Leishmaniasis Thomas Fourie MD M. Taher Shabani-Rad MD CLS, Division of Hematopathology

Leishmaniasis HLH Transfusion Chagas Disease

What is Leishmaniasis? Leishmaniasis is caused by infection with a protozoan parasite that is spread by the bite of infected sandflies Protozoans are historically defined as a single-celled organisms with animal-like behaviour, such as motility and predation (attacking)

Two forms of Leishmaniasis Amastigote of Leishmania

The life cycle of Leishmania

Sand fly At least 93 sandfly species are proven or probable vectors worldwide.

World distribution of Visceral Leishmaniasis Canada is not highlighted on leishmana map and No leishmaniasis had been previously reported in Alberta

What is HLH? Hemophagocytic LymphoHistiocytosis Immunologic disorder Over production and –activation of T cells and histiocytes Phagocytosis of normal hematopoietic cells by histiocytes

Primary/inherited HLH Rare – 1 case per million children Primary HLH is caused by an inherited problem with the immune system 5 genes have been identified, including the perforin gene Onset of the disease occurs in first year of life in 70% of cases

Secondary/reactive HLH No family history No genetic abnormalities Triggers: Infection - Viral, Bacterial, Protozoan, Fungi Malignancy – T cell lymphoma Auto-immune - SLE

Visceral Leishmaniasis HLH Enlarged liver or spleen Fever Anemia HLH Enlarged liver or spleen Fever Cytopenias

Visceral Leishmaniasis (kala-azar) HLH Mortality rate of more than 90% within 2 years if left untreated Antibiotics including Amphotericin B HLH Mortality rate of 100% over the course of 2 months if left untreated Cytotoxic chemotherapy to supress the immune system

Case 2 year old child Diagnosed with HLH Bone marrow: Routine pre-BMT Assessment for Cord Stem Cell Transplant for HLH

It is difficult to differentiate leishmania bodies from platelet and cellular debris (Double dot nucleus)

Presence of leishman bodies in BM H&E sections are very diagnostic of BM leishmaniosis (Platelets are not seen in BM biopsy sections)

BM performed 6 months earlier

Canadian born child No sandfly of the type that transmit Leishmaniasis in North America Leishmaniasis does not exist in Alberta History of blood transfusions Biting midge, Sand fly or Punkies

Could this have been transmitted by a blood transfusion? Cryptic infection in blood donors from endemic areas Cases of transfusion transmitted Leishmaniasis have been reported in non-endemic areas Most of these cases involved infants or children Yes

CBS screening for Leishmaniasis Ask donors if they ever had Leishmaniasis If yes – deferred indefinitely Lab test? Not really

Chagas disease (Trypanosomiasis) Also transmitted by an insect Mexico, Central- and South America

Chagas disease Donors from endemic areas are tested Abbott Chagas antibody test Some cross reactivity with Leishmaniasis Not reliable for exclusion of Leishmaniasis

What was the source of infection? Travel history Family visited Albania after the child's birth Albania is endemic for Leishmaniasis Mediterranean Visceral Leishmaniasis affects primarily children or immunocompromised individuals It is known to occur since 1938, typically as a childhood disease in Albania Developing country with suboptimal disease specific surveillance Newborns can be infected, even with asymptomatic mother

Conclusion (1) HLH can occur in cases with Leishmaniasias Leishmaniasis can be difficult to diagnose if you are not looking for it Leishmania parasites can be mistaken for phagocytosed platelets or cellular debris

Conclusion (2) Leishmaniasis can be transmitted by transfused blood of asymptomatic, infected individuals Very rare - only 11 reports of transfusion transmitted Leishmaniasis worldwide All reports were from Asia and Europe 9 of the 11 cases occurred in children less than 6 years of age

Conclusion (3) Chagas antibody test can be “false” positive in a patient with Leishmaniasis PCR technology can be used for mass screening of donor blood samples for Leishmaniasis In Canada the cost outweigh the benefit Currently donors are deferred only if they where diagnosed with Leishmaniasis Transmission of Leishmaniasis by an asymptomatic individual is a possibility, but very unlikely