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Cited by 35Malaria Research and ControlPregnancy and preeclampsia studiesPhytochemical compounds biological activities

Artemether-lumefantrine to treat malaria in pregnancy is associated with reduced placental haemozoin deposition compared to quinine in a randomized controlled trial

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Muehlenbachs, Atis, Nabasumba, Carolyn, McGready, Rose, Turyakira, Eleanor, Tumwebaze, Benon, Dhorda, Mehul, Nyehangane, Dan, Nalusaji, Aisha +3 more·2012·Malaria Journal
DOI 10.1186/1475-2875-11-150PMC PMC3487992
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Abstract

BACKGROUND: Data on efficacy of artemisinin-based combination therapy (ACT) to treat Plasmodium falciparum during pregnancy in sub-Saharan Africa is scarce. A recent open label, randomized controlled trial in Mbarara, Uganda demonstrated that artemether-lumefantrine (AL) is not inferior to quinine to treat uncomplicated malaria in pregnancy. Haemozoin can persist in the placenta following clearance of parasites, however there is no data whether ACT can influence the amount of haemozoin or the dynamics of haemozoin clearance. METHODS: Women attending antenatal clinics with weekly screening and positive blood smears by microscopy were eligible to participate in the trial and were followed to delivery. Placental haemozoin deposition and inflammation were assessed by histology. To determine whether AL was associated with increased haemozoin clearance, population haemozoin clearance curves were calculated based on the longitudinal data. RESULTS: Of 152 women enrolled in each arm, there were 97 and 98 placental biopsies obtained in the AL and quinine arms, respectively. AL was associated with decreased rates of moderate to high grade haemozoin deposition (13.3% versus 25.8%), which remained significant after correcting for gravidity, time of infection, re-infection, and parasitaemia. The amount of haemozoin proportionately decreased with the duration of time between treatment and delivery and this decline was greater in the AL arm. Haemozoin was not detected in one third of biopsies and the prevalence of inflammation was low, reflecting the efficacy of antenatal care with early detection and prompt treatment of malaria. CONCLUSIONS: Placental haemozoin deposition was decreased in the AL arm demonstrating a relationship between pharmacological properties of drug to treat antenatal malaria and placental pathology at delivery. Histology may be considered an informative outcome for clinical trials to evaluate malaria control in pregnancy. REGISTRY: http://clinicaltrials.gov/ct2/show/NCT00495508.

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  • Hemozoin can persist for months following treatment of a documented infection, and the extent of hemozoin deposition is thought to correlate with cumulative exposure, with levels associated with gravidity, degree of parasitemia at treatment and reinfection before delivery.

    “Hemozoin can persist for months in women following treatment of a documented infection [58], and the extent of hemozoin deposition is thought to correlate with cumulative exposure [54] such that levels have been associated with gravidity, the degree of parasitemia at the time of treatment and reinfection before delivery [57].”

    From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [57]

  • Women with malaria detected by weekly antenatal screenings and effective treatment often have no histological changes at delivery.

    “women with malaria detected by weekly ante natal screenings and effective treatment often have no histological changes at delivery [56,57].”

    From Diagnosing malaria in pregnancy: An update (2012) · cites this paper as [57]

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Authors
Muehlenbachs, A., Nabasumba, C., McGready, R., Turyakira, E., Tumwebaze, B., Dhorda, M., Nyehangane, D., Nalusaji, A., Nosten, F., Guerin, P. J., & Piola, P.
Affiliations
  • University of Washington (US)
  • Epicentre Uganda (UG)
  • Mahidol University (TH)
  • University of Oxford (GB)
Corresponding author
Muehlenbachs, Atis
ORCID
Venue
Malaria Journal
Publisher
Springer Science and Business Media LLC
Published
2012-05-03
Volume
11
Issue
1
Pages
150-150
ISSN
1475-2875 (ISSN-L)
DOI
10.1186/1475-2875-11-150
PMC
PMC3487992
OpenAlex
W2157847822
Cited by
35
References
43
Citations by year
2026: 1 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 15 · 2018: 1 · 2016: 3 · 2015: 3 · 2014: 2 · 2013: 1 · 2012: 1
FWCI
2.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Malaria Journal (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Medecins Sans Frontieres Field Research (Medecins Sans Frontieres) (submittedVersion, other-oa)
  • Greater South Information System
Funders
  • Wellcome Trust (089275)
  • European Commission
  • Mahidol University
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phytochemical compounds biological activities
Keywords
artemether-lumefantrine, quinine, malaria in pregnancy, Plasmodium falciparum, placental histology, placental inflammation, artemisinin-based combination therapy, prenatal care
MeSH terms
Artemether, Lumefantrine Drug Combination, Adult, Antimalarials, Drug Combinations, Ethanolamines, Female, Fluorenes, Hemeproteins, Histocytochemistry, Humans, Infant, Newborn, Placenta, Pregnancy, Pregnancy Complications, Infectious, Quinine, Uganda, Malaria, Falciparum, Treatment Outcome, Artemisinins, Young Adult

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