1. ADITI PAI BIOLOGY DEPARTMENT SPELMAN COLLEGE APAI@SPELMAN.EDU Learning concepts in evolution with malaria as the case study

2. What is malaria? http://www.flickr.com/photos/ajc1/3420714787/

3. http://www.flickr.com/photos/atwj/3347071689/ http://www.flickr.com/photos/lamerie/407337286/

4. 10 facts on malaria WHO/S. Hollyman March 2009 About 3.3 billion people - half of the world's population - are at risk of malaria. Every year, this leads to about 250 million malaria cases and nearly one million deaths. People living in the poorest countries are the most vulnerable. Malaria is especially a serious problem in Africa, where one in every five (20%) childhood deaths is due to the effects of the disease. An African child has on average between 1.6 and 5.4 episodes of malaria fever each year. And every 30 seconds a child dies from malaria. This fact file presents the extent and effects of malaria and how it can be prevented and controlled. 10 facts on malaria http://www.who.int/features/factfiles/malaria/en/index.html

5. Facts about malaria Caused by a trypanosome: Plasmodium Transmitted by a vector: mosquito Prevalent in tropical and sub-tropical areas Symptoms: fever, chills, joint pain, vomitting etc.

7. Case study 1 A mutation story  http://www.pbs.org/

8. Objectives explain how mutations may be neutral, beneficial or harmful depending on the environment list conditions for natural selection to take place discuss how natural selection acts on individuals but evolution is seen at a population level predict whether the mutation will spread or not when given the nature of a mutation and the nature of the environment it is in

9. How is the gene that makes hemoglobin relevant to the effect of malaria on a patient? A. Hb is a part of mosquito and malaria affects mosquitoes B. Hb is a disease like malaria C. Hb is an essential part of the RBC and malaria affects RBC D. Hb is not relevant to the effect of malaria

10. What is the adaptive mutation described in the video?

11. Sickle Cell Anemia is codominant AA = normal AS = sickle cell trait (few symptoms) SS = sickle cell anemia http://www.flickr.com/photos/wellcomeimages/4013247943/

12. The effect of mutations are______ A. Beneficial B. Detrimental C. Neutral D. Dependent on the environment

13. http://www.mydochub.com/blog/index.php/2007/03/16/photo-project-sheds-light-on-sickle-cell-anemia/

14. What is the consequence if a person has only 1 copy of sickle cell allele and 1 normal copy of Hb allele? A. They could survive malaria B. They could grow up and marry C. They could have children D. All of the above

15. What if a person has two copies of sickle cell allele? A. They could survive malaria B. They could grow up and marry C. They could have children D. They had sickle cell anemia

16. What is the evolutionary process described in the video?

17. People in Africa have a high frequency of sickle cell mutation because A. They need it to survive malaria B. The allele increased in frequency in the population due to natural selection favoring those who had one copy of the allele C. Both of the above

18. Malaria has been a major selective agent for human populations in their evolutionary history!

19. Diseases such as malaria have a strong impact on evolution of organisms….

20. According to the video why is genetic diversity important? A. If a population is genetically identical, an epidemic could wipe out the entire population B. Having genetic diversity improves the chances that some are able to survive future epidemics C. Having genetic diversity guarantees that the population survives future epidemics D. A and C E. A and B

21. Case study 2 Who has sickle cell disease and why? Reading from Bloom 1995 Complete assignment in your group

22. Objectives list conditions for natural selection to take place discuss how natural selection acts on individuals but evolution is seen at a population level predict whether the mutation will spread or not when given the nature of a mutation and the nature of the environment it is in explain how evolution is not goal oriented propose explanations for why people in different parts of the world differ with respect to sickle cell frequency

23. Sickle cell is allele common in human populations Do you know some one with sickle disease?

24. Many famous people have it! http://www.flickr.com/photos/exquisitur/2553768995/ http://www.flickr.com/photos/darienlibrary/2893149535/

25. End of Part 1

26. What is common about the two people with sickle cell disease I just showed you?

27. Heterozygote advantage of the sickle-cell allele  Causes mutations in hemoglobin but also confers malaria resistance  Exemplifies the heterozygote advantage Comparison of the distribution of malaria (left) and sickle-cell trait (right). Original work by Anthony Allison http://commons.wikimedia.org/wiki/File:Malaria_versus_sickle-cell_trait_distributions.png

28. Sickle cell frequency is higher in Africa than America because the mutation never arose in America but it arose in Africa. A. True B. False

29. Sickle cell frequency is higher in Africa than America because the mutation was advantageous in Africa but disadvantageous in America. A. True B. False

30. Comparison of the distribution of malaria (left) and sickle-cell trait (right). Original work by Anthony Allison http://commons.wikimedia.org/wiki/File:Malaria_versus_sickle-cell_trait_distributions.png

31. Sickle cell frequency is higher in Africa than America because the mutation did NOT cause sickle cell disease in Africa but caused it in America A. True B. False

32. http://www.mydochub.com/blog/index.php/2007/03/16/photo-project-sheds-light-on-sickle-cell-anemia/

33. End of part 2

34. Case study 3 Malaria drug resistance warning Read BBC article from 2005 Do assignment with group  Main point?  Implication for malaria control?  Drawing natural selection.

35. Objectives explain how drug resistance arises in malaria parasites propose explanations for why different parts of the world where malaria is prevalent, differ with respect to malaria parasite drug resistance state the main point of an article in the context of the class

36. WHO calls for an immediate halt to provision of single-drug artemisinin malaria pills New malaria treatment guidelines issued by WHO 19 JANUARY 2006 | WASHINGTON, DC -- The World Health Organization (WHO) today requested pharmaceutical companies to end the marketing and sale of “ single-drug ” artemisinin malaria medicines, in order to prevent malaria parasites from developing resistance to this drug. The use of single-drug artemisinin treatment – or monotherapy – hastens development of resistance by weakening but not killing the parasite. When used correctly in combination with other anti-malarial drugs in Artemisinin Combination Therapies (ACTs), artemisinin is nearly 95% effective in curing malaria and the parasite is highly unlikely to become drug resistant. ACTs are currently the most effective medicine available to treat malaria. "It is critical that artemisinins be used correctly," said Dr LEE Jong- wook, WHO's Director-General. "We request pharmaceutical companies to immediately stop marketing single-drug artemisinin tablets and instead market artemisinin combination therapies only. The new treatment guidelines we are releasing today provide countries with clear and evidence-based direction on the best treatment options for malaria." According to the new WHO malaria treatment guidelines, uncomplicated falciparum malaria must be treated with ACTs and not by artemisinin alone or any other monotherapy. www.who.int

37. The main point of the article was that- A. Artemesinin is a very strong drug B. Malaria is a very bad disease C. Malaria parasites are evolving resistance to anti- malarial drugs D. None of the above

38. The implications for malaria control from this finding is that…. A. Malaria control will become harder if drug- resistant parasites emerge B. Scientists can easily control malaria with artemesinin C. None of the above

39. IN A SMALL COMMUNITY IN WESTERN CAMBODIA, SCIENTISTS ARE PUZZLING OVER WHY MALARIA PARASITES SEEM TO BE DEVELOPING A RESISTANCE TO DRUGS - AND FEARING THE CONSEQUENCES. TEN DAYS AGO, CHHEM BUNCHHIN, A TEACHER IN BATTAMBANG PROVINCE, BECAME ILL WITH CHILLS, FEVER, HEADACHE AND VOMITING. AT A NEARBY HEALTH CENTRE HE WAS TREATED WITH DRUGS CONSIDERED A "SILVER BULLET" IN THE BATTLE AGAINST FALCIPARUM MALARIA. THIS TREATMENT WITH ARTESUNATE DRUGS WAS PART OF A CLINICAL STUDY BEING CARRIED OUT BY THE US ARMED FORCES RESEARCH INSTITUTE OF MEDICAL SCIENCE (AFRIMS). IN THE PAST, ARTESUNATES HAVE ALWAYS CLEARED MALARIA PARASITES FROM THE BLOOD IN TWO OR THREE DAYS. BUT AFTER FOUR DAYS OF MONITORED TREATMENT, CHHEM BUNCHHIN WAS STILL TESTING POSITIVE FOR PARASITES. Drug resistance could set back malaria control success US$ 22.5 million grant from Gates Foundation to contain malaria parasites resistant to artemisinin 25 FEBRUARY 2009 | GENEVA -- WHO today said that the emergence of parasites resistant to artemisinin at the Thai-Cambodia border could seriously undermine the success of the global malaria control efforts. Surveillance systems and research studies supported by WHO to monitor antimalarial drug efficacy in countries are providing new evidence that parasites resistant to artemisinin have emerged along the border between Cambodia and Thailand. If local people, who walk for miles every day to clear forests, were infected with a drug-resistant form of malaria, it could set back recent successes to control the disease. Huge strides have been made in the past 10 years to reduce the burden of malaria, one of the world's major killer diseases. Strong malaria control programmes have helped to lower infection rates in several countries. The recent shift from failing drugs to the highly effective artemisinin-based combination therapies (ACTs) has been a breakthrough. Appropriate treatment with ACTs succeeds in more than 90% of cases. But malaria drug resistance now emerging along the Thai-Cambodia border threatens these gains. www.who.int

40. End of Part 3

41. Case study 4 WHO report. It shows whether or not malaria parasite in different regions of the world are resistant to certain drugs that are used to treat malaria. Study the table carefully and answer questions in the assignment.

42. Objectives propose explanations for why different parts of the world where malaria is prevalent, differ with respect to malaria parasite drug resistance predict what would happen if infected people or mosquitoes moved from populations with drug resistant malaria, to populations without drug resistant parasites propose solutions to controlling malaria using evolutionary thinking state the main point of a table and a figure give two examples of how evolutionary thinking is relevant to human health and disease management

43. Drug resistance could set back malaria control success US$ 22.5 million grant from Gates Foundation to contain malaria parasites resistant to artemisinin 25 FEBRUARY 2009 | GENEVA -- WHO today said that the emergence of parasites resistant to artemisinin at the Thai-Cambodia border could seriously undermine the success of the global malaria control efforts. Surveillance systems and research studies supported by WHO to monitor antimalarial drug efficacy in countries are providing new evidence that parasites resistant to artemisinin have emerged along the border between Cambodia and Thailand. If local people, who walk for miles every day to clear forests, were infected with a drug-resistant form of malaria, it could set back recent successes to control the disease. Huge strides have been made in the past 10 years to reduce the burden of malaria, one of the world's major killer diseases. Strong malaria control programmes have helped to lower infection rates in several countries. The recent shift from failing drugs to the highly effective artemisinin-based combination therapies (ACTs) has been a breakthrough. Appropriate treatment with ACTs succeeds in more than 90% of cases. But malaria drug resistance now emerging along the Thai-Cambodia border threatens these gains. www.who.int

44. TABLE 3. DISTRIBUTION OF DRUG-RESISTANT PLASMODIUM FALCIPARUM MALARIA Region Resistance reported Comments CQ SP MQ Others Central AmericaN N N North-west of Panama Canal only Caribbean N N N South America Y Y Y QN MQ and QN infrequently Western Africa Y Y Y Incidence of resistance to CQ variable, but very common in most areas Eastern Africa Y Y N Incidence o f resistance to SP highly variable, with some reports of focally high incidence, but generally uncommon Southern Africa Y Y N Resistance to SP, although reported, is considered to be generally uncommon Indian Subcontinent Y N N South-East Asia and Oceania Y Y Y HAL, QN Border areas of Thailand, Cambodia, and Myanmar highest risk for multiple-drug- resistant infections; in other areas, incidence of resistance to SP and MQ highly variable and absent in many areas East Asia (China) Y Y ? Resistance greatest problem in southern China CQ = chloroquine QN = quinine SP = sulfadoxine-pyrimethamine HAL = halofantrine MQ = mefloquine Bloland 2001, www.who.int

45. www.who.int

46. Discuss in your group How does this relate to: Natural selection? Gene flow? Mutation?

47. If infected mosquitoes from areas with resistant malaria parasite flew to areas with populations of susceptible malaria parasite, this would be an example of A. Gene flow B. Genetic drift C. Mutation D. All of the above

48. If malaria parasites in an area exposed to a certain malaria drug suddenly show some individuals with resistance to the malaria drug where none existed before, this might be an example of A. Genetic drift B. Mutation C. None of the above

49. Based on what you have learned about malaria.. How is evolutionary thinking relevant to understanding and treating human disease?

50. End of part 4