A technician at a Chinese pharmaceutical company works to grow the sweet wormwood plant used to create artemisinin, the basic drug to kill the malaria parasite.

Huang Xiaobang/Xinhua via Getty Images/Xinhua News Agency

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Huang Xiaobang/Xinhua via Getty Images/Xinhua News Agency

Lately, Dr. Ruth Namazzi and her colleagues stopped each other in their hospital ward with worried looks.

In between treating patients, she says, they voice their concerns: “Malaria is very stubborn,” she says they tell her. “”Not responding to treatment.”

Namazzi is a pediatrician at Mulago Hospital in Uganda, where – several times a day – she admits a child with severe malaria.

“These are very sick children,” she says, explaining that children are at greater risk of severe malaria than adults because they have not yet developed immunity. Severe malaria in a child can involve high fever, seizures, anemia, kidney damage, and respiratory distress, among other problems. “A child can become extremely weak. He can’t stand or feed himself.”

For years, Namazzi – who is also a lecturer at Makerere University’s College of Health Sciences – has turned to a drug called artemisinin. The drug is derived from an ancient Chinese malaria treatment that was rediscovered a few decades ago and saved millions of lives. It made such a profound difference that one of the people who helped revive prescription medicine received a Nobel Prize for her work.

“It works like magic,” Namazzi says. “Clearing the parasites was very fast (compared to other antimalarial drugs). It had fewer complications. Mortality was lower.”

Is the “magic” fading?

But lately, the magic hasn’t been working so well.

After an infected mosquito bites you and deposits the malaria parasite in your body, the parasite begins to replicate. That’s where artemisinin comes in. Administered intravenously at regular intervals, can kill most parasites in a patient’s blood within hours. But now, Namazzi has seen patients for whom the drug takes days to work.

He wanted to understand what was happening. So he teamed up with others to figure it out. They had several hypotheses: Maybe the dose is too low, or maybe the patients don’t finish the entire course of medication.

But it was something else entirely—an alarming new twist.

Between 2021 and 2022, in Jinja, Uganda, researchers studied 100 children with severe malaria, closely monitoring their mediate intake and regularly assessing the parasite load in their blood.

“What we found was that children with severe malaria have evidence of drug resistance,” he says Dr Chandy Johndirector of the Indiana University School of Medicine Ryan White Center for Infectious Diseases and Global Health and co-author of the study, which was published Thursday in the medical journal JAMA. “The reason this is important is because those children with severe malaria are at the highest risk of death.”

Malaria kills more than half a million people every year, most of them are young children in Africa. This study is the first time researchers have documented signs of resistance in African children with severe malaria. An estimated one to five million children in Africa suffer from severe malaria each year, John says. Unlike patients with uncomplicated malaria, these children have few other options for antimalarial drugs.

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

Three worries

As the study authors scrutinized the findings, three things concerned them: First, they found that for 11 of the 100 children, it took longer than normal—more than 5 hours—to for artemisinins to kill at least half of the parasites in the blood. These children are considered to have partial drug resistance as defined by the World Health Organization. (It’s not complete resistance, because the kids eventually got better.) “Think about it, for any infection, more than 10 out of 100 people you treat don’t get better (rapidly). It’s pretty bad,” says Haldar.

Timing is important because “the higher the parasite load, the more likely you are to have bad outcomes – and that’s death, but there are other complications,” says John. “Survivors (of severe malaria) can have long-term effects. About 25% of them suffer from neurodevelopmental disorders. And we’re also now looking at kidney damage.”

Second, the researchers discovered that some of the children were infected with a mutated malaria parasite; the altered gene they found in this parasite is associated with resistance to malaria drugs.

Finally, on top of all this, researchers found signs of resistance to an oral antimalarial drug children are often sent home with: artemether lumefantrine. The medication should help make sure there are no parasites left in your body. But about 10 percent of the patients the doctors thought were better came back sick within a month.

“So the combination (of drugs) should get rid of malaria, but we haven’t gotten rid of it completely,” says John. He says this is an indication that the parasite may develop resistance to artemether lumefantrine as well.

While all of this has experts worried, they say it’s not entirely surprising.

Artemisinin resistance has been seen before. And it makes sense: diseases evolve to evade drugs. In the past two years, studies in East Africa have shown partial resistance to artemisinin in children with uncomplicated malaria. Additionally, “this is quite similar to what happened in Southeast Asia, where there was clinical resistance to (artemisinin),” says Haldar.

She says the situation in Southeast Asia is different because malaria rates are nowhere near as high as in Africa, “and (researchers) understand the parasites in Southeast Asia — their genetics and resistance profiles drugs – probably much better than new African parasites. “

Still, there are lessons to be learned from Southeast Asia, including close monitoring to see how widespread resistance is and whether new mutations are emerging. Namazzi says it’s also important to make sure patients—both with uncomplicated and severe malaria—maintain their full dose of medication so they don’t build up more resistance.

“Another lesson is that as soon as you’re aware of the problem, you should start thinking about a solution,” says John.

Scientists in Africa and Southeast Asia are studying whether prescribing an additional third malaria drug could combat partial resistance. In addition to the drug options that already exist, Haldar says the study shows “a greater need for new treatment.” But, she says, “developing a new drug is a very long process,” and no new drug is ready to take the place of artemisinin.

Experts say one thing gives them hope: Over the past few years, malaria vaccines have become available.

“All of us in the field feel that it’s a race here – that we have to beat malaria before there is widespread drug resistance,” says John.