Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya
<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP i...
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| Format: | Article |
| Language: | English |
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BMC
2010-11-01
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| Series: | Malaria Journal |
| Online Access: | http://www.malariajournal.com/content/9/1/338 |
| _version_ | 1818146572871925760 |
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| author | Prigge Sean T Bedno Sheryl A Akala Hoseah M Eyase Fredrick L Spalding Maroya D Coldren Rodney L Moss William J Waters Norman C |
| author_facet | Prigge Sean T Bedno Sheryl A Akala Hoseah M Eyase Fredrick L Spalding Maroya D Coldren Rodney L Moss William J Waters Norman C |
| author_sort | Prigge Sean T |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL.</p> <p>Materials and methods</p> <p>Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. <it>In vitro </it>IC<sub>50 </sub>values for antifolates and quinolones were determined for isolates from the follow-up study.</p> <p>Results</p> <p>The prevalence of isolates containing the <it>pfdhfr </it>N51I/C59R/S108N/<it>pfdhps </it>A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the <it>pfdhfr </it>I164L mutation were absent from both studies. The <it>pfdhps </it>mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five <it>pfdhps </it>codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations <it>pfcrt </it>K76T and <it>pfmdr1 </it>N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up.</p> <p>Conclusions</p> <p>During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring <it>pfdhps </it>mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, its use as a first-line anti-malarial should be discouraged, particularly for populations without acquired immunity to malaria. The increase in the <it>pfcrt </it>K76T prevalence, despite efforts to reduce CQ use, suggests that either these efforts are not adequate to alleviate CQ pressure in Kisumu, or that drug pressure is derived from another source, such as the second-line anti-malarial amodiaquine.</p> |
| first_indexed | 2024-12-11T12:21:29Z |
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| id | doaj.art-8961d69b008a45e18923db0c87283f36 |
| institution | Directory Open Access Journal |
| issn | 1475-2875 |
| language | English |
| last_indexed | 2024-12-11T12:21:29Z |
| publishDate | 2010-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Malaria Journal |
| spelling | doaj.art-8961d69b008a45e18923db0c87283f362022-12-22T01:07:32ZengBMCMalaria Journal1475-28752010-11-019133810.1186/1475-2875-9-338Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, KenyaPrigge Sean TBedno Sheryl AAkala Hoseah MEyase Fredrick LSpalding Maroya DColdren Rodney LMoss William JWaters Norman C<p>Abstract</p> <p>Background</p> <p>Anti-malarial drug resistance in Kenya prompted two drug policy changes within a decade: sulphadoxine-pyrimethamine (SP) replaced chloroquine (CQ) as the first-line anti-malarial in 1998 and artemether-lumefantrine (AL) replaced SP in 2004. Two cross-sectional studies were conducted to monitor changes in the prevalence of molecular markers of drug resistance over the period in which SP was used as the first-line anti-malarial. The baseline study was carried out from 1999-2000, shortly after implementation of SP, and the follow-up study occurred from 2003-2005, during the transition to AL.</p> <p>Materials and methods</p> <p>Blood was collected from malaria smear-positive, symptomatic patients presenting to outpatient centers in Kisumu, Kenya, during the baseline and follow-up studies. Isolates were genotyped at codons associated with SP and CQ resistance. <it>In vitro </it>IC<sub>50 </sub>values for antifolates and quinolones were determined for isolates from the follow-up study.</p> <p>Results</p> <p>The prevalence of isolates containing the <it>pfdhfr </it>N51I/C59R/S108N/<it>pfdhps </it>A437G/K540E quintuple mutant associated with SP-resistance rose from 21% in the baseline study to 53% in the follow-up study (p < 0.001). Isolates containing the <it>pfdhfr </it>I164L mutation were absent from both studies. The <it>pfdhps </it>mutations A581G and A613S/T were absent from the baseline study but were present in 85% and 61%, respectively, of isolates from the follow-up study. At follow-up, parasites with mutations at five <it>pfdhps </it>codons, 436, 437, 540, 581, and 613, accounted for 39% of isolates. The CQ resistance-associated mutations <it>pfcrt </it>K76T and <it>pfmdr1 </it>N86Y rose from 82% to 97% (p = 0.001) and 44% to 76% (p < 0.001), respectively, from baseline to follow-up.</p> <p>Conclusions</p> <p>During the period in which SP was the first-line anti-malarial in Kenya, highly SP-resistant parasites emerged, including isolates harboring <it>pfdhps </it>mutations not previously observed there. SP continues to be widely used in Kenya; however, given the highly resistant genotypes observed in this study, its use as a first-line anti-malarial should be discouraged, particularly for populations without acquired immunity to malaria. The increase in the <it>pfcrt </it>K76T prevalence, despite efforts to reduce CQ use, suggests that either these efforts are not adequate to alleviate CQ pressure in Kisumu, or that drug pressure is derived from another source, such as the second-line anti-malarial amodiaquine.</p>http://www.malariajournal.com/content/9/1/338 |
| spellingShingle | Prigge Sean T Bedno Sheryl A Akala Hoseah M Eyase Fredrick L Spalding Maroya D Coldren Rodney L Moss William J Waters Norman C Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya Malaria Journal |
| title | Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya |
| title_full | Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya |
| title_fullStr | Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya |
| title_full_unstemmed | Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya |
| title_short | Increased prevalence of the <it>pfdhfr/phdhps </it>quintuple mutant and rapid emergence of <it>pfdhps </it>resistance mutations at codons 581 and 613 in Kisumu, Kenya |
| title_sort | increased prevalence of the it pfdhfr phdhps it quintuple mutant and rapid emergence of it pfdhps it resistance mutations at codons 581 and 613 in kisumu kenya |
| url | http://www.malariajournal.com/content/9/1/338 |
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