micr 454l emerging and re-emerging infectious diseases lecture 8: plasmodium, trypanosoma dr. nancy...
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MICR 454L
Emerging and Re-EmergingInfectious Diseases
Lecture 8:Plasmodium, Trypanosoma Dr. Nancy McQueen & Dr. Edith Porter
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Overview
Plasmodium Trypanosoma
Protozoa Morphology Growth Life cycles Vectors Pathogenesis Diseases Diagnosis Therapy Prevention Threats
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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
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Plasmodium
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Plasmodium: the Parasite
Four species of Plasmodium can infect humans P. falciparum
P. vivax P. ovale
P. malariae
Fatal malaria
Hypnozoites in liver cellsRelapse
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The Vector of Plasmodium
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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
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http://www.cdc.gov/malaria/ppt/Malaria_HIV_Rick_website.ppt#441,6,Slide 6
Liver stage
Sporozoites
Mosquito Salivary Gland
Malaria Life Cycle
Gametocytes
Oocyst
Red Blood Cell Cycle
Zygote
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Plasmodium: Life Cycle
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Malaria: Symptoms 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
http://www.ratsteachmicro.com/Assets/Malaria/jaundice_splen.JPG
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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
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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
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Malaria: Diagnosis
Microscopy Ring Trophozoite Schizont Gametocyte
Molecular PCR
Patient antibodies
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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)
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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
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Malaria: Distribution of the Disease
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Malaria: Distribution of the Vector
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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
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Threats by Plasmodium
Drug resistance in P. falciparum 11 cases of severe Plasmodium vivax
malaria in Bikaner (western India)
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Trypanosoma
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Life Cycle of American Trypanosomiasis
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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
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Trypanosoma: Gene Conversion and Antibody Response
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Trypanosomiasis: Diseases
African Trypanosomiasis
Sleeping sickness Transmitted by tsetse
fly Large and aggressive fly Painful bites
American Trypanosomiasis
Chagas disease Transmitted by kissing
bug Triatomid insect
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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
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Chagas Disease: Diagnosis 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
Large kinetoplast
IFA
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Chagas Disease: Therapy
Benznidazole Nifurtimox
Must be individualized with expert advice
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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
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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
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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).
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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; 9 th 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