Table 1 Overview of model estimates from experimental data.

From: Modelling mosquito infection at natural parasite densities identifies drugs targeting EF2, PI4K or ATP4 as key candidates for interrupting malaria transmission

Compound

Target/mechanism

baseline infection intensity (95% CI)

VMR

Hill slope (95% CI)

pIC50 intensity (95% CI)

pIC50 prevalence (95% CI)

normalized pIC50 prevalence, µ0=3

pIC50 asexual asexual bloodstage

human dose (mg)

pCavg, 0–24 hrs

ΔpIC50 prevalence,µ0=3;pCavg

ΔpIC50asexuals;prevalence,µ0=3

ELQ300

BC1 / ATP production

31.82 (27.5; 36.2)

14.50

−3.44 (−4.5; −2.4)

8.81 (8.7; 8.9)

8.58 (8.5; 8.6)

8.69

8.3233

   

−0.4

DDD107498

eEF2 / protein synthesis

37.08 (28.7; 45.4)

14.80

−1.07 (−1.3; −0.9)

9 (8.8; 9.2)

8.12 (8.1; 8.1)

8.63

9.0020

   

0.4

KDU691

PI4K / membrane trafficking

40.17 (37.6; 42.7)

9.46

−4.05 (−4.9; −3.2)

6.52 (6.5; 6.6)

6.24 (6.2; 6.3)

6.42

7.2421

   

0.8

MMV390048

PI4K / membrane trafficking

31.28 (28.9; 33.6)

8.42

−2.42 (−3.1; −1.7)

6.76 (6.7; 6.9)

6.32 (6.3; 6.3)

6.60

7.5534

80(☥)

6.29

0.30

1.0

LMV599

PI4K / membrane trafficking

3.21 (2.1; 4.3)

4.75

−2.41 (−3.4; −1.5)

7.79 (7.7; 7.9)

7.81 (7.7; 7.9)

7.62

8.72(*)

   

1.1

PA21A092

ATP4 / sodium homeostasis

12.4 (11.2; 13.6)

2.29

−2.61 (−3.3; −1.9)

6.83 (6.7; 6.9)

6.57 (6.5; 6.6)

6.68

8.3035

   

1.6

SJ557733

ATP4 / sodium homeostasis

23.88 (21.4; 26.3)

13.61

−1.99 (−2.6; −1.4)

5.99 (5.8; 6.1)

5.67 (5.6; 5.7)

5.79

7.5236

   

1.7

KAE609

ATP4 / sodium homeostasis

3.9 (3.2; 4.6)

2.79

−2.22 (−3; −1.5)

7.54 (7.4; 7.7)

7.4 (7.3; 7.5)

7.36

9.337

7529

6.00

1.35

1.9

ACT451840

PfMDR1 / transporter

28.53 (25.8; 31.2)

12.17

−1.67 (−2; −1.3)

7.57 (7.5; 7.7)

7.06 (7; 7.1)

7.33

9.4038

   

2.1

OZ439

heme metabolism

3.01 (2.4; 3.6)

2.40

−1.19 (−1.5; −0.9)

6.89 (6.7; 7.1)

6.78 (6.6; 6.9)

6.55

8.7239

80040

6.15

0.40

2.2

pyronaridine

heme metabolism

9.03 (7.8; 10.3)

6.85

−18.27 (na;na)

6 (na; na)

5.98 (na; na)

5.98

8.3125

18041

6.49

−0.51

2.3

DHA

heme metabolism

19.26 (17.5; 21)

4.07

−0.95 (−1.1; −0.8)

7.03 (6.8; 7.2)

5.98 (6; 6)

6.61

8.9625

48042

6.91

−0.30

2.3

lumefantrine

heme metabolism

5.99 (4.8; 7.2)

3.69

−0.88 (−1.4; −0.4)

6.37 (5.8; 6.9)

5.96 (5.7; 6.1)

5.92

8.5525

96043

5.02

0.89

2.6

artemisone

heme metabolism

5.55 (4.7; 6.4)

3.23

−1.69 (−2.2; −1.2)

6.68 (6.5; 6.9)

6.47 (6.4; 6.6)

6.45

9.1025

   

2.6

ferroquine

heme metabolism

18.93 (17.4; 20.5)

8.09

−3.95 (−5.2; −2.7)

6.07 (6; 6.1)

5.87 (5.8; 5.9)

5.97

8.7244

   

2.8

  1. Columns list the following parameter estimates (for parameters see Methods, Statistical analyses): 1) Baseline infection intensity (μ 0): average number of oocysts per mosquito midgut for the experiments analysed here. 2) VMR: variance to mean ratio as estimated by the BBD model. 3) Hill slope (s): slope of the Hill function. 4) pIC50intensity: IC50 of infection intensity. 5) pIC50prevalence: IC50 of oocyst prevalence (see Methods, logistic regression). 6) normalized pIC50prevalence, µ0=3: pIC50 for infection prevalence normalized on a baseline infection intensity of 3 oocysts per midgut according to formula (2), allowing for comparisons between compounds and experiments. In addition, the table lists pIC50 values as reported for activity against the asexual blood stages. To compare pIC50prevalence values to human exposure data the table lists previously published plasma concentration as a pCavg (−log Cavg) for the first 24 hours (pCavg,0–24hrs) following administration of the dose indicated in the column ‘human dose’. The column next to the pCavg values lists the difference between the normalized pIC50prevalence value and the pCavg value, to indicate the level of exposure above the transmission-blocking pIC50 value. Lastly, the table lists the difference between the asexual blood stage pIC50 and normalized pIC50prevalence. This value indicates the gap between the therapeutic and the transmission-blocking activity. The compounds are sorted from smallest to largest gap from top to bottom. CI: confidence interval. na: confidence interval not computed as the model did not fully converge at very steep Hill slopes. *Bryan Yeung, personal communication, ☥DL, unpublished data.
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