenesis of fatal cerebral malaria (CM) is not well understood, in part because data from patients in whom a clinical diagnosis was established prior to death are rare. In a murine CM model, platelets accumulate in brain microvasculature, and antiplatelet therapy can improve outcome. We determined whether platelets are also found in cerebral vessels in human CM, and we performed immunohistopathology for platelet-specific glycoprotein, GPIIb-IIIa, on tissue from multiple brain sites in Malawian children whose fatal illness was severe malarial anemia, CM, or nonmalarial encephalopathy. Platelets were observed in 3 locations within microvessels: between malaria pigment and leukocytes, associated with malaria pigment, or alone. The mean surface area of platelet staining and the proportion of vessels showing platelet accumulation were significantly higher in patients with CM than in those without it. Platelet accumulation occurs in the microvasculature of patients with CM and may play a role in the pathogenesis of the disease.

Matched MeSH terms: Malaria, Cerebral/blood*; Malaria, Cerebral/mortality
Imported tropical neuroinfections: practice skills and knowledge among nurses and nursing students

Rajoo M, Sulicova A, Mroskova S, Supinova M, Plackova A, Bystra M, et al.

Neuro Endocrinol. Lett., 2013 Sep;34(Suppl 1):45-7.
PMID: 24013609

OBJECTIVE: Tropical neuroinfections are still cause of substantial mortality in travelers. Therefore, good knowledge of early symptoms is very important for nurses acting as first contact persons.
METHODS: Nurse's practical skills and knowledge of signs and early recognition of tropical neuroinfections, providing first aid and quick action has been studied among graduates of two Tropical Nursing PhD programs (in EU-Countries vs. tropical country) using a standardized questionnaire. Statistical package EPI info was used to determine potential differences between both groups of graduates.
RESULTS: Acceptable knowledge on early symptoms and signs of cerebral malaria and meningococcal meningitis in returning travelers was found among 121 graduates of two PhD programs who were included in the study. Of these, 99 questionnaires were filled in Slovakia, Czech Republic and Germany and another 22 were filled in Malaysia, as a part of the Tropical Nursing PhD Study Programs.
CONCLUSION: Nursing students and recent graduates in two PhD programs demonstrated acceptable, although not large-scaled, knowledge of early signs and symptoms of tropical neuroinfections.

Matched MeSH terms: Malaria, Cerebral
Fulltext Neuroleptic malignant syndrome masked by cerebral malaria

Rajesh KM, Sinnathamby V, Sakthi AN

BMJ Case Rep, 2013;2013.
PMID: 23704432 DOI: 10.1136/bcr-2013-009061

A 38-year-old man with an underlying psychiatric illness presented with altered sensorium and abnormal behaviour. He was febrile at 38°C and weak looking; otherwise no other abnormalities were detected. A blood film conducted for malarial parasite (BFMP) revealed Plasmodium falciparum; hence a diagnosis of cerebral malaria was made. He was treated with antimalarial drugs for 2 days prior to being transferred out to the ward following clinical improvement. He subsequently developed episodes of stupor and refusal of feeding. Following an evaluation by the psychiatrist, a diagnosis of catatonic schizophrenia was made and he was started on oral sulpiride and benhexol. Unfortunately, he developed high-grade fever at 40°C with muscle rigidity and fasciculation. The diagnosis of neuroleptic malignant syndrome (NMS) was clinched and the antipsychotics were discontinued. However he succumbed to NMS several days later due to multiorgan failure.

Matched MeSH terms: Malaria, Cerebral/complications*; Malaria, Cerebral/drug therapy; Malaria, Cerebral/microbiology
Fulltext Synthesis, characterization and biological properties of copper(II) and zinc(II) complexes against blood-stage Plasmodium falciparum

Lai, Jing-Wei, Ng, Chew-Hee, Lim, Yvonne Ai-Lian, Mohd Jamil Maah

Malaysian Journal of Medicine and Health Sciences, 2019;15(102):1-1.
MyJurnal

Introduction: The spread of multidrug-resistant malaria parasite – Plasmodium sp. to commercially available antimalarial drugs, i.e. artemisinin-based combination therapies (ACTs) and chloroquine (CQ), has become a global treat to eliminate malaria. To limit the impact of antimalarial drug resistance, a new potent and affordable alternative is urgently needed. A number of metal-based compounds (metallodrugs) have been found active against Plasmodium falciparum, the species that causes potentially fatal cerebral malaria, as they are ease in ligand grafting of multi-functional groups. Ferroquine (FQ) is one of the metalloantimalarial drugs that is currently undergoing clinical trials. Methods: In this study, a series of ternary copper(II) and zinc(II) complexes – Cu(phen)(edda) 1, Zn(phen)(edda) 2, [Cu(phen)(cdmg)] NO3 3 and [Zn(phen)(c-dmg)]NO3 4 were synthesized and characterized by the following tests: Fourier transformed infrared (FTIR), CHN elemental analysis, UV-Vis spectroscopy, molar conductivity and magnetic susceptibility measurements. Results: In vitro hemolytic and antimalarial assays using SYBR Green I dye were done to determine the biological properties of these complexes. Preliminary biological evaluation demonstrated that all the complexes 1, 2, 3 and 4 exhibit toxicity against the sensitive blood-stage Plasmodium falciparum 3D7 with IC50 in μM range. Conclusion: Thus, metal complex is a potentially viable candidate as antimalarial drug to overcome the emergence of drug resistance.

Matched MeSH terms: Malaria, Cerebral
Fulltext Cytokine response during non-cerebral and cerebral malaria: evidence of a failure to control inflammation as a cause of death in African adults

Dieye Y, Mbengue B, Dagamajalu S, Fall MM, Loke MF, Nguer CM, et al.

PeerJ, 2016;4:e1965.
PMID: 27168977 DOI: 10.7717/peerj.1965

Background. With 214 million cases and 438,000 deaths in 2015, malaria remains one of the deadliest infectious diseases in tropical countries. Several species of the protozoan Plasmodium cause malaria. However, almost all the fatalities are due to Plasmodium falciparum, a species responsible for the severest cases including cerebral malaria. Immune response to Plasmodium falciparum infection is mediated by the production of pro-inflammatory cytokines, chemokines and growth factors whose actions are crucial for the control of the parasites. Following this response, the induction of anti-inflammatory immune mediators downregulates the inflammation thus preventing its adverse effects such as damages to various organs and death. Methods. We performed a retrospective, nonprobability sampling study using clinical data and sera samples from patients, mainly adults, suffering of non-cerebral or cerebral malaria in Dakar, Sénégal. Healthy individuals residing in the same area were included as controls. We measured the serum levels of 29 biomarkers including growth factors, chemokines, inflammatory and anti-inflammatory cytokines. Results. We found an induction of both pro- and anti-inflammatory immune mediators during malaria. The levels of pro-inflammatory biomarkers were higher in the cerebral malaria than in the non-cerebral malaria patients. In contrast, the concentrations of anti-inflammatory cytokines were comparable in these two groups or lower in CM patients. Additionally, four pro-inflammatory biomarkers were significantly increased in the deceased of cerebral malaria compared to the survivors. Regarding organ damage, kidney failure was significantly associated with death in adults suffering of cerebral malaria. Conclusions. Our results suggest that a poorly controlled inflammatory response determines a bad outcome in African adults suffering of cerebral malaria.

Matched MeSH terms: Malaria, Cerebral