Therapeutic efficacy of chloroquine and sequence variation in pfcrt gene among patients with falciparum malaria in central India
OBJECTIVES: To assess the therapeutic efficacy of chloroquine (CQ) treatment against uncomplicated Plasmodium falciparum infections in a tribal population of central India (Madhya Pradesh) and to investigate the prevalence of mutant P. falciparum chloroquine-resistant transporter (pfcrt) gene in the parasite population.
METHODS: Clinical and parasitological response was determined by in-vivo testing. For molecular testing, the parasite DNA was extracted from blood samples and used to amplify and sequence parts of the pfcrt (44-177 codons), MSP1 (block 2) and MSP2 (central repeat region) genes.
RESULTS: Of 463 patients presenting fever, 137 tested positive for P. falciparum. They were treated with CQ. Of these, 58% participated in the study. Overall, treatment failure occurred in 53% of participants. Children under 5 years of age showed significantly more CQ resistance than adults. Mutant genotype S(72)V(73)M(74)N(75)T(76) was prevalent among both CQ responders (61.29%) and non-responders (66.7%). Interestingly, several patients from the CQ non-responder group (33.3%, n = 39) were harbouring parasite with wild type C(72)V(73)M(74)N(75)K(76) genotype of the pfcrt gene. Microsatellite sequences downstream of exon 2 varied widely among both wild type and mutant pfcrt haplotypes.
CONCLUSION: The high rate of treatment failure in the present study clearly indicates the need to reassess the use of CQ as first-line antimalarial therapy in central India. This is supported by the presence of mutant pfcrt genotype among majority of the parasite population of the CQ non-responder group of patients. However, the presence of wild type amino acid at codon 76 of the pfcrt gene among several patients with CQ non-responders requires further investigations.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Tropical medicine & international health : TM & IH - 15(2010), 1 vom: 01. Jan., Seite 33-40 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bharti, Praveen Kumar [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 06.05.2010 Date Revised 21.11.2013 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/j.1365-3156.2009.02425.x |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM192821423 |
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| 041 | |a eng | ||
| 100 | 1 | |a Bharti, Praveen Kumar |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Therapeutic efficacy of chloroquine and sequence variation in pfcrt gene among patients with falciparum malaria in central India |
| 264 | 1 | |c 2010 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 06.05.2010 | ||
| 500 | |a Date Revised 21.11.2013 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a OBJECTIVES: To assess the therapeutic efficacy of chloroquine (CQ) treatment against uncomplicated Plasmodium falciparum infections in a tribal population of central India (Madhya Pradesh) and to investigate the prevalence of mutant P. falciparum chloroquine-resistant transporter (pfcrt) gene in the parasite population | ||
| 520 | |a METHODS: Clinical and parasitological response was determined by in-vivo testing. For molecular testing, the parasite DNA was extracted from blood samples and used to amplify and sequence parts of the pfcrt (44-177 codons), MSP1 (block 2) and MSP2 (central repeat region) genes | ||
| 520 | |a RESULTS: Of 463 patients presenting fever, 137 tested positive for P. falciparum. They were treated with CQ. Of these, 58% participated in the study. Overall, treatment failure occurred in 53% of participants. Children under 5 years of age showed significantly more CQ resistance than adults. Mutant genotype S(72)V(73)M(74)N(75)T(76) was prevalent among both CQ responders (61.29%) and non-responders (66.7%). Interestingly, several patients from the CQ non-responder group (33.3%, n = 39) were harbouring parasite with wild type C(72)V(73)M(74)N(75)K(76) genotype of the pfcrt gene. Microsatellite sequences downstream of exon 2 varied widely among both wild type and mutant pfcrt haplotypes | ||
| 520 | |a CONCLUSION: The high rate of treatment failure in the present study clearly indicates the need to reassess the use of CQ as first-line antimalarial therapy in central India. This is supported by the presence of mutant pfcrt genotype among majority of the parasite population of the CQ non-responder group of patients. However, the presence of wild type amino acid at codon 76 of the pfcrt gene among several patients with CQ non-responders requires further investigations | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antigens, Protozoan |2 NLM | |
| 650 | 7 | |a Antimalarials |2 NLM | |
| 650 | 7 | |a DNA, Protozoan |2 NLM | |
| 650 | 7 | |a Membrane Transport Proteins |2 NLM | |
| 650 | 7 | |a Merozoite Surface Protein 1 |2 NLM | |
| 650 | 7 | |a PfCRT protein, Plasmodium falciparum |2 NLM | |
| 650 | 7 | |a Protozoan Proteins |2 NLM | |
| 650 | 7 | |a merozoite surface protein 2, Plasmodium |2 NLM | |
| 650 | 7 | |a Chloroquine |2 NLM | |
| 650 | 7 | |a 886U3H6UFF |2 NLM | |
| 700 | 1 | |a Alam, Mohammad Tauqeer |e verfasserin |4 aut | |
| 700 | 1 | |a Boxer, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Shukla, Man Mohan |e verfasserin |4 aut | |
| 700 | 1 | |a Gautam, Sant P |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Yagya D |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Neeru |e verfasserin |4 aut | |
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