What is the recommended treatment for malaria in the 3rd trimester of pregnancy?

Treatment of Malaria in the 3rd Trimester

Artemether-lumefantrine (AL) is the recommended first-line treatment for uncomplicated malaria in the third trimester of pregnancy, administered at the same doses as for non-pregnant women: 4 tablets at hour 0,4 tablets at hour 8 on day 1, then 4 tablets twice daily on days 2 and 3. 1, 2

Efficacy in Third Trimester

The evidence strongly supports artemether-lumefantrine use in late pregnancy:

• Cure rates with AL in the second and third trimesters range from 94.9% to 100%, demonstrating excellent efficacy 1
• AL performs equal to or better than quinine-based regimens, with a pooled risk ratio of treatment failure of 0.41 (95% CI 0.16-1.06) compared to non-ACTs 1
• Despite initial concerns about reduced lumefantrine bioavailability in pregnancy, treatment efficacy remains high at standard non-pregnant dosing 1

Safety Profile in Third Trimester

Multiple studies demonstrate favorable safety outcomes:

• No differences in pregnancy outcomes (miscarriage, stillbirth, preterm birth, low birth weight, or congenital abnormalities) were identified when comparing AL to quinine-based regimens 1
• Meta-analyses of women treated in the second and third trimesters found no association between ACT treatment and adverse pregnancy outcomes 1
• AL has superior tolerability compared to quinine, with significantly lower rates of tinnitus, dizziness, and vomiting 1
• One pharmacovigilance study in Rwanda found no specific safety concerns related to AL treatment, though obstetric complications were slightly more frequent in the treatment group (7.3% vs 5.0%), likely attributable to the malaria episode itself rather than the medication 3

Critical Administration Details

AL must be taken with a fatty meal or drink to ensure adequate absorption 2. This is a common pitfall—failing to take AL with fat can lead to subtherapeutic drug levels and treatment failure 2.

The specific dosing regimen is:

• Hour 0: 4 tablets
• Hour 8 (day 1): 4 tablets
• Day 2: 4 tablets twice daily
• Day 3: 4 tablets twice daily 1, 2

Alternative Options

For patients in whom ACTs are contraindicated (e.g., risk of QTc prolongation):

• Atovaquone-proguanil is recommended as second-line treatment: 4 tablets daily for 3 days, taken with a fatty meal 2
• Quinine 10 mg/kg every 8 hours for 7 days remains an option, though with inferior tolerability 1

Severe Malaria in Third Trimester

For severe P. falciparum malaria:

• Intravenous artesunate is first-line treatment, with monitoring of parasitemia every 12 hours until <1%, then every 24 hours until negative 2
• Once clinically improved (parasitemia <1%) and able to take oral medications, complete treatment with a full course of oral ACT 2

Important Monitoring

• Monitor for delayed hemolysis after artemisinin-based treatment (PADH), particularly on days 7,14,21, and 28 after treatment 2
• Both AL and other ACTs can cause QTc prolongation and should be avoided in patients at risk or taking QTc-prolonging medications 2

Species-Specific Considerations

For P. vivax or P. ovale malaria in the third trimester:

• Initial treatment with ACT should be followed by radical cure with primaquine after delivery to eliminate hepatic hypnozoites and prevent relapses 2

The CDC formally updated its recommendations in 2018 to include AL as an additional treatment option for uncomplicated malaria in pregnant women during the second and third trimesters, based on the strength and quality of accumulated evidence 1.