The Effect of Folic Acid on Efficacy of Sulfadoxine-pyrimethamine in Pregnant Women in Western Kenya
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether folic acid, which is often routinely given
      to pregnant women to prevent birth defects and anemia, affects the efficacy of
      sulfadoxine-pyrimethamine, another drug that is routinely given to pregnant women in highly
      malarious areas, for prevention of the adverse effects of malaria during pregnancy.
    

Detailed description: 
      In malaria endemic areas in sub-Saharan Africa, pregnant women, especially primi- and
      secundi-gravidae, are more likely to have placental and peripheral parasitemia with
      Plasmodium falciparum than non-pregnant women. Adverse consequences of malaria in pregnancy
      include maternal anemia, and low birth weight of the new born. Low birth weight is known to
      be the most important risk factor for infant mortality.

      Intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) during pregnancy
      can mitigate the adverse effects of malaria in pregnancy and is the current standard of care
      in areas of high malaria transmission in sub-Saharan Africa, as recommended by the World
      Health Organization.

      SP acts by inhibiting parasite enzymes in the metabolism of folic acid. However, in vitro
      studies indicate that folic acid can antagonize the antimalarial parasite activity of SP.
      Furthermore, in one West African study, supplementary folic acid compromised the antimalarial
      efficacy of SP in children with acute malaria aged 6 months to 12 years.

      Folic acid requirements are increased during pregnancy, and supplementation with folic acid
      in pregnancy is recommended. Although in most countries a daily supplementation of 400 to 600
      micrograms is considered sufficient, for logistical reasons the daily recommended dose in
      Kenya is 5 mg of folic acid during pregnancy. It is unknown whether folic acid
      supplementation might compromise the efficacy of IPT with SP in pregnant women living in
      malaria endemic areas.

      Several studies have shown that HIV-seropositive pregnant women have a higher risk of malaria
      than HIV-seronegative pregnant women. In addition, HIV-infected women are more likely to be
      anemic compared with HIV-uninfected women. A few studies have also shown that
      HIV-seropositive women do not appear to respond as well to IPT with SP compared to
      HIV-seronegative pregnant women.

      In a recent study in pregnant women in Zimbabwe, HIV-infection was a negative predictor of
      serum folate, and the authors suggested this may be because of reduced intake and absorption,
      and increased catabolism in HIV-infected pregnant women. Because HIV-seropositive women as a
      group may have a different folic acid status (and a potential different reaction to folic
      acid supplementation) than HIV-seronegative women, it is important to assess HIV-status in
      study participants. It is also important to confirm that no difference exists between
      HIV-seropositive and HIV-seronegative women in efficacy of SP for clearance of peripheral
      parasitemia.

      Comparison: Parasitemic pregnant women are randomized to receive either SP with folic acid 5
      mg, or SP with folic acid 0.4 mg, or SP and placebo. The placebo and the folic acid 0.4 mg
      are given for two weeks, and then are replaced by folic acid 5 mg.
    

Intervention name(s): Sulfadoxine-pyrimethamine/folic acid; Sulfadoxine-pyrimethamine/placebo
Intervention type(s): Drug; Drug
Intervention MeSH terms: Folic Acid; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Malaria; Pregnancy; Sulfadoxine-pyrimethamine; Folic acid; Folate