Key Antimalarial Drug Artemisinin-Based Therapies May Be Losing Effectiveness

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Key Antimalarial Drug Artemisinin-Based Therapies May Be Losing Effectiveness

In East Africa, malaria parasites are developing resistance to artemisinin-based therapies, which are crucial for treating malaria.

If partner drugs also become ineffective in the future, it could pose a significant threat to the health of local populations.

A research report from Eritrea indicates that this alarming development suggests a decline in the effectiveness of artemisinin-based combination therapies, along with the emergence of parasite gene mutations and deletions that render them resistant to these drugs, making them undetectable through routine diagnostic tests.

Key Antimalarial Drug Artemisinin-Based Therapies May Be Losing Effectiveness

In East Africa, malaria parasites are developing resistance to artemisinin-based therapies, which are currently a cornerstone of malaria treatment. If partner drugs fail in the future, this development could greatly exacerbate the impact of malaria.

A research team led by Dr. Didier Ménard from the University of Strasbourg/Basler Institute and including microbiologist Dr. David Fidock from Columbia University recently reported these findings in the New England Journal of Medicine, based on their research conducted in Eritrea.

Malaria treatment relies on a combination of artemisinin drugs and antimalarial medications. Since the early 2000s, these drug combinations have been highly effective in treating uncomplicated cases, typically clearing the malaria parasites from a patient’s bloodstream within three days.

However, the deadly malaria parasite is developing resistance, which could potentially roll back the progress made in combating malaria between 2000 and 2015 when malaria deaths in Africa decreased by 66%. In 2009, resistance to artemisinin-based therapies first emerged in Southeast Asia, followed shortly by resistance to partner drugs. By 2016, treatment failure rates in some parts of Southeast Asia had reached 85%. Resistance to artemisinin components is caused by mutations in the malaria parasite gene Pfkelch13.

In the case of drug-resistant malaria, situations that occur in Southeast Asia often take about a decade to appear in Africa, possibly due to drug-resistant parasites crossing into Africa or because the same resistance mechanisms take longer to establish themselves in the high-transmission environments of Africa. Over 95% of malaria-related deaths occur in Africa, making the increase in drug resistance there particularly alarming.

Key Antimalarial Drug Artemisinin-Based Therapies May Be Losing Effectiveness

New discovery: Drug resistance in the Horn of Africa

In this new study, Ménard’s research team, along with colleagues from the Eritrean Ministry of Health, assessed the effectiveness of artemisinin-based combination therapy in nearly 1,000 patients in Eritrea from 2016 to 2019.

The researchers found that during this period, the effectiveness of the drug therapy had declined. In 2016, 0.4% of patients could not clear the parasites, which rose to 4.2% in 2019, surpassing the threshold for declaring drug resistance set by the World Health Organization. By 2019, about one in every five patients was infected with artemisinin-resistant Pfkelch13 mutant parasites.

Dr. Fidock’s research team at Columbia subsequently conducted genetic experiments using laboratory-cultured parasites, demonstrating that the most common Pfkelch13 mutations found in Eritrea were a direct cause of artemisinin resistance.

The pressing question now is how widespread these Pfkelch13 mutations are across the entirety of Africa. “What we’re seeing is not the emergence of new strains recently. It’s just taken this long to be discovered,” Fidock remarked. “Malaria incidence is high in central and western Africa, but we don’t know what’s happening there. There needs to be more genetic surveillance and efficacy studies.”

Parasites also learn to evade detection

The study also found a more concerning situation in Eritrea, where many parasites had gene deletions, causing the most common malaria rapid diagnostic tests to miss detecting the parasites.

Approximately 17% of patients in Eritrea tested negative when using this diagnostic method, leading Eritrea to discontinue its use. However, this test is still widely used throughout Africa. The transmission of these test-negative parasites poses a significant barrier to accurate diagnosis.

Fidock explained, “This means that if someone presents with symptoms at a clinic and tests negative for malaria, they won’t receive the correct treatment. Their symptoms might worsen, or they might even die. Since artemisinin-based drugs are only used for severe malaria and must be administered intravenously, the risk becomes even greater. Parasites with the Pfkelch13 gene mutation may not be eliminated quickly, increasing the risk of fatality. Clinical practitioners in the region need to be aware that patients with negative test results may indeed have malaria.”

Why it deserves attention

Ménard emphasized, “Unfortunately, our research has found that drug resistance has firmly taken hold in the Horn of Africa, making it more likely that partner drugs could fail due to artemisinin resistance, leading to a potential surge in malaria cases and deaths.”

While partner drugs have not yet developed resistance to artemisinin therapy, the current situation is not without concern. Fidock stated, “But if these partner drugs fail, the situation could deteriorate rapidly. We are working hard to develop new drugs, but the available options are currently very limited.”