Autor: Mary Flor Alberca Díaz-Plaza, 3º, Parasitología, Farmacia y Biotecnología bilingüe.
Resistance against Malaria drugs has been a battle since day one. This article will be focused on Malaria caused by Plasmodium falciparum even if there are more species causing this disease. This parasite has evolved to evade many of the drugs that researchers have developed to fight tropical diseases. The timeline of resistance can be summarized in this table:
The last discover was Artemisinin-combination therapies (ACTs). Plasmodium falciparum resistance to these therapies started to crop up around 2007. Infections, especially in the Greater Mekong area of Southeast Asia, seemingly survived treatment. This was largely due to the pairing of artemisinin derivatives with older drugs that had existing resistance problems. But some experts think the emergence of partial resistance to artemisinin itself (which allows parasites to persist for longer in the body following treatment) could also play a role.
Investigations into delayed-clearance mechanisms pointed to various mutations in the kelch13 gene, which codes for a poorly understood kinase-binding protein. In vitro studies show that the parasite’s resistance is effective at a specific life stage—the early ring stage, which occurs soon after P. falciparum enters a red blood cell but before it starts replicating. Artemisinin derivatives get metabolized by the body very quickly, so “resistant” parasites appear to evade the drug by lingering longer in the ring stage.
Of all the kelch13 mutants, one haplogroup, called the KEL1 lineage, appeared to have the potential to spread more aggressively than others together with PLA1 parasites. These mutants came to dominate the landscape in Cambodia and soon spread to Thailand, Laos, and Vietnam. By 2013, more than 90% of resistant parasites carried alleles from both lineages.
Ultimately, most experts agree that ACT resistance needs to be monitored, but when it comes to extinguishing malaria, which has stubbornly maintained a constant global burden since 2015 there are bigger fish to fry.
Rather, experts say, logistical challenges of delivering ACT therapies, diagnostic tools, and other life-saving interventions such as insecticide-treated bed nets have caused declining mortality rates. Some, however, continue to sound the alarm. Even if delayed clearance doesn’t directly lead to treatment failure, it puts more pressure on partner drugs to succeed in mopping up lingering parasites.
Noticia original: https://www.the-scientist.com/features/are-we-headed-for-a-new-era-of-malaria-drug-resistance--65496
Otras fuentes: https://aac.asm.org/content/59/6/3156.long
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