Background
Methods
Study sites
Blood sample collection
Drugs and drug preparation
Ex vivo assay
DNA extraction and genotyping
Statistical analysis
Results
Ex vivo susceptibility of Plasmodium falciparum parasites from Thiès
Drug | 2012 | 2013 |
p value | ||||||
---|---|---|---|---|---|---|---|---|---|
3D7 IC50 (nM) | Mean with 95 % IC (nM) | Range (nM) | 3D7 IC50 (nM) | Mean with 95 % IC (nM) | Range (nM) | ||||
Min | Max | ||||||||
Min | Max | ||||||||
AMQ | 5.488 | 13.84 (11.84–16.13) | 0.7425 | 63.13 | 3.321 | 6.484 (5.208–8.071) | 1.925 | 43.85 | <0.0001 |
LUM | 417.5 | 173.4 (142.0–211.8) | 21.26 | 981.1 | 164.3 | 113.2 (85.9–149.1) | 17.05 | 414 | 0.01 |
ARS | 17.88 | 3.322 (2.852–3.869) | 0.5222 | 10.16 | 2.805 | 3.673 (3.046–4.428) | 1.22 | 18.54 | 0.34 |
AMT | – | – | – | 7 | 6.222 (5.013–7.724) | 1.188 | 33.6 | – | |
CQ | 17.58 | 39.72 (30.92–51.02) | 2.850 | 402.9 | 9.287 | 18.29 (29.07–87.59) | 6.474 | 384.1 | <0.0001 |
Polymorphism assessment of pfmdr1 and pfcrt genes and haplotype of mdr1 gene analysis
pfmdr1 genotype | 2012 (120) | 2013 (N = 50) | p value |
---|---|---|---|
N86 | 97 % (84/87) | 98 % (49/50) | 0.63 |
86Y | 2 % (2/87) | 2 % (1/50) | 0.1151 |
MIXTE (N86Y) | 1 % (1/87) | 0 % | 0.44 |
Y184 | 20 % (22/119) | 34 % (17/50) | 0.029 |
184F | 78 % (93/119) | 60 % (30/50) | 0.0155 |
MIXTE (Y184F) | 3 % (4/119) | 6 % (3/50) | 0.42 |
D1246 | 100 % (119/119) | 100 % (50/50) | – |
K76 | 78 % (47/60) | 80 % (40/50) | 0.83 |
76T | 20 % (12/60) | 20 % (10/50) | 1 |
MIXTE | 2 % (1/60) | 0 % | 0.36 |
NYD | 18 % (18/102) | 35.85 % (18/50) | 0.012 |
NFD | 79 % (81/102) | 62.26 % (31/50) | 0.022 |
YFD | 3 % (3/102) | 1.89 % (1/50) | 0.72 |
Genotype and phenotype analysis
Drugs | Year | IC50 geometric mean (nM) | ||
---|---|---|---|---|
Y184 | 184F | p value | ||
Amodiaquine | 2012 | 10.51 (19) | 15.02 (69) | 0.0671 |
2013 | 5.1 (16) | 6.277 (24) | 0.1992 | |
Chloroquine | 2012 | 117.8 (20) | 104 (89) | 0.1094 |
2013 | 24.18 (15) | 28.10 (27) | 0.1036 | |
Lumefantrine | 2012 | 493.6 (15) | 179.2 (69) | 0.0008 |
2013 | 155.9 (15) | 68.13 (23) | 0.1277 | |
Artesunate | 2012 | 4.034 (12) | 3.041 (60) | 0.3808 |
2013 | 3.365 (17) | 3.693 (25) | 0.5729 | |
Artemether | 2012 | – | – | – |
2013 | 5.997 (17) | 5.936 (25) | 0.9387 |