Pathogen Safety Data Sheets: Infectious Substances – Trypanosoma brucei ssp.

SECTION I - INFECTIOUS AGENT

NAME: Trypanosoma brucei ssp.

SYNONYM OR CROSS REFERENCE: African trypanosomiasis, Human African trypanosomiasis (HAT), sleeping sickness, African sleeping sickness, African lethargy, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense Footnote 1-3. Nagana in domestic and wild ruminants Footnote 4.

CHARACTERISTICS: Trypanosoma brucei are extracellular flagellate protozoa belonging to the Trypanosomatidae family, in the order Kinetoplastida, and consist of three subspecies Footnote 2Footnote 5: T. brucei gambiense causes chronic trypanosomiasis in humans, T. brucei rhodesiense causes acute trypanosomiasis in humans, and T. brucei brucei infects wild and domestic animals (not humans) and causes a disease called nagana Footnote 1Footnote 2. Trypanosoma brucei trypomastigotes circulate in blood and have either a long, slender body, or a short, stumpy body Footnote 6. The slender form (23-33 µm in length) divides every 5 to 10 hours, whereas the shorter, stumpy form (17-22 µm in length) does not divide but is more infective to vector tsetse flies Footnote 7Footnote 8. Trypanosoma brucei exists as epimastigotes and metacyclic trypomastigotes in the tsetse fly vectors Footnote 6. Like all trypanosomes and kinetoplatstidian pathogens including Leishmania spp., they are unique in using trans splicing exclusively to complete their mRNAs for expression Footnote 9. This has been an important focus and target for disease intervention including drug development. Such an intervention has also major implications for the management of trematode and nematode infections as they also use trans splicing for some but not all messenger RNAs Footnote 10

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: T. bruceicauses African Trypanosomiasis in humans Footnote 2.  The first stage of African trypanosomiasis is haemolymphatic, which commences 1–3 weeks after an infective tsetse fly bite. Clinical features include headache, chronic and intermittent fever, pruritus, lymphadenopathy, mild hepatosplenomegaly, and occasionally, trypanosomal ulcers. The second stage of African trypanosomiasis is meningoencephalitic, characterized by the invasion of the central nervous system. Clinical features include sleep disorder, tremor, fasciculations, general motor weakness, limb paralysis, hemiparesis, akinesia, abnormal movements, irritability, psychotic reactions, aggressive behaviour, or inactivity. Somnolence is observed in 80% of late-stage patients of T. brucei gambiense. If untreated, trypanosomiasis results in coma and death. With T. brucei gambiense, this may take up to three years, whereas with the more virulent T. brucei rhodesiense, death may occur within weeks or months. Asymptomatic cases have also been reported.

EPIDEMIOLOGY: Human African trypanosomiasis (HAT) is restricted to sub-Saharan Africa where the tsetse fly vector, the parasite (and its reservoir hosts), and humans co-existFootnote 11. The available estimates for HAT indicate that 60 million people are at risk (both forms combined) in sub-Saharan Africa. T. brucei gambiense is associated with over 90% of reported sleeping sickness casesFootnote 12. Sleeping sickness affects people in 36 countries in sub-Saharan Africa1. T. brucei gambiense typically causes disease in central and west Africa, T. brucei rhodesiense causes disease in east and southern Africa Footnote 2. The disease is more prevalent in poor and remote rural regions, although urban areas are affected as well Footnote 2. A notable outbreak of African sleeping sickness extended from 1896 to 1996, killing 800 000 people Footnote 2.

HOST RANGE: For T. brucei rhodesiense: humans, wild and domestic animals, including cattle, chickens, dogs, antelopes, lions, hyenas, and pigs Footnote 2Footnote 6Footnote 13Footnote 14. For T. brucei gambiense: mainly humans, some wild and domestic animals, including pigs Footnote 2.

INFECTIOUS DOSE: Unknown

MODE OF TRANSMISSION: Transmitted by the bite of an infected tsetse fly of the genus Glossina Footnote 2. Once the tsetse fly is infected by a zoonotic reservoir, the parasite differentiates for 3-5 weeks before migrating to the salivary glands Footnote 2. Only about 0.1% of tsetse flies carry a mature infection that can be transmitted to humans Footnote 2. Laboratory, blood transfusion, congenital and sexual transmission are possible, although rare Footnote 15Footnote 16.

INCUBATION PERIOD: Incubation time for T. brucei gambiense can be several months to several years Footnote 12. Incubation time for T. brucei rhodesiense can be one day to a few weeks Footnote 12Footnote 15.

COMMUNICABILITY: Person to person transmission is rare, but congenital, sexual, and blood transfusion transmission are possible Footnote 15Footnote 16.

SECTION III - DISSEMINTATION

RESERVOIR: Reservoirs for T. brucei rhodesiense are humans, and domestic and wild animals, including cattle Footnote 2. Reservoirs for T. brucei gambiense are mainly human, but there have been reports of some domestic and wild animals carrying trypanosomes Footnote 2. Domestic animals (pigs, goats, dogs, sheep, cattle and even chickens) can be infected with T. brucei gambiense.  However, the importance of these animal reservoirs is probably marginal in high-incidence countries of Central Africa, but they might play a role in the persistence of the disease in countries of West Africa, where the size of the human reservoir has been reduced through control efforts Footnote 17 .

ZOONOSIS: Yes, by bite of a tsetse fly that has fed from an infected animal host Footnote 1.

VECTORS: Male and female tsetse flies of the genus Glossina Footnote 2.

SECTION IV - STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: To treat first-stage trypanosomiasis, pentamidine can be used for T. brucei gambiense, and suramin can be used for T. brucei rhodesiense Footnote 2. With second-stage trypanosomiasis, eflornithine is the preferred drug for T. brucei gambiense, but melarsoprol can be used for both T. brucei gambiense and T. brucei rhodesiense Footnote 2. In April 2009, a new treatment option, nifurtimox-eflornithine combination therapy (NECT), was added to the WHO Essential Medicines List (EML) for the treatment of second-stage T. b. gambiense HAT Footnote 18.

DRUG RESISTANCE: Some strains of T. brucei gambiense are resistant to melarsoprolFootnote 6. T. brucei rhodesiense is not susceptible to eflornithine treatment Footnote 2.

SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 0.05% sodium hypochlorite, 2% TriGene, 70% ethanol, 0.1% hand soap, 2% formaldehyde, 0.05% glutaraldehyde Footnote 19Footnote 20 .

PHYSICAL INACTIVATION: The lethal temperature for 100% of trypomastigotes is 50°C Footnote 19.

SURVIVAL OUTSIDE HOST: T. brucei can survive for longer than 72 hours in refrigerated pig blood, depending on the initial parasitaemia concentration of the blood Footnote 21. Studies have also found that organisms can survive in blood taken out of the body for a few hours, or for 3 days if kept in a sterile flask with adequate oxygen, or for 6 days if desiccation is prevented Footnote 22.

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Suggestive clinical features merit further screening Footnote 2. Infection with T. brucei gambiense can be confirmed using the card agglutination test for trypanosomiasis Footnote 2. Immunofluorescence or enzyme-linked immunosorbent assays can also be used to identify T. brucei gambiense infection Footnote 2, PCR, and loop-mediated isothermal amplification (LAMP Footnote 23). Microscopic examination of lymph node aspirate, blood, CSF, sternum bone marrow, or chancre fluid for trypanosomes is also required because serological tests are not 100% sensitive Footnote 2Footnote 6Footnote 15. Screening for T. brucei rhodesiense relies on clinical presentation and microscopic examination Footnote 2. PCR testing using the splice leader genes as amplification targets is the most sensitive diagnostic assay.

Note: All diagnostic methods are not necessarily available in all countries.

FIRST AID/TREATMENT: Treatment for T. brucei gambiense involves: pentamidine (first-stage disease), melarsoprol (second-stage disease), or eflornithine (preferred second-stage treatment) Footnote 2Footnote 24Footnote 25. Treatment for T. brucei rhodesiense involves: suramin (first-stage disease) or melarsoprol (second-stage disease) Footnote 2Footnote 25. A combination of eflornithine and nifurtimox is safer and easier than eflornithine on its own, and is at least as effective as eflornithine Footnote 26. Melarsoprol is arsenic-based and kills 3-10% of patients using it Footnote 1.

IMMUNIZATION: None Footnote 5.

PROPHYLAXIS: None Footnote 5.

SECTION VI - LABORATORY HAZARDS

LABORATORY-ACQUIRED INFECTIONS: As of 2001, 4 cases of infection from T. brucei gambiense, 2 cases from T. brucei rhodesiense were reported, and 17 cases from unspecified species of Trypanosoma were reported Footnote 15.

SOURCE/SPECIMENS: Trypomastigote (infectious stage) may be in blood, chancre fluid, cerebrospinal fluid (CSF), or arthropod vectors Footnote 15.

PRIMARY HAZARDS: Parenteral inoculation, contact with broken skin or mucous membrane, arthropod vector, aerosols Footnote 15.

SPECIAL HAZARDS: Contact with blood, CSF, or tissue from infected animals Footnote 15.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2 Footnote 27.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures Footnote 28.

PROTECTIVE CLOTHING: Lab coat. Gloves when direct skin contact with infected materials or animals is unavoidable. Eye protection must be used where there is a known or potential risk of exposure to splashes Footnote 28.

OTHER PRECAUTIONS: All procedures that may produce aerosols, or involve high concentrations or large volumes should be conducted in a biological safety cabinet (BSC). The use of needles, syringes, and other sharp objects should be strictly limited. Additional precautions should be considered with work involving animals or large scale activities Footnote 28.

SECTION VIII - HANDLING AND STORAGE

SPILLS: Allow aerosols to settle and, wearing protective clothing, gently cover spill with paper towels and apply an appropriate disinfectant, starting at the perimeter and working towards the centre. Allow sufficient contact time before clean up Footnote 28.

DISPOSAL: Decontaminate all wastes that contain or have come in contact with the infectious organism by autoclave, chemical disinfection, gamma irradiation, or incineration before disposing Footnote 28.

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled Footnote 28.

SECTION IX - REGULATORY AND OTHER INFORMATION

REGULATORY INFORMATION: The import, transport, and use of pathogens in Canada is regulated under many regulatory bodies, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment Canada, and Transport Canada. Users are responsible for ensuring they are compliant with all relevant acts, regulations, guidelines, and standards.

UPDATED: December 2011

PREPARED BY: Pathogen Regulation Directorate, Public Health Agency of Canada

Although the information, opinions and recommendations contained in this Pathogen Safety Data Sheet are compiled from sources believed to be reliable, we accept no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information. Newly discovered hazards are frequent and this information may not be completely up to date.

Copyright © Public Health Agency of Canada, 2011 Canada

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