TABLE 1.
Patients reported in the study
| Patienta | Sexb | Age (yr) | Wt (kg) | Isolate (day)c | Drugd | Parasitemia (%)e | Plasma drug concn (μM)e,f |
Parasite geneticse,g |
|||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| cytb | dhfr | Microsatellites |
|||||||||||||||
| Ato | Pro | Cyc | Others | TAA81 | TAA87 | PfPk2 | Ara2 | TAA 60 | |||||||||
| P1 | M | 24 | 55 | d0 | AP | <0.005 | – | – | – | – | Y | – | 179 | 93 | – | – | 94 |
| d25/d0 | AP | 0.1 | – | – | – | – | S | IRN | 179 | 93 | 169 | 103 | 94 | ||||
| d26/d1 | — | 1.20 | 0.48 | 0.18 | Neg | – | – | – | – | – | – | – | |||||
| d45/d20 | QN | 0.4 | – | – | – | – | S | IRN | 179 | 93 | 169 | 103 | 94 | ||||
| P2 | M | 12 | 40 | d0 | AP | 2.9 | Neg | Neg | Neg | Neg | Y | IRN | 173 | 84 | 172 | 106 | 82 |
| d8 | Neg | – | – | – | – | – | – | – | – | – | – | – | |||||
| d35/d0 | AP | 0.5 | Neg | Neg | Neg | Neg | S | IRN | 173 | 84 | 172 | 106 | 82 | ||||
| d65/d30 | MFQ | <0.1 | – | – | – | – | S | IRN | 173 | 84 | 172 | 106 | 82 | ||||
| P3 | M | 9 | 53 | d0 | AP | 6.6 | Neg | Neg | Neg | Neg | Y | IRN | 182 | – | 172 | 103 | 95 |
| d7 | Neg | 4.12 | 0.02 | Neg | Neg | Y | IRN | 182 | – | 172 | 103 | – | |||||
| d29/d0 | AP | 12.5 | – | – | – | – | C | IRN | 182 | – | 172 | 103 | 95 | ||||
| d32/d3 | 0.01 | – | – | – | – | C | – | – | – | 172 | 103 | 95 | |||||
| d49/d20 | QN | 3.5 | 0.39 | Neg | Neg | Neg | C | IRN | 182 | – | 172 | 103 | 95 | ||||
| P4 | F | 59 | 64 | d0 | AP | 1 | – | – | – | – | – | – | – | – | – | – | – |
| d12 | Neg | 2.39 | Neg | Neg | Neg | Y | – | – | – | – | – | – | |||||
| d24/d0 | AP | 1 | – | – | – | – | C | IRN | 179 | 81 | 163 | 109 | 95 | ||||
| d32/d8 | Neg | 7.98 | 0.04 | Neg | Neg | C | – | – | 81 | 163 | – | 95 | |||||
| d46/d22 | QN | 0.2 | 2.54 | Neg | Neg | Neg | C | IRN | 179 | 81 | 163 | 109 | 94 | ||||
| P5 | F | 14 | 52 | d0 | AP | 0.3 | – | – | – | – | Y | IRN | 179 | 84 | 169, 172 | 103 | 79 |
| d10 | Neg | – | – | – | – | – | – | – | – | – | – | – | |||||
| d23/d0 | AP | 0.1 | – | – | – | – | S | IRN | – | – | – | – | – | ||||
| d31/d8 | <0.1h | 4.10 | Neg | Neg | – | S | IRN | – | – | – | – | – | |||||
| d39/d16 | MFQ | 0.25 | – | – | – | – | S | IRN | 179 | 84 | 172 | 103 | 79 | ||||
| P6 | M | 0.5 | 8 | d0 | AP | 4 | – | – | – | – | – | – | – | – | – | – | – |
| d3 | <0.1 | – | – | – | – | Y | IRN | 179 | 96 | 190 | 112 | 91 | |||||
| d19/d0 | AP | 6 | – | – | – | – | Y+C | IRN | 179 | 96 | 190 | 112 | 91 | ||||
| d22/d3 | MFQ | 0.2 | – | – | – | – | – | – | – | – | – | – | – | ||||
| P7 | M | 58 | 70 | d0 | AP | 2 | Neg | Neg | Neg | Neg | Y | IRN | 164 | 93 | 166 | 127 | 91 |
| d22 | Neg | – | – | – | – | – | – | – | – | – | – | – | |||||
| d27/d0 | AP | 1.5 | 0.10 | Neg | Neg | Neg | C+Sj | IRN | 164 | 93 | 166 | 127 | 91 | ||||
| d32/d5 | QN | 0.0003i | 3.62 | 0.09 | 0.04 | Neg | C+S | IRN | 164 | 93 | 166 | 127 | 91 | ||||
Patients P1 to P7 were infected in The Union of the Comoros, Mali, Senegal, Gabon, Ivory Coast, The Union of the Comoros, and Togo, respectively. All were of African ethnicity except P7, who is Caucasian; patient P5 was already reported (11); additional information and a full case report are provided here.
M, male; F, female.
d0 corresponds to the day of diagnosis and treatment initiation.
That is, the drug used for treatment. AP, atovaquone-proguanil; MFQ, mefloquine; QN, quinine.
Neg, not detected; –, not done.
Ato, atovaquone; Pro, proguanil; Cyc, cycloguanil; Others, monodesethyl-chloroquine, chloroquine, doxycycline, sulfadoxine, pyrimethamine, mefloquine, carboxy-mefloquine, amodiaquine, monodesethyl-amodiaquine, desbutyl-halofantrine, lumefantrine, and dihydro-artemisinin. The lower limit of quantification was 5 μg/liter, which corresponds to 0.014, 0.020, and 0.020 μM for atovaquone, cycloguanil, and proguanil, respectively.
cytb, codon 268 was analyzed; the wild type is tyrosine (Y), and the mutants are serine (S) and cysteine (C). The mutations cytb Y268S and Y268C confer resistance to atovaquone. dhfr, the triple dhfr mutation N51I+C59R+S108N (IRN) confers resistance to cycloguanil. For microsatellites, the allele size (in base pairs) is reported.
A few trophozoites were detected on the thin and thick smears.
Calculated peripheral parasitemia, based on 14 parasites/μl detected on the thick smear and a measured erythrocyte concentration of 3.7 T/liter.
The presence of the two mutations Y268S and Y268C within the same isolate was confirmed by cloning the PCR product and subsequent sequencing of multiple clones (see Fig. S1 in the supplemental material).