Trypanosoma cruzi

Pathogen Safety Data Sheets: Infectious Substances – Trypanosoma cruzi

SECTION I – INFECTIOUS AGENT

Name: Trypanosoma cruzi

Agent type: Parasite

Family: Trypanosomatidae

Genus: Trypanosoma

Species: cruzi

Synonym or cross–reference: Chagas disease, American trypanosomiasis.

Characteristics

Trypanosoma cruzi (T. cruzi) is a protozoan parasite. Cellular features include a kinetoplast comprised of 20,000 to 30,000 circular mitochondrial DNA molecules, and the presence of a flagella for 2 of the 3 morphological stages^{Footnote1Footnote2}. The epimastigote form is flagellated, measures 20 to 40 μm in length, and has replicative activity^Footnote3. Trypomastigotes have a long slender shape with a shorter flagella, are non-replicating, and measure 12 to 20 μm in length^{Footnote1Footnote3}. The amastigote forms are non-mobile, roughly spherical and measure 2 to 6.5 μm in diameter^Footnote3. The genome of T. cruzi is arranged in 41 chromosome pairs^Footnote4. The genome varies in size and structure for different strains, ranging from approximately 45 to 95 mega base pairs (Mbp) in length^Footnote5.

Properties

T. cruzi is the causative agent of Chagas disease. The life cycle of T. cruzi begins when an insect takes a blood meal from an infected host with T. cruzi trypomastigotes circulating in the blood. The trypomastigotes migrate to the insect midgut where they differentiate into epimastigotes and replicate^Footnote2. In the rectum of the insect, T. cruzi differentiates into the infectious metacyclic trypomastigote form that is excreted in insect feces and comes into contact with mucosal tissue or the bloodstream of a vertebrate host^Footnote2. In a newly infected host, the metacyclic trypomastigote invades a host cell and differentiates into the amastigote form^{Footnote2Footnote6}; the amastigotes then multiply by binary fission in the cytoplasm. Amastigotes can persist within the host cell as a transient, dormant non-proliferating amastigote form^{Footnote7Footnote8}, or differentiate into a trypomastigote, lyse the infected cell, and proceed to infect adjacent cells or migrate through the bloodstream to infect other host tissues^Footnote2. T. cruzi can infect many types of host cells, but have high affinity for cardiac and other muscle tissue (e.g., colon, esophagus)^{Footnote9Footnote10}. Genetic exchange through sexual reproduction occurs, but appears to be rare^Footnote11.

Seven discrete typing units of T. cruzi have been defined: TcI-TcVI and TcBat^{Footnote12Footnote13Footnote14}. Chagas disease progression^Footnote15 and virulence varies according to strain^Footnote16.

Section II – Hazard identification

Pathogenicity and toxicity

There are two distinct phases of T. cruzi infection. During the acute phase of illness, approximately 90% of T. cruzi-infected individuals are asymptomatic or have mild symptoms^{Footnote9Footnote17}. Clinical signs of illness include fever, anorexia, malaise, headache, generalized or local edema, and enlargement of the liver, spleen, and lymph nodes^{Footnote9Footnote17}. Some signs will vary according to the portal of entry^Footnote9. There may be swelling (chagoma) on the skin at the site of the insect bite, or in the case of parasite entry via ocular mucous membranes, signs may include unilateral conjunctivitis and swelling of the eyelid (Romaña sign)^Footnote9. The duration of the acute phase is 1 to 2 months^Footnote17. Approximately 1-5% of symptomatic acute cases are severe with hemorrhagic, jaundice, cardiac, and meningoencephalitis manifestations^{Footnote9Footnote17}. Acute illness mortality is less than 5% of symptomatic cases^Footnote9, although infections acquired via oral route have higher mortality (8 to 35%)^{Footnote9Footnote18}. The majority of T. cruzi-infected individuals (70%) remain asymptomatic for life with the indeterminate chronic form of Chagas disease^Footnote17. Approximately 20-30% of individuals with the chronic form of Chagas disease will develop cardiomyopathy and/or digestive disease slowly over decades following initial T. cruzi infection^{Footnote17Footnote19}.

The clinical manifestation of T. cruzi infection in dogs is similar to disease in humans^{Footnote20Footnote21Footnote22}. Cardiac changes have been observed in other T. cruzi-infected animals, including raccoons and opossums^{Footnote23Footnote24}. Severe manifestations have been reported in some species (e.g., horse, red panda) but appear to be infrequent^{Footnote25Footnote26}.

Epidemiology

Chagas disease is endemic in Mexico, Central America, and South America, where an estimated 5.7 million people are infected with T. cruzi in these regions^Footnote27. Estimated T. cruzi infection prevalence varies according to the country, from less than 1% of the population in many Latin American countries to 6% of the population in Bolivia^Footnote27. There was a significant decline in Chagas disease prevalence (17.4 million to 7.7 million cases)^Footnote28, deaths (45,000 to 12,000 per year)^{Footnote28Footnote29}, and incidence (700,000 to less than 50,000 new cases per year)^{Footnote28Footnote29} from the 1980s to 2005, due in part to widely implemented vector control measures^Footnote27. Outbreaks in Chagas-disease endemic areas due to consumption of contaminated fruits and/or fruit juices are not uncommon^{Footnote30Footnote31Footnote32}.

Global prevalence of T. cruzi infection is 6 to 7 million cases^{Footnote6Footnote27}. Chronic Chagas disease is increasingly observed in non-endemic areas including the United States, Canada, Europe, and Western Pacific countries due to migration of individuals from Chagas disease-endemic areas^{Footnote33Footnote34}. Locally acquired cases of Chagas disease in the United States are rare (28 cases from 1955 to 2015)^Footnote35.

The genetic polymorphism IL17A rs2275913 has been associated with Chagas disease susceptibility^Footnote36. Immunosuppressed individuals with chronic Chagas disease have a higher risk of disease reactivation^{Footnote9Footnote17Footnote37Footnote38}.

Host range

Natural host(s): T. cruzi can infect many mammalian species, including humans, non-human primates^{Footnote39Footnote40}, armadillos^Footnote6, anteaters^Footnote40, goats^Footnote41, horses^Footnote26, swine^Footnote6, otters^Footnote40, raccoons^Footnote6, skunks^Footnote6, bats, domestic and exotic felids^{Footnote40Footnote42}, cervids^Footnote43, canids (e.g., dogs, wolves, fox)^Footnote40, bears^{Footnote25Footnote40}, and rodents (e.g., squirrels, wood rats)^{Footnote6Footnote44}, as well as marsupials (e.g., opossum)^Footnote6.

Other host(s): None.

Infectious dose: Unknown.

Incubation period

7 to 15 days for vectorborne transmission, 8 to 120 days for transfusion transmission, 3 to 22 days for oral transmission^{Footnote9Footnote17}.

Communicability

In Chagas disease-endemic areas, T. cruzi is primarily transmitted via contact with excretions and body fluids of infected triatomine insects^Footnote9. T. cruzi can gain entry through contact with mucous membranes or through broken skin when feces of an infected triatomine is inadvertently rubbed into the bite wound. Transmission can also occur via consumption of food and drink, especially fruits and fruit juices, contaminated with T. cruzi^{Footnote17Footnote45Footnote46}. Modes of T. cruzi transmission also include sexual transmission^Footnote47, congenital transmission (5%)^Footnote48, blood transfusion, and solid organ transplantation^{Footnote6Footnote17}. T. cruzi transmission in breastmilk is possible but not efficient^Footnote49. In some animal species, such as dogs, transmission can occur via intentional ingestion of triatomine insects^{Footnote22Footnote50}.

Section III – Dissemination

Reservoir

Reservoirs in the sylvatic transmission cycle include rodents (e.g., wood rats)^{Footnote44Footnote51}, raccoons^Footnote52, and opossums^{Footnote23Footnote24Footnote53}. In some areas, dogs are a reservoir host in the domestic transmission cycle of T. cruzi^{Footnote54Footnote55}.

Zoonosis

Direct transmission between animals and humans has not been documented. Transmission occurs between animals and humans via a triatomine vector.

Vectors

T. cruzi can be transmitted through the feces of triatomine insects of the Reduviidae family. There are 152 species of triatomine insects, some of which have common names, including the kissing bug^{Footnote24Footnote56Footnote57Footnote58}. Some vector species include Triatoma infestans, Panstrongylus megistus, T. dimidiata, and Rhodnius prolixus^Footnote6. Different species have different transmission efficiencies^Footnote33. Triatomine insects can colonize nests of reservoir hosts and human dwellings. Indoor residual spraying interventions, using pyrethroids (e.g., deltamethrin), have been an effective means of vector control, although resistance has been described in some areas^{Footnote59Footnote60}.

Section IV – Stability and viability

Drug susceptibility/resistance

T. cruzi is susceptible to benznidazole and nifurtimox, which are used to treat clinical Chagas disease^Footnote61. Azoles in phase I or II clinical studies include posaconazole, ravuconazole, itraconazole, voriconazole, and albaconazole. Many other compounds have shown antitrypanosomal activity in vitro and/or small animal studies, including amiodarone and fexinidazole^{Footnote61Footnote62}. Drug repurposing studies have identified many candidates for the treatment of Chagas disease, such as benidipine, clofazimine, and tamoxifen^{Footnote62Footnote63}. Natural compounds from plants have shown activity against T. cruzi and are a promising source for discovery of new drugs^Footnote64.

T. cruzi strains that are highly resistant (e.g., Colombian strain) and partially resistant to benznidazole have been described^{Footnote10Footnote65}.

Susceptibility to disinfectants

Unknown for T. cruzi. Sodium hypochlorite (0.05%), TriGene (0.2%), liquid hand soap, and ethanol are effective against other Trypanosoma species^Footnote66.

Physical inactivation

Heat treatment at 70 °C for 10 seconds and 50 °C for 5 minutes effectively eliminated Trypanosoma species^{Footnote66Footnote67}. Riboflavin/UV light treatment has been used to inactivate T. cruzi in donated blood products^Footnote68.

Survival outside host

T. cruzi can survive for up to 72 hours on sugar cane and fruits^{Footnote69Footnote70}. T. cruzi can survive in juice for up to 144 h at 4 °C and in refrigerated blood for over 18 days^{Footnote70Footnote71}.

Section V – First aid/medical

Surveillance

For acute phase disease, T. cruzi trypomastigotes can be observed by microscopy of a blood smear^Footnote17. PCR has been used to detect T. cruzi DNA in blood for the diagnosis of acute phase of the chagas disease^{Footnote6Footnote12Footnote72}. In the chronic phase of Chagas disease, IgG antibodies against T. cruzi can be detected in serum and saliva using ELISA and immunofluorescence assays^{Footnote6Footnote17Footnote73}. Xenodiagnosis has also been used^Footnote74.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

Acute phase illness can be treated successfully with benznidazole or nifurtimox (for 2 to 3 months)^{Footnote17Footnote75Footnote76}. Indeterminate chronic phase Chagas disease treatment can decrease the risk of developing, but not the progression of pre-existing, cardiomyopathy^Footnote10. Cure rates are low when drugs are administered during the chronic phase of disease^{Footnote6Footnote61}.

T. cruzi-infected dogs treated with a combination of itraconazole and amiodarone showed clinical improvement and tested negative for T. cruzi DNA in blood^{Footnote20Footnote21}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine is currently available.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

Sixty-five T. cruzi laboratory-acquired infections prior to 2001 were documented^Footnote77. The most common route of exposure was parenteral^Footnote77. In 2003, a laboratory technician was infected with T. cruzi following an accidental autoinoculation incident^Footnote78.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood, saliva, tissue biopsy, cerebrospinal fluid.

Primary hazards

Primary hazards include autoinoculation with infectious material and exposure of mucous membranes or abraded skin to infectious material^Footnote79. Work with triatomines infected with T. cruzi poses an additional risk to personnel^Footnote79.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

T. cruzi is a Risk Group 2 (RG2) Human Pathogen and RG2 Animal Pathogen^{Footnote80Footnote81}.

Containment requirements

Containment Level 2 facilities, equipment, and operational practices outlined in the CBS are required for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 2 requirements for personal protective equipment and clothing outlined in the CBS to be followed. At minimum, use of a labcoat and closed-toe cleanable shoes, gloves when direct skin contact with infected materials or animals is unavoidable, and eye protection where there is a known or potential risk of exposure to splashes.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone and work activities must be documented.

Other precautions

A biological safety cabinet (BSC) or other primary containment devices to be used for activities with open vessels, based on the risks associated with the inherent characteristics of the regulated material, the potential to produce infectious aerosols or aerosolized toxins, the handling of high concentrations of regulated materials, or the handling of large volumes of regulated materials.

Use of needles and syringes to be strictly limited. Bending, shearing, re-capping, or removing needles from syringes to be avoided, and if necessary, performed only as specified in standard operating procedures (SOPs). Additional precautions are required with work involving animals or large-scale activities.

Additional information

For diagnostic laboratories handling primary specimens that may contain T. cruzi, the following resources may be consulted:

• Human Diagnostic Activities Biosafety Guideline
• Local Risk Assessment Biosafety Guideline

Section VIII – Handling and storage

Spills

Allow aerosols to settle. Wearing personal protective equipment, gently cover the spill with absorbent paper towel and apply suitable disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up (CBH).

Disposal

All materials/substances that have come in contact with the regulated materials should be completely decontaminated before they are removed from the containment zone or standard operating procedures (SOPs) to be in place to safely and securely move or transport waste out of the containment zone to a designated decontamination area / third party. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the regulated material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 2 requirements for storage outlined in the CBS are to be followed. Primary containers of regulated materials removed from the containment zone to be labelled, leakproof, impact resistant, and kept either in locked storage equipment or within an area with limited access.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with T. cruzi require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of Canada^Footnote80. The following is a non-exhaustive list of applicable designations, regulations, or legislations:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

2020

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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