What is antimalaria? Understanding Medications for Malaria

October 5, 2025 •

6 min read

According to the World Health Organization, there were an estimated 249 million cases of malaria and 608,000 deaths in 2022, highlighting the continued global threat of this disease. An antimalaria drug is a medication used to combat the parasitic infection caused by Plasmodium parasites, which are transmitted by infected mosquitos.

Quick Summary

Antimalarial drugs are medications that treat or prevent malaria by targeting the Plasmodium parasite at different stages of its life cycle. Drug classifications, mechanisms of action, and the global challenge of parasite resistance are key factors influencing treatment and prophylaxis strategies.

Key Points

Antimalarial Function: Antimalaria is a drug class that treats or prevents malaria by killing the Plasmodium parasites that cause the disease at various stages of their life cycle.
Artemisinin Combination Therapies (ACTs): ACTs are the gold standard for treating uncomplicated malaria due to their high efficacy and ability to slow resistance by combining a fast-acting artemisinin derivative with a long-acting partner drug.
Drug Resistance is Widespread: The Plasmodium parasite has developed resistance to many traditional antimalarials like chloroquine, necessitating a shift towards combination therapies and the development of new drugs.
Treatment vs. Prophylaxis: Some antimalarials are used for treatment of an active infection, while others are used for prevention (prophylaxis) for travelers, with regimens varying based on destination and personal health.
New Drug Development: Ongoing research is discovering new compounds with novel mechanisms of action, such as MED6-189, to combat emerging drug resistance and improve future treatment strategies.
Patient Safety and G6PD Screening: Before administering drugs like primaquine, screening for G6PD deficiency is mandatory to prevent severe adverse effects, highlighting the need for careful patient evaluation.
Beyond Medication: Effective malaria control requires more than just drugs; it also depends on personal protective measures like insect repellents, bed nets, and high-quality, compliant drug use.

What are Antimalarial Drugs?

Antimalarial drugs are a diverse group of medications designed to treat or prevent malaria, a parasitic disease caused by Plasmodium parasites. These medications work by killing the parasites at various points in their complex life cycle, which involves both mosquitoes and humans. Some drugs target the parasites while they are multiplying in the liver (liver-stage or causal prophylaxis), while others act on the parasites during the red blood cell phase, which causes the disease's symptomatic illness (blood-stage or suppressive prophylaxis). Due to the parasite's ability to develop resistance, a single drug is rarely sufficient, and treatment often involves combination therapy to increase efficacy and slow the development of resistance.

Classification and Mechanisms of Antimalarial Drugs

Antimalarial drugs are categorized based on their chemical structure and mode of action. Understanding these classifications is crucial for selecting the appropriate treatment or prophylaxis for a given geographical region and Plasmodium species.

Artemisinin-Based Combination Therapies (ACTs)

Artemisinins, derived from the plant Artemisia annua, are the most potent and fast-acting antimalarial drugs available.

Mechanism: Artemisinins contain a unique endoperoxide bridge that is activated by iron (from heme in the parasite's food vacuole), producing free radicals that damage parasite proteins and membranes. This broad action targets a wide range of parasite stages.
Combination Therapy: Because of their rapid elimination from the body, artemisinins are always combined with a longer-acting partner drug (e.g., lumefantrine or mefloquine) to ensure the complete clearance of parasites and prevent resistance. ACTs are the recommended first-line treatment for uncomplicated P. falciparum malaria in most parts of the world.
Examples: Artemether-lumefantrine (Coartem) and Artesunate-mefloquine.

Quinolines and Related Compounds

This is a large and historically significant class of antimalarials, including quinine and its synthetic derivatives.

Mechanism: Many quinolines, such as chloroquine, work by inhibiting the detoxification of heme within the parasite's food vacuole, leading to the accumulation of toxic heme and parasite death. Quinine and mefloquine have similar but not identical mechanisms.
Drug Resistance: Widespread resistance to chloroquine has rendered it ineffective in many areas. Resistance is linked to mutations in the Plasmodium falciparum chloroquine resistance transporter (pfcrt) gene. Mefloquine resistance involves gene amplification.
Examples: Chloroquine, Quinine, Mefloquine.

Antifolates

Antifolates interfere with the synthesis of folic acid, a critical nutrient for parasite reproduction.

Mechanism: Drugs like pyrimethamine inhibit the enzyme dihydrofolate reductase, while sulfonamides inhibit dihydropteroate synthetase. Used synergistically in combinations, they create a sequential blockade of the folate pathway.
Drug Resistance: Resistance to antifolates is caused by point mutations in the genes encoding the target enzymes.
Examples: Sulfadoxine-pyrimethamine (SP) is one example, though its effectiveness is limited by widespread resistance.

8-Aminoquinolines

These drugs are critical for eliminating the dormant liver stages of certain Plasmodium species.

Mechanism: Primaquine and tafenoquine are effective against hypnozoites, the dormant liver stages of P. vivax and P. ovale. This is essential for achieving a radical cure and preventing malarial relapse.
G6PD Deficiency: These drugs can cause hemolytic anemia in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency and require pre-treatment screening.

Antimalarial Prophylaxis and Treatment

Antimalarials are used in two main ways: prophylaxis (preventing infection) and treatment (curing an existing infection). The choice of drug depends on the traveler's destination (and local resistance patterns), the specific Plasmodium species, and patient factors.

Prophylaxis Considerations

Travelers to malaria-endemic areas should consult a healthcare provider to determine the appropriate prophylactic regimen. Key considerations include the duration of medication, common side effects, and regional resistance patterns.

Atovaquone/Proguanil (Malarone): Effective for short trips, started 1-2 days before travel and continued for 7 days after. Generally well-tolerated.
Doxycycline: Inexpensive and effective for longer trips, started 1-2 days before travel and continued for 4 weeks after. Common side effects include photosensitivity and gastrointestinal upset. Not for pregnant women or children under 8.
Mefloquine (Lariam): Once-weekly dosing for long-term travel. Associated with neuropsychiatric side effects, so a trial period is recommended.

Treatment Considerations

Treatment for confirmed malaria is tailored to the parasite species, severity, and local drug resistance. In many areas, especially those with chloroquine-resistant P. falciparum, ACTs are the standard of care. For severe malaria, parenteral (intravenous) administration may be required initially. Eradicating dormant liver stages for P. vivax and P. ovale requires a drug like primaquine after initial treatment.

Drug Resistance and New Hope

The emergence and spread of drug-resistant parasites is a major threat to global malaria control efforts. Artemisinin resistance, characterized by delayed parasite clearance, has emerged in Southeast Asia and parts of Africa. This highlights the urgent need for new antimalarial drugs with novel mechanisms of action.

A Comparison of Common Antimalarial Medications


Drug (Example)	Mechanism	Used For	Prophylaxis Regimen	Key Considerations
Atovaquone/Proguanil (Malarone)	Inhibits mitochondrial electron transport and folate synthesis	P. falciparum, P. vivax treatment & prophylaxis	Daily, for 7 days after travel	Well-tolerated, good for short-term trips
Doxycycline	Inhibits protein synthesis	P. falciparum treatment & prophylaxis	Daily, for 4 weeks after travel	Potential photosensitivity and GI upset
Mefloquine (Lariam)	Similar to quinine, inhibits heme detoxification	P. falciparum treatment & prophylaxis	Weekly, for 4 weeks after travel	Neuropsychiatric side effects possible
Artemisinin-based (Coartem)	Free radical generation via endoperoxide bridge	P. falciparum treatment (ACT)	N/A	Fast-acting, used in combination therapy
Primaquine	Disrupts mitochondrial function	Radical cure for P. vivax/ovale	Daily, for 14 days after travel	Requires G6PD screening due to hemolysis risk

Recent Developments

In September 2024, researchers announced the discovery of a new chemical compound, MED6-189, that shows promise as a potent inhibitor against both drug-sensitive and drug-resistant malaria parasites. This discovery offers new hope in the ongoing fight against malaria and the evolution of drug resistance. Researchers also continue to develop new combination therapies and improve existing drugs.

Conclusion

What is antimalaria? It is a complex and evolving field of pharmacology dedicated to the prevention and treatment of a dangerous parasitic disease. The fight against malaria has seen significant breakthroughs, from the historical use of quinine to modern artemisinin-based combination therapies. However, the relentless development of drug resistance by the Plasmodium parasite continues to pose a major public health challenge. The success of future malaria control hinges on responsible drug use, effective monitoring of resistance, and sustained investment in research to develop new, innovative compounds like MED6-189. This collaborative effort between researchers, clinicians, and global health organizations is essential to protect the efficacy of our current antimalarial toolkit and develop the treatments of tomorrow.

How to Select the Right Prophylaxis for Travel

To determine the best antimalarial prophylactic medication, consult a healthcare provider or a specialized travel medicine clinic. Several factors guide the decision:

Destination: The specific geographical location is crucial, as drug resistance patterns vary significantly.
Travel Duration: Some medications are better suited for short trips, while others are more convenient for extended travel.
Side Effects: Individual tolerance to side effects is an important consideration, especially for drugs with potential neuropsychiatric effects like mefloquine.
Patient Health: Underlying health conditions, pregnancy, or age can influence which drugs are safe to use.

Preventing Malaria Beyond Medication

Antimalarial drugs are only one part of a comprehensive prevention strategy. Travelers and residents in endemic areas should also use personal protective measures to avoid mosquito bites. This includes using insect repellent containing DEET, wearing long-sleeved clothing and pants, and sleeping under insecticide-treated bed nets. Additionally, indoor residual spraying helps control mosquito populations.

Addressing Drug Quality and Compliance

Poor quality or counterfeit antimalarial drugs are a serious problem that contributes to treatment failure and accelerates the development of drug resistance. Ensuring patients have access to and correctly complete their full course of high-quality medication is critical for effective treatment and global disease control. Poor adherence to a drug regimen is a known contributor to resistance development.

The Role of G6PD Screening

Testing for glucose-6-phosphate dehydrogenase (G6PD) deficiency is essential before prescribing certain antimalarial drugs, such as primaquine and tafenoquine. This genetic condition can lead to severe hemolytic anemia when exposed to these medications. Proper screening prevents potentially fatal complications and ensures patient safety. Link to CDC resource

Frequently Asked Questions

Malaria treatment involves medications to cure an existing infection and resolve symptoms, typically with a multi-day course of drugs. Prevention, or prophylaxis, involves taking medication before, during, and after travel to an endemic area to kill parasites before they can cause illness.

Combination therapy is used to increase efficacy and prevent drug resistance. Using two or more drugs with different mechanisms of action makes it much harder for parasites to develop resistance to both simultaneously. This is especially important for ACTs, where the artemisinin component is combined with a longer-acting drug.

The risk and type of side effects vary by drug. Common side effects can include nausea, headaches, and dizziness. Some drugs like mefloquine can have more serious neuropsychiatric side effects, while others like doxycycline can cause photosensitivity.

G6PD deficiency is a genetic condition that, in combination with certain antimalarial drugs like primaquine, can cause severe hemolytic anemia. Therefore, G6PD screening is a mandatory safety measure before prescribing these specific medications.

No prophylactic regimen is 100% effective. Antimalarials significantly reduce your risk but should be combined with other protective measures, such as using repellent and insecticide-treated bed nets, to minimize the chances of infection.

Drug resistance, which has emerged for nearly all antimalarial drug classes, threatens to make existing treatments ineffective. This can lead to higher rates of morbidity and mortality. New resistance, including to artemisinins, necessitates ongoing research and development of novel drugs.

Recent research has led to the discovery of promising new compounds like MED6-189, which targets multiple parasite processes and is effective against resistant strains. Ongoing efforts also focus on improved drug formulations and new combination therapies.