title: Malaria prevalence, severity and treatment outcome in relation to day 7 lumefantrine plasma concentration in pregnant women.
abstract: Day 7 plasma concentrations of lumefantrine (LF) can serve as a marker to predict malaria treatment outcome in different study populations. Two main cut-off points (175 and 280 ng/ml) are used to indicate plasma concentrations of LF, below which treatment failure is anticipated. However, there is limited data on the cumulative risk of recurrent parasitaemia (RP) in relation to day 7 LF plasma concentrations in pregnant women. This study describes the prevalence, severity, factors influencing treatment outcome of malaria in pregnancy and day 7 LF plasma concentration therapeutic cut-off points that predicts treatment outcome in pregnant women.
  
  
  
  This was a one-arm prospective cohort study whereby 89 pregnant women with uncomplicated Plasmodium falciparum malaria receiving artemether-lumefantrine (ALu) participated in pharmacokinetics and pharmacodynamics study. Blood samples were collected on days 0, 2, 7, 14, 21 and 28 for malaria parasite quantification. LF plasma concentrations were determined on day 7. The primary outcome measure was an adequate clinical and parasitological response (ACPR) after treatment with ALu.
  
  
  
  The prevalence of malaria in pregnant women was 8.1 % (95 % CI 6.85-9.35) of whom 3.4 % (95 % CI 1.49-8.51) had severe malaria. The overall PCR-uncorrected treatment failure rate was 11.7 % (95 % CI 0.54-13.46 %). Low baseline hemoglobin (<10 g/dl) and day 7 LF concentration <600 ng/ml were significant predictors of RP. The median day 7 LF concentration was significantly lower in pregnant women with RP (270 ng/ml) than those with ACPR (705 ng/ml) (p = 0.016). The relative risk of RP was 4.8 folds higher (p = 0.034) when cut-off of <280 ng/ml was compared to ≥280 ng/ml and 7.8-folds higher (p = 0.022) when cut-off of <600 ng/ml was compared to ≥600 ng/ml. The cut-off value of 175 ng/ml was not associated with the risk of RP (p = 0.399).
  
  
  
  Pregnant women with day 7 LF concentration <600 ng/ml are at high risk of RP than those with ≥600 ng/ml. To achieve effective therapeutic outcome, higher day 7 venous plasma LF concentration ≥600 ng/ml is required for pregnant patients than the previously suggested cut-off value of 175 or 280 ng/ml for non-pregnant adult patients.
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania. rittdavisrida@yahoo.com.
authors.forename: Ritah F
authors.initials: RF
authors.lastname: Mutagonda
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
authors.forename: Appolinary A R
authors.initials: AA
authors.lastname: Kamuhabwa
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
authors.forename: Omary M S
authors.initials: OM
authors.lastname: Minzi
authors.affiliation: Department of Obstetrics and Gynaecology, School of Medicine, Muhimbili University of Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
authors.forename: Siriel N
authors.initials: SN
authors.lastname: Massawe
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, School of Pharmacy, Muhimbili University of Health and Allied Sciences, P.O. BOX 65013, Dar es Salaam, Tanzania.
authors.forename: Betty A
authors.initials: BA
authors.lastname: Maganda
authors.affiliation: Department of Laboratory of Medicine, Division of Clinical Pharmacology, Karolinska Institutet, 141 86, Stockholm, Sweden.
authors.forename: Eleni
authors.initials: E
authors.lastname: Aklillu
mesh_terms: D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004338:Drug Combinations; D004983:Ethanolamines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005449:Fluorenes / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000473:pathology*; D010949:Plasma / Q000737:chemistry*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000473:pathology*; D015995:Prevalence; D011446:Prospective Studies; D012008:Recurrence; D055502:Secondary Prevention; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000962:Antimalarials; D000077611:Artemether, Lumefantrine Drug Combination; D037621:Artemisinins; D004338:Drug Combinations; D004983:Ethanolamines; D005449:Fluorenes
keywords: Lumefantrine; Malaria; Pregnancy; Recurrent parasitaemia; Tanzania