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Table 1 Identification of resistance/reduced sensitivity of P. falciparum isolates to artesunate (AS)-mefloquine (MQ) combination therapy was analysed based on clinico-parasitological response, and in vitro sensitivity and systemic drug exposure during the acute phase of infection and relationship with pfmdr1 copy number in 17 cases with treatment failure following a three-day combination regimen

From: Identification of resistance of Plasmodium falciparum to artesunate-mefloquine combination in an area along the Thai-Myanmar border: integration of clinico-parasitological response, systemic drug exposure, and in vitro parasite sensitivity

Systemic drug exposure

Case No.

Parasite slope half-life (h)a

In vitro sensitivity (IC50: nM)b

Pfmdr1 copy number

MQ/DHA Systemic exposure

Conclusion on cause(s) of treatment failure

   

AS

MQ

 

AUC0-7d/ AUC0-24h/

Day Re

 

Adequate DHA exposure alone (n=5)

1

3.12

Reduced (3.5±0.42)

Resistant (58.8±5.1)

>1

7.55c

610 (day 21)

-Possible AS resistant

-MQ resistant + Inadequate MQ exposure

-Predicted by increased in pfmdr1 copy number

2

3.56

Reduced (4.8±1.07)

Resistant (69.5±4.7)

>1

8.02c

100 (day 28)

-Possible AS resistant

-MQ resistant + Inadequate MQ exposure

-Predicted by increased in pfmdr1 copy number

3

4.23

Sensitive (1.2±0.27)

Sensitive (10.6±1.9)

1

6.98c

300 (day 28)

-Inadequate MQ exposure

4

3.88

Sensitive (0.7±0.13)

Sensitive (6.6±0.4)

1

7.99c

600 (day 33)

-Inadequate MQ exposure

5

3.42

Sensitive (0.9±0.10)

Sensitive (19.4±0.7)

>1

8.07c

720 (day 14)

-Inadequate MQ exposure

-Predicted by increased in pfmdr1 copy number

Adequate MQ exposure alone (n=5)

6

3.55

Reduced (3.0±0.06)

Resistant (45.3±3.1)

>1

320d

324 (day 27)

-Possible AS resistant + Inadequate DHA exposure

-MQ resistant

-Predicted by increased in pfmdr1 copy number

7

3.39

Reduced (3.1±0.05)

Resistant (70.3±6.3)

>1

208d

212 (day 28)

-Possible AS resistant + Inadequate DHA exposure

-MQ resistant

-Predicted by increased in pfmdr1 copy number

8

3.56

Reduced (4.2±0.07)

Resistant (50.0±4.2)

>1

309d

489 (day 21)

-Possible AS resistant + Inadequate DHA exposure

-Mefloquine resistant

-Predicted by increased in pfmdr1 copy number

 

9

3.64

Sensitive (1.8±0.30)

Resistant (55.3±4.4)

>1

378d

510 (day 28)

- Inadequate DHA concentration

-MQ resistant

-Predicted by pfmdr1 copy number

10

3.22

Sensitive (1.4)

Resistant (35.0±2.9)

>1

489d

402 (day 21)

- Inadequate DHA exposure

-MQ resistant

-Predicted by pfmdr1 copy number

Adequate DHA and MQ exposure (n=7)

11

3.97

Reduced (2.9±0.01)

Resistant (118.4±6.1)

>1

-

1,250 (day 17)

-Possible AS resistant

-MQ resistant,

-Predicted by increased in Pfmdr1 copy number

12

3.45

Reduced (3.7±0.32)

Resistant (95.8±5.4)

>1

-

578 (day 14)

-Possible AS resistant

-MQ resistant

-Predicted by increased in Pfmdr1 copy number

13

3.33

Sensitive (1.7±0.16)

Resistant (28.8±5.5)

>1

-

102 (day 35)

-MQ resistant

-Predicted by pfmdr1 copy number

14

3.56

Sensitive (1.9±0.10)

Resistant (60.8±7.1)

>1

-

620 (day 14)

-MQ resistant

-Predicted by pfmdr1 copy number

15

3.65

Reduced (3.7±0.21)

Resistant (25.5±0.2)

1

-

610 (day 24)

-Possible AS resistant

-MQ resistant

16

3.56

Reduced (5.2±0.85)

Sensitive (16.6±0.8

1

-

107 (day 35)

-Possible AS resistant

 

17

3.44

Sensitive (0.9±0.08)

Sensitive (16.5±2.4)

1

-

67 (day 42)

-Other host-related factors

  1. a Delayed parasite slope half-life if >2.99 h.
  2. b Mean + SD of three experiments, triplicate each.
  3. c MQ AUC 0-7d which was lower than the lower limit of 95% CI (8.48 mg.day/ml).
  4. d DHA AUC 0-24h which was lower than the lower limit of 95% CI (8.48 ng.h/ml).
  5. e Day of recrudescence.