Trypanosomiasis
Species
Trypanosoma cruzi
Overview of Life Cycle
- Trypomastigotes are deposited in the feces of an infected triatome insect (reduviid/”kissing bug”) near the feeding site; trypomastigotes then enter the vertebrate host through the bite wound or penetrate intact mucous membranes.
- Additional routes of transmission are discussed below.
- Trypomastigotes either remain in circulation to disseminate throughout the body or enter a host cell, most commonly macrophages or myocardiocytes.
- Within the host cell, trypomastigotes transform into the asexually reproducing stage, amastigotes.
- Asexual reproduction of amastigotes by binary fission occurs rapidly.
- Once the host cell is full, amastigotes transform back into trypomastigotes before rupturing the host cell and re-entering circulation.
- The new trypomastigotes then either enter another host cell or remain in circulation.
- Triatome insects acquire infection through ingestion of blood containing circulating trypomastigotes.
- Trypomastigotes convert to epimastigotes within the insect, replicate by binary fission, and then convert back into trypomastigotes prior to exiting in the feces of the vector.
Example of a kissing bug, a triatome that can vector Trypanosoma cruzi
Trypomastigotes of Trypanosoma cruzi in a canine blood smear
Stages
Epimastigote (present in triatome insect vector; replicates asexually)
Trypomastigote (infective stage; in feces of triatome orblood of vertebrate)
Amastigote (present in vertebrate host; replicates asexually)
Disease
- Disease due to infection with T. cruzi is termed Chagas disease.
- More severe disease often develops in animals less than 6 months of age; prognosis is worse in animals diagnosed at a younger age.
- Acute disease occurs within the first 30 days.
- Parasitemia appears around 3 days post-infection, peaks around 2-3 weeks after infection, and wanes by the end of the first month.
- Clinical signs may include generalized lymphadenopathy, lethargy, organomegaly (spleen and liver), pallor, and acute myocarditis.
- Lab abnormalities may include elevated troponin I, AST, ALT, creatinine, BUN.
- An evaluation of the heart via electrocardiogram (ECG) may reveal a number of conduction abnormalities.
- Sudden death, usually attributable to the cardiac malfunction, can be seen during this phase.
- From 1 to as long as 8 months after infection, parasitemia, clinical signs, and ECG abnormalities are usually absent.
- After 8 months post-infection, chronic infection and disease usually establish.
- Clinical signs return associated with chronic myocarditis and dilation of the heart.
- Abnormalities again appear on the ECG.
- Death is the eventual outcome due to the cardiac complications.
Incidence and Prevalence
T. cruzi is endemic in parts of South and Central America as well as Mexico. Cases of autochthonous transmission also are reported in the southern United States, although infection of people and dogs in this region is lower than that seen in Latin America.
Host Associations and Transmission Between Hosts
- Transmission from insect vector to vertebrate host is via a stercorarian (deposited in feces of bug) route.
- Upon taking a blood meal, the vector often defecates near the bite wound. Trypomastigotes that are present in the bug feces can then enter the vertebrate host’s body.
- Ingestion of infected vectors, transplacental transmission, and transfusion of infected blood are also means of acquiring infection.
- Transmammary transmission and ingestion of infected meat have been suggested as potential routes of transmission, although neither has been experimentally proven.
- Insect vectors become infected from ingesting circulating trypomastigotes during a blood meal.
- In order for transmission of T. cruzi to occur, the relationship between the vectors, parasite, reservoir, and naïve hosts has to exist.
- In the United States, transmission is more limited than in Central and South America:
- The triatome vectors in the US tend to not defecate until 20 minutes post-feeding; at this point they are usually off the host.
- Housing conditions in the US often limit the ability of the triatomes to establish home infestations, thereby limiting exposure of people and dogs.
- In the United States, transmission is more limited than in Central and South America:
Site of Infection and Pathogenesis
- Trypomastigotes infect macrophages and myocardiocytes.
- Myocardiocytes are damaged when ruptured by replicating T. cruzi.
- A large number of cells can be infected and damaged due to the fast replication of T. cruzi within the host.
- Inflammation and eventual fibrosis result. With enough inflammation, death can occur due to the acute myocarditis; if the animal survives the initial insult, the heart may lose the ability to compensate for the scarred cells, and death subsequent to congestive heart failure occurs.
Diagnosis
- Clinical suspicion of infection is key to making a diagnosis; age of the dog, appropriate clinical signs, and any travel history to an endemic area would support a diagnosis of trypanosomiasis.
- Trypomastigotes can be detected on a Wright’s or Giemsa stained blood smear if the animal is in the parasitemic phase.
- Trypomastigotes may also be seen in aspirates of cavitary effusions or lymph nodes.
- Serology for detection of antibodies against T. cruzi is available and often useful, however, cross-reactivity to Leishmania exists.
- Antibodies are usually detectable by 3 weeks after infection and remain for the life of the animal.
- PCR and culture are also available.
- The gold standard for the diagnosis of T. cruzi is a combination of clinical signs and positive serology.
Treatment
- Benznidazole is the drug of choice for treating T. cruzi in dogs but is not available in the United States.
- Dose: 5-10 mg/kg PO every 24 hours for 2 months.
- Vomiting is the main side effect.
- Acquisition of this drug for use in dogs in the US is currently difficult or impossible.
- Because treatment is not available, many infected dogs are euthanized once a diagnosis is made.
- Additional therapy should target the cardiac dysfunction.
Control and Prevention
- Restricting contact with vectors is central to limiting T. cruzi transmission.
- Insecticides may be used to reduce the vector population in and around where the dog lives. Routine use of persistent insecticides on dogs has been shown to reduce the feeding of the vectors on dogs and the vector populations in and around the home.
- Limiting vector populations prevents both stercorarian transmission and transmission by dogs ingesting infected bugs.
- Blood-donor dogs should be serologically screened to ensure transfusion products are free of T. cruzi.
- Although not experimentally confirmed, dogs should not be allowed to ingest potential reservoir hosts, such as opossums, raccoons, armadillos, and skunks.
- To limit transplacental transmission, any female dog that is to be used for breeding should be screened for antibodies to T. cruzi.
Public Health Considerations
Trypanosoma cruzi is a zoonotic pathogen and is transmitted to people through the same routes as dogs, with stercorarian transmission from bug vectors considered the most common route.
Although autochthonous maintenance cycles exist, most human cases in the United States are the result of iatrogenic transmission or travel history to an endemic region.
People in contact with contaminated blood products (human or canine) should take additional precautions as infection from blood-to-blood contact could occur.
Human infection with T. cruzi is difficult to treat, as it is in animals.
Selected References
Barr SC, 2009. Canine Chagas’ Disease (American Trypanosomiasis) in North America. Vet Clin North Am Small Anim Pract 39: 1055-1064.
Esch KJ, Petersen CA, 2013. Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals. Clin Microbiol Rev 26: 58-85.
Kjos SA, Snowden KF, Craig TM, Lewis B, Ronald N, Olson JK, 2008. Distribution and characterization of canine Chagas’ disease in Texas. Vet Parasitol 152: 249-256.
Species
Trypanosoma cruzi
Overview of Life Cycle
- Trypomastigotes are deposited in the feces of an infected triatome insect (reduviid/”kissing bug”) near the feeding site; trypomastigotes then enter the vertebrate host through the bite wound or penetrate intact mucous membranes.
- Additional routes of transmission are discussed below.
- Trypomastigotes either remain in circulation to disseminate throughout the body or enter a host cell, most commonly macrophages or myocardiocytes.
- Within the host cell, trypomastigotes transform into the asexually reproducing stage, amastigotes.
- Asexual reproduction of amastigotes by binary fission occurs rapidly.
- Once the host cell is full, amastigotes transform back into trypomastigotes before rupturing the host cell and re-entering circulation.
- The new trypomastigotes then either enter another host cell or remain in circulation.
- Triatome insects acquire infection through ingestion of blood containing circulating trypomastigotes.
- Trypomastigotes convert to epimastigotes within the insect, replicate by binary fission, and then convert back into trypomastigotes prior to exiting in the feces of the vector.
Example of a kissing bug, a triatome that can vector Trypanosoma cruzi
Trypomastigotes of Trypanosoma cruzi in a canine blood smear
Stages
Epimastigote (present in triatome insect vector; replicates asexually)
Trypomastigote (infective stage; in feces of triatome orblood of vertebrate)
Amastigote (present in vertebrate host; replicates asexually)
Disease
- Disease due to infection with T. cruzi is termed Chagas disease.
- More severe disease often develops in animals less than 6 months of age; prognosis is worse in animals diagnosed at a younger age.
- Acute disease occurs within the first 30 days.
- Parasitemia appears around 3 days post-infection, peaks around 2-3 weeks after infection, and wanes by the end of the first month.
- Clinical signs may include generalized lymphadenopathy, lethargy, organomegaly (spleen and liver), pallor, and acute myocarditis.
- Lab abnormalities may include elevated troponin I, AST, ALT, creatinine, BUN.
- An evaluation of the heart via electrocardiogram (ECG) may reveal a number of conduction abnormalities.
- Sudden death, usually attributable to the cardiac malfunction, can be seen during this phase.
- From 1 to as long as 8 months after infection, parasitemia, clinical signs, and ECG abnormalities are usually absent.
- After 8 months post-infection, chronic infection and disease usually establish.
- Clinical signs return associated with chronic myocarditis and dilation of the heart.
- Abnormalities again appear on the ECG.
- Death is the eventual outcome due to the cardiac complications.
Incidence and Prevalence
T. cruzi is endemic in parts of South and Central America as well as Mexico. Cases of autochthonous transmission also are reported in the southern United States, although infection of people and dogs in this region is lower than that seen in Latin America.
Host Associations and Transmission Between Hosts
- Transmission from insect vector to vertebrate host is via a stercorarian (deposited in feces of bug) route.
- Upon taking a blood meal, the vector often defecates near the bite wound. Trypomastigotes that are present in the bug feces can then enter the vertebrate host’s body.
- Ingestion of infected vectors, transplacental transmission, and transfusion of infected blood are also means of acquiring infection.
- Transmammary transmission and ingestion of infected meat have been suggested as potential routes of transmission, although neither has been experimentally proven.
- Insect vectors become infected from ingesting circulating trypomastigotes during a blood meal.
- In order for transmission of T. cruzi to occur, the relationship between the vectors, parasite, reservoir, and naïve hosts has to exist.
- In the United States, transmission is more limited than in Central and South America:
- The triatome vectors in the US tend to not defecate until 20 minutes post-feeding; at this point they are usually off the host.
- Housing conditions in the US often limit the ability of the triatomes to establish home infestations, thereby limiting exposure of people and dogs.
- In the United States, transmission is more limited than in Central and South America:
Site of Infection and Pathogenesis
- Trypomastigotes infect macrophages and myocardiocytes.
- Myocardiocytes are damaged when ruptured by replicating T. cruzi.
- A large number of cells can be infected and damaged due to the fast replication of T. cruzi within the host.
- Inflammation and eventual fibrosis result. With enough inflammation, death can occur due to the acute myocarditis; if the animal survives the initial insult, the heart may lose the ability to compensate for the scarred cells, and death subsequent to congestive heart failure occurs.
Diagnosis
- Clinical suspicion of infection is key to making a diagnosis; age of the dog, appropriate clinical signs, and any travel history to an endemic area would support a diagnosis of trypanosomiasis.
- Trypomastigotes can be detected on a Wright’s or Giemsa stained blood smear if the animal is in the parasitemic phase.
- Trypomastigotes may also be seen in aspirates of cavitary effusions or lymph nodes.
- Serology for detection of antibodies against T. cruzi is available and often useful, however, cross-reactivity to Leishmania exists.
- Antibodies are usually detectable by 3 weeks after infection and remain for the life of the animal.
- PCR and culture are also available.
- The gold standard for the diagnosis of T. cruzi is a combination of clinical signs and positive serology.
Treatment
- Benznidazole is the drug of choice for treating T. cruzi in dogs but is not available in the United States.
- Dose: 5-10 mg/kg PO every 24 hours for 2 months.
- Vomiting is the main side effect.
- Acquisition of this drug for use in dogs in the US is currently difficult or impossible.
- Because treatment is not available, many infected dogs are euthanized once a diagnosis is made.
- Additional therapy should target the cardiac dysfunction.
Control and Prevention
- Restricting contact with vectors is central to limiting T. cruzi transmission.
- Insecticides may be used to reduce the vector population in and around where the dog lives. Routine use of persistent insecticides on dogs has been shown to reduce the feeding of the vectors on dogs and the vector populations in and around the home.
- Limiting vector populations prevents both stercorarian transmission and transmission by dogs ingesting infected bugs.
- Blood-donor dogs should be serologically screened to ensure transfusion products are free of T. cruzi.
- Although not experimentally confirmed, dogs should not be allowed to ingest potential reservoir hosts, such as opossums, raccoons, armadillos, and skunks.
- To limit transplacental transmission, any female dog that is to be used for breeding should be screened for antibodies to T. cruzi.
Public Health Considerations
Trypanosoma cruzi is a zoonotic pathogen and is transmitted to people through the same routes as dogs, with stercorarian transmission from bug vectors considered the most common route.
Although autochthonous maintenance cycles exist, most human cases in the United States are the result of iatrogenic transmission or travel history to an endemic region.
People in contact with contaminated blood products (human or canine) should take additional precautions as infection from blood-to-blood contact could occur.
Human infection with T. cruzi is difficult to treat, as it is in animals.
Selected References
Barr SC, 2009. Canine Chagas’ Disease (American Trypanosomiasis) in North America. Vet Clin North Am Small Anim Pract 39: 1055-1064.
Esch KJ, Petersen CA, 2013. Transmission and Epidemiology of Zoonotic Protozoal Diseases of Companion Animals. Clin Microbiol Rev 26: 58-85.
Kjos SA, Snowden KF, Craig TM, Lewis B, Ronald N, Olson JK, 2008. Distribution and characterization of canine Chagas’ disease in Texas. Vet Parasitol 152: 249-256.