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Figure 1 | Malaria Journal

Figure 1

From: The last man standing is the most resistant: eliminating artemisinin-resistant malaria in Cambodia

Figure 1

Schematic diagram of the structure of the mathematical modeling framework. The structure of the model is built up as follows: natural history and pharmacodynamics incorporated as a repeating unit (A) with four compartments – susceptible people, people with liver stage infection, people with noninfectious blood stage infection and people with infectious (blood) stage infection, rates of flow between these compartments (βI/N, δ, γ and σ) and rates of recovery due to each of artesunate and piperaquine treatment (c Bda , c Ida , c Bdb and c Idb ) (Additional file 1- Table S2) is shown. The times to recovery (1/rate) following treatment are then adjusted by a multiplying factor (erada or erbdb) (0 ≤ e ≤ 1) depending on the degree of resistance to each drug, giving three possible linked variants of unit A (resistant to no drug, artesunate only and piperaquine only) making up a repeating pattern (B). Finally the population dynamics of transmission is shown in (C). This consists of multiple repetitions of (B) with different rates of flow between them at different time points depending on which treatments and interventions are used. For example, for individuals with blood stage infections to begin treatment with ACT, they will move from the 'No drugs' box (1) to the equivalent parts of an 'ACT' box (2) at a rate determined by the time to begin treatment. The dynamics in the 'ACT' box are different from the 'No drugs' box as these individuals will be subjected to faster rates of recovery due to the ACT. Each box is also subject to pharmacokinetic dynamics independent of infection dynamics. This is in the form of waning pharmacodynamic drug effect over time ('loss of...') with sequential loss of DHA and then piperaquine. This results in a percentage of the entire unit moving to a new box 'Piperaquine' (3) which again has different dynamics representing the effect of piperaquine on recovery rates. Interventions shown here are elimation of artemisinin monotherapy and replacement with ACT ('Switch to ACT') and MSAT and MDA with ACT. Each circle represents a population exposed to a particular drug or combination. Key: ACT = dihydroartemisinin/piperaquine combination therapy, Rx = treatment, DHA = dihydroartemisinin. (For more details, please see the Full Model Code in Additional File 2.)

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