By Zheng Qi 2020-06-16

The effectiveness of every WHO-recommended Artemisinin-based Combination Therapy (ACT) around the world is rigorously evaluated through standardized, gold-standard research known as therapeutic efficacy studies, or TES for short. Unlike informal clinical observations or scattered patient reports, these studies follow a strict, globally harmonized protocol designed by WHO, tracking hundreds of confirmed malaria patients over several weeks to carefully measure how well the ACT clears parasites, prevents symptom relapse, and delivers a complete cure. When these studies are repeated at regular, consistent intervals at the exact same surveillance sites, they create a long-term, continuous data record that acts as an early warning system for public health teams. This consistent, repeated monitoring makes it possible to spot even subtle, gradual declines in drug performance months or even years before widespread treatment failures start appearing in local clinics, generating the hard, evidence-based data that national malaria control programs rely on to update their official treatment policies, adjust drug recommendations, and protect patients from ineffective therapies.

While artemisinin partial resistance on its own very rarely causes full treatment failure, the situation in the Greater Mekong Subregion (GMS) has grown far more complex over the past two decades. In this part of Southeast Asia, the partial loss of artemisinin effectiveness has been paired with a parallel, growing resiastance to several of the partner drugs that are meant to finish clearing any remaining parasites after the artemisinin component acts. This dangerous double layer of resistance — where both parts of the two-part ACT formula are losing their power at the same time — is the root cause that has led to multiple standard ACTs failing completely across large swathes of the GMS. Even so, the situation is far from hopeless: managing this evolving drug resistance landscape does demand constant, close surveillance, rapid data sharing between neighboring countries, and careful adjustments to local treatment guidelines, but there are still fully effective ACT formulations available today that can reliably cure patients, even in the areas where drug resistance is at its most severe. These remaining effective therapies are being prioritized for distribution, paired with enhanced community outreach to ensure every patient completes their full treatment course, preventing further spread of resistant parasite strains.

In the four African countries where artemisinin partial resistance has already been officially confirmed — Eritrea, Rwanda, Uganda, and the United Republic of Tanzania — national health authorities have ramped up their TES programs to unprecedented levels. These ongoing, systematic studies are designed to continuously verify that the ACTs currently listed in each country’s national malaria treatment policy still maintain their full, expected level of efficacy, catching any small drop in performance before it can escalate into a public health crisis. This proactive monitoring is especially critical in Africa, where the vast majority of global malaria cases occur, and where even small declines in ACT effectiveness could put millions of vulnerable children and pregnant people at risk. In other, broader regions of the African continent, a small number of recent TES studies have already reported unexpected cases of treatment failure in patients using two of the most widely deployed ACTs globally: artemether-lumefantrine and dihydroartemisinin-piperaquine. Right now, WHO is working side by side with national health ministries, local research institutions, and global public health partners to carry out urgent, in-depth investigations to confirm exactly what is driving these rare treatment failures, and to determine if they are linked to emerging resistance in the partner drug component of these ACTs. This coordinated, rapid response is designed to stop any potential resistance from spreading further, protecting the decades of hard-won progress against malaria that has saved millions of lives across Africa.