This resistance, already reported in some countries of the continent, simply translates into longer recovery time. But it is feared that in the long term, it might cause the treatment to become totally ineffective.
Malaria experts are concerned about the increasing resistance of the malaria pathogen Plasmodium falciparum to artemisinin-based combination therapies (ACTs), the only truly effective drug against malaria today. Researchers highlighted this resistance in Uganda in an article published in the New England Journal of Medicine (NEJM) in September 2021. This kind of resistance had already been documented in the Mekong Valley in Southeast Asia, where countries are moving towards malaria elimination. Resistance in a malaria-endemic area is a real concern for disease control.
However, Elisabeth Juma, a public health specialist at the World Health Organization (WHO) office for Africa, underscored that, as the name suggests, ACTs are a combination of drugs in which artemisinin is combined with either amodiaquine or lumefantrine. “The resistance we’re talking about is partial resistance, because it concerns artemisinin and not the partner drug. So it is not accurate to talk about resistance to ACTs,” she explains.
Matthew Coldiron, a researcher at Epicentre, the medical research department of Doctors Without Borders (MSF), explains that ACTs were so effective that after 24 hours, no parasite could be found in the patient’s bloodstream. But, as the first sign of this resistance, it was discovered that it required more time to clear the parasite. “We realized that instead of getting rid of the parasite in the bloodstream in 24 hours, it now took 36 or 48 hours. And this is very annoying for us as researchers,” he says.
Insights
The problem is not that it is the first time the scientific community is faced with the resistance of Plasmodium falciparum to antimalarial drugs. Indeed, it is due to this same problem of resistance that some drugs such as chloroquine and Fansidar, formerly used against malaria, became ineffective and were no longer administered as first-line drugs in Africa. But the real concern for experts is that for the first time, a form of resistance has emerged in Africa, the world’s main malaria breeding ground. “What happened with chloroquine and Fansidar is that resistance emerged in Asia and then spread to Africa later on. And this took about 20 years,” explains Matthew Coldiron.
According to his clarifications, the scientific community knew that artemisinin resistance existed in Southeast Asia (Vietnam, Thailand, Cambodia, Laos) since 2005 and expected these mutations to spread and reach Africa in five or ten years. But the novelty is that the mutations recently recorded in Uganda and Rwanda that resulted in artemisinin resistance are new. “The mutation that emerged in Uganda is not the same mutation that was recorded in Asia. And the one observed in Rwanda is also not the same as the one in Uganda; but, they both have the same effect.”
Experts blame the emergence of such resistance on the natural tendency of parasites to find ways to escape the body’s immune system and the drugs that are supposed to fight them. But Philippe Guérin, Director of the Infectious Diseases Data Observatory (IDDO) believes that there are certain circumstances that may have contributed to the emergence of this resistance. Among these circumstances, he mentions the use of fake drugs.
“Adulterated drugs that have no antimalarial action at all are indirectly a risk because patients will not be treated and their parasitaemia will increase. The higher the parasitaemia, the more difficult the following treatment will be and therefore, it indirectly facilitates resistance” explains Philippe Guérin.
Combination
He further explains that poor quality drugs that are not appropriately dosed could also contribute to the emergence of resistance. An assumption that Elisabeth Juma confirms by pointing out that “when the parasite is exposed to an insufficient dose of the drug, it can learn to survive it”.
She also reminds us that “in the case of South-East Asia, this resistance to artemisinin may be due to the fact that each sick person used to go directly to the store and simply buy artemisinin and take it. The combination was adopted to delay the development of resistance.
Currently, it is difficult to have a clear picture of the extent of ACT resistance in Africa. Uganda, Rwanda, Eritrea, Mali and Burkina Faso are some of the countries where such resistance has already been detected on the continent. But,” emphasizes Philippe Guérin, “it is possible that this kind of resistance exists elsewhere and we are simply not aware. So, it is extremely important to build our capacity to monitor antimalarial drug resistance to determine the extent of the problem in Africa today.
Elisabeth Juma adds that this is precisely why WHO calls on countries to conduct the efficacy monitoring of the antimalarial drugs they administer. “This means that when you receive patients with malaria, you give them drugs and you monitor the rate at which the parasite decreases in their body each day until it completely disappears. Then you follow-up these patients for up to 28 days or up to 42 days. At the end, you retest to see if the disease is completely cleared or if it has reappeared.”
New drugs
This is the process through which Rwanda and Uganda noticed the presence in their territories of this parasite’s mutation with the gene that makes it resistant to artemisinin. Experts insist that if this monitoring is not carried out, the existence of this resistance will be hidden. “Simply because having this partial resistance to ACTs does not mean that you will not be cured of the disease. The partner drug is still working and you will be cured, but it will take a little longer than before. So, even if patients continue to be cured, it’s important for us to know how this phenomenon spreads,” explains Elisabeth Juma.
At the moment, the greatest worry at WHO and other organizations working in malaria control is that this resistance will also affect artemisinin’s partner drugs. And it is largely believed that this will happen sooner or later. This would mean that the drug will no longer be able to cure patients. Hence, the unanimous call to develop new drugs in addition to the usual prevention methods.
Julien Chongwang
