From the Guidelines
Dual antimalarial therapy with artemisinin-based combination therapy (ACT) is the recommended treatment for uncomplicated Plasmodium falciparum malaria, as it provides the most effective approach to reducing parasite load and preventing resistance. The choice of ACT should be based on the specific patient population and the presence of any contraindications or resistance patterns in the region of infection. For example, artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHAePPQ) are commonly used ACTs, with AL being given as a 3-day regimen and DHAePPQ being given as a 3-day regimen as well 1.
Key Considerations for Dual Antimalarial Therapy
- The use of ACTs is recommended for uncomplicated P. falciparum malaria due to their rapid parasite clearance and good safety profile 1.
- The choice of ACT should be based on the specific patient population, with considerations for pregnancy, weight, and potential drug interactions.
- Atovaquone-proguanil (Malarone) is another effective combination therapy that can be used as an alternative to ACTs in certain cases, such as in areas with high levels of resistance to ACTs or in patients with contraindications to ACTs 1.
- The treatment regimen should be completed as directed, with the full course of medication being taken to ensure complete clearance of the parasite.
Treatment Regimens for Uncomplicated P. falciparum Malaria
- Artemether-lumefantrine (AL): 3-day regimen, with doses based on weight, typically 4 tablets twice daily for adults 1.
- Dihydroartemisinin-piperaquine (DHAePPQ): 3-day regimen, with doses based on weight, typically 4 tablets once daily for adults 1.
- Atovaquone-proguanil (Malarone): 3-day regimen, with doses based on weight, typically 4 tablets once daily for adults 1.
Important Safety Considerations
- Post-artemisinin delayed haemolysis (PADH) is a potential adverse event associated with ACTs, particularly in patients with severe malaria or those receiving intravenous artesunate 1.
- The use of ACTs in pregnancy is recommended, with the benefits of treatment outweighing the potential risks 1.
- Patients should be monitored for potential adverse events, such as nausea, vomiting, and diarrhea, and treated promptly if they occur.
From the FDA Drug Label
Among 156 evaluable patients, the parasitological cure rate was 59/89 (66%) with atovaquone alone, 1/17 (6%) with proguanil hydrochloride alone, and 50/50 (100%) with the combination of atovaquone and proguanil hydrochloride. Atovaquone and proguanil hydrochloride was evaluated for treatment of acute, uncomplicated malaria caused by P. falciparum in 8 phase III controlled clinical trials The overall efficacy in 521 evaluable patients was 98.7%
The combination of atovaquone and proguanil hydrochloride is effective for the treatment of acute, uncomplicated malaria caused by P. falciparum, with a parasitological cure rate of 100% in one study and an overall efficacy of 98.7% in 8 phase III controlled clinical trials 2.
- Key points:
- The combination of atovaquone and proguanil hydrochloride is more effective than atovaquone or proguanil hydrochloride alone.
- The overall efficacy of the combination is high, with a cure rate of 98.7% in a large number of patients.
- The combination is effective for the treatment of acute, uncomplicated malaria caused by P. falciparum.
From the Research
Dual Anti-Malaria Treatment
- The use of dual anti-malaria treatment is a common practice in areas where malaria is prevalent, especially in cases where the parasite has developed resistance to single-drug treatments 3, 4.
- One such combination is artemether plus lumefantrine, which has been shown to be effective in treating uncomplicated malaria in African trials, with efficacy similar to or even superior to that of the amodiaquine + sulfadoxine + pyrimethamine combination 3.
- Another combination is artesunate-mefloquine, which has been compared to artemether-lumefantrine in a randomised, multicentre, phase 4 trial in children younger than 5 years in sub-Saharan Africa, showing similar efficacy and safety profiles 5.
- The World Health Organization (WHO) recommends combinations of an artemisinin derivative plus an antimalarial drug of longer half-life as treatment options for uncomplicated Plasmodium falciparum infection 4, 5.
Efficacy and Safety
- The efficacy of dual anti-malaria treatments has been demonstrated in various studies, with artemether plus lumefantrine showing a PCR-corrected rate of adequate clinical and parasitological response (ACPR) at day 63 of 90.9% in one study 5.
- The safety profiles of these combinations have also been evaluated, with artesunate-mefloquine and artemether-lumefantrine showing similar rates of early vomiting, neurological adverse events, and no detectable psychiatric adverse events 5.
- However, the emergence of artemisinin-resistant parasites in SE Asia has highlighted the need to optimise drug dosing and investigate novel therapies to maintain the reduction in malaria mortality 6.
Novel Therapies
- Researchers have proposed the use of artesunate-quercetin/luteolin dual drug nanofacilitated synergistic treatment as a plausible approach to overcome artemisinin combination therapy resistance 7.
- This novel approach aims to provide an alternate drug combination to ACT-induced P. falciparum resistance, with the potential to reduce dose and dosing frequency, enhance patient compliance, and decrease drug toxicity 7.