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Cited by 53Malaria Research and ControlPregnancy and Medication ImpactPharmaceutical Quality and Counterfeiting

Randomized Trial of Artesunate+Amodiaquine, Sulfadoxine-Pyrimethamine+Amodiaquine, Chlorproguanal-Dapsone and SP for Malaria in Pregnancy in Tanzania

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Mutabingwa, Theonest K., Muze, Kandi, Ord, Rosalynn, Briceño, Marnie, Greenwood, Brian M., Drakeley, Chris, Whitty, Christopher J. M.·2009·PLoS ONE
DOI 10.1371/journal.pone.0005138PMC PMC2662423
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Abstract

BACKGROUND: Malaria in pregnancy is serious, and drug resistance in Africa is spreading. Drugs have greater risks in pregnancy and determining the safety and efficacy of drugs in pregnancy is therefore a priority. This study set out to determine the efficacy and safety of several antimalarial drugs and combinations in pregnant women with uncomplicated malaria. METHODS: Pregnant women with non-severe, slide proven, falciparum malaria were randomised to one of 4 regimes: sulfadoxine-pyrimethamine [SP]; chlorproguanil-dapsone [CD]; SP+amodiaquine [SP+AQ] or amodiaquine+artesunate [AQ+AS]. Randomisation was on a 1ratio2ratio2ratio2 ratio. Women were admitted for treatment, and followed at days 7, 14, 21, 28 after the start of treatment, at delivery and 6 weeks after delivery to determine adverse events, clinical and parasitological outcomes. Primary outcome was parasitological failure by day 28. RESULTS: 1433 pregnant women were screened, of whom 272 met entry criteria and were randomised; 28 to SP, 81 to CD, 80 to SP+AQ and 83 to AQ+AS. Follow-up to day 28 post treatment was 251/272 (92%), and to 6 weeks following delivery 91%. By day 28 parasitological failure rates were 4/26 (15%, 95%CI 4-35) in the SP, 18/77 (23%, 95%CI 14-34) in the CD, 1/73 (1% 95%CI 7-0.001) in the SP+AQ and 7/75 (9% 95%CI 4-18) in the AQ+AS arms respectively. After correction by molecular markers for reinfection the parasitological failure rates at day 28 were 18% for CD, 1% for SP+AQ and 4.5% for AQ+AS. There were two maternal deaths during the trial. There was no apparent excess of stillbirths or adverse birth outcomes in any arm. Parasitological responses were strikingly better in pregnant women than in children treated with the same drugs at this site. CONCLUSIONS: Failure rates with monotherapy were unacceptably high. The two combinations tested were efficacious and appeared safe. It should not be assumed that efficacy in pregnancy is the same as in children. TRIAL REGISTRATION: ClinicalTrials.gov NCT00146731.

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  • Amodiaquine has been shown to be efficacious in pregnant women with falciparum malaria in Ghana and Tanzania.

    “Amodiaquine (AQ) has been shown to be efficacious in pregnant women with falciparum malaria in Ghana and Tanzania.122,125”

    From Malaria in pregnancy. (2013) · cites this paper as [125]

    The Discussion (page not supplied) reports that amodiaquine-containing combinations were efficacious in pregnant women in Tanzania and cites a previous trial of the SP+AQ combination in Ghana. It does not establish the efficacy of amodiaquine alone in pregnant women, as the unqualified claim could imply. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Data available indicate that ACTs are relatively safe for the foetus when taken after the first trimester of pregnancy.

    “Data available indicate that ACTs are relatively safe for the foetus when taken after the first trimester of pregnancy.”

    From Malaria in pregnancy. (2013) · cites this paper as [125]

  • Day 28 parasitological failure rates were 3% for AQ monotherapy, 0-1% for the combination AQ+SP, and 4.5% for the combination AS+AQ.

    “Day 28 parasitological failure rates were 3% for AQ monotherapy,122 0–1% for the combination AQ+SP,122,125 and 4.5% for the combination AS+AQ.125”

    From Malaria in pregnancy. (2013) · cites this paper as [125]

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References 41 · Cited by 53

Research works printed but not linked: 36

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Authors
Mutabingwa, T. K., Muze, K., Ord, R., Briceño, M., Greenwood, B. M., Drakeley, C., & Whitty, C. J. M.
Affiliations
  • London School of Hygiene & Tropical Medicine (GB)
  • Government of Tanzania (TZ)
  • University of Washington (US)
Corresponding author
Mutabingwa, Theonest K.
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2009-04-08
Volume
4
Issue
4
Pages
e5138
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0005138
PMC
PMC2662423
OpenAlex
W1986113463
Cited by
53
References
41
Citations by year
2025: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 8 · 2012: 2
FWCI
5.38
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
Funders
  • Bill and Melinda Gates Foundation
  • Pfizer
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pregnancy and Medication Impact
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pharmaceutical Quality and Counterfeiting
Keywords
malaria in pregnancy, falciparum malaria, sulfadoxine-pyrimethamine, chlorproguanil-dapsone, amodiaquine, artesunate, combination antimalarial therapy, drug resistance, treatment efficacy, drug safety in pregnancy, adverse birth outcomes, stillbirth, maternal mortality, Tanzania, uncomplicated malaria
MeSH terms
Artesunate, Adult, Amodiaquine, Proguanil, Dapsone, Drug Combinations, Drug Therapy, Combination, Female, Humans, Malaria, Pregnancy, Pyrimethamine, Sulfadoxine, Tanzania, Pregnancy Complications, Parasitic, Artemisinins, Young Adult

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