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MICR 420
Emerging and Re-EmergingInfectious Diseases
Lecture 8:Trypanosoma, PlasmodiumDr. Nancy McQueen & Dr. Edith Porter
Overview
Trypanosoma Plasmodium
Protozoa Morphology Growth Life cycles Vectors Pathogenesis Diseases Diagnosis Therapy Prevention Threats
Protozoa
Eukaryotic Always unicellular Chemoheterotrophs Digestion in
vacuoles Often life cycles
Some produce cysts Resistant survival
forms Vegetative form is a
trophozoite Reproduction
Asexual Sexual reproduction
?
Microbiology: An Evolving Science © 2009 W. W. Norton & Company, Inc.
Classification of Protozoa
Amoebozoa: motile, pseudopodia Ciliophora: motile, cilia Archaezoa: motile, flagella, no mitochondria Euglenozoa: flagella, disk shaped mitochondria Apicomplexa: non-motile, complex life cycles
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Trypanosoma
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Characteristics of Trypanosoma
Flagella Undulating
membrane
Kinetoplast Elongated mitochondrion with K-
DNA Thousands of mini-circles and a
few macro circles Involved in RNA editing Adjacent to flagellar basal body
Trypanosomiasis: Diseases
African Trypanosomiasis
Sleeping sickness Transmitted by tsetse
fly Large and aggressive fly Painful bites
American Trypanosomiasis
Chagas disease Transmitted by kissing
bug Triatomine insect
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Life Cycle of American Trypanosomiasis
Chagas Disease Endemic in Mexico, Central America, and South America
~ 8 to 11 million people are infected 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
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
Trypanosoma: Gene Conversion in the Variable Surface Glycoprotein and Antibody Response
Chagas Disease: Diagnosis Blood smear
Only during acute phase
Patient antibodies Two or more serological tests
Indirect fluorescence assay ELISA
Xenodiagnosis To detect low levels of parasitemia Laboratory-raised non-infected
vectors (triatomine or kissing bug) feed on patient
Triatomines are later dissected and examined for trypanosoma via microscopy or PCR
T. cruzi
Large kinetoplast
IFA
Chagas Disease: Therapy
Only acute, congenital, chronic in children and adults less than 50 years of age without cardiomyopathy
Not FDA approved and available only from CDC under investigational protocols Benznidazole Nifurtimox
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 Screening of blood products
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 and organ transplants
Plasmodium
Plasmodium: the Parasite
Apicomplexa Four species of Plasmodium can infect
humans P. falciparum
P. vivax P. ovale
P. malariae
Fatal malaria
Hypnozoites in liver cellsRelapse
The Vector of Plasmodium
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
Plasmodium: Life Cycle
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
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
Cerebral Malaria Erythrocyte aggregation in
small blood vessels and binding of infected erythrocytes to endothelium
Rosetting of uninfected erythrocytes around infected erythrocytes
Coagulation disorder Activation of endothelial
cells (EC) Increase in inflammatory
cytokines
Abnormal behavior Impairment of
consciousness Seizures Coma
Chen et al., 2000
Malaria: Diagnosis
Microscopy Ring Trophozoite Schizont Gametocyte
Molecular PCR
Patient antibodies
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)
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
Malaria: Distribution of the Disease
Malaria: Distribution of the Vector
Malaria Transmission in the US
Mosquito-Borne Malaria Southern States
"Airport" Malaria Congenital Malaria Transfusion-Transmitted Malaria
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
Threats by Plasmodium
Drug resistance in P. falciparum 11 cases of severe Plasmodium vivax
malaria in Bikaner (western India)
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).
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 Chen Q, Schlichtherle M, Wahlgren M. Molecular aspects of severe malaria. Clin
Microbiol Rev. 2000 Jul;13(3):439-50.
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