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Scientists Design New Drug To Fight Malaria

In 2022, nearly 619,000 global deaths due to malaria were caused by Plasmodium falciparum, the most virulent, prevalent, and deadly human malaria parasite. For decades, the parasite's resistance to all antimalarial drugs has posed a big challenge for researchers working to stop the spread of the disease.

A team led by scientists at UC Riverside, UC Irvine, and Yale School of Medicine has now designed a new drug against malaria and identified its mechanism of action. The researchers found the drug, called MED6-189, is effective against drug-sensitive and drug-resistant P. Falciparum strains in vitro as well as in a humanized mouse model (the mice were engineered to have human blood).

The researchers report in the journal Science this week that MED6-189 works by targeting and disrupting not only the apicoplast, an organelle found in P. Falciparum cells, but also the vesicular trafficking pathways. They found that this dual mode of action prevents the pathogen from developing resistance, making the drug a highly effective antimalarial compound and a promising new lead in the fight against malaria.

"Disruption of the apicoplast and vesicular trafficking blocks the parasite's development and thus eliminates infection in red blood cells and in our humanized mouse model of P. Falciparum malaria," said Karine Le Roch, a professor of molecular, cell and systems biology at UCR and the paper's senior author. "We found MED6-189 was also potent against other zoonotic Plasmodium parasites, such as P. Knowlesi and P. Cynomolgi."

MED6-189 is a synthetic compound inspired by a compound extracted from marine sponges. The lab of Christopher Vanderwal, a professor of chemistry and pharmaceutical sciences at UC Irvine, synthesized the compound.

"Many of the best antimalarial agents are natural products, or are derived from them," he said. "For example, artemisinin, initially isolated from the sweet wormwood plant, and analogues thereof, are critically important for treatment of malaria. MED6-189 is a close relative of a different class of natural products, called isocyanoterpenes, that seem to target multiple pathways in P. Falciparum. That is beneficial because had only one pathway been targeted, the parasite could develop resistance to the compound more quickly."

When researchers at GSK, a pharmaceutical company in Spain, administered MED6-189 to the mice infected with P. Falciparum, they found it cleared the mice of the parasite. In collaboration with Choukri Ben Mamoun, a professor of medicine and microbial pathogenesis at the Yale School of Medicine, the team also tested the compound against P. Knowlesi, a parasite that infects monkeys, and found it worked as intended, clearing the monkey's parasite-infected red blood cells.

Next, the team plans to continue the optimization of MED6-189 and further confirm the modified compound's mechanisms of action using a systems biology approach. Systems biology is a biomedical research approach to understanding the larger picture of a biological system. It offers researchers a way to examine how different living organisms and cells interact at larger scales.

Le Roch, Vanderwal, and Ben Mamoun were joined in the research by fellow scientists at the Stowers Institute for Medical Research in Kansas City, Missouri; GSK; and the University of Georgia.

The research was supported by a grant to Le Roch, Vanderwal, and Ben Mamoun and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health. At UCR, Le Roch directs the Center for Infectious Disease and Vector Research.

The title of the research paper is "A Potent Kalihinol Analogue Disrupts Apicoplast Function and Vesicular Trafficking in P. Falciparum Malaria."

Bill Gates-funded Company Did Not Cause Malaria 'outbreak' In The US

A number of widely shared posts suggest that malaria outbreaks are happening in the "exact places" that a company backed by Bill Gates has been releasing mosquitoes. The posts also note that "it must be a coincidence that from 2003-2023 there wasn't one case of Malaria spread by mosquitos [sic]".

The posts on Twitter and Facebook appear to be referring to locally-transmitted malaria cases recorded in the United States—the first such cases in the country in 20 years. But there is no evidence this has been caused by a Bill Gates-backed company which produces genetically modified mosquitoes, as the posts appear to imply. The company in question has itself described the suggestion as "scientifically impossible".

Health misinformation that spreads at scale can introduce confusion about the causes and treatments of illnesses, and distract from or undermine medical consensus and public health messaging.

Where in the world are malaria cases "suddenly" rising?

The posts don't mention any particular location, but considering the "2003-2023" time frame referenced, it seems likely that they are referring to the United States. In 2023, 10 cases of locally acquired mosquito-transmitted malaria were identified in Florida, Texas, Maryland and Arkansas; the first of any such cases in the US since 2003.

Each year there are around 2,000 cases of malaria reported in the US, most of these are contracted while people travel to other countries, or spread when an infected person returns.

On a global scale, hundreds of thousands of people die from malaria each year. Cases have been increasing in recent years, with the World Health Organisation reporting that global malaria cases rose by 16 million to 249 million between 2019 and 2022.

Bill Gates-backed company did not cause locally-transmitted malaria cases

As we wrote when we previously fact checked this claim, the posts are likely referring to Oxitec, a biotechnology company that has received funding from the Bill & Melinda Gates Foundation. The Foundation did not fund this particular project, however.

Oxitec produces genetically modified mosquitoes intended to be released into the wild to mate with local pests, to produce offspring that will not survive into adulthood, thereby reducing local mosquito populations. 

The mosquitoes, which were first released in Florida in April 2021 with the help of Florida Keys Mosquito Control, belong to a species called Aedes aegypti and are all male. The only mosquitoes that can transmit malaria are infected female Anopheles mosquitoes: a different sex and genus.

Furthermore, male mosquitoes don't have the proper body parts to pierce human skin, so Oxitec's mosquitoes don't bite.

Given that the mosquitoes Oxitec has released are male Aedes aegypti, rather than female Anopheles, these insects can't be the cause of any transmission of malaria.

And as for the four states which saw locally-transmitted malaria cases in 2023, Oxitec has only released its mosquitoes in Florida. So the increase in cases did not occur in the "exact places" they were released, as the posts claim.

A spokesperson for Oxitec told Full Fact last year there was "absolutely no truth to these claims" and that they were "scientifically impossible".

The increasing cases in the US are likely to have been caused by female Anopheles mosquitoes, which, as the CDC stated last year, are "found throughout many regions of the country" and "are capable of transmitting malaria if they feed on a malaria-infected person".

Full Fact checks a lot of claims about Bill Gates, especially on the subject of public health due to his charitable work in the area. We've previously fact checked false claims that Mr Gates is seeking to introduce "maggot milk" into the general population's food supply, that his Foundation paralysed 300,000 children in India following a vaccine trial, and that he plans to "euthanise billions" by attacking the global food supply to create a market for his bird flu vaccine.

Why Are Treatments That Were Developed For Malaria Now Used For Lupus?

Most physicians with experience in lupus agree that antimalarial treatments such as hydroxychloroquine (Plaquenil), chloroquine (Aralen) or quinicrine (Atabrine) should be used long-term, year-after-year, in all lupus patients who can tolerate them. Why?  

The answer is that these drugs have a range of effects on people, so what they do for malaria is not necessarily the same as what they do for lupus. And yet, there are similarities.

How chloroquine treats malaria

Malaria is caused by a parasite, usually found in tropical regions, that infects humans after they have been bitten by a mosquito. This parasite is transmitted directly from the saliva of the mosquito into the bloodstream of a person who has been bitten. Under the microscope a malaria parasite can actually be seen literally crawling inside of people's red blood cells.

In order to survive, the malaria parasite has to break down a part of the red blood cell called hemoglobin, but this results in toxic by-products which need to be processed and contained by the malaria parasite. The malaria parasite has a little digestive pouch inside it, rather like a primitive stomach, that turns the toxic products into crystals. This provides a way to contain them and keep them from harming the parasite. Chloroquine stops this from happening and even binds directly to the toxic product to disrupt and break up the malaria invader.

All cells, whether parasitic or human, must break down and recycle substances that come in from the blood stream in order to survive. Just like a malaria parasite, the specialized proteins that work for human cells are stored in little acid filled protective pouches inside the cell called lysosomes. Antimalarials go directly into these lysosomes and decrease the acid levels in there that the digestive proteins require in order to work best. In doing so, antimalarials can really gum up some critical activities of hyperactive immune cells.

How chloroquine inhibits overactive immune cells

Our DNA is the blueprint for every protein in the body. Thymine is one of the building blocks of DNA and is needed to replenish new cells all over the body and to build the armies of immune cells we need to fight disease (which are the same cells that we wish would calm down a little in lupus). Chloroquine inhibits the ability of cells to take in and process thymine. This may keep immune cells from regenerating out of control.

As you can see, when you put any substance into a cell it has complicated chemical processes in place to break it down, use some of it for nutrition, recycle parts of it, and dispose of the waste. This is true whether the cell is a parasite trying to survive by eating human red blood cells, or a human cell. Human cells have a big job to do because we humans are complicated beings. We must deal with hostile invaders (bacteria, viruses, parasites), as well as the good (or bad) things that we put into our bodies on purpose, in the form of food and medicine.  

What is hydroxychloroquine?

Some of the breakdown products of medicines also are useful as treatments, even without giving the "parent" drug initially. Hydroxychloroquine (Plaquenil) is a breakdown product of chloroquine, and is, in fact, the most common antimalarial given to treat lupus.

How hydroxychloroquine works to fight lupus

Hydroxychloroquine has a number of effects on the immune system. Recently, hydroxychloroquine has been found to interfere in the internal communications of an immune cell, by inhibiting important proteins that recognize danger signals (either from infectious invaders or from byproducts of lupus inflammation). These proteins, which hydroxychloroquine inhibits, are called Toll-Like Receptors. When they are stimulated, the body makes a lot of a protein called type one interferon. Interferon can be very helpful if you are trying to fight off a virus, but it can cause a great deal of trouble in lupus by stimulating a vicious, self-perpetuating circle of inflammation.  By inhibiting the production of interferon just enough (but not too much) a proper balance might be found between protecting the body from lupus flares and protecting the body from viruses.

Hydroxychloroquine is probably only a weak inhibitor of Toll-Like Receptors. Some potentially stronger biologic drugs, which target the specific Toll-Like Receptors that are acting up in lupus, are currently in the early stages of being studied.

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