L3: Leishmaniasis Flashcards
What is the definition of visceral leishmaniasis?
A chronic and potentially fatal parasitic disease of the viscera (particularly the liver, spleen, bone marrow and lymph nodes) due to infection by Leishmania parasite . Also known as Kala-azar.
What is the definition of cutaneous leishmaniasis?
- Cutaneous form of the disease causes skin sores and is usually named for a geographic place (for example, Baghdad, Delhi sore)
What are the causative organisms of visceral leishmaniasis?
All species of Leishmania donovani complex cause visceral leishmaniasis and are distributed as:
- In old world:
- L. donovani: India, Pakistan, Indonesia, Thailand, Central Africa and Sudan.
- L. infantum: Mediterranean area, Middle East and China. - In new world:
- L. chagasi: America (Central and South America).
What are the causitive organisms of cutaneous leishmaniasis?
L.Major
L.Athiopica
L.Tropica
What is the morphology of amastigote “leishman Donovan body” according to:
Site Size Shape Nucleus Flagellum Kinetoplast Significance
Site: typically intracellular in macrophages, In reticuloendothelial cells (RECs) all over the human body and reservoir host (vertebrate hosts),
Size: 2-3μ
Shape: ovoid
Nucleus: spherical nucleus (stain red with Giemsa)
Flagellum: Abscent
Kinetoplast: formed of
(a) parabasal body (rod-shaped, deep blue).
(b) Basal granule (blepharoplast), from which arises an intracytoplasmic axoneme (no free flagellum).
Significance: Diagnostic in biopsy
What is a morphology of promastigote acc to:
Site Size Shape Nucleus Flagellum Kinetoplast Significance
Site: In insect vector (invertebrate host) and culture.
Size: 4×12μ
Shape: fusiform (spindle-shaped)
Nucleus: central vesicular nucleus
Flagellum: anterior free flagellum
Kinetoplast: anterior kinetoplast (no undulating membrane)
Significance: infective stage
What is the habitat of visceral leishmaniasis?
- Leishmania amastigotes live intracellular in macrophages of reticuloendothelial ( R.E.S. )tissue., especially spleen, liver, bone marrow, intestinal mucosa and mesenteric lymph nodes.
What are other names of visceral Leishmanisis?
- Kala Azar
- Black fever
- Dum-Dum fever
What is the vector of visceral leishmaniasis?
- Female sand flies of the genus Phelebotomus in the old world, and Lutzomyia in the new world.
What is the reservoir host of visceral leishmaniasis?
Dogs, rodents, wild and domestic animals.
What is the infective stage of visceral leishmaniasis?
L.promastigotes.
- Site: sand fly gut.
What are the methods of infection by visceral leishmaniasis?
1- regurgitation of promastigotes into bite wound.
2- Rare modes: (by amastigotes):
(a) Blood transfusion.
(b) Transplacental.
(c) Accidental laboratory wound.
(d) Mechanical by blood sucking flies (e.g. Stomoxys).
How is visceral leishmaniasis transmitted?
Biological cyclo-propagation transmission
What is a diagnostic stage for visceral leishmaniasis?
- L. Amastigote (in tissue smear)
2. L. Promastigote (in culture typically arranged in rosettes)
How is visceral leishmaniasis treated?
Pentostam
What is the lifecycle of leishmania?
- Man acquires the infection when the infected female sand fly attempts a blood meal, where some of the promastigotes in the buccal cavity are regurgitated, and introduced into the skin bite by their motility.
- Promastigotes are phagocytosed by skin macrophages, where they metamorphose into amastigotes that reproduce by binary fission.
- Ruptured parasitized cells release large number of amastigotes into circulation
- Blood monocytes phagocytose the free amastigotes and carry them to the viscera, where they produce generalized infection of the RECs.
- Amastigotes in blood are taken by the female sand fly during blood meal.
- In the mid-gut of the sand fly, the amastigotes are metamorphosed into promastigotes and multiplied by binary fission (Cyclo-propagative development), until the lumen of the mid-gut is completely blocked.
- After 6-9 days, the promastigotes migrate to the pharynx which becomes blocked by the parasites, then to buccal cavity and proboscis.
- When blocked sand fly attempts subsequent blood meal, some of promastigotes are regurgitated, and introduced into the skin bite and the cycle is repeated.
“Just understand and write on your own words”
What is the pathogenesis and clinical picture of a visceral leishmaniasis?
” Fever + HS + Pan + DD + Skin”
- Fever
- Hepatosplenomegaly + generalized lymphadenopathy
- Pancytopenia
- Diarrhoea or dysentery
- Skin changes
What is the mechanism of pathogenicity in kala azar?
- Amastigotes multiply in macrophages (rupture + reinvasion) compensatory and reactive hyperplasia of R.E.Cs.
What are the characteristics of fever in visceral leishmaniasis?
intermittent (40 c, 2 peaks in one day).
What are the characteristics of pancytopenia in visceral leishmaniasis?
(aplastic anaemia + leucopenia + thrombocytopenia).
What are the characteristics of diarrhea and dysentery visceral leishmaniasis?
- ulceration of intestinal mucosa
- amastigote is found in stool
What are the causes of diarrhea and dysentery visceral leishmaniasis?
- Invasion of payers patches ——> hyperplasia—-> ischemia —-> ulceration of intestinal mucosa
What are the skin changes that happen in visceral leishmaniasis?
a) early: hyperpigmentation (circumoral on face – hence the
name: black fever).
(b) PKDL (post kala azar dermal leishmanoids): diffuse depigmented nod
How is visceral leishmaniasis diagnosed?
Clinical and laboratory
What is the laboratory diagnosis of visceral leishmaniasis?
Direct and indirect
What are the direct methods for diagnosis of visceral leishmaniasis?
- Microscopic Detection of amastigotes in Leishman or Giemsa-stained smears.
- Culture on NNN media
- Intraperitoneal Animal inoculation in hamsters by aspirated Specimens
“MCA”
What are the indirect methods for diagnosis of visceral leishmaniasis?
- Immunological diagnosis
A. Serological tests
B. Leishmanin skin test. (Montenegro test) - Molecular diagnosis
- Blood picture
Where is the sample for microscopic detection of amastigote in case of direct diagnosis taken from?
Taken from Sample:
- Peripheral blood
- Bone marrow.
- Splenic aspirates.
- Liver puncture.
- Enlarged LNs & nodular lesions.
- Nasopharyngeal secretion, Stool & urine.
Describe culture of promastigotes on NNN media
Detect Promastigotes in Rosette grouping,can be detected 1-4 weeks after cultivation.
What happens in positive cases after intraperitoneal animal inoculation in case of visceral leishmaniasis?
- In positive cases : Amastigotes can be seen in smears taken from ulcers or nodules at site of inoculation or from spleen, weeks post infection.
What are the serological tests done to diagnose visceral Leishmaniasis?
- Specific leishmanial antigens prepared from cultures used to delect anti-leishmanial antibodies by IFA, IHA, ELISA, Complement fixation test (CFT), direct agglutination test (DAT) & specific rapid immunochromatographic dipstick (ICT).
What is leishmania skin test? (Montenegro test)
Delayed hypersensitivity skin test.
How is Montenegro test done?
0.1 ml Killed promastigotes injected intradermal.
What is the result of Montenegro test?
Result: induration & erythema within 48-72 h indicate positive test.
- Positive result indicates past infection & Becomes positive 6-8 weeks after cure.
- Negative during active infection & PKDL, Why? Due to marked depression of cell-meciated immunity.
What is the molecular diagnosis of visceral leishmaniasis?
PCR for species identification.
What does a blood picture of visceral leishmaniasis show?
- Shows Aplastic anemia : Normocytic normochromic anemia, leucopenia & thrombocytopenia.
- Serum shows hypergammaglobulinemia & low albumin level. “Inverted A/G ratio”
How is visceral leishmaniasis treated?
A. Supportive treatment;
- Diel rich in vitamins, iron & liver therapy.
- Antibiotics for 2ry bacterial infection.
- Blood transfusion for severe anemia or bleeding.
B. Specific treatment:
a. Systemic therapy. “Parenteral”.
- Pentostam (Sodium stibogluconate).
- Amphotericin B.
- Interferon-gamma with pentostam effective for relapse.
b. Systemic therapy. “Oral”
: Miltefosine.
How is visceral leishmaniasis prevented and controlled?
- Control of sand flies : by destruction of their breeding grounds near human habitations & by use of residual chlorinated hydrocarbon.
- Treatment of infected patients
- Control of reservoir hosts will reduce sources of infection
- Personal prophylaxis by using :
- Bed nets
- Window mesh screen
- Insect repellents
What is the difference between the morphology and lifecycle of causative organism of cutaneous leishmaniasis and L.donovani ?
- The difference is that Leishmania amastigotes remain in skin macrophages without invasion of other organs
What is ….. of L. Major?
Habitat Distribution D.H I.H R.H Infective Stage Mode Of Infection
Habitat: RES of skin
Distribution: Rural distribution ( near desert : Libya, Egypt”Sohage &Sinai)
D.H: Man
I.H(vector): Female Sandfly “Phelebotomus”.
R.H: Rodents & Desert Gerbil.
Infective Stage: Promastigotes in sandfly midgut & pharynx .
Mode Of Infection:
1) Bite of infected female sandfly & Regurgitation of promastigotes into bite wound.
2) Direct contact.
3) Stable fly (Stomoxys calcitrans) may transmit organisms
mechanically from an open ulcer or through unbroken skin. “No blood amastigote”
What is the pathogenicity of cutaneous leishmaniasis?
- Multiplication of amastigotes in skin macrophages —–> formation of papule, nodule & ulcer.
- Ulcer may be single or multiple, that heals over months to years leaving scar.
- Recovery from cutaneous leishmaniasis gives a life-long immunity against the Same leishmania species
What is the clinical picture of infection with L.major?
L. Major : Cause Wet “Moist - Oriental Sore .
Course: acute
Incubation period: SHORT (2-6 WEEKS)
Number: Multiple
Healing: Rapid (3-6 months ).
What are the characters of moist ulcer?
Starts by: Small itchy erythmatous papule
Site: Located on exposed part of skin “upper limb & L.L”
Edge: Sharp raised edge (volcano sign)
Margin: Red indurated (firm) margin
Floor: Necrotic base
Fate: Heal by depressed depigmented scar in moist type
What is a diagnosis of cutaneous leishmaniasis?
Clinical and laboratory
What is a laboratory diagnosis of cutaneous leishmaniasis?
Direct and indirect
What is the direct laboratory diagnosis of cutenous leishmaniasis?
- Microscopic examination of :
- Smears aspirated or scraped from edge of lesion & stained with Leishman or Giemsa
- Skin Biopsy stained with H & E. - Culture “NNN media”: Detect Promastigote.
- Animal inoculation.
What is the indirect laboratory diagnosis of cutaneous leishmaniasis?
- Leishmanin (Montenegro) skin test :
- Helpful
- Becomes positive few days after infection - Serological diagnosis : Of limited value because antibody levels are undetectable.
What is the treatment of cutaneous leishmaniasis?
Local and systemic measures
What are the local meausures followed for treatment of cutaneous leishmaniasis?
- Surgical excision.
- Scraping (curettage).
- Plastic surgery for Scars or disfiguring nodules.
Cleanliness to prevent 2ry bacterial infection. - Systemic/local antibiotic : for 2ry infection needs.
- Local heating of lesion by infra-red rays
- Freezing therapy by carbon dioxide
“Cryotherapy” - Local injection of 10% atebrine, solution.
- ID. injection of interferon gamma around lesions promotes healing of ulcers.
What are the systemic treatment of cutaneous leishmaniasis?
Systemic therapy (parenteral): Pentostam “of choice”.
- 2 or 3 courses may be needed.
- If sores 1-3 in number, treatment facilitated by local
infiltration of drug into edges of ulcers.
