A female Anopheles stephensi mosquito devouring a blood meal [Image credits: Jim Gathany, Public domain, via Wikimedia Commons]
A mosquito bite may look like a minor prick, but it might be the beginning of a life-threatening sickness. Malaria, which affects nearly 75 lakh people across the globe, is a mosquito-borne disease caused by a group of microscopic protozoans called Plasmodium. India is estimated to have half of these cases caused by Plasmodium vivax, a species of this protozoa that is prevalent in Southeast Asia. Anopheles stephensi is the most common mosquito that is a vector of malaria.
Plasmodium vivax has a complex life cycle with mosquitoes and humans acting as host. The parasite can live inside our liver cells for prolonged times without being detected by the immune system. From time to time, it can get into the bloodstream, multiply quickly, destroy the red blood cells, and cause Malaria. Although less lethal than Plasmodium falciparum, the main malaria-causing parasite, recurring episodes of P. vivax attacks may lead to severe anaemia, damage vital organs including the brain, and even death.
Although anti-malarial drugs like chloroquine, which gained fame this year in the context of Covid-19, are used to treat malaria, they only help when the parasite is in the bloodstream. Apart from primaquine, there aren’t any drugs to target the P. vivax lurking in the liver. However, this drug is not recommended for susceptible groups including pregnant women, infants, and patients with a particular form of genetic mutation called Glucose 6 phosphate dehydrogenase (G6PD) deficiency. Hence, we need a drug that targets the liver parasites and can be used by all.
Scientists have long attempted to grow P. vivax in human livers in laboratories. “There have to be high numbers of parasites present in the liver cells to carry out drug-related studies. Currently, the infection levels are low with P. vivax,” explains Vardharajan Sundarmurthy from NCBS, who studies parasites in liver cells. “Once we cross this major hurdle, we can conduct experiments to look for prospective drugs that kill the parasite present in the liver of malaria patients.”
In a new study, Varadharajan and his colleagues from the National Centre for Biological Sciences (NCBS), Bengaluru, and National Institute of Malaria Research (NIMR), Bengaluru, Foundation of Neglected Disease Research (FNDR), Bengaluru, inStem, Bengaluru and Kyoto University, Japan, have successfully grown Indian isolates of P. vivax in different types of human liver cells. The findings of the study, funded by NCBS-TIFR, Medicines for Malaria Venture (MMV), and Bill and Melinda Gates Foundation, were published in the Malaria Journal.
The researchers used different kinds of liver cells, including liver cell lines, primary human hepatocytes, and liver cells obtained using stem cell technology from vivax patients. Using the P. vivax derived from the blood of patients suffering from malaria, they infected the liver cells.
“P. vivax has been resistant to several attempts of growing them inside the lab, so to study them, they have to be freshly isolated from patients’ blood,” explains Vardharajan Sundarmurthy from NCBS, who is an author of the study.
After rearing Anopheles stephensi mosquitoes in the lab, the researchers fed them the blood of P. vivax malaria patients. Then obtained the parasites from the mosquitoes’ salivary glands and used them to infect human liver cells. Finally, they assessed the success of infection of the liver cells using a special dye to stain and count the parasites present in the liver cells. This dye binds specifically to the parasite, allowing the researchers to observe the parasites using an advanced microscope.
The study demonstrates a way of understanding the interactions between liver cells and P. vivax, and the cellular and molecular processes that occur in both. The researchers hope to refine their strategy to facilitate drug discovery against vivax malaria in the future using the methods they have established.
This article has been run past the researchers, whose work is covered, to ensure accuracy.
Editor's note: There were some minor edits to the content. The error is regretted.