Exposure to suboptimal doses of the antiparasitic artemisinin could increase the sexual conversion rate of the malaria parasite Plasmodium falciparum and thus increase the probability of transmission, according to a study by the Barcelona Institute for Global Health (ISGlobal), one of the “la Caixa” foundation.
Findings published in eLife may have public health implications, particularly in the context of mass anti-malarial drug administration campaigns.
The malaria parasite P. falciparum replicates asexually in human blood every 48 hours and causes the typical clinical symptoms of the disease. With each cycle of replication, a small number of parasites take a different route: that of sexual conversion to produce gametocytes.
This sexual form of the parasite is the only one that can be transmitted to the mosquito. Sexual conversion is a highly regulated process as the parasite must maintain a balance between asexual replication within the host and transmission between hosts.
“From an evolutionary point of view, the parasite’s ability to adapt its sexual conversion rate to host conditions is clearly beneficial,” explains Alfred Cortés, ICREA researcher at ISGlobal and study coordinator. One factor that significantly reduces the “comfort” of the parasite in the host is exposure to parasiticidal drugs.
To determine whether artemisinin (the drug of choice for treating falciparum malaria) or artemisinin-related drugs could affect the parasite’s sexual conversion rate, Cortés and his team used a transgenic line of parasites that quantified sexual conversion in a bowl under various conditions can be experimental conditions.
They found that exposure of parasites to artemisinin can lead to significant increases in sexual conversion rates and gametocyte counts. However, this effect was only observed with suboptimal drug doses and was dependent on the stage of the parasite cycle (it was observed in trophozoites, but not in the previous ring stage).
“Our results show that there is a complex interaction between anti-malarial drugs and sexual conversion, which depends on the parasite stage, its metabolic status and the drug doses,” says Harvie Portugaliza, lead author of the study.
It is possible that patients with most of the parasites in the trophozoite stage at the time of treatment may have a peak in gametocyte production ten days later (the time it takes to mature) if the drug has failed to kill all of the parasites . “”
Alfred Cortés, Study Coordinator and ICREA Researcher, Barcelona Institute for Global Health (ISGlobal)
Exposure to sub-optimal drug concentrations can be caused by the use of poor quality drugs or poor adherence to treatment. Currently, the team led by Cortés is conducting epidemiological studies to determine whether sexual conversion is actually higher in patients treated with artemisinin.
Barcelona Institute for Global Health (ISGlobal)
Portugaliza, HP et al. (2020) Exposure to artemisinin in the ring or trophozoite stage has different effects on the sexual conversion of Plasmodium falciparum. eLife. doi.org/10.7554/eLife.60058.