Goat and SodaExBulletin

Engineers at a Chinese pharmaceutical company are working to breed sweet mugwort, a plant used to create artemisinin, the go-to drug for killing malaria parasites.

Huang Xiaobang/Xinhua News Agency, via Getty Images/Xinhua News Agency

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Huang Xiaobang/Xinhua News Agency, via Getty Images/Xinhua News Agency

These days, Dr. Ruth Namazzi and her colleagues stop each other in the hospital ward with worried looks on their faces.

In between treating patients, they express concerns: “They say, 'Malaria is so stubborn,'” she says. “It's not responding to treatment.”

Namazzi is a pediatrician At Mulago At a hospital in Uganda, she admits children with severe malaria several times a day.

“These are very seriously ill children,” she says, explaining that children are at higher risk of severe malaria than adults because they have not yet developed immunity. Severe malaria in children can cause problems, especially high fever, convulsions, anemia, kidney damage, and difficulty breathing. “Children can become extremely weak and unable to stand or feed themselves.”

Mr Namazzi, who is also a lecturer at Makerere University's Faculty of Health Sciences, has relied on a drug called artemisinin for many years. This drug is derived from ancient Chinese malaria treatments. rediscovered decades ago And it has saved millions of lives. It made a huge difference. One of the people who contributed to the revival of medical recipes was received nobel prize for her work.

“It works like magic,” Namazzi said. “The parasite removal was very quick. [compared to other malaria medications]. There were also fewer complications. Mortality rates were low. ”

Is “magic” disappearing?

But lately, that magic hasn't been working as well.

When malaria parasites enter the body through the bite of an infected mosquito, the parasites begin to multiply. This is where artemisinin comes in. When administered intravenously on a regular basis, It can kill most parasites in a patient's blood within a few hours. But now Namazzi is seeing patients whose drugs take several days to work.

She wanted to understand what was going on. So she worked with others to solve it. They made several hypotheses. Perhaps the dose was too low, or perhaps the patient did not complete the full course of medication.

But it was something else entirely, and a worrying new development.

In Jinja, Uganda, from 2021 to 2022, researchers studied 100 children with severe malaria, carefully monitoring their vector intake and regularly measuring parasite loads in their blood. Evaluated.

“What we found was that children with severe malaria had evidence of drug resistance,” he says. Dr. Candi JohnDirector of the Ryan White Center for Infectious Diseases and Global Health, Indiana University School of Medicine. He is a co-author of the study, published Thursday in the medical journal JAMA and presented at the annual meeting of the American Academy of Tropical Medicine and Hygiene. “This is important because children with severe malaria are at the highest risk of death.”

The number of deaths due to malaria is 500,000 people Each year, most of them are young African children. The study is the first time researchers have documented signs of resistance in African children with severe malaria. According to John, it is estimated that between 1 million and 5 million children in Africa contract severe malaria each year. Unlike patients with uncomplicated malaria, these children have few other options for malaria treatment.

“Clinically, this is very worrying because there is still a lot of malaria in Africa,” he says. Kasturi HaldarA professor of biological sciences at the University of Notre Dame, who has studied malaria for decades, was not involved in this study.

three worries

When the study authors took a closer look at their findings, they found three concerns. First, they found that in 11 out of 100 children, artemisinin took longer than usual (more than 5 hours) to kill at least half of the parasites in the bloodstream. These children are considered partially drug resistant, as defined by the World Health Organization. (The kids eventually got better, so it's not completely resistant.) “Think about it: With any infection, more than 10 out of 100 people you treat don't get better.” [quickly]. That’s really terrible,” Halder says.

“The longer you have a high parasite load, the more likely you are to have a bad outcome, because it not only leads to death, but also other complications,” John says. “Survivors [of severe malaria] It can have long-term effects. About 25% of them have neurodevelopmental disorders. And we're now looking at kidney damage as well. ”

Second, researchers discovered that some children were infected with mutated malaria parasites. The researchers believed that the genetic changes discovered in the parasite were associated with resistance to malaria drugs.

Finally, on top of all this, the researchers found signs of resistance to artemether lumefantrine, an oral antimalarial drug that often causes children to be sent home. It is believed that this drug helps to ensure that there are no parasites left in the body. But about 10% of patients whose doctors thought they were getting better ended up getting sick again within a month.

“So that combination is [of drugs] It's supposed to get rid of malaria, but it doesn't actually get rid of it completely,'' John said. This suggests that the parasite may also have developed resistance to artemether lumefantrine.

All of this worries experts, but they say it's not entirely surprising.

Resistance to artemisinin has been seen before. That's natural. Diseases evolve to avoid drugs. Over the past few years, studies in East Africa have shown partial resistance to artemisinin in children with uncomplicated malaria. He added: “This is very similar to what happened in Southeast Asia where there was clinical resistance. [artemisinin]” says Halder.

She says the situation in Southeast Asia is different because the incidence of malaria is not as high as in Africa. ” [researchers] We probably understand the genetics and drug resistance profiles of Southeast Asian parasites much better than we do of African parasites. ”

Still, there are lessons to be learned from Southeast Asia, including closely monitoring how widespread resistance is and whether new mutations emerge. Namazzi says it's also important to ensure that patients with both uncomplicated and severe malaria continue on their full dose of medication to avoid developing further resistance.

“Another lesson is that as soon as you notice a problem, you should start thinking about solutions,” says John.

Scientists in Africa and Southeast Asia are studying whether partial resistance can be countered by prescribing an additional (third) malaria drug. Halder said the study showed “an increasing need for new treatments” in addition to existing treatment options. But “developing new drugs is a very long process,” and new drugs to replace artemisinin are not yet ready, she says.

Experts say one thing is giving them hope. malaria vaccine is now available.

“All of us on the ground feel this is a race, and we need to eliminate malaria before drug resistance becomes widespread,” says John.