Successfully reported this slideshow.
We use your LinkedIn profile and activity data to personalize ads and to show you more relevant ads. You can change your ad preferences anytime.

04.29.09: Parasitology


Published on

Slideshow is from the University of Michigan Medical
School's M1 Infectious Disease / Microbiology sequence

View additional course materials on Open.Michigan:

  • Be the first to comment

04.29.09: Parasitology

  1. 1. Author(s): Vernon Carruthers, Ph.D., Cary Engleberg, M.D., D.T.M.&H., 2009License: Unless otherwise noted, this material is made available under the terms of theCreative Commons Attribution 3.0 License: have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use, share, and adapt it.The citation key on the following slide provides information about how you may share and adapt this material.Copyright holders of content included in this material should contact with any questions, corrections, orclarification regarding the use of content.For more information about how to cite these materials visit medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medicalevaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to your physician if you have questions about yourmedical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  2. 2. Citation Key for more information see: + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC § 105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. PARASITOLOGY M1 Infectious Diseases Sequence Vernon Carruthers Cary EnglebergSpring 2009
  4. 4. What do you need to learn for this course?• Recognize the names of pathogens associated with characteristic diseases (Don t memorize names or spellings)• Remember the key features of the life cycles (i.e., how do the parasite get from one host to the next?)• Remember the main mechanisms of disease (i.e., how does damage to the host occur?) 3
  5. 5. Definitions•  zoonosis•  enzootic ~ endemic•  epizootic ~ epidemic•  reservoir•  vector 4
  6. 6. Major Human ParasitesProtozoan (single-celled) parasitesLow branching protozoa (Entamoeba)Kinetoplastids (African trypanosomes, Leishmania)Apicomplexa (Plasmodium, Toxoplasma)Fungus-like protozoa (Microsporidia)Metazoan (multicellular) parasitesNematode (Onchocerca or hookworm)Trematode (Schistosoma)Cestode (Tapeworm e.g., Echinococcus) 5
  7. 7. MicrosporidiaParasites on the Tree of Life Apicomplexan Metazoans Entamoeba* Kinetoplastids Giardia *low-branching eukaryote Sandy Baldauf / Boris Striepen 6
  8. 8. Parasite Diversity 100m 10m 1m 10cm 1cm 1mm 100mm 10mm 1mm N NMicrosporidia Apicomplexa Kinetoplastid Trematode Cestode Nematode Protozoa Metazoa 7 Vernon Carruthers
  9. 9. Global Morbidity and Mortality from Parasitic Diseases * * * 1700 *Annual West Nile Virus <0.5 <0.01 <0.3 8Source Undetermined
  10. 10. New Trends in Emerging Infectious Diseases 9Jones et. al., Nature Feb 2008
  11. 11. Factors influencing the geography of parasitic infections •  Local ecology – vectors – reservoirs (animal and human) – local habitats •  Local socioeconomic conditions – sanitation – exposure to vectors – untreated carriers 10
  12. 12. ProtozoalInfections 11
  13. 13. Classification of protozoa Entamoebae (shapeless) Source Undetermined FlagellatesAlveolates Source Undetermined(sub-membranecytoskeleton confers Apicomplexaa fixed shape) (Sporozoa) Source Undetermined (Ciliates) 12
  14. 14. Outline of protozoal diseases Intestinal protozoal infection Systemic protozoal infection 13
  15. 15. Outline of protozoal diseases Intestinal protozoal infection -Invasive (dysentery/bloodstream invasion)entamoeba * Entamoeba histolytica -Non-invasive (watery diarrhea/weight loss)dinoflagellate * Giardia lamblia (G. intestinalis)apicomplexa * Cryptosporidia and Cyclospora * microsporidia Systemic protozoal infection 14
  16. 16. Amebiasis•  Entamoeba - an enteric amoeba, i.e., not free-living.•  histolytica - human invasion by the parasite involves tissue lysis (histo-lytica) 15
  17. 17. E. histolytica - parasitic formsCary Engleberg 16
  18. 18. Trophozoites in Ulcerwith Ingested Red BloodCells William Petri 17
  19. 19. Entamoeba histolytica -- life cycle•  Humans are the only reservoir excreting amoebic cysts•  Cysts resist environmental conditions•  Fecal-oral transmission (food, water)•  In response to gastric acid, ingested cysts release trophozoites in the upper intestine•  Trophozoites invade the large intestine and replicate by fission.•  Trophozoites that reach the lower colon encyst again. 18
  20. 20. Source Undetermined Source UndeterminedTrophozoite in stool Cyst in stool 19
  21. 21. Entamoeba histolytica -- pathogenesis •  Trophozoites disrupt mucus layer •  Key virulence factors: – amebic lectin: binds parasite to galactose- containing sugars on host cells – amoebapores: adherence-dependent cytolysis – cysteine protease: cleaves preIL-1β to IL-1β which triggers NF-kB and pro-inflammatory cytokines; also cleaves antibodies and C3 •  Trophozoites ingest human cells •  Colonic ulceration 20
  22. 22. Risk Factors for Amebiasis in the United States•  Hispanic/Asian/Pacific Islanders - 50% of U.S. cases reported to CDC•  Travelers - 0.3% incidence in one study•  Institutions for mentally retarded•  Men who have sex with men•  Men - 90% amebic liver abscesses in men (male mice also more susceptible, in part because of lower IFNγ and fewer functional NKT cells) 21
  23. 23. Carbohydrate side-chains terminating in gal - galNAc ( ) 22Cary Engleberg
  24. 24. 1. Adherence Ameba Intestinal Lumen 2. Lectin Signal4. Phagocytosisand Invasion 3. Cell killing 23 William Petri
  25. 25. TUNEL Stain Demonstrates Apoptosis atSites of Amebic Invasion of Mouse Colon William Petri 24
  26. 26. Histopathology of amebiasis Tissue Destruction in Amebic Colonic Ulcer William Petri Classic Flask-Shaped Ulcers (side view) 25
  27. 27. Source Undetermined 26
  28. 28. Source Undetermined 27
  29. 29. Amebiasis - clinical syndromes•  Intestinal – Ranges from asymptomatic to chronic diarrhea to amebic dysentery•  Extraintestinal – amebic liver abscess – other metastatic foci (e.g., brain) Dx: identification of trophozoites or cysts in the stool, stool antigen tests, serology 28
  30. 30. Two microscopicallyindistinguishable Entamoeba sp. •  E. histolytica – invades tissues – should always be treated, even in asx patients •  E. dispar – is non-pathogenic, even in AIDS – should not be treated 29
  31. 31. Treatment of amebiasis•  The parasites in two locations are treated sequentially with two drugs – For invasive forms: metronidazole – For luminal forms: diiodohydroxyquin, paromomycin, diloxanide furoate•  Do not treat asymptomatic intestinal E. dispar infection 30
  32. 32. Giardiasis 31
  33. 33. Giardiasis - life cycle Trophozoite Cyst Giardia•  G. lamblia is a zoonosis (infected small mammals pass cysts and contaminate surface waters)•  Waterborne transmission is most common, but can also be spread person-to-person by young children (e.g., day-care centers)•  Ingested as cysts•  Excystation of the trophozoite and attachment to the mucosa occurs in the upper small intestine. 32 Vernon Carruthers
  34. 34. Source Undetermined Source UndeterminedTrophozoites in duodenum Cyst in stool 33
  35. 35. Giardia pathogenesis•  Parasites elicits localized hypersensitivity•  Intestinal villi become blunted•  Malabsorption develops 34
  36. 36. Dorsal Suction DiscVentral Source Undetermined 35
  37. 37. Giardia - clinical features•  Acute, self-limited diarrhea•  Chronic diarrhea with malabsorption, steatorrhea, and weight loss•  Chronic asymptomatic cyst passage Dx: stool antigen testing, stool examination, duodenal aspirate. 36
  38. 38. Giardiasis - treatment•  Metronidazole (or nitazoxanide) Giardiasis - prevention•  Filtration of water•  Heating water to >50oC•  2% iodine x 30 minutes 37
  39. 39. Generalizations about other intestinal protozoa(Cryptosporidium, Cyclospora, Microsporidia)•  All acquired by fecal-oral route•  All grow abundantly inside of mucosal cells•  All cause watery diarrhea, cramps, anorexia (not inflammatory) - pathogenesis uncertain•  All require special stains or examinations of stool for dx. 38
  40. 40. Cryptosporidium in tissueOrganisms attached Intestinal organismsto an intestinal villus by scanning EM Source Undetermined Source Undetermined 39
  41. 41. Cryptosporidium parvum•  Associated with- – prolonged self-limited diarrhea in immunocompetent individuals – traveler s diarrhea – chronic, unrelenting diarrhea in AIDS•  Usual acquired from – drinking water (e.g., Milwaukee, 1993) – swimming pools•  Relative chlorine resistance 40
  42. 42. Number of cryptosporidiosis cases, bydate of onset, Delaware Co., Ohio, Jun–Sep 2000 Center for Disease Control and Prevention •  Relative risk of swimming at a private swim club = 42.3 (12.3–144.9) •  At least 5 fecal accidents witnessed 41
  43. 43. Cryptosporidium Source Undetermined Source UndeterminedIodine stain of stool Acid-fast stain of stool 42
  44. 44. Treatment of cryptosporidiosis•  Supportive (rehydration, antimotility agents)•  No FDA-approved rx•  Nitazoxanide? 43
  45. 45. CyclosporaSource Undetermined 44
  46. 46. Cyclospora•  Food and waterborne transmission – 1996-97 outbreaks associated with Guatemalan raspberries shipped to U.S.•  Also replicates within mucosal cells•  Diarrhea may persist for 1-2 months without treatment•  Trimethoprim/sulfa x 7 days is effective therapy (unlike Cryptosporidium) 45
  47. 47. Microsporidia•  Primitive fungi that were initially thought to be protozoa•  Long recognized as animal pathogens – human cases in AIDS – recent human cases also seen in immunocompetent persons•  Hundreds of species identified 46
  48. 48. Louis Weiss Ex, exospore Louis Weiss En, endospore AD, achoring disc PT, polar tube 47 Sp, sporoplasm
  49. 49. Explosive Discharge of the Invasion Tube •  4-30 coils depending on spp •  Stimulus varies depending on spp, can be pH shift, dehydratioin/rehydration, mucin, UV, etc •  Stimulus increases osmotic pressure, water influx 48
  50. 50. Outline of protozoal diseases Intestinal protozoal infection Systemic protozoal infection 50
  51. 51. Outline of protozoal diseases Intestinal protozoal infection Systemic protozoal infection - Malaria (Plasmodium sp.) (RBC infection and fever) apicomplexa - Babesiosis (Babesia sp.) - Toxoplasmosis (T. gondii) (Intracellular - Leishmaniasis infections)dinoflagellates - Others: African trypanosomiasis (sleeping sickness) American trypanosomiasis (Chagas disease) 51
  52. 52. Toxoplasmosis 52
  53. 53. Toxoplasma Features•  Apicomplexan parasite (similar to Cryptosporidium, Cyclospora and Plasmodium) 53
  54. 54. Gliding Motility of Apicomplexa Cary Engleberg DanielCD, wikimedia commons 54
  55. 55. Entry of Apicomplexa into cells Cary Engleberg 55
  56. 56. •  Cats infected bypredation•  107 oocysts passedin feces•  Stable in soil/waterfor months•  Either indirect thruintermediatehost or direct viafood/water Ingests•  Vertical Contamination of food/water cysts in raw ortransmission during undercooked meatpregnancy Center for Disease Control and Prevention 56
  57. 57. McGill University Department of Medicine 57
  58. 58. Toxoplasmosis - clinical syndromes•  acute acquired toxoplasmosis•  congenital toxoplasmosis•  ocular toxoplasmosis•  cerebral toxoplasmosis (AIDS) 58
  59. 59. congenital toxoplasmosis•  30-40% transplacental if mother is infected during pregnancy•  60% of infected newborns are asymptomatic (but later show chorioretinitis)•  affected infants may have hydrocephalus, hepatosplenomegaly, jaundice, fever, anemia, pneumonia 59
  60. 60. Source Undetermined 60
  61. 61. Source Undetermined 61
  62. 62. Source Undetermined Source Undetermined 62
  63. 63. Source Undetermined 63
  64. 64. Diagnosis of toxoplasmosis•  direct identification is difficult•  culture is not routinely done•  serology – IFA or ELISA – single high IgM or very high IgG level – seroconversion not reliable in AIDS•  clinical features and response to rx 64
  65. 65. Treatment of toxoplasmosisWhen RX is indicated . . . sulfadiazine + pyrimethamine* OR clindamycin + pyrimethamine* * plus folinic acid 65
  66. 66. Malaria 66
  67. 67. Source Undetermined 67
  68. 68. Center for Disease Control and Prevention 68
  69. 69. Asexual replication Exoerythrocytic "ring" cycle form trophozoite Sporozoitesreleased frommosquito salivaryglands invade merozoiteshepatocytes released Erythrocyticw ithin 30 mins. cycle schizont Male and f emale ruptured g ametocytes RBC releases merozoites Sexual replication • Fertilization and invasion of mosquito gut • Infected cell releases sporozoites, which migrate to the salivary glands. 69 Cary Engleberg
  70. 70. Asexual stages Exoerythrocytic cycle Erythrocytic cycle 6-15 days 2-3 days 70Cary Engleberg
  71. 71. Sporozoites and hepatic schizont McGill University Department of MedicineMcGill University Department of Medicine 71
  72. 72. Center for Disease Control and Prevention 72
  73. 73. Center for Disease Control and Prevention 73
  74. 74. Center for Disease Control and Prevention 74
  75. 75. Plasmodium species ERYTHROCYTIC HEPATICSPECIES CYCLE LATENCY RECURRENCESP. falciparum 48 hrs no noP. vivax 48 hrs yes yesP. ovale 48 hrs yes yesP. malariae 72 hrs no yes 75
  76. 76. Imported malaria cases, by species andinterval between date of arrival and onset of illness — U.S., 1992 180 140 No. 100 of cases 60 20 P. vivax <1 P. malariae 1-2 P. ovale 3-5 6-12 P. falciparum Months >12 76Vernon Carruthers
  77. 77. Imported malaria cases, by year, 1973-2000, U,S.200018001600 ~ 1/2 are imported1400 from1200 Africa1000 800 600 400 U.S. civilians 200 Total 0 Year Source Undetermined 77
  78. 78. Stable and unstable malaria transmission stable unstable continuous epidemic transmission malariaClinical disease children all agesMortality children all agesEnl. Spleen rate (2-9 yrs) >10% <10%Immunity among adults high lowParasitism rate high low 78
  79. 79. Malaria - clinical features•  paroxysms associated with synchronous release of merozoites from RBCs – Infected RBCs release substances that stimulate the release of TNFα and IL-1 from host cells – rigorous chills, fever, myalgia, severe headache ± GI symptoms (5-6 hours) – profuse sweating and exhaustion (2-3 hours) 79
  80. 80. Malaria - clinical features•  immunologically-mediated hematologic changes – anemia – thrombocytopenia – leukopenia 80
  81. 81. Enhanced virulence of P. falciparum•  merozoites can enter RBCs of any age•  parasitemias reach very high levels•  adhesin proteins deployed on infected RBCs (trophozoites and schizonts) – attachment to venular endothelial cells (e.g., via ICAM-1) – reduced blood flow in small vessels --> microinfarction, hemorrhage 81
  82. 82. Adherent P. falciparum schizonts KNOBJ.D. Maclean, McGill Univ. J.D. Maclean, McGill Univ. Schizonts adhering to retinal blood vessels 82
  83. 83. Source Undetermined 83
  84. 84. Source Undetermined 84
  85. 85. Antimalarial treatment•  based on species and location acquired – chloroquine-sensitive species rx: chloroquine (blocks heme iron detoxification) – Chloroquine ® P. falciparum Rx (quinine + doxycycline) or Malarone®•  Add primaquine for P. vivax and P. ovale 85
  86. 86. Hemezoin Formation: Eatingthe Host From the Inside Out•  Hemeglobin 300 mg/ml inside RBC!•  Parasite digests hemeglobin fornutrients and to create room for growth Source Undetermined Source Undetermined•  Problem: Free heme is extremelytoxic because generates oxygenradicals•  Solution: sequester in hemezoincrystals! Tulane University Madame Curie Bioscience Database•  Most malaria drugs interfere withhemezoin formation 86
  87. 87. Sequence of the creation ofhemozoin in red cell removed 87
  88. 88. Based on what you have just learned, suggest three simple strategies to prevent the propagation of malaria. 1) _________________ 2) _________________ 3) _________________ 88
  89. 89. Strategies to prevent malaria1) mosquito control (insecticides, remove habitats)2) mosquito protection (nets, screens, repellants)3) mass treatment•  vaccines (immunity is species and stage-specific)•  release of genetically altered mosquitoes 89
  90. 90. Leishmaniasis 90
  91. 91. Center for Disease Control and Prevention 91
  92. 92. Source Undetermined 92
  93. 93. Source UndeterminedLeishmania are intracellular parasites that reside in macrophage phagolysosomes 93
  94. 94. Source Undetermined Chronic skin ulcerations with raised edges at site of sand fly bite.(organisms do not survive well at 37oC, therefore, they don t tend to disseminate) 94
  95. 95. Source Undetermined 95
  96. 96. Source Undetermined 96
  97. 97. Cary Engleberg Cary Engleberg L. braziliensis lasts longer and may recur later with destructive lesions in the nose and throat 97
  98. 98. McGill University Department of Medicine 98
  99. 99. J.D. Maclean, McGill Univ. 99
  100. 100. Visceral leishmaniasis - Kala-azar•  Infection of macrophages in the liver, spleen and lymph nodes•  Fever, malaise, weight loss, abdominal pain•  Dx: aspirate of bone marrow, spleen or liver; serology•  Outcome: 75-90% fatal if untreated (death 2o to bacterial pneumonia) 100
  101. 101. Contributed from H. Zaiman ©1996 101
  102. 102. Additional Source Information for more information see: 7: Sandy Baldauf / Boris StriepenSlide 8: Vernon CarruthersSlide 9: Source UndeterminedSlide 10: Jones et. al., Nature Feb 2008Slide 13: Source UndeterminedSlide 17: Cary EnglebergSlide 18: William PetriSlide 20: Source UndeterminedSlide 23: Cary EnglebergSlide 24: William PetriSlide 25: William PetriSlide 26: William PetriSlide 27: Source UndeterminedSlide 28: Source UndeterminedSlide 33: Vernon CarruthersSlide 34: Sources UndeterminedSlide 36: Source UndeterminedSlide 40: Sources UndeterminedSlide 42: Center for Disease Control and Prevention, MMWR 2000; 50:406, 43: Sources UndeterminedSlide 45: Source UndeterminedSlide 48: Louis WeissSlide 54: Cary Engleberg; DanielCD, Wikimedia Commons,, CC:BY-SA, 55: Cary EnglebergSlide 56: Center for Disease Control and Prevention, Alexander J. da Silva, PhD / Melanie Moser, CDC PHIL #3421, http://www.cdc.govSlide 57: McGill University Department of Medicine, 60: Source UndeterminedSlide 61: Source UndeterminedSlide 62: Sources UndeterminedSlide 63: Source UndeterminedSlide 67: Source UndeterminedSlide 68: Center for Disease Control and Prevention, James Gathany, CDC PHIL #7950 http://www.cdc.govSlide 69: Vernon CarruthersSlide 70: Vernon CarruthersSlide 71: McGill University Department of Medicine, (Both Images)Slide 72: Center for Disease Control and Prevention
  103. 103. Slide 73: Center for Disease Control and PreventionSlide 74: Center for Disease Control and Prevention/ Steven Glenn, CDC PHIL #5941Slide 76: Source UndeterminedSlide 77: Source UndeterminedSlide 82: J.D. Maclean, McGill University (Both Images)Slide 83: Source UndeterminedSlide 84: Source UndeterminedSlide 86: Source Undetermined; Undetermined; Tulane University, ; Madame Curie Bioscience Database, 87: Source UndeterminedSlide 91: Center for Disease Control and Prevention, Frank Collins, James Gathany, CDC PHIL #10275, http://www.cdc.govSlide 92: Source UndeterminedSlide 93: Source UndeterminedSlide 94: Source UndeterminedSlide 95: Source UndeterminedSlide 96: Source UndeterminedSlide 97: Cary EnglebergSlide 98: McGill University Department of Medicine, 99: J.D. Maclean, McGill UniversitySlide 101: Contributed from H. Zaiman ©1996