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Exploring Antimalarial Drugs
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- 2. Read the dailymessage and record notes of important points and deliverables. (5 min) Open your pinned Daily Message Notes • Interns should add today’s date and the subject of the message (Drugs to Treat Malaria) at the top of the note. All of the notes they take for this message should fall under this heading. • Add (Copy/Paste) summary of deliverables and/or important information under heading. NSEI 4.1 WARM-UP
- 3. Interns interpret twotypes of visual representations of a malaria parasite population to understand the distribution of drug resistance traits. NSEI ANALYZING DIAGRAMS AND HISTOGRAMS Key Points: • Using a single-drug treatment results in the distribution of traits in a malaria population that shift toward having more resistance to the drug used in that treatment. • Once there is high resistance to a drug, that drug may no longer effectively treat malaria and the population will increase. • Preventing an increase in the total population of malaria parasites is a constraint of this engineering problem.
- 4. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS Each parasite is represented once on each histogram. Each pair of histograms (top and bottom) show the same population visualized in two different ways 1. sorted according to the parasites’ resistance to Red Drug (top histogram in the set), 2. and then sorted according to the parasites’ resistance to the Blue Drug (bottom histogram in the set).
- 5. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •The histograms on the left show the initial population, before any drug was applied. The histograms on the right show the same population after treatment with Red Drug. It is clear that the distribution of traits have shifted.
- 6. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •The top histograms show changes in the number of individuals with traits for resistance to Red Drug (red stripes) at a some specific points in time. The bottom set of histograms reflects the same population, but focusing on the number of individuals with traits for resistance to Blue Drug (blue stripes).
- 7. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •Trace the connection between the initial population diagram and each histogram set, pointing out how the one individual with high resistance to Red Drug is shown in the top histogram, and the remaining five individuals account for none (no traits for resistance to Red Drug). The fact that some parasites have blue stripes (resistance to Blue Drug) is of no interest when constructing the Red Drug histogram.
- 8. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •Repeat this same thought exercise using the Blue Drug and the histograms at the bottom of the projection: there is one individual with the trait for high resistance to Blue Drug (two blue stripes), one with some resistance (one blue stripe), and the remaining four have no traits for resistance to Blue Drug.
- 9. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •Why has the percentage of the population with high resistance to Red Drug increased? •Because the treatment that used the Red Drug didn’t kill those individuals with high resistance to Red Drug, so more survived and can continue to reproduce.
- 10. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •Why has the percentage of the population with high resistance to Blue Drug decreased? •Because the treatment that used Red Drug killed most of those individuals with no resistance to Red Drug. Even if the individuals had a high resistance to a different drug (Blue), that did not help them in the presence of Red Drug, and they were killed.
- 11. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •What do you expect to see if you treat the same initial population with the Blue Drug? •The percentage of the population with traits for resistance to Blue Drug will increase, but the percentage of population with traits for resistance to Red Drug will decrease.
- 12. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS •Note that many individuals with resistance to Blue Drug survived the use of that drug and then reproduced, passing their traits for resistance to the offspring.
- 13. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS • Recall the MalariaMed histograms showing the traits for resistance to three different drugs: A, B, and C.
- 14. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS • Recall the MalariaMed histograms showing the traits for resistance to three different drugs: A, B, and C.
- 15. NSEI ANALYZING DIAGRAMSAND HISTOGRAMS • Recall the MalariaMed histograms showing the traits for resistance to three different drugs: A, B, and C.
- 16. NSEI 1.4.2 READING ANTIMALARIALDRUG RESISTANCE Interns use Active Reading to learn about and then summarize the characteristics of the antimalarial drugs they can use in their malaria treatments. Open the Futura Biomedical Engineer’s Dossier. Selecting the link in the Daily Message and use the table of contents to navigate to Chapter 5: “Antimalarial Drugs.” • Today’s research describes the characteristics of each drug and how they affect the project criteria. Review the three project criteria, if desired. • Locate the Pros and Cons of Antimalarial Drugs table from Analyzing Single-Drug Treatments sheet from the previous day. Add items to the table as you read. • Actively read and annotate this section of the Dossier.
- 17. NSEI 4.2 READING ANTIMALARIALDRUG RESISTANCE Key Points • Different drugs are more or less effective at killing parasites than others. More effective drugs will shift the distribution of traits toward drug resistance more quickly. • Different drugs cause different patient side effects, some of which can interfere with an effective drug treatment if the side effects are more serious. Review the meaning of the words mild, moderate, and severe, as necessary. • It is important to consider cost when designing malaria treatments so that it is accessible to those who need it most.
- 18. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Interns continue to run isolated tests in MalariaMed to understand how different drugs, doses, and numbers of treatment days affect the project criteria. • List the things you can change in MalariaMed. • drug type, • drug dose, • number of days.
- 19. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES • What variable was isolated in the single- drug treatment analysis. • Drug type: for each test we used only one drug: A, B, or C • In those single-drug tests you were testing for the effects of each drug type; you isolated the drug type variable, and kept the number of days and dose size the same in each test.
- 20. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES • When you did the single- drug treatments tests, you gathered data about how each drug type affected a malaria treatment, keeping dose size and number of days the same. • Today, you will use MalariaMed to investigate these questions by isolating different variables: either number of days or dose size. How do you think you could use MalariaMed to figure out how dose size might affect a single-drug treatment?
- 21. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES For today’s testing you and your partner are going to vary the size of the dose, and the number of testable days. For example: One partner could test Drug A for three days at large doses while the other partner tests Drug A for three days at small doses. Interns could then do another test for a different number of days or for a different drug.
- 22. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Review the histograms with each test and record observations, just as you did yesterday during the Analyzing Single-Drug Treatments task. Complete at least three tests, and discuss your results and record your ideas on the Conclusions table.
- 23. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES
- 24. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Summarize your conclusions for Total Parasite Population. If you don’t use enough days of the drug, too many parasites can survive and the population will increase. If you use larger doses, more parasites will die (depends on drug) and the population will increase.
- 25. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Summarize your conclusions for Drug Resistance. When using large doses, the percentage of resistance is higher after 10 years, and you see parasites with high resistance in fewer years compared to small doses. When using one drug for only 1–3 days, the percentage of resistance is smaller after 10 years, and it takes more years to see parasites with high resistance compared to treatments that are 5–7 days.
- 26. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Are the trends the same for all drugs? Discuss why or why not.. Drug B already has individuals with high resistance so using only that drug results in the majority (larger percent) of population with traits for high resistance in fewer years. Drug C is the least effective drug, so it takes longer to see parasites with high resistance, or the final percentage is lower compared to other drugs.
- 27. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Summarize your conclusions for Patient Side Effects. In general, fewer days of a drug result in lower side effects, but it depends on the drug. Small doses of a drug result in lower side effects.
- 28. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Summarize your conclusions for Total Cost. Fewer days of a drug result in lower costs (depends on drug). Smaller doses cost less so treatment costs are lower.
- 29. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES Use evidence from the Dossier to help explain why you are seeing these results. If you don’t use large enough doses, even those individuals with some resistance can survive and reproduce to pass on their traits; Those individuals with no resistance are more likely to survive a low dose, and all surviving individuals have a chance of producing offspring that develop mutations for stronger drug resistance; If you don’t use drugs for enough days, you will see something similar—more individuals surviving, reproducing, and possibly producing offspring which have developed traits for higher drug resistance through mutation.
- 30. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES What might happen to the population if more than one drug is used? Resistance would be minimized because it is likely that the second drug would kill the parasites that were resistant to the first drug.
- 31. NSEI 4.2 INVESTIGATINGMALARIAMED VARIABLES What might happen to the population if more than one drug is used? Resistance would be minimized because it is likely that the second drug would kill the parasites that were resistant to the first drug.
- 32. NSEI 4.3 AFTER-HOURSWORK Complete the Project Summary form as a prewriting activity for the introduction of the final proposal. You have worked with the different antimalarial drugs today and have learned more about how each contributes to the various project criteria. This form will be submitted to our project leader Ken so he can see what interns understand about the project and some early ideas about malaria treatment designs.
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