Dihydroartemisinin–Piperaquine for the Prevention of Malaria in Pregnancy

Jordan Alava, Mercer University College of Pharmacy

The Centers for Disease Control and Prevention (CDC) reports that no antimalarial drug is 100% protective and that a combination of prophylactic medications and personal protective measures must be taken to prevent infection.  [1]

The World Health Organization (WHO) recommends intermittent preventative treatment with sulfadoxine-pyrimethamine in pregnant patients.  The WHO further suggests that preventative treatment be given to all pregnant women in all areas with moderate to high malaria transmission in Africa during each scheduled antenatal care visit except during the first trimester.  [2]

Title: Dihydroartemisinin–Piperaquine for the Prevention of Malaria in Pregnancy
Design Double-blind, randomized, controlled; N= 300
Objective To determine the efficacy of dihydroartemisinin-piperaquine in the prevention of malaria in pregnant patients
Study Groups Sulfadoxine-pyrimethamine (n= 106); three-dose dihydroartemisinin-piperaquine (n= 94); monthly dihydroartemisinin-piperaquine (n= 100)
Methods Pregnant adolescents or women at least 16 years of age that were human immunodeficiency virus (HIV)-uninfected were randomized to receive malaria prevention with either sulfadoxine-pyrimethamine, three-dose dihydroartemisinin-piperaquine, or monthly dihydroartemisinin-piperaquine.
Duration June 2014 – October 2014
Primary Outcome Measure Prevalence of histopathologically confirmed placental malaria
Baseline Characteristics Baseline characteristics were similar among the three treatment groups.  The mean age at enrollment was 22 years, 69% of the participants were enrolled at 16 weeks of gestation or earlier, 37% were primigravid, 87% reported owning a long-lasting insecticide–treated net, and 57% had malaria parasites detected by loop-mediated isothermal amplification (LAMP).
Results   Sulfadoxine-pyrimethamine (n= 106) Three-dose dihydroartemisinin-piperaquine (n= 94) Monthly dihydroartemisinin-piperaquine (n= 100)
      RR (95% CI) p value   RR (95% CI) p value
Histopathological assessment of placenta No. (%) 49 (50.0) 30 (34.1%) 0.68 (0.48–0.97) 0.03 26 (27.1%) 0.54 (0.37–0.79) 0.001
Abbreviations: relative risk (RR), confidence interval (CI)
Adverse Events Common Adverse Events: N/A
Serious Adverse Events: Congenital anomaly (4.5%), stillbirth (2.1%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions The burden of malaria in pregnancy was significantly lower among adolescent girls or women who received intermittent preventive treatment with dihydroartemisinin–piperaquine than among those who received sulfadoxine–pyrimethamine, and monthly treatment with dihydroartemisinin–piperaquine was superior to three-dose dihydroartemisinin–piperaquine with regard to several outcomes.

This study shows that intermittent preventative treatment with dihydroartemisinin-piperaquine resulted in a lower burden of malaria than sulfadoxine-pyrimethamine in pregnant patients.  The study also demonstrated that dihydroartemisinin–piperaquine given on a monthly basis provided greater protection than the three-dose regimen. While these results show promise of an alternative therapy to parasites that are resistant to the standard treatment, it was only conducted in one of the 48 Sub-Saharan countries where malaria is rampant. Future studies are needed to assess the efficacy of dihydroartemisinin-piperaquine in other high-risk regions and to better determine the safety and risks associated with selecting drug-resistant parasites using this particular therapy.

References

  1. Choosing a drug to prevent malaria. The Centers for Disease Control and Prevention. 2012. Available at: http://www.cdc.gov/malaria/travelers/drugs.html Accessed March 17, 2016.
  2. World Health Organization. 2015. Available at: http://www.who.int/malaria/areas/preventive_therapies/pregnancy/en/. Accessed March 17, 2016.
  3. Kakuru A – N Engl J Med (2016) Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.pdf.
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