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MICR 454L

MICR 454L. Emerging and Re-Emerging Infectious Diseases Lecture 8: Plasmodium, Trypanosoma Dr. Nancy McQueen & Dr. Edith Porter. Plasmodium Trypanosoma. Protozoa Morphology Growth Life cycles Vectors Pathogenesis Diseases Diagnosis Therapy Prevention Threats. Overview.

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MICR 454L

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  1. MICR 454L Emerging and Re-Emerging Infectious Diseases Lecture 8: Plasmodium, Trypanosoma Dr. Nancy McQueen & Dr. Edith Porter

  2. Plasmodium Trypanosoma Protozoa Morphology Growth Life cycles Vectors Pathogenesis Diseases Diagnosis Therapy Prevention Threats Overview

  3. Classification of Protozoa • Archaezoa: motile, flagella, no mitochondria • Amoebozoa: motile, pseudopodia • Apicomplexa: non-motile, complex life cycles • Ciliophora: motile, cilia • Euglenozoa: flagella, disk shaped mitochondria

  4. Plasmodium

  5. Plasmodium: the Parasite • Four species of Plasmodium can infect humans • P. falciparum • P. vivax • P. ovale • P. malariae Fatal malaria Hypnozoites in liver cells Relapse

  6. The Vector of Plasmodium

  7. Plasmodium: Vector • Anopheles mosquitoes • ~ 3,500 species of mosquitoes grouped into 41 genera • 430 Anopheles species • only 30-40 transmit malaria (i.e., are "vectors") • Human malaria is transmitted only by females of the genus • Need blood for the development of eggs

  8. Oocyst Sporozoites Mosquito Salivary Gland Zygote Gametocytes Red Blood Cell Cycle Malaria Life Cycle Liver stage http://www.cdc.gov/malaria/ppt/Malaria_HIV_Rick_website.ppt#441,6,Slide 6

  9. Plasmodium: Life Cycle

  10. Fever Chills Malaria quartana 3-day cycle P. malariae Malaria tertiana 2-day cycle P. ovale/vivax (P. falciparum) Headache Flu-like symptoms Muscle aches Fatigue Anemia Jaundice Enlarged spleen Enlarged liver Malaria: Symptoms http://www.ratsteachmicro.com/Assets/Malaria/jaundice_splen.JPG

  11. Severe Malaria • Cerebral malaria • Severe anemia due to hemolysis • Hemoglobinuria (hemoglobin in the urine) due to hemolysis • Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS) • Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets) • Cardiovascular collapse and shock

  12. Cerebral Malaria • Erythrocyte aggregation in small blood vessels • Coagulation disorder • Activation of endothelial cells (EC) • Increase in inflammatory cytokines • Abnormal behavior • Impairment of consciousness • Seizures • Coma Carl Johan Treutigera, Carin Scholander et a., 1999

  13. Malaria: Diagnosis • Microscopy • Ring • Trophozoite • Schizont • Gametocyte • Molecular • PCR • Patient antibodies

  14. Malaria: Treatment • Is considered medical emergency • Must know species and area from where contracted • P. falciparum • Oral chloroquine if from non-resistant area • Quinine sulfate plus doxycycline, tetracycline, or clindamycin if from resistant area • P. malaria • Chloroquine • P. ovale/vivax • Chloroquine • Primaquine (hypnozoites)

  15. Malaria: Epidemiology • 350-500 million cases of malaria occur worldwide/year • > 1 million people die, most of them young children in sub-Saharan Africa/year • Pregnant women also more vulnerable

  16. Malaria: Distribution of the Disease

  17. Malaria: Distribution of the Vector

  18. Malaria: Prevention • Insecticide-treated bed nets • Repeat every 6 - 12 months • Window screens • Indoor residual spraying • Acts on mosquitoes resting after blood meal • DTT • Source reduction • Larval control • Destruction of breeding grounds

  19. Threats by Plasmodium • Drug resistance in P. falciparum • 11 cases of severe Plasmodium vivax malaria in Bikaner (western India)

  20. Trypanosoma

  21. Life Cycle of American Trypanosomiasis

  22. Trypanosoma: Pathogenesis • Antigenic variation • Surface variant-specific glycoprotein (VSG) • Each trypanosome has about 1000 genes encoding different VSGs • Only the gene in a specific expression site within the telomere at one end of the chromosome is active • Gene conversion • Mechanism for changing the VSG gene expressed • An inactive gene is copied and transposed into the telomeric expression site • Spontaneous switch • Survival advantage when antibodies are produced against the original VSG type

  23. Trypanosoma: Gene Conversion and Antibody Response

  24. African Trypanosomiasis Sleeping sickness Transmitted by tsetse fly Large and aggressive fly Painful bites American Trypanosomiasis Chagas disease Transmitted by kissing bug Triatomid insect Trypanosomiasis: Diseases

  25. Chagas Disease • Local lesion (chagoma, palpebral edema) at the site of inoculation • Acute phase (2 -3 months) • Usually asymptomatic • Fever, anorexia • Lymphadenopathy • Mild hepatosplenomegaly • Myocarditis • Asymptomatic chronic stage (years- decades) • Symptomatic chronic stage • Cardiomyopathy (the most serious manifestation) • Megaesophagus • Megacolon • Weight loss • Can be fatal

  26. Chagas Disease: Diagnosis Large kinetoplast • Blood smear • Patient antibodies • Indirect fluorescence assay • ELISA • Xenodiagnosis • To detect low levels of parasitemia • Laboratory-raised non-infected vectors (triatomids or kissing bug) feed on patient • Triatomids are later dissected and examined for trypanosoma via microscopy or PCR T. cruzi IFA

  27. Benznidazole Nifurtimox Chagas Disease: Therapy Must be individualized with expert advice

  28. Trypanosoma: Prevention • Vector reduction • Spray • Replacement of wood with metal • In Uruguay from 80% infected households to 0.1 % in 16 years • Safe work practice • Highly infectious

  29. Threats by Trypanosoma • Vector-borne infectious diseases are emerging or resurging • Changes in public health policy • Shift in emphasis from prevention to emergency response • Insecticide and drug resistance • Demographic and societal changes • Genetic changes in pathogens • Possibility of transmission by blood transfusion

  30. Take Home Message • Plasmodium and Trypanosoma have life cycles with major changes in their life form. • Plasmodium and Trypanosoma are transmitted through biological vectors. • Plasmodium infects erythrocytes and causes malaria with fever, anemia, jaundice, and for P. falciparum possibly cerebral malaria. • American trypanosomiasis is cause by T. cruzi leading to intracellular replication and subsequent inflammation of organs in particular the heart, esophagus and colon (chagas disease).

  31. Resources • The Microbial Challenge, by Krasner, ASM Press, Washington DC, 2002. • Brock Biology of Microorganisms, by Madigan and Martinko, Pearson Prentice Hall, Upper Saddle River, NJ, 11th ed, 2006. • Microbiology: An Introduction, by Tortora, Funke and Case; Pearson Prentice Hall; 9th ed, 2007. • http://www.cdc.gov/malaria/ • Francischetti IM et al (2006) Plasmodium falciparum-infected erythrocytes induce tissue factor expression in endothelial cells and support the assembly of multimolecular coagulation complexes. J Thromb Haemost. 2007 Jan;5(1):155-65. • http://www.cdc.gov/ncidod/dpd/parasites/cryptosporidiosis/default.htm • Raether W, Hanel H. (2003) Nitroheterocyclic drugs with broad spectrum activity. Parasitol Res. 2003 Jun;90 Supp 1:S19-39. • Dann SM, Wang HC, et al. (2005) Interleukin-15 activates human natural killer cells to clear the intestinal protozoan cryptosporidium. J Infect Dis. Oct 1;192(7):1294-302. • Elliott DA, Clark DP (2000) Cryptosporidium parvum induces host cell actin accumulation at the host-parasite interface. Infect Immun. Apr;68(4):2315-22. • http://www.dpd.cdc.gov/dpdx/HTML/TrypanosomiasisAmerican.htm

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