Ma Cruzi
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Trypanosoma cruzi CHAGAS DISEASE
1520 million people are infected
T. cruzi :
Transmission Associated with poor living conditions
Armadillo reservoir
Fig. 1. Intracellular replication cycle of Trypanosoma cruzi in the vertebrate host. (a) A bloodstream trypomastigote (brown) approaches a host cell (yellow). (b) The trypomastigote becomes stably attached at the periphery of the host cell, and initiates a signaling process that results in elevation of the intracellular free Ca2+ concentration. Host cell lysosomes (dark pink) gradually migrate to the trypomastigote attachment site and fuse with the plasma membrane. As lysosomes fuse, the parasite moves into the cell and is internalized in a tight vacuole formed by lysosomal membranes. This lysosomederived vacuole is subsequently disrupted, releasing the parasite into the cytosol (see animated version at: http://archive.bmn.com/supp/part/andrews.html). (c) In the host cell cytosol, the parasites differentiate into amastigotes. (d) Amastigotes replicate by binary fission with an approximate doubling time of 12 h. (e) Amastigotes differentiate back into infective trypomastigotes, which are released into the bloodstream upon rupture of the host cell. (f) Bloodstream trypomastigotes circulate, infecting new cells or initiating the insect replicative cycle, when ingested by a reduviid vector. From Tan and Andrews (2002) Trends in Parasitology 8, 427.
American trypanosomiasis Etiologic agent (T. cruzi)
Metacyclic trypomastigotes and epimastigotes of T cruzi attached to the epithelium of the rectal gland of Triatoma dimidiata
Triatoma sp. Vinchuca Assassin bug
Clinical syndromes • Asymptomatic • Acute • Chronic
Asymptomatic There are no symptoms in this stage, which may last for many years. There are no trypomastigotes in the bloodstream, but antibody (IgG; immunoglobulin G) against T. cruzi is present.
Pathogenesis •
The ACUTE stage
•
The site of infection develops a localized inflammatory reaction "chagoma nodule". If the infection is on the eye, a unilateral edemea and conjunctivitis develops known as “ Chagoma/ Romana's sign". Trypanosomes appear in the blood in about 10 days. Systemic signs appear in 23 weeks after infection: High fevers Myalgia CNS may be affected
• • • • • •
Disease more severe in children < 5 years
Chagas’ disease: T. Cruzi in tissue
The chronic stage • Approximately 1030% percent of individuals progress from the asymptomatic stage to the chronic stage. There are very low levels of parasites in the blood. • The adverse effects of chronic Chagas disease include enlargement and aberrant function of the liver, spleen,heart, esophagus and large intestine.
Chagas’ disease: megacolon
Chagas’ disease: megacardium
Pathogenesis Autoimmune disease? B13=cardiac myosin Cruzipain=210kDa antigen from a skeletal muscle extract
Diagnosis • Blood Microscopy • Low sensitivity during the chronic stage • Xenodiagnosis (50% efficiency) • Serological detection • Elisa: Chagas kit • PCR
Example of antibody based molecular diagnosis Chagas’ Disease 1. FATALA kit : measures T. cruzi antibodies in blood using 2 recombinant proteins 2. BIO CHAGAS kit: uses cocktail recombinant T. cruzi antigens. Infection sera produces blue precipitate on strip in 60 minutes. (25 US dollars per kit).
Chagas' disease: prevention and treatment
•
•
Nifurtimox (Lampit, Bayer 205) (a derivative of nitrofufurlidine) decreases the duration and severity of the acute phase. But it is taken orally for long periods severe side effects pain, nausea, vomiting, neurologic symptoms. No effect on chronic phase. Benzimidazole can also suppress parasites in the acute phase. This drug is also taken orally for long periods and has many side effects.
Avoid and control the insect population No vaccine
1520 million people are infected
T. cruzi :
Transmission Associated with poor living conditions
Armadillo reservoir
Fig. 1. Intracellular replication cycle of Trypanosoma cruzi in the vertebrate host. (a) A bloodstream trypomastigote (brown) approaches a host cell (yellow). (b) The trypomastigote becomes stably attached at the periphery of the host cell, and initiates a signaling process that results in elevation of the intracellular free Ca2+ concentration. Host cell lysosomes (dark pink) gradually migrate to the trypomastigote attachment site and fuse with the plasma membrane. As lysosomes fuse, the parasite moves into the cell and is internalized in a tight vacuole formed by lysosomal membranes. This lysosomederived vacuole is subsequently disrupted, releasing the parasite into the cytosol (see animated version at: http://archive.bmn.com/supp/part/andrews.html). (c) In the host cell cytosol, the parasites differentiate into amastigotes. (d) Amastigotes replicate by binary fission with an approximate doubling time of 12 h. (e) Amastigotes differentiate back into infective trypomastigotes, which are released into the bloodstream upon rupture of the host cell. (f) Bloodstream trypomastigotes circulate, infecting new cells or initiating the insect replicative cycle, when ingested by a reduviid vector. From Tan and Andrews (2002) Trends in Parasitology 8, 427.
American trypanosomiasis Etiologic agent (T. cruzi)
Metacyclic trypomastigotes and epimastigotes of T cruzi attached to the epithelium of the rectal gland of Triatoma dimidiata
Triatoma sp. Vinchuca Assassin bug
Clinical syndromes • Asymptomatic • Acute • Chronic
Asymptomatic There are no symptoms in this stage, which may last for many years. There are no trypomastigotes in the bloodstream, but antibody (IgG; immunoglobulin G) against T. cruzi is present.
Pathogenesis •
The ACUTE stage
•
The site of infection develops a localized inflammatory reaction "chagoma nodule". If the infection is on the eye, a unilateral edemea and conjunctivitis develops known as “ Chagoma/ Romana's sign". Trypanosomes appear in the blood in about 10 days. Systemic signs appear in 23 weeks after infection: High fevers Myalgia CNS may be affected
• • • • • •
Disease more severe in children < 5 years
Chagas’ disease: T. Cruzi in tissue
The chronic stage • Approximately 1030% percent of individuals progress from the asymptomatic stage to the chronic stage. There are very low levels of parasites in the blood. • The adverse effects of chronic Chagas disease include enlargement and aberrant function of the liver, spleen,heart, esophagus and large intestine.
Chagas’ disease: megacolon
Chagas’ disease: megacardium
Pathogenesis Autoimmune disease? B13=cardiac myosin Cruzipain=210kDa antigen from a skeletal muscle extract
Diagnosis • Blood Microscopy • Low sensitivity during the chronic stage • Xenodiagnosis (50% efficiency) • Serological detection • Elisa: Chagas kit • PCR
Example of antibody based molecular diagnosis Chagas’ Disease 1. FATALA kit : measures T. cruzi antibodies in blood using 2 recombinant proteins 2. BIO CHAGAS kit: uses cocktail recombinant T. cruzi antigens. Infection sera produces blue precipitate on strip in 60 minutes. (25 US dollars per kit).
Chagas' disease: prevention and treatment
•
•
Nifurtimox (Lampit, Bayer 205) (a derivative of nitrofufurlidine) decreases the duration and severity of the acute phase. But it is taken orally for long periods severe side effects pain, nausea, vomiting, neurologic symptoms. No effect on chronic phase. Benzimidazole can also suppress parasites in the acute phase. This drug is also taken orally for long periods and has many side effects.
Avoid and control the insect population No vaccine
