Emergence of antimalarial drug resistance in Africa

Malaria is widespread in the tropics and subtropics. In 2019, more than 200 million cases and more than 400,000 deaths related to the disease were reported. Malaria is caused by parasites of the Plasmodium group. The most common treatment involves the drug artemisinin, but over the past 10 years, P. falciparum parasites – causing most malaria deaths – resistant to artemisinin have emerged and spread in Southeast Asia. Also in Africa, resistant to artemisinin P. falciparum parasites have been discovered in recent years, posing a serious threat to the fight against malaria. Now, Toshihiro Mita of Juntendo University and his colleagues carried out a quantitative study of the clinical resistance to artemisinin of the parasite in the north Uganda and identified parasitic mutations associated with resistance.

Scientists worked with data collected from 2015 to 2019 at a hospital in Gulu, Uganda. They looked at the effect of treatment with an artemisinin drug (called artesunate) on more than 200 P. falciparum-infected patients. Patients received three doses of the drug within 24 hours. The blood was regularly analyzed for traces of the parasite; these measurements made it possible to estimate the parasite clearance half-life. A clearance half-life greater than 5 hours (meaning that more than half of the parasites still survived 5 hours after the initial drug dose) was found to be significant. in vivo resistance to artemisinin. In most cases, the parasites were quickly eliminated, but 5.8% of cases showed resistance, which was otherwise stable over the period 2017-2019.

The researchers also looked at the genotype (the relevant genetic information) of the parasites with which the patients were infected. Seven so-called kelch13 mutations were detected in 15.8% of cases, two (labeled A675V and C469Y) being prevalent. The latter have been shown to be correlated with a longer clearance half-life, suggesting that they can be used as predictive markers of in vivo resistance to artemisinin. Currently, A675V and C469Y are classified by the World Health Organization as candidate markers. Mita and colleagues’ evidence for A675V implies that its status should be updated to become that of an appropriate molecular resistance marker.

Finally, by comparing the Asian and African A675V mutants, the scientists were able to show that the two had different origins – in other words, resistance to artemisinin emerged independently in Africa, not because of immigration. As a potential cause for the emergence of resistant mutants, researchers suggest overuse of injectable artesunate.

Mita and colleagues’ results clearly demonstrate the independent emergence of artemisinin resistant strains P. falciparum in Africa, which, citing the scientists, “presents a potential risk of cross-border spread through Africa, emphasizing the need for large-scale surveys. “

Background

Malaria

Malaria is a disease caused by microorganisms in the Plasmodium group. It is usually transmitted by an infected mosquito: a mosquito bite introduces the Plasmodium parasites in a person’s blood. There are five species of Plasmodium that can infect humans, with most deaths caused by P. falciparum.

Symptoms of malaria include fever, chills, headache, muscle pain, and fatigue. In addition, nausea, vomiting, and diarrhea can also occur, as well as anemia and jaundice (yellowing of the skin and eyes) due to the loss of red blood cells. The diagnosis of malaria is usually made by examining the blood.

The recommended treatment for malaria is a combination drug that almost always includes artemisinin. In areas where malaria is prevalent, it is recommended to confirm the disease first before starting treatment because of fears of developing drug resistance. Indeed, resistance to artemisinin is now well established in Southeast Asia. Now, Toshihiro Mita from Juntendo University and colleagues confirmed resistance to artemisinin in Africa also, with resistance in Africa not due to immigration but having emerged independently.

Artemisinin

Artemisinin and its derivative molecules are a group of drugs used to treat malaria caused by the parasite Plasmodium falciparum. Tu Youyou discovered artemisinin in 1972 and received the Nobel Prize in Physiology or Medicine in 2015 for its discovery. Nowadays, therapies involving the administration of artemisinin are not only standard for a cure P. falciparum malaria but also for malaria caused by other species of the Plasmodium group.

The advantage of artemisinin and its derivatives for treating malaria over other drugs is that they quickly kill all life cycles of a parasite.

Reference

Betty Balikagala, Naoyuki Fukuda, Mie Ikeda, Osbert T. Katuro, Shin Ichiro Tachibana, Masato yamauchi, Walter Opio, Sakurako Emoto, Denis A. Anywar, Eisaku Kimura, Nirianne MQ Palacpac, Emmanuel I. Odongo-Aginya, Martin ogwang, Toshihiro Horii & Toshihiro Mita. Evidence of artemisinin-resistant malaria in Africa. New England Journal of Medicine, 385: 1163-1171 (2021).

Posted online September 2021
DOI: 10.1056 / NEJMoa2101746
Url: https://www.nejm.org/doi/full/10.1056/NEJMoa2101746

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The mission of Juntendo University is to strive for the advancement of society through education, research and healthcare. To accomplish this mission, based on the Japanese idiom “Sanmu Syugi”, Juntendo University accepts anyone, regardless of gender, nationality or academic background, who embodies the university motto “Jin – I exist as you exist ”and the principle of“ Fudan Zenshin – Continuously moving forward ”. By creating an environment focused on how improvements can be made in the future, Juntendo University helps highly motivated people who care for others become healthcare professionals that patients can believe in, capable scientists. discoveries and innovative inventions and citizens of the world ready to serve society.

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Juntendo was founded in 1838 as a Dutch medical school at a time when Western medical education was not yet integrated into Japanese society. With the creation of Juntendo, the founders hoped to create a place where people could come together with the common goal of helping society through the powers of education and medical practices. Their aspirations led to the creation of Juntendo Hospital, the first private hospital in Japan. Over the years, the institution’s experience and perspective as an institution of higher education and a place of clinical practice has enabled Juntendo University to play an essential role in the formation of teaching and Japanese medical practices. Along the way, the focus of the institution has also expanded, now comprising six undergraduate and three graduate programs, the university specializes in the fields of health sciences, science of health and sports, health care and nursing and international liberal arts, as well as medicine. Today, Juntendo University continues to pursue innovative approaches in education and research at the international level with the aim of applying the results to society.

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