Effect of Low Temperature On the In Vitro Growth of <i>Plasmodium falciparum</i>

Rojas, Mauricio; Wasserman, Moisés

doi:10.1111/j.1550-7408.1993.tb04895.x

Cited by 22 publications

(15 citation statements)

References 19 publications

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“…ajtmh.org. 11,12 During that trial, hypothermia had no negative impact on the activity of the antimalarial drugs, namely, chloroquine, mefloquine, and artemisinin derivatives. On the other hand, other reports suggest that hyperthermia would also inhibit plasmodial growth, 13 yet the use of hyperthermia would worsen brain edema and accelerate neurological damage.…”

Section: Discussionmentioning

confidence: 98%

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

Gad

Ali

Zahoor

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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Malarial infections are uncommon in the United States and almost all reported cases stem from recent travelers coming from endemic countries. Cerebral malaria (CM) is a severe form of the disease usually affecting children and individuals with limited immunity. Despite proper management, mortality from CM can reach up to 25%, especially when it is associated with brain edema. Inefficient management of the edema may result in brain herniation and death. Uniform guidelines for management of CM-associated brain edema are lacking. In this report, we present a case of CM with associated severe brain edema that was successfully managed using a unique combination of therapeutic hypothermia, hypertonic saline, mannitol, and hyperventilation along with the antimalarial drugs quinidine and doxycycline. Our use of hypothermia was based on its proven benefit for improving neurological outcomes in post-cardiac arrest patients and previous in vitro research, suggesting its potential inhibitory role on malaria growth.

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Section: Discussionmentioning

confidence: 98%

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

Gad

Ali

Zahoor

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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“…However, before testing this hypothesis in human patients, the preclinical evaluation of the effect of hypothermia on the growth of P. falciparum and the potential impact on the activity of anti-malarial drugs require investigation. Although hypothermia has been previously shown to reduce growth of P. falciparum [ 7 , 8 ], this has not been investigated in the target range of mild medical hypothermia. Importantly, the effect of mild medical hypothermia on the pharmacodynamics of anti-malarial drugs has not been investigated before.…”

Section: Introductionmentioning

confidence: 99%

Effect of mild medical hypothermia on in vitro growth of Plasmodium falciparum and the activity of anti-malarial drugs

Rehman

Sauerzopf

Veletzky

et al. 2016

Malar J

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BackgroundCerebral malaria remains a medical emergency with high mortality. Hypo-perfusion due to obstructed blood vessels in the brain is thought to play a key role in the pathophysiology of cerebral malaria leading to neurological impairment, long-term neuro-cognitive sequelae and, potentially, death. Due to the rapid reversibility of vascular obstruction caused by sequestered Plasmodium falciparum, it is hypothesized that mild medical hypothermia—a standard intervention for other medical emergencies—may improve clinical outcome. This preclinical in vitro study was performed to assess the impact of mild hypothermia on parasite growth and the intrinsic activity of anti-malarials drugs.MethodsThree laboratory-adapted clones and two clinical isolates were used for growth assays and standardized drug sensitivity assessments using the standard HRP2 assay. All assays were performed in parallel under normothermic (37 °C), mild hypothermic (32 °C), and hyperthermic (41 °C) conditions.ResultsParasite growth was higher under standard temperature condition than under hypo- or hyperthermia (growth ratio 0.85; IQR 0.25–1.06 and 0.09; IQR 0.05–0.32, respectively). Chloroquine and mefloquine had comparable in vitro activity under mild hypothermic conditions (ratios for IC50 at 37 °C/32 °C: 0.88; 95 % CI 0.25–1.50 and 0.86; 95 % CI 0.36–1.36, respectively) whereas dihydroartemisinin was more active under mild hypothermic conditions (ratio for IC50 at 37 °C/32 °C: 0.27; 95 % CI 0.19–0.27). Hyperthermia led by itself to almost complete growth inhibition and precluded further testing of the activity of anti-malarial drugs.ConclusionThis preclinical evaluation demonstrates that mild medical hypothermia inhibits in vitro growth of P. falciparum and enhances the pharmacodynamic activity of artemisinin derivatives. Based on these preclinical pharmacodynamic data, the further clinical development of mild medical hypothermia as adjunctive treatment to parenteral artesunate for cerebral malaria is warranted.

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“…Synchronisation is well developed for Plasmodium [41-45], Toxoplasma [46] and Theileria [47], but was barely achieved for Babesia [32]. A synchronised culture of P. falciparum with a large age range (3-5 h) was obtained by density gradients [41,42], differential osmotic lysis of parasitised erythrocytes [43], temperature shifts [44], and recently optimised to a specific cell-cycle phase with growth inhibitors [45]. Further improvement of the synchronisation of B. divergens cultures will probably rely on drugs that specifically block key points in the cell cycle.…”

Section: Discussionmentioning

confidence: 99%

The invasion process of bovine erythrocyte by Babesia divergens: knowledge from an in vitro assay

Sun

Moreau

Chauvin

et al. 2011

Vet Res

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Babesia divergens is a tick-transmitted apicomplexan parasite for which asexual multiplication in its vertebrate hosts is restricted to erythrocytes. Current knowledge of invasion of these target cells is limited. An efficient in vitro invasion assay was set up to gain access to this information. Parasites prepared from infected RBC, lysed by electroporation, and mixed with bovine RBC in a selected synthetic medium (RPMI 1640 supplemented with calcium) were able to establish subsequent cultures with parasitemia ranging from 6 to 14%. Free parasites remaining in the invasion medium could be eliminated by Percoll gradient and culture could be pursued with the freshly invaded erythrocytes. In this way, the invasion time window could be shortened to obtain a synchronised start of the culture or to study the kinetics of invasion. With this assay we demonstrate that 1) erythrocyte invasion by B. divergens is a rapid process since 70% of the invasion-competent parasites invaded the RBC in less than 45 s; 2) all invasion-competent parasites achieved invasion within 10 min of contact; 3) one erythrocyte could be invaded concomitantly by two merozoites; 4) despite a synchronous start, the parasite population evolved heterogeneously resulting in a progressive loss of synchronisation. Western blot analysis of proteins collected from invasion medium were performed with sera from animals experimentally infected with B. divergens and highlighted several proteins. The dose-dependent, inhibitory effects of these sera on B. divergens invasion suggest that these proteins might be involved in the invasion process. Further investigations are required for their characterisation.

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Effect of Low Temperature On the In Vitro Growth of Plasmodium falciparum

Cited by 22 publications

References 19 publications

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

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

Effect of mild medical hypothermia on in vitro growth of Plasmodium falciparum and the activity of anti-malarial drugs

The invasion process of bovine erythrocyte by Babesia divergens: knowledge from an in vitro assay

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