Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment.

Hdl Handle:
http://hdl.handle.net/10144/17720
Title:
Molecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment.
Authors:
Mugittu, K; Priotto, G; Guthmann, J P; Kiguli, J; Adjuik, M; Snounou, G; Beck, H P; Mshinda, H; Olliaro, P; Taylor, W R J
Journal:
Tropical Medicine & International Health
Abstract:
Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.
Affiliation:
Ifakara Health Research and Development Centre, Ifakara, Tanzania.
Issue Date:
Feb-2007
URI:
http://hdl.handle.net/10144/17720
DOI:
10.1111/j.1365-3156.2007.01813.x
PubMed ID:
17300628
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.authorMugittu, K-
dc.contributor.authorPriotto, G-
dc.contributor.authorGuthmann, J P-
dc.contributor.authorKiguli, J-
dc.contributor.authorAdjuik, M-
dc.contributor.authorSnounou, G-
dc.contributor.authorBeck, H P-
dc.contributor.authorMshinda, H-
dc.contributor.authorOlliaro, P-
dc.contributor.authorTaylor, W R J-
dc.date.accessioned2008-02-07T16:21:27Z-
dc.date.available2008-02-07T16:21:27Z-
dc.date.issued2007-02-
dc.identifier.citationMolecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment. 2007, 12 (2):219-23 Trop. Med. Int. Healthen
dc.identifier.issn1360-2276-
dc.identifier.pmid17300628-
dc.identifier.doi10.1111/j.1365-3156.2007.01813.x-
dc.identifier.urihttp://hdl.handle.net/10144/17720-
dc.description.abstractPolymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.en
dc.language.isoenen
dc.relation.urlhttp://www.blackwell-synergy.com/loi/tmi-
dc.rightsArchived on this site with the kind permission of Wiley-Blackwellen
dc.subject.meshAnimalsen
dc.subject.meshAntimalarialsen
dc.subject.meshArtemisininsen
dc.subject.meshChilden
dc.subject.meshDrug Combinationsen
dc.subject.meshDrug Therapy, Combinationen
dc.subject.meshEndemic Diseasesen
dc.subject.meshGenes, Protozoanen
dc.subject.meshGenotypeen
dc.subject.meshHumansen
dc.subject.meshMalaria, Falciparumen
dc.subject.meshMerozoite Surface Protein 1en
dc.subject.meshParasitemiaen
dc.subject.meshPlasmodium falciparumen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshProtozoan Proteinsen
dc.subject.meshPyrimethamineen
dc.subject.meshRecurrenceen
dc.subject.meshSesquiterpenesen
dc.subject.meshSulfadoxineen
dc.subject.meshUgandaen
dc.titleMolecular genotyping in a malaria treatment trial in Uganda - unexpected high rate of new infections within 2 weeks after treatment.en
dc.contributor.departmentIfakara Health Research and Development Centre, Ifakara, Tanzania.en
dc.identifier.journalTropical Medicine & International Healthen

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