What is the recommended treatment for malaria in pregnancy?

Treatment of Malaria in Pregnancy

For uncomplicated malaria in pregnancy, use artemether-lumefantrine (AL) in the second and third trimesters, and either mefloquine or quinine plus clindamycin in the first trimester, though AL should be considered when these are unavailable as the risks of untreated malaria far exceed any theoretical artemisinin risks. 1

Treatment Algorithm by Trimester

First Trimester (Weeks 1-13)

First-line options:

• Mefloquine (single dose 25 mg/kg) OR
• Quinine 10 mg/kg every 8 hours for 7 days PLUS clindamycin 5 mg/kg every 8 hours for 7 days 2, 1

When first-line options are unavailable:

• Artemether-lumefantrine (AL) should be used rather than delaying treatment, with cure rates of 98.2% in clinical trials 1
• The CDC explicitly warns against withholding artesunate-based treatment when other options are unavailable, as untreated malaria causes far greater harm than any theoretical artemisinin risks 1

Second and Third Trimesters (Weeks 14-40)

First-line treatment:

• Artemether-lumefantrine (AL) 20/120 mg: 4 tablets at 0 and 8 hours on day 1, then twice daily for 2 additional days 2, 1
• This regimen achieves cure rates ≥94.9% and performs equal to or better than quinine-based regimens 2

Alternative if AL unavailable:

• Quinine 10 mg/kg every 8 hours for 7 days plus clindamycin 2

Evidence Supporting Artemether-Lumefantrine

The 2018 CDC systematic review of 21 studies demonstrated:

• Efficacy: Cure rates of 99.3-100% in randomized trials from Uganda and Thailand 2
• Safety: Meta-analyses found no association between ACT treatment and congenital malformations in early pregnancy 1
• Tolerability: ACTs showed 30% fewer maternal adverse events compared to quinine-based regimens, with significantly lower rates of tinnitus, dizziness, and vomiting 1

Special Considerations for Plasmodium vivax

Acute treatment:

• Chloroquine 600 mg base initially, followed by 600 mg at 24 hours, and 300 mg at 48 hours (total 1,500 mg base over 3 days) 3
• Chloroquine is safe throughout all trimesters 3

Critical pitfall:

• Never use primaquine during pregnancy as it crosses the placenta and can cause life-threatening hemolytic anemia in G6PD-deficient fetuses 3
• Provide weekly chloroquine suppression throughout pregnancy to prevent relapses 3
• After delivery, administer primaquine 15 mg daily for 14 days for radical cure, but only after G6PD testing 3

Safety Profile Comparison

Quinine concerns (from FDA label):

• Crosses placenta with fetal concentrations 32% of maternal levels 4
• Increased risk of maternal hypoglycemia, especially third trimester 4
• Higher rates of tinnitus, vomiting, dizziness (odds ratio 2.5 vs ACTs) 1
• Stillbirth rate 1.6% (similar to untreated controls at 1.8%) 4

Artemisinin safety data:

• Meta-analysis showed adjusted hazard ratio of 0.73 for miscarriage and 0.29 for stillbirth compared to quinine 1
• No increased congenital malformation rates in studies of >893 first-trimester exposures 2
• One concerning signal: artesunate-mefloquine showed 21% miscarriage rate vs 11% for quinine in Thai studies, though other artemisinin combinations showed only 4% 5

Critical Clinical Pitfalls

Never delay treatment waiting for "preferred" medications - untreated malaria causes maternal anemia, severe malaria, spontaneous abortion, stillbirth, preterm delivery, low birth weight, and maternal/neonatal mortality 4, 6

Monitor glucose levels in pregnant women taking quinine, particularly in the third trimester, due to increased risk of hypoglycemia from enhanced pancreatic insulin secretion 4

Avoid primaquine entirely during pregnancy - it cannot be used for P. vivax radical cure until after delivery due to risk of fetal hemolysis 3

Consider folate supplementation - while proguanil inhibits dihydrofolate reductase, women taking folate supplements to prevent neural tube defects may continue them with atovaquone-proguanil 7