Monitoring Efficacy and Safety of Antimalarial Drug and Resistance
Malaria is an acute febrile illness caused by Plasmodium parasites, which are spread to people through the bites of infected female Anopheles mosquitoes.
Malaria is a treatable disease. Artemisinin-based combination therapies (ACTs) are the most effective antimalarial medicines available today and the mainstay of recommended treatment for Plasmodium falciparum malaria, the deadliest malaria parasite globally.
ACTs combine 2 active pharmaceuticals with different mechanisms of action, including derivates of artemisinin extracted from the plant Artemisia annua and a partner drug. The role of the artemisinin compound is to reduce the number of parasites during the first 3 days of treatment, while the role of the partner drug is to eliminate the remaining parasites.
The emergence of multidrug resistance is a public health concern that threatens the sustainability of global efforts to eliminate and reduce the burden of malaria. Regular monitoring of drug efficacy is needed to inform treatment policies in malaria-endemic countries, and to ensure early detection of, and response to, drug resistance.
Artemisinin-based combination therapies (ACTs), recommended by WHO for the treatment of uncomplicated malaria caused by Plasmodium falciparum and for chloroquine-resistance P. vivax, have been an integral part of the remarkable recent success in global malaria control. Protecting the efficacy of these combination medicines is now seen as a top global public health priority.
The development of resistance to drugs poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. Resistance to currently available antimalarial drugs has been confirmed in only two of the four human malaria parasite species, Plasmodium falciparum and P. vivax. It is unknown if P. malariae or P. ovale has developed resistance to any antimalarial drugs. P. knowlesi, a zoonotic monkey malaria that infects humans in forest fringe areas of Southeast Asia, is thought to be fully susceptible to chloroquine and other currently used drugs. Parasite resistance results in a delayed or incomplete clearance of parasites from the patient’s blood when the person is being treated with an antimalarial.
Drug-resistant P. falciparum
Chloroquine-resistant P. falciparum first developed independently in three to four areas in Southeast Asia, Oceania, and South America in the late 1950s and early 1960s. Since then, chloroquine resistance has spread to nearly all areas of the world where falciparum malaria is transmitted, with the exception of Central America west of Panama Canal, Haiti, and the Dominican Republic.
P. falciparum has also developed resistance to nearly all of the other currently available antimalarial drugs, such as sulfadoxine/ pyrimethamine, mefloquine, and quinine. Although resistance to these drugs tends to be less widespread geographically, in some areas of the world, the impact of multi-drug resistant malaria can be substantial. Most recently, partial artemisinin resistance has independently emerged in parts of Southeast Asia, South America, and East Africa, impacting the efficacy of artemisinin-based combination therapy, the main class of antimalarials used worldwide.
Drug-resistant P. vivax
Chloroquine-resistant P. vivax malaria was first identified in 1989 among Australians living in or traveling to Papua New Guinea. P. vivax resistance to chloroquine is a major challenge in Oceania and some countries in Southeast Asia. Emerging evidence has suggested chloroquine-resistant P. vivax in other countries and regions but has not impacted treatment policies and further evaluation is needed.
Strategic Outlook to deal with Antimalarial drug Resistance
In November 2022, the World Health Organization (WHO) published four pillar strategy comprising a set of interventions to be adapted to specific contexts and implemented at local, regional and global levels:
- Strengthening antimalarial resistance surveillance.
- Optimizing and better regulating the use of medicines and diagnostics to reduce selection for resistance.
- Limiting the spread of drug-resistant parasites.
- Stimulating research and innovation to develop new tools against resistance and to better leverage existing ones.
My Takeaways
Never use single-drug artemisinin therapies, as this worsens resistance. Treatment must be guided by local resistance data and confirmed by a doctor.
Pairing a fast-acting artemisinin derivative with a longer-lasting partner drug clears the infection and protects the medicine.
Countries must track treatment failures early to change drug policies before outbreaks worsen.
Are people with sickle cell anaemia more susceptible to malaria?
MBH/PS