What is the recommended treatment for malaria in pregnancy?

Treatment of Malaria in Pregnancy

For uncomplicated malaria in pregnancy, mefloquine or quinine plus clindamycin should be used during the first trimester, while artemether-lumefantrine (AL) is recommended for the second and third trimesters. 1

First Trimester Treatment

• Women with uncomplicated malaria during the first trimester should be treated with either mefloquine or quinine plus clindamycin 1
• When neither mefloquine nor quinine plus clindamycin is available, artemether-lumefantrine (AL) should be considered as an alternative treatment option 1
• Quinine has been associated with higher rates of adverse effects including tinnitus, dizziness, and vomiting compared to artemisinin-based combination therapies (ACTs) 1
• Quinine plus clindamycin has shown cure rates of 98.2% in clinical trials for treatment of uncomplicated P. falciparum malaria in pregnancy 1

Second and Third Trimester Treatment

• Artemether-lumefantrine (AL) is recommended as an additional treatment option for uncomplicated malaria during the second and third trimesters at the same doses used for non-pregnant women 1
• AL has demonstrated cure rates ≥94.9% in clinical trials, performing equal to or better than quinine-based regimens 1
• ACTs have shown fewer maternal adverse events compared to quinine-based regimens in multiple studies 1
• No significant differences in rates of serious adverse maternal effects have been observed between different ACT regimens 1

Severe Malaria in Pregnancy

• Intravenous artesunate is the preferred treatment for severe malaria in all trimesters of pregnancy 2
• Studies comparing intravenous quinine with intravenous artesunate have shown that artesunate is more efficacious and safe for use in pregnant women with severe malaria 2

Safety Considerations

• Studies have not detected an increased risk of miscarriage, stillbirth, or congenital anomalies associated with first-trimester exposure to artesunate 2
• Meta-analyses of studies examining ACT use in early pregnancy found no association between ACT treatment and congenital malformations 1
• Pregnant women taking quinine had higher rates of tinnitus, dizziness, and vomiting than those taking ACTs 1
• Pregnant women are at risk for hypoglycemia when taking quinine, especially during the third trimester, due to increased pancreatic secretion of insulin 3

Treatment Algorithm

1. Determine severity of malaria:

   • For severe malaria: Use intravenous artesunate in all trimesters 2
   • For uncomplicated malaria: Proceed to next step

2. Determine trimester of pregnancy:

   • First trimester: Use mefloquine or quinine plus clindamycin 1
   • Second/third trimester: Use artemether-lumefantrine 1

3. If first-line treatments are unavailable:

   • First trimester: Consider artemether-lumefantrine 1
   • Monitor closely for adverse effects in all cases 1

Common Pitfalls and Caveats

• Delaying treatment of malaria during pregnancy can result in serious maternal and fetal complications including maternal anemia, severe malaria, spontaneous abortion, stillbirths, and preterm delivery 4
• Pharmacokinetics of most antimalarial drugs are modified in pregnancy, which may affect dosing requirements 5, 6
• Monitoring for hypoglycemia is particularly important when using quinine in pregnant women 3
• Proguanil (often used in combination with atovaquone) acts by inhibiting parasitic dihydrofolate reductase, but there are no clinical data indicating that folate supplementation diminishes drug efficacy 7
• Women of childbearing age receiving folate supplements to prevent neural tube birth defects may continue these supplements while taking antimalarial medications 7