Table 1.
SNP and haplotype estimates from Papua New Guinea (PNG) and Tanzanian (TNZ) datasets
| SNP/haplotype | Data | Prevalence | MOI = 1 | MOI ≤ 2 | Unambiguous (no GSL) | Unambiguous (no GSL) | ML (no GSL) | ML (with GSL) |
|---|---|---|---|---|---|---|---|---|
| dhfr SNP C59R | PNG | 0.58 (0.48–0.67) | 0.53 (0.39–0.68)N = 45 | 0.56 (0.46–0.65) N = 117 | 0.56 (0.48–0.64) N = 167 | 0.54 (0.46–0.62) N = 159 | 0.56 (0.48–0.63) N = 170; LL = −39.5 | 0.55 (0.47–0.6) N = 170; LL = −36.6 |
| dhfr SNP S108N | PNG | 0.64 (0.54–0.73) | 0.56 (0.41–0.70)N = 45 | 0.64 (0.55–0.73) N = 117 | 0.66 (0.58–0.73) N = 167 | 0.64 (0.56–0.72) N = 159 | 0.66 (0.58–0.73) N = 167; LL = −44.3 | 0.65 (0.57–0.72) N = 167; LL = −42.0 |
| dhfr 2C hap (– –) | PNG | 0.38 (0.29–0.48) | 0.44 (0.30–0.59)N = 45 | na | 0.35 (0.27–0.42) N = 162 | 0.36 (0.28–0.44) N = 154 | 0.34 (0.27–0.42) N = 167; LL = −63.6 | 0.35 (0.27–0.42) N = 167; LL = −60.7 |
| dhfr 2C hap (−+) | PNG | 0.12 (0.07–0.21) | 0.022 (0.0002–0.097) | na | 0.10 (0.06–0.15) | 0.10 (0.06–0.16) | 0.10 (0.06–0.16) | 0.10 (0.06–0.16) |
| dhfr 2C hap (++) | PNG | 0.58 (0.48–0.67) | 0.53 (0.38–0.68) | na | 0.56 (0.48–0.63) | 0.53 (0.45–0.61) | 0.56 (0.48–0.63) | 0.55 (0.47–0.622) |
| dhfr SNP N51L | TNZ | 0.16 (0.10–0.26) | 0.00 (0.00–0.49)N = 3 | 0.075 (0.027–0.15) N = 67 | 0.062 (0.036–0.097) N = 257 | 0.12 (0.066–0.21) N = 88 | 0.083 (0.053–0.12) N = 289; LL = −41 | 0.16 (0.11–0.22) N = 289; LL = −26.5 |
| dhfr SNP C59R | TNZ | 0.32 (0.23–0.43) | 0.33 (0.020–0.85)N = 3 | 0.22 (0.13–0.34) N = 67 | 0.11 (0.076–0.16) N = 228 | 0.25 (0.16–0.35) N = 85 | 0.15 (0.11–0.20) N = 296; LL = −45 | 0.26 (0.20–0.31) N = 296; LL = −30 |
| dhfr SNP S108N | TNZ | 0.47 (0.36–0.59) | 0.33 (0.020–0.85)N = 3 | 0.36 (0.24–0.49) N = 61 | 0.43 (0.36–0.49) N = 229 | 0.47 (0.36–0.58) N = 79 | 0.43 (0.37–0.50) N = 260; LL = −115 | 0.45 (0.39–0.52) N = 260; LL = −60 |
| dhps SNP A437G | TNZ | 0.10 (0.05–0.19) | 0.00 (0.00–0.49)N = 3 | 0.10 (0.044–0.19) N = 67 | 0.054 (0.031–0.086) N = 278 | 0.11 (0.053–0.18) N = 94 | 0.060 (0.036–0.093) N = 289; LL = −39 | 0.12 (0.076–0.17) N = 289; LL = −25 |
| dhps SNP K540E | TNZ | 0.14 (0.08–0.23) | 0.00 (0.00–0.49) N = 3 | 0.095 (0.03–0.19) N = 63 | 0.080 (0.050–0.12) N = 263 | 0.10 (0.048–0.18) N = 90 | 0.093 (0.062–0.13) N = 292; LL = −55 | 0.17 (0.12–0.22) N = 292; LL = −36 |
| dhfr 3C hap (– – –) | TNZ | 0.62 (0.51–0.73) | 0.67 (0.15–0.98) N = 3 | na | 0.74 (0.67–0.80) N = 130 | 0.58 (0.46–0.69) N = 79 | 0.58 (0.5–0.64) N = 260; LL = −164 | 0.55 (0.48–0.61) N = 260; LL = −99 |
| dhfr 3C hap (– – +) | TNZ | 0.32 (0.22–0.43) | 0.00 (0.00–0.63) | na | 0.11 (0.067–0.16) | 0.11 (0.052–0.20) | 0.20 (0.14–0.26) | 0.15 (0.097–0.21) |
| dhfr 3C hap (+−+) | TNZ | 0.11 (0.05–0.21) | 0.00 (0.00–0.63) | na | 0.011 (0.001–0.035) | 0.028 (0.004–0.086) | 0.014 (0.002–0.041) | 0.028 (0.004–0.072) |
| dhfr 3C hap (−++) | TNZ | 0.31 (0.21–0.42) | 0.33 (0.020–0.85) | na | 0.09 (0.053–0.14 | 0.15 (0.082–0.25) | 0.15 (0.097–0.21) | 0.15 (0.10–0.22) |
| dhfr 3C hap (+++) | TNZ | 0.15 (0.09–0.26) | 0.00 (0.00–0.63) | na | 0.05 (0.02–0.09) | 0.13 (0.06–0.22) | 0.065 (0.035–0.10) | 0.12 (0.072–0.177) |
| dhps 2C hap (– –) | TNZ | 0.94 (0.86–0.98) | 1.00 (0.51–1.00) N = 3 | na | 0.94 (0.91–0.97) N = 256 | 0.89 (0.81–0.94) N = 90 | 0.93 (0.89–0.96) N = 285; LL = −50 | 0.85 (0.79–0.89) N = 285; LL = −39 |
| dhps 2C hap (+−) | TNZ | 0.04 (0.01–0.11) | 0.00 (0.00–0.49) | 0.0039 (0.000–0.018) | 0.011 (0.000–0.049) | 0.0036 (0.000–0.017) | 0.0065 (0.000–0.029) | |
| dhps 2C hap (−+) | TNZ | 0.06 (0.02–0.14) | 0.000 (0.000–0.49) | na | 0.000 (0.000–0.0080) | 0.000 (0.000–0.022) | 0.011 (0.0021–0.030) | 0.021 (0.0047–0.055) |
| dhps 2C hap (++) | TNZ | 0.09 (0.04–0.18) | 0.000 (0.000–0.49) | na | 0.055 (0.031–0.089) | 0.10 (0.048–0.18) | 0.057 (0.033–0.089) | 0.12 (0.081–0.18) |
There are six methods of estimating frequency (see Text), noting that the MOI ≤ 2 approach cannot be used for haplotypes frequency estimate. Numbers in parentheses are the 95% CIs. SNP nomenclature is self-explanatory. The dhfr two-codon haplotypes (dhfr 2C hap) are defined at positions 59 and 108 with − indicating wild-type SNP and + indicating mutant, so that, for example, – – is wild type at both positions and −+ is wild type at 59 but mutant at 108. The three-codon dhfr haplotypes (dhfr 3C hap) are defined at positions 51, 59, and 108, and the two-codon dhps haplotypes (dhps 2C hap) are defined at positions 437 and 540, with − and + again indicating wild type and mutant at these codons. Mutations at dhfr codons 51 and 59 very rarely occur without the presence of a mutation at 108, and therefore, two-codon haplotype +− and three-codon haplotypes +–, −+−, and ++− are omitted. Note that prevalence is for multilocus genotypes and not for haplotypes, because prevalence estimates cannot distinguish linkage phase within a sample (see Materials and Methods). GSL = genotyping sensitivity limit; N = number of clones entering the analyses; LL = the maximum log likelihood obtained in the ML analyses. The same data are analyzed simultaneously when estimating frequencies of haplotypes, and therefore, N and LL are the same for each haplotype and consequently, are only given for the wild type.