Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax.
BACKGROUND: Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia. METHODS: In vitro drug susceptibility and pvmdr1 genotype were determined in P. vivax field isolates from Indonesia and Thailand. RESULTS: Increased pvmdr1 copy number was present in 21% of isolates from Tha...
| Hoofdauteurs: | , , , , , , , , , , , , , , |
|---|---|
| Formaat: | Journal article |
| Taal: | English |
| Gepubliceerd in: |
2008
|
| _version_ | 1826279776368721920 |
|---|---|
| author | Suwanarusk, R Chavchich, M Russell, B Jaidee, A Chalfein, F Barends, M Prasetyorini, B Kenangalem, E Piera, K Lek-Uthai, U Anstey, N Tjitra, E Nosten, F Cheng, Q Price, R |
| author_facet | Suwanarusk, R Chavchich, M Russell, B Jaidee, A Chalfein, F Barends, M Prasetyorini, B Kenangalem, E Piera, K Lek-Uthai, U Anstey, N Tjitra, E Nosten, F Cheng, Q Price, R |
| author_sort | Suwanarusk, R |
| collection | OXFORD |
| description | BACKGROUND: Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia. METHODS: In vitro drug susceptibility and pvmdr1 genotype were determined in P. vivax field isolates from Indonesia and Thailand. RESULTS: Increased pvmdr1 copy number was present in 21% of isolates from Thailand (15/71) and none from Indonesia (0/114; P < .001). Compared with Indonesian isolates, the median IC(50) of Thai isolates was lower for chloroquine (36 vs. 114 nmol/L; P < .001) but higher for amodiaquine (34 vs. 13.7 nmol/L; P = .032), artesunate (8.33 vs. 1.58 nmol/L; P < .001), and mefloquine (111 vs. 9.87 nmol/L; P < .001). In 11 cryopreserved Thai isolates, those with increased pvmdr1 copy number had a higher IC(50) for mefloquine (78.6 vs. 38 nmol/L for single-copy isolates; P = .006). Compared with isolates with the wild-type allele, the Y976F mutation of pvmdr1 was associated with reduced susceptibility to chloroquine (154 nmol/L [range, 4.6-3505] vs. 34 nmol/L [range, 6.7-149]; P < .001) but greater susceptibility to artesunate (1.8 vs. 9.5 nmol/L; P = .009) and mefloquine (14 vs. 121 nmol/L; P < .001). CONCLUSIONS: Amplification of pvmdr1 and single-nucleotide polymorphisms are correlated with susceptibility of P. vivax to multiple antimalarial drugs. Chloroquine and mefloquine appear to exert competitive evolutionary pressure on pvmdr1, similar to that observed with pfmdr1 in Plasmodium falciparum. |
| first_indexed | 2024-03-07T00:03:50Z |
| format | Journal article |
| id | oxford-uuid:76e002e9-f487-4d81-912c-3543f3d6364d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:03:50Z |
| publishDate | 2008 |
| record_format | dspace |
| spelling | oxford-uuid:76e002e9-f487-4d81-912c-3543f3d6364d2022-03-26T20:19:17ZAmplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:76e002e9-f487-4d81-912c-3543f3d6364dEnglishSymplectic Elements at Oxford2008Suwanarusk, RChavchich, MRussell, BJaidee, AChalfein, FBarends, MPrasetyorini, BKenangalem, EPiera, KLek-Uthai, UAnstey, NTjitra, ENosten, FCheng, QPrice, R BACKGROUND: Multidrug-resistant strains of Plasmodium vivax are emerging in Southeast Asia. METHODS: In vitro drug susceptibility and pvmdr1 genotype were determined in P. vivax field isolates from Indonesia and Thailand. RESULTS: Increased pvmdr1 copy number was present in 21% of isolates from Thailand (15/71) and none from Indonesia (0/114; P < .001). Compared with Indonesian isolates, the median IC(50) of Thai isolates was lower for chloroquine (36 vs. 114 nmol/L; P < .001) but higher for amodiaquine (34 vs. 13.7 nmol/L; P = .032), artesunate (8.33 vs. 1.58 nmol/L; P < .001), and mefloquine (111 vs. 9.87 nmol/L; P < .001). In 11 cryopreserved Thai isolates, those with increased pvmdr1 copy number had a higher IC(50) for mefloquine (78.6 vs. 38 nmol/L for single-copy isolates; P = .006). Compared with isolates with the wild-type allele, the Y976F mutation of pvmdr1 was associated with reduced susceptibility to chloroquine (154 nmol/L [range, 4.6-3505] vs. 34 nmol/L [range, 6.7-149]; P < .001) but greater susceptibility to artesunate (1.8 vs. 9.5 nmol/L; P = .009) and mefloquine (14 vs. 121 nmol/L; P < .001). CONCLUSIONS: Amplification of pvmdr1 and single-nucleotide polymorphisms are correlated with susceptibility of P. vivax to multiple antimalarial drugs. Chloroquine and mefloquine appear to exert competitive evolutionary pressure on pvmdr1, similar to that observed with pfmdr1 in Plasmodium falciparum. |
| spellingShingle | Suwanarusk, R Chavchich, M Russell, B Jaidee, A Chalfein, F Barends, M Prasetyorini, B Kenangalem, E Piera, K Lek-Uthai, U Anstey, N Tjitra, E Nosten, F Cheng, Q Price, R Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title | Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title_full | Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title_fullStr | Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title_full_unstemmed | Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title_short | Amplification of pvmdr1 associated with multidrug-resistant Plasmodium vivax. |
| title_sort | amplification of pvmdr1 associated with multidrug resistant plasmodium vivax |
| work_keys_str_mv | AT suwanaruskr amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT chavchichm amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT russellb amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT jaideea amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT chalfeinf amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT barendsm amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT prasetyorinib amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT kenangaleme amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT pierak amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT lekuthaiu amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT ansteyn amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT tjitrae amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT nostenf amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT chengq amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax AT pricer amplificationofpvmdr1associatedwithmultidrugresistantplasmodiumvivax |