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

Area of Science:

• Malariology
• Drug Resistance
• Therapeutic Hypothermia

Background:

• Clinical studies indicate managed hypothermia may improve outcomes for hospitalized malaria patients.
• Artemisinin-based therapies are crucial for malaria treatment, but parasite resistance is a growing concern.

Purpose of the Study:

• To investigate the in vitro effect of short low-temperature pulses on Plasmodium falciparum ring-stage susceptibility to artemisinin.
• To explore the impact of hypo- and hyper-thermic conditions on parasite drug response.

Main Methods:

• Exposure of artemisinin-sensitive Plasmodium falciparum (clone 3D7) to a 5-hour low-temperature pulse (down to 17°C) with dihydro-artemisinin (700 nM) for 4 hours.
• Assessment of parasite growth and susceptibility to artemisinin, chloroquine, and pyronaridine after temperature pulses.
• Inclusion of fever-like temperature pulses (up to 40°C) to evaluate hyperthermia effects.

Main Results:

• A 4-hour pulse of dihydro-artemisinin during a 5-hour low-temperature pulse significantly reduced ring-stage susceptibility in the 3D7 clone.
• Subsequent parasite growth was unaffected by the temperature pulse.
• Brief exposure to low temperatures did not alter susceptibility to chloroquine or pyronaridine.
• Fever-like temperatures (40°C) also enhanced ring-stage survival with artemisinin pulses, though overall growth was attenuated.

Conclusions:

• Hypo- and hyper-thermic conditions may activate parasite stress responses, potentially affecting artemisinin efficacy.
• Physiological temperature variations in patients could influence the effectiveness of artemisinin-based malaria treatments.
• Further research is needed to understand the clinical implications of temperature modulation on malaria parasite drug susceptibility.