1. “The awkward fact with which US policy wrestles is that People flee the world’s Haitis for a combination of motives. All are deserving of some compassion but how much?” Newsweek, Dec. 4 1991 “Give me your tired, your poor, Your huddled masses yearning to breathe free, The wretched refuse of your teeming shore. Send these, the homeless, tempest-tossed, to me” Inscribed at base of Statue of Liberty, by Emma Lazarus

2. Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age 0-44 (World Health Organization) As you know in the developing world treatable infectious diseases remain big killers

3. Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age 0-44 (World Health Organization) Now it’s time to look at number 3: Malaria

4. Leading causes of death in Sub-Saharan Africa, South Asia, and Southeast Asia for persons age 0-44 (World Health Organization) That’s right: 300 million new cases per year making it the most prevalent serious infectious disease!

5. –2.1 billion people live in MALARIOUS areas

6. –Like HIV and TB, malaria is –unequally distributed, even in the tropics

7. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf –In areas of Africa with high transmission –there are 2700 deaths per day = 2 per minute

8. It’s especially hard on kids

9. 75% of the deaths are among African children

10. www.uhhg.org/mcrh/resources/video/malariappt.pdf

11. What Is malaria? u A mosquito-borne infectious disease caused by Protozoan parasites of the genus Plasmodium

12. What Is malaria? u Transmitted only by Anopheles Mosquitoes (>60 species!) (>60 species!) Seattle Biomedical Research Institute

13. What Is malaria? u The Disease can be Acute or Chronic

14. Acute Symptoms u u Classical features include cyclic symptoms – –Cold stage: chills and shaking – –Hot stage: fever, headache, vomiting, seizures in children – –Sweating stage: weakness – –Feel well for period of time, then cycle repeats itself www.uhhg.org/mcrh/resources/video/malariappt.pdf

15. In fact it is several different diseases

16. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

17. Each disease has a distinct course

18. “Tertian Malaria” (P.falciparum, P.ovale and P.vivax) fever occurs every third day. “Quartan Malaria” (P. malariae) fever occurs every fourth day. www.uhhg.org/mcrh/resources/video/malariappt.pdf

19. Each disease has a distinct course P.ovale and P.vivax can cause chronic malaria, reappearing after months or years due to latent parasites in liver www.uhhg.org/mcrh/resources/video/malariappt.pdf

20. Each disease also has a distinct geographical distribution www.uhhg.org/mcrh/resources/video/malariappt.pdf

21. Each disease also has a distinct geographical distribution www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

22. Each disease also has a distinct geographical distribution www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

24. Malaria damages the body in a number of ways u Red blood cell destruction -> anemia u Waves of parasites bursting red blood cells Lead to classic cycles of fever and chills

25. Malaria damages the body in a number of ways u Changes adhesive properties of infected Red blood cells -> blocking blood vessels leading to Tissue hypoxia Red blood cells -> blocking blood vessels leading to Tissue hypoxia

26. Malaria damages the body in a number of ways u If this happens in brain it is cerebral malaria which is often fatal which is often fatal Blocking blood vessels can also cause kidney failure

27. Malaria damages the body in a number of ways In severe cases 20% of patients can die, even with the best care

28. u Gold standard: Multiple thick and thin smears DIAGNOSIS

31. www.uhhg.org/mcrh/resources/video/malariappt.pdf u 1300 cases in US per year u Essentially all “imported” u Also transfusion related malaria Malaria is not currently a serious threat in the US

32. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf Although….

33. Malaria is not currently a serious threat in the US

34. However, this was not always the case

35. Not that long ago…. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

37. It could come back! www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

38. Let step back and look at the parasites that cause malaria

39. A French army doctor in Algeria observed parasites inside red blood cells of malaria patients and proposed for the first time that a protozoan caused disease A French army doctor in Algeria observed parasites inside red blood cells of malaria patients and proposed for the first time that a protozoan caused disease Algeriared blood cells Algeriared blood cells www.uhhg.org/mcrh/resources/video/malariappt.pdf It was discovered more than 100 years ago Charles Louis Alphonse Laveran Charles Louis Alphonse Laveran

40. French army doctor in Algeria observed parasites inside red blood cells of malaria patients and proposed for the first time that a protozoan caused disease French army doctor in Algeria observed parasites inside red blood cells of malaria patients and proposed for the first time that a protozoan caused disease Algeriared blood cells Algeriared blood cells www.uhhg.org/mcrh/resources/video/malariappt.pdf Charles Louis Alphonse Laveran Charles Louis Alphonse Laveran 1907 Nobel Prize for Physiology Nobel Prize for Physiology Nobel Prize for Physiology or Medicine or Medicine ! or Medicine ! or Medicine

41. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf So just who is this Plasmodium?

42. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf It’s not a bacterium or virus but a eukaryote like us

43. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf However, unlike us it lives a solitary life as a single cell

44. Let’s go back to the family tree

45. http://drnelson.utmem.edu/Woods.Hole/slide5.png Let’s go back to the family tree

46. http://drnelson.utmem.edu/Woods.Hole/slide5.png Let’s go back to the family tree You and me

47. http://drnelson.utmem.edu/Woods.Hole/slide5.png You and me mushrooms

48. http://drnelson.utmem.edu/Woods.Hole/slide5.png You and me mushrooms plants

49. http://drnelson.utmem.edu/Woods.Hole/slide5.png We are family…. You and me mushrooms plants Plasmodium

50. http://drnelson.utmem.edu/Woods.Hole/slide5.png They are on the same region of the eukaryote tree as plants You and me plants Plasmodium

51. Consistent with this, we now know Plasmodium and its relatives have a remnant of the chloroplast called the apicoplast which may help it digest heme and other things It harvests from red blood cells

52. Consistent with this, we now know Plasmodium and its relatives have a remnant of the chloroplast called the apicoplast which may help it digest heme and other things It harvests from red blood cells We don’t have this sort of organelle How might we use that fact??!

53. Plasmodium and its relatives also have a specialized Structure at one end of the cell Involved in invading other cells

54. www.columbia.edu/itc/hs/medical/pathophys/parasitology/2006/PAR-05Color.pdf

55. Plasmodium’s closer relatives Include parasites causing Babesiosis, Toxoplasmosis, And Cryptosporidiosis

56. Purves et al., Life: The Science of Biology, 4th Edition Plasmodium has a wildly complex life cycle 2 3 4 5 1 6

57. Purves et al., Life: The Science of Biology, 4th Edition And that’s just in the mosquito! 2 3 4 5 1 6

58. Purves et al., Life: The Science of Biology, 4th Edition 7 8 The wildly complex life cycle continued

59. Purves et al., Life: The Science of Biology, 4th Edition 9 Had enough yet??

60. Purves et al., Life: The Science of Biology, 4th Edition Now we get to the troublesome stage Cycles of replication inside red blood cells Lead to cycles of fever and chills And aggregated blood cells block blood vessels 10

61. Purves et al., Life: The Science of Biology, 4th Edition We also need to get back to the next mosquito to complete the cycle 11

62. Here’s Glaxo- SmithKline’s Cliff Notes version