Phylum Apicomplexa – Chapters 8 & 9

1. Phylum Apicomplexa – Chapters 8 & 9 Phylum Apicomplexa consists of 4 groups of protozoan parasites: 1. 2. 3. 4. We will examine the first 3 groups, as they contain many parasites of medical and veterinary importance. We will omit the gregarines as they are parasites of invertebrates and are not important.

2. Characteristics of the Phylum Apicomplexa 1. ______________________________________________________________ 2. Possess _______________________________________________________ - these organelles are concentrated at _______________________________ - function? ____________________________________ - see diagram in text p. 124 3. _______________________________________ 4. _______________________________________ - alternation of _____________________________ - hosts?

3. Plasmodium and Malaria – Chapter 9 Malaria is one of the most important diseases of mankind. It has played an important part in the rise and fall of nations and has killed untold millions of persons. Today, __________________________are infected with malaria 1.5 billion people (2/3 of the world's population) live in endemic areas and are potential hosts. Malaria kills _____________________ people each year.

4. Plasmodium and Malaria – Chapter 9 • In areas of Africa with high malaria transmission, an estimated ________________people die of malaria each year – over 2700 deaths per day or 1 death every 30 seconds. • Uganda – 12 million infections/population 31 million • Tanzania – 11 million infections/population 40 million • Ethiopia – 9 million infections/population 78 million

5. Species of Plasmodium • The genus Plasmodium contains 127 species in lizards, birds, and mammals. • life cycle worked out in a bird species (Plasmodium relictum) • rodent species (P. berghei) important in research (we will do an experimental infection of this parasite in lab) • several species in monkeys and apes are similar to human species - important in drug studies • four species infect humans – they are: • P. vivax, P. falciparum, P. malariae, P. ovale

6. Species of Plasmodium • VECTOR – ____________________________________________ • several species can serve as vectors • ___________________feed on blood and vector malaria • RESERVOIR HOSTS – __________________________________ • SURVIVAL OF MALARIA is dependent upon: • 1. Many infected humans • 2. Many Anopheles mosquitoes • 3. Good contact between these 2 hosts

7. Life Cycle of Plasmodium The life cycle is complex, so we will go through it step by step to understand it.

8. Life Cycle of Plasmodium – Human Cycle • An infected Anopheles mosquito bites a human and _______________________________ into the bloodstream • Within 30 minutes, the sporozoites enter_________________________ and begin the PRE-ERYTHROCYTIC INCUBATION (lasts for about a week). • Within the liver cell, the sporozoite becomes a trophozoite • divides by schizogony to form a multinucleate form called a ____________________________ • individual nuclei will form ____________________________

9. Life Cycle of Plasmodium – Human Cycle • 4. Liver cell ruptures to release the merozoites  • In 2 species of malaria, some of these merozoites will re-invade liver cells to begin a new cycle in the liver - called the EXO-ERYTHROCYTIC CYCLE. • Cryptozoites in these liver cells become dormant and are called _________________________________ • Merozoites may break out of hypnozoites years later and enter rbc's causing a _________________________________ • In all species, most or all of the merozoites leave the liver and enter the bloodstream

10. Life Cycle of Plasmodium – Human Cycle • In the ERYTHROCYTIC CYCLE, a merozoite penetrates a rbc and transforms into a uninucleate_______________________________ • Trophozoite undergoes schizogony and becomes a multinucleate ______________________________ • 7. Schizont ruptures rbc to release ______________________________ • - This coincides with the onset of a fever followed by a period of chills. •   - Length of time of fever/chill cycle varies by species • 8. Merozoites re-invade erythrocytes initiating a new erythrocytic cycle. This process is repeated over and over again resulting in the destruction of rbc's.

11. Life Cycle of Plasmodium – Human Cycle • 9. Not all the merozoites re-entering rbc's become trophozoites - some transform into gametocytes. • _____________________________are female • _____________________________are male. • 10. Rbc's containing gametocytes are infective to an Anopheles mosquito when she bites and takes another blood meal.

12. Life Cycle of Plasmodium – Mosquito Cycle • 11. In the mosquito stomach: • macrogametocyte undergoes meiosis to become a __________________________ • microgametocyte undergoes meiosis to form 6 - 8 elongate ___________________________ in a process called ___________________________ • The microgametes detach. Each swims to find a macrogamete, penetrates it, and syngamy occurs to form a ____________________ • 13. Zygote elongates to form an ___________________________which penetrates the stomach wall and comes to lie on the outside of the stomach.

13. Life Cycle of Plasmodium – Mosquito Cycle • 14. Ookinete rounds up to form the _________________________ • 15. Within the oocyst, sporogony (a type of asexual multiple fission) occurs, resulting in an enlarged oocyst containing thousands of __________________________ • 16. Oocyst bursts releasing the sporozoites into the body cavity. • Sporozoites migrate to the __________________________ • __________________________ and are injected into the human bloodstream with the next blood meal.

14. Life Cycle of Plasmodium – Review of Human Cyclefrom text page 150

15. Life Cycle of Plasmodium – Review of Mosquito Cyclefrom text page 150

16. Some Stages of Malaria in Anopheles Feeding female Anopheles Oocysts on outside of mosquito stomach Exflagellation showing microgametes Sporozoites from salivary gland

17. Some Stages of Malaria in the human Cryptozoite in liver cell – it will burst releasing merozoites Schizont – multinucleate form in rbc Trophozoite – uninucleate form in rbc Gametocyte – uninucleate form in rbc

18. Plasmodium vivax • Disease is ________________________________________________________ •  "tertian" indicates that the parasite undergoes a ____________ erythrocytic cycle in human rbc's (parasites invade rbc's every third day, hence tertian) • "benign" indicates that the species is ____________________________ • Has an exo-erythrocytic cycle resulting in ____________________________ occurring every 2-3 years up to 8 years. • Was once the most common and widely distributed species - occurred throughout tropical and temperate regions of the world. • once occurred in Wisconsin Habitat now -______________________________________________________ This species is responsible for ____________ of malaria in the world.

19. Plasmodium falciparum distribution (2005) Plasmodium vivax distribution (2005)

20. Plasmodium vivax – stages in human blood Ring-stage Trophozoite - ________________________________________________________________ - cannot distinquish from other species Mature Trophozoite - trophozoite ____________________ - ______________________________ due to ameboid movement of parasite - reddish ______________________ appear (diagnostic!)

21. Plasmodium vivax – stages in human blood • Schizont • ______________________________ • mature schizont forms ____ merozoites • Schuffner’s dots present • rbc enlarged • Gametocyte (we will not distinguish between macro- and microgametocytes) • ______________________________ • blue cytoplasm nearly fills rbc • Schuffner’s dots present • rbc enlarged

22. Plasmodium ovale • Disease is _____________________________________________________ • produces mild disease • 48 hour erythrocytic cycle • _______________________________________ - occurs in scattered areas of western Africa, India, and islands of the western Pacific (Philippines, New Guinea) • Nearly identical to P. vivax and is difficult to differentiate from this species from P. vivax • we will not distinguish between P. vivax and P. ovale in human blood smears examined in lab • Is responsible for ___________________ % of world malaria.

23. Plasmodium ovale – stages in human blood Ring-stage Trophozoite - nucleus and thin ring of cytoplasm - cannot distinquish from other species Mature Trophozoite - trophozoite ________________________ - reddish __________________________ appear (diagnostic!)

24. Plasmodium ovale – stages in human blood • Schizont • _____________________________ • mature schizont forms ____ merozoites • Schuffner’s dots present • rbc enlarged • Gametocyte • - single nucleus • blue cytoplasm fills _______________ • Schuffner’s dots present • rbc enlarged

25. Plasmodium malariae Causes _________________________________ - quartan indicates a ______________________ erythrocytic cycle Occurs throughout the tropics but has a discontinuous distribution Also occurs in chimpanzees but is not considered a zoonosis as wild chimps and humans do not live together in nature for disease transmission to occur between them Relapse? ______________________________________________________ A human can be infected for many years with no apparent symptoms, and the parasite can suddenly become pathogenic. This phenomenon is called __________________________________. Fatalities are not uncommon. Is responsible for ___________% of world's malaria.

26. Plasmodium malariae – stages in human blood Ring-stage Trophozoite - nucleus and thin ring of cytoplasm - cannot distinquish from other species Mature Trophozoite - trophozoite often forms a __________________ across the rbc (diagnostic!) - trophozoite does not enlarge rbc - no Schuffner’s dots

27. Plasmodium malariae – stages in human blood • Schizont • multinucleate • mature schizont forms ____ merozoites (diagnostic) • no Schuffner’s dots present • no enlargement of rbc • Gametocyte • single nucleus • blue cytoplasm nearly fills most of rbc • no Schuffner’s dots present • no rbc enlargement

28. Plasmodium falciparum • Disease is __________________________________________________________ • "tertian" indicates a 40-48 hr. cycle in rbc's • "malignant" indicates it is the most virulent of the 4 human species • P. falciparum is the greatest killer of humanity in the tropics. • it was responsible for the decline of the Greek civilization, the destruction of the Crusades, and caused more death in the Pacific in WWII than battles. • it is the most dangerous because more rbc's are infected and destroyed - death occurs commonly 8-10 months after infection. • Relapse? __________________________________________________________ • Occurs today throughout the tropics and is responsible for ___________ % of the world's malaria.

29. Plasmodium falciparum distribution (2005) Plasmodium vivax distribution (2005)

30. Plasmodium falciparum – stages in human blood • Ring-stage Trophozoite • single nucleus and thin ring of cytoplasm • _______________________ in a rbc common • Mature Trophozoites and Schizonts disappear from peripheral blood and are not seen • Gametocyte • single nucleus • __________________________ (diagnostic!) • can often see outline of rbc

31. History of Malaria • Disease has been known since antiquity - one of first reports described fevers in 1550 BC. • Malaria was commonly found in swampy areas and was thought to be contracted by breathing in "bad air" (= mal aria) in the swamps. • Much effort was directed towards finding a causative agent in the water or air of these swamps. • We now know that the mosquitoes that vector the disease lived in these swamps.

32. History of Malaria • First breakthrough - French physician _______________________ identified the parasites in the rbc's of malaria patients in 1880. • Laveran also witnessed an unusual step in the life cycle called exflagellation. • _____________________ (1885) differentiated some species of Plasmodium and noted changes in the parasites associated with the fever - chill cycle.

33. History of Malaria • Next breakthrough involved the mode of transmission. • In the 1890's a famous British scientist ___________________________________ theorized that mosquitoes may be involved in malaria transmission. • Manson had recently found that mosquitoes could vector filarial worms that caused elephantiasis • So why couldn't they also vector malaria?

34. History of Malaria • Manson convinced one of his students ________________________, a physician on leave from the Indian Medical Service, to test his hypothesis. • Ross went back to India and began dissecting mosquitoes. • After 2 years of dissecting mosquitoes, _____________ • ___________________________________________________ • In 1897 ___________________________________________ • __________________________________by feeding Anopheles mosquitoes on infected birds. • Before Ross could prove transmission to humans, he was transferred to work on kala azar. He was awarded a Nobel Prize in Medicine in 1902.

35. History of Malaria Two Italians ____________________________________(1898) experimentally transmitted malaria from mosquitoes to humans. It was not until 1948 that the complete life cycle was known when the pre-erythrocytic and exo-erythrocytic stageswere found in the liver of infected humans by ________________________________.

36. History of Malaria • Last name important in the history of malaria is that of ________________________________, a sanitation officer (ENPH!) in the Panama Canal Zone. • In 1906, he used the knowledge of mosquito transmission of malaria and yellow fever (a viral disease) to begin a _____________________________________________. • By 1913, the number of malaria cases had been greatly reduced and the building of the Panama Canal was undertaken.

37. Pathology of Malaria Infections During the pre-erythrocytic and exo-erythocytic cycles in the liver, there is no pathology and no symptoms. Why? ___________________________________________________ Pathology of all 4 species occurs during the erythrocytic cycle by the synchronousrupture of schizonts and release of merozoites which destroy erythrocytes.

38. Pathology of Malaria Infections • All 4 species show the following 3 pathological effects: • 1.____________________________________ - as the rbc's are invaded and destroyed, there is a _______________________ • _________________________________________________. • __________________________________________________ • - shown by a low hematocrit • ___________________________________ - liver and spleen are overwhelmed in the breakdown and recycling of these destroyed rbc's • results? ___________________________________________

39. Pathological Differences among the 4 speciesPlasmodium vivax and Plasmodium ovale In vivax and ovale malaria, merozoites primarily invade __________________________ These malarias rarely cause death but make a person quite ill during a malarial paroxysm.

40. Pathological Differences among the 4 speciesPlasmodium vivax and Plasmodium ovale Paroxysm lasts ________________ and represents the time from invasion of rbc’s by merozoites until new merozoites are produced (length of erythrocytic cycle)

41. Plasmodium vivax and Plasmodium ovale pathology • These malarias cause a long-term disease because they have the ability to ___________________________. • Relapse involves the ability of cryptozoites in the liver cells during the exo-erythrocytic cycle to become dormant for long periods. The dormant cryptozoites are called _________________________________. • Drug treatment or the immune system will effectively remove the erythrocytic forms, and the symptoms of malaria disappear - often for 2-3 years. • For some reason (we do not know why), the hypnozoites become active and release new merozoites to invade the rbc’s - the person has a malarial relapse.

42. Plasmodium vivax and Plasmodium ovale pathology Most individuals recover from these infections and the parasites are __________________________. Generally, the immune system totally eliminates the parasites after about 8 years.

43. Plasmodium malariae pathology In quartan malaria, merozoites of Plasmodium malariae primarily invade _________________________. There is no exo-erythrocytic cycle, so all the merozoites formed from cryptozoites invade rbc’s after the pre-erythrocytic incubation (no relapse). Malarial paroxysms occur every __________________ and represent the time from merozoite invasion of rbc’s to the formation of new merozoites (length of erythrocytic cycle).

44. Plasmodium malariae pathology • This parasite produces a phenonomen called a _____________________________________. • Numbers of infected rbc's can become very low that a person shows no signs of the disease. This period may last for years and the person believes he/she is free of the disease. • For some unknown reason, the parasites increase their numbers, invade many new rbc’s, destroy them, and cause severe anemia. • Longest lasting recrudescence was 53 years. • recent problem in __________________________________ • How dangerous?____________________________________

45. Plasmodium falciparum pathology Falciparum malaria is the most serious of the 4 species, usually resulting in a fatality. Remember that only the ring-stage trophozoites and gametocytes are found in peripheral blood – mature trophozoites and schizonts are in rbc’s of the spleen and bone marrow. There is _____________________________________, so all merozoites from the liver enter rbc’s - ______________________

46. Plasmodium falciparum pathology The erythrocytic cycle lasts from ______________ hours. Malarial paroxysm is unusual: ____________________________ _____________________________________________________

47. Plasmodium falciparum pathology • Falciparum malaria is the most pathogenic for the following reasons: • 1. Merozoites invades _______________________________ - thus, more rbc's are infected and destroyed. • More destroyed rbc’s leads to serious _____________________. • With more destroyed rbc’s to recycle, liver and spleen enlarge - _______________________________- and often fail. • Infected blood becomes viscous, often plugging capillaries in the brain causing ______________________________________

48. Plasmodium falciparum pathology • 5. Massive rbc destruction results in high levels of hemoglobin removed by the kidneys. Urine often becomes dark. Result? _________________________________________ • 6. ______________________________________ occurs when plasma fills the lungs • 7. ______________________________________occurs – failure of many organs leads to shock • A combination of any of these pathologies leads to death in 8-10 months.

49. Sickle Cell Anemia Presence of falciparum malaria has resulted in the maintenance of another disease which affects black persons in Africa. Cause:

50. Sickle Cell Anemia Persons who are ___________________________ have rbc’s that are sickle shaped, and die of other factors by age 30. They are hh. H - normal gene h - sickle cell gene