FIGHTING DRUG-RESISTANT MALARIA

Transcription

1 FIGHTING DRUG-RESISTANT MALARIA

2 Read the daily message and record notes of important points and deliverables. (5 min) NSEI WARM-UP Open your pinned Daily Message Notes Add the today s date and the subject of the message (Causes of Drug Resistance) at the top of the note. Add (Copy/Paste) summary of deliverables and/or important information under heading.

3 NSEI REVIEW NS IN PARASITES Interns re-watch a video to review what you have learned about parasite populations and antimalarial drugs. (5 min)

4 NSEI REVIEW NS IN PARASITES What have you learned about antimalarial drug resistance? Share with your table. Key Points: Antimalarial drugs act as a selection pressure on a population of malaria parasites. Every time a malaria parasite reproduces, a mutation that could lead to resistance to a drug has a chance to occur. A mutation can result in a new trait that is adaptive or non-adaptive, or the mutation may have no noticeable effect. Parasites with the adaptive trait of drug resistance will be more likely to survive the exposure to that drug and be able to reproduce and pass this trait to their offspring. This shifts the distribution of traits in that population, so that many more individual parasites have resistance for that drug. In the presence of this selection pressure, the distribution of traits in a population of malaria parasites may shift toward increased drug resistance.

5 NSEI READING ANTIMALARIAL DRUG RESISTANCE Interns actively read from the Dossier to learn more about how single-drug and combination treatments affect drug resistance. (25 min) Open the Futura Biomedical Engineer s Dossier. Selecting the link in the Daily Message and use the table of contents to navigate to Ch 4: Antimalarial Drug Resistance. Today s research connects what you have learned about antimalarial drugs as a selection pressure to how drug resistance develops in a diverse population of parasites. You should make annotations that help answer the question on the board: How do malaria treatments influence drug resistance?

6 NSEI READING ANTIMALARIAL DRUG RESISTANCE Read and annotate independently. Actively read and annotate Ch.4 Antimalarial Drug Resistance of the Dossier. Carefully review the diagrams and captions, and to look at the glossary if you need more support with engineering and project terms.

7 NSEI READING ANTIMALARIAL DRUG RESISTANCE Share and discuss your annotations with your partner. Talk about what you have learned from the chapter. What ideas do you have about how antimalarial drugs influence drug resistance?

8 NSEI READING ANTIMALARIAL DRUG RESISTANCE Let s review the diagrams to check for understanding. When the Red Drug was used, the percentage of Red Drugresistant parasites increases. What do you notice when the Blue Drug is used on the same population instead. The percent of individual parasites that are resistant to Blue Drug increases.

9 NSEI READING ANTIMALARIAL DRUG RESISTANCE When a combination of drugs is used, resistance stays low. Remember that an individual parasite can have more than one trait for resistance some individuals are resistant to more than one drug.

10 NSEI READING ANTIMALARIAL DRUG RESISTANCE Summarizing key points Using a single-drug treatment results in a shift in the distribution of traits in a malaria population toward having more resistance to the drug used in that treatment. Once there is resistance to a drug, that drug may no longer effectively treat malaria. Using a combination of drugs is preferable to a treatment with a single drug.

11 TESTING FOR RESISTANCE Use the MalariaMed Design Tool to observe the effects of single-drug treatments and to discuss the pros and cons of each drug type. (15 min) Design Tool activity. It is important to isolate the different drugs to understand their effects on the malaria population over the ten years of the MalariaMed model. Play and discuss the MalariaMed Design Tool Demo video.

12 TESTING FOR RESISTANCE This is different from the word criteria. It is important to prevent an increase in the total parasite population. You are working to address each of the criteria to a greater or lesser extent, but the constraint of avoiding an increase in the malaria parasite population is something that must be accomplished. The Global Health Organization won t even consider a treatment design that causes an overall increase in the parasite population. Before you can determine which malaria treatments are ideal for addressing the project criteria and this constraint, you must better understand the drugs you have available.

13 TESTING FOR RESISTANCE Analyzing Single-Drug Treatments sheets You will record the results of these tests to help with your research. We will run the first test together as a team.

14 TESTING FOR RESISTANCE Open Futura MalariaMed and we will model building and recording a single-drug treatment for Drug A. Set up and test a 7-day treatment of Drug A at small doses.

15 Run the test The results for Percentage of Parasite Population with High Resistance at the end of 10 years. Record these values in the first table on your sheets. TESTING FOR RESISTANCE

16 Point out the result for Total Parasite Population and direct interns to record this on their sheets. No change TESTING FOR RESISTANCE This result compares the size of the total parasite population from year 0 to year 10, so there was roughly no difference in the number of individuals in the sample population.

17 TESTING FOR RESISTANCE Record the results for Patient Side Effects and Cost on your sheets. Mild side effects, $5,250. These results are directly related to the project criteria and the constraint you must consider in order to make sure your treatments do not result in an increase in malaria parasites. While you should be concerned with minimizing drug resistance, minimizing patient side effects, and keeping costs low, it is also important to try to reduce the malaria parasite population. The ways to reduce the malaria parasite population and the ways to keep resistance low can sometimes conflict.

18 How to analyze test result histograms The histogram bars in each graph reflect the same population of malaria parasites at year 10. What traits for drug resistance exist in the population at year 10? Almost all the parasites have high resistance to Drug A, most have no resistance to Drug B and Drug C, but a small number have some resistance to these drugs. TESTING FOR RESISTANCE

19 Show the percentage by selecting the % button. TESTING FOR RESISTANCE This helps you look at the population in a different way (by displaying the percentage that the number of parasites represents in each bar). Note that for each graph the total should equal 100% because each histogram represents the same total parasite population.

20 Compare this distribution of traits to the population at the beginning. Move the time slider to year 0. What do you notice? The population started with 90% of no resistance to Drug A and 10% of some resistance to Drug A. For Drug B, 40% had no resistance, 40% had some resistance, and 20% already had high resistance. For Drug C, 20% had no resistance and 80% had some resistance. TESTING FOR RESISTANCE

21 TESTING FOR RESISTANCE Let s talk through the observations for the effect of 7 days of Drug A at small doses. As you move the time slider to each year, note that the total parasite population decreased during the first 5 years. Record that observation on your sheets.

22 Focus on Resistance to Drug A histogram. Note when the majority (over 50%) of parasites in the population had the trait for high resistance to Drug A 57% by year 5. Record this in the observations section of your sheets. TESTING FOR RESISTANCE

23 TESTING FOR RESISTANCE Once most of the parasites in the population have high resistance to Drug A, the population begins to increase. Record that observation on your sheets. What does this observation suggest? The malaria treatment, using only Drug A, isn t working anymore to kill the parasites, so the individuals with traits for resistance are more likely to produce offspring with that same trait.

24 Predict what would happen if you continue to use this same malaria treatment and could see the results for Year 15? Year 20? The population would continue to increase because continuing to use Drug A acts as a selection pressure on the population, so individuals with traits for resistance tend to survive and the trait becomes more common. TESTING FOR RESISTANCE

25 TESTING FOR RESISTANCE By year 10, 99% had high resistance to Drug A and 1% had some resistance to Drug A. Record this observation on your sheets.

26 Focus on Resistance to Drug B histogram. Review the years again and note that by year 10, parasites with high resistance to Drug B had decreased from 20% to 0%, and parasites with some resistance to Drug B decreased from 40% to 6%. Record this observation on your sheets. What does this observation suggest? By not using Drug B, parasites with the trait for resistance to Drug B can be killed by using a different drug. TESTING FOR RESISTANCE

27 Focus on Resistance to Drug C histogram. Review the years again and note that by year 10, there were still 0% of the parasites with high resistance to Drug C and parasites with some resistance to Drug C decreased from 80% to 16%. TESTING FOR RESISTANCE

28 TESTING FOR RESISTANCE In pairs - complete the remaining two tests and discuss pros and cons. Each partner will select one drug (B or C), complete the test, and record the results. Which drug will result in the highest percentage of high resistance or which one will reach 50% high resistance in the fewest number of years. Share and record the results from your partners so everyone has a complete analysis. Discuss and record the pros and cons among the three different drugs, using the results of each test.

29 TESTING FOR RESISTANCE Debrief the results and connect back to the Dossier reading. In each case, we isolated variables so each test was the same except for one thing. Each test used drugs for 7 days. Each test used small doses. We only varied the drug type in each test. What are the pros and cons of each single-drug test? Try to consider other ways you could better understand the effects of a single-drug. Try larger doses, Try fewer days.

30 TESTING FOR RESISTANCE Debrief the results and connect back to the Dossier reading. Tomorrow you will wrap-up your research by isolating for other variables to better understand how the drugs affect the traits for drug resistance in the malaria population. You may wish to point out that, as you just saw in the Design Tool, the constraint of killing malaria parasites can be at odds with the criterion of minimizing drug resistance. The best way to minimize drug resistance is to not give any drugs at all. One of the challenges of this engineering problem is finding a good solution that addresses the three criteria within the constraint of killing malaria.

31 After-Hours Work: NSEI 1.3 HOMEWORK Revisit Chapter 4 in the Dossier and revise or add new annotations.