Lecture 8 Leishmania- Leishmaniasis

Question 1

What are the three forms of leishmaniasis?

Answer 1

-Visceral(most serious)
-Cutaneous(most common)
-mucocutaneous

Question 2

How is leishmaniasis caused?

Answer 2

-Through leishmania parasites that are transmitted through the bite of female phlebotomine sand flies

Question 3

Does everyone who gets infected by the leishmania parasite get the disease?

Answer 3

No only some

Question 4

What is the leishmania life cycle?

Answer 4

1. sand fly injects promastigotes into the skin(infected stage)
2. Promastigotes are phagocytized by macrophages or other types of mononuclear phagocytic cells
   3.Promastigotes transforms into amastigotes
3. Promastigotes multiply in cells of various tissues and infect other cells
   (2-4 Human stage)
4. sandfly ingests macrophages infected with amastigotes
5. ingestion of parasitized cells
6. amastigotes transform into promastigote stage in the gut
7. divide in the gut and migrate to proboscis

Question 5

Leishmania development within the sand fly

Answer 5

Amastigote–> procyclic promastigote–> nectomonad promastigote–> leptomonad promastigote–> haptemonad promastigote–> metacyclic promastigote

Question 5

Leishmania cellular characteristics

Answer 5

• are considered as aneuploid organisms
• Differential gene expression in the different life cycle stages seems to be regulated
  by sensing and integrating two major environmental clues: temperature and pH.
• No functional RNAi machinery present
• They replicate by binary fission, but there are some evidences of sexual
  reproduction in the flies.
  Daughter with short flagellum
  Daughter with long flagellum

Question 6

How do promastigotes interact with non phagocytic cells?

Answer 6

-GIPLs and and GPI anchored glycans cover all the surfaces of the parasite
-Gp63 is the predominant surface protein of the promastigoTes
-Leishmania do not actively invade the cells but instead induces its own receptor mediated endocytosis

Question 7

Promastigote interaction with phagocytic host cells

Answer 7

• promastigotes become predominantly phagocytosed predominantly by neutrophils
  -are taken up by these cells via CR3

Question 8

Immune response against leishmania

Answer 8

1) Mast cells collaborate in disease progression by secreting IL-
4 and IL-13 fostering Th2 responses and parasite survival
2) Neutrophils eliminate leishmanial parasites through
phagocytosis, ROS, and NETs release
Leishmania can survive transiently within neutrophils by:
- inhibiting phagolysosome biogenesis and oxidative stress
- delaying neutrophil apoptosis.
Infected neutrophils secrete IL-8 and MIP1 , which attract
additional neutrophils and other phagocytic cells, favoring
Leishmania survival and pathology

Macrophages can be differentiated in M1 or M2
during leishmaniasis.
* M1 macrophages produce proinflammatory
cytokine and chemokines, NO and ROS, booster
Th1 responses, and favor disease control.
* M2 macrophages increase the production of IL-
10 and TGF and support Th2 response and
disease progression

4) Dendritic cells (DCs) regulate immune responses against Leishmania by migrating to the
draining lymph nodes to present Leishmania-derived antigen to naïve T cells.
DCs can induce the differentiation of Th1 by secreting IL-12 and IL-27 or Th2, by blocking IL-12
secretion.
5) NK cells have a protective role in leishmaniasis by secreting IFN to boost Th1 response IL;
interleukin IFN leading to the eventual elimination of the parasite

Question 9

what is the causative agent of visceral leishmaniasis?

Answer 9

-leishmania donovani

Question 10

What is the incubation period for visceral leishmaniasis?

Answer 10

between 2weeks-18 months

Question 11

what are some of the symptoms of visceral leishmaniasis?

Answer 11

-abdominal swelling
-hepamegaly and spleenomegaly
-anemia and weightless
-diarrhea and fever
-low platelet count

Question 12

what is the mortality rate for VL?

Answer 12

Mortality rate between 75%-95% with death occurring within 2 years.

Question 13

What is correlated with an asymptomatic outcome of VL?

Answer 13

balance of IFN-gamma and IL-10 and low cytokine levels

Question 14

what is correlated with active visceral leishmania?

Answer 14

Inbalance of IFN-gamma and IL-10 and high levels of cytokines.

Question 15

Diagnosis methods for VL

Answer 15

-splenic puncture
- liver puncture
-bone marrow aspiration
-ELISA(antibody detection)
-PCR

Question 16

Which is the most common of the leishmaniases?

Answer 16

Cutaneous

Question 17

Cutaneous Leishmaniasis

Answer 17

-relatively mild skin disease
-causative agent include L. tropic, L. major, L. aethiopica
-amastigotes are found primarily in macrophages around cutaneous sites
-sandflies must feed at these sites in order to acquire the infectious amastigotes

Question 18

What is the incubation period for cutaneous leishmaniasis?

Answer 18

-couple months to 3 years but shorter in L. major which is in little as 2 weeks

Question 19

What are the signs of infection in cutaneous leishmaniasis?

Answer 19

-first sign of infection are small papules
-papules are dry and ulcerate every couple months
-lesions evolve from papules(dry) to nodular plaques to ulcerative lesions with scab or crust.

Question 20

What are the diagnosis methods for cutaneous leishmaniasis?

Answer 20

Biopsy Specimen/ Aspirates
-culture and PCR

Dermal scraping
-thin smearsH

Question 21

How do patients react to cutaneous leishmaniasis?

Answer 21

• The anergic patient is incapable of mounting a response to infection, which therefore
  can proliferate indefinitely, forming many lesions This type of disease, known as
  diffuse cutaneous leishmaniasis. It is seen primarily in infections caused by L.
  aethiopica and L. pifanoi.
• The hypersensitive patient is capable of excellent antibody and cellular responses
  but cannot completely eliminate the parasites, so as the central lesion heals, active
  peripheral ones continue to form. This type is known as leishmaniasis recidiva.
  Diffuse CL
  Recidiva CL

Question 22

Mucocutaneous leishmaniasis

Answer 22

• Caused by Leishmania braziliensis, L. guyanensis and L. panamensis
• Amastigotes are found in macrophages in ulcerations at mucocutaneous junctures
  of the skin.
• This disease is also known by various other names, including American
  leishmaniasis, espundia, uta, pian bois, and chiclero ulcer.
• In some parts of Brazil, such lesions are said to occur in about one fifth of cases of
  the disease.
• Various forest rodents and dogs are naturally infected.
• Sandflies belonging to the genera Lutzomyia and Psychodopygus are vectors.
• A clinically similar disease is seen in Ethiopia and Sudan and the causative agent is
  believed to be L. tropica and possibly L. major.
• Diagnosis and treatment follow the recommendations of severe cutaneous
  leishmaniasis.