The Tu Yu team issued a document: Artemisinin faces the challenge of resistance? Still the first choice for anti-malaria

The Tu Yu team issued a document: Artemisinin faces the challenge of resistance? Still the first choice for anti-malaria

April 26, 2019 Source: New Perspectives in Medicine

Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];

Since the birth of the Nobel Prize in 2015, the antimalarial artemisinin has once again “blushing” into the public eye. For over forty years, this drug has saved millions of lives worldwide.

In the past, faced with the challenge of solving the drug resistance, the researchers brought about the discovery of artemisinin through decades of hard work. However, antimalarial drug resistance is a recurring problem. At present, about half of the world's population still faces the risk of malaria, and more than 90 countries and regions have persistent malaria transmission.

In this context, the Tucson research team published an article in the New England Journal of Medicine (NEJM) on the status and solutions of artemisinin resistance.

Combination therapy based on artemisinin and its derivatives is a first-line antimalarial treatment recommended by the World Health Organization. Artemisinin can rapidly improve parasitemia, and other drugs used in combination can help remove residual Plasmodium.

In recent years, five countries in the Mekong River Basin (Cambodia, Myanmar, Thailand, Laos, and China) have found signs of slowing the clearance of malaria parasites after artesunate. Further studies revealed mutations in the K13 gene of these hard-to-eliminate Plasmodium. Although the K13 gene mutation is not completely related to the risk of treatment failure, the Plasmodium with this mutation is still defined as the "artemisinin-resistant" type. Patients who are infected with this type of Plasmodium are more likely to relapse after a standard 3-day course of artemisinin combination therapy (ACTs).

But clinical research in China quickly brought new clues. Studies have shown that strengthening the dose of artemisinin may solve this problem. Even if the early detection of Plasmodium is slow, the infection can be effectively cured after 7 days of continuous administration.

So, should the delay in the elimination of malaria parasites by artemisinin be defined as “resistance”? In any case, the 3-day treatment is no longer effective in the Mekong River Basin. How to deal with this threat is a top priority.

The team's advice is that the continued rational and strategic use of artemisinin combination therapy remains the best and perhaps the only solution for the foreseeable future. This is mainly based on two considerations.

An important supporting evidence is that artemisinin "resistance" is currently manifested by delayed malaria parasite clearance and there is no evidence of complete resistance. Artemisinin is still effective after prolonging the course of treatment or adjusting the combination regimen. For example, in some areas where piperazine plus dihydroartemisinin is not optimal, mefloquine in combination with artesunate may be very effective. In contrast, other drugs with drug resistance problems, even after the course of treatment, the cure rate is also falling. This suggests that the sensitivity of the malaria parasite to artemisinin combination therapy is reduced by the other component drugs, or their interaction with artemisinin, rather than artemisinin itself.

The mechanism of action of artemisinin also supports this. Recent studies have shown that artemisinin requires iron or heme to be activated, and both reach maximum concentration during the trophozoite maturation of Plasmodium. Once activated, artemisinin can act on multiple Plasmodium proteins and Heme. This unique activation and broad targeting mechanism suggests that mutations in individual protein targets are less likely to cause resistance.

At the same time, artemisinin has a short half-life in the blood, while iron or heme concentration fluctuates sharply during the life cycle of the malaria parasite. This explains the delay in the clearance of malaria parasites and brings new ideas to solve the so-called "artemisinin resistance". Artemisinin has good safety tolerance, and it is another strategy to strengthen the drug dosage in the trophozoite stage.

The second factor is, do we have drugs that can replace artemisinin? Although there is a lot of progress in the front of anti-malaria in the field of new drug research and development, the development of new drugs is still a long and arduous process. The snail ketone is a newly discovered potent antimalarial drug, but related resistance mutations have also appeared in the malaria parasite. Therefore, the combination of new drugs with existing antimalarial drugs can help reduce the risk of drug resistance, but non-artemisinin drugs commonly used in combination therapy tend to reduce the efficacy.

The development of next-generation drugs that are more advantageous in terms of effectiveness, safety and risk of resistance remains a major challenge in the short term. At the same time, artemisinin combination therapy is currently inexpensive. Therefore, the team has pointed out that artemisinin is still the first choice for antimalarial combination therapy after 40 years of clinical application. In remote Zambian villages, even artesunate suppository monotherapy has reduced malaria mortality. 96%. Optimizing the current treatment portfolio to maximize the potential of existing anti-malaria weapons is an urgent need for action.

Medical Product

Insulin Syringes Needle,Disable Syringe,Monoject Syringe,10 Ml Syringe

FOSHAN PHARMA CO., LTD. , https://www.fospharma.com