By growing an anti-malarial drug resistant parasite, Plasmodium Vivax, scientists feel new drugs can be created to counter malaria.
Bangalore, March 6, 2018: In an advance that might lead to eradication of malaria, a team of scientists at the Massachusetts Institute of Technology have been able to grow and study a dormant form of malaria causing parasite—Plasmodium Vivax. This form of parasite causes the maximum cases of malaria in Karnataka.
“Plasmodium vivax causes more malaria outbreak than Plasmodium falciparum. As for eradication, we are aiming to bring down the number malaria cases in the state below 10 per cent of the population by 2025. If such a study has been conducted then it can prove useful,” says Dr. Shivaraj Sajjan Shetty, Joint Director, National Vector Borne Disease Control Programme.
Plasmodium falciparum and Plasmodium vivax are the two parasites known to cause most human cases of malaria. While less deadly, Plasmodium vivax, produces dormant forms known as hypnozoites (so called because they are “hypnotized”), and can lead to recurring infections.
“After 10 years of hard work, we were able to grow the organism, show it had all the functional hallmarks, perform a drug screen against it, and report the first transcript and genome of this elusive form. I’m really excited because I believe it will open the door to both the basic biology of dormancy as well as the possibility of better medicines,” says Sangeeta Bhatia, senior author of the study and professor of health sciences at MIT.
This dormant form of parasite which hides in the liver of some patients is one of the biggest impediments in eradicating malaria. This dormant form can re awaken months or years later causing disease relapse.
It is also resistant to most anti-malarial drugs as malaria researchers know little about the biology of these dormant parasites and have not been able to develop drugs that target them.
After verifying that they had successfully cultivated the dormant form of the parasite, the researchers showed that they could also sequence its Ribonucleic acid (RNA) and test its response to known and novel anti-malarial drugs — both important steps toward finding ways to eradicate the disease.
The dormant parasite were grown in engineered human liver tissue for several weeks, which allowed the researchers to closely study how the parasite becomes dormant, what vulnerabilities it may have, and how it springs back to life.
The first paper appears in Feb. 22 issue of the journal Cell Host and Microbe authored by MIT graduate student Nil Gural.
Malaria is a life-threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. It is preventable and curable.
The World Health Organization (WHO) reported that in 2016, there were an estimated 216 million cases of malaria in 91 countries, which is an increase of 5 million cases over 2015. Malaria deaths reached 445 000 in 2016, a similar number (446 000) to 2015.
WHO estimates India not only accounts for 75 per cent of all malaria cases in South-East Asia but also has 95 per cent of its population living in malaria endemic areas.
Malaria in Karnataka has been due to Plasmodium vivax and Plasmodium falciparum infections with a high proportion of vivax compared to falciparum says the Malaria Elimination Plan in Karnataka issued by the government.
“This dormant form has been seen as the critical barrier to eradication,” Bhatia says. “You can treat the symptoms of vivax malaria by killing all the parasites in the blood, but if hypnozoites linger in someone’s liver, these forms can reactivate and reinfect the blood of a patient. If a mosquito comes along and takes a blood meal, the cycle starts all over again. So, if we want to eradicate malaria, we have to eradicate the hypnozoite.”
The only existing drug that can kill hypnozoites is primaquine, but this drug cannot be used in large-scale eradication campaigns because it causes blood cells to rupture in people with a certain enzyme deficiency.
Using new technology, Bhatia’s team showed that they could grow small forms of the parasite that had all of the known features of hypnozoites: persistence, sensitivity to primaquine, and the ability to “wake up” after a few weeks.
In future studies, Bhatia, in collaboration with other MIT labs, hopes to identify biomarkers that could be used to diagnose patients who have an otherwise undetectable dormant infection.
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