Pharmacology Lab — ACT Resistance & Treatment Failure Simulator

💊 Artemisinin combination therapies (ACTs) rely on a fast-acting artemisinin component to reduce parasite biomass and a longer-acting partner drug to eliminate residual parasites. Partial artemisinin resistance (PfKelch13 mutations) slows early clearance; partner drug resistance removes the second-line firewall, causing treatment failure.

Drug Regimen

Resistance Genotype

Select resistance mutations present in infecting strain:

Patient & Treatment Parameters

Initial parasite density parasites/µL at presentation 50k

Treatment adherence Fraction of doses taken 100%

Artemisinin kill rate modifier 1.0 = fully sensitive 1.00

Partner drug kill rate modifier 1.0 = fully sensitive 1.00

Clinical Outcomes

PCT (days)

—

parasite clearance time

Day 28 outcome

—

cure or failure

Nadir density

—

parasites/µL

Recrudescence

—

day if occurs

Area under curve

—

parasite exposure (log)

R-allele spread

—

selection index

PK/PD Model

dP/dt = r·P − k_arte(t)·P − k_part(t)·P

k_arte = K_A·C_A(t)·f_K13·RingStage(t)

k_part = K_P·C_P(t)·f_MDR

C_A(t) = Σ Dose·exp(−λ_A·t) sum over doses

C_P(t) = Dose·exp(−λ_P·t) partner drug

Ring-stage parasite is ~10× less sensitive to artemisinin (dormancy)

Parasite Density — Clearance Curve

Fig. I · Days 0–28

Log₁₀ parasite density per µL. Threshold of detection ~10 parasites/µL (microscopy), ~0.01/µL (PCR).

Drug Concentrations

Fig. II · PK

Artemisinin component (fast; hours) and partner drug (slow; days). MIC threshold shown.

Kill Rates over Time

Fig. III · PD

Daily parasite kill rate from each drug component. Partner drug sustains killing after artemisinin wanes.

Resistance Evolution — Population Level

Fig. IV · 5-year projection

Allele frequency dynamics of resistance mutations under ongoing ACT selection pressure (replicator equation).

Treatment Failure Probability vs Adherence

Fig. V · sensitivity

Probability of day-28 treatment failure as adherence decreases, for each resistance genotype combination.

Clinical & Pharmacological Interpretation

Select a drug and resistance genotype to generate interpretation.

ACT Pharmacokinetics &Drug Resistance Dynamics

PK/PD Model

ACT Pharmacokinetics &
Drug Resistance Dynamics