A vector refers to an organism that carries and transmits an infectious disease, such as mosquitoes, malaria.
Lead compounds are chemical compounds that show promise as a treatment for a disease and may lead to the development of a new drug.
Antiplasmodial lead compounds are those that counteract parasites of the genus Plasmodium, a parasite that infects mosquitoes and causes malaria in humans.
The study results were published in Nature Communications on January 11, 2021, at a time when malaria incidence generally peaks after the holiday season.
MOSQUITO INFECTION EXPERIMENT CENTER
Professor Lizette Koekemoer, co-director of WRIM and the SARChI Chair of Medical Entomology and Control of the National Research Foundation and Honorary Member of the Center for Emerging Zoonotic and Parasitic Diseases of the National Institute for Communicable Diseases, co-authored the paper.
Koekemoer and her team at WRIM established a unique mosquito malaria infection center in the Faculty of Health Sciences at Wits University, where the experiments to block mosquito transmission took place.
“The WRIM Infection Center is the only facility in South Africa and the South African region that can artificially infect mosquitoes with the human malaria parasite,” says Koekemoer. “The Infection Center had the expertise to infect mosquitoes with the human malaria parasite Plasmodium falciparum and made this unique study possible.”
COURING CHEMICALS TO FIGHT THE GEAR
Medicines are used to fight malaria in humans, but resistance to these drugs is developing rapidly. Additionally, the drugs primarily target only one phase of the parasite’s life cycle and are not good candidates for blocking transmission.
In order to widen the suitability of drugs in malaria eradication strategies, drugs must be able to act as a chemotype [a chemically distinct entity in a plant or microorganism] This blocks both human-to-mosquito transmission and mosquito-to-human transmission.
Koekemoer carried out special experiments with WRIM colleagues and co-authors, Erica Erlank, Luisa Nardini, Nelius Venter, Sonja Lauterbach, Belinda Bezuidenhout and Theresa Coetzer to measure the reduction in mosquito infection and the “deadly effect” [endectocide effect] in the vectors.
Scientists studied 400 chemical compounds available in Medicines for Malaria Venture’s (MMV) Pandemic Response Box to identify the compounds that are most effective at the parasite life stages that are commonly found in the human host .
The Pandemic Response Box contains 400 different drug-like molecules that are effective against bacteria, viruses or fungi. It is available free of charge, provided researchers share data obtained from research into the molecules in the box to the public within two years of their creation.
The compounds that showed good activity on late-stage gametocytes (those that circulate in the blood and are transmitted to a mosquito when it feeds on an infected human) were tested for their transmission-blocking potential.
Mosquitoes were fed infected blood that was treated with or without the compound. After eight to 10 days, the mosquito will have entrails [stomach] were removed and the number of parasites (called oocysts) counted and compared to mosquitoes that received only an infected blood meal without treatment.
Find the spark
Mass Drug Administration (MDA) is the administration of antimalarial drugs to the parasite reservoir in humans without necessarily testing whether they are carrying the parasite that causes malaria.
The World Health Organization (WHO) recommends MDA to eradicate the malaria parasite Plasmodium falciparum. However, the effort and cost of implementing MDA on a large scale is prohibitive.
Identifying the potential compounds for MDA is one of the biggest hurdles to overcome, so it is an intense research pipeline for development.
Leveraging the scarce skills and expertise available at various research institutes such as WRIM, this study published in Nature Communication established the first such pipeline screening in South Africa.
This opens the door to effective and rapid screening of additional chemistry to help eradicate malaria.
TO ZERO TRANSMISSION DESTINATIONS
Although there were still an estimated 229 million cases of malaria and 409,000 deaths during that period in 2019 (compared to 88 million reported Covid-19 cases), the successes in reducing malaria cases over the past two decades have inspired many countries to seek elimination to undertake transfer in total.
So far, the WHO has certified 38 countries and areas as malaria-free. In southern Africa, eight countries – including South Africa – have made malaria eradication a political goal.
However, advances in eradicating transmission pose numerous challenges and new drugs and insecticides are urgently needed to combat the development of drug resistance in the parasite and vector.
The WRIM and studies like this are groundbreaking new approaches. However, there is still a long way to go between laboratory and field operations. But the first steps have been taken.