Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.

Hdl Handle:
http://hdl.handle.net/10144/16874
Title:
Artesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.
Authors:
Swarthout, T D; van den Broek, I; Kayembe, G; Montgomery, J; Pota, H; Roper, C
Journal:
Tropical Medicine & International Health
Abstract:
We undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.
Affiliation:
Médecins Sans Frontières, London, UK.
Publisher:
Wiley-Blackwell
Issue Date:
Oct-2006
URI:
http://hdl.handle.net/10144/16874
DOI:
10.1111/j.1365-3156.2006.01710.x
PubMed ID:
17002724
Additional Links:
http://www.blackwell-synergy.com/loi/tmi
Language:
en
ISSN:
1360-2276
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorSwarthout, T D-
dc.contributor.authorvan den Broek, I-
dc.contributor.authorKayembe, G-
dc.contributor.authorMontgomery, J-
dc.contributor.authorPota, H-
dc.contributor.authorRoper, C-
dc.date.accessioned2008-01-25T14:54:28Z-
dc.date.available2008-01-25T14:54:28Z-
dc.date.issued2006-10-
dc.identifier.citationArtesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes. 2006, 11 (10):1503-11 Trop. Med. Int. Healthen
dc.identifier.issn1360-2276-
dc.identifier.pmid17002724-
dc.identifier.doi10.1111/j.1365-3156.2006.01710.x-
dc.identifier.urihttp://hdl.handle.net/10144/16874-
dc.description.abstractWe undertook a trial of artesunate + amodiaquine (AS + AQ) and artesunate + sulphadoxine-pyrimethamine (AS + SP) in 180 children of age 6-59 months with uncomplicated malaria in Democratic Republic of Congo. Children were randomly allocated to receive 3 days observed treatment of AS + AQ (n = 90) or 3 days of AS + SP (n = 90). Primary efficacy outcomes were 28-day parasite recurrence rates, and recrudescence rates were adjusted by genotyping to distinguish new infection and recrudescence. In addition, we determined the prevalence of molecular markers of resistance to sulphadoxine and pyrimethamine. Day 28 parasite recurrence rates were 16.9% (14/83; 95% CI: 9.5-26.7) in the AS + AQ group and 34.6% (28/81; 95% CI: 24.3-46.0) in the AS + SP group (P = 0.009). After PCR correction, recrudescence rates were 6.7% (5/74; 95% CI: 2.2-15.1) for AS + AQ and 19.7% (13/66; 95% CI: 10.9-31.3) for AS + SP (P = 0.02). There was no significant difference between the two arms in time to parasite clearance, fever clearance and gametocyte clearance. Parasite genotyping showed high frequencies of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) molecular SP-resistance markers, with 57% of the samples showing more than three mutations linked to SP resistance, and 27% with triple-dhfr/double-dhps haplotype, confirming that SP treatment failure rates are likely to be high. AS + AQ had significantly higher efficacy than AS + SP. These results contributed to the subsequent change to AS + AQ as first-line regimen in the country. Efforts to properly implement the new protocol and maintain adherence at acceptable levels should include health staff and patient sensitization. The 6.8% recrudescence rate indicates that AS + AQ should be monitored closely until a more effective artemisinin combination therapy regimen is needed and can be introduced.en
dc.language.isoenen
dc.publisherWiley-Blackwell-
dc.relation.urlhttp://www.blackwell-synergy.com/loi/tmi-
dc.rightsArchived on this site with the kind permission of Wiley-Blackwellen
dc.subject.meshAmodiaquineen
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChild, Preschoolen
dc.subject.meshDNA, Protozoanen
dc.subject.meshDemocratic Republic of the Congoen
dc.subject.meshDrug Combinationsen
dc.subject.meshDrug Resistanceen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshFemaleen
dc.subject.meshHaplotypesen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalariaen
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshPlasmodiumen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshPyrimethamineen
dc.subject.meshSesquiterpenesen
dc.subject.meshSulfadoxineen
dc.subject.meshTreatment Outcomeen
dc.titleArtesunate + amodiaquine and artesunate + sulphadoxine-pyrimethamine for treatment of uncomplicated malaria in Democratic Republic of Congo: a clinical trial with determination of sulphadoxine and pyrimethamine-resistant haplotypes.en
dc.contributor.departmentMédecins Sans Frontières, London, UK.en
dc.identifier.journalTropical Medicine & International Healthen

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