Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations.

Hdl Handle:
http://hdl.handle.net/10144/17680
Title:
Malaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations.
Authors:
Hamour, S; Melaku, Y; Keus, K; Wambugu, J; Atkin, S; Montgomery, J; Ford, N; Hook, C; Checchi, F
Journal:
Transactions of the Royal Society of Tropical Medicine and Hygiene
Abstract:
Both northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.
Affiliation:
Médecins Sans Frontières, Plantage Middenlaan 14, 1018 DD Amsterdam, The Netherlands.
Publisher:
Elsevier
Issue Date:
Jul-2005
URI:
http://hdl.handle.net/10144/17680
DOI:
10.1016/j.trstmh.2004.10.003
PubMed ID:
15869770
Additional Links:
http://www.sciencedirect.com/science/journal/00359203
Language:
en
ISSN:
0035-9203
Appears in Collections:
Malaria

Full metadata record

DC FieldValue Language
dc.contributor.authorHamour, S-
dc.contributor.authorMelaku, Y-
dc.contributor.authorKeus, K-
dc.contributor.authorWambugu, J-
dc.contributor.authorAtkin, S-
dc.contributor.authorMontgomery, J-
dc.contributor.authorFord, N-
dc.contributor.authorHook, C-
dc.contributor.authorChecchi, F-
dc.date.accessioned2008-02-07T12:39:55Z-
dc.date.available2008-02-07T12:39:55Z-
dc.date.issued2005-07-
dc.identifier.citationMalaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations. 2005, 99 (7):548-54 Trans. R. Soc. Trop. Med. Hyg.en
dc.identifier.issn0035-9203-
dc.identifier.pmid15869770-
dc.identifier.doi10.1016/j.trstmh.2004.10.003-
dc.identifier.urihttp://hdl.handle.net/10144/17680-
dc.description.abstractBoth northern and southern Sudan are deploying artemisinin-based combinations against uncomplicated Plasmodium falciparum malaria (artesunate+sulfadoxine-pyrimethamine [AS+SP] in the north, artesunate+amodiaquine [AS+AQ] in the south). In 2003, we tested the efficacy of 3 day AS+SP and AS+AQ regimens in vivo in the isolated, seasonally endemic Nuba Mountains region (the first study of AS combinations in southern Sudan). We also analysed pre-treatment blood samples for mutations at the P. falciparum chloroquine transporter (Pfcrt) gene (associated with CQ resistance), and at the dihydrofolate reductase (Dhfr) gene (associated with pyrimethamine resistance). Among 161 randomized children under 5 years, PCR-corrected cure rates after 28 days were 91.2% (52/57, 95% CI 80.7-97.1) for AS+SP and 92.7% (51/55, 95% CI 82.4-98.0) for AS+AQ, with equally rapid parasite and fever clearance. The Pfcrt K76T mutation occurred in 90.0% (144/160) of infections, suggesting CQ would work poorly in this region. Overall, 82.5% (132/160) carried mutations at Dhfr (N51I, C59R or S108N, but not I164L), but triple mutants (more predictive of in vivo SP failure) were rare (3.1%). CQ use should be rapidly discontinued in this region. SP resistance may propagate rapidly, and AS+AQ is likely to be a better long-term option, provided AQ use is limited to the combination.en
dc.language.isoenen
dc.publisherElsevier-
dc.relation.urlhttp://www.sciencedirect.com/science/journal/00359203-
dc.rightsArchived on this site with the kind permission of Elsevier Ltd. and the Royal Society of Tropical Medicine and Hygiene, http://www.rstmh.org/transactions.aspen
dc.subject.meshAmodiaquineen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChild, Preschoolen
dc.subject.meshChloroquineen
dc.subject.meshDrug Combinationsen
dc.subject.meshDrug Resistanceen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshInfanten
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMaleen
dc.subject.meshMembrane Proteinsen
dc.subject.meshMembrane Transport Proteinsen
dc.subject.meshProtozoan Proteinsen
dc.subject.meshPyrimethamineen
dc.subject.meshSesquiterpenesen
dc.subject.meshSudanen
dc.subject.meshSulfadoxineen
dc.subject.meshTetrahydrofolate Dehydrogenaseen
dc.subject.meshTreatment Outcomeen
dc.titleMalaria in the Nuba Mountains of Sudan: baseline genotypic resistance and efficacy of the artesunate plus sulfadoxine-pyrimethamine and artesunate plus amodiaquine combinations.en
dc.contributor.departmentMédecins Sans Frontières, Plantage Middenlaan 14, 1018 DD Amsterdam, The Netherlands.en
dc.identifier.journalTransactions of the Royal Society of Tropical Medicine and Hygieneen

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