SYDNEY, 26.12.19 (SciDev.Net):  Australian scientists have successfully blocked the deadliest malaria parasite —- Plasmodium falciparum — in its transmission stage, paving the way for developing preventative therapies to stop the spread of the disease.

Lead researcher Justin Boddey from the Walter and Eliza Hall Institute of Medical Research and University of Melbourne says, “We have built on our previous studies, where we identified in the P. falciparum parasite an enzyme called plasmepsin V, an enzyme essential for the parasite to grow inside red blood cells. We showed that if you inhibit the enzyme’s activity then you can kill the parasites as they are growing in red blood cells.”

The new findings (opens in new tab), published 18 December in Cell Reports, show that plasmepsin V is also essential in a subset of parasites called gametocytes (sexual form of the malaria parasite) that transition to infect the mosquito. 

“They [gametocytes] go via a blood meal into the mosquito’s stomach. They fertilise in the gut and develop into another parasite form that can then productively infect that mosquito. We have developed small molecule compounds that act as an ‘inhibitor’, and by inhibiting the plasmepsin V enzyme in gametocytes, we can block them from transmitting to mosquitoes,” Boddey tells SciDev.net.

Globally, there were an estimated 228 million cases of malaria resulting in an estimated 405,000 related deaths in 2018, according to the WHO’s World Malaria Report 2019(opens in new tab). Most of the deaths were caused by P. falciparum.

Malaria is spread to people through the bites of infected Anopheles mosquito vectors. When a mosquito bites a person, the parasites first infect the liver, where they live for about seven days.

“The liver is also a fantastic place for intervention because one can then prevent that person from getting malaria by stopping parasites from coming out of their liver. We are testing if we can develop drugs that block plasmepsin V not just in blood and gametocyte stages but also during liver infection as a prophylactic,” Boddey tells SciDev.Net.

“The potential for chemoprophylaxis (administration of drug to prevent the development of a disease) is to protect people living in, or travelling to, malaria endemic areas, and you might also initiate immunity,” he adds.

Classically, anti-malarial drugs tend to focus on one part of the parasite lifecycle i.e. when people’s blood is infected and they need treatment. New drug development for malaria is focused on all stages of the malaria parasite’s lifecycle — liver, blood and gametocyte.

“So far, our published studies show that inhibiting plasmepsin V blocks two of the three lifecycle stages — the blood phase (sickness) as well as the gametocyte stage (transmission) with a single drug, and we are currently seeing positive results against the liver stage,” says Boddey. “Such breadth of efficacy of an antimalarial therapy would help accelerate the elimination of malaria.”

According to the 2018 WHO report, there has been a resurgence of malaria in certain countries because of mosquitoes becoming resistant to insecticides, and bed nets used between dusk and dawn are not providing complete protection because mosquitoes are biting earlier than they used to.

“With the increasing occurrence of resistance to currently used anti-malarial drugs, there remains an urgent need for new chemical entities in the drug discovery pipeline. Our study provides a valuable starting point for development of urgently needed drugs, and further validates the importance of plasmepsin V as a drug target,” says Vicky Avery from Griffith University(opens in new tab), Queensland, which collaborated in the study.

“The study holds the promise of an effective approach being developed to interrupt malaria transmission and reduce malaria burden. It has the potential of addressing challenges such as drug resistance, asymptomatic reservoirs of infection and insecticide resistance,” Sanjeev Gaikwad, India country director of Malaria No More, (opens in new tab)tells SciDev.Net.

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