Understanding Drug Resistance

FIGHTING DRUG-RESISTANT MALARIA

Read the daily message and record notes of

important points and deliverables. (5 min)

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.

NSEI 1.3.1 WARM-UP

NSEI REVIEW NS IN PARASITES

Interns re-watch a video to review what you have learned about parasite populations and

antimalarial drugs. (5 min)

What have you learned about antimalarial drug resistance? Share with your table.

NSEI REVIEW NS IN PARASITES

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.

NSEI 1.3.2 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?

https://drm.learning.amplify.com/ereader/#/reader/dde7aa64-c6ce-42e1-973a-6e20e4f5d622


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.


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?


Let’s review the diagrams to check for understanding.

When the Red Drug was used,

the percentage of Red Drug-

resistant 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.


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.


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.

TESTING FOR RESISTANCE USING ONE DRUG

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.


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.

This is different from the

word criteria.

It is important to prevent an

increase in the total parasite

population.


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.


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.

https://apps.learning.amplify.com/malariamed


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.


Record the result for Total Parasite Population

on your sheet.

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.

No change


Record the results for Patient Side Effects and Cost on

your sheet.

These results are directly related to the project criteria

and the constraint you must consider so your

treatments do not result in an increase in malaria

parasites.

While you should be concerned with…it is also

important to try to reduce the malaria parasite

population.

• minimizing drug resistance,

• minimizing patient side effects, and

• keeping costs low,

The ways to reduce the malaria parasite population and

the ways to keep resistance low can sometimes conflict.

Mild side effects, $5,250.


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.


Show the percentage by selecting the % button.

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.


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.


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.


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.


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.


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.


By year 10, 99% had high resistance to Drug A

and 1% had some resistance to Drug A.

Record this observation on your sheets.


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.


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%.


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.


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.


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.

NSEI 1.3 HOMEWORK

After-Hours Work:

Revisit Chapter 4 in the Dossier and revise or add new annotations.

Understanding Drug Resistance

Education

Transcript of Understanding Drug Resistance