DEADINBURGH

1. An unknown pathogen ravages Scotland’s capital, turning the unlucky souls into bloodthirsty ambling beasts. You are one of the last uninfected citizens in a city under martial law, cut off from the rest of the UK. Now, with help from real scientists, you have only hours to decide how to save Edinburgh, and perhaps the world.

4. DEADINBURGH Route of Infection

5. What we need to do It is important that we quickly identify the route of infection of a new disease outbreak, that scientists are calling Lazarus, so we can take measures to prevent transmission of the infection. We have received information about cases reported around the country but the scientists have not had time to analyse the reports. In order to help the scientists in the safe zone interpret the data that has been collected we need to present them in a way that is easy to understand. You will need to put the case reports into a table and draw a pie chart to show the likely route of infection. You should be able to: • Present data in tables and pie charts • Choose the correct way to present data • Calculate the mode • Calculate percentages Keywords Virus, bacteria, route of infection, symptomatic, percentage, mode, pie chart

6. Recent scientific research New technology and laboratory breakthroughs, such as the discovery of a gene in flu that causes severe infections and the ‘barcoding’ of viral diseases to rapidly test new outbreaks for potentially lethal mutations, are changing the potential for us to understand the progress of illness and identify new threats. Scientists have gained fresh insights into how the bacteria Salmonella is able to change key cells that line the intestine and how Campylobacter survive in the acid conditions of our stomach, enabling the bugs to thrive. By changing the make-up of intestinal cells, Salmonella bacteria are able to cross the gut wall and infect vital organs such as the kidneys and the liver. When exposed to the highly acidic conditions of our stomach Campylobacter change their behaviour and focus on movement, making them better at invading our tissues. These findings may help explain how eating infected meat enables bacteria to infect us and causes changes in healthy bodies leading to more severe illness.

7. Activity 1: We have received case reports from nine infected individuals. Information on how they were possibly infected is provided below, but the scientists have not had time to process the data. You will need to decide how the disease was transmitted in each case! Possible routes of transmission are: Contact – direct physical contact such as touching an infected individual Saliva – saliva from an infected individual comes into contact with the victim such as being bitten Blood – blood from an infected individual comes into contact with a victim such as through a cut in the skin

8. Cases • Bite on the forearm by symptomatic individual that drew blood • Scratched on the face by a panicking injured man leading to bleeding • Fingers chewed off by symptomatic individual • Coughed on by an individual who went on to develop symptoms • Cut themselves on a rusty nail in a plank of wood that had been used to fight off symptomatic individuals • Got spit in the eye when surrounded by a horde of slobbering symptomatic individuals • Got blood in the mouth in an attack on a group of symptomatic individuals • Policeman who was in close contact with a crowd of infected people trying to break out of a quarantined area, no obvious injuries. • Suffered a needle stick injury after trying to sedate a symptomatic individual Contact·Saliva·Blood

9. Question 1: How many were infected by each of the following routes? • Contact • Saliva • Blood Draw a table to show your results.

10. Question 2: Plot the data in a pie chart. Question 3: Which is the most common route of infection (mode)? Question 4: What percentage of the cases was transmitted by saliva?

11. Answers Activity 1, Question 1: How many were infected by each of the following routes? Question 2: Plot the data in a pie chart. Question 3: Which is the most common route of infection (mode)? Blood Question 4: What percentage of the cases was transmitted by saliva? 33.3%

12. Glossary Bacteria – A very large group of single celled organisms that lack organelles or a nucleus, some of which can cause disease. Campylobacter – A group of bacteria that are spiral in shape and have a flagella at one or both ends. They are one of the main causes of bacterial foodborne disease. Culture – A method of multiplying microorganisms by growing them in a liquid or gel under laboratory conditions so they can be studied. Intestinal – In the region of the digestive tract after the stomach. Route of transmission – The passing of a disease from an infected individual or group to a previously uninfected individual. Salmonella – A group of rod shaped bacteria that cause infections in humans and animals. Symptomatic – Displaying symptoms Virus – A small infectious agent made of nucleic acid and a protein coat that can only replicate inside cells.

13. You should be able to: • Present data in tables and pie charts • Choose the correct way to present data • Calculate the mode • Calculate percentages

15. DEADINBURGH Progress of disease

16. What we need to do Scientists are working on how the infection gets into the body and spreads. They need to find out what the infectious agent is doing when it gets in to the body and how it spreads around. Research on the evolution of viruses suggests they kill the cells they infect faster if they are competing with another infection in the body. You will need to carry out calculations to see if a bacteria suspected to be involved in the disease survives in the acidic conditions found in our stomach. You should be able to: • Present data in tables and bar charts • Choose the correct way to present data • Calculate fractions and percentages • Use percentages to calculate ratios Keywords Bacteria, pH, route of transmission, symptomatic, ratio, percentage, mean, histogram

17. Scientists have discovered new evidence about the evolution of viruses showing that when they infect a host they cooperate with other similar viruses to kill cells slowly but speed up the rate at which they kill the cells if there is an unrelated infection in the cells. This discovery will help scientists understand how an illness progresses. Scientists have gained fresh insights into how the Salmonella bacteria are able to change key cells that line the intestine and how Campylobacter survive in the acid conditions of our stomach, enabling the bugs to thrive. When exposed to the highly acidic conditions of our stomach Campylobacter change their behaviour and focus on movement, making them better at invading our tissues.

18. Activity 1 Question 1: Bacteria were grown in the following concentrations of Nitrogen (N2), Oxygen (O2) and Carbon dioxide (CO2): 85 % N2 5 % O2 10 % CO2 Express the percentages as a ratio in simplest form?

19. Activity 2 Question 1: One ml (1000 µl) of bacterial culture were grown in varying pH.Complete the table by calculating the missing values. Question 2: Plot the results in a graph or a chart. Think about the best way to present your data. Question 3: Human stomach acid can be as high as pH 7 if you have eaten a large meal or as low as pH 2 if you are producing a lot of stomach acid on an empty stomach. Scientists are worried that if even 0.5% of these bacteria can survive you may become infected. What would your stomach pH have to be to kill more than 99.5% of the bacteria?

20. Answers Activity 1 Question 1: Bacteria were grown in the following ratios of Nitrogen (N2), Oxygen (O2) and Carbon dioxide (CO2): 17:1:2 What were the percentage concentrations of the three gases? 85% N2 5% O210% CO2

21. Answers Activity 2 Question 1: One ml (1000 µl) of bacterial culture were grown in varying pH.Complete the table by calculating the missing values. Question 2: Plot the results in a graph or a chart. Think about the best way to present your data.

22. Answers Activity 2 Question 3: Human stomach acid can be as high as pH 7 if you have eaten a large meal or as low as pH 2 if you are producing a lot of stomach acid on an empty stomach. Scientists are worried that if even 0.5% of these bacteria can survive you may become infected. What would your stomach pH have to be to kill more than 99.5% of the bacteria? pH 3.75

23. Glossary Bacteria – A very large group of single celled organisms that lack organelles or a nucleus, some of which can cause disease. Campylobacter – A group of bacteria that are spiral in shape and have a flagella at one or both ends. They are one of the main causes of bacterial foodborne disease. Culture – A method of multiplying microorganisms by growing them in a liquid or gel under laboratory conditions so they can be studied. Intestinal – In the region of the digestive tract after the stomach. Route of transmission – The passing of a disease from an infected individual or group to a previously uninfected individual. Salmonella – A group of rod shaped bacteria that cause infections in humans and animals. Symptomatic – Displaying symptoms Virus – A small infectious agent made of nucleic acid and a protein coat that can only replicate inside cells.

24. You should be able to: • Present data in tables and bar charts • Choose the correct way to present data • Calculate fractions and percentages • Use percentages to calculate ratios

26. DEADINBURGH Infectious or not

27. What we need to do Scientists have been monitoring the movements of groups of people since the start of the outbreak hoping to predict and identify infected individuals. We have received data on the movement of groups of individuals. The scientists need you to calculate how fast the individuals are moving and how far they can travel in a day. You will also need to analyse the results of observers to determine if you can tell the difference between infected and uninfected individuals. You must then decide if we should fit monitoring devices to healthy people so we can get early warning of potentially infected individuals? You should be able to: • Convert percentages to decimals • Multiply probabilities Keywords Symptomatic, percentage, probability

28. New technology and laboratory breakthroughs, such as the monitoring of healthy cows with electronic tags are changing the potential for us to detect and understand the progress of illness. Researchers are using mathematical techniques and statistical analysis alongside wireless tracking sensors to monitor the health of a herd of dairy cows in new research aimed at helping farmers spot that cows are unwell before symptoms appear. It is hoped that such early detection of illnesses such as lameness and mastitis would result in less suffering for the cows as well as ensuring milk yields.

29. Activity 1 Complete the table to work out how fast each individual is moving. Speed = Distance ÷ Time Question 1: The group is 45 miles away. If they do not stop moving how long will it take for the first individual to reach our position?

30. Activity 2 Question 1: For each of the 5 individuals calculate the probability of the given sequence of behaviours being carried out: a) assuming that they are normal (uninfected) b) assuming that they are infected

31. Activity 2 Question 2: Should all of the individuals that were observed who reach the quarantine zone be treated as if they have succumbed to infection? If not which of the individuals should be protected from the rest of the horde heading towards our position? Question 3: Is the monitoring of the behaviour of individuals able to distinguish between those that are infected and those that are not? Would you recommend that everyone wears a monitoring sensor and would it be ethical to require everyone to wear one at all times?

32. Answers Activity 1 Question 1: The group is 45 miles away. If they do not stop moving how long will it take for the first individual to reach our position? 10 hours 51 minutes

33. Answers Activity 2 Question 1:

34. Answers Activity 2 Question 2: Should all of the individuals that were observed who reach the quarantine zone be treated as if they have succumbed to infection? If not which of the individuals should be protected from the rest of the horde heading towards our position? Individuals 2 and 5 seem have a low probability of carrying out the sequence of behaviours recorded if they were infected. They are probably not infected and instead trying to escape the horde of infected without drawing too much attention to themselves. Question 3: Is the monitoring of the behaviour of individuals able to distinguish between those that are infected and those that are not? In this case the monitoring seems to have identified a clear difference in the probability of individuals being infected. However, there are other factors to consider such as the individuals being carriers of the disease, because they are not susceptible to the infection but can still pass it on to others.

35. You should be able to: • Convert percentages to decimals • Multiply probabilities

37. DEADINBURGH Viral replication

38. What we need to do Scientists from the Roslin Institute have collected samples of infected cells from members of the public. In order to determine the concentration of the virus and establish how much virus is enough to infect someone, the scientists infect human cells grown in culture with dilutions of the virus. The scientists need your help to work out the concentrations of the samples and the infectivity. You will then need to present your results to the scientist using the appropriate graphs and tables. You should be able to: • Write numbers in standard form • Choose appropriate results to draw conclusions • Present data in a line graph • Solve simultaneous equations using substitution Keywords Agar, assay, bacteria, concentration, culture, dilution, DNA, growth media, pathogen, plaque, PFU, RNA, symptomatic, virus

39. Viruses evolve to cause disease. The immune system and medicines ‘evolve’ to kill viruses. There are many types of viruses and some are more harmful than others. For example, the common cold and winter flu are quite common and for most people they are not especially dangerous. Other viruses, like SARS or rabies, can be very dangerous. Viral diagnostics could become far quicker with the development of 'barcodes' of viral diseases to identify potentially lethal mutations. There is even the potential for diagnosing viral infections without having to use cultures of cells to grow the virus or carrying out sequencing to identify the genes

40. Activity 1: Dilution calculations Question 1: Calculate how much of the original sample is in each tube and show your answer in decimals. Write the volumes in standard form for each tube e.g. 1 x 10-1. Calculate the dilution factor for each tube. Record your results in the table below

41. Activity 2: Calculating the level of infectivity Question 1: Calculate the number of PFU’s in the original sample by multiplying the number of plaques on your chosen petri dish with the dilution factor of the tube the sample was taken from. PFUs = plaques x dilution factor Convert to standard form.

42. Activity 3: Testing the effectiveness of treatments Question 1: Data has been received for some other anti-viral drugs. The data we received from the experiments show that: 17 PFUs and 33 doses of Moroxydine = 14 plaques 22 PFUs and 40 doses of Metisazone = 20 plaques 15 PFUs and 20 doses of Peramivir = 15 plaques 45 PFUs and 15 doses of Zanamivir = 42 plaques How many plaque forming units does each dose of anti-viral drug prevent? Is it better or worse than Cidofovir? By how much?

43. Activity 3: Testing the effectiveness of treatments Question 2: Plotting data and interpretation of results The scientists have collected data on different doses of Arbidol. 25 PFUs and 0 doses of Arbidol results in 25 plaques 25 PFUs and 5 doses of Arbidol results in 15 plaques Assuming that people who are exposed to 25 PFUs of virus have symptoms, plot a graph of doses of Arbidol versus number of plaques formed. How many doses of Arbidol should a person take to make sure that the virus is stopped?

44. Answers Activity 1: Dilution calculations Question 1: Activity 2: Calculating level of infectivity Question 1: 1.16 x 108 PFUs

45. Answers Activity 3: Testing the effectiveness of treatments Question 1: How many doses of anti-viral drug are required to prevent each plaque? Is it better or worse than Cidofovir? By how much? 11 doses of Moroxydine prevents 1 plaque 20 doses of Metisazone prevents 1 plaque 20 doses of Peramivir did not prevent any plaques 5 doses of Zanamivir prevents 1 plaque Question 2: Extrapolating from the graph 12.5 doses of Arbidol would be required to prevent the infection.

46. Glossary Assay - a procedure for measuring the biochemical or immunological activity of a sample. Agar – A gelatinous material derived from certain marine algae. It is used as a base for bacterial culture media that can be poured when heated up and which sets solid at body temperature. Bacteria – A very large group of single celled organisms that lack organelles or a nucleus, some of which can cause disease. Culture – A method of multiplying microorganisms by growing them in a liquid or gel under laboratory conditions so they can be studied. Dilution - The process of making weaker or less concentrated. DNA – Deoxyribonucleic acid. A self-replicating material made of a double-stranded nucleic acid  which is present in nearly all living organisms. It is the carrier of genetic information for cell growth, division, and function. Growth media - a liquid or gel designed to support the growth of microorganisms or cells. Pathogen – a broad term for a replicating agent such as an organism or infectious particle which causes disease in another organism, typically a virus or bacterium. Plaque – a visible region of dead cells formed within a cell culture, such as bacterial cultures within a growth media. PFU - Plaque forming unit. A measure of the number of particles capable of forming plaques per unit volume is a measure of viral concentration. The PFU of a solution is the concentration of viruses in a solution which are capable of lysing host cells and forming a plaque in a culture. RNA – The genetic material of many viruses, that code for the proteins and enzymes needed by the virus to replicate and survive. Symptomatic – Displaying symptoms. Virus – A small infectious agent made of nucleic acid and a protein coat that can only replicate inside cells.

47. You should be able to: • Write numbers in standard form • Choose appropriate results to draw conclusions • Present data in a line graph • Solve simultaneous equations using substitution