dhfr and dhps genotype and sulfadoxine-pyrimethamine treatment failure in children with falciparum malaria in the Democratic Republic of Congo.

dhfr and dhps genotype and sulfadoxine-pyrimethamine treatment failure in children with falciparum malaria in the Democratic Republic of Congo.
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DOI:
10.1111/j.1365-3156.2008.02150.x
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发表时间:
2008-11
期刊:
Tropical medicine & international health : TM & IH
影响因子:
--
通讯作者:
Meshnick SR
Meshnick SR
中科院分区:
其他
文献类型:
--
作者:
Alker AP;Kazadi WM;Kutelemeni AK;Bloland PB;Tshefu AK;Meshnick SR

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To determine the relationship between mutations in dhfr and dhps and SP treatment failure in Plasmodium falciparum malaria in the Democratic Republic of the Congo (DRC) Between June and September 2002, a therapeutic efficacy trial was conducted in Rutshuru, Eastern DRC, comparing sulfadoxine-pyrimethamine (SP), SP plus amodiaquine (AQSP), and artesunate plus SP (ASSP) regimens for treating malaria in children under 5 years old. We genotyped 212 samples for mutations associated with SP resistance and investigated their association with treatment failure. In the SP arm, 61% of the subjects experienced treatment failure after 14 days. The failure rate was lower in the combination arms (AQSP: 32%, ASSP: 21%). The dhfr-108 and dhfr-51 mutations were nearly universal while 89% of the samples had at least one additional mutation at dhfr-59, dhps-437, or dhps-540. Dhps mutations had a bigger impact on treatment failure in children with high parasite density: for children with a parasite density less than 45,000 parasites/μl, the risk of treatment failure was 37% for mutations at dhps-437 and dhps-540 mutation and 21% for neither mutation (risk difference (RD) = 17%, 95%CI: −3%, 36%). In children with a parasite density greater than 45,000 parasites/μl, the treatment failure risk was 58% and 8% for children with both mutations or neither mutation, respectively (RD = 51%, 95%CI: 34%, 67%). Dhps-437 and dhps-540 are strongly associated with SP treatment failure and should be evaluated further as a method for surveillance of SP-based therapy in the DRC.
DOI: 10.1046/j.1360-2276.2003.01144.x
发表时间: 2003-12-01
影响因子: 3.3
作者:
Anderson, TJC;Nair, S;Balkan, S
通讯作者: Balkan, S
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发表时间: 2004-12-01
影响因子: 3.2
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通讯作者: D'Alessandro, Umberto
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发表时间: 2001-05-01
影响因子: 2.2
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通讯作者: Warhurst, DC
DOI: 10.1093/oxfordjournals.aje.a113015
发表时间: 1980-01-01
影响因子: 5
作者:
ROTHMAN, KJ;GREENLAND, S;WALKER, AM
通讯作者: WALKER, AM