TABLE 2.
Characterization of P. vivax samples associated with a recurrent parasitemia after chloroquine treatment, French Guiana, 2009 to 2015a
| ID | BT (°C) | Parasitemia (%) | Treatment | Treatment response on D28 |
CQ+dCQ (ng/ml) |
Pvmdr1
copy no. |
Pvmdr1
sequence |
Pvcrt-o
copy no. |
Insertion of pvcrt-o K10 |
Sizes of microsatellite loci 13.239, 3.27, 5.504, 11.162, MS9, and MS8f |
|---|---|---|---|---|---|---|---|---|---|---|
| Recurrence in patients followed D28 ± 2 days | ||||||||||
| Not determinable reasonsb | ||||||||||
| P063 | ||||||||||
| D0 | 39.0 | 0.1000 | CQ | ND | A/WT | 0.94 ± 0.19 | Yes | 192–196, 109–117, 206–213–272, 182–186, 112–120, 199–207–211 | ||
| D22 | 36.1 | 0.1000 | No | LPF | NR | ND | A | ND | ND | 192–196, 109, ND, 182–186, 112–120, 199–207 |
| N183 | ||||||||||
| D0 | 39.0 | 0.1800 | CQ | NR | NR | NR | NR | NR | ||
| D30 | 38.7 | 0.3000 | CQ | LCF | NR | NR | NR | NR | NR | NR |
| NR | ||||||||||
| D0 | 38.9 | 0.1000 | CQ | NR | NR | NR | NR | NR | ||
| D22 | 39.0 | 1.2000 | CQ | LCF | NR | NR | NR | NR | NR | NR |
| Subtherapeutic chloroquine concentrations observedc | ||||||||||
| P100 | ||||||||||
| D0 | 39.6 | 0.1600 | CQ | 2 | A | 0.76 ± 0.02 | No | 192, 133, 199, 262–266–270, 116, 203 | ||
| D29 | 36.8 | 0.0010 | No | LPF | 36 + <10 | 2 | A | 0.61 ± 0.01 | No | Identical to D0 |
| Q082 | ||||||||||
| D0 | 38.1 | 0.0300 | CQ | 1 | A | 0.79 ± 0.05 | Yes | 191–196, 109, 59, 182, 112–116–120, 207 | ||
| D14 | 37.0 | 0.0300 | No | LPF | <10 + <10 | 1 | A | 0.73 ± 0.01 | Yes | Identical to D0 |
| R263 | ||||||||||
| D0 | 36.0 | 0.0020 | CQ | 1 | A | 0.69 ± 0.07 | Yes | 192, 109, 213, 186, 116-120-124, 199 | ||
| D28 | 39.0 | 0.1400 | CQ | LCF | 17 + 15 | 1 | A | 0.97 ± 0.01 | Yes | Identical to D0 |
| Chloroquine therapeutic failure associated with parasite resistanced | ||||||||||
| M513 | ||||||||||
| D0 | 38.9 | 0.2500 | CQ | 1 | A | 1.01 ± 0.08 | Yes | 200, 129, 213, 186, 108, 207 | ||
| D2 | 36.7 | 0.0005 | ||||||||
| D6 | 36.5 | 0.0000 | ||||||||
| D13 | 37.6 | 0.0000 | ||||||||
| D20 | 36.5 | 0.0000 | 93 + 53 | |||||||
| D26 | 36.7 | 0.0005 | No | LPF | NR | 1 | A | ND | ND | Identical to D0 |
| N518 | ||||||||||
| D0 | 38.8 | 0.7600 | CQ | 1 | A | 1.09 ± 0.04 | No | 192, 109, 213, 186, 116–120, 207 | ||
| D1 | NR | 0.0000 | ||||||||
| D3 | NR | 0.0000 | ||||||||
| D13 | NR | 0.0000 | ||||||||
| D29 | 39.5 | 0.2000 | CQ | LCF | 224 + 379 | 1 | A | 0.78 ± 0.03 | No | Identical to D0 |
| Extended or no follow-upe |
||||||||||
| Not determinable reasonsb | ||||||||||
| NR | ||||||||||
| D0 | 39.2 | 1.0000 | CQ | NR | NR | NR | NR | NR | ||
| D35 | 40.0 | 0.6000 | CQ | ACPR | NR | NR | NR | NR | NR | NR |
| Subtherapeutic chloroquine concentrations observedc | ||||||||||
| O284 | ||||||||||
| D0 | 39.2 | 0.5000 | CQ | 1 | A/WT | 1.48 ± 0.04 | No | 192, 109–129-149, 213, 186, 116–120-124, 207 | ||
| D32 | 38.6 | 0.4500 | CQ | Lost | <10 + <10 | 1 | A/WT | 0.96 ± 0.15 | No | Identical to D0 |
| P092 | ||||||||||
| D0 | 39.0 | 0.4600 | CQ | 1 | A | 0.83 ± 0.09 | No | 188, 109, 213, 186, 116–120–124, 199 | ||
| D34 | 39.7 | 0.1700 | CQ | Lost | <10 + <10 | 2 | A | 1.33 ± 0.21 | Yes | 192, 109, 213, 186, 116-120-124, 199 |
| P213 | ||||||||||
| D0 | 39.0 | 0.1000 | CQ | 2 | A | 0.80 ± 0.06 | No | 196, 121, 262, 186, 116–120–124, 215-219 | ||
| D32 | 39.0 | 0.0700 | CQ | ACPR | 17 + 10 | 2 | A | 0.70 ± 0.08 | No | Identical to D0 |
| P367 | ||||||||||
| D0 | 38.3 | 0.1000 | CQ | 1 | A | 0.75 ± 0.03 | Yes | 196, 109, 213, 182, 116-120, 207 | ||
| D33 | 38.6 | 0.1100 | CQ | Lost | 15 + <10 | 1 | A | 1.19 ± 0.15 | Yes | Identical to D0 |
| Q332 | ||||||||||
| D0 | 37.6 | 0.3500 | CQ | 1 | A | 1.11 ± 0.03 | No | 192–196, 97–145, 206–213, 182–186, 112–116–120, 207 | ||
| D31 | 40.0 | 0.0500 | CQ | Lost | <10 + <10 | 1 | A | 1.00 ± 0.04 | No | Identical to D0 |
| S674 | ||||||||||
| D0 | 39.5 | 0.1800 | CQ | 1 | A | 1.02 ± 0.02 | No | 192, 129, 59-206, 182, 124–128–132, 199 | ||
| D30 | 38.1 | 0.0200 | CQ | Lost | <10 + <10 | 1 | A | 0.74 ± 0.13 | No | Identical to D0 |
| Chloroquine therapeutic failure associated with parasite resistanced | ||||||||||
| M226 | ||||||||||
| D0 | 38.6 | 0.2000 | CQ | 2 | A | 0.89 ± 0.02 | Yes | 196, 109, 213, 186, 120–124, 219 | ||
| D7 | 0.0000 | |||||||||
| D26 | 38.6 | 0.0500 | CQ | Lost | 65 + 204 | 2 | A | 0.64 ± 0.06 | Yes | Identical to D0 |
A, Guy-A; ACPR, adequate clinical and parasitological response; BT, body temperature; D0 to D35, days 0 to 35; dCQ, desethylchloroquine; ID, identification; LCF, late clinical response; Lost, lost to follow-up; LPF, late parasitological response; ND, not determinable; No, no modification of the treatment; NR, not received; pvmdr1, Plasmodium vivax multidrug resistance 1 gene; WT, wild type. Pvcrt-o gene copy numbers have been determined based on two technical replicates.
Reasons for recurrence not determinable because no drug concentration was available.
Recurrence linked to subtherapeutic concentration of drug: the CQ+dCQ concentration was <100 ng/ml.
Treatment failure (i.e., parasite resistance): the CQ+dCQ concentration was >100 ng/ml, with the same parasite genotype observed on D0 and DF.
Recurrence observed in patients with extended follow-up (D31 to D35) or patients without follow-up (D1 to D35).
Values separated with a hyphen mean that this microsatellite has a multiclonal stucture represented by the different observed sizes at the studied locus.