Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema

Gad, AbdAllah; Ali, Sajjad; Zahoor, Talal; Azarov, Nick

doi:10.4269/ajtmh.17-0794

Cited by 4 publications

(2 citation statements)

References 12 publications

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“…In contrast to these previous results, our data suggest that environmental temperature and ring-stage artemisinin susceptibility in the 3D7 reference parasite line are negatively correlated in vitro (Fig. 1A) (Gad et al, 2018). In the RSA, reduced susceptibility to artemisinin is expressed as enhanced survival following a pulse of 700 nM DHA, compared to known susceptible parasites.…”

Section: Resultscontrasting

confidence: 99%

“…Survivors frequently suffer measurable neurological deficit during convalescence (Mishra and Newton, 2009; Idro et al, 2016). A recent case report suggested the use of controlled hypothermia (32-34 °C) improved the resolution of neurological consequences of cerebral oedema and reduced cranial perfusion, as in other vascular medical emergencies like heart attack and stroke (Gad et al, 2018). Additionally, an in vitro model of mild hypothermia suggested that this treatment may also potentiate certain frontline antimalarials including artemisinin (Rehman et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro

Henrici

Schalkwyk

Sutherland

2019

International Journal for Parasitology: Drugs and Drug Resistan

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Clinical studies suggest that outcomes for hospitalised malaria patients can be improved by managed hypothermia during treatment. We examined the impact of short pulses of low temperature on ring-stage susceptibility of Plasmodium falciparum to artemisinin in vitro. The usually artemisinin-sensitive clone 3D7 exhibited substantially reduced ring-stage susceptibility to a 4-h pulse of 700 nM dihydro-artemisinin administered during a 5-h pulse of low temperature down to 17 °C. Parasite growth through the subsequent asexual cycle was not affected by the temperature pulse. Chloroquine and pyronaridine susceptibility, in a standard 48-h test, was not affected by brief exposures to low temperature. Fever-like temperature pulses up to 40 °C were also accompanied by enhanced ring-stage survival of 700 nM artemisinin pulses, but parasite growth was generally attenuated at this temperature. We discuss these findings in relation to the possible activation of parasite stress responses, including the unfolded protein response, by hypo- or hyper-thermic conditions. Physiological states may need to be considered in artemisinin-treated P. falciparum patients.

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Section: Resultscontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro

Henrici

Schalkwyk

Sutherland

2019

International Journal for Parasitology: Drugs and Drug Resistan

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Protein prenylation and Hsp40 in thermotolerance ofPlasmodium falciparummalaria parasites

Mathews¹,

Jezewski²,

John³

2019

Preprint

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Infection with the protozoan parasite Plasmodium falciparum causes the majority of cases of severe 38 and fatal malaria. P. falciparum must recognize and adapt to dramatic temperature swings, as its 39 complex life cycle requires development in both an invertebrate mosquito vector and the warm-blooded 40 vertebrate human host. Temperature is critical at every stage of the parasite life cycle. In the mosquito 41 vector, many temperature-sensitive factors contribute to human transmission, such as biting rate, 42 vector longevity, parasite development, and vector competence 1 . Human infection begins upon the 43 bloodmeal of a female Anopheles mosquito. Entering the human host, where the normal physiological 44 temperature is 37°C, sporozoite-stage parasites experience heat shock. However, this temperature 45 stress is necessary for efficient hepatocyte infection and the resulting amplification of infection 2,3 . The 46 parasite emerges from the liver to initiate asexual replication within erythrocytes, the clinically 47 symptomatic stage of Plasmodium infection. A pathognomonic feature of falciparum malaria is periodic 48 episodes of fever (to 41°C or more) recurring every 48 hours, corresponding to the synchronous rupture 49 of infected erythrocytes and daughter merozoite release 4 . In contrast, the sexual-stage parasites that 50 return to the mosquito vector are again exposed to cold temperature shock, as the parasite must now 51 re-adjust to approximately 25°C. While temperature fluctuations are an inherent part of the malaria life 52 cycle, how the parasite copes with thermal stress is not well understood. 53 54Temperature also regulates malaria parasite virulence and antimalarial sensitivity. Controlled 55 hypothermia (32°C) has been clinically used to improve outcomes of severe cerebral malaria 5 . In vitro, 56 hypothermia (32°C) inhibits P. falciparum growth, 6 and a similar effect occurs at lower temperatures 57 (28°C) 7 . While the potency of many antimalarials (e.g., chloroquine, mefloquine, and pyronaridine) are 58 unaffected by lower temperatures 6,8 , susceptibility to artemisinin-the backbone of front-line 59 artemisinin-based combination therapies-is modulated by both cold and heat stresses 6,8 . As 60 temperature fluctuations are an inherent part of the P. falciparum life cycle, this common environmental 61 stress may impact the ability of antimalarials to influence essential parasite targets. Rising rates of 62 4 delayed clearance to artemisinin-based combination therapies, including resistance to artemisinin 63 partner drugs, has raised concerns about emerging multi-drug resistance 9-17 . Thus, there is a pressing 64 need to identify essential survival pathways in P. falciparum, such as thermotolerance, in order to 65 support ongoing development of new antimalarial agents. 66 67During intraerythrocytic development, P. falciparum assembles isoprenoids de novo through the 68 methylerythritol 4-phosphate (MEP) pathway 18-20 , localized to the unusual plastidial organelle of the 69 parasite, the apic...

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Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites

Mathews

Jezewski

John

2021

mBio

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Case Report: A Case of Severe Cerebral Malaria Managed with Therapeutic Hypothermia and Other Modalities for Brain Edema

Cited by 4 publications

References 12 publications

Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro

Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro

Protein prenylation and Hsp40 in thermotolerance ofPlasmodium falciparummalaria parasites

Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites

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