Trial reportPloS one2008
Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi.
Trial report in PloS one, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- Intermittent preventive treatment for malaria in children living in areas with seasonal transmission.The Cochrane database of systematic reviews · 2012Pooled it
- Patterns of chloroquine use and resistance in sub-Saharan Africa: a systematic review of household survey and molecular data.Malaria journal · 2011Pooled it
- Artemisinin-based combination therapy for treating uncomplicated malaria.The Cochrane database of systematic reviews · 2009Pooled it
- A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria.Malaria journal · 2009Pooled it
- Trial
- Artemisinin-based combinations versus amodiaquine plus sulphadoxine-pyrimethamine for the treatment of uncomplicated malaria in Faladje, Mali.Malaria journal · 2009Trial
- Impact of dhps mutations on sulfadoxine-pyrimethamine protective efficacy and implications for malaria chemoprevention.Nature communications · 2025Article
- Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data.BMC medicine · 2022Article
- Gaps between Knowledge and Malaria Treatment Practices after Intensive Anti-Malaria Campaigns in Western Kenya: 2004-2016.The American journal of tropical medicine and hygiene · 2020Article
- Molecular surveillance of Plasmodium falciparum drug resistance in the Republic of Congo: four and nine years after the introduction of artemisinin-based combination therapy.Malaria journal · 2017Article
- Article
- Drug resistance maps to guide intermittent preventive treatment of malaria in African infants.Parasitology · 2011Review
- A study of toxicity and differential gene expression in murine liver following exposure to anti-malarial drugs: amodiaquine and sulphadoxine-pyrimethamine.Malaria journal · 2011Article
- Five years of large-scale dhfr and dhps mutation surveillance following the phased implementation of artesunate plus sulfadoxine-pyrimethamine in Maputo Province, Southern Mozambique.The American journal of tropical medicine and hygiene · 2010Article
- Selection of known Plasmodium falciparum resistance-mediating polymorphisms by artemether-lumefantrine and amodiaquine-sulfadoxine-pyrimethamine but not dihydroartemisinin-piperaquine in Burkina Faso.Antimicrobial agents and chemotherapy · 2010Article
- Plasmodium falciparum and dihydrofolate reductase I164L mutations in Africa.Antimicrobial agents and chemotherapy · 2009Article
- Plasmodium falciparum strains harboring dihydrofolate reductase with the I164L mutation are absent in Malawi and Zambia even under antifolate drug pressure.Antimicrobial agents and chemotherapy · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
backgroundIn Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxine-pyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria. METHODOLOGY AND
findings455 children aged 1-5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p<0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p<0.001. Nineteen children developed a neutropenia of </=0.5x10(3) cells/microl by day 14, more commonly after AQ+SP (p = 0.03). The mutation pfcrt 76T, associated with CQ resistance, was detected in none of the pre-treatment or post-treatment parasites. The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP, p = 0.002.
conclusionsThe combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny.
trial registrationControlled-Trials.com ISRCTN22075368.
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