Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana
Efficacy,Safety and Tolerability of Dihydroartemisinin-Piperaquine for Uncomplicated Malaria in Pregnancy in Ghana
Malaria in pregnancy poses enormous public health challenges, contributing to significant
 maternal and infant deaths yearly. Adverse outcomes include maternal anaemia and low
 birthweight. Down regulation of cellular immunity increases pregnant women's susceptibility
 to malaria and mediate these adverse outcomes.

 The World Health Organization recommends treatment with artemisinin-combination therapy.
 Ghana uses quinine for malaria in first trimester pregnancies while artesunate-amodiaquine
 (AS-AQ) and quinine again are used in later trimesters. Recent amendments added
 artesunate-lumefantrine and dihydroartemisinin-piperaquine (DHA-PPQ) to the antimalarials
 used in the country. A high degree of safety and efficacy of DHA-PPQ is documented in several
 studies. DHA-PPQ, though not specified for use in pregnancy as of now, is accessible and
 available following its inclusion in the national malaria guidelines and may inadvertently be
 used to treat malaria in pregnancy. Paucity of data on DHA-PPQ use in pregnancy makes it
 pertinent to study its safety, tolerability and efficacy in pregnancy.

 We propose an open label, randomized controlled non-inferiority comparison of DHA-PPQ and
 AS-AQ for treatment of uncomplicated malaria in pregnancy in second and third trimesters to
 assess safety, tolerability and efficacy of DHA-PPQ. Outcomes of interest include
 PCR-corrected cure rates at days 28 and 42, maternal haemoglobin levels at days 14 and 42,
 prevalence of congenital abnormalities and pregnancy wastage. Proportions and percentages
 will be described at 95% Confidence Intervals and compared using chi-square tests. Parametric
 and non-parametric tests of significance will be applied as appropriate to determine
 significance of differences in outcomes between the treatment groups.
Pregnant women of all ages, gravidity and with gestational ages 16-30 weeks, living within 15
 km of the study center and presenting for antenatal care or diagnosed with uncomplicated
 malaria will be screened with P.falciparum rapid diagnostic test kits after obtaining
 consent. Those testing positive will have blood film microscopy done and only those with
 positive blood film microscopy will be recruited to participate in the study. Participants
 will be randomized to receive either dihydroartemisinin-piperaquine at an estimated total
 dosing of 6.75mg/kg of dihydroartemisinin and 55mg/kg of piperaquine for 3 days rounded to
 the nearest half tablet) or artesunate-amodiaquine(artesunate 4mg/kg and amodiaquine 10mg/kg
 in two twelve hourly doses daily for 3 days) after giving informed consent and a physical
 examination. This will be followed by home visits on days 1, 3, 7, 14, 28 and 42
 post-treatment to assess occurrence of adverse events and to obtain blood samples for
 microscopy, filter paper blots for PCR analysis and haematology. The mentioned laboratory
 investigations will also be conducted at recruitment.

 Participants will be followed up to delivery and 6 weeks post-partum to gather data on
 maternal peripheral and placental parasitaemia, cord parasitaemia, maternal haemoglobin
 levels, low birth weights, stillbirths, preterm deliveries, neonatal jaundice, birth defects
 and infant deaths.
Inclusion Criteria:

 -  RDT positive + microscopy confirmed P. falciparum parasitaemia. ii) Informed consent.
 iii) Resident within the defined 15km radius of the study center. iv) No history of
 antimalarial treatment in the preceding two weeks. v) Assurance of adherence to study
 requirements, follow-up and delivery at the hospital.

 vi) Haemoglobin ≥ 7g/dl.

 Exclusion Criteria:

 -  i) Confirmed multiple gestation. ii) Severe malaria or disease likely to influence
 pregnancy outcome eg renal/ cardiac disease, diabetes mellitus, known pregnancy
 induced hypertension, known human immunodeficiency virus infection.

 iii) Known allergies to study medication. iv) Antimalarial treatment administered by a
 third party during the follow-up.