LEISHMANIA SPP.

PATHOGEN SAFETY DATA SHEET - INFECTIOUS SUBSTANCES

SECTION I - INFECTIOUS AGENT

NAME: Leishmania spp.

SYNONYM OR CROSS REFERENCE: Leishmaniasis, kala-azar, Dum-Dum fever, black fever. The causative agents are members of the L. donovani complex, L. tropica, L. major, L. aethiopica, L. Mexicana complex, and Braziliensis complex ^{(1, 2)}.

CHARACTERISTICS: Leishmania spp. belong to the family Trypanosomatidae, order Kinetoplastida ⁽¹⁾. Leishmania spp. are characterized by a flagellated promastigote stage in a sandfly, and a non-motile amastigote stage within macrophages in mammals ^{(3, 4)}. The amastigotes, known as Leishman-Donovan (LD) bodies, are small, round or oval, and measures 3 to 5 µm ⁽⁵⁾. Eastern hemisphere: L. tropica, L. major, L. aethiopica. Western hemisphere: L. braziliensis and L. mexicana complexes.

SECTION II - HAZARD IDENTIFICATION

PATHOGENICITY/TOXICITY: The clinical presentation of leishmaniasis is dependent on immune status, nutritional status, species, and strain. A spectrum of findings is observed within each of the three major clinical syndromes: cutaneous, mucocutaneous and visceral leishmaniasis. Cutaneous leishmaniasis (CL), due to L. tropica, L. mexicana, L. braziliensis or L. major, is characterized by ulcerative skin lesions. The morphology of the cutaneous lesions may vary depending of the Leishmania species. The symptoms can be pruritic, painful, and scarring is possible. Cutaneous leishmaniasis may include local/diffuse skin lesions, ulceration, adenopathy, satellite lesions, and subcutaneous nodules ^{(4, 6)}. Systemic symptoms are often absent. Mucocutaneous leishmaniasis (ML) caused by L. braziliensis and occasionally with other Leishmania spp, occurs years after the onset of cutaneous leishmaniasis. ML is characterized by one or several cutaneous lesions, and secondary infection is a risk, and progressive tissue destruction. Symptoms can include mucosal lesions, nasal obstruction/bleeding, deformation of palates, gingival oedema, and periodontitis ⁽⁴⁾. Nasopharyngeal lesions can be fatal due to secondary infection or respiratory complications. Visceral leishmaniasis, usually caused by the parasites of the L. donovani complex, is fatal if left untreated. Symptoms include fever with two daily peaks, hepatosplenomegaly with pancytopenia, wasting and weakness, darkening skin and anemia ⁽⁴⁾. Post-kala-azar dermal leishmaniasis (also caused by L. donovani) follows 6 months to 5 years after an attack and/or complete cure of VL, causing hypopigmented macules, nodules and plaques, and erythema of the face ⁽⁷⁾.

EPIDEMIOLOGY: Worldwide distribution. It is endemic in 88 countries, mostly developing countries, including parts of Europe, South America, Africa and Asia ⁽¹⁾. It is estimated that 12 million are infected worldwide, with 2 million new cases occurring every year, 1.5 million for cutaneous leishmaniasis and 500,000 for visceral leishmaniasis ^{(4, 8, 9)}. Ninety percent of visceral leishmaniasis cases occur in Bangladesh, Brazil, India, Nepal, and Sudan; ninety percent of cutaneous leishmaniasis cases occur in Afghanistan, Algeria, Brazil, Iran, Peru, Saudi Arabia, and Syria ^{(4, 8)}.

HOST RANGE: Humans, warm-blooded mammals including dogs, cats, and small rodents ⁽²⁾.

INFECTIOUS DOSE: Unknown.

MODE OF TRANSMISSION: Transmitted by the bite of an infected female sandfly of the genus Phlebotemus or Lutzomyia ^{(10, 11)}. The sand fly acquires the parasite from a zoonotic reservoir. Laboratory, blood transfusion, congenital and sexual transmission are possible, and transmission by domestic or wild mammals has also been reported ^{(1, 12)}.

INCUBATION PERIOD: At least a week but can be up to many months.

COMMUNICABILITY: Communicable via sandflies as long as parasites are circulating in blood or are present in skin lesions, although person to person infection through blood transfusion, sexual contact or placenta (mother to child) is rare ⁽¹⁾. Parasites may still circulate in the blood after symptoms are no longer apparent.

SECTION III - DISSEMINATION

RESERVOIR: Humans and warm-blooded mammals including dogs, foxes, rats, cats, small rodents, sloths, and marsupials ^{(2, 4, 14, 15)}.

ZOONOSIS: Yes, by bite of sandfly that has fed off an infected mammalian host ⁽¹⁾.

VECTORS: Sand flies of the genus Phlebotemus or Lutzomyia ^{(10, 11)}.

SECTION IV – STABILITY AND VIABILITY

DRUG SUSCEPTIBILITY: Susceptibility has been observed for systemic agents such as antimony-based drugs, amphotericin, paromomycin, and oral miltefosine ⁽⁸⁾. Pentamidine is not preferred but has shown efficacy against relapse patients. A new agent, sitamaquine, has shown a 50% cure rate ⁽⁸⁾. Combination treatments may be used against pathogens with developed drug resistance. When administering parenteral treatment such as sodium-stibogluconate, factors such as risk for mucosal leishmaniasis development, and number, size, or complication of lesions of ulceration should be considered ⁽¹⁶⁾.

DRUG RESISTANCE: Resistance against sodium antimony gluconate has been documented for all species ⁽⁴⁾.

SUSCEPTIBILITY TO DISINFECTANTS: Susceptible to 1% sodium hypochlorite, 2% TriGene, 70% ethanol, 0.1% hand soap, 2% glutaraldehyde, formaldehyde ^{(17, 18)}.

PHYSICAL INACTIVATION: Leishmania spp. do not survive autoclaving condition of 121^oC for 15 minutes ⁽¹⁷⁾. Their 100% lethal temperature is much lower than this (50^oC).

SURVIVAL OUTSIDE HOST: Does not survive outside host or culture, but remains viable for 35 days in whole blood kept at 4 ^oC ⁽¹⁹⁾.

SECTION V - FIRST AID / MEDICAL

SURVEILLANCE: Monitor for symptoms. Diagnosis is made through microscopic identification of amastigotes in stained specimens from lesions. Identify parasite with real-time PCR of biopsy specimens from lesion fluid, western blot, rk39 immunochromatographic test, serological tests such as immunofluorescence assay (IIFA) and ELISA, and direct agglutination test ⁽⁴⁾. Species can be distinguished by targeting repetitive and polymorphic sequences by restriction enzymes ⁽²⁰⁾.

FIRST AID/TREATMENT: Administer appropriate drug therapy.

IMMUNIZATION: None

PROPHYLAXIS: None

SECTION VI - LABORATORY HAZARD

LABORATORY-ACQUIRED INFECTIONS: Twelve reported laboratory acquired infections ⁽²¹⁾.

SOURCE/SPECIMENS: Infective stages may be present in blood, faeces, lesion exudates, and infected arthropods ⁽²¹⁾.

PRIMARY HAZARDS: Accidental parenteral exposures, aerosols, vector-borne transmission, mucosal (mouth, nose, eyes), ingestion ⁽²¹⁾.

SPECIAL HAZARDS: Contact with lesion material, faeces, or blood, or receiving a bite from experimentally or naturally infected mammals ⁽²¹⁾.

SECTION VII - EXPOSURE CONTROLS / PERSONAL PROTECTION

RISK GROUP CLASSIFICATION: Risk Group 2 ⁽²²⁾.

CONTAINMENT REQUIREMENTS: Containment Level 2 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures. (Please note that containment requirements may differ depending on volume, production method, concentration, or additional factors which may alter the risk of potential infection, exposure, and/or environmental release).

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 ⁽²³⁾.

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 ⁽²³⁾.

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 ⁽²³⁾.

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 ⁽²³⁾.

STORAGE: The infectious agent should be stored in leak-proof containers that are appropriately labelled ⁽²³⁾.

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: September 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

REFERENCES:

1. Dey, A., & Singh, S. (2006). Transfusion transmitted leishmaniasis: a case report and review of literature. Indian Journal of Medical Microbiology, 24(3), 165-170.
   
   
2. Petersen, C. A. (2009). Leishmaniasis, an emerging disease found in companion animals in the United States. Topics in Companion Animal Medicine, 24(4), 182-188. doi:10.1053/j.tcam.2009.06.006
   
   
3. Li, Q., Zhou, Y., Yao, C., Ma, X., Wang, L., Xu, W., Wang, Z., & Qiao, Z. (2009). Apoptosis caused by Hsp90 inhibitor geldanamycin in Leishmania donovani during promastigote-to-amastigote transformation stage. Parasitology Research, 105(6), 1539-1548. doi:10.1007/s00436-009-1582-y
   
   
4. Sinha, P. K., Pandey, K., & Bhattacharya, S. K. (2005). Diagnosis & management of leishmania/HIV co-infection. The Indian Journal of Medical Research, 121(4), 407-414.
   
   
5. Murray, P. R., Baron, E. J., Jorgensen, J. H., Landry, M. L., Pfaller, M. A., & Yolken, R. H. (Eds.). (2003). Manual of Clinical Microbiology (8th ed.). Herdon, VA, United States of America: American Society for Microbiology.
   
   
6. Kedzierski, L. (2010). Leishmaniasis Vaccine: Where are We Today? Journal of Global Infectious Diseases, 2(2), 177-185. doi:10.4103/0974-777X.62881
   
   
7. Rathi, S. K., Pandhi, R. K., Chopra, P., & Khanna, N. (2005). Post-kala-azar dermal leishmaniasis: a histopathological study. Indian Journal of Dermatology, Venereology and Leprology, 71(4), 250-253.
   
   
8. Moore, E. M., & Lockwood, D. N. (2010). Treatment of visceral leishmaniasis. Journal of Global Infectious Diseases, 2(2), 151-158. doi:10.4103/0974-777X.62883
   
   
9. Clem, A. (2010). A current perspective on leishmaniasis. Journal of Global Infectious Diseases, 2(2), 124-126. doi:10.4103/0974-777X.62863
   
   
10. Rocha, L. S., Falqueto, A., Dos Santos, C. B., Ferreira, A. L., da Graca, G. C., Grimaldi, G.,Jr, & Cupolillo, E. (2010). Survey of natural infection by Leishmania in sand fly species collected in southeastern Brazil. Transactions of the Royal Society of Tropical Medicine and Hygiene, doi:10.1016/j.trstmh.2010.02.005
    
    
11. Gonzalez, M., Benito, F., Garcia, L., & Iglesias, A. (2009). Mucocutaneous Leishmaniasis: an imported illness with ENT repercussions. [Leishmaniasis mucocutanea: una enfermedad importada con repercusion en ORL] Acta Otorrinolaringologica Espanola, 60(4), 298-300. doi:10.1016/j.otorri.2009.01.006
    
    
12. Quinnell, R. J., & Courtenay, O. (2009). Transmission, reservoir hosts and control of zoonotic visceral leishmaniasis. Parasitology, 136(14), 1915-1934. doi:10.1017/S0031182009991156
    
    
13. Weiss, F., Vogenthaler, N., Franco-Paredes, C., & Parker, S. R. (2009). Leishmania tropica-induced cutaneous and presumptive concomitant viscerotropic leishmaniasis with prolonged incubation. Archives of Dermatology, 145(9), 1023-1026. doi:10.1001/archdermatol.2009.181
    
    
14. Dougall, A., Shilton, C., Low Choy, J., Alexander, B., & Walton, S. (2009). New reports of Australian cutaneous leishmaniasis in Northern Australian macropods. Epidemiology and Infection, 137(10), 1516-1520. doi:10.1017/S0950268809002313
    
    
15. Christensen, H. A., Arias, J. R., de Vasquez, A. M., & de Freitas, R. A. (1982). Hosts of sandfly vectors of Leishmania braziliensis guyanensis in the central Amazon of Brazil. The American Journal of Tropical Medicine and Hygiene, 31(2), 239-242.
    
    
16. Zaghi, D., Panosian, C., Gutierrez, M. A., Gregson, A., Taylor, E., & Ochoa, M. T. (2010). New World cutaneous leishmaniasis: Current challenges in diagnosis and parenteral treatment. Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2009.08.045
    
    
17. Wang, X., Jobe, M., Tyler, K. M., & Steverding, D. (2008). Efficacy of common laboratory disinfectants and heat on killing trypanosomatid parasites. Parasites & Vectors, 1(1), 35. doi:10.1186/1756-3305-1-35
    
    
18. World Health Organization. (1993). Laboratory Biosafety Manual (2nd ed.)
    
    
19. Grogl, M., Daugirda, J. L., Hoover, D. L., Magill, A. J., & Berman, J. D. (1993). Survivability and infectivity of viscerotropic Leishmania tropica from Operation Desert Storm participants in human blood products maintained under blood bank conditions. The American Journal of Tropical Medicine and Hygiene, 49(3), 308-315.
    
    
20. Goto, H., & Lindoso, J. A. (2010). Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Review of Anti-Infective Therapy, 8(4), 419-433. doi:10.1586/eri.10.19
    
    
21. Herwaldt, B. L. (2001). Laboratory-acquired parasitic infections from accidental exposures. Clinical Microbiology Reviews, 14(4), 659-88, table of contents. doi:10.1128/CMR.14.3.659-688.2001
    
    
22. Human pathogens and toxins act. S.C. 2009, c. 24, Second Session, Fortieth Parliament, 57-58 Elizabeth II, 2009. (2009).
    
    
23. Public Health Agency of Canada. (2004). In Best M., Graham M. L., Leitner R., Ouellette M. and Ugwu K. (Eds.), Laboratory Biosafety Guidelines (3rd ed.). Canada: Public Health Agency of Canada.