Leishmaniasis

Question 1

Leishmaniasis - organism

Answer 1

Kinetoplastid [same order as trypanosomiasis]
Flagellate protozoa

Intracellular amastigote:
-1-2um diameter
-No flagellum
-Survive in macrophages of liver, spleen, BM and skin
-Reside within phagolysosomal vacuole - not free in cytoplasm

Digenetic single celled organism - exists in 2 forms:
-In humans = obligate intracellular amastigotes
-In sandfly = flagellated promastigotes

Question 2

Leishmaniasis - epidemiology

Answer 2

Tropical and subtropical worldwide
VL 0.5 million cases/year
CL 10 million cases/year

Question 3

Leishmaniasis - lifecycle

Answer 3

Sandfly takes a blood meal - injects promastigote stage into skin
Promastigotes are phagocytosed by macrophages
Promastigotes transform into amastigotes inside macrophages
Amastigotes multiply in cells of various tissues
Sandly takes a blood meal - ingestion of parasite cells
Amsatigotes transform into promastigotes stage in midgut of sandfly

Question 4

Leishmaniasis - transmission

Answer 4

50 species of sandfly:
-Phlebotomus spp [Europe, Africa, S Asia]
-Lutzomyia spp [South America]

Unique sand fly - Leishmania species:
-Ph sergenti and L tropica
-Ph papatasi and L major

Vertical transmission
Mechanical transmission - IVDU

Question 5

Leishmaniasis - intracellular survival

Answer 5

Amastigotes survive within macrophage by modifying innate pathogen-killing mechanisms such as:
-Inhibiting the generation of free radicals and downrefular IL-12 and suppressing Th1 cell activation
-Promoting the production of immunosuppressive molecules

Question 6

Leishmaniasis - immunology

Answer 6

VL = IL-10 and IL-13 and INF-gamma elevated
CL = IL-4 and IL-10 elevated, low IFN-gamma

Question 7

Visceral leishmaniasis/kala azar - causative organism

Answer 7

L donovani
L infantum

Question 8

Visceral leishmaniasis - symptoms

Answer 8

2 weeks of fever [rule out malaria]
HSmegaly
Cachexia
Anaemia
Positive test [non-invasive]

Question 9

Post Kala-azar dermal leishmaniasis [PKDL] - presentation

Answer 9

South Asia = macular, 10-30% frequency after VL, 0-3 years after infection

East Africa = papular, 50-60% after VL, 0-13 months after infection

Question 10

Cutaneous leishmaniasis - localised disease

Answer 10

Caused by:
L major
L tropica
L mexicana
L braziliensis

Single or limited number of discrete lesions
Self cure - months to years
DTH positive [delayed type hypersensitivity]

Question 11

Cutaneous leishmaniasis - mucosal leishmaniasis

Answer 11

Caused by:
-L mexicana
-L aethiopica

Multiple, coalesced lesions, non-ulcerative
High number of amastrigotes

General T cell hypo-responsiveness [DTH negative]

Question 12

Cutaneous leishmaniasis - recidivans [reactivation]

Answer 12

Caused by:
-L tropica

Rare, relapsing
Amastigotes very sparse
Difficult to treat

Question 13

Cutaneous leishmaniasis - mucocutaneous leishmaniasis

Answer 13

Caused by:
-L viannia sub-genus [Latin America]

Immune over-reaction causing tissue destruction
10% will develop MCL

Tissue of soft palate infected - destructive

Question 14

Leishmaniasis - diagnosis

Answer 14

Parasitology [microscopy +/- culture]
-LN puncture, BL or spleen aspiration
-CL = lesion biopsy [at clean adge of lesion, not necrotic core]
-Microscopy = kinetoplast - diagnostic feature

Immunodiagnosis:
-IFAT/ELISA
-DAT [expensive]
-rK39 antigen-based [ELISA and dipstick format] RDT = most commonly used
-Katex [antigen detection] = antigen detected in urine, not widely used

PCR - kinetoplast DNA