APPENDIX 2 Leishmania Species • Fewer than 15 probable or confirmed cases of trans- mission by blood transfusion and 10 reported cases of Disease Agent: congenital transmission worldwide • Leishmania species At-Risk Populations: Disease Agent Characteristics: • Residents of and travelers to endemic areas Vector and Reservoir Involved: • Protozoan, 2.5 ¥ 5.0 mm • Order: Kinetoplastida • Phlebotomine sandflies: Phlebotomus genus (Old • Family: Trypanosomatidae World) and Lutzomyia genus (New World) • Intracellular pathogen of macrophages/monocytes • Only the amastigote stage is found in humans. Blood Phase: • Leishmania parasites survive and multiply in mono- Disease Name: nuclear phagocytes. Parasite circulation in peripheral • Leishmaniasis blood has been reported in asymptomatic L. dono- • Visceral leishmaniasis is called kala-azar in India and vani, L. tropica, and L. infantum infections, and in various names elsewhere. treated and inapparent L. braziliensis infections. • Cutaneous forms have a variety of colloquial names Survival/Persistence in Blood Products: around the world. • Leishmania species are known to survive in human Priority Level: RBCs under blood bank storage conditions for as long as 15 days and longer in experimental animal models. • Scientific/Epidemiologic evidence regarding blood safety: Low Transmission by Blood Transfusion: • Public perception and/or regulatory concern regard- ing blood safety: Low • Transfusion transmission has been documented in at • Public concern regarding disease agent: Low, but least three cases in nonendemic areas in which the moderate among military personnel recipients who received transfusion were either infants or immunocompromised patients. One pro- Background: bable case of L. donovani transmission by platelet transfusion has been reported. • Generally limited to tropical and sub-tropical cli- • No transfusion cases reported in the US mates, sometimes referred to as Old World and New • Leishmania species have been transmitted via clinical World forms transfusions from seropositive donor dogs to recipi- • Considered stable, but with sporadic outbreaks like ent dogs. those recently observed in Sudan and India • 2 million new cases of Leishmania worldwide each Cases/Frequency in Population: year: 1.5 million cutaneous and 0.5 million visceral • No cases, and unknown frequency in nonmilitary, • Nine US soldiers who served in the Persian Gulf area nonexpatriate US population in 1990 were found to have viscerotropic L. tropica • Worldwide, leishmaniasis is found in 88 countries. infections. They experienced a nonspecific febrile There are 350 million people at risk and 12 million illness with fatigue, arthralgia, and diarrhea. Some people are infected. The estimated annual number of soldiers recovered spontaneously, whereas others new cases of visceral leishmaniasis is about 500,000, progressed and developed a chronic condition with of which 90% are found in India, Bangladesh, Nepal, adenopathy or splenomegaly. These events led to Sudan and Brazil. Approximately 10,000,000 annual concern about the safety of returnees from the cases of cutaneous infection are estimated Persian Gulf as blood donors. That concern continues worldwide. with the recent deployment. Incubation Period: Common Human Exposure Routes: • Weeks to months following bite of infected sandfly • Bite of infected sandfly vector Likelihood of Clinical Disease: Likelihood of Secondary Transmission: • Variable depending upon infecting Leishmania • Minimal species, host genetics, and immune status Volume 49, August 2009 Supplement TRANSFUSION 221S APPENDIX 2 Primary Disease Symptoms: • Military blood banks ask a question about lifetime history of leishmaniasis and enforce a permanent • Cutaneous leishmaniasis: cutaneous lesion/ulcer at deferral for an affirmative response. the bite site, variable in size, can be active for months but usually self-healing (caused by L. major, L. Laboratory Test(s) Available: tropica, L. aethiopica, and L. mexicana subspecies). • No FDA-licensed blood donor screening test exists. Diffuse cutaneous leishmaniasis with lesions that do • There are several FDA-licensed diagnostic tests. not heal has been reported in Ethiopia and South • Options for laboratory testing include blood smear America and has been attributed to L. aethiopica and microscopy, culture, IFA, EIA, western blot, NAT, and L. mexicana amazonensis, respectively. antigen-based rapid diagnostic tests. • Visceral leishmaniasis: (caused by L. donovani, L. infantum, and L. chagasi); characterized in diseased Currently Recommended Donor Deferral Period: individuals by intermittent fever, massive hepatosplenomegaly, anemia, and hypergamma- • One-year deferral from the last date of departure from globulinemia. However, a significant proportion of Iraq the population in areas of endemic infection shows • Deferral for a history of leishmaniasis has been dis- subclinical infection (L. infantum). cussed, but no regulation or standard exists covering • Mucocutaneous leishmaniasis: (e.g., L. braziliensis) civilian blood banks. The initial skin lesion may cure spontaneously, but Impact on Blood Availability: metastatic lesions develop in the mucosa of the nasopharynx. • Agent-specific screening question(s): Existing defer- ral for travel to Iraq negatively impacts blood avail- Severity of Clinical Disease: ability, especially for the military. A deferral for travel • Visceral leishmaniasis: fatal if not treated to or immigration from other endemic countries • Other forms: can be severely disfiguring (social could have a significant impact. impact) • Laboratory test(s) available: Not applicable Mortality: Impact on Blood Safety: • Visceral leishmaniasis: usually fatal if untreated • Agent-specific screening question(s): The impacts of the Iraq deferral and the potential deferral for travel to Chronic Carriage: or immigration from other endemic countries are unknown. • Viable parasites can remain in the host for months to • Laboratory test(s) available: Not applicable years, if not lifetime, in both visceral and cutaneous infections. Disease can be reactivated by immuno- Leukoreduction Efficacy: suppression. Visceral leishmaniasis is a common • Moderate to high. Because Leishmania are found in reactivating syndrome in AIDS patients. blood cells of the monocyte/macrophage lineage, Treatment Available/Efficacious: leukocyte reduction could be an efficient method to reduce the risk of transfusion-transmitted leishma- • When treatment is needed, antimonial compounds niasis. Laboratory spiking studies indicate that not (e.g., sodium stibogluconate) are efficacious, but have all parasites are removed, particularly if found toxic side effects. Amphotericin B and miltefosine are extracellularly. alternative therapies being used with increasing • Universal leukocyte reduction has been implemented frequency. in at least 15 countries, including France and Spain, that have regions of high prevalence of Leishmania Agent-Specific Screening Question(s): seropositivity. Although surveillance for transfusion- • Presently, military and civilians who have traveled to transmission of Leishmania is of unknown quality, Iraq are deferred for 1 year, but effectiveness is there have been no reported cases of Leishmania unknown. transmission by blood transfusion in these countries. • Of the 88 countries endemic for leishmaniasis, all but Pathogen Reduction Efficacy for Plasma Derivatives: 20 are also endemic for malaria, and travelers to malaria areas are currently deferred for 1 year, which • No specific data are available but it is presumed that likely reduces the number of Leishmania-infected the agent should be sensitive to many measures used donors. in the fractionation process. 222S TRANSFUSION Volume 49, August 2009 Supplement APPENDIX 2 Other Prevention Measures: pheresis platelets by a psoralen (amotosalen HCl) and long-wavelength ultraviolet irradiation. Transfusion • Avoidance of the sandfly vector 2005;45:1459-63. • Leishmania parasite can be inactivated in plasma or 7. Grogl M, Daugirda JL, Hoover DL, Magill AJ, Berman platelet concentrates using riboflavin and ultraviolet JD. Survivability and infectivity of viscerotropic Leish- light (Mirasol PRT System). mania tropica from Operation Desert Storm partici- • A second study showed Leishmania inactivation in pants in human blood products maintained under human apheresis platelets by a psoralen and a long blood bank conditions. Am J Trop Med Hyg 1993;49: wavelength ultraviolet irradiation (more than 10,000- 308-15. fold reduction in viability). 8. Herwaldt BL. Leishmaniasis. Lancet 1999;354:1191-9. • No vaccine available, but some communities inten- 9. le Fichoux Y, Quaranta JF, Aufeuvre JP, Lelievre A, tionally infect children to provide protection Marty P, Suffia I, Rousseau D, Kubar J. Occurrence of Suggested Reading: Leishmania infantum parasitemia in asymptomatic blood donors living in an area of endemicity in south- 1. Cardo LJ. Leishmania: risk to the blood supply. Trans- ern France. J Clin Microbiol 1999;3:1953-7. fusion 2006;46:1641-5. 10. Mathur P, Samantaray JC. The first probable case of 2. Cardo LJ, Rentas FJ, Ketchum L, Salata J, Harman R, platelet transfusion-transmitted visceral leishmania- Melvin W, Weina PJ, Mendez J, Reddy H, Goodrich R. sis. Transfus Med 2004;14:319-21. Pathogen inactivation of Leishmania donovani infan- 11. Owens SD, Oakly DA, Maryott K, Hatchett W, Walton tum in plasma and platelet concentrates using ribo- R, Nolan TJ, Newton A, Steurer F, Schantz P, Giger U. flavin and ultraviolet