Disturbing Trend: Essential Malaria Treatment Shows Signs of Ineffectiveness

In Eastern Africa, there are emerging signs that malaria parasites are growing resistant to artemisinins, the drugs central to existing treatment protocols. This worrisome trend, documented in research studies conducted in Eritrea, reveals a decline in the efficacy of artemisinin-based combination therapies (ACTs) and the appearance of drug-resistant parasites with genetic mutations and deletions. These mutations make the parasites both resistant to medication and unidentifiable by commonly used diagnostic methods.

The research in question was recently published in the New England Journal of Medicine and spearheaded by a team led by Didier Ménard, Ph.D., from the Université de Strasbourg/Institut Pasteur in France, along with David Fidock, Ph.D., from Columbia University’s Vagelos College of Physicians and Surgeons.

Present-day malaria treatments rely heavily on a combination of artemisinin drugs and partner antimalarial medications. Since the early 2000s, these combined drugs have effectively treated non-severe malaria cases, typically eliminating the parasite from a patient’s bloodstream within a three-day treatment period.

However, Plasmodium falciparum parasites are increasingly showing resistance to these drugs, jeopardizing the strides made in malaria control between 2000 and 2015, during which period malaria-related fatalities in Africa were reduced by 66%. Artemisinin resistance first appeared in Southeast Asia in 2009 and was followed by resistance to partner drugs. By 2016, in some Southeast Asian regions, the failure rate for treatment had soared to 85%. Such resistance arises from mutations in the parasite gene Pfkelch13.

Historically, drug resistance observed in Southeast Asia often spreads to Africa after a delay of approximately a decade. This is concerning, given that over 95% of all malaria-related deaths occur on the African continent.

New Evidence of Drug Resistance in the Horn of Africa

The study, led by Ménard, in collaboration with the Ministry of Health in Eritrea, examined the performance of ACTs in almost 1,000 patients from 2016 to 2019. Their findings indicate that drug efficacy has diminished over this period: failure rates for clearing the parasites increased from 0.4% in 2016 to 4.2% in 2019, surpassing the World Health Organization’s threshold for declaring resistance.

Furthermore, the research discovered that as of 2019, around 20% of patients were infected with parasites carrying artemisinin-resistant Pfkelch13 mutations. The Columbia University team, led by Fidock, conducted laboratory tests confirming that this common Pfkelch13 mutation is directly responsible for artemisinin resistance.

A key question now is how prevalent these Pfkelch13 mutations are across Africa, especially since most malaria deaths occur in the central and western parts of the continent. According to Fidock, more extensive genetic surveillance and studies on therapeutic efficacy are needed.

Elusive Parasites Complicate Diagnosis

Adding to the urgency of the situation, many parasites in Eritrea possess genetic deletions that make them undetectable through the most commonly used rapid diagnostic tests for malaria. Approximately 17% of patients in Eritrea would receive a negative result using this diagnostic test, which has since been phased out in Eritrea but is still widely used elsewhere in Africa.

This implies that individuals presenting with symptoms at clinics might be misdiagnosed, putting them at risk of worsening illness or even death. Especially concerning is that artemisinins are used in isolation for severe cases of malaria that require intravenous administration. Parasites possessing the Pfkelch13 mutation may not be swiftly eradicated, increasing the probability of severe outcomes. Health professionals across the region need to recognize that a negative test result may not necessarily rule out malaria.

The Importance of the Study

According to Ménard, the established presence of drug resistance in the Horn of Africa increases the likelihood that partner antimalarials will also become ineffective, potentially causing a surge in malaria cases and fatalities. While the parasites have not yet shown resistance to partner drugs, should such resistance emerge, the situation could escalate quickly. While efforts to develop new treatments are ongoing, options remain severely limited at present.

References

The study was funded through a variety of sources, including the Bill and Melinda Gates Foundation, the Global Fund to Fight AIDS, Tuberculosis, and Malaria, the Ministry of Health in Eritrea, the Institut Pasteur, the French Government, and the U.S. National Institutes of Health. The paper was published under the title “Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea” in the New England Journal of Medicine. The DOI is 10.1056/NEJMoa2210956.

Frequently Asked Questions (FAQs) about Artemisinin-Resistant Malaria

More about Artemisinin-Resistant Malaria

• New England Journal of Medicine: Increasing Prevalence of Artemisinin-Resistant HRP2-Negative Malaria in Eritrea
• World Health Organization: Malaria
• Bill and Melinda Gates Foundation: Malaria Strategy Overview
• The Global Fund to Fight AIDS, Tuberculosis, and Malaria
• U.S. National Institutes of Health: Malaria Research
• Institut Pasteur: Malaria Research Program
• Université de Strasbourg: Medical Research
• Columbia University Vagelos College of Physicians and Surgeons: Department of Microbiology & Immunology
• Agence Nationale de la Recherche (French National Research Agency)