Researchers have made a significant discovery regarding malaria parasites, revealing their synchronization with the internal rhythms of their human hosts. This finding opens up possibilities for the development of innovative anti-malarial drugs designed to disrupt this synchronization, effectively inducing a “jet lag” effect on the parasites. By doing so, the immune system can more easily combat the parasites and aid in the battle against malaria.
The potential development of novel anti-malarial drugs, aimed at inducing a “jet lag” effect on the disease-causing parasites, could be a crucial breakthrough in the fight against malaria.
Health authorities have expressed concerns about the emergence of drug resistance, which threatens recent progress in malaria eradication, particularly in Africa and Southeast Asia. In the pursuit of alternative methods to combat the parasites transmitted by mosquitoes, researchers have identified biological clocks as a potential new target.
Virtually all living organisms possess internal clocks that regulate various processes, including appetite, hormone levels, and gene activity throughout the day. In a study published in the journal Proceedings of the National Academy of Sciences on June 6, a team of researchers examined gene activity in individuals presenting signs of malaria infection in their blood, who sought medical attention along the Thailand-Cambodia border.
The researchers discovered that malaria parasites somehow synchronize their molecular rhythms with their hosts’ internal 24-hour clocks. Their respective genes rise and fall in perfect coordination over the course of a day, like two synchronized pendulum clocks.
The team, consisting of researchers from Duke University, Florida Atlantic University, and the Armed Forces Research Institute of Medical Sciences, believes that these findings could pave the way for new anti-malarial drugs that disrupt the internal clock of the parasites, essentially “jet-lagging” them.
Steve Haase, the senior author of the study and a professor of biology at Duke, explained the importance of the research, stating, “We’re on our last line of drugs, artemisinin-based combination therapies, and we’re already seeing resistance to those in southeast Asia. Exploring some new ideas for fighting malaria makes sense.”
Malaria follows a deadly cycle within the human body, where recurring fever spikes are caused by microscopic Plasmodium parasites invading and multiplying within red blood cells. The parasites subsequently burst out, releasing millions of new parasites into the bloodstream to invade other cells and repeat the cycle.
The duration of this cycle varies, ranging from 24 to 72 hours depending on the specific Plasmodium species. This led scientists to question whether the parasites coordinate their rhythms with the 24-hour circadian rhythms of their hosts.
To investigate, the researchers collected blood samples from individuals infected with Plasmodium vivax, the predominant malaria parasite species in Asia and Latin America. They analyzed the RNA in these samples every three hours over two days to determine the active genes as the parasites matured within the red blood cells. By employing RNA sequencing, the researchers tracked the expression of over 1,000 genes in both the patients’ immune cells and the malaria parasites in their blood.
The study revealed hundreds of genes that exhibit a clock-like rhythm, increasing or decreasing their activity at specific times of the day. Using this data, the researchers calculated the internal clock time for each patient and their corresponding parasites, evaluating the alignment of gene expression rhythms.
The researchers confirmed that Plasmodium vivax parasites, with a life cycle repeating every 48 hours, precisely matched the 24-hour body clock of their host.
Although malaria parasites were already known to possess their own internal timekeeping mechanism, as demonstrated in a 2020 study, this new research indicates that the parasite clock and the host clock interact with each other. The exact reasons behind this coordination remain unclear, but it is hypothesized that the parasites take advantage of their host’s rhythms to further their own survival.
One theory suggests that the parasites time their emergence from red blood cells to avoid periods when the host’s immune system is most active, reducing their vulnerability to attack. Another possibility is that they synchronize their developmental cycle with the host’s rhythms to ensure optimal nutrition. However, further investigation is needed to validate these theories.
Malaria remains a leading cause of death in poorer and tropical regions, claiming the lives of 619,000 individuals in 2021 alone, with children being the most affected. The ability of malaria to evade existing drugs contributes to the ongoing challenge. While medicines for malaria have existed for centuries, the effectiveness of many drugs is diminishing as parasite populations develop resistance.
Understanding how malaria parasites synchronize with human hosts offers hope for the development of new drugs that can disrupt this coordination, thereby empowering the immune system to more effectively combat the invaders. Encouraging findings have already emerged from studies involving other host species, such as mice, where parasites with disrupted rhythms are significantly less efficient at spreading infection.
Moving forward, the researchers aim to unravel the molecular signals that facilitate communication between the parasite and human clocks, ensuring their synchronization. By disrupting these signals, interventions may be possible in the future.
The study received funding from the Defense Advanced Research Projects Agency, the National Institutes of Health, and the National Science Foundation.
Frequently Asked Questions (FAQs) about malaria parasites
What did the researchers discover about malaria parasites and their hosts’ internal rhythms?
The researchers found that malaria parasites synchronize their molecular rhythms with the internal 24-hour clocks of their human hosts. Their genes rise and fall in coordination with the host’s genes, indicating a synchronization between the parasite and the host’s biological clocks.
How can disrupting the synchronization of malaria parasites with their hosts’ internal rhythms help combat the disease?
Disrupting the synchronization of malaria parasites with their hosts’ internal rhythms can make it easier for the immune system to combat the parasites. By inducing a “jet lag” effect on the parasites, new anti-malarial drugs can throw off their internal clock and weaken their ability to survive and reproduce within the host.
Why is it important to develop new anti-malarial drugs?
The rise of drug resistance poses a significant threat to existing anti-malarial drugs. Exploring new ideas and developing innovative drugs to combat malaria is crucial, especially since current treatments, such as artemisinin-based combination therapies, are already facing resistance in some regions, like Southeast Asia.
What is the significance of the synchronization between malaria parasites and their hosts’ internal clocks?
The synchronization suggests that the parasites may be taking advantage of their hosts’ internal rhythms for their own survival. By coordinating their rhythms, the parasites may be able to avoid the host’s immune system or time their developmental cycle to optimize nutrient availability. Understanding this synchronization could provide insights into the parasite’s strategies and potentially lead to new intervention approaches.
How can disrupting the molecular signals between malaria parasites and human hosts be achieved?
Further research is needed to uncover the specific molecular signals involved in the communication between malaria parasites and human hosts. By identifying and disrupting these signals, it may be possible to decouple the parasite’s internal clock from that of its host, providing a potential avenue for developing interventions to combat malaria.
More about malaria parasites
- “The parasite intraerythrocytic cycle and human circadian cycle are coupled during malaria infection” (Proceedings of the National Academy of Sciences) Link
- Defense Advanced Research Projects Agency Link
- National Institutes of Health Link
- National Science Foundation Link