Chloroquine resistance before and after its withdrawal in Kenya. Journal Article


Authors: Leah Mwai; Edwin Ochong; Abdi Abdirahman; Steven M Kiara; Ward, Steve; Kokwaro, Gilbert; Sasi, Philip; Marsh, Kevin; Borrmann, Steffen; Mackinnon, Margaret; Nzila, Alexis
Article Title: Chloroquine resistance before and after its withdrawal in Kenya.
Keywords: MALARIA; DRUG resistance; ANTIMALARIALS; PLASMODIUM falciparum; AFRICA, Sub-Saharan
Journal Title: Malaria Journal
Volume: 8
ISSN: 14752875
Publisher: BioMed Central  
Date Published: 2009-01
Start Page: 1
End Page: 10
DOI/URL:
Notes: --- - Article - ! 'Background: The spread of resistance to chloroquine (CQ) led to its withdrawal from use in most countries in sub-Saharan Africa in the 1990s. In Malawi, this withdrawal was followed by a rapid reduction in the frequency of resistance to the point where the drug is now considered to be effective once again, just nine years after its withdrawal. In this report, the polymorphisms of markers associated with CQ-resistance against Plasmodium falciparum isolates from coastal Kenya (Kilifi) were investigated, from 1993, prior to the withdrawal of CQ, to 2006, seven years after its withdrawal. Changes to those that occurred in the dihydrofolate reductase gene (dhfr) that confers resistance to the replacement drug, pyrimethamine/sulphadoxine were also compared. Methods: Mutations associated with CQ resistance, at codons 76 of pfcrt, at 86 of pfmdr1, and at codons 51, 59 and 164 of dhfr were analysed using PCR-restriction enzyme methods. In total, 406, 240 and 323 isolates were genotyped for pfcrt-76, pfmdr1-86 and dhfr, respectively. Results: From 1993 to 2006, the frequency of the pfcrt-76 mutant significantly decreased from around 95% to 60%, while the frequency of pfmdr1-86 did not decline, remaining around 75%. Though the frequency of dhfr mutants was already high (around 80%) at the start of the study, this frequency increased to above 95% during the study period. Mutation at codon 164 of dhfr was analysed in 2006 samples, and none of them had this mutation. Conclusion: In accord with the study in Malawi, a reduction in resistance to CQ following official withdrawal in 1999 was found, but unlike Malawi, the decline of resistance to CQ in Kilifi was much slower. It is estimated that, at current rates of decline, it will take 13 more years for the clinical efficacy of CQ to be restored in Kilifi. In addition, CQ resistance was declining before the drug''s official withdrawal, suggesting that, prior to the official ban, the use of CQ had decreased, probably due to its poor clinical effectiveness. [ABSTRACT FROM AUTHOR]' - Copyright of Malaria Journal is the property of BioMed Central and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) - ! 'Accession Number: 42094370; Leah Mwai 1,2; Email Address: lmwai@kilifi.kemri-wellcome.or Edwin Ochong 3; Email Address: eochong@liv.ac.uk Abdi Abdirahman 1; Email Address: aabdi001@udcf.gla.ac.uk Steven M Kiara 1; Email Address: smuriithi@kilifi.kemri-wellcome.org Ward, Steve 3; Email Address: saward@liverpool.ac.uk Kokwaro, Gilbert 4; Email Address: Gkokwaro@nairobi.kemriwellcome.org Sasi, Philip 1; Email Address: psasy@kilifi.kemri-wellcome.org Marsh, Kevin 1,2; Email Address: kmarsh@kilifi.kemri-wellcome.org Borrmann, Steffen 1,5; Email Address: sborrmann@kilifi.kemri-wellcome.org Mackinnon, Margaret 1,6; Email Address: mmackinnon@kilifi.kemri-wellcome.org Nzila, Alexis 1,2,3,7; Email Address: anzila@kilifi.kemri-wellcome.org; Affiliation: 1: Kenya Medical Research Institute (KEMRI)/Wellcome Trust Collaborative Research Programme, PO Box 230, 80108, Kilifi, Kenya 2: University of Oxford, Nuffield Department of Medicine, John Radcliffe Hospital, Oxford, UK 3: Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK 4: Kenya Medical Research Institute (KEMRI)/Wellcome Trust Collaborative Research Programme, PO Box 43640, 00100, Nairobi, Kenya 5: Heidelberg University School of Medicine, Institute of Hygiene, FRG, Heidelberg, Germany 6: Department of Pathology, University of Cambridge, Tennis Court Rd, Cambridge, CB2 1QP, UK 7: Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK; Source Info: 2009, Vol. 8, p1; Subject Term: DRUG resistance; Subject Term: ANTIMALARIALS; Subject Term: PLASMODIUM falciparum; Subject Term: MALARIA; Subject Term: AFRICA, Sub-Saharan; Number of Pages: 10p; Illustrations: 3 Graphs; Document Type: Article'
SU Authors
  1. Prof. Gilbert Kokwaro
    26 Kokwaro