The liver and blood stages of the parasite are targeted; transmission foiled
A candidate drug (ELQ-300) was found capable of treating and preventing malaria infection, and even blocking transmission during a trial on mice. While the currently available drugs target the parasite at the blood stage of infection, the candidate drug was able to target both the liver and blood stages.
Going beyond destroying the parasite in the body, the drug (quinolone-3-diaryether) was found to be effective in preventing infection by attacking the parasite forms that are crucial to disease transmission (gametocytes, and the vector stages — zygote, ookinete and oocyst).
“ELQ-300 has potential as a new drug for the treatment, prevention, and, ultimately, eradication of human malaria,” notes a paper published today (March 21) in the Science Translational Medicine journal.
The Editor’s summary also underlines the same message: “ELQ-300…[can] prevent and treat malaria, with the potential to aid in eradication of the disease.”
Any drug that does even half of what ELQ-300 is capable of will be a boon — nearly 200 million people in the world suffer from malaria every year, and the mortality is as high as 1.2 million. To make matters worse, resistance to currently available drugs is emerging.
Two candidate drugs — ELQ-300 and P4Q-391 — were tested against both Plasmodium falciparum and Plasmodium vivax species. Isolates of P. falciparum and P. vivax taken from patients infected with malaria in southern Papua, Indonesia were tested using both the drug candidates. ELQ-300 was found to be superior against both drug-resistant species.
The ability to block the development of the parasite in the blood and liver was found to be superior. According to the authors, the ELQ-300 was “potently” inhibiting erythrocytic (red blood cells) stages of the species.
However, both the drugs were also able to block the development of schizont in the liver. Schizont is a matured malaria parasite that contains many merozoites, which is the parasite stage that infects red blood cells.
Both the drugs were found to cause low side effects (as they targeted specific targets).
More importantly, the parasites did not develop resistance to ELQ-300 even at the end of eight weeks. The results were the same even when the experiment was repeated another time.
Next the efficacy of the two drugs and another potent drug atovaquone was tested on three different species — P. yoelii, P. berghei and P. falciparum.
Both the test drugs were found to be “highly active” against murine malaria. But only ELQ-300 was found to be “equally potent” against P. falciparum introduced into the mice. The authors next tested the drugs’ ability to prevent transmission of malaria to the mosquito. Both the drugs were able to “inhibit development” of early-stage gametocytes (cells that are capable of producing both male and female gametes that fuse to finally produce oocytes in the mosquito).
The gametes were unable to develop past stage III even when a low dose was used. In the case of ELQ-300, it was able to “inhibit” even the later stage of gametocyte “viability” throughout the testing period of 72 hours.
Next, the ability of ELQ-300 to reduce the number of oocysts in the P. berghei mosquitoes was tested.
This was done by feeding the mosquitoes ELQ-300 mixed with blood feed infected with P. berghei. What they found was quite impressive — the blood feed reduced the number of oocysts in the mosquitoes.
At one micro mole concentration, ELQ-300 was able to reduce 99.4 per cent of oocyte count in the mosquito.
The transmission potential was tested in other malaria causing species as well, and the results were the same.