Study Title:~Efficacy and Safety of Quinine vs Artemether/Lumefantrine in uncomplicated malaria during pregnancy, Mbarara, Uganda (2006/2007).~Regulatory Status:~Investigational - Phase IV~Investigational Product and route:~Quinine hydrochloride, oral route.~Coartem® (Novartis Pharma AG, Basel, Switzerland), oral route.~Lead Investigator and Study Centre Primary objective - To establish that, in pregnant women with uncomplicated Plasmodium falciparum malaria, the PCR-adjusted efficacy of Artemether/Lumefantrine is not inferior to oral Quinine.~Secondary objectives~To define the pharmacokinetics of the combination artemether-lumefantrine (AL) in the treatment of uncomplicated P. falciparum infections in the last two trimesters of pregnancy.~To collect baseline data on maternal, obstetric and infant outcomes.~To estimate the incidence of malaria infection, both microscopic and sub-microscopic (by PCR) during pregnancy.~women attending Mbarara National Referral Hospital (MNRH) ante-natal clinic (ANC).~Women with a positive blood smear during follow-up will be invited to participate in a non-inferiority, open, randomised, non- inferiority trial comparing the efficacy and tolerance of Coartem® (Artemether-Lumefantrine) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion.~Women with uncomplicated malaria from the efficacy study, will be followed to obtain an efficacy endpoint at 42 days OR at delivery, whichever timepoint is the last.~Newborns will be followed monthly up to the age of 1 year.~Inclusion Criteria (Efficacy Study):~Pregnant woman~Malaria infection, detected by microscopy, with P. falciparum (mixed or mono-infection)~Age of gestation: 13 weeks and beyond~Efficacy study signed informed consent form~Exclusion Criteria (Efficacy Study):~P. falciparum parasitaemia above 250,000 parasites/μl~Severe anaemia~Signs or symptoms of severe/complicated malaria requiring parenteral treatment (WHO 2000)~Known allergy to artemisinin derivatives, lumefantrine or quinine;~Previous participation in the efficacy study~Inability to attend the efficacy study follow-up schedule.~Study drugs and Administration~Group 1 (Active Control): Quinine hydrochloride (10 mg/Kg/8h for 7 days) administered orally.~Group 2 (Test): Coartem®, fixed Artemether-Lumefantrine (20/120 mg) GMP manufactured by Novartis Pharma AG (Basel, Switzerland), 4 tablets twice a day for 3 days with 200 ml of milk tea at each dose .~Endpoints~- Primary efficacy endpoint: PCR-corrected adequate clinical and parasitological response (ACPR) on Day 42.~Secondary efficacy endpoints:~PCR-corrected(ACPR)at delivery~Pharmacokinetic parameters~Symptom clearance Time~Proportion of patients who have fever cleared at Day 1, 2 and 3~Safety endpoints:~Incidence of any adverse events~Pregnancy outcome~Infant development during the first year of life
A) for the treatment of uncomplicated malaria during second and third trimester pregnancy to oral Quinine hydrochloride. The PCR-corrected adequate clinical and parasitological response (ACPR) on day 42 is considered as the primary efficacy criterion. Newborns will be followed for growth and development indicators.